A case of minor salivary gland sialolithiasis of the upper lip

Abstract

Background

Sialolithiasis is the most common disease of the salivary glands. Sialolithiasis usually develops in the major salivary glands, and rarely in the minor salivary glands, with only 2% of all cases of sialolithiasis occurring in the minor salivary glands and sublingual glands. Sialoliths in the minor salivary glands result in few or no clinical symptoms and are seldom identified on imaging.

Case presentation

We report herein our experience with a case of minor salivary gland sialolithiasis in a 67-year-old woman. On examination, an elastic soft, mobile, and well-circumscribed mass was palpable within the left upper lip. Ultrasound examination revealed a hypoechoic mass with heterogeneous internal echoes. The mass was excised under local anesthesia. Based on histopathological findings, a diagnosis of minor salivary gland sialolithiasis was established.

Conclusions

Diagnosis of minor salivary gland sialolithiasis is challenging due to the difficulty of detecting sialoliths on imaging. A well-circumscribed mass was detected in the upper lip, and ultrasound examination revealed a round lesion, raising the suspicion of a benign tumor. Other diseases that can develop at the upper lip are calcified lymph node, phlebolith, fibroma, pleomorphic adenoma, myxoma, vascular malformation, salivary gland tumor, non-specific sialadenitis, and malignant tumor. Surgical excision is the favored approach for confirming a diagnosis of intramucosal nodular lesions.

http://bit.ly/2SnDODn

A Practical Approach for the Verification and Determination of Site- and Trimester-Specific Reference Intervals for Thyroid Function Tests in Pregnancy

Thyroid, Ahead of Print.


http://bit.ly/2DSC8JM

Cochlear implantation as a treatment for single-sided deafness and asymmetric hearing loss: a randomized controlled evaluation of cost-utility

Abstract

Background

Single-sided deafness (SSD) and asymmetric hearing loss (AHL) have recently been proposed as a new indication for cochlear implantation. There is still no recommended treatment for these hearing deficits, and most options considered rely on the transfer of sound from the poor ear to the better ear, using Contralateral Routing of the Signal (CROS) hearing aids or bone conduction (BC) devices. In contrast, cochlear implantation allows the poor ear to be stimulated and binaural hearing abilities to be partially restored. Indeed, most recently published studies have reported an improvement in the spatial localisation of an incoming sound and better speech recognition in noisy environments after cochlear implantation in SSD/AHL subjects. It also provides consistent relief of tinnitus when associated. These encouraging hearing outcomes raise the question of the cost-utility of this expensive treatment in an extended indication.

Methods

The final endpoint of this national multicentre study is to determine the incremental cost-utility ratio (ICUR) of cochlear implantation in comparison to the current standard of care in France through simple observation, using a randomised controlled trial. Firstly, the study comprises a prospective and descriptive part, where 150 SSD/AHL subjects try CROS hearing aids and a BC device for three weeks each. Secondly, the choice is made between CROS hearing aids, BC implanted device and cochlear implantation. Hearing outcomes and quality of life measurements are described after 6 months for the subjects who chose CROS, BC or declined any option. The subjects who opt for cochlear implantation are randomised between one group where the cochlear implant is inserted without delay and one group of simple initial observation. Hearing outcomes and quality of life measurements are compared after 6 months.

Discussion

The present study was designed to assess the efficiency of cochlear implantation in SSD/AHL. A favourable cost-utility ratio in this extended indication would strengthen the promising clinical results and justify a reimbursement by the health insurance. The efficiency of other options (CROS, BC) will also be described.

Trial registration

This research has been registered in ClinicalTrials.gov (http://www.clinicaltrials.gov/), the 29th July 2014 under the n°NCT02204618.

http://bit.ly/2UGSSsW

An update on clinical safety of adalimumab in treating psoriasis: A systematic review and meta‐analysis based on 20 randomized controlled trials

Summary

Purpose

The current meta‐analysis was conducted to better evaluate the role of adalimumab for patients with psoriasis in terms of its safety profile on the basis of eligible randomized controlled trials (RCTs).

Methods

The following electronic databases such as Cochrane, PubMed, and Embase database involving the index words were screened and identified for qualified studies updated to December 2018. Associated publications and sources were hand‐searched for more related details. To further analyze the main outcomes, the odds ratio (OR) and mean difference (MD) with its 95% confidence interval (95% CI) were utilized.

Results

There were a total of 20 RCTs involving respective 3795 and 3266 patients in the adalimumab and control group that met our inclusion criteria. According to the aggregated results, the adalimumab group was highly associated with significant improvement in the incidence of adverse event (AE), infection, and injection site reaction on comparison of the control group. Nevertheless, no remarkable differences were found between the two study groups in terms of the incidence of serious AE, serious infection as well as the discontinuation of study drug caused by AE.

Conclusion

Adalimumab was proved to be linked to higher incidence of AE, infection, and injection site reaction during the therapy process of psoriasis based on high‐quality RCTs. In addition, there was no association between adalimumab therapy and serious AE, serious infection and the discontinuation of study drug caused by AE in patients harboring psoriasis according to eligible RCTs.

http://bit.ly/2RF7oQ3

Frontal Sinus Fractures: Evolving Clinical Considerations and Surgical Approaches

Cranial Maxillofac Trauma Reconstruction
DOI: 10.1055/s-0039-1678660

Frontal sinus fractures are an uncommon injury of the maxillofacial skeleton, and account for 5–15% of all maxillofacial fractures. As the force of impact increases, fractures may extend beyond the anterior table to involve adjacent skull, posterior table and frontal sinus outflow tract (FSOT). Fractures at these subsites should be evaluated independently to assess the need for and type of operative intervention. Historically, these fractures were managed aggressively with open techniques resulting in obliteration or cranialization. With significant injuries, these approaches are still indispensable. However, the treatment of frontal sinus fractures has changed dramatically over the past half-century, and recent case series have demonstrated favorable outcomes with conservative management. Concurrently, there has been an increasing role of minimally invasive endoscopic techniques, both for primary and expectant management, with a focus on sinus preservation. Here, we review the diagnosis and management of frontal sinus fractures, with an emphasis on subsite evaluation. Following a detailed assessment, an appropriate treatment strategy is selected from a variety of open and minimally invasive approaches available in the surgeon's armamentarium.
[...]

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Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://bit.ly/2UI7qZI

Cochlear implantation as a treatment for single-sided deafness and asymmetric hearing loss: a randomized controlled evaluation of cost-utility

Single-sided deafness (SSD) and asymmetric hearing loss (AHL) have recently been proposed as a new indication for cochlear implantation. There is still no recommended treatment for these hearing deficits, and ...

http://bit.ly/2UHSWZt

Incidence and Risk of Photosensitivity with Targeted Anticancer Therapies

http://bit.ly/2S6OyGN

Intralesional sodium stibogluconate under inhaled anesthesia for the treatment of cutaneous leishmaniasis in children: A retrospective cohort

http://bit.ly/2UEXFLx

Estimating CDKN2A mutation carrier probability among global familial melanoma cases using GenoMELPREDICT

Although rare in the general population, highly penetrant germline mutations in CDKN2A are responsible for 5-40% of melanoma cases reported in melanoma-prone families. We sought to determine whether MELPREDICT was generalizable to a global series of melanoma families and whether performance improvements can be achieved.

http://bit.ly/2RG7O8S

Liposuction-like Sclerotherapy Technique: a Deep Approach to Superficial Lymphatic Malformation

http://bit.ly/2S9kom9

The Hydroxychloroquine–Interferon Gamma Release Assay Question: TB or not TB?

http://bit.ly/2UEmFm8

Early Detection of Acral Melanoma: A Review of Clinical, Dermoscopic, Histopathologic, and Molecular Characteristics

Acral lentiginous melanoma is a distinct subtype of melanoma on acral skin. Patient presentation at later stages as well as delayed diagnosis by physicians contribute to a worse associated prognosis and survival rate. Despite our progress on understanding the key features of this disease, the diagnosis of early stage acral melanoma is still challenging. It is essential to integrate clinical, dermoscopic, and histological findings in the diagnosis of acral lentiginous melanoma. In addition, molecular studies can be helpful.

http://bit.ly/2RApLpz

Pigments in American Tattoo Inks and their Propensity to Elicit Allergic Contact Dermatitis

Tattoos have become increasingly common in the United States. Historically, tattoo inks were comprised of metallic pigments which had the potential to cause allergic contact dermatitis. Data have been lacking on the current use of these pigments in tattoo ink.

http://bit.ly/2S9ko5D

Determining patient preferences and willingness to pay related to scar length and appearance following skin cancer treatment on the face and trunk: A multi-center discrete choice experiment

http://bit.ly/2UEmDe0

Coffee, tea, caffeine, and risk of non-melanoma skin cancer in a Chinese population: The Singapore Chinese Health Study

1.Although studies in Caucasians suggest that caffeine may reduce the risk of non-melanoma skin cancer (NMSC), studies among darker-skinned populations are lacking. 2.We showed that intake of coffee or caffeine may reduce the risk of squamous cell and basal cell carcinomas among Chinese in Singapore.

http://bit.ly/2WJpLHF

Recommendations for the definition, evaluation, and treatment of nail psoriasis in adult patients with no or mild skin psoriasis: a dermatologist and nail expert group consensus

Nail involvement in psoriasis is common, and the severity of it does not always parallel the intensity of cutaneous disease.We created a consensus group, of which the aim was to provide practical recommendations for the treatment of nail psoriasis in patients without skin psoriasis, or with mild skin lesions with no indication for a systemic treatment. This collaborative process was conducted by an international panel of dermatologists with special expertise in nail disorders, using a formal consensus methodology.

http://bit.ly/2t70Pw4

Whats Bred in the Bone: Calcium Channels in Lymphocytes [BRIEF REVIEWS]

Calcium (Ca²⁺) is an important second messenger in lymphocytes and is essential in regulating various intracellular pathways that control critical cell functions. Ca²⁺ channels are located in the plasma membrane and intracellular membranes, facilitating Ca²⁺ entry into the cytoplasm. Upon Ag receptor stimulation, Ca²⁺ can enter the lymphocyte via the Ca²⁺ release-activated Ca²⁺ channel found in the plasma membrane. The increase of cytosolic Ca²⁺ modulates signaling pathways, resulting in the transcription of target genes implicated in differentiation, activation, proliferation, survival, and apoptosis of lymphocytes. Along with Ca²⁺ release-activated Ca²⁺ channels, several other channels have been found in the membranes of T and B lymphocytes contributing to key cellular events. Among them are the transient receptor potential channels, the P2X receptors, voltage-dependent Ca²⁺ channels, and the inositol 1,4,5-trisphosphate receptor as well as the N-methyl-d-aspartate receptors. In this article, we review the contributions of these channels to mediating Ca²⁺ currents that drive specific lymphocyte functions.

http://bit.ly/2UG7WHs

Leishmania donovani Induces Autophagy in Human Blood-Derived Neutrophils [INFECTIOUS DISEASE AND HOST RESPONSE]

Neutrophils, the essential components of the innate immune system, are recruited in large numbers to the pathogen site of entry. Several pathogens induce neutrophil autophagy; however, function of autophagic events during Leishmania parasite infection remain unknown. In this article, we report a finding that is new, to our knowledge, of how Leishmania-induced human polymorphonuclear neutrophil (hPMN) autophagy regulates the silent mode of parasite transfer to macrophages by influencing the engulfment of infected cells. Leishmania infection induced a time-dependent autophagy increase responsive to block by 3-methyladenine but sensitive to ULK1/2 inhibition only after 3 h. This suggested the prevalence of canonical autophagy during later hours, ULK1/2 inhibition being able to block only canonical autophagy. Interaction of Rubicon and Beclin-1 at 1 h postinfection affirmed the prevalence of noncanonical autophagy during early infection. There was a reduction in macrophage uptake of parasite-exposed hPMNs treated with 3-methyladenine or ULK1/2 inhibitor, suggesting the involvement of both noncanonical and canonical autophagy in neutrophil engulfment. Autophagy inducer rapamycin augmented neutrophil engulfment by macrophages. Redistribution of hPMN surface CD47 encouraged neutrophil uptake. Activation of ERK, phosphoinositide 3-kinase, and NADPH oxidase–mediated reactive oxygen species generation were induced after parasite binding. The lpg1-knockout parasites expressing defective lipophosphoglycan did not induce autophagy, indicating that lipophosphoglycan is necessary for interaction with the neutrophils. Autophagy induction was TLR2/4 independent because the receptor blockade did not interfere with infection-induced autophagy. In summary, the engulfment of neutrophils by the macrophages was influenced by the escalation of hPMN autophagy, which is an important event during Leishmania infection.

http://bit.ly/2UE1hgT

A Prime-Pull-Amplify Vaccination Strategy To Maximize Induction of Circulating and Genital-Resident Intraepithelial CD8+ Memory T Cells [MUCOSAL IMMUNOLOGY]

Recent insight into the mechanisms of induction of tissue-resident memory (T_RM) CD8⁺ T cells (CD8⁺ T_RM) enables the development of novel vaccine strategies against sexually transmitted infections. To maximize both systemic and genital intraepithelial CD8⁺ T cells against vaccine Ags, we assessed combinations of i.m. and intravaginal routes in heterologous prime-boost immunization regimens with unrelated viral vectors. Only i.m. prime followed by intravaginal boost induced concomitant strong systemic and intraepithelial genital-resident CD8⁺ T cell responses. Intravaginal boost with vectors expressing vaccine Ags was far superior to intravaginal instillation of CXCR3 chemokine receptor ligands or TLR 3, 7, and 9 agonists to recruit and increase the pool of cervicovaginal CD8⁺ T_RM. Transient Ag presentation increased trafficking of cognate and bystander circulating activated, but not naive, CD8⁺ T cells into the genital tract and induced in situ proliferation and differentiation of cognate CD8⁺ T_RM. Secondary genital CD8⁺ T_RM were induced in the absence of CD4⁺ T cell help and shared a similar TCR repertoire with systemic CD8⁺ T cells. This prime-pull-amplify approach elicited systemic and genital CD8⁺ T cell responses against high-risk human papillomavirus type 16 E7 oncoprotein and conferred CD8-mediated protection to a vaccinia virus genital challenge. These results underscore the importance of the delivery route of nonreplicating vectors in prime-boost immunization to shape the tissue distribution of CD8⁺ T cell responses. In this context, the importance of local Ag presentation to elicit genital CD8⁺ T_RM provides a rationale to develop novel vaccines against sexually transmitted infections and to treat human papillomavirus neoplasia.

http://bit.ly/2UD9nX3

Characterization of Subpopulations of Chicken Mononuclear Phagocytes That Express TIM4 and CSF1R [INNATE IMMUNITY AND INFLAMMATION]

The phosphatidylserine receptor TIM4, encoded by TIMD4, mediates the phagocytic uptake of apoptotic cells. We applied anti-chicken TIM4 mAbs in combination with CSF1R reporter transgenes to dissect the function of TIM4 in the chick (Gallus gallus). During development in ovo, TIM4 was present on the large majority of macrophages, but expression became more heterogeneous posthatch. Blood monocytes expressed KUL01, class II MHC, and CSF1R-mApple uniformly. Around 50% of monocytes were positive for surface TIM4. They also expressed many other monocyte-specific transcripts at a higher level than TIM4^– monocytes. In liver, highly phagocytic TIM4^hi cells shared many transcripts with mammalian Kupffer cells and were associated with uptake of apoptotic cells. Although they expressed CSF1R mRNA, Kupffer cells did not express the CSF1R-mApple transgene, suggesting that additional CSF1R transcriptional regulatory elements are required by these cells. By contrast, CSF1R-mApple was detected in liver TIM4^lo and TIM4^– cells, which were not phagocytic and were more abundant than Kupffer cells. These cells expressed CSF1R alongside high levels of FLT3, MHCII, XCR1, and other markers associated with conventional dendritic cells in mice. In bursa, TIM4 was present on the cell surface of two populations. Like Kupffer cells, bursal TIM4^hi phagocytes coexpressed many receptors involved in apoptotic cell recognition. TIM4^lo cells appear to be a subpopulation of bursal B cells. In overview, TIM4 is associated with phagocytes that eliminate apoptotic cells in the chick. In the liver, TIM4 and CSF1R reporters distinguished Kupffer cells from an abundant population of dendritic cell–like cells.

http://bit.ly/2UE1ctB

Cutting Edge: HDAC3 Protects Double-Positive Thymocytes from P2X7 Receptor-Induced Cell Death [CUTTING EDGE]

Intricate life-versus-death decisions are programmed during T cell development, and the regulatory mechanisms that coordinate their activation and repression are still under investigation. In this study, HDAC3-deficient double-positive (DP) thymocytes exhibit a severe decrease in numbers. The thymic cortex is rich in ATP, which is released by macrophages that clear apoptotic DP thymocytes that fail to undergo positive selection. We demonstrate that HDAC3 is required to repress expression of the purinergic receptor P2X7 to prevent DP cell death. HDAC3-deficient DP thymocytes upregulate the P2X7 receptor, increasing sensitivity to ATP-induced cell death. P2rx7/HDAC3-double knockout mice show a partial rescue in DP cell number. HDAC3 directly binds to the P2rx7 enhancer, which is hyperacetylated in the absence of HDAC3. In addition, RORt binds to the P2rx7 enhancer and promotes P2X7 receptor expression in the absence of HDAC3. Therefore, HDAC3 is a critical regulator of DP thymocyte survival and is required to suppress P2X7 receptor expression.

http://bit.ly/2Sf6BLa

Cadmium Induces Glomerular Endothelial Cell-Specific Expression of Complement Factor H via the -1635 AP-1 Binding Site [INNATE IMMUNITY AND INFLAMMATION]

Cadmium (Cd) is an environmental toxin that induces nephrotoxicity. Complement factor H (CFH), an inhibitor of complement activation, is involved in the pathogenesis of various renal diseases. In this study, we investigated the effects of Cd on CFH production by the kidney. In C57B6/J mice, an increased CFH level was found in renal blood and glomerular endothelial cells after Cd treatment. In vitro, Cd induces an increased CFH secretion and mRNA expression in human renal glomerular endothelial cells but not in human podocytes or human mesangial cells. Cd activates the JNK pathway and increases c-Jun and c-Fos in human renal glomerular endothelial cells. A JNK inhibitor, SP600125, specifically abolishes Cd-induced CFH production. By chromatin immunoprecipitation assay and EMSA, the –1635 AP-1 motif on human CFH promoter was identified as the binding element for c-Jun and c-Fos. In a luciferase activity assay, mutation of the AP1 site eliminates Cd-induced increase of CFH promoter activity. Thus, the –1635 AP-1 motif on the CFH promoter region mediates Cd-inducible CFH gene expression.

http://bit.ly/2UHzEDO

Cutting Edge: ICOS-Deficient Regulatory T Cells Display Normal Induction of Il10 but Readily Downregulate Expression of Foxp3 [CUTTING EDGE]

The ICOS pathway has been implicated in the development and functions of regulatory T (Treg) cells, including those producing IL-10. Treg cell–derived IL-10 is indispensable for the establishment and maintenance of intestinal immune homeostasis. We examined the possible involvement of the ICOS pathway in the accumulation of murine colonic Foxp3- and/or IL-10–expressing cells. We show that ICOS deficiency does not impair induction of IL-10 by intestinal CD4 T cells but, instead, triggers substantial reductions in gut-resident and peripherally derived Foxp3⁺ Treg cells. ICOS deficiency is associated with reduced demethylation of Foxp3 CNS2 and enhanced loss of Foxp3. This instability significantly limits the ability of ICOS-deficient Treg cells to reverse ongoing inflammation. Collectively, our results identify a novel role for ICOS costimulation in imprinting the functional stability of Foxp3 that is required for the retention of full Treg cell function in the periphery.

http://bit.ly/2UE1vEL

In This Issue [IN THIS ISSUE]

http://bit.ly/2SdFy2R

Neutrophil Cathepsin G Regulates Dendritic Cell Production of IL-12 during Development of CD4 T Cell Responses to Antigens in the Skin [ALLERGY AND OTHER HYPERSENSITIVITIES]

Contact hypersensitivity (CHS) is a CD8 T cell–mediated response to hapten skin sensitization and challenge. Sensitization of wild-type (WT) mice induces hapten-reactive effector CD8 T cells producing IFN- and IL-17– and IL-4–producing CD4 T cells that cannot mediate CHS. Although CXCR2-dependent Ly6G⁺ (neutrophil) cell recruitment into hapten-challenged skin is required to direct effector CD8 T cell infiltration into the challenge site to elicit CHS, 2,4-dinitrofluorobenezene (DNFB) sensitization of CXCR2^–/– mice and neutrophil-depleted WT mice induced both hapten-reactive CD4 and CD8 T cells producing IFN- and IL-17. CD4 T cell–mediated CHS responses were not generated during DNFB sensitization of neutrophil-depleted WT mice treated with anti–IL-12 mAb or neutrophil-depleted IL-12^–/– mice. Neutrophil depletion during DNFB sensitization of WT mice markedly increased IL-12–producing hapten-primed dendritic cell numbers in the skin-draining lymph nodes. Sensitization of mice lacking the neutrophil serine protease cathepsin G (CG)–induced hapten-reactive CD4 and CD8 T cells producing IFN- and IL-17 with elevated and elongated CHS responses to DNFB challenge. Induction of CHS effector CD4 T cells producing IFN- in neutrophil-depleted WT mice was eliminated by s.c. injection of active, but not inactivated, CG during sensitization. Thus, hapten skin sensitization induces neutrophil release of CG that systemically inhibits hapten-presenting dendritic cell production of IL-12 and the development of hapten-reactive CD4 T cells to IFN-–producing CHS effector cells.

http://bit.ly/2SbzRCo

Immune Cell Infiltration into the Eye Is Controlled by IL-10 in Recoverin-Induced Autoimmune Retinopathy [AUTOIMMUNITY]

Autoimmune retinopathy (AIR) is a treatable condition that manifests in acute and progressive vision loss in patients. It has recently been determined that AIR is associated with an imbalance of T_H1 versus regulatory T cell immunity toward the retinal protein, recoverin. This study describes a new murine model to understand the immunopathology of AIR and its association with T cell responses toward recoverin. Immunization of C57BL/6 mice with recoverin resulted in ocular inflammation including infiltration of CD4⁺ and CD8⁺ T lymphocytes, B cells, and CD11b⁺Ly6C⁺ inflammatory monocytes in the eyes. Production of IFN- and IL-17 from T cells was exacerbated in IL-10 knockout (KO) mice and kinetics of disease development was accelerated. Infiltration of T cells and inflammatory monocytes into the eyes dramatically increased in recoverin-immunized IL-10 KO mice. An immunodominant peptide of recoverin, AG-16, was capable of inducing disease in IL-10 KO mice and resulted in expansion of AG-16 tetramer-specific CD4⁺ T cells in lymphoid organs and eyes. Adoptive transfer of recoverin-stimulated cells into naive mice was sufficient to induce AIR, and immunization of B cell–deficient mice led to a milder form of the disease. This model supports the hypothesis that recoverin-specific T cell responses are major drivers of AIR pathogenesis and that IL-10 is an important factor in protection.

http://bit.ly/2UE1u3F

Angiogenic Host Defense Peptide AG-30/5C and Bradykinin B2 Receptor Antagonist Icatibant Are G Protein Biased Agonists for MRGPRX2 in Mast Cells [INNATE IMMUNITY AND INFLAMMATION]

AG-30/5C is an angiogenic host defense peptide that activates human mast cells (MC) via an unknown mechanism. Using short hairpin RNA–silenced human MC line LAD2 and stably transfected RBL-2H3 cells, we demonstrate that AG-30/5C induces MC degranulation via Mas-related G protein–coupled receptor X2 (MRGPRX2). Most G protein–coupled receptors signal via parallel and independent pathways mediated by G proteins and β-arrestins. AG-30/5C and compound 48/80 induced similar maximal MC degranulation via MRGPRX2, which was abolished by pertussis toxin. However, compound 48/80 induced a robust β-arrestin activation as determined by transcriptional activation following arrestin translocation (Tango), but AG-30/5C did not. Overnight culture of MC with compound 48/80 resulted in reduced cell surface MRGPRX2 expression, and this was associated with a significant decrease in subsequent MC degranulation in response to compound 48/80 or AG-30/5C. However, AG-30/5C pretreatment had no effect on cell surface MRGPRX2 expression or degranulation in response to compound 48/80 or AG-30/5C. Icatibant, a bradykinin B₂ receptor antagonist, promotes MC degranulation via MRGPRX2 and causes pseudoallergic drug reaction. Icatibant caused MC degranulation via a pertussis toxin–sensitive G protein but did not activate β-arrestin. A screen of the National Institutes of Health Clinical Collection library led to the identification of resveratrol as an inhibitor of MRGPRX2. Resveratrol inhibited compound 48/80–induced Tango and MC degranulation in response to compound 48/80, AG-30/5C, and Icatibant. This study demonstrates the novel finding that AG-30/5C and Icatibant serve as G protein–biased agonists for MRGPRX2, but compound 48/80 signals via both G protein and β-arrestin with distinct differences in receptor regulation.

http://bit.ly/2UAmVmi

The Autoimmune Susceptibility Gene C5orf30 Regulates Macrophage-Mediated Resolution of Inflammation [AUTOIMMUNITY]

Genetic variants in C5orf30 have been associated with development of the autoimmune conditions primary biliary cirrhosis and rheumatoid arthritis. In rheumatoid arthritis, C5orf30 expression is cell-specific, with highest expression found in macrophages and synovial fibroblasts. C5orf30 is highly expressed in inflamed joints and is a negative regulator of tissue damage in a mouse model of inflammatory arthritis. Transcriptomic analysis from ultrasound-guided synovial biopsy of inflamed joints in a well characterized clinical cohort of newly diagnosed, disease-modifying antirheumatic drugs–naive rheumatoid arthritis patients was used to determine the clinical association of C5orf30 expression with disease activity. A combined molecular and computational biology approach was used to elucidate C5orf30 function in macrophages both in vitro and in vivo. Synovial expression of C5orf30 is inversely correlated with both clinical measures of rheumatoid arthritis disease activity and with synovial TNF mRNA expression. C5orf30 plays a role in regulating macrophage phenotype and is differentially turned over in inflammatory and anti-inflammatory macrophages. Inhibition of C5orf30 reduces wound healing/repair–associated functions of macrophages, reduces signaling required for resolution of inflammation, and decreases secretion of anti-inflammatory mediators. In an animal model of wound healing (zebrafish), C5orf30 inhibition increases the recruitment of macrophages to the wound site. Finally, we demonstrate that C5orf30 skews macrophage immunometabolism, demonstrating a mechanism for C5orf30-mediated immune regulation.

http://bit.ly/2S7WpUu

Growth Factor-like Gene Regulation Is Separable from Survival and Maturation in Antibody-Secreting Cells [SYSTEMS IMMUNOLOGY]

Recurrent mutational activation of the MAP kinase pathway in plasma cell myeloma implicates growth factor–like signaling responses in the biology of Ab-secreting cells (ASCs). Physiological ASCs survive in niche microenvironments, but how niche signals are propagated and integrated is poorly understood. In this study, we dissect such a response in human ASCs using an in vitro model. Applying time course expression data and parsimonious gene correlation network analysis (PGCNA), a new approach established by our group, we map expression changes that occur during the maturation of proliferating plasmablast to quiescent plasma cell under survival conditions including the potential niche signal TGF-β3. This analysis demonstrates a convergent pattern of differentiation, linking unfolded protein response/endoplasmic reticulum stress to secretory optimization, coordinated with cell cycle exit. TGF-β3 supports ASC survival while having a limited effect on gene expression including upregulation of CXCR4. This is associated with a significant shift in response to SDF1 in ASCs with amplified ERK1/2 activation, growth factor–like immediate early gene regulation and EGR1 protein expression. Similarly, ASCs responding to survival conditions initially induce partially overlapping sets of immediate early genes without sustaining the response. Thus, in human ASCs growth factor–like gene regulation is transiently imposed by niche signals but is not sustained during subsequent survival and maturation.

http://bit.ly/2UGlTVP

A Functional Idiotype/Anti-Idiotype Network Is Active in Genetically Gluten-Intolerant Individuals Negative for Both Celiac Disease-Related Intestinal Damage and Serum Autoantibodies [AUTOIMMUNITY]

An unbalance between Abs that recognize an autoantigen (idiotypes; IDs) and Igs that bind such Abs (anti-IDs) is considered a functional event in autoimmune disorders. We investigated the presence of an ID/anti-ID network in celiac disease (CD), a condition in which antitissue transglutaminase 2 (TG2) Abs are suspected to contribute to CD pathogenesis. To characterize the ID side, we reproduced by in vitro yeast display the intestine-resident Abs from CD and control patients. These TG2-specific IDs were used to identify potential anti-IDs in the serum. We observed elevated titers of anti-IDs in asymptomatic patients with predisposition to CD and demonstrated that anti-ID depletion from the serum restores a detectable humoral response against TG2. Our study provides an alternative approach to quantify CD-related autoantibodies in cases that would be defined "negative serology" with current diagnostic applications. Therefore, we suggest that developments of this technology could be designed for perspective routine tests.

http://bit.ly/2UG7OHY

Cyclic Dinucleotide-Adjuvanted Dengue Virus Nonstructural Protein 1 Induces Protective Antibody and T Cell Responses [IMMUNOTHERAPY AND VACCINES]

Endothelial dysfunction and vascular leak, pathogenic hallmarks of severe dengue disease, are directly triggered by dengue virus (DENV) nonstructural protein 1 (NS1). Previous studies have shown that immunization with NS1, as well as passive transfer of NS1-immune serum or anti-NS1 mAb, prevent NS1-mediated lethality in vivo. In this study, we evaluated the immunogenicity and protective capacity of recombinant DENV NS1 administered with cyclic dinucleotides (CDNs), potent activators of innate immune pathways and highly immunogenic adjuvants. Using both wild-type C57BL/6 mice and IFN-α/β receptor–deficient mice, we show that NS1-CDN immunizations elicit serotype-specific and cross-reactive Ab and T cell responses. Furthermore, NS1-CDN vaccinations conferred significant homotypic and heterotypic protection from DENV2-induced morbidity and mortality. In addition, we demonstrate that high anti-NS1 Ab titers are associated with protection, supporting the role of humoral responses against DENV NS1 as correlates of protection. These findings highlight the potential of CDN-based adjuvants for inducing Ab and T cell responses and validate NS1 as an important candidate for dengue vaccine development.

http://bit.ly/2S7WpDY

Histone H3K27 Demethylase Negatively Controls the Memory Formation of Antigen-Stimulated CD8+ T Cells [IMMUNE REGULATION]

Although the methylation status of histone H3K27 plays a critical role in CD4⁺ T cell differentiation and its function, the role of Utx histone H3K27 demethylase in the CD8⁺ T cell–dependent immune response remains unclear. We therefore generated T cell–specific Utx^flox/flox Cd4-Cre Tg (Utx KO) mice to determine the role of Utx in CD8⁺ T cells. Wild-type (WT) and Utx KO mice were infected with Listeria monocytogenes expressing OVA to analyze the immune response of Ag-specific CD8⁺ T cells. There was no significant difference in the number of Ag-specific CD8⁺ T cells upon primary infection between WT and Utx KO mice. However, Utx deficiency resulted in more Ag-specific CD8⁺ T cells upon secondary infection. Adoptive transfer of Utx KO CD8⁺ T cells resulted in a larger number of memory cells in the primary response than in WT. We observed a decreased gene expression of effector-associated transcription factors, including Prdm1 encoding Blimp1, in Utx KO CD8⁺ T cells. We confirmed that the trimethylation level of histone H3K27 in the Prdm1 gene loci in the Utx KO cells was higher than in the WT cells. The treatment of CD8⁺ T cells with Utx-cofactor α-ketoglutarate hampered the memory formation, whereas Utx inhibitor GSK-J4 enhanced the memory formation in WT CD8⁺ T cells. These data suggest that Utx negatively controls the memory formation of Ag-stimulated CD8⁺ T cells by epigenetically regulating the gene expression. Based on these findings, we identified a critical link between Utx and the differentiation of Ag-stimulated CD8⁺ T cells.

http://bit.ly/2S6u7ts

Ablation and Inhibition of the Immunoproteasome Catalytic Subunit LMP7 Attenuate Experimental Abdominal Aortic Aneurysm Formation in Mice [INNATE IMMUNITY AND INFLAMMATION]

Low–molecular mass protein 7 (LMP7) is a proteolytic subunit of the immunoproteasome that is involved in regulating inflammatory responses. However, the role of LMP7 in the pathogenesis of abdominal aortic aneurysm (AAA) remains unknown. In this study, ApoE knockout (KO) or LMP7/ApoE double KO (dKO) mice were infused with angiotensin II (Ang II, 1000 ng/kg per minute) for up to 28 d. We found that LMP7 expression was significantly upregulated in AAA tissues from ApoE KO mice and human patients. Moreover, Ang II infusion markedly increased the incidence and severity of AAA in ApoE KO mice, which was considerably reduced in LMP7/ApoE dKO mice. Histological alterations, including aortic wall thickening, collagen deposition, elastin fragmentation, and vascular smooth muscle cell apoptosis in AAA tissue of ApoE KO mice, were also significantly attenuated in LMP7/ApoE dKO mice. Interestingly, LMP7/ApoE dKO mice showed a marked reduction of infiltration of CD3⁺ T cells, especially CD4⁺ T cells in AAA tissues compared with ApoE KO mice. Moreover, ablation of LMP7 substantially inhibited the differentiation of CD4⁺ T cells into Th1 and Th17 cells by reducing the activation of multiple transcriptional factors. We also investigated the effects of an LMP7-specific inhibitor PR-957 (also known as ONX 0914) on AAA formation in ApoE KO mice. PR-957 treatment could reduce the AAA incidence and severity. In conclusion, our results provide, to our knowledge, novel evidence that ablation or pharmacological inhibition of LMP7 attenuates Ang II–induced AAA formation, and LMP7 might be a novel therapeutic target for treating AAA in humans.

http://bit.ly/2SdC3sX

ADAR1 Is Required for Dendritic Cell Subset Homeostasis and Alveolar Macrophage Function [IMMUNE REGULATION]

RNA editing by adenosine deaminases acting on dsRNA (ADAR) has become of increasing medical relevance, particularly because aberrant ADAR1 activity has been associated with autoimmunity and malignancies. However, the role of ADAR1 in dendritic cells (DC), representing critical professional APCs, is unknown. We have established conditional murine CD11c Cre-mediated ADAR1 gene ablation, which did not induce general apoptosis in CD11c⁺ cells but instead manifests in cell type–specific effects in DC subpopulations. Bone marrow–derived DC subset analysis revealed an incapacity to differentiate CD103 DC⁺ in both bulk bone marrow and purified pre-DC lineage progenitor assays. ADAR1 deficiency further resulted in a preferential systemic loss of CD8⁺/CD103⁺ DCs, revealing critical dependency on ADAR1, whereas other DC subpopulations were moderately affected or unaffected. Additionally, alveolar macrophages were depleted and dysfunctional, resembling pulmonary alveolar proteinosis. These results reveal an unrecognized role of ADAR1 in DC subset homeostasis and unveils the cell type–specific effects of RNA editing.

http://bit.ly/2UE1oJl

C1s Inhibition by BIVV009 (Sutimlimab) Prevents Complement-Enhanced Activation of Autoimmune Human B Cells In Vitro [INNATE IMMUNITY AND INFLAMMATION]

The classical pathway of complement (CP) can mediate C3 opsonization of Ags responsible for the costimulation and activation of cognate B lymphocytes. In this manner, the complement system acts as a bridge between the innate and adaptive immune systems critical for establishing a humoral response. However, aberrant complement activation is often observed in autoimmune diseases in which C3 deposition on self-antigens may serve to activate self-reactive B cell clones. In this study, we use BIVV009 (Sutimlimab), a clinical stage, humanized mAb that specifically inhibits the CP-specific serine protease C1s to evaluate the impact of upstream CP antagonism on activation and proliferation of normal and autoimmune human B cells. We report that BIVV009 significantly inhibited complement-mediated activation and proliferation of primary human B cells. Strikingly, CP antagonism suppressed human Ig–induced activation of B cells derived from patients with rheumatoid arthritis. These results suggest that clinical use of CP inhibitors in autoimmune patients may not only block complement-mediated tissue damage, but may also prevent the long-term activation of autoimmune B cells and the production of autoantibodies that contribute to the underlying pathologic condition of these diseases.

http://bit.ly/2S9q3ca

Lack of Ikaros Deregulates Inflammatory Gene Programs in T Cells [IMMUNE REGULATION]

CD4 Th cells are organizers of the immune response, directing other immune cells to initiate and maintain effective humoral and cellular immunity. CD4 T cells differentiate into distinct Th effector or regulatory subsets in response to signals delivered to them during the course of infection. Ikaros is a transcription factor that is expressed in blood cells from the level of the hematopoietic stem cell. It is required for normal thymic T cell development and serves as a tumor suppressor, as lack of Ikaros in developing lymphoid cells results in leukemia. To study the role of Ikaros in CD4 T cell differentiation and function, an Ikaros conditional knockout mouse was developed such that Ikaros expression was deleted specifically in mature T cells, thus avoiding defects observed in germline Ikaros mutant mice. Using this model system, we have shown that in the absence of Ikaros, CD4 T cells are able to attain Th1, Th2, and Th17, but not inducible regulatory T, cell fates. However, they show enhanced expression of a cohort of proinflammatory cytokines, resulting in differentiation of Th17 cells with a phenotype that has been associated with autoimmunity and pathological inflammation. In addition, we define Ikaros as a repressor of the gene program associated with the response to type I IFNs, another key pathway whose deregulation is linked to autoimmunity. Taken together, these data definitively define Ikaros as a critical regulator at the center of the inflammatory response in T cells and highlight a potential role in suppressing autoimmunity.

http://bit.ly/2SbtaAi

Levels of horse allergen Equ C 4 in dander and saliva from ten horse breeds

Abstract

Background

Horses are an important source of allergens, but the distribution of horse allergens is poorly understood. Five horse allergens have been identified, Equ c 1‐4 and 6. Equ c 4 seems to be an important allergen, with an IgE‐binding frequency of 77% in horse‐sensitized individuals.

Objectives

The aim of this study was to investigate levels of horse allergen Equ c 4 in dander, saliva and urine from ten horse breeds.

Method: The study population included 170 horses (87 mares, 27 stallions, 56 geldings) from ten breeds. Horse dander, saliva and urine samples were collected. Levels of horse allergen Equ c 4 were quantified using a two‐site sandwich ELISA (mAb 103 and 14G4) and were expressed as Equ c 4 U/μg protein.

Results

The horse allergen Equ c 4 was present in all dander and saliva samples from ten horse breeds, with high within‐breed and inter‐breed variations; GM values were 639 Equ c 4 U /μg protein (range 5 – 15264) for dander and 39.5 (4 – 263) for saliva. Equ c 4 was found in 19/21 urine samples. Adjusted for age, sex and changes over time, no differences between breeds could be seen in dander, while in saliva the North Swedish horse showed lower levels of Equ c 4 than any other breed. The levels of Equ c 4 protein in dander and saliva were significantly higher in samples from stallions compared to mares and geldings, independent of breed.

Conclusions & Clinical Relevance

The results show a high variability in allergen levels of Equ c 4 in dander and saliva both within and between breeds. Significantly higher levels were found in stallions compared to mares and geldings, independent of breed. Results suggest that none of the horse breeds studied can be recommended for individuals allergic to Equ c 4.

This article is protected by copyright. All rights reserved.

http://bit.ly/2Tvxqar

Alopecic patches of the scalp: a variant of primary cutaneous follicle center B‐cell lymphoma reported in a series of 14 cases

Abstract

Primary cutaneous follicle center lymphoma (PCFCL) is the most frequent primary cutaneous B‐cell lymphoma. It presents usually with erythematous papules, plaques and tumors that predominate on the head, neck and upper trunk. The evolution is indolent but relapses are frequent. Atypical presentations of PCFCL have been occasionally described, such as diffuse facial erythema, one case of scarring alopecia (1), macular lesions, including 2 cases of scarring alopecia (2), miliary agminated papules (3), or extensive telangiectasia of the scalp (4). The incidence and prognosis of these atypical forms are unknown.

This article is protected by copyright. All rights reserved.

http://bit.ly/2WP3U1s

A deep convolutional neural network for the diagnosis of thyroid nodules on ultrasound

Abstract

Background

We designed a deep convolutional neural network (CNN) to diagnose thyroid malignancy on ultrasound (US) and compared the diagnostic performance of CNN with that of experienced radiologists.

Methods

Between May 2012 and February 2015, 589 thyroid nodules in 519 patients were diagnosed as benign or malignant by surgical excision. Experienced radiologists retrospectively reviewed the US of the thyroid nodules in a test set. CNNs were trained and tested using retrospective data of 439 and 150 US images, respectively. Diagnostic performances were compared between the two groups.

Results

Of the 589 thyroid nodules, 396 were malignant and 193 were benign. The area under the curve (AUC) for diagnosing thyroid malignancy was 0.805‐0.860 for radiologists. The AUCs for diagnosing thyroid malignancy for the three CNNs were 0.845, 0.835, and 0.850. There was no significant difference in AUC between radiologists and CNNs.

Conclusions

CNNs showed comparable diagnostic performance compared to experienced radiologists in differentiating thyroid malignancy on US.

http://bit.ly/2BdGWI7

Stepwise approach towards adoption of allergen immunotherapy for allergic rhinitis and asthma patients in daily practice in Belgium: a BelSACI-Abeforcal-EUFOREA statement

Allergic rhinitis (AR) affects 23–30% of the European population with equal prevalence reported in Belgium. Despite guidelines on the correct use of effective treatment, up to 40% of AR patients remain uncontr...

http://bit.ly/2Sur9hO

Using Data Mining Techniques to Examine Domestic Violence Topics on Twitter

Violence and Gender, Ahead of Print.


http://bit.ly/2S9XLOD

Treatment of oral cancers during pregnancy: a case-based discussion

Malignancies occur in approximately 1:1000 pregnancies; the most common being breast (46%) and hematological (18%) malignancies. Oral cancers account for only 2% of all cancers in pregnant women, and there are...

http://bit.ly/2UGyacY

Pressure induced tissue resection in the larynx: A preliminary canine study

Objectives

The application of laser (light amplification by stimulated emission of radiation) energy in the larynx relies on thermal injury. The impact of this injury on adjacent tissue can be undesirable. Attempts have been made to limit the extent and range of injury to adjacent tissue. The O‐Pel Surgical System (Precise Light Surgical, Inc., Campbell, CA), a new technology, utilizes kinetic energy through Pressure Induced Tissue Resection (PITR) (Precise Light Surgical, Inc.) to cut tissue, theoretically eliminating injury to adjacent tissue. The purpose of this study was to evaluate the PSL in canine vocal folds.

Methods

Four dogs underwent PITR incisions (4 mJ pulses at 200 Hz) on their vocal folds, through mucosa into the muscle. The animals were sacrificed at days 0, 3, 7, and 21 days postsurgery. The larynges were harvested and histology was performed with hematoxylin and eosin, Masson trichrome, and Verhoeff‐van Gieson.

Results

At day 0, focal denudation of the epithelium and coagulation necrosis in the lamina propria and adjacent connective tissue are noted. On days 3 and 7, an inflammatory infiltrate of neutrophils is seen within the lamina propria and surrounding connective tissue with minimal edema and early deposition of collagen. At day 21, the mucosa is completely regenerated with the area of previous PITR into the muscle replaced with thick bundles of collagen.

Conclusion

The unique PITR characteristics offer a potentially unique cutting technology for laryngeal microsurgery. The current canine study suggests appropriate and rapid healing. With refinements of the tip size of the probe and adjustment of energy, PITR will likely be an appropriate alternate to traditional lasers in laryngeal surgery.

Level of Evidence

NA. Laryngoscope, 2019

http://bit.ly/2SsWMZg

Toripalimab or Placebo With Paclitaxel and Cisplatin in Esophageal Squamous Cell Carcinoma

Condition:   Advanced or Metastatic Esophageal Squamous Cell Cancer Without Previous Systemic Chemotherapy
Intervention:   Biological: JS001
Sponsor:   Shanghai Junshi Bioscience Co., Ltd.
Recruiting

http://bit.ly/2I3HMx5

TreatmENT of AnastomotiC Leakage After Esophagectomy

Conditions:   Esophageal Cancer;   Esophageal Neoplasms
Intervention:   Other: Intervantions for anastomotic leakage after esophagectomy
Sponsors:   Radboud University;   Dutch Upper-GI Cancer Audit group (DUCA);   Oesophago-Gastric Anastomosis Audit (OGAA)
Not yet recruiting

http://bit.ly/2t5qNQw

Radiotherapy, Carboplatin/Paclitaxel and Nivolumab for High Risk HPV-related Head and Neck Cancer

Condition:   Oropharynx Squamous Cell Carcinoma
Interventions:   Drug: Nivolumab;   Drug: Carboplatin;   Drug: Paclitaxel;   Radiation: Radiation Therapy
Sponsors:   University of Michigan Rogel Cancer Center;   Bristol-Myers Squibb
Not yet recruiting

http://bit.ly/2HPI6iB

TPST-1120 as Monotherapy and in Combination With (Nivolumab, Docetaxel or Cetuximab) in Subjects With Advanced Cancers

Conditions:   Hepatocellular Carcinoma;   Metastatic Castration Resistant Prostate Cancer;   Renal Cell Carcinoma;   Non-small Cell Lung Cancer;   Colorectal Cancer;   Squamous Cell Carcinoma of Head and Neck;   Triple-Negative Breast Cancer;   Urothelial Carcinoma;   Cholangiocarcinoma;   GastroEsophageal Cancer;   Pancreatic Cancer;   Sarcoma
Interventions:   Drug: Part 1 TPST-1120;   Drug: Part 2a TPST-1120 + nivolumab;   Drug: Part 2b TPST-1120 + docetaxel;   Drug: Part 2c TPST-1120 + cetuximab;   Drug: Part 3 TPST-1120;   Drug: Part 4a TPST-1120 + nivolumab;   Drug: Part 4b TPST-1120 + docetaxel;   Drug: Part 4c TPST-1120 + cetuximab
Sponsor:   Tempest Therapeutics
Not yet recruiting

http://bit.ly/2G8dbMR

Safety and Efficacy of KY1044 and Atezolizumab in Advanced Cancer

Conditions:   Squamous Cell Carcinoma of Head and Neck;   Non-small Cell Lung Cancer;   Hepatocellular Carcinoma;   Esophageal Cancer;   Gastric Cancer;   Melanoma;   Renal Cell Carcinoma;   Pancreatic Cancer;   Cervical Cancer;   Triple Negative Breast Cancer;   Advanced Cancer
Interventions:   Drug: KY1044;   Drug: KY1044 and atezolizumab
Sponsor:   Kymab Limited
Recruiting

http://bit.ly/2D7Dm2g

Photon Therapy Versus Proton Therapy in Early Tonsil Cancer.

Condition:   Tonsil Cancer
Intervention:   Radiation: Radiotherapy
Sponsor:   Lund University Hospital
Recruiting

http://bit.ly/2GeoFi7

PD-L1 ImagiNg to prediCt Durvalumab Treatment Response in HNSCC

Condition:   Head and Neck Cancer
Interventions:   Diagnostic Test: PD-L1 imaging;   Drug: Durvalumab
Sponsors:   Radboud University;   AstraZeneca
Not yet recruiting

http://bit.ly/2D9Ywwy

Intrascleral Fixation of an Intraocular Lens through the Pars Plana Prevents Corneal Endothelial Damage

We report two cases of aphakia in whom an intraocular lens (IOL) was intrasclerally fixated through the pars plana to minimize further corneal endothelial damage. A modified lock-and-lead technique was used. A sclerotomy and scleral incision were made 2.5 mm from the limbus. A 24-G catheter needle was used for penetration of the leading haptic, and two ultrathin 30-G needles were used to bury the ends of the haptics. The scleral incision was sutured with 8-0 nylon. Corneal endothelial cells were preserved after surgery. Neither intra- nor postoperative complications were observed. Intrascleral fixation of an IOL through the pars plana effectively minimizes further damage to corneal endothelial cells in select cases.
Case Rep Ophthalmol 2019;10:53–60

http://bit.ly/2GlbQlg

Treatment of oral cancers during pregnancy: a case-based discussion

Abstract

Background

Malignancies occur in approximately 1:1000 pregnancies; the most common being breast (46%) and hematological (18%) malignancies. Oral cancers account for only 2% of all cancers in pregnant women, and there are no standard guidelines for the treatment of oral cancer during pregnancy.

Methods

Between 2007 and 2014, our department managed 1109 patients with oral cancers; four (0.4%) had tongue carcinomas during pregnancy. These cases were retrospectively reviewed.

Results

The four women were aged 29–39 (median 32.5) years. Two underwent partial glossectomy at 39 and 40 weeks' gestation, respectively, one received radiotherapy at 17 weeks' gestation, and one underwent supraomohyoid neck dissection and hemi-glossectomy with a forearm flap reconstruction.

Conclusion

In addition to tumor factors, the wishes of the patient and her family, gestational age, and fetal and maternal conditions are important factors in deciding on a treatment protocol. Moreover, treatment decisions require multidisciplinary approach.

http://bit.ly/2MNDgRY

25-Hydroxyvitamin D variability within-person due to diurnal rhythm and illness: a case report

Vitamin D nutrition research requires accurate measures of circulating 25-hydroxyvitamin D. Our objectives were to test whether a diurnal fluctuation in blood-spot concentrations of 25-hydroxyvitamin D can be ...

http://bit.ly/2HPuhRb

Activation of Group 2 innate lymphoid cells after allergen challenge in asthmatics

Publication date: Available online 4 February 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Carla Winkler, Thomas Hochdörfer, Elisabeth Israelsson, Annemarie Hasselberg, Anders Cavallin, Kristofer Thörn, Daniel Muthas, Shervin Shojaee, Katrin Lueer, Meike Mueller, Jenny Mjösberg, Outi Vaarala, Jens Hohlfeld, Katerina Pardali

Abstract

Background

Group 2 innate lymphoid cells (ILC2) are effective producers of IL-5 and IL-13 during allergic inflammation and bridge the innate and adaptive immune response. ILC2 are increased in asthmatics compared to healthy controls. So far human data describing their phenotype during acute allergic inflammation in the lung is incomplete.

Objectives

This study aims to characterize and compare blood- and lung-derived ILC2 before and after segmental allergen challenge in mild to moderate asthmatic individuals with high blood eosinophil levels (≥300/μl).

Methods

ILC2 were isolated from blood and bronchoalveolar lavage (BAL) before and after segmental allergen challenge. Cells were sorted by flow cytometry, cultured and analyzed for cytokine release or migration, and sequenced for RNA expression.

Results

ILC2 were nearly absent in the alveolar space under baseline conditions but increased significantly after allergen challenge (P < 0.05) , whilst at the same time ILC2 numbers in blood were reduced (P<0.05). Prostaglandin D₂ (PGD₂) and CXCL12 levels in BAL correlated with decreased ILC2 numbers in blood (P = 0.004, respective P = 0.024). After allergen challenge several genes promoting type 2 inflammation were higher expressed in BAL compared to blood ILC2, while blood ILC2 remain unactivated.

Conclusion

ILC2 accumulate at the site of allergic inflammation and are recruited from the blood. Their transcriptional and functional activation pattern promote type 2 inflammation.

http://bit.ly/2WNWo70

Respiratory And Volumetric Changes Of The Upper Airways In Craniofacial Synostosis Patients

Publication date: Available online 4 February 2019

Source: Journal of Cranio-Maxillofacial Surgery

Author(s): Mannelli Giuditta, Arcuri Francesco, Spacca Barbara, Genitori Lorenzo, Spinelli Giuseppe

Summary

To assess postoperative changes of the upper airway in a pediatric syndromic cranial-synostosis (SCS) population who underwent Le Fort III (LFIII) or frontofacial advancement by distraction osteogenesis (DO).

Charts' review of 25 SCS infants presented at our tertiary-care children's hospital between January 2005 and December 2016 was performed. Preoperative (T0) and postoperative (T1) three-dimensional computed tomography (3D-CT) and polysomnography (PSG) were recorded. Differences between T0 and T1 airway volumes and changes in PSG data were analyzed.

18 patients were included. The mean T0 and T1 volumes were calculated as 15.963 mm³ ± 7.181 SD and 24.550 mm³ ± 12.946 SD, respectively. Airway areas increased significantly (p<0.05) in the total study-group by a median value of 8.004 mm³, together with a global 72.22% improvement in respiratory parameters.

A statistically significant gain of the upper airway after LF III and DO in SCS patients has been demonstrated. Given the absence of a direct relationship between post-operative upper airway volume increase and OSAS degree improvement, further insights should consider performing T0 and T1 sleep endoscopy analysis to complete the diagnostic workup and to better assess the level of residual or recurrent upper airway obstruction in patients who experience unsuccessful surgical treatment.

http://bit.ly/2SvxnOm

Preliminary clinical study of Chinese standard alloplastic temporomandibular joint prosthesis

Publication date: Available online 4 February 2019

Source: Journal of Cranio-Maxillofacial Surgery

Author(s): Luxiang Zou, Jieyun Zhao, Dongmei He

Abstract

Purpose

To evaluate the preliminary clinical outcomes on the Chinese standard temporomandibular joint (TMJ) prostheses.

Patients and Methods

Patients who underwent Zimmer Biomet and Chinese standard prostheses by one surgeon between January 1^st 2016 and June 30^th 2017 were included in the study. Maximum incisal opening (MIO), pain, diet, and joint function were measured; CT scans were taken before and after the operation and during at least a 12-months follow-up for evaluation.

Results

Thirty-five patients including 12 with Chinese standard prostheses and 23 with Biomet stock prostheses participated in the study. After an average of 14.3 months follow-up, both types of prostheses could significantly improve MIO, diet, and joint function, and relieve pain (p<0.05). There were no significant differences in diet, pain level and joint function either before or after the operation between the two types of prostheses, whereas after the operation, the MIO with Chinese standard prostheses was significantly larger than with the Biomet stock prostheses (p<0.05). However, there was no significant difference before operation (p>0.05). A computed tomography (CT) scan showed that no prostheses dislocated or broke, no screws loosened, and ectopic bone formation appeared around the alloplastic condyle.

Conclusion

Chinese standard TMJ prostheses are effective and stable in clinical application. They can significantly improve mouth opening, diet, and joint function and relieve pain.

http://bit.ly/2GsBkxd

Facial and midfacial symmetry in cleft patients: comparison to non-cleft children and influence of the primary treatment concept

Publication date: Available online 4 February 2019

Source: Journal of Cranio-Maxillofacial Surgery

Author(s): Nabil Ben Bouhjar, Johannes Kleinheinz, Dieter Dirksen, Philipp Berssenbrügge, Christoph Runte, Kai Wermker

Summary

Purpose

Patients with cleft lip, alveolus and palate (CLAP) may suffer from marked asymmetry with an impact on attractiveness and psychosocial aspects. The aim of this study was to assess symmetry in CLAP patients compared to non-cleft controls of similar age with regard to cleft type and treatment concept.

Materials and Methods

In CLAP patients with different cleft forms and in healthy non-cleft subjects (control group) a three-dimensional stereophotogrammetric face scan was performed and an objective 3D asymmetry index (AI) was calculated for the whole face, the midface, the upper lip and the nose.

Results

In total, 305 patients were included: 140 CLAP patients (90 male, 50 female, mean age 9.9 ± 3.6 years) and 165 controls (87 male, 78 female, mean age 8.7 ± 2.1 years). In general, CLAP patients showed significantly higher asymmetry than controls, with the most severe asymmetry found in unilateral complete CLAP. Patients treated according to an actual concept considering reconstruction of all affected muscular systems had a significant lower and more favourable AI than patients not treated according to this concept (p<0.05).

Conclusion

An adequate treatment concept is essential to achieve better results concerning symmetry in CLAP, but symmetry values of healthy non-cleft controls are not reached.

http://bit.ly/2Sp3bV7

A new multilayered membrane for tissue engineering of oral hard- and soft tissue by means of melt electrospinning writing and film casting – an in vitro study

Publication date: Available online 4 February 2019

Source: Journal of Cranio-Maxillofacial Surgery

Author(s): Andreas Fuchs, Almoatazbellah Youssef, Axel Seher, Stefan Hartmann, Roman C. Brands, Urs D.A. Müller-Richter, Alexander C. Kübler, Christian Linz

Summary

Membranes that form a mechanical barrier not only for cells but also for the bacterial flora of the oral cavity may be helpful in infection-free wound healing for guided tissue regeneration (GTR) applications in the field of oral- and maxillofacial surgery. Controlled wound healing without interference from bacterial contamination appears to be achievable in combination with surface scaffolds for bone- and soft tissue regeneration. As this has not yet been realized, we developed multilayered membranes in this study consisting of specific surface scaffolds for bone- and mucosal regeneration as well as bacteria-tight core membranes. These membranes were evaluated in terms of cell growth of osteoblast- (MG63), keratinocyte- (HaCaT), and fibroblast (L929) cell lines. Scaffolds were fabricated via melt electrospinning writing (MEW), while the core membrane was produced via film casting. All constructs were made of medical-grade poly(ε-caprolactone) (PCL). The bacteria-tightness was tested via a bacterial transmigration-assay. PCL scaffolds and core membranes alone demonstrated good cytocompatibility for all cell lines, which was even enhanced by fusing both components together. The core membrane displayed complete bacteria-tightness over two weeks. These bacteria-tight, individually-designed membranes from medical-grade PCL represent a high-potential, clinically oriented method of GTR in the field of oral- and maxillofacial surgery.

http://bit.ly/2GmT1Ol

Successful treatment of refractory cutaneous lupus vasculitis with i.v. immunoglobulin

http://bit.ly/2t0qGpo

The protective role of ferulic acid against cisplatin-induced ototoxicity

Publication date: Available online 4 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Eu-Ri Jo, Cha Kyung Youn, Yonghyun Jun, Sung Il Cho

Abstract

Objectives

While cisplatin is an effective chemotherapeutic agent, it can cause irreversible hearing loss. Ototoxicity leads to dose reduction during the cisplatin chemotherapy and results in inadequate treatment of malignant tumors. This study aimed to investigate the protective effects of ferulic acid on cisplatin-induced ototoxicity.

Methods

House Ear Institute-Organ of Corti 1 (HEI-OC1) cells were exposed to 30 μM of cisplatin for 24 h with or without pretreatment with ferulic acid. Cell viability was determined using the WST assay. Apoptotic cells were identified using TUNEL assay. Western blot analysis was performed to examine the change in expression of cleaved caspase, cleaved poly-ADP-ribose polymerase (PARP), nuclear factor erythroid 2-related factor 2 (Nrf2), and catalase. Intracellular reactive oxygen species (ROS) were determined by flow cytometry. Real-time PCR analyses were performed to examine the mRNA levels of antioxidant enzymes including glutamate-cysteine ligase catalytic subunit (Gclc), glutathione peroxidase 2 (Gpx2), catalase, and superoxide dismutase 2 (SOD2). Phalloidin staining of the organ of Corti was performed to determine hair cell survival or degeneration.

Results

Pretreatment with ferulic acid before cisplatin exposure significantly increased cell viability, levels of antioxidant enzymes, and hair cell survival. In addition, pretreatment with ferulic acid significantly reduced apoptotic cells, levels of cleaved caspase, levels of cleaved PARP, and intracellular ROS production.

Conclusion

Our results demonstrated that ferulic acid inhibited cisplatin-induced cytotoxicity by preventing ROS formation and inducing the production of endogenous antioxidants and indicated that ferulic acid might be used as a protective agent against cisplatin-induced ototoxicity.

http://bit.ly/2DRpf2B

Patient injuries in pediatric otorhinolaryngology

Publication date: Available online 3 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Johanna Nokso-Koivisto, Karin Blomgren, Leena-Maija Aaltonen, Lasse Lehtonen, Päivi Helmiö

Abstract

Objectives

Patient injuries in children can have lifelong effects on the patient and a marked impact on the whole family. The aim of this study was to identify the errors and incidents leading to patient injuries in pediatric otorhinolaryngology (ORL) by evaluating accepted patient injury claims.

Methods

The records of all accepted patient injury claims in ORL between 2001 and 2011 were searched from the nationwide Patient Insurance Centre registry. Pediatric injuries were reviewed and evaluated in detail, and factors contributing to injury were identified.

Results

In the 10-year study period, 17 (7.6%) of the 223 patient injuries occurred in children, and of these, 15 (88%) were considered operative care. The median age of the patients was 8 years (range 3 to 16 years). All operations were performed as daytime elective surgery and by a fully trained specialist in 93% of the cases. One-half of the cases were routine surgeries for common ORL diseases. The most common incidences were incomplete surgery, retained gauze or foreign body, injury to adjacent anatomic structure, and insufficient charts or instructions (each occurred in 3 cases). The most frequent consequence was burn (n=4). One child died because of post-tonsillectomy hemorrhage.

Conclusions

Patient injuries in pediatric ORL are strongly related to surgery. Most injuries occurred after routine operations by a fully trained specialist. Clinicians should be aware of the most likely scenarios resulting in claims.

http://bit.ly/2MMoWcg

Comparative study on laser and LED influence on tissue repair and improvement of neuropathic symptoms during the treatment of diabetic ulcers

Abstract

To compare the influence of laser and LED on tissue repair and neuropathic symptoms during treatment of diabetic foot. An intervention survey conducted in a health center located in Brazil, contemplating ten sessions, twice a week, with randomization in two groups. In one group, the wounds were treated with GaAlAs laser, with a wavelength of 830 nm, 30 mW, and power density 0.84 W/cm², the other group by LED 850 nm, 48 mW, and power density 1.05 W/cm². For the analysis of wound size, photographic records analyzed by the ImageJ® software were used, and the neuropathy evaluation card examined. With regard to the laser group, a reduction in wound extension of 79.43% was observed at the end of the 10th session; the patients in the LED group had a 55.84% decrease in the healing process; comparing the two therapies was observed a better healing in the participants of the laser group, with 81.17%, in relation to the LED after the end of the sessions; regarding the evaluation of the neuropathic condition, there was a significant improvement in both therapies. There was improvement of the neuropathic signs and symptoms, also improvement of the tissue repair in the two therapeutic modalities; however, the laser presented a higher rate of speed in relation to the LED.

http://bit.ly/2DRUM4I