Evaluation of the frequency of food allergens based on skin prick test in children in Kurdistan Province – Iran

Publication date: Available online 24 July 2017
Source:Allergologia et Immunopathologia
Author(s): R. Kalmarzi, P. Ataee, Gh. Homagostar, M. Tagik, E. Ghaderi, W. Kooti
IntroductionFood allergy refers to abnormal reactions of the body caused by an immune system response to food. This study was conducted aiming to investigate allergy to food allergens in children with food allergies.Materials and methodsThis study was conducted as a cross-sectional one on 304 children aged six months to seven years with food allergies admitted to the tertiary referral hospital in Kurdistan Province – Iran, during 2014–2015. All the patients were examined for skin prick test using 49 allergens. Finally, the obtained data were analysed using SPSS15 and chi-square and t tests.ResultsThe highest percentage of occurrence of bump reaction (wheal) and redness (flare) was due to the consumption of fish, eggs, tomatoes, and cocoa. Moreover, the lowest rate of wheal and flare was caused by exposure to allergens like latex, tea, malt, and wheat flour. The reaction most created due to the consumption of foods was flare which was higher among under three-year-olds group (p<0.05), and between the sexes, girls showed the most common allergic reactions (p<0.05).ConclusionSince food allergy has a high prevalence in children, it should be considered with great interest. Considering that avoiding food allergens is the first step in the treatment of food allergies, the present study may be a useful guide in this regard.



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Outcomes of office-based temporomandibular joint arthroscopy: a 5-year retrospective study

Publication date: Available online 24 July 2017
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): R.H. Hossameldin, J.P. McCain
Temporomandibular joint (TMJ) arthroscopy is a minimally invasive surgical approach for intra-articular TMJ diseases. Office-based arthroscopy using the smallest TMJ scope allows for good visualization, as well as the ability to lavage the joint in an office setting. This study aimed to assess the efficacy of an office-based TMJ arthroscopic technique. A retrospective evaluation of 363 patients with a TMJ disorder was performed. These patients underwent office-based arthroscopy using the OnPoint 1.2mm Scope System (Biomet Microfixation, Jacksonville, FL, USA) in Florida, USA, from July 2007. The following outcomes of the procedure were assessed: improvement in painless range of mandibular motion, pain on loading, and functional jaw pain; these were evaluated using a visual analog scale (VAS) over an average follow-up period of 263.81±142.1 days. The statistical analysis was performed using IBM SPSS Statistics version 20. Statistically significant improvements in TMJ pain and function, and other variables (P=0.001) were shown following TMJ arthroscopic lysis and lavage. Office-based arthroscopy using the OnPoint System was demonstrated to be a safe and efficient procedure for the treatment of patients with TMJ disorders as the first level of the algorithm of care.



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Short implants (6mm) vs. vertical bone augmentation and standard-length implants (≥9mm) in atrophic posterior mandibles: a 5-year retrospective study

Publication date: Available online 24 July 2017
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): F. Pieri, C. Forlivesi, E. Caselli, G. Corinaldesi
This retrospective study compared the 5-year clinical and radiographic outcomes of short implants (6 mm) (short group), and standard-length implants (≥9mm) placed after a vertical augmentation with autologous bone blocks (augmentation group), supporting partial fixed prostheses in the posterior mandible. Forty-five partially edentulous patients were enrolled in the study and evaluated after 5 years: 22 (51 implants) in the augmentation group and 23 (46 implants) in the short group. Eight surgical complications occurred in the augmentation group versus none in the short group (P=0.003). One short implant failed before loading and one standard-length implant failed after 4 years because of peri-implantitis (P=1.0). Eight biological and two prosthetic complications occurred in the augmentation group vs. three biological and three prosthetic complications in the short group (P=0.09 and P=1.0, respectively). A mean marginal bone loss of 1.61±1.12mm in the augmentation group and 0.68±0.68mm in the short group was found (P=0.002). Within the limitations of this study, both techniques resulted in successful clinical results after 5 years, but short implants exhibited less surgical complications and marginal bone loss than standard-length implants placed in augmented bone.



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Restoration of Sleep Architecture after Maxillomandibular Advancement: Success Beyond the Apnea–Hypopnea Index

Publication date: Available online 24 July 2017
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): S.Y.-C. Liu, L.-K. Huon, C. Ruoff, R.W. Riley, K.P. Strohl, Z. Peng
While effects of maxillomandibular advancement (MMA) on respiratory parameters for patients with obstructive sleep apnea (OSA) are well described, effects on sleep architecture before and after MMA are not. A retrospective cohort analysis on sleep architecture was examined in 10 OSA patients who underwent MMA surgery between July 2013 and November 2014, and had prespecified complete polysomnography (PSG) datasets. Sleep stages were examined relative to a Western European population-based control group. All of the respiratory parameters improved significantly post MMA. Rapid eye movement (REM) latency decreased from 178.0±142.8 to 96.6±64.5min (P=0.035). %NREM (non-rapid eye movement)1 (P=0.045) and %WASO (wakefulness after sleep onset) (P=0.006) decreased, while %REM increased (P=0.002) after MMA. WASO decreased from 64.2±57min to 22.4±15.4min (P=0.017). Preoperatively, OSA subjects showed significantly lower sleep efficiency (P=0.016), sleep onset latency (P=0.015), and % REM (P<0.001) than the normative population dataset, while post MMA there was a significant decrease in %NREM1 sleep (P<0.001) and in %WASO (P<0.001). MMA results in a marked decrease in WASO and increase in REM, and to a lesser extent NREM sleep. Patients after MMA show values similar to population controls except for a lower WASO.



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Unilateral blindness after orthognathic surgery: hypotensive anaesthesia is not the primary cause

Publication date: Available online 24 July 2017
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): Á. Rodríguez-Navarro, F.M. Gonzalez-Valverde
Perioperative vision loss in non-ocular surgery represents a rare but devastating complication and multiple causes have been proposed. Any portion of the visual system may be involved and several authors have tried to relate that complication with deliberate hypotension anaesthetic technique, used to control intraoperative bleeding. We report a patient operated for orthognathism who suffered unilateral blindness. After review of similar cases, we can state that the transmission of forces generated during Le fort I osteotomy is related to the complication. This osteotomy technique is regularly performed in our hospital using a curved osteotome to achieve the pterygomaxillary disjunction and the adverse transmission of forces via the sphenoid bone is the main reason for indirect damage to the optic nerve and its vascular structures causing the neuropathy and blindness. Hypotensive anaesthesia may certainly lead to transient ischaemia but only in specific cases because of decreased ocular perfusion pressured.



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Three-dimensional aesthetic assessment of class II patients before and after orthognathic surgery and its association with quantitative surgical changes

Publication date: Available online 24 July 2017
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): A.S. Storms, L. Vansant, E. Shaheen, W. Coucke, Cadenas de Llano-Pérula, R. Jacobs, C. Politis, G. Willems
The aim of this study was to compare evaluations of the aesthetic outcome of class II orthognathic patients, as performed by observers with varying expertise using three-dimensional (3D) facial images, and to examine the relationship of aesthetic ratings in relation to quantitative surgical changes. Pre- and postoperative 3D facial images of 20 surgically treated class II patients (13 female, 7 male) were assessed for aesthetics by orthodontists, maxillofacial surgeons, and laypeople. Attractiveness ratings for the lips, chin, and overall facial aesthetics were evaluated on a 5-point Likert scale. Correlation between the aesthetic scores was obtained and quantitative surgical changes were examined. For all groups of observers, significant improvements in attractiveness scores were found, especially for the chin assessment. Orthodontists perceived the greatest improvement and laypeople the smallest. Overall, laypeople scored higher with less variability, but with lower intra- and inter-observer agreement. No significant correlation was found between the aesthetic improvement and soft tissue surgical changes. To avoid patient dissatisfaction, it is important to bear in mind that the demands and perception of aesthetic improvement after orthognathic surgery are higher for clinicians than for the general public.



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External carotid artery sacrifice in the treatment of infantile haemangiopericytoma in a neonate

Publication date: Available online 24 July 2017
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): R. Pokrowiecki, K. Dowgierd
Haemangiopericytoma of the head and neck (HN-HPC) is a rare neoplasm occurring in children. The rarity of the tumour poses a diagnostic and therapeutic challenge. Despite protocols that recommend the use of chemotherapy prior to surgery, no treatment standard has yet been proposed. This article reports the case of a 5-month-old infant with a rapidly growing, giant life-threatening HN-HPC that was treated successfully by two-stage surgery without adjuvant chemotherapy.



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Sorafenib in Japanese Patients with Locally Advanced or Metastatic Medullary Thyroid Carcinoma and Anaplastic Thyroid Carcinoma

Thyroid , Vol. 0, No. 0.


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Comparison of the Seventh and Eighth Editions of the American Joint Committee on Cancer/Union for International Cancer Control Tumor-Node-Metastasis Staging System for Differentiated Thyroid Cancer

Thyroid , Vol. 0, No. 0.


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PMab-52: Specific and Sensitive Monoclonal Antibody Against Cat Podoplanin for Immunohistochemistry

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy , Vol. 0, No. 0.


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Mast Cell and M1 Macrophage Infiltration and Local Pro-Inflammatory Factors Were Attenuated with Incretin-Based Therapies in Obesity-Related Glomerulopathy

Metabolic Syndrome and Related Disorders , Vol. 0, No. 0.


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Psoriasis: a mixed autoimmune and autoinflammatory disease

Yun Liang | Mrinal K Sarkar | Lam C Tsoi | Johann E Gudjonsson

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The immunopathology of dengue and Zika virus infections

Abigail Culshaw | Juthathip Mongkolsapaya | Gavin R Screaton

http://ift.tt/2urdjjm

Germinal center enhancement by extended antigen availability

Kimberly M Cirelli | Shane Crotty

http://ift.tt/2urI0VO

Top Reviewers

Publication date: July–August 2017
Source:American Journal of Otolaryngology, Volume 38, Issue 4





http://ift.tt/2gYwBb7

More on molar incisor hypomineralisation (MIH) and linear enamel hypoplasia (LEH) in archaeological human remains

http://ift.tt/2uRZbAK

Outcomes of office-based temporomandibular joint arthroscopy: a 5-year retrospective study

Temporomandibular joint (TMJ) arthroscopy is a minimally invasive surgical approach for intra-articular TMJ diseases. Office-based arthroscopy using the smallest TMJ scope allows for good visualization, as well as the ability to lavage the joint in an office setting. This study aimed to assess the efficacy of an office-based TMJ arthroscopic technique. A retrospective evaluation of 363 patients with a TMJ disorder was performed. These patients underwent office-based arthroscopy using the OnPoint 1.2mm Scope System (Biomet Microfixation, Jacksonville, FL, USA) in Florida, USA, from July 2007.

http://ift.tt/2uuqJcN

Short implants (6mm) vs. vertical bone augmentation and standard-length implants (≥9mm) in atrophic posterior mandibles: a 5-year retrospective study

This retrospective study compared the 5-year clinical and radiographic outcomes of short implants (6 mm) (short group), and standard-length implants (≥9mm) placed after a vertical augmentation with autologous bone blocks (augmentation group), supporting partial fixed prostheses in the posterior mandible. Forty-five partially edentulous patients were enrolled in the study and evaluated after 5 years: 22 (51 implants) in the augmentation group and 23 (46 implants) in the short group. Eight surgical complications occurred in the augmentation group versus none in the short group (P=0.003).

http://ift.tt/2uRJ6Lp

Unilateral blindness after orthognathic surgery: hypotensive anaesthesia is not the primary cause

Perioperative vision loss in non-ocular surgery represents a rare but devastating complication and multiple causes have been proposed. Any portion of the visual system may be involved and several authors have tried to relate that complication with deliberate hypotension anaesthetic technique, used to control intraoperative bleeding. We report a patient operated for orthognathism who suffered unilateral blindness. After review of similar cases, we can state that the transmission of forces generated during Le fort I osteotomy is related to the complication.

http://ift.tt/2uuGn7Y

Three-dimensional aesthetic assessment of class II patients before and after orthognathic surgery and its association with quantitative surgical changes

The aim of this study was to compare evaluations of the aesthetic outcome of class II orthognathic patients, as performed by observers with varying expertise using three-dimensional (3D) facial images, and to examine the relationship of aesthetic ratings in relation to quantitative surgical changes. Pre- and postoperative 3D facial images of 20 surgically treated class II patients (13 female, 7 male) were assessed for aesthetics by orthodontists, maxillofacial surgeons, and laypeople. Attractiveness ratings for the lips, chin, and overall facial aesthetics were evaluated on a 5-point Likert scale.

http://ift.tt/2uROCOh

External carotid artery sacrifice in the treatment of infantile haemangiopericytoma in a neonate

Haemangiopericytoma of the head and neck (HN-HPC) is a rare neoplasm occurring in children. The rarity of the tumour poses a diagnostic and therapeutic challenge. Despite protocols that recommend the use of chemotherapy prior to surgery, no treatment standard has yet been proposed. This article reports the case of a 5-month-old infant with a rapidly growing, giant life-threatening HN-HPC that was treated successfully by two-stage surgery without adjuvant chemotherapy.

http://ift.tt/2uuGmRs

Restoration of Sleep Architecture after Maxillomandibular Advancement: Success Beyond the Apnea–Hypopnea Index

While effects of maxillomandibular advancement (MMA) on respiratory parameters for patients with obstructive sleep apnea (OSA) are well described, effects on sleep architecture before and after MMA are not. A retrospective cohort analysis on sleep architecture was examined in 10 OSA patients who underwent MMA surgery between July 2013 and November 2014, and had prespecified complete polysomnography (PSG) datasets. Sleep stages were examined relative to a Western European population-based control group.

http://ift.tt/2uRovag

Activation of Complement by Pigment Epithelium-Derived Factor in Rheumatoid Arthritis [INNATE IMMUNITY AND INFLAMMATION]

The aim of this study was to identify molecules that trigger complement activation in rheumatic joints. C4d, the final cleavage product of C4 activation, is found in the diseased joint and can bind covalently to complement-activating molecules. By using a highly specific Ab against a cleavage neoepitope in C4d, several molecules that were specifically bound to C4d were identified from pooled synovial fluid (SF) from four rheumatoid arthritis (RA) patients. One of these molecules, pigment epithelium–derived factor (PEDF), is a broadly expressed multifunctional member of the serine proteinase inhibitor family. Using ELISA, we confirmed the presence of various amounts of complexes between PEDF and C4d in the SF from 30 RA patients, whereas none were detected in SF from control subjects. Correlation analyses suggested that, in arthritis patients, C4d–PEDF complexes found in sera arise from the joints, as well as from other tissues, and levels of the complexes did not differ in sera of RA patients and healthy controls. When immobilized, recombinant PEDF expressed in eukaryotic cells activated the classical complement pathway but not the alternative or lectin pathways. C1q protein was demonstrated to bind immobilized PEDF, and PEDF was shown to bind to immobilized C1q, in particular its head regions, which are known to interact with other activators of the classical pathway. Our results call for further investigation into the role of PEDF in inflammatory processes in the joint, which, in combination with classical complement activation, appears to be part of a (patho-)physiologic response.

http://ift.tt/2gY00Ct

Interaction between Multimeric von Willebrand Factor and Complement: A Fresh Look to the Pathophysiology of Microvascular Thrombosis [INNATE IMMUNITY AND INFLAMMATION]

von Willebrand factor (VWF), a multimeric protein with a central role in hemostasis, has been shown to interact with complement components. However, results are contrasting and inconclusive. By studying 20 patients with congenital thrombotic thrombocytopenic purpura (cTTP) who cannot cleave VWF multimers because of genetic ADAMTS13 deficiency, we investigated the mechanism through which VWF modulates complement and its pathophysiological implications for human diseases. Using assays of ex vivo serum-induced C3 and C5b-9 deposits on endothelial cells, we documented that in cTTP, complement is activated via the alternative pathway (AP) on the cell surface. This abnormality was corrected by restoring ADAMTS13 activity in cTTP serum, which prevented VWF multimer accumulation on endothelial cells, or by an anti-VWF Ab. In mechanistic studies we found that VWF interacts with C3b through its three type A domains and initiates AP activation, although assembly of active C5 convertase and formation of the terminal complement products C5a and C5b-9 occur only on the VWF-A2 domain. Finally, we documented that in the condition of ADAMTS13 deficiency, VWF-mediated formation of terminal complement products, particularly C5a, alters the endothelial antithrombogenic properties and induces microvascular thrombosis in a perfusion system. Altogether, the results demonstrated that VWF provides a platform for the activation of the AP of complement, which profoundly alters the phenotype of microvascular endothelial cells. These findings link hemostasis-thrombosis with the AP of complement and open new therapeutic perspectives in cTTP and in general in thrombotic and inflammatory disorders associated with endothelium perturbation, VWF release, and complement activation.

http://ift.tt/2gXW3xJ

Lack of Both Nucleotide-Binding Oligomerization Domain-Containing Proteins 1 and 2 Primes T Cells for Activation-Induced Cell Death [TRANSPLANTATION]

Nucleotide-binding oligomerization domain (Nod)–containing proteins Nod1 and Nod2 play important roles in the innate immune response to pathogenic microbes, but mounting data suggest these pattern recognition receptors might also play key roles in adaptive immune responses. Targeting Nod1 and Nod2 signaling pathways in T cells is likely to provide a new strategy to modify inflammation in a variety of disease states, particularly those that depend on Ag-induced T cell activation. To better understand how Nod1 and Nod2 proteins contribute to adaptive immunity, this study investigated their role in alloantigen-induced T cell activation and asked whether their absence might impact in vivo alloresponses using a severe acute graft versus host disease model. The study provided several important observations. We found that the simultaneous absence of Nod1 and Nod2 primed T cells for activation-induced cell death. T cells from Nod1 x 2^–/– mice rapidly underwent cell death upon exposure to alloantigen. The Nod1 x 2^–/– T cells had sustained p53 expression that was associated with downregulation of its negative regulator MDM2. In vivo, mice transplanted with an inoculum containing Nod1 x 2^–/– T cells were protected from severe graft versus host disease. The results show that the simultaneous absence of Nod1 and Nod2 is associated with accelerated T cell death upon alloantigen encounter, suggesting these proteins might provide new targets to ameliorate T cell responses in a variety of inflammatory states, including those associated with bone marrow or solid organ transplantation.

http://ift.tt/2gXVLa7

Neutrophils Induce Astroglial Differentiation and Migration of Human Neural Stem Cells via C1q and C3a Synthesis [INNATE IMMUNITY AND INFLAMMATION]

Inflammatory processes play a key role in pathophysiology of many neurologic diseases/trauma, but the effect of immune cells and factors on neurotransplantation strategies remains unclear. We hypothesized that cellular and humoral components of innate immunity alter fate and migration of human neural stem cells (hNSC). In these experiments, conditioned media collected from polymorphonuclear leukocytes (PMN) selectively increased hNSC astrogliogenesis and promoted cell migration in vitro. PMN were shown to generate C1q and C3a; exposure of hNSC to PMN-synthesized concentrations of these complement proteins promoted astrogliogenesis and cell migration. Furthermore, in vitro, Abs directed against C1q and C3a reversed the fate and migration effects observed. In a proof-of-concept in vivo experiment, blockade of C1q and C3a transiently altered hNSC migration and reversed astroglial fate after spinal cord injury. Collectively, these data suggest that modulation of the innate/humoral inflammatory microenvironment may impact the potential of cell-based therapies for recovery and repair following CNS pathology.

http://ift.tt/2gXW1G7

Menin Controls the Memory Th2 Cell Function by Maintaining the Epigenetic Integrity of Th2 Cells [MOLECULAR AND STRUCTURAL IMMUNOLOGY]

Posttranslational modifications of histones are well-established epigenetic modifications that play an important role in gene expression and regulation. These modifications are partly mediated by the Trithorax group (TrxG) complex, which regulates the induction or maintenance of gene transcription. We investigated the role of Menin, a component of the TrxG complex, in the acquisition and maintenance of Th2 cell identity using T cell–specific Menin-deficient mice. Our gene expression analysis revealed that Menin was involved in the maintenance of the high expression of the previously identified Th2-specific genes rather than the induction of these genes. This result suggests that Menin plays a role in the maintenance of Th2 cell identity. Menin directly bound to the Gata3 gene locus, and this Menin-Gata3 axis appeared to form a core unit of the Th2-specific gene regulatory network. Consistent with the phenotype of Menin-deficient Th2 cells observed in vitro, Menin deficiency resulted in the attenuation of effector Th2 cell–induced airway inflammation. In addition, in memory Th2 (mTh2) cells, Menin was found to play an important role in the maintenance of the expression of Th2-specific genes, including Gata3, Il4, and Il13. Consequently, Menin-deficient mTh2 cells showed an impaired ability to recruit eosinophils to the lung, resulting in the attenuation of mTh2 cell–induced airway inflammation. This study confirmed the critical role of Menin in Th2 cell–mediated immune responses.

http://ift.tt/2gXVRhZ

Immune Cell Dynamics in Rhesus Macaques Infected with a Brazilian Strain of Zika Virus [INFECTIOUS DISEASE AND HOST RESPONSE]

Zika virus (ZIKV) is a mosquito-borne and sexually transmitted flavivirus that is associated with fetal CNS-damaging malformations during pregnancy in humans. This study documents the viral kinetics and immune responses in rhesus macaques infected with a clinical ZIKV Brazilian isolate. We evaluated the viral kinetics and immune responses induced after an i.v. infection with a Brazilian ZIKV clinical isolate (HS-2015-BA-01) in rhesus macaques for up to 142 d. ZIKV-specific Ab-secreting cells, germinal center reactions, and monocyte, dendritic cell, NK, and T cell frequencies were monitored. ZIKV loads were readily detected in plasma (until day 5 or 7), semen and urine (until days 7 and 14), and saliva (until day 42), but the viremia was rapidly controlled. No detectable clinical manifestations were observed. However, lymph node hyperplasia was clearly visible postviremia but was associated with low frequencies of ZIKV-specific Ab-secreting cells in lymph nodes and bone marrow, correlating with low Ab titers. CD14⁺/CD16^– monocytes and myeloid CD11c^hi dendritic cells decreased in blood, whereas NK and T cell numbers were only marginally altered during the course of the study. ZIKV infection caused a significant lymphoid tissue activation but limited induction of ZIKV-specific B cells, suggesting that these parameters need to be considered for ZIKV vaccine design.

http://ift.tt/2gXW4Sj

Dietary Salt Exacerbates Experimental Colitis [INNATE IMMUNITY AND INFLAMMATION]

The Western diet is characterized by high protein, sugar, fat, and low fiber intake, and is widely believed to contribute to the incidence and pathogenesis of inflammatory bowel disease (IBD). However, high sodium chloride salt content, a defining feature of processed foods, has not been considered as a possible environmental factor that might drive IBD. We set out to bridge this gap. We examined murine models of colitis on either a high salt diet (HSD) or a low salt diet. We demonstrate that an HSD exacerbates inflammatory pathology in the IL-10–deficient murine model of colitis relative to mice fed a low salt diet. This was correlated with enhanced expression of numerous proinflammatory cytokines. Surprisingly, sodium accumulated in the colons of mice on an HSD, suggesting a direct effect of salt within the colon. Similar to the IL-10–deficient model, an HSD also enhanced cytokine expression during infection by Salmonella typhimurium. This occurred in the first 3 d of infection, suggesting that an HSD potentiates an innate immune response. Indeed, in cultured dendritic cells we found that high salt media potentiates cytokine expression downstream of TLR4 activation via p38 MAPK and SGK1. A third common colitis model, administration of dextran sodium sulfate, was hopelessly confounded by the high sodium content of the dextran sodium sulfate. Our results raise the possibility that high dietary salt is an environmental factor that drives increased inflammation in IBD.

http://ift.tt/2gXW2Kb

Leukotriene C4 Potentiates IL-33-Induced Group 2 Innate Lymphoid Cell Activation and Lung Inflammation [INNATE IMMUNITY AND INFLAMMATION]

Asthma is a complex disease that is promoted by dysregulated immunity and the presence of many cytokine and lipid mediators. Despite this, there is a paucity of data demonstrating the combined effects of multiple mediators in asthma pathogenesis. Group 2 innate lymphoid cells (ILC2s) have recently been shown to play important roles in the initiation of allergic inflammation; however, it is unclear whether lipid mediators, such as cysteinyl leukotrienes (CysLTs), which are present in asthma, could further amplify the effects of IL-33 on ILC2 activation and lung inflammation. In this article, we show that airway challenges with the parent CysLT, leukotriene C4 (LTC4), given in combination with low-dose IL-33 to naive wild-type mice, led to synergistic increases in airway Th2 cytokines, eosinophilia, and peribronchial inflammation compared with IL-33 alone. Further, the numbers of proliferating and cytokine-producing lung ILC2s were increased after challenge with both LTC4 and IL-33. Levels of CysLT1R, CysLT2R, and candidate leukotriene E4 receptor P2Y12 mRNAs were increased in ILC2s. The synergistic effect of LTC4 with IL-33 was completely dependent upon CysLT1R, because CysLT1R^–/– mice, but not CysLT2R^–/– mice, had abrogated responses. Further, CysLTs directly potentiated IL-5 and IL-13 production from purified ILC2s stimulated with IL-33 and resulted in NFAT1 nuclear translocation. Finally, CysLT1R^–/– mice had reduced lung eosinophils and ILC2 responses after exposure to the fungal allergen Alternaria alternata. Thus, CysLT1R promotes LTC4- and Alternaria-induced ILC2 activation and lung inflammation. These findings suggest that multiple pathways likely exist in asthma to activate ILC2s and propagate inflammatory responses.

http://ift.tt/2gXVZht

Activation of Mouse Tcrb: Uncoupling RUNX1 Function from Its Cooperative Binding with ETS1 [MOLECULAR AND STRUCTURAL IMMUNOLOGY]

T lineage commitment requires the coordination of key transcription factors (TFs) in multipotent progenitors that transition them away from other lineages and cement T cell identity. Two important TFs for the multipotent progenitors to T lineage transition are RUNX1 and ETS1, which bind cooperatively to composite sites throughout the genome, especially in regulatory elements for genes involved in T lymphopoiesis. Activation of the TCR β (Tcrb) locus in committed thymocytes is a critical process for continued development of these cells, and is mediated by an enhancer, Eβ, which harbors two RUNX-ETS composite sites. An outstanding issue in understanding T cell gene expression programs is whether RUNX1 and ETS1 have independent functions in enhancer activation that can be dissected from cooperative binding. We now show that RUNX1 is sufficient to activate the endogenous mouse Eβ element and its neighboring 25 kb region by independently tethering this TF without coincidental ETS1 binding. Moreover, RUNX1 is sufficient for long-range promoter-Eβ looping, nucleosome clearance, and robust transcription throughout the Tcrb recombination center, spanning both DβJβ clusters. We also find that a RUNX1 domain, termed the negative regulatory domain for DNA binding, can compensate for the loss of ETS1 binding at adjacent sites. Thus, we have defined independent roles for RUNX1 in the activation of a T cell developmental enhancer, as well as its ability to mediate specific changes in chromatin landscapes that accompany long-range induction of recombination center promoters.

http://ift.tt/2gXVTq7

Early Postnatal Secondhand Smoke Exposure Disrupts Bacterial Clearance and Abolishes Immune Responses in Muco-Obstructive Lung Disease [MUCOSAL IMMUNOLOGY]

Secondhand smoke (SHS) exposure has been linked to the worsening of ongoing lung diseases. However, whether SHS exposure affects the manifestation and natural history of imminent pediatric muco-obstructive airway diseases such as cystic fibrosis remains unclear. To address these questions, we exposed Scnn1b transgenic (Scnn1b-Tg⁺) mice to SHS from postnatal day (PND) 3–21 and lung phenotypes were examined at PND22. Although a majority of filtered air (FA)-exposed Scnn1b-Tg⁺ (FA-Tg⁺) mice successfully cleared spontaneous bacterial infections by PND22, the SHS-exposed Scnn1b-Tg⁺ (SHS-Tg⁺) mice failed to resolve these infections. This defect was associated with suppressed antibacterial defenses, i.e., phagocyte recruitment, IgA secretion, and Muc5b expression. Whereas the FA-Tg⁺ mice exhibited marked mucus obstruction and Th2 responses, SHS-Tg⁺ mice displayed a dramatic suppression of these responses. Mechanistically, downregulated expression of IL-33, a stimulator of type II innate lymphoid cells, in lung epithelial cells was associated with suppression of neutrophil recruitment, IgA secretions, Th2 responses, and delayed bacterial clearance in SHS-Tg⁺ mice. Cessation of SHS exposure for 21 d restored previously suppressed responses, including phagocyte recruitment, IgA secretion, and mucous cell metaplasia. However, in contrast with FA-Tg⁺ mice, the SHS-Tg⁺ mice had pronounced epithelial necrosis, alveolar space consolidation, and lymphoid hyperplasia; indicating lagged unfavorable effects of early postnatal SHS exposure in later life. Collectively, our data show that early postnatal SHS exposure reversibly suppresses IL-33 levels in airspaces which, in turn, results in reduced neutrophil recruitment and diminished Th2 response. Our data indicate that household smoking may predispose neonates with muco-obstructive lung disease to bacterial exacerbations.

http://ift.tt/2gXDHNd

Correction: DNA Repair Interacts with Autophagy To Regulate Inflammatory Responses to Pulmonary Hyperoxia [CORRECTIONS]

http://ift.tt/2gXVKD5

Inflammasome and Fas-Mediated IL-1{beta} Contributes to Th17/Th1 Cell Induction in Pathogenic Bacterial Infection In Vivo [INNATE IMMUNITY AND INFLAMMATION]

CD4⁺ Th cells play crucial roles in orchestrating immune responses against pathogenic microbes, after differentiating into effector subsets. Recent research has revealed the importance of IFN- and IL-17 double-producing CD4⁺ Th cells, termed Th17/Th1 cells, in the induction of autoimmune and inflammatory diseases. In addition, Th17/Th1 cells are involved in the regulation of infection caused by the intracellular bacterium Mycobacterium tuberculosis in humans. However, the precise mechanism of Th17/Th1 induction during pathogen infection is unclear. In this study, we showed that the inflammasome and Fas-dependent IL-1β induces Th17/Th1 cells in mice, in response to infection with the pathogenic intracellular bacterium Listeria monocytogenes. In the spleens of infected wild-type mice, Th17/Th1 cells were induced, and expressed T-bet and Rort. In Pycard^–/– mice, which lack the adaptor molecule of the inflammasome (apoptosis-associated speck-like protein containing a caspase recruitment domain), Th17/Th1 induction was abolished. In addition, the Fas-mediated IL-1β production was required for Th17/Th1 induction during bacterial infection: Th17/Th1 induction was abolished in Fas^–/– mice, whereas supplementation with recombinant IL-1β restored Th17/Th1 induction via IL-1 receptor 1 (IL-1R1), and rescued the mortality of Fas^–/– mice infected with Listeria. IL-1R1, but not apoptosis-associated speck-like protein containing a caspase recruitment domain or Fas on T cells, was required for Th17/Th1 induction, indicating that IL-1β stimulates IL-1R1 on T cells for Th17/Th1 induction. These results indicate that IL-1β, produced by the inflammasome and Fas-dependent mechanisms, contributes cooperatively to the Th17/Th1 induction during bacterial infection. This study provides a deeper understanding of the molecular mechanisms underlying Th17/Th1 induction during pathogenic microbial infections in vivo.

http://ift.tt/2eJ7UyO

Defining the Kinetics, Phenotype, and Function of T Cells Induced by Mycobacterium tuberculosis: Pillar of Immunity to Tuberculosis [PILLARS OF IMMUNOLOGY]

http://ift.tt/2eJ8CMw

Type I IFN Is Necessary and Sufficient for Inflammation-Induced Red Blood Cell Alloimmunization in Mice [INNATE IMMUNITY AND INFLAMMATION]

During RBC transfusion, production of alloantibodies against RBC non-ABO Ags can cause hemolytic transfusion reactions and limit availability of compatible blood products, resulting in anemia-associated morbidity and mortality. Multiple studies have established that certain inflammatory disorders and inflammatory stimuli promote alloimmune responses to RBC Ags. However, the molecular mechanisms underlying these findings are poorly understood. Type I IFNs (IFN-α/β) are induced in inflammatory conditions associated with increased alloimmunization. By developing a new transgenic murine model, we demonstrate that signaling through the IFN-α/β receptor is required for inflammation-induced alloimmunization. Additionally, mitochondrial antiviral signaling protein–mediated signaling through cytosolic pattern recognition receptors was required for polyinosinic-polycytidylic acid–induced IFN-α/β production and alloimmunization. We further report that IFN-α, in the absence of an adjuvant, is sufficient to induce RBC alloimmunization. These findings raise the possibility that patients with IFN-α/β–mediated conditions, including autoimmunity and viral infections, may have an increased risk of RBC alloimmunization and may benefit from personalized transfusion protocols and/or targeted therapies.

http://ift.tt/2eJ8gFG

Pillars Article: The Kinetics of Emergence and Loss of Mediator T Lymphocytes Acquired in Response to Infection with Mycobacterium Tuberculosis. J. Immunol. 1987. 138: 293-298 [PILLARS OF IMMUNOLOGY]

http://ift.tt/2gXJiDn

Retraction: Hypoxia-Inducible Factor (HIF) 1{alpha} Accumulation and HIF Target Gene Expression Are Impaired after Induction of Endotoxin Tolerance [LETTERS OF RETRACTION]

http://ift.tt/2eJ1Zd3

Here, There, and Anywhere? Arguments for and against the Physical Plasma Cell Survival Niche [BRIEF REVIEWS]

To maintain Ab titers, individual plasma cells must survive for extended periods, perhaps even for the life of the host. Although it is clear that plasma cell survival requires cell extrinsic signals, the nature and source of these signals remains open for debate. It is commonly postulated that plasma cells only gain access to these signals within specialized regulatory microenvironments, or niches, in the bone marrow or in the gut. In this review we discuss current concepts and information surrounding plasma cell survival niches, and consider two opposing models to explain long-term serologic immunity.

http://ift.tt/2eJ8BIs

Deficiency of Phosphatidylinositol 3-Kinase {delta} Signaling Leads to Diminished Numbers of Regulatory T Cells and Increased Neutrophil Activity Resulting in Mortality Due to Endotoxic Shock [INNATE IMMUNITY AND INFLAMMATION]

Despite decades of clinical and biomedical research, the pathogenesis of sepsis and its spectrum of diseases (severe sepsis and septic shock), which are leading causes of death in intensive care units, are still poorly understood. In this article, we show that signaling via the p110 isoform of PI3K is critical for survival in experimental sepsis. Mice with an inactive knock-in mutation in the p110 gene (p110^D910A) succumbed acutely to nonlethal dose LPS challenge. The susceptibility of p110^D910A mice to LPS was associated with increased neutrophil numbers and activities in the tissues, due in part to delayed apoptosis resulting mostly from inherent reduced regulatory T cell (Treg) numbers. Adoptive transfer of wild-type or p110^D910A Tregs abrogated exaggerated neutrophil activity, increased neutrophil apoptosis, and rescued p110^D910A mice from mortality after LPS challenge. We confirmed the clinical relevance of these findings by showing that human Tregs also regulate neutrophil function and survival. Collectively, our results show that PI3K is essential for survival during sepsis. In addition, our data highlight the importance of Tregs in regulating the pathogenesis of sepsis and septic shock via their effects on neutrophil survival and function, and provide evidence of regulation of innate immunity by cells of the adaptive immune system.

http://ift.tt/2eJ8cWs

Cutting Edge: Eosinophils Undergo Caspase-1-Mediated Pyroptosis in Response to Necrotic Liver Cells [CUTTING EDGE]

Many chronic liver disorders are characterized by dysregulated immune responses and hepatocyte death. We used an in vivo model to study the immune response to necrotic liver injury and found that necrotic liver cells induced eosinophil recruitment. Necrotic liver induced eosinophil IL-1β and IL-18 secretion, degranulation, and cell death. Caspase-1 inhibitors blocked all of these responses. Caspase-1–mediated cell death with accompanying cytokine release is the hallmark of a novel form of cell death termed pyroptosis. To confirm this response in a disease model, we isolated eosinophils from the livers of Schistosoma mansoni–infected mice. S. mansoni eggs lodge in the hepatic sinusoids of infected mice, resulting in hepatocyte death, inflammation, and progressive liver fibrosis. This response is typified by massive eosinophilia, and we were able to confirm pyroptosis in the infiltrating eosinophils. This demonstrated that pyroptosis is a cellular pathway used by eosinophils in response to large-scale hepatic cell death.

http://ift.tt/2gXWfgr

IFN-{gamma}-Expressing Th17 Cells Are Required for Development of Severe Ocular Surface Autoimmunity [MUCOSAL IMMUNOLOGY]

Th17 cells are critical effectors mediating the ocular surface autoimmunity in dry eye disease (DED). Increased IFN- has also been implicated in DED; however, it remains unclear to what extent Th1 cells contribute to DED pathogenesis. In this study, we investigated the cellular source of IFN- and assessed its contribution to corneal epitheliopathy in DED mice. We discovered a significant IL-17A⁺IFN-⁺ (Th17/1) population and determined that these cells are derived from Th17 precursors. Adoptive transfer of Th17/1, but not Th1, cells confers the disease to naive recipients as effectively as do Th17 cells alone. DED-induced IL-12 and IL-23 are required for in vivo transition of pathogenic Th17 cells to IFN- producers. Furthermore, using IFN-–deficient Th17 cells, we demonstrate the disease-amplifying role of Th17-derived IFN- in DED pathogenesis. These results clearly demonstrate that Th17 cells mediate ocular surface autoimmunity through both IL-17A and IFN-.

http://ift.tt/2eJ27t3

Activation of Human Basophils by A549 Lung Epithelial Cells Reveals a Novel IgE-Dependent Response Independent of Allergen [ALLERGY AND OTHER HYPERSENSITIVITIES]

Evidence for epithelial cell (EC)–derived cytokines (e.g., thymic stromal lymphopoietin [TSLP]) activating human basophils remains controversial. We therefore hypothesize that ECs can directly activate basophils via cell-to-cell interaction. Basophils in medium alone or with IL-3 ± anti-IgE were coincubated with TSLP, IL-33, or IL-25. Analogous experiments cocultured basophils (1–72 h) directly with EC lines. Supernatants were tested for mediators and cytokines. Abs targeting receptors were tested for neutralizing effects. Lactic acid (pH 3.9) treatment combined with passive sensitization tested the role of IgE. Overall, IL-33 augmented IL-13 secretion from basophils cotreated with IL-3, with minimal effects on histamine and IL-4. Conversely, basophils (but not mast cells) released histamine and marked levels of IL-4/IL-13 (10-fold) when cocultured with A549 EC and IL-3, without exogenous allergen or IgE cross-linking stimuli. The inability to detect IL-33 or TSLP, or to neutralize their activity, suggested a unique mode of basophil activation by A549 EC. Half-maximal rates for histamine (4 h) and IL-4 (5 h) secretion were slower than observed with standard IgE-dependent activation. Ig stripping combined with passive sensitization ± omalizumab showed a dependency for basophil-bound IgE, substantiated by a requirement for cell-to-cell contact, aggregation, and FcRI-dependent signaling. A yet unidentified IgE-binding lectin associated with A549 EC is implicated after discovering that LacNAc suppressed basophil activation in cocultures. These findings point to a lectin-dependent activation of basophil requiring IgE but independent of allergen or secreted cytokine. Pending further investigation, we predict this unique mode of activation is linked to inflammatory conditions whereby IgE-dependent activation of basophils occurs despite the absence of any known allergen.

http://ift.tt/2eIKV7d

Involvement of NK Cells in IL-28B-Mediated Immunity against Influenza Virus Infection [INNATE IMMUNITY AND INFLAMMATION]

IL-28B is a member of the newly discovered type III IFN family and exhibits unique antiviral properties compared with other family members. NK cells play a critical role in defending against viruses; however, little is known about the role of IL-28B in NK cell function. In a mouse model of influenza A virus (mouse adapted influenza A/PR/8/34 strain) infection, long-term overexpression of IL-28B induced by hepatocyte-specific gene delivery exerted a strong antiviral effect in the presence of NK cells. In IL-28B–overexpressing wild-type mice, the percentages and absolute numbers of NK cells in the spleen, liver, and lung were markedly increased, with higher proliferation and accelerated NK cell maturation based on phenotypes staining with CD11b and CD27 or CD11b and KLRG1. Furthermore, the effect of IL-28B on NK cells was macrophage dependent, as confirmed in an in vitro coculture assay and in in vivo macrophage- or alveolar macrophage–depletion experiments. Transwell studies demonstrated that CFSE-labeled NK cell proliferation was driven, in a dose-dependent manner, by unknown soluble factor(s) secreted by IL-28B–stimulated alveolar macrophages, without requiring direct cell–cell contact. An understanding of the NK cell–promoting features of IL-28B will facilitate future clinical application of this cytokine.

http://ift.tt/2eJ8jBm

TGF-{beta}1 Suppresses IL-33-Induced Mast Cell Function [ALLERGY AND OTHER HYPERSENSITIVITIES]

TGF-β1 is involved in many pathological conditions, including autoimmune disorders, cancer, and cardiovascular and allergic diseases. We have previously found that TGF-β1 can suppress IgE-mediated mast cell activation of human and mouse mast cells. IL-33 is a member of the IL-1 family capable of inducing mast cell responses and enhancing IgE-mediated activation. In this study, we investigated the effects of TGF-β on IL-33–mediated mast cell activation. Bone marrow–derived mast cells cultured in TGF-β1, β2, or β3 showed reduced IL-33–mediated production of TNF, IL-6, IL-13, and MCP-1 in a concentration-dependent manner. TGF-β1 inhibited IL-33–mediated Akt and ERK phosphorylation as well as NF-B– and AP-1–mediated transcription. These effects were functionally important, as TGF-β1 injection suppressed IL-33–induced systemic cytokines in vivo and inhibited IL-33–mediated cytokine release from human mast cells. TGF-β1 also suppressed the combined effects of IL-33 and IgE-mediated activation on mouse and human mast cells. The role of IL-33 in the pathogenesis of allergic diseases is incompletely understood. These findings, consistent with our previously reported effects of TGF-β1 on IgE-mediated activation, demonstrate that TGF-β1 can provide broad inhibitory signals to activated mast cells.

http://ift.tt/2gXXM5X

Aging Impairs Alveolar Macrophage Phagocytosis and Increases Influenza-Induced Mortality in Mice [INNATE IMMUNITY AND INFLAMMATION]

Influenza viral infections often lead to increased mortality in older people. However, the mechanisms by which aging impacts immunity to influenza lung infection remain unclear. We employed a murine model of influenza infection to identify these mechanisms. With aging, we found reduced numbers of alveolar macrophages, cells essential for lung homeostasis. We also determined that these macrophages are critical for influenza-induced mortality with aging. Furthermore, aging vastly alters the transcriptional profile and specifically downregulates cell cycling pathways in alveolar macrophages. Aging impairs the ability of alveolar macrophages to limit lung damage during influenza infection. Moreover, aging decreases alveolar macrophage phagocytosis of apoptotic neutrophils, downregulates the scavenging receptor CD204, and induces retention of neutrophils during influenza infection. Thus, aging induces defective phagocytosis by alveolar macrophages and increases lung damage. These findings indicate that therapies that enhance the function of alveolar macrophages may improve outcomes in older people infected with respiratory viruses.

http://ift.tt/2eIKMkb

Caveolin-1 Influences LFA-1 Redistribution upon TCR Stimulation in CD8 T Cells [ANTIGEN RECOGNITION AND RESPONSES]

TCR stimulation by peptide–MHC complexes on APCs requires precise reorganization of molecules into the area of cellular contact to form an immunological synapse from where T cell signaling is initiated. Caveolin (Cav)1, a widely expressed transmembrane protein, is involved in the regulation of membrane composition, cellular polarity and trafficking, and the organization of signal transduction pathways. The presence of Cav1 protein in T cells was identified only recently, and its function in this context is not well understood. We show that Cav1-knockout CD8 T cells have a reduction in membrane cholesterol and sphingomyelin, and upon TCR triggering they exhibit altered morphology and polarity, with reduced effector function compared with Cav1 wild-type CD8 T cells. In particular, redistribution of the β₂ integrin LFA-1 to the immunological synapse is compromised in Cav1-knockout T cells, as is the ability of LFA-1 to form high-avidity interactions with ICAM-1. Our results identify a role for Cav1 in membrane organization and β₂ integrin function in primary CD8 T cells.

http://ift.tt/2eJ8wo8

Suppression of Lipopolysaccharide-Induced Inflammatory Response by Fragments from Serum Amyloid A [INNATE IMMUNITY AND INFLAMMATION]

Serum amyloid A (SAA) is known as an acute-phase protein and a biomarker for inflammatory diseases. Published studies have shown that SAA possesses proinflammatory cytokine-like activity and is chemotactic for phagocytes, but the structural basis for these activities remains unidentified. In this article, we report that truncated SAA1 proteins lacking N- and C-terminal sequences exhibit reduced proinflammatory activity and strongly suppress LPS-induced expression of IL-1β, IL-6, and TNF-α in macrophages. A truncated SAA1 containing aa 11–58 was examined further and found to facilitate p38 MAPK phosphorylation while reducing LPS-stimulated phosphorylation of ERK and JNK. In LPS-challenged mice, aa 11–58 reduced the severity of acute lung injury, with significantly less neutrophil infiltration in the lungs and attenuated pulmonary expression of IL-1β, IL-6, and TNF-α. Coadministration of aa 11–58 markedly improved mouse survival in response to a lethal dose of LPS. A potent induction of IL-10 was observed in a TLR2-dependent, but TLR4-independent, manner in macrophages stimulated with aa 11–58. However, the aa 11–58 fragment of SAA1 was unable to induce chemotaxis or calcium flux through formyl peptide receptor 2. These results indicate that the N- and C-terminal sequences contain structural determinants for the proinflammatory and chemotactic activities of SAA1, and their removal switches SAA1 to an anti-inflammatory role. Given that proteolytic processing of SAA is associated with the pathological changes in several diseases, including secondary amyloidosis, our findings may shed light on the structure–function relationship of SAA1 with respect to its role in inflammation.

http://ift.tt/2eIqFCF

B Cell-Extrinsic Myd88 and Fcer1g Negatively Regulate Autoreactive and Normal B Cell Immune Responses [ANTIGEN RECOGNITION AND RESPONSES]

MyD88 and FcR common -chain (Fcer1g, FcR) elicit proinflammatory responses to exogenous Ags. Deletion of these receptors in autoimmune models has generally led to reduced overall disease. In B cells, Myd88 is required for anti-DNA and anti-RNA autoantibody responses, whereas Fcer1g is not expressed in these cells. The roles of these receptors in myeloid cells during B cell autoimmune activation remain less clear. To investigate the roles of Myd88 and Fcer1g in non-B cells, we transferred anti–self-IgG (rheumatoid factor) B cells and their physiologic target Ag, anti-chromatin Ab, into mice lacking Fcer1g, Myd88, or both and studied the extrafollicular plasmablast response. Surprisingly, we found a markedly higher and more prolonged response in the absence of either molecule; this effect was accentuated in doubly deficient recipients, with a 40-fold increase compared with wild-type recipients at day 10. This enhancement was dependent on CD40L, indicating that Myd88 and FcR, presumably on myeloid APCs, were required to downregulate T cell help for the extrafollicular response. To extend the generality, we then investigated a classic T cell–dependent response to (4-hydroxy-3-nitrophenyl)acetyl conjugated to chicken globulin and found a similar effect. Thus, these results reveal novel regulatory roles in the B cell response for receptors that are typically proinflammatory.

http://ift.tt/2gXBIbI

Structural and Mechanistic Implications of Rearrangement Frequencies within Human TCRBV Genes [MOLECULAR AND STRUCTURAL IMMUNOLOGY]

The T cell repertoire is a function of thymic V(D)J rearrangement and of peripheral selection. The mature repertoire embodies TCR sequences that are important for survival and can identify important structural aspects of the TCR. Analysis of the circulating TCRBV19 CD8 T cell repertoire showed that a majority of NDN-encoded CDR3 amino acid motifs start at CDR3 position four, well within the V region. Rearrangement at this position indicates that the DNA hairpin loop is not opened at the position adjacent to the recombination signal sequence, but rather is trimmed back three or more bases. In this article, we show that the rearrangement frequency distribution within the V region reveals selection on CDR3 position four. The selection is already established in single-positive CD8 thymocytes. Crystal structures reveal a possible basis for this selection due to the location of this residue in a bend that positions the remaining portion of CDR3 to interact with the peptide and MHC. Examination of other TCRBV families also shows selection for rearrangement within the V region of a number of genes and for CD8 and CD4 cells. The exact profile of rearrangement within the V region appears to be V gene specific. The frequent observation of side chains associated with turn motifs at CDR3 positions three and four fits with the structural need for a bend. The data are discussed in terms of the generation of a structural turn motif, the rearrangement mechanism, and selection of the repertoire on the peptide and MHC.

http://ift.tt/2eJ29Bb

On the Role IL-4/IL-13 Heteroreceptor Plays in Regulation of Type 1 Diabetes [AUTOIMMUNITY]

Type 1 diabetes (T1D) manifests when the insulin-producing pancreatic β cells are destroyed as a consequence of an inflammatory process initiated by lymphocytes of the immune system. The NOD mouse develops T1D spontaneously and serves as an animal model for human T1D. The IL-4Rα/IL-13Rα1 heteroreceptor (HR) serves both IL-4 and IL-13 cytokines, which are believed to function as anti-inflammatory cytokines in T1D. However, whether the HR provides a responsive element to environmental (i.e., physiologic) IL-4/IL-13 in the regulation of peripheral tolerance and the development of T1D has yet to be defined. In this study, NOD mice deficient for the HR have been generated by means of IL-13Rα1 gene disruption and used to determine whether such deficiency affects the development of T1D. Surprisingly, the findings indicate that NOD mice lacking the HR (13R^–/–) display resistance to T1D as the rise in blood glucose level and islet inflammation were significantly delayed in these HR-deficient relative to HR-sufficient (13R^+/+) mice. In fact, the frequency and spleen-to-pancreas dynamics of both Th1 and Th17 cells were affected in 13R^–/– mice. This is likely due to an increase in the frequency of mTGFβ⁺Foxp3^int regulatory T cells and the persistence of CD206⁺ macrophages in the pancreas as both types of cells confer resistance to T1D upon transfer to 13R^+/+ mice. These findings reveal new insights as to the role environmental IL-4/IL-13 and the HR play in peripheral tolerance and the development of T1D.

http://ift.tt/2eJ8vk4

CD36 and Platelet-Activating Factor Receptor Promote House Dust Mite Allergy Development [MUCOSAL IMMUNOLOGY]

Over 89% of asthmatic children in underdeveloped countries demonstrate sensitivity to house dust mites (HDMs). The allergic response to HDMs is partially mediated by epithelial cell–derived cytokines that activate group 2 innate lymphoid cells, induce migration and activation of dendritic cells, and promote effector differentiation of HDM-specific TH2 cells. However, the contribution of innate receptor engagement on epithelial or dendritic cells by HDMs that ultimately mediates said innate and adaptive allergic responses is poorly understood. We and other investigators have demonstrated that HDMs express phosphorylcholine (PC) moieties. The major PC receptors involved in immune responses include CD36 and platelet-activating factor receptor (PAFR). Because CD36 and PAFR are expressed by epithelial cells and dendritic cells, and expression of these receptors is higher in human asthmatics, we determined whether engagement of CD36 or PAFR on epithelial or dendritic cells contributes to HDM allergy development. Testing bone marrow chimeric mice revealed that CD36 engagement on radioresistant cells and PAFR engagement on radioresistant and radiosensitive cells in the lung promote allergic responses to HDMs. Additionally, passive anti–PC IgM Abs administered intratracheally with HDMs decreased allergen uptake by epithelial cells and APCs in the lungs of C57BL/6 mice but not CD36^–/– or PAFR^–/– mice. These results show that CD36 and PAFR are important mediators of HDM allergy development and that inhibiting HDM engagement with PC receptors in the lung protects against allergic airway disease.

http://ift.tt/2eJ23tj

IL-23 Limits the Production of IL-2 and Promotes Autoimmunity in Lupus [CLINICAL AND HUMAN IMMUNOLOGY]

The IL-23/IL-17 pathway is important in multiple autoimmune diseases, but its effect on lupus pathology remains unclear, with opposing trials in murine models of the disease. In this study, we show a disease activity–related upregulation of serum IL-23 and IL-23 receptor in patients with systemic lupus erythematosus (SLE) as compared with healthy controls. When added in SLE T cell in vitro cultures, IL-23 induced IL-17 and limited IL-2 production, whereas T follicular helper and double negative (DN) T cells significantly expanded. To further dissect the role of IL-23 in the expression of autoimmunity and related pathology, we generated IL-23 receptor–deficient MRL.lpr mice. These IL-23R^–/–MRL.lpr mice displayed attenuated lupus nephritis with a striking decrease in the accumulation of DN T cells in the kidneys and secondary lymphoid organs. Moreover, T cells from IL-23R^–/–MRL.lpr mice produced increased amounts of IL-2 and reduced amounts of IL-17 compared with T cells from wild type animals. In vitro IL-23 treatment promoted IL-17 production and downregulated IL-2 production. The IL-23R^–/–MRL.lpr had fewer T follicular helper cells, B cells, and plasma cells, leading to decreased production of anti-dsDNA Abs. Our results show that IL-23 accounts for the main aspects of human and murine lupus including the expansion of DN T cells, decreased IL-2, and increased IL-17 production. We propose that blockade of IL-23 should have a therapeutic value in patients with SLE.

http://ift.tt/2gXSfwh

Effects of deoxynivalenol (DON) and its microbial biotransformation product deepoxy-deoxynivalenol (DOM-1) on a trout, pig, mouse, and human cell line

Abstract

Deoxynivalenol (DON), a trichothecene produced by various Fusarium species, is one of the most prevalent food- and feed-associated mycotoxins. The effects of DON and deepoxy-deoxynivalenol (DOM-1) were assessed in five different cell lines from different tissues and species starting from the first line of defense, the trout gill (RTgill-W1) and pig intestinal cells (IPEC-1 and IPEC-J2) over immune cells, as second line of defense (mouse macrophages RAW 264.7) to human liver cells (HepG2). Viability was assessed with a WST-1 assay, except for RTgill-W1, where a neutral red (NR) and sulforhodamine B (SRB) assay was performed. Additionally, more sensitive parameters, such as interleukin-, nitric oxide (NO)-, and albumin-release were determined. Viability was affected by DON at concentrations starting at 10 μmol/L (RTgill-W1), 0.9 μmol/L (IPEC-1), 3.5 μmol/L (IPEC-J2), and 0.9 μmol/L (HepG2), whereas DOM-1 did not have such an effect. Additionally, NO was decreased (0.84 μmol/L DON), whereas interleukin (IL)-6 was increased (0.42 μmol/L DON) in lipopolysaccharide (LPS)-stimulated DON-, but not DOM-1-treated RAW cells. Tumor necrosis factor (TNF)-α release, however, was not affected. Interestingly, albumin secretion of HepG2 cells was decreased by both DON and DOM-1 but at a much higher concentration for DOM-1 (228 versus 0.9 μmol/L for DON). 98.9% of DOM-1 was retrieved by liquid chromatography tandem mass spectrometry at the end of the experiment, proving its stability. In this study, IL-6 was the most sensitive parameter, followed by NO and albumin release and viability for HepG2 and IPEC-1.

http://ift.tt/2uQNF8I

Tips on Finding a Reputable Plastic Surgeon for Patient Referral

Drs Granick and Lee share their personal views on becoming plastic surgeons and offer resources on where to find reputable ones for patient referrals.
Medscape Plastic Surgery

http://ift.tt/2uizdDH

Protective antibodies against HSP60 for autoimmune inflammatory diseases

Publication date: Available online 24 July 2017
Source:Clinical Immunology
Author(s): Rina Ulmansky, Yaakov Naparstek




http://ift.tt/2vC7myS

Radiological Evaluation of Cochlear Orientation and Its Implications in Cochlear Implantation

Abstract

To test whether there are variations in cochlear orientation with respect to age and sex, and its relevance in cochlear implant surgery. Implant otologists rely upon the anatomic landmarks including the facial recess and round window niche and round window membrane for accessibility and placement of electrode array into scala tympani of basal turn of cochlea. Anecdotally, surgeons note variations in cochlear orientation with respect to age. Cochlear orientation studied radiologically by pre-operative CT scan of temporal bone can guide a Surgeon's approach to cochlear implantation. To investigate the changes in cochlear orientation with respect to age and sex; and its relevance in cochlear implantation. A retrospective analytical study was performed on CT scans of temporal bones in patients (of our hospital from July 2013 to January 2015 i.e. for a period of 18 months) with no congenital or radiological abnormalities of cochlea. The basal turn angulations of cochlea varied with age and majority of change occurred during early age. The basal turn angulations of cochlea in difficult situations during cochlear implantation were correlated with the data. There is a significant variation in cochlear orientation as measured radiologically by basal turn angulations relative to midsagittal plane. The more obtuse and acute basal turn angulations have implications like difficulty in cochleostomy and electrode placement during cochlear implantation.

http://ift.tt/2eImarH

Normal carboxyhaemoglobin level in carbon monoxide poisoning treated with hyperbaric oxygen therapy

Throughout the world both intentional and inadvertent exposure to carbon monoxide (CO) remains an important public health issue. While CO poisoning can be lethal, the morbidity is predominantly due to nervous system injury. A previously healthy 22-year-old woman was found unconscious at home by her sister. Her parents were found dead in the house with a recent history of a dysfunctional furnace. She was presumed to have CO poisoning despite an initial carboxyhaemoglobin level of 2.5%. Patient had both clinical and radiological evidence of neurological damage. However, with multiple sessions of hyperbaric oxygen (HBO) therapy she recovered to a near normal functional status. There is no consensus that exists among treating physicians about the role of hyperbaric oxygen in management of neurological injury. The case described here has significant neurological damage related to CO exposure but improved after HBO therapy.

http://ift.tt/2uQK36e

Case of a strangulated right paraduodenal fossa hernia in a malrotated gut

We report an unusual case of a strangulated internal hernia resulting from a right paraduodenal fossa hernia (PDH) in the context of bowel malrotation. There are few documented cases of PDHs associated with a concomitant gut malrotation. Emergency laparotomy was performed based on clinical and radiological. Intraoperatively, the proximal jejunum was seen to enter a hernia sac formed by an aberrant duodenojejunal flexure located to the right of the aorta. This was presumed to be a strangulated internal hernia of the paraduodenal recess in a malrotated gut. The hernia neck was widened and the sac obliterated to allow reduction of the contents. On reduction and warming, the insulted small bowel appeared viable and returned to the abdominal cavity without resection.

http://ift.tt/2usDrZz

Silent tracheobronchial chondritis in a patient with a delayed diagnosis of relapsing polychondritis

Relapsing polychondritis is a very rare autoimmune disease characterised by a relapsing inflammation of hyaline, elastic and fibrous cartilaginous tissues. The incidence is estimated to be between 3.5 and 4.5 per million people per year. Clinical signs and symptoms can be very subtle, and if left undiagnosed for a prolonged period, airway involvement can cause fibrosis of the tracheobronchial wall, leading to a fixed tracheobronchial stenosis. Eventually, this can progress to life-threatening tracheobronchomalacia due to irreversible damage and loss of tissue integrity. We report an elderly man who presented with recurrent bilateral ear inflammation and intermittent polyarthritis who was diagnosed with relapsing polychondritis with asymptomatic involvement of his large airways.

http://ift.tt/2uRaiJP

Loculated empyema due to tuberculosis in a child

A 9-year-old girl from black ethnic origin presented with a history of fever, cough, loss of weight and right-sided chest wall pain for 2 weeks. Chest X-ray demonstrated an effusion, which was shown to be loculated on chest CT scan. She was not responding to medical treatment and at thoracotomy loculated pus was drained. Mycobacterium tuberculosis (TB) was cultured from the pus. TB is a rare cause of loculated empyema with an overlapping clinical and radiological picture with pyogenic infections.

http://ift.tt/2usB8WC

Unusual genitourinary tract activity

A 23-year-old woman presented to the emergency department after manually inserting foreign bodies into the urinary bladder through her urethra. A plain abdominal film of the kidneys, ureters and bladder confirmed three radio-opaque densities in the urinary bladder. She was taken to the operating room where cystourethroscopy was performed. At cystoscopy 2 'corn-on-the-cob' skewers and 1 battery were identified but were too large to be retrieved safely with a grasper through the protective sheath. The objects were grasped with a 'sponge-holding forceps' (placed alongside the cystoscope) and extracted one at a time. A psychiatric consultation was sought and the patient was diagnosed and treated for borderline personality disorder. Unusual genitourinary activity (UGUA) has been described for several centuries and is characterised by the deposition of foreign objects in the genitalia.¹ The most common incentive for UGUA is sexual stimulation, but psychiatric disorders and intoxication are also associated.² Management involves retrieval of foreign bodies and evaluation of psychosocial factors.

http://ift.tt/2uQR0Eu

Posterior meningeal artery DMSO injection resulting in reproducible asystole prior to Onyx therapy of a dural arteriovenous fistula: a previously undescribed variant of the trigeminocardiac reflex or a new phenomenon?

We describe a case of reproducible asystole during endovascular treatment of a posterior fossa dural arteriovenous fistula. Catheterisation of the posterior meningeal artery, a branch of the vertebral artery in this patient, followed by dimethyl sulfoxide injection prior to Onyx administration resulted in two episodes of asystole.

To the best of our knowledge, this is the first reported case of asystole occurring during endovascular intervention in the posterior meningeal artery. This may represent a previously undescribed variant of the trigemino-cardiac reflex (TGCR) caused by chemical stimulation of small areas of trigeminally innervated posterior fossa dura. Alternatively, this may represent a newly identified phenomenon with chemical stimulation of regions of posterior fossa dura innervated by branches of the vagus nerve leading to increased parasympathetic activity and resultant asystole.

In either case, it is important to recognise the potential for such episodes in this vascular territory to allow case planning and management.

http://ift.tt/2usGWzn

Dengue fever presenting as cauda equina syndrome

Description

Dengue is an arboviral disease transmitted by Aedes sp. mosquitoes. A wide spectrum of illness is observed, ranging from dengue fever to dengue shock syndrome. The common neurological complications noted are encephalitis and encephalopathy. Haemorrhagic complications due to thrombocytopenia can result in various neurological sequelae.1 We report a case of dengue fever with spontaneous spinal hematoma presenting as cauda equina syndrome.

A 47-year-old man presented with moderate grade fever and arthralgia for 5 days. On day 6 of illness, he got admitted with complaints of lower backache, urinary retention, bilateral lower limb weakness and numbness below ankle. This was followed by reduced perianal sensations. On clinical examination, the patient was found to have MRC grade 4/5 power in extensor hallucis longus and ankle plantar flexors. The ankle reflexes were absent bilaterally with other deep tendon reflexes being normal. Babinski reflex was negative. The patient had...

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Efficacy of new low-dose oral anticoagulants in recalcitrant livedoid vasculopathy

Livedoid vasculopathy (LV) is a thrombotic skin disease characterised by recurrent painful ulcerations and irreversible scar formation on the lower legs, which is caused by occlusion of the cutaneous microcirculation. Edoxaban is one of new oral anticoagulants. It directly inhibits factor Xa in the coagulation pathway and prevents thrombus formation. A 17-year-old Japanese male presented with a 1-year history of recalcitrant cutaneous ulcers and livedo racemosa on his lower extremities. Initially, the ulcers were treated with antiplatelets therapies; however, he experienced recurrence of ulcerations during summer time. A histological examination revealed dermal vessel thrombosis consistent with occlusive vasculopathy. These findings were diagnostic for LV. The patient was treated with oral low-dose edoxaban (15 mg/day). The skin ulcers were epithelised and livedo racemosa disappeared within 8 weeks. We herein report the successful treatment of recalcitrant LV with low-dose edoxaban in a patient with no identifiable coagulopathy.

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Radiological Evaluation of Cochlear Orientation and Its Implications in Cochlear Implantation

Abstract

To test whether there are variations in cochlear orientation with respect to age and sex, and its relevance in cochlear implant surgery. Implant otologists rely upon the anatomic landmarks including the facial recess and round window niche and round window membrane for accessibility and placement of electrode array into scala tympani of basal turn of cochlea. Anecdotally, surgeons note variations in cochlear orientation with respect to age. Cochlear orientation studied radiologically by pre-operative CT scan of temporal bone can guide a Surgeon's approach to cochlear implantation. To investigate the changes in cochlear orientation with respect to age and sex; and its relevance in cochlear implantation. A retrospective analytical study was performed on CT scans of temporal bones in patients (of our hospital from July 2013 to January 2015 i.e. for a period of 18 months) with no congenital or radiological abnormalities of cochlea. The basal turn angulations of cochlea varied with age and majority of change occurred during early age. The basal turn angulations of cochlea in difficult situations during cochlear implantation were correlated with the data. There is a significant variation in cochlear orientation as measured radiologically by basal turn angulations relative to midsagittal plane. The more obtuse and acute basal turn angulations have implications like difficulty in cochleostomy and electrode placement during cochlear implantation.

http://ift.tt/2eImarH

Effects of Combined Surgery on Obstructive Sleep Apnea in Obese Patients: an Open-label Randomized Controlled Clinical Trial

Condition:   To Compare the Difference of AHI Variation Between LSG and Combined Surgery
Interventions:   Procedure: Laparoscopic sleeve gastrectomy（LSG）;   Procedure: Uvulopalatopharyngoplasty(UPPP) and Adenoidectomy/Tonsillectomy
Sponsor:   Bing Wang
Not yet recruiting - verified July 2017

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New Modalities for Detection of Oropharyngeal Cancer

Conditions:   Human Papillomavirus Positive Oropharyngeal Squamous Cell Carcinoma;   Oropharynx Cancer;   Base of Tongue Carcinoma;   Tonsil Cancer
Interventions:   Device: Transcervical Oropharyngeal Ultrasound;   Procedure: Oral Rinse Collection;   Procedure: Blood Draw
Sponsors:   Vanderbilt University Medical Center;   American Cancer Society, Inc.
Recruiting - verified July 2017

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Nivolumab in Recurrent and/or Metastatic SCCHN

Condition:   Recurrent and/or Metastatic Platinum-refractory SCCHN
Intervention:   Drug: Nivolumab Injection
Sponsors:   UNICANCER;   Bristol-Myers Squibb
Not yet recruiting - verified July 2017

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Cricopharyngeal Dysfunction and Esophageal Diverticulum

Conditions:   Zenker's Esophageal Diverticulum;   Cricopharyngeal Dysfunction;   Progressive Dysphagia
Intervention:   Other: open, transcervical versus rigid endoscopic treatment
Sponsor:   University of Cincinnati
Recruiting - verified July 2017

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Paediatric chest wall trauma causing delayed presentation of ventricular arrhythmia

This report describes a paediatric patient presenting with haemodynamically stable non-sustained ventricular tachycardia 1 day after minor blunt chest trauma. Initial laboratory studies, chest X-ray and echocardiography were normal; however, cardiac MRI revealed precordial haematoma, myocardial contusion and small pericardial effusion. Throughout her hospital course, she remained asymptomatic aside from frequent couplets and triplets of premature ventricular contractions. Ectopy was controlled with oral verapamil. This case highlights how significant cardiac injury may be missed with standard diagnostic algorithms.

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An unusual presentation of a benign pancreatic lesion containing amyloid

We present a unique case of a benign pancreatic lesion which was positive for amyloid in a 55-year-old female patient without systemic amyloidosis. Further testing revealed islet-type amyloid polypeptide (or amylin), a protein found in various diseases such as diabetes, insulinoma and pancreatic adenocarcinoma—none of which was seen in our patient.

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Lipoma of superior vena cava: a rare occurrence

Most benign primary cardiac tumours are myxomas; non-myxomatous tumours are less common but comprise a wide variety. Cardiac lipoma is a rare non-myxomatous variety. A 70-year-old Caucasian woman with right breast cancer status postpartial mastectomy underwent surveillance MRI of the breast and was found to have a possible right atrial (RA) mass. She also reported frequent headaches and palpitations. She underwent a transoesophageal echocardiogram which showed a 2.6x1.6x1.6 cm echogenic mass at the superior vena cava (SVC) and RA junction. She was anticoagulated for a possible thrombus without resolution. Surgical excision was undertaken in view of ongoing symptoms and partial occlusion of the SVC. Intraoperatively, a 2–3 cm smoothly textured lobulated mass was found and histopathology showed adipose tissue consistent with lipoma. The postoperative course was uneventful, and the patient was discharged in stable condition.

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Benign paroxysmal positional vertigo (BPPV) diagnosis and treatment in an elite professional football (soccer) player

A 33-year-old male professional football player suffered from acute-onset dizziness following a lower limb soft tissue treatment in prone lying. Symptoms included spinning vertigo lasting for 30's, headache, visual vertigo and disorientation. Clinical examination of balance and vestibular systems confirmed a left posterior canalithiasis benign paroxysmal positional vertigo (BPPV) and excluded other central and peripheral causes of dizziness. Two cycles of a left Epley manoeuvre were performed. An Epley manoeuvre abolished the BPPV and negated the need for medication. The player was able to return to play without dizziness within 24 hours completely symptom free. BPPV can be successfully identified and treated in elite football players and they can see a return to training and games within 24 hours. There are no epidemiology studies for this group of elite athletes either male or female despite increased occupational risk factors.

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Q fever prosthetic joint infection

Coxiella burnetii is the causative pathogen of the zoonotic infection Q fever. Most patients with Q fever experience a non-specific febrile illness, hepatitis or pneumonia. Q fever has recently been described as a cause of prosthetic joint septic arthritis, but remains very uncommonly reported. We present a case of Q fever prosthetic joint septic arthritis that has responded to a combination of two-stage surgical exchange and prolonged medical treatment with doxycycline and hydroxychloroquine.

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Soft tissue laceration caused by lower extremity intraosseous access insertion in an obese patient

Description

Intravenous access placement in the obese could be challenging due to unreliable anatomical landmarks and impact overall care. Intraosseous (IO) access remains a quick and reliable alternative to emergent intravenous access.1 2 The adult IO demonstrates an excellent safety profile with serious complications, such as compartment syndrome, osteomyelitis and skin abscesses, occurring in less than 1% of insertions.3

An 85-year-old woman presented with septic shock due to lobar pneumonia. Physical examination revealed a dehydrated, hypotensive, morbidly obese woman with anasarca and lower extremity lymphoedema. After several failed peripheral intravenous access attempts, IO access was achieved using the Arrow® EZ-IO® system, 2 cm distal and slightly medial to the tibial tuberosity in the right lower extremity during first attempt by an experienced emergencist without difficulties. The IO needle length was 45 mm and its gauge 15 Ga. EZ-IO® stabiliser dressing was not used during placement. IO...

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Importance of temporal changes in myocardial strain in Takotsubo cardiomyopathy

Strain imaging is a sensitive marker of myocardial dysfunction and may be underused in Takotsubo cardiomyopathy (TC). We present a case of biventricular TC in which early improvement in left ventricular longitudinal strain predated subsequent improvement in ejection fraction. Early temporal patterns of strain of the left and right ventricles have not previously been described in TC. Our case illustrates how strain can be a sensitive marker for myocardial dysfunction and recovery in TC. Increased use of strain in TC may have further implications on prognosis and management.

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Apical ballooning (takotsubo) syndrome with concurrent ST-segment elevation myocardial infarction

We present the case of a 61-year-old woman admitted with chest pain and an ECG demonstrating ST-segment elevation in the lateral leads. Emergency coronary angiography demonstrated an occluded obtuse marginal branch. Percutaneous intervention was unsuccessful as the lesion could not be crossed with a wire. Left ventriculography and transthoracic echocardiography demonstrated hypokinesis of the entire apex but preserved contractility of the basal segments, consistent with a diagnosis of apical ballooning syndrome (ABS). Cardiac MRI demonstrated myocardial oedema in all mid to apical segments, with a left ventricular ejection fraction (LVEF) of 38%. Repeat study at 5 months demonstrated an infarct in the distribution of the occluded artery with late gadolinium enhancement, consistent with a diagnosis of a lateral wall myocardial infarction and an improvement in the LVEF to 51%. The case illustrates the novel observation that ABS and acute myocardial infarction may rarely occur simultaneously.

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Atypical presentation of Parsonage-Turner syndrome confounded by surgical rotator cuff injury

Parsonage-Turner syndrome (PTS) is a rare neuropathy that commonly presents as unexpected severe shoulder and arm pain that eventually subsides while weakness or paralysis ensues. During exceptions to this classic presentation, confirming PTS can be challenging. Alternative causes of upper extremity pain may confound the diagnostic algorithm. Moreover, objective findings from necessary diagnostic tests depend on when those tests are performed. We present an atypical onset of PTS, whereby the initial presentation of severe neuropathic pain was preceded by mild shoulder pain that should decrease one's clinical suspicion for PTS. This milder pain coincided with the presence of a rotator cuff injury, whereby surgical intervention preceded impending paralysis and hindered postoperative rehabilitation. Physicians should be aware of the possibility of atypical presentations of PTS in hopes of avoiding either untimely surgery or delays in diagnosis.

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Primary bilateral adrenal nodular disease with Cushing's syndrome: varying aetiology

Primary adrenal disorders contribute 20%â"30% of patients with endogenous Cushing's syndrome. Most of the primary adrenal diseases are unilateral and include adenoma and adrenocortical carcinoma, whereas bilateral adrenal lesions are uncommon and include primary pigmented nodular adrenocortical disease, primary bilateral macronodular adrenocortical hyperplasia, isolated micronodular adrenocortical disease, bilateral adenomas or carcinomas, and rarely pituitary adrenocorticotropic hormone-dependent adrenal nodular disease. Cyclic adenosine monophosphate-dependent protein kinase A signalling is the major activator of cortisol secretion in primary adrenal nodular disorders. We report two cases of bilateral adrenal nodular disease with endogenous Cushing's syndrome, including one each of primary pigmented nodular adrenocortical disease and primary bilateral macronodular adrenocortical hyperplasia.

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A rare case of fatal meningoencephalitis with septic thromboembolism due to otitis media: a forensic case and review of literature

Description

Meningitis is an inflammatory syndrome involving the meninges, and it manifests with headache and stiff neck. On the contrary, encephalitis refers to the inflammation of the brain parenchyma. The causative pathogens can be manifold though, except for immunocompromised patients; in literature, there are no cases of meningoencephalitis caused by bacteria usually present in the bowel.

We report the case of a 40-year-old man. Following an earache, the man went to the hospital. In anamnesis, the man reported a chronic otitis media for many years, and clinicians, noting auricular bleeding, advised local antibiotic treatment. The next day, he had fever, treated with paracetamol. After 3 days, following the worsening of the clinical condition, the man returned to the hospital where physicians detected temporal and spatial disorientation, neck stiffness and fever of 39.5°C. Despite medical therapy, the man died after a few hours. An autopsy was performed. It showed an abscess...

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Awakening with amantadine from a persistent vegetative state after subarachnoid haemorrhage

We report the case of a 36-year-old woman with a subarachnoid haemorrhage (SAH) caused by a rupture of a right-sided middle cerebral artery aneurysm and subsequent malignant infarction of the right hemisphere leading to a persistent vegetative state and severe spastic tetraparesis with recurrent myocloni. Nine months after disease onset, the patient was transferred to our department for diagnostic and therapeutic re-evaluation. The poor clinical condition could not be explained by the brain lesion caused by the SAH or infarction. Moreover, glucose metabolism was normal in brain regions not affected by SAH and infarction as shown by positron emission tomography with ¹⁸F-fluorodeoxyglucose. We terminated baclofen and reduced antiepileptics known to impair vigilance and cognitive functions. However, only after starting amantadine treatment we observed a stunning awakening of the patient fully orientated within days. Our findings warrant trials to investigate amantadine in the treatment of unresponsive wakefulness syndromes due to acute central nervous system diseases.

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An unusual case of interstitial lung disease in a patient with cardiopulmonary syndrome as the initial presentation of Erdheim-Chester disease

Erdheim-Chester disease (ECD) is a very rare disorder with only approximately 600 cases reported in the literature. ECD has been recently reclassified as a histiocytic dendritic cell neoplasm. The clinical spectrum ranges from asymptomatic tissue accumulation of histiocytes to invasive tissue infiltration, which can cause fulminant multisystem failure. It typically presents with bone pain and constitutional symptoms. Extraosseous manifestations are not uncommon. ECD-associated interstitial lung disease has been described in 20%-35% of patients. Diagnosis is primarily by tissue biopsy and immunohistochemistry showing xanthogranulomas composed of foamy histiocytes that stain positive for CD68, CD14 and CD163 and negative for CD1á and langerin. We report a case of ECD in a young man with cardiopulmonary involvement who presented with haemoptysis and dyspnoea.

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Klippel-Trenaunay syndrome: diagnosis in a neonate

Description

A male newborn was evaluated due to a port-wine stain. Mother, 40 years old, father and brother were healthy. Gestation was uneventful. Amniocentesis revealed a normal male karyotype. A caesarean delivery was performed at 38 weeks. First physical examination showed a port-wine stain affecting the abdomen, back and left limb (figure 1) and hypertrophy of the affected limb. A biopsy was performed and histological findings revealed capillary malformations. Therefore, a Klippel-Trenaunay syndrome was diagnosed. Abdominal and lower limb doppler ultrasound and brain MRI excluded other vascular abnormalities. He was followed by a multidisciplinary team. At 9 months, there was a slight difference in the length of legs and the circumference of thighs (figure 2).

Figure 1

A port-stain affecting the abdomen and left limb at first physical examination of the neonate.

Figure 2

Appearance of the...

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Reconstruction of urethra using appendix in a patient with cloacal malformation

We report a case of 21-year-old young woman with congenital cloacal malformation. She was operated at the age of 1.5 years separating the rectum from common opening as a two-stage repair. She was incontinent in the earlier part of her life but she became continent to some extent later in early adulthood. She presented with urinary stress incontinence following delivery of dead fetus of 6 months. She underwent multiple investigations revealing common opening of bladder neck and vagina. A multidisciplinary evaluation was done and she underwent closure of common channel and neourethra reconstruction using pedicled appendix. Patient was continent and voiding by herself on discharge.

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Trans-scaphoid perilunate fracture dislocation: 'notjust a scaphoid fracture

Description

Perilunate dislocations are uncommon high-energy injuries which are missed in approximately 25% of cases on initial presentation.1 We present the X-rays of a 25-year-old man who fell from a height of approximately 2 metres onto an extended wrist. Plain radiographs (figure 1) show classical signs of a trans-scaphoid perilunate fracture dislocation. Pre-reduction, he had median nerve symptoms which settled with reduction and elevation. Reduction was performed in the emergency department with analgesia/sedation.

Figure 1

Posteroanterior and lateral pre-reduction radiographs of the wrist.

The sequence of events in this injury is well described: (1) the force begins radially and passes through the scaphoid causing it to fracture; (2) the force is transmitted ulnarly through the lunocapitate interval, and the lunate projects through the space of Poirier (between the intercarpal ligaments volar to the bones); (3) the distal portion...

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Patient-reported outcome measures (PROMs): enhancing decision making and follow-up

A case presentation of patient undergoing elective total knee replacement. Patient-reported outcome measures prospectively collected electronically pre and postoperatively allowed real-time review, aiding follow-up and reducing the need for clinical, face-to-face follow-up.

http://ift.tt/2v01Rge

Angioscopic observation of an atherosclerotic coronary aneurysm without yellow plaque

Description

A-58-year-old man with diabetes mellitus was admitted to our hospital with angina following physical effort. Coronary CT angiography (CCTA) revealed a saccular coronary aneurysm at the left main trunk bifurcation and a significant stenosis at the middle portion of the calcified left anterior descending artery (LAD) (figure 1). Invasive coronary angiography showed a large coronary aneurysm (12.3x11.0 mm) arising from the ostial LAD and stenoses in the middle of the LAD and in the middle of the left circumflex artery (figure 2). Intravascular ultrasound showed a severely calcified LAD, as shown on CCTA; however, it failed to reveal the entire picture with regard to the aneurysm because of the limited echo depth. Non-obstructive angioscopy (NOA)1 was performed to investigate the intimal injury of the aneurysm and demonstrated a rough, salmon-pink coloured surface without the presence of thrombus or atheromatous yellow plaque

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Silicone implant incompatibility syndrome (SIIS) in a 57-year-old woman with unilateral silicone breast implant

Since the 1960s, silicone implants have been used for breast augmentations, both cosmetically and in reconstructive surgery. Tissue exposed to silicone can react with multiple adverse advents. Autoimmune/inflammatory syndrome induced by adjuvants due to silicone exposure from ruptured silicone implants can lead to different interstitial lung manifestations predominantly with granuloma evolvement, leading to the so-called silicone implant incompatibility syndrome (SIIS). This case describes a 57-year-old woman with multiple lung infiltrations and a left-sided breast implant. The implant had been replaced twice, once due to implant rupture 36 years ago. The nodular infiltrates could not be related to infection, malignancy, interstitial lung disease, vasculitis or connective tissue disorder, and it was concluded that the nodular infiltrations were of inflammatory origin due to an autoimmune response secondary to the silicone implants (SIIS). After explantation, the patient's symptoms subsided and her physical condition has remarkably improved.

http://ift.tt/2v02WVw

Antibody reactivity against Helicobacter pylori proteins in a sample of the Spanish adult population in 2008-2013

Abstract

Background

Differences in Helicobacter pylori protein expression have been related to the risk of severe gastric diseases. In Spain, a marked geographic pattern in gastric cancer mortality has long been reported. Objective: To characterize antibody reactivity patterns against 16 H. pylori proteins, by age, sex, and region of birth, in a large sample of the Spanish adult population.

Materials and Methods

Antibody reactivity was quantified by H. pylori multiplex serology in a sample from the control group of the multicase-control study MCC-Spain. For this analysis, 2555 population-based controls were included. Each participant was classified as seropositive or seronegative for each protein according to specific cutoffs. Overall H. pylori seroprevalence was defined as positivity against ≥4 proteins. Descriptive analyses by age, sex, and region of birth were performed for both seroprevalence and seroreactivity (continuous measure). Differences among groups were tested by logistic and linear regression models.

Results

Overall H. pylori seroprevalence increased with age in both sexes. For ages 55-74, seroprevalence was lower in women than in men (84% vs 92%, P<.001). Region of birth explained 7% of the variability in seroprevalence. Among H. pylori seropositive subjects, proteins with the highest seroprevalence were GroEL, NapA, HP231, and Omp. Seropositivity for most of the proteins increased or remained stable with age, rising mainly for CagA, GroEL, and HyuA in women. A clear cohort effect was not observed.

Conclusions

This is the first study to describe the antibody patterns against 16 H. pylori proteins in the Spanish population. We found variability in the H. pylori antibody profiles according to both individual factors such as age and sex, and environmental factors such as the region of birth. The slightness of the reduction in seropositivity with decreasing age highlights the ongoing importance of this infection.

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Odontogenic Fungal Maxillary Sinusitis: A Case Report of a Displaced Dental Foreign Body

Abstract

Odontogenic etiology accounts for 10–12% of cases of maxillary sinusitis. Although uncommon, direct spread of dental infections into the maxillary sinus is possible due to the close relationship of the maxillary posterior teeth to the maxillary sinus. An odontogenic infection is a polymicrobial aerobic–anaerobic infection, with anaerobes out numbering the aerobes. Diagnosis requires a thorough dental and clinical evaluation, including radiographs. Management of sinus disease of odontogenic origin often requires medical treatment with appropriate antibiotics, surgical drainage when indicated, and treatment to remove the offending dental etiology. A 35-year-old, non-smoking woman visited our clinic, with a history of 6 months of facial pain, purulent nose discharge, and a foul taste in her mouth. The patient was otherwise healthy. Nasal endoscopy showed purulent discharge coming from the left middle meatus with a congested nasal mucosa and with a past history of dental treatments. CT PNS showed fractured free floating and an impacted foreign body through the premolar tooth and a right maxillary polyp with evidence of similar dental procedure done bilaterally. Functional endoscopic sinus surgery with extraction of the affected tooth and closure of oroantral fistula was done. The association between an odontogenic condition and maxillary sinusitis requires a thorough dental examination of patients with sinusitis. Concomitant management of the dental origin and the associated sinusitis will ensure complete resolution of the infection and may prevent recurrences and complications. A combination of a medical and surgical approach is generally required for the treatment of odontogenic sinusitis. An endoscopic shaver-assisted approach to is a reliable, minimally invasive method associated with less morbidity and lower incidence of complications.

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Ruptured Retinal Arterial Macroaneurysm Secondary to Toxoplasmic Kyrieleis Arteriolitis: A Case Report

Purpose: The aim of this report was to describe multimodal ocular imaging findings in a patient who presented with a ruptured retinal arterial macroaneurysm (RAM) associated with toxoplasmic Kyrieleis arteriolitis. Methods: We report the case of a 64-year-old man with a history of systemic hypertension and dense amblyopia of the left eye who presented with decreased vision and new floaters in the left eye. Color fundus photography, spectral-domain optical coherence tomography, fluorescein angiography, and indocyanine green angiography were used as diagnostic imaging tools. Results: No signs of hypertensive retinopathy were noted in the right eye. Multiple chorioretinal scars characteristic of previous toxoplasmosis were revealed in the left eye, with one covering most of the macula. Periarterial plaques or Kyrieleis arteriolitis were observed in retinal arteries surrounding the toxoplasmic retinal scars. Multiple RAMs were observed in these vessels, one of which was acutely ruptured. A perivenular plaque associated with a chronic branch retinal vein occlusion (BRVO) was noted along the same arcade at the arteriovenous crossing. Conclusion: RAM formation and BRVO can present as possible long-term complications of toxoplasmic Kyrieleis arteriolitis. This is the first reported case demonstrating an association between toxoplasmic Kyrieleis arteriolitis and RAM formation.
Case Rep Ophthalmol 2017;8:390–395

http://ift.tt/2uZVB8r

Odontogenic Fungal Maxillary Sinusitis: A Case Report of a Displaced Dental Foreign Body

Abstract

Odontogenic etiology accounts for 10–12% of cases of maxillary sinusitis. Although uncommon, direct spread of dental infections into the maxillary sinus is possible due to the close relationship of the maxillary posterior teeth to the maxillary sinus. An odontogenic infection is a polymicrobial aerobic–anaerobic infection, with anaerobes out numbering the aerobes. Diagnosis requires a thorough dental and clinical evaluation, including radiographs. Management of sinus disease of odontogenic origin often requires medical treatment with appropriate antibiotics, surgical drainage when indicated, and treatment to remove the offending dental etiology. A 35-year-old, non-smoking woman visited our clinic, with a history of 6 months of facial pain, purulent nose discharge, and a foul taste in her mouth. The patient was otherwise healthy. Nasal endoscopy showed purulent discharge coming from the left middle meatus with a congested nasal mucosa and with a past history of dental treatments. CT PNS showed fractured free floating and an impacted foreign body through the premolar tooth and a right maxillary polyp with evidence of similar dental procedure done bilaterally. Functional endoscopic sinus surgery with extraction of the affected tooth and closure of oroantral fistula was done. The association between an odontogenic condition and maxillary sinusitis requires a thorough dental examination of patients with sinusitis. Concomitant management of the dental origin and the associated sinusitis will ensure complete resolution of the infection and may prevent recurrences and complications. A combination of a medical and surgical approach is generally required for the treatment of odontogenic sinusitis. An endoscopic shaver-assisted approach to is a reliable, minimally invasive method associated with less morbidity and lower incidence of complications.

http://ift.tt/2vSa824

Development of paradoxical inflammatory disorders during treatment of psoriasis with TNF inhibitors: a review of published cases

Abstract

Background

TNF inhibitors have proven to be effective and relatively safe in the management of psoriasis. While infections and certain malignancies are established as acknowledged side effects, paradoxical inflammatory, non-neoplastic, noninfectious adverse events are being recognized less frequently. We aimed to identify published, peer-reviewed cases of paradoxical inflammatory, non-neoplastic, noninfectious adverse events in psoriasis patients during TNF inhibitor therapy.

Methods

A literature search in MEDLINE was performed for articles published from inception through the 8th of June 2016 that reported suspected incidents fulfilling a predefined search strategy. In addition, articles identified by reference lists were added.

Results

A total of 295 cases from various organ systems among 13 269 patients were identified: 91 cases were related to infliximab, 101 cases were related to etanercept, and 102 cases were related to adalimumab. One case report was related to both etanercept and adalimumab.

Conclusion

Induction of paradoxical non-neoplastic noninflammatory adverse events in psoriasis patients treated with a TNF inhibitor is worth recognizing. The amount of cases identified by this study suggests that continuous surveillance and research into these adverse effects is relevant. Nondermatologic paradoxical inflammatory reactions may be underreported.

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Skin manifestations are common and associated with a higher prevalence of congenital abnormalities in Zika virus infection

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Geographical foci and epidemiological changes of pemphigus vulgaris in four decades in Southeastern Brazil

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The challenge in the diagnosis and management of an advanced abdominal pregnancy in a resource-low setting: a case report

Abdominal pregnancy is a rare form of ectopic pregnancy that is frequently left undiagnosed by inexperienced obstetricians and radiologists. It is associated with higher risk of maternal hemorrhage at any gest...

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Tobacco Use and Smoke Exposure in Children: New Trends, Harm, and Strategies to Improve Health Outcomes

Abstract

Purpose of Review

Every day in the USA, approximately 4000 adolescents begin smoking and the adolescent brain is particularly susceptible to nicotine addiction. We present current pediatric trends on tobacco use and exposures, various new products used by adolescents, the adverse biological and behavioral effects of tobacco use and exposures, and tobacco control strategies to eliminate tobacco-related illnesses and deaths in the pediatric population.

Recent Findings

Twelve—20% of women continue to smoke during pregnancy. New research reveals cognitive differences and behavior-control disorders are seen in elementary school children from prenatal and postnatal exposures. Traditional cigarette smoking has decreased in adolescents; novel and appealing tobacco products have captured their attention, particularly electronic cigarettes, and rates double and often triple from middle to high school. Children with asthma and those living in multi-housing units have higher rates of secondhand smoke exposure than non-asthmatics and children living in single-home dwellings.

Summary

There is no "safe or risk-free" level of tobacco use or exposure. Tobacco use and exposure in childhood and adolescence must be decreased using evidenced-based strategies to improve child health.

http://ift.tt/2uP9RQJ

Hair transplantation for the treatment of lichen planopilaris and frontal fibrosing alopecia: A report of two cases

Abstract

The efficacy of current medical treatments for lichen planopilaris (LPP) and its variant, frontal fibrosing alopecia (FFA), both lymphocyte-mediated primary cicatricial alopecias, is limited. Hair regrowth from scar tissue is usually not possible. Although hair transplantation restores the hairline and increases hair density in patients with cicatricial alopecia, the timing of the transplantation is crucial. Here, we report two Chinese patients with LPP or FFA who underwent the follicular unit extraction method of hair transplantation after the diseases were stabilised with therapy, with satisfactory results for 3–4 years of follow up.

http://ift.tt/2gWzl9g

Tobacco Use and Smoke Exposure in Children: New Trends, Harm, and Strategies to Improve Health Outcomes

Abstract

Purpose of Review

Every day in the USA, approximately 4000 adolescents begin smoking and the adolescent brain is particularly susceptible to nicotine addiction. We present current pediatric trends on tobacco use and exposures, various new products used by adolescents, the adverse biological and behavioral effects of tobacco use and exposures, and tobacco control strategies to eliminate tobacco-related illnesses and deaths in the pediatric population.

Recent Findings

Twelve—20% of women continue to smoke during pregnancy. New research reveals cognitive differences and behavior-control disorders are seen in elementary school children from prenatal and postnatal exposures. Traditional cigarette smoking has decreased in adolescents; novel and appealing tobacco products have captured their attention, particularly electronic cigarettes, and rates double and often triple from middle to high school. Children with asthma and those living in multi-housing units have higher rates of secondhand smoke exposure than non-asthmatics and children living in single-home dwellings.

Summary

There is no "safe or risk-free" level of tobacco use or exposure. Tobacco use and exposure in childhood and adolescence must be decreased using evidenced-based strategies to improve child health.

http://ift.tt/2uP9RQJ

Hair loss associated with imatinib treatment: a dermoscopic study

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The possible role of human papillomavirus infection in the development of lichen sclerosus

Abstract

Lichen sclerosus (LS) is a chronic inflammatory skin disease of unknown origin predominantly affecting the anogenital area that causes pruritus and pain and is associated with an increased risk of malignancy. In some cases, LS vanishes after application of imiquimod, raising the question whether human papillomavirus (HPV) may have an etiopathogenic role in anogenital LS. The databases MEDLINE and Embase were systematically searched using the PRISMA guidelines. Twenty-seven papers were included that reported the prevalence of HPV in LS and in LS associated with neoplasia. HPV was identified in 0–80% (median 22%) of all LS cases. The prevalence of HPV was higher among male patients with LS (median 29%) than among female patients (median 8%). HPV16 was the most prevalent genotype, but the distribution of genotypes indicates that even low-risk HPV can cause LS. The diverging detection rates are probably due to small sample sizes in the reviewed papers and different detection methods. Factors possibly underestimating the prevalence of HPV are a selective search for high-risk HPV, DNA destruction in fixed tissue, focally residing HPV, and possibly a clearing of HPV before the time of biopsy. Seventy-five percent of sexually active people acquire HPV during their lifetime, thus HPV alone is not a cause of LS. Genetic and immunological host factors and viral factors other than type are likely to contribute. Future studies should include patients with a short duration of symptoms, and biopsies should be multiple and fresh.

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