Radiology

European Society of Paediatric Radiology Computed Tomography and Dose Task Force: European guidelines on diagnostic reference levels for paediatric imaging Abstract The recent European Council Directive 2013/59/EURATOM requires the establishment of diagnostic reference levels (DRLs) to optimise radiation dose in diagnostic and interventional radiology procedures. At the time this directive was enacted, just a few European countries had already set paediatric DRLs and many of these were outdated. For this reason, the European Commission launched a project addressing European Guidelines on Diagnostic Reference Levels for Paediatric Imaging that was awarded to a consortium led by the European Society of Radiology with the collaboration of the European Society of Paediatric Radiology and other European stakeholders involved in the radiation protection of children. The main aims of this project were to establish European DRLs to be used by countries without their own national paediatric DRLs and to provide a consistent method to establish new DRLs in the future. These European guidelines have been very recently endorsed by the European Commission and published in issue N° 185 of the Radiation Protection series. The purpose of this article is to introduce these guidelines to the wide community of paediatric radiologists.

Magnetic resonance imaging of cerebellar cysts in a neonate with congenital cytomegalovirus infection Abstract Congenital cytomegalovirus infection is one of the most common congenital viral infections in the world. Brain magnetic resonance imaging plays a key role in evaluating brain involvement and establishing prognosis; several characteristic features have been described. We present a description of cerebellar cysts in a neonate with polymerase chain reaction-confirmed cytomegalovirus congenital infection, and discuss the differential diagnosis and potential pathophysiological mechanisms.

Hermes

Idiopathic, heritable and veno-occlusive pulmonary arterial hypertension in childhood: computed tomography angiography features in the initial assessment of the disease Abstract Background In children, idiopathic and heritable pulmonary arterial hypertension present echocardiographic and heart catheterization findings similar to findings in pulmonary veno-occlusive disease. Objective To provide a systematic analysis of CT angiography anomalies in children with idiopathic or heritable pulmonary arterial hypertension, or pulmonary veno-occlusive disease. We also sought to identify correlations between CT findings and patients' baseline characteristics. Materials and methods We retrospectively analyzed CT features of children with idiopathic and heritable pulmonary arterial hypertension or pulmonary veno-occlusive disease and 30 age-matched controls between 2008 and 2014. We compared CT findings and patient characteristics, including gene mutation type, and disease outcome until 2017. Results The pulmonary arterial hypertension group included idiopathic (n=15) and heritable pulmonary arterial hypertension (n=11) and pulmonary veno-occlusive disease (n=4). Median age was 6.5 years. Children with pulmonary arterial hypertension showed enlargement of pulmonary artery and right cardiac chambers. A threshold for the ratio between the pulmonary artery and the ascending aorta of ≥1.2 had a sensitivity of 90% and a specificity of 100% for pulmonary arterial hypertension. All children with pulmonary veno-occlusive disease had thickened interlobular septa, centrilobular ground-glass opacities, and lymphadenopathy. In children with idiopathic and heritable pulmonary arterial hypertension, presence of intrapulmonary neovessels and enlargement of the right atrium were correlated with higher mean pulmonary artery pressure (P=0.011) and pulmonary vascular resistance (P=0.038), respectively. Mediastinal lymphadenopathy was associated with disease worsening within the first 2 years of follow-up (P=0.024). Conclusion CT angiography could contribute to early diagnosis and prediction of severity in children with pulmonary arterial hypertension.

Pediatric ovarian volumes measured at ultrasound after contralateral unilateral oophorectomy Abstract Background Changes that occur in the remaining ovary after contralateral oophorectomy are not well described. Objective To determine average ovarian volume in pediatric patients after contralateral oophorectomy compared to age-matched controls with two normal ovaries. Materials and methods We performed a retrospective review of ultrasound examinations and electronic medical records of patients ages 0–18 years who had unilateral oophorectomy from 2000 to 2017 (n=64). We used 384 consecutive normal age-matched ovaries for comparison, analyzing mean ovarian volumes. Results Higher mean ovarian volume (mL) was observed in patients who had oophorectomy compared to controls in the first decade of life (P<0.003) and second decade of life (P<0.0003). Higher mean ovarian volume was seen in both premenarchal and menstruating patients with prior oophorectomy when compared to controls (P<0.05 and P<0.0001, respectively). When comparing volume during menstrual cycle, we saw higher mean ovarian volumes in the oophorectomy group compared to the control group for the follicular (P<0.0001), pre-ovulatory (P=0.0005) and luteal phases (P<0.0003). We provide an updated reference of normal ovarian volumes for pediatric patients, with values similar to those already reported in the literature. Conclusion Ovarian volume is higher in pediatric patients with one normal ovary following contralateral oophorectomy. The provided normative volumes can be used in evaluating these patients.

ESPR 2019

Comparison of diagnostic accuracy for fistulae at ultrasound and voiding cystourethrogram in neonates with anorectal malformation Abstract Background Recently, it has been reported that anorectal malformation with rectourethral fistula in male neonates can be managed by primary neonatal reconstruction without colostomy. To prevent urethral injury during anorectoplasty, the fistula's location is important. To date, the use of voiding cystourethrograms to determine the presence and location of fistulas in neonates with anorectal malformations has not been studied. Objective To compare the accuracy of ultrasound (US) and voiding cystourethrogram for determining the presence and location of fistulas in neonates with anorectal malformation. Materials and methods We included 21 male neonates with anorectal malformation with rectourethral fistula (n=16), rectovesical fistula (n=1) or no fistula (n=4) who underwent US and voiding cystourethrogram preoperatively on the day of surgery. Fistula imaging was classified into three grades (0–2), and grades 1–2 were considered fistula positive. We compared the imaging-based location of the fistula with surgical findings. Results US performed significantly better than voiding cystourethrogram for determining the presence of fistulas (area under the receiver operating characteristic curve, 0.90 vs. 0.71, respectively; P=0.044) (diagnostic accuracy 85.7%, 95% confidence interval [95% CI] 63.7–97.0% and 52.4%, 95% CI 29.8–74.3%, respectively). In cases with fistulas detected by either modality, the accuracy of locating the fistula by US was 50.0% (95% CI 24.7–75.3%) and by voiding cystourethrogram was 100% (95% CI: 59.0–100%). Conclusion US accurately detected, but did not accurately locate, fistulas in neonates with anorectal malformation. When planning primary neonatal reconstruction of anorectal malformation without colostomy, voiding cystourethrogram could provide additional information about fistula location.

Congenital diaphragmatic hernia sacs: prenatal imaging and associated postnatal outcomes Abstract Background The presence of a hernia sac in congenital diaphragmatic hernia (CDH) has been reported to be associated with higher lung volumes and better postnatal outcomes. Objective To compare prenatal imaging (ultrasound and MRI) prognostic measurements and postnatal outcomes of CDH with and without hernia sac. Materials and methods We performed database searches from January 2008 to March 2017 for surgically proven cases of CDH with and without hernia sac. All children had a detailed ultrasound (US) examination and most had an MRI examination. We reviewed the medical records of children enrolled in our Pulmonary Hypoplasia Program. Results Of 200 cases of unilateral CDH, 46 (23%) had hernia sacs. Cases of CDH with hernia sac had a higher mean lung-to-head ratio (LHR; 1.61 vs. 1.17; P<0.01), a higher mean observed/expected LHR (0.49 vs. 0.37; P<0.01), and on MRI a higher mean observed/expected total lung volume (0.53 vs. 0.41; P<0.01). Based on a smooth interface between lung and herniated contents, hernia sac or eventration was prospectively questioned by US and MRI in 45.7% and 38.6% of cases, respectively. Postnatally, hernia sac is associated with shorter median periods of admission to the neonatal intensive care unit (45.0 days vs. 61.5 days, P=0.03); mechanical ventilation (15.5 days vs. 23.5 days, P=0.04); extracorporeal membrane oxygenation (251 h vs. 434 h, P=0.04); decreased rates of patch repair (39.0% vs. 69.2%, P<0.01); and pulmonary hypertension (56.1% vs. 75.4%, P=0.03). Conclusion Hernia sac is associated with statistically higher prenatal prognostic measurements and improved postnatal outcomes. Recognition of a sharp interface between lung and herniated contents may allow for improved prenatal diagnosis; however, delivery and management should still occur at experienced quaternary neonatal centers.

Human immunodeficiency virus-related cerebral white matter disease in children Abstract The human immunodeficiency virus (HIV) epidemic seems largely controlled by anti-retroviral treatment with resultant large numbers of children growing up with the disease on long-term treatment, placing them at higher risk to develop HIV-related brain injury, ongoing cognitive impairment and treatment-related neurological complications. Cerebral white matter involvement is a common radiologic finding in HIV infection and the causes of this have overlapping appearances, ranging from diffuse widespread involvement to focal lesions. The varied pathophysiology is broadly grouped into primary effects of HIV, opportunistic infection, vascular disease and neoplasms. White matter changes in children can be different from those in adults. This review provides guidance to radiologists with the diagnostic dilemma of nonspecific cerebral white matter lesions in children with HIV. The authors discuss common causes of HIV-related cerebral white matter disease as well as the role of neuroimaging in the management of these children.

Neurochemistry

Increased REDD1 facilitates neuronal damage after subarachnoid hemorrhage Publication date: September 2019 Source: Neurochemistry International, Volume 128 Author(s): Jianyou Su, Meng Wang, Yaohua Yan, Shaoqing Ju, Jian Chen, Xiaomei Wu Abstract Regulated in development and DNA damage responses 1 (REDD1) is a highly conserved stress-response protein and can be induced by hypoxia/ischemia and DNA damage. However, it is not known whether REDD1 involves in neuronal damage caused by subarachnoid hemorrhage (SAH) that is known as one of the most important causes of disability and death worldwide. Here, we first found that SAH markedly induced the increase of REDD1 (35.467 ng/ml) in cerebrospinal fluid (CSF) of patients at acute stage (within 24 h from bleeding) compared to that of control (0.644 ng/ml). And, REDD1 level was positively correlated with severity of brain injuries (Hunt-Hess grade of SAH), but it showed an obvious decline at recovery stage 6.201 ng/ml (before discharge from hospital) because of good recovery. Moreover, it was found that the expression of REDD1 was significantly induced by hemolysate in a dose-dependent way in neurons. Knockdown of REDD1 by lentivirus encoded REDD1-shRNA could inhibit the neuronal apoptosis and LDH leakage caused by hemolysate. Importantly, the level of REDD1 in peripheral blood of SAH patients was significantly higher (4.364 ng/ml) than that of healthy persons (1.317 ng/ml) and also was positively correlated with that in CSF. Taken together, our findings provide the novel and direct evidence that REDD1 could play a critical role of process of neuronal damage caused by SAH, suggesting a new molecular target to protect brain function from SAH injury.

Long-term exposure of 2450 MHz electromagnetic radiation induces stress and anxiety like behavior in rats Publication date: September 2019 Source: Neurochemistry International, Volume 128 Author(s): Sukesh Kumar Gupta, Shishir Kumar Patel, Munendra Singh Tomar, Shio Kumar Singh, Manoj Kumar Mesharam, Sairam Krishnamurthy Abstract Long term exposure of electromagnetic radiations (EMR) from cell phones and Wi-Fi hold greater propensity to cause anxiety disorders. However, the studies investigating the effects of repeated exposure of EMR are limited. Therefore, we investigated the effects of repeated exposure of discrete frequencies of EMR in experimental animals. Male rats were exposed to EMR (900, 1800 and 2450 MHz) for 28 (1 h/day) days. Long term exposure of EMR (2450 MHz) induced anxiety like behavior. It deregulated the hypothalamic pituitary adrenal (HPA) axis in rats as observed by increase in plasma corticosterone levels apart from decreased corticotrophin releasing hormone-2 (CRH-2) and Glucocorticoid receptor (GR) expression in amygdala. Further, it impaired mitochondrial function and integrity. The expression of Bcl2 showed significant decrease while Bax and ratio of Bax: Bcl2 were increased in the mitochondria and vice versa in cytoplasm indicating altered regulation of apoptosis. EMR exposure caused release of cytochrome-c and expression of caspase-9 ensuing activation of apoptotic cell death. Additional set of experiments performed to estimate the pattern of cell death showed necrotic and apoptotic amygdalar cell death after EMR exposure. Histopathological studies also revealed a significant decrease in neuronal cells in amygdala. The above findings indicate that long-term exposure of EMR radiation (2450 MHz) acts as a stressor and induces anxiety-like behaviors with concomitant pathophysiological changes in EMR subjected rats. Graphical abstract

Pharmacological HIF inhibition prevents retinal neovascularization with improved visual function in a murine oxygen-induced retinopathy model Publication date: September 2019 Source: Neurochemistry International, Volume 128 Author(s): Yukihiro Miwa, Yusuke Hoshino, Chiho Shoda, Xiaoyan Jiang, Kazuo Tsubota, Toshihide Kurihara Abstract Neovascular retinal diseases are the leading causes of blindness in advanced countries. To date, anti-VEGF (vascular endothelial growth factor) drugs are clinically effective and widely used for these diseases. However, recent animal and clinical studies reported that potent and long-term VEGF antagonism may induce chorioretinal atrophy. Thus, physiological amount of VEGF is required for the homeostasis in the retina. Hypoxia-inducible factors (HIFs) are transcription factors located upstream of VEGF. We hypothesized that ectopically stabilized HIFs induce pathological amount of VEGF involved with retinal neovascularization. Therefore, HIF inhibition could be an alternative therapeutic candidate targeting the pathological amount of VEGF while holding a physiological amount of VEGF. To test this hypothesis, topotecan and doxorubicin, HIF inhibitors with different mechanisms were administered to the murine oxygen-induced retinopathy (OIR) model. We found that both topotecan and doxorubicin significantly prevented pathological but not physiological neovascularization in OIR. Furthermore, impaired visual function observed in OIR can also be suppressed by administering topotecan. These data suggested that HIF inhibition may be effective for pathological angiogenesis and neurodegeneration of the retina. Graphical abstract

Neuro-protective effect of monomethyl fumarate on ischemia reperfusion injury in rats: Role of Nrf2/HO1 pathway in peri-infarct region Publication date: June 2019 Source: Neurochemistry International, Volume 126 Author(s): Devendra Singh, K.H. Reeta, Uma Sharma, N.R. Jagannathan, A.K. Dinda, Y.K. Gupta Abstract Post stroke recanalization has been associated with increased risk of oxidative stress. Stimulating endogenous antioxidant pathway by activation of nuclear factor erythroid-2-related factor-2 (Nrf2) plays a key role in neuronal defense against inflammation and oxidative stress in penumbra. Here, we explored whether monomethyl fumarate (MMF) could produce neuro-protection after ischemia/reperfusion (I/R) injury via Nrf2/HO1 activation. In male SD rats, middle cerebral artery was occluded for 90 min and confirmed using Laser Doppler flowmeter. MMF (10, 20 and 40 mg/kg) was administered in two divided doses at 30 min post ischemia and 5–10 min after reperfusion. After 24 h, effect on neurobehavioral parameters, infarct damage by TTC staining and MRI, oxidative stress and inflammatory cytokines were assessed. Expression studies of nuclear Nrf2 and cytoplasmic HO1 were performed in peri-infarct cortex and striatum; followed by dual immunofluorescence study to check the specific cell type. I/R induced neurobehavioral deficits and infarct damage were significantly (p < 0.05) attenuated by MMF (20 and 40 mg/kg). MMF, 20 mg/kg, significantly normalized I/R induced altered redox status and increased levels of TNF-α, IL-1β in the ipsilateral cortex. MRI data showed significantly reduced infarct in cortex but not in striatum after MMF treatment. Expression of nuclear Nrf2 and cytoplasmic HO1 were significantly (p < 0.05) increased in peri-infarct cortex after treatment with MMF. Additionally, dual immunofluorescence showed increased Nrf2 expression in neurons and HO1 expression in neurons as well as astrocytes in peri-infarct cortex after MMF treatment. Our results show the neuro-protective potential of MMF probably by restricting the progression of damage from striatum to cortex through activation of Nrf2/HO1 pathway in peri-infarct cortex. Graphical abstract

Cerebrovascular inflammation: A critical trigger for neurovascular injury? Publication date: June 2019 Source: Neurochemistry International, Volume 126 Author(s): Muhammad Naveed, Qi-Gang Zhou, Feng Han Abstract The cerebrovascular system is not only inert bystandard that support the metabolic demands of the brain but also elicit the barrier functions against risk factors mediated neurovascular injury. The onsets of cerebrovascular inflammation are considered as stimuli that can provoke the host defense system and trigger the development of neurological disorders. Homeostasis of the brain function is regulated by the movement of endothelial, glial, and neuronal cells within the neurovascular unit (NVU), which acts as a "platform" for the coordinated action of anti- and pro-inflammatory mechanisms. The cerebrovascular system plays an integral role in the inflammatory response by either producing or expressing a variety of cytokines, adhesion molecules, metalloproteinases, and serine proteases. Excessive inflammatory cytokine production can further be affecting the blood-brain barrier (BBB) integrity and lead to brain tissue damage. In this review, we summarize the more recent evidence highlighting the importance of cerebrovascular injury in terms of risk prediction, and the mechanisms mediating the upregulation of inflammatory mediators in cerebrovascular dysfunction and neurodegeneration.

Defective vascular signaling & prospective therapeutic targets in brain arteriovenous malformations Publication date: June 2019 Source: Neurochemistry International, Volume 126 Author(s): Ethan A. Winkler, Alex Y. Lu, Kunal P. Raygor, Joseph R. Linzey, Soren Jonzzon, Brian V. Lien, W. Caleb Rutledge, Adib A. Abla Abstract The neurovascular unit is composed of endothelial cells, vascular smooth muscle cells, pericytes, astrocytes and neurons. Through tightly regulated multi-directional cell signaling, the neurovascular unit is responsible for the numerous functionalities of the cerebrovasculature – including the regulation of molecular and cellular transport across the blood-brain barrier, angiogenesis, blood flow responses to brain activation and neuroinflammation. Historically, the study of the brain vasculature focused on endothelial cells; however, recent work has demonstrated that pericytes and vascular smooth muscle cells – collectively known as mural cells – play critical roles in many of these functions. Given this emerging data, a more complete mechanistic understanding of the cellular basis of brain vascular malformations is needed. In this review, we examine the integrated functions and signaling within the neurovascular unit necessary for normal cerebrovascular structure and function. We then describe the role of aberrant cell signaling within the neurovascular unit in brain arteriovenous malformations and identify how these pathways may be targeted therapeutically to eradicate or stabilize these lesions.

Blood vessels as a scaffold for neuronal migration Publication date: June 2019 Source: Neurochemistry International, Volume 126 Author(s): Teppei Fujioka, Naoko Kaneko, Kazunobu Sawamoto Abstract Neurogenesis and angiogenesis share regulatory factors that contribute to the formation of vascular networks and neuronal circuits in the brain. While crosstalk mechanisms between neural stem cells (NSCs) and the vasculature have been extensively investigated, recent studies have provided evidence that blood vessels also play an essential role in neuronal migration in the brain during development and regeneration. The mechanisms of the neuronal migration along blood vessels, referred to as "vascular-guided migration," are now being elucidated. The vascular endothelial cells secrete soluble factors that attract and promote neuronal migration in collaboration with astrocytes that enwrap the blood vessels. In addition, especially in the adult brain, the blood vessels serve as a migration scaffold for adult-born immature neurons generated in the ventricular-subventricular zone (V-SVZ), a germinal zone surrounding the lateral ventricles. The V-SVZ-derived immature neurons use the vascular scaffold to assist their migration toward an injured area after ischemic stroke, and contribute to neuronal regeneration. Here we review the current knowledge about the role of vasculature in neuronal migration and the molecular mechanisms controlling this process. While most of this research has been done in rodents, a comprehensive understanding of vasculature-guided neuronal migration could contribute to new therapeutic approaches for increasing new neurons in the brain after injury.

Preproenkephalin-expressing ventral pallidal neurons control inhibitory avoidance learning Publication date: June 2019 Source: Neurochemistry International, Volume 126 Author(s): Tom Macpherson, Hiroyuki Mizoguchi, Akihiro Yamanaka, Takatoshi Hikida Abstract The ventral pallidum (VP) is a critical component of the basal ganglia neurocircuitry regulating learning and decision making; however, its precise role in controlling associative learning of environmental stimuli conditioned to appetitive or aversive outcomes is still unclear. Here, we investigated the expression of preproenkephalin, a polypeptide hormone previously shown to be expressed in nucleus accumbens neurons controlling aversive learning, within GABAergic and glutamatergic VP neurons. Next, we explored the behavioral consequences of chemicogenetic inhibition or excitation of preproenkephalin-expressing VP neurons on associative learning of reward- or aversion-paired stimuli in autoshaping and inhibitory avoidance tasks, respectively. We reveal for the first time that preproenkephalin is expressed predominantly in GABAergic rather than glutamatergic VP neurons, and that excitation of these preproenkephalin-expressing VP neurons was sufficient to impair inhibitory avoidance learning. These findings indicate the necessity for inhibition of preproenkephalin-expressing VP neurons for avoidance learning, and suggest these neurons as a potential therapeutic target for psychiatric disorders associated with maladaptive aversive learning.

Contribution of cholinergic interneurons to striatal pathophysiology in Parkinson's disease Publication date: June 2019 Source: Neurochemistry International, Volume 126 Author(s): Samira Ztaou, Marianne Amalric Abstract Parkinson's disease (PD) is a neurodegenerative disorder caused by the loss of nigral dopaminergic neurons innervating the striatum, the main input structure of the basal ganglia. This creates an imbalance between dopaminergic inputs and cholinergic interneurons (ChIs) within the striatum. The efficacy of anticholinergic drugs, one of the earliest therapy for PD before the discovery of L-3,4-dihydroxyphenylalanine (L-DOPA) suggests an increased cholinergic tone in this disease. The dopamine (DA)-acetylcholine (ACh) balance hypothesis is now revisited with the use of novel cutting-edge techniques (optogenetics, pharmacogenetics, new electrophysiological recordings). This review will provide the background of the specific contribution of ChIs to striatal microcircuit organization in physiological and pathological conditions. The second goal of this review is to delve into the respective contributions of nicotinic and muscarinic receptor cholinergic subunits to the control of striatal afferent and efferent neuronal systems. Special attention will be given to the role played by muscarinic acetylcholine receptors (mAChRs) in the regulation of striatal network which may have important implications in the development of novel therapeutic strategies for motor and cognitive impairment in PD.

PPAR-γ agonist GL516 reduces oxidative stress and apoptosis occurrence in a rat astrocyte cell line Publication date: June 2019 Source: Neurochemistry International, Volume 126 Author(s): Letizia Giampietro, Marialucia Gallorini, Barbara De Filippis, Rosa Amoroso, Amelia Cataldi, Viviana di Giacomo Abstract Aims The worldwide increase in aging population is prevalently associated with the increase of neurodegenerative diseases. Peroxisome Proliferator-Activated Receptors (PPARs) are ligand-modulated transcriptional factors which belong to the nuclear hormone receptor superfamily which regulates peroxisome proliferation. The PPAR-γ is the most extensively studied among the three isoforms and the neuroprotective effects of PPAR-γ agonists have been recently demonstrated in a variety of preclinical models of neurological disorders. The aim of the study is to biologically evaluate the neuroprotective effects of new PPAR-γ selective agonists in an in vitro model. Main methods CTX-TNA2 rat astrocytes were treated with G3335, a PPAR-γ antagonist, to simulate the conditions of a neurological disorder. Newly synthetized PPAR-γ selective agonists were added to the cell culture. Cytotoxicity was assessed by MTT assay, catalase activity was investigated by a colorimetric assay, Reactive Oxygen Species (ROS) production and apoptosis occurrence were measured by flow cytometry. Western blotting were performed to measure the levels of protein involved in the apoptotic pathway. Key findings Four PPAR-γ agonists were selected. Among them, the GL516, a fibrate derivative, showed low cytotoxicity and proved effective in restoring the catalase activity, reducing ROS production and decreasing the apoptosis occurrence triggered by the G3335 administration. The effects of this molecule appear to be comparable to the reference compound rosiglitazone, a potent and selective PPAR-γ agonist, mainly at prolonged exposure times (96 h). Significance Based on recent evidence, hypofunctionality of the PPAR-γ in glial cells could be present in neurodegenerative diseases and could participate in pathological mechanisms through peroxisomal damage. The fibrate derivative PPAR-γ agonist GL516 emerged as the most promising molecule of the series and could have a role in preventing the pathophysiology of neurodegenerative disorders. Graphical abstract

Oral Biology

Corrigendum to "Efficacy of different strategies to treat root dentin eroded by liquid or gaseous hydrochloric acid associated with brushing abrasion" [Arch. Oral Biol. Vol. 89 (2018), Pages 65–69] Publication date: June 2019 Source: Archives of Oral Biology, Volume 102 Author(s): Juliana Jendiroba Faraoni, Carmen Victoria Torres Toro, Laís Lopes Machado de Matos, Regina Guenka Palma-Dibb

The pH-dependent effect of cationic and non-ionic delmopinol on planktonic and biofilm bacteria Publication date: June 2019 Source: Archives of Oral Biology, Volume 102 Author(s): Torgny Sjödin Abstract Objectives The primary purpose was to evaluate the antimicrobial effects of cationic and non-ionic delmopinol on planktonic and biofilm bacteria. Methods Determination of the minimum inhibitory concentrations on planktonic and biofilm bacteria was performed below and above the pKa-value of delmopinol. Test bacteria were Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Pseudomonas aeruginosa. Comparisons were made with three antimicrobial agents and "quaternary" delmopinol. Synergy testing of delmopinol was determined with serial dilutions of delmopinol with the other compounds in a checkerboard fashion, and the fractional inhibitory concentration index (FIC) was calculated. Results Delmopinol showed minor differences between its MIC- and MBEC-values for all bacterial strains (MBEC/MIC-ratios of 1–2). For the other compounds the difference between their MIC- and MBEC-values were higher and varied considerably between the bacteria. The MIC- and MBEC-concentrations were lower at pH where the non-ionic form of delmopinol dominates. "Quaternary" delmopinol showed the same MIC-concentrations as delmopinol, but needed much higher concentrations to kill biofilm bacteria. Synergy testing showed FIC-indices of 0.5–1. Conclusions The biofilm penetration of non-ionic delmopinol is better than for cationic delmopinol. Likewise, the cationic test reference samples exerted limited biofilm penetration. The increased efficacy of non-ionic delmopinol is probably due to reduced binding to negative groups in the extracellular matrix of polymeric substances surrounding biofilm bacteria. It is also proposed that the non-ionised form of delmopinol deposits on the biofilm surface. Higher amounts of delmopinol than expected will therefore accumulate. Combinations of delmopinol with other compounds suggests an additive antimicrobial effect.

Tea polyphenols: The application in oral microorganism infectious diseases control Publication date: June 2019 Source: Archives of Oral Biology, Volume 102 Author(s): Yuan Li, Xiaoge Jiang, Jianqi Hao, Yifei Zhang, Ruijie Huang Abstract One of the most popular drinks worldwide, tea is rich in polyphenols and is beneficial to our health because it contributes to the prevention of many diseases. In the human oral cavity, there are more than 750 different species of bacteria living together within dental plaque. Some of the bacteria are pathogens that contribute to the development of oral diseases such as dental caries, periodontitis, pulpitis, mucosal disease, or halitosis through their virulence factors and their metabolites. Until now, many studies have reported that tea polyphenols (TPs) have evident inhibitory effects on some oral pathogenic microorganisms by suppressing pivotal steps of their pathogenic processes. The aim of this review is to summarize the effectiveness and mechanisms of TPs in inhibiting microorganisms, so as to provide new ideas for the prevention and treatment of oral diseases, and to contribute to the global dental public health.

Influence of adjuvant therapy with green tea extract in the treatment of experimental periodontitis Publication date: June 2019 Source: Archives of Oral Biology, Volume 102 Author(s): Juliano Milanezi de Almeida, Bianca Mayara Marques, Vivian Cristina Noronha Novaes, Fred Lucas Pinto de Oliveira, Henrique Rinaldi Matheus, Luiz Guilherme Fiorin, Edilson Ervolino Abstract Aim This study evaluated the effects of topical green tea extract solution (GTE) as adjuvant therapy to mechanical debridement for the treatment of experimental periodontitis (EP). Material and methods We used 120 male rats (Rattus norvegicus albinus – Wistar), divided into the following four groups: NEP (sham) (n = 30): no experimental periodontitis (NEP), only simulation of EP by installation and removal of a ligature; EP (n = 30): EP induction by ligature; SRP (n = 30): EP, scaling and root planing (SRP), and irrigation with physiological saline solution; SRP/GT (n = 30): EP, SRP, and irrigation with GTE. Histologic analysis and immunohistochemistry were performed for detection of interleukin (IL)1ß, tumor necrosis factor-alpha (TNF-α), IL-10, and anti-tartrate resistant acid phosphatase (TRAP) in the furcation area. The percentage of bone in the furcation (PBF) was considered the primary variable and evaluated at 14, 22, and 37 days. The data from the histological analysis and the IL- 1B, TNF- A, and IL-10 were submitted to a Kruskal-Wallis variance test and Dunn's posttest (p ≤ 0.05). The histometric data and TRAP were submitted to analysis of variance (ANOVA) and Tukey's posttest (p ≤ 0.05). Results The SRP/GT group showed lower inflammatory process, lower immunolabeling pattern of IL-1ß and TNF-α, and greater immunolabeling pattern of IL-10 compared with the EP and SRP groups at 22 days. Fewer TRAP-positive multinucleated osteoclasts were observed in all periods in the SRP/GT group (5.22 ± 0.65; 7.33 ± 0.80; 8.55 ± 1.15) compared with the SRP group (30.67 ± 8.55; 13.22 ± 0.77; 13.87 ± 0.77). Higher PBF was observed in all periods in the SRP/GT group (74.65 ± 7.14; 76.61 ± 5.36; 79.24 ± 3.75) compared with the SRP group (61.60 ± 9.48; 54.84 ± 9.06; 53.25 ± 9.66). Conclusion GTE adjuvant to SRP reduced inflammation, osteoclastic activity, and alveolar bone loss in EP.

Autophagy in periodontal disease: Evidence from a literature review Publication date: June 2019 Source: Archives of Oral Biology, Volume 102 Author(s): Alejandro I. Lorenzo-Pouso, Pablo Castelo-Baz, Mario Pérez-Sayáns, Jason Lim, Yago Leira Abstract Objective To summarize evidence and data relating to the implications of autophagy in periodontal disease (PD) and to describe potential nutraceuticals or pharmaceuticals that could modulate this cell death subtype. Design Literature searches of various electronic databases (Medline via PubMed, SCOPUS, Web of Science, and EMBASE) using appropriate keywords (e.g., periodontal disease, periodontitis, alveolar bone loss, periodontal infection, tooth loss, autophagy, programmed cell death, and type 2 cell death) were performed. Then, a comprehensive literature review of the current understanding of this link was elaborated. Results Autophagy plays a pivotal role in PD, and its regulation seems to be an interesting avenue for future periodontal research, according to several in vivo and in vitro reports. Conclusion Today's research has ascertained the role of autophagy in PD, especially its role in the host's defence against periodontal disease drivers. A bulk of the research recognised several pharmaceuticals and nutraceuticals that could potentially modulate this kind of cell death and serve as useful therapies. However, further research is warranted to reach a clinical translation, which could help in the discovery of novel host modulation therapies for PD.

Characterization of titanium surface coated with epidermal growth factor and its effect on human gingival fibroblasts Publication date: June 2019 Source: Archives of Oral Biology, Volume 102 Author(s): Taisa Nogueira Pansani, Fernanda Gonçalves Basso, Isabela dos Reis Souza, Josimeri Hebling, Carlos Alberto de Souza Costa Abstract Objectives Different strategies, such as modifications on the implant abutments surface have been proposed to accelerate and improve the formation of the biological seal (BS). The aim of this study was to characterize a titanium (Ti) surface impregnated with epidermal growth factor (EGF) and to assess its influence on the metabolism and adhesion of oral mucosal cells. Design Ti discs were coated with EGF (100 nM) conjugated with a fluorophore and analyzed by fluorescence microscopy. The surface roughness analysis (Ra) of the EGF-coated Ti was performed by confocal microscopy. The EGF released in the wet environment was determined at 0, 24, 48 and 72 h by fluorimetric quantification. For assessment of the biological effects of EGF-coated Ti, gingival fibroblasts were seeded (5 × 104 cells) onto the substrate coated or not with this growth factor. After 24 h, cell adhesion and viability were evaluated by ANOVA and Tukey tests, α = .05. Results Immediate release of EGF as well as its incorporation by fibroblasts within 1 h after cells were seeded was observed. EGF-coated Ti discs presented significantly enhance surface roughness. Increased cell viability was observed on the EGF-coated discs. Conclusion EGF applied to Ti discs stimulated the adhesion and metabolism of gingival fibroblasts and could be considered as an interesting alternative for improving the BS.

Acetaminophen reduces apical root resorption during orthodontic tooth movement in rats Publication date: June 2019 Source: Archives of Oral Biology, Volume 102 Author(s): Masato Kaku, Taeko Yamamoto, Yuka Yashima, Jin Izumino, Haruka Kagawa, Kazutaka Ikeda, Kotaro Tanimoto Abstract Objective The present study aimed to investigate the inhibitory effect of acetaminophen on apical root resorption during orthodontic tooth movement by controlling inflammation in the periodontal ligament and apical pulp tissue. Methods Human periodontal ligament and pulp cells were subjected to 10 kPa of cyclic tensile force (CTF) in a Flexcell Strain Unit for 48 h. Then, 10 and 100 μM acetaminophen were added to the culture medium, and the expression of interleukin (IL)-1B, receptor activator of nuclear factor kappa-B ligand (RANKL), tumor necrosis factor (TNF)α, and colony stimulating factor 1 (CSF1) were evaluated. In an animal experiment, the upper first molars of 7-week-old rats were moved mesially by applying 10 g of orthodontic force. After 30 days of force application, the effects of acetaminophen on apical root resorption were examined. Results In both the periodontal ligament and pulp cells, the expression levels of IL-1B, TNFα, RANKL, and CSF1 were significantly higher in the CTF-treated group than in the control group. However, the expression levels of these factors were decreased by acetaminophen administration. High expression of IL-1B, TNFα, RANKL, and CSF1 at the root apex were also detected immunohistochemically in rats after tooth movement, but were decreased by acetaminophen administration. In addition, the number of odontoclasts and the amount of apical root resorption were significantly decreased in the acetaminophen group. Importantly, no significant difference in tooth movement was observed between the acetaminophen and control groups. Conclusions These results suggest that acetaminophen can reduce severe root resorption in the apex area without disturbing orthodontic tooth movement.

Combination of estrogen deficiency and excessive mechanical stress aggravates temporomandibular joint osteoarthritis in vivo Publication date: June 2019 Source: Archives of Oral Biology, Volume 102 Author(s): Yuyun Wu, Chiho Kadota-Watanabe, Takuya Ogawa, Keiji Moriyama Abstract Objective It has been suggested that degenerative conditions of the temporomandibular joint (TMJ), such as osteoarthritis (OA) and progressive condylar resorption, are caused by multiple etiological factors, such as hormonal imbalance and excessive mechanical stress. However, it is unclear whether these factors interrelate in the degenerative process of the condyle. The aim of this study was to observe the effects of combined hormonal imbalance and excessive mechanical stress on the condyle using a mouse model. Materials and methods Ovariectomy (OVX) was performed in 8-week-old female mice. Three weeks after OVX, a build-up resin was bonded to the right maxillary molars to create imbalanced occlusion (increased occlusal vertical dimension, iOVD). Mice were divided into four groups: control, OVX, iOVD, and OVX + iOVD. Results Histomorphometric analysis showed the lowest cartilage thickness and the highest TMJ-OA score in the OVX + iOVD group. Bone structural analysis showed significantly lower subchondral bone mass in all experimental groups. Additionally, the OVX + iOVD group showed up-regulated osteoclastic activity and increased apoptosis in the condyle. Gene expression analysis showed significantly elevated expression of pre-inflammatory cytokines in the OVX + iOVD group. These data showed that the OVX + iOVD group exhibited the most severe inflammatory TMJ-OA. Upregulation of ERα and activation of the ERK pathway was observed in the OVX + iOVD group. Conclusions Additive effects of estrogen deficiency and excessive mechanical stress on the condyle exacerbate TMJ-OA. Furthermore, estrogen deficiency and excessive mechanical stress combined may exacerbate TMJ-OA though activation of the ERK pathway.

Small molecules enhance neurogenic differentiation of dental-derived adult stem cells Publication date: June 2019 Source: Archives of Oral Biology, Volume 102 Author(s): Boon Chin Heng, Shan Jiang, Baicheng Yi, Ting Gong, Lee Wei Lim, Chengfei Zhang Abstract Objective Dental-derived stem cells originate from the embryonic neural crest, and exhibit high neurogenic potential. This study aimed to investigate whether a cocktail of eight small molecules (Valproic acid, CHIR99021, Repsox, Forskolin, SP600125, GO6983, Y-27632 and Dorsomorphin) can enhance the in vitro neurogenic differentiation of dental pulp stem cells (DPSCs), stem cells from apical papilla (SCAPs) and gingival mesenchymal stem cells (GMSCs), as a preliminary step towards clinical applications. Materials and Methods Neural induction was carried out with a small molecule cocktail based two-step culture protocol, over a total duration of 14 days. At the 8 and 14 day timepoints, the cells were analyzed for expression of neural markers with immunocytochemistry, qRT-PCR and Western Blot. The Fluo 4-AM calcium flux assay was also performed after a further 14 days of neural maturation. Results More pronounced morphological changes characteristic of the neural lineage (i.e. neuritogenesis) were observed in all three cell types treated with small molecules, as compared to the untreated controls. This was corroborated by the immunocytochemistry, qRT-PCR and western blot data, which showed upregulated expression of several early and mature neural markers in all three cell types treated with small molecules, versus the corresponding untreated controls. Finally, the Fluo-4 AM calcium flux assay showed consistently higher calcium transient (F/Fo) peaks for the small molecule-treated versus untreated control groups. Conclusions Small molecules can enhance the neurogenic differentiation of DPSCs, SCAPs and GMSCs, which offer much potential for therapeutic applications.

Experimental study of rhBMP-2 chitosan nano-sustained release carrier-loaded PLGA/nHA scaffolds to construct mandibular tissue-engineered bone Publication date: June 2019 Source: Archives of Oral Biology, Volume 102 Author(s): Nan Deng, Jian Sun, Yali Li, Liqiang Chen, Chen Chen, Yutong Wu, Zhihao Wang, Li Li Abstract Objectives To develop PLGA/nHA scaffold containing BMP-2 cell growth factor chitosan sustained release system as tissue engineered bone for repairing large jaw defects, test its sustained release rhBMP-2 efficiency in vitro, and evaluate its Osteogenesis in rabbit mandibular defects. Methods Tissue engineered bone scaffold complexes were prepared by complexing rhBMP-2 loaded chitosan (CS / rhBMP-2) nano sustained release carrier with PLGA / nHA scaffold carrier by 3D printing. In vitro, the porosity, pore size and degradation rate and the dose-time effect relationship of cytokine release were examined. Micro-CT, hematoxylin/eosin staining, Masson staining and immunohistochemistry were determined at week 4, week 8 and week 12 in 18 rabbits. Results In vitro, the porosity was (73.64 ± 1.82)%, and the average pore diameter was (431.31 ± 18.40) μm. The cumulative release was only 9.54 ± 0.86% within 48 h and 61.38 ± 2.39% on the 30th day. In vivo, Micro-CT examination showed that the BMD and the bone volume fraction at 4, 8, and 12 weeks were higher in the implantation group than in the control group. In the 12th week, Masson staining showed that new bone occupied 19.2% of the defect area in the control group, whereas the proportion of new bone reached 45.5% in the experimental group. Conclusions PLGA/nHA/CS/rhBMP-2 scaffold complex effectively controlled the early burst effect of rhBMP-2. The bone tissue engineering scaffold complex had good biocompatibility and induced osteogenic effects. It successfully repaired the experimental bone defect area of the rabbit mandible.

Applied and Basic Medical Research

Quality medical research and publications in India: Time to introspect Anil Kapoor International Journal of Applied and Basic Medical Research 2019 9(2):67-68

Asynchronous versus traditional teaching for MBBS undergraduate students-effectiveness and students perspectives - A pilot study Vijendra Devisingh Chauhan, Juhi Kalra, Vinita Kalra, Gita Negi, Pradeep Agarwal International Journal of Applied and Basic Medical Research 2019 9(2):69-72 Background: Traditional lectures continue to be one of the common ways of teaching practiced in medical schools across India. However, there are many other effective ways of teaching in large groups and lately e-learning modules, which can be synchronous, asynchronous, or blended, have been used to complement face-to-face interactions. E-assignments have been effectively used to engage students into meaningful learning. Aim: The aim of the study is to compare asynchronous teaching with traditional teaching in terms of student perspectives and learning. Materials and Methods: After taking ethical clearance from the Institutional Ethics Committee, the study was conducted involving 66 student volunteers from MBBS 2nd year. All the students were subjected to a pretest on the topic – “low backache” prior to the intervention. The students were then divided into two groups: Group A and Group B of 33 students each. Group A was taught by traditional lecture method, while Group B was given an e-assignment on the topic for which no face-to-face interaction was done earlier. The students from both the groups were then subjected to a posttest followed by feedback. Results: Analysis of covariance, considering the pretest score as a covariate, revealed that the two groups were comparable to begin with P = 0.632. After the intervention, posttest mean scores improved significantly (P < 0.001) within each group, for both the groups, but there was no significant difference in posttest scores on intergroup comparison (P = 0.507). Student feedback brought to light that 85% of the students felt that the traditional lecture method followed by e-learning would be of a great benefit to them. Conclusion: Although no single method emerged as superior over the other, student feedback revealed that 90% of the students graded e-module as either satisfactory to good. Most felt that lecture followed by e-modules will help them to learn better.

Impact of sputum volume in the diagnosis of smear-positive pulmonary tuberculosis T Jaya Chandra International Journal of Applied and Basic Medical Research 2019 9(2):73-74 Objective: To find the impact of sputum volume in the diagnosis of smear-positive (SP) pulmonary tuberculosis (PT) and its association with gender. Materials and Methods: The study was conducted in the Department of Microbiology, GSL Medical College. PT patients were included and informed to provide good-quality sputum; volume was not mentioned. Smears were stained by Ziehl–Neelsen technique. Based on the volume of sample submitted, the participants were divided into three groups. Chi-square test was used to find the statistical significance; P < 0.05 was considered statistically significant. Results: Volume-wise, 22, 38, and 74 participants submitted sputum, respectively, in groups, <2 mL, 2–5 mL, and >5 mL; statistically, the difference was significant (P < 0.05). The smear positivity was 13% (15), 28% (32), and 59% (68), respectively, in groups, <2 mL, 2–5 mL, and >5 mL; statistically, the difference was significant (P < 0.05). Among the missed cases, the difference was statistically significant (P < 0.05) in males and the difference was statistically not significant (P > 0.05) in females. Conclusions: Notable number of SP cases are identified in ≤5 mL sputum. Hence, sample should not be discarded/rejected if the volume is <5 mL.

Implementing resident research program to enhance physicians research in the United Arab Emirates Mahera Abdulrahman, Ashraf Ahmed, Frederick Robert Carrick International Journal of Applied and Basic Medical Research 2019 9(2):75-79 Objectives: The Dubai Residency Training Program (DRTP) commenced in the year 1993; then, a “Residency Research Program (RRP)” has implemented from 2011 to promote research among young physicians. This study was conducted by the Dubai Health Authority to review the RRP to assess its effectiveness in meeting original objectives and generating desired outcomes. Methods: Source documents such as the chronicles of the DRTP, communication between the stakeholders, resident feedback, research director, and program director reports were accessed and retrospectively reviewed. Results: Seven research workshops and ten advanced statistics courses were held. Ten scholarships were provided to the residents for “Introduction to Clinical Research Training” held by Harvard Medical School. Of 370 residents, a total of 156 residents submitted their research proposal, of which 128 residents presented their thesis. Nineteen residents presented their research on international conferences, 12 published their study, and 9 got award locally. Conclusions: Efforts are focused on improving the quality of the research projects, as well as getting residents involved in research that leads eventually to publication. Research is a major component of DRTP; nevertheless, it is challenging for residents to conduct research successfully because of some barriers inherent in residency training. This experience was the first in the United Arab Emirates, and we believe that this paper will contribute to the integrating research in residency programs by the educators and academics in across countries within the region.

Variations in nitric oxide and endothelin serum levels in extracorporeal shock wave lithotripsy-treated patients Emir Milisic, Mustafa Hiros, Edin Begic International Journal of Applied and Basic Medical Research 2019 9(2):80-84 Introduction: Renal vasculature is extremely sensitive to vasoconstrictor effects of endothelin (ET), while nitric oxide (NO) has special role in several pathological renal conditions. Aim: The aim of this study to examine the presence, character, and degree of changes in NO and ET levels in the serum of extracorporeal shock wave lithotripsy (ESWL)-treated patients with nephrolithiasis. Patients and Methods: This study included a total of 60 patients that were divided in two groups: Group I (n = 24), in which a total of 2000SWs were administered; 0–2 units; (0.5 units per each 500SWs), and Group II (n = 36), in which a total of 4000SWs were administered; 0–4 units; (0.5 units per each 500SWs). Results: In the Group I median NO serum concentration increased in relation to pretreatment levels (39.04 ± 8.29 μmol/L) specifically 30 min, 60 min, and 24 h following the treatment (39.11 ± 12.60), (41.80 ± 6.89), and (46.33 ± 9.03), where concentration growth after 24 h was statistically significant P < 0.01. The NO serum concentration in the Group II increased in relation to pretreatment levels (38.90 ± 10.33 μmol/L) after 30 min (48.71 ± 30.09), 60 min (54.57 ± 39.76), and 24 h (97.95 ± 72.07). The NO concentration increase after 60 min and 24 h is statistically significant, respectively, P < 0.03 and P < 0.0001. Conclusion : NO and ET serum levels are changing under the influence of ESWL, and that the NO and ET changes are directly correlated with the number of administered shock waves and administered energy.

Morphometric analysis of the orbital aperture in North Indian Population: A retrospective digital forensic study Varsha Kanjani, Abha Rani, Deepak Kanjani International Journal of Applied and Basic Medical Research 2019 9(2):85-88 Introduction: The morphometric variations seen in the orbital aperture play a significant role in forensic anthropology, for determining the personal and gender identification, especially in case of mass disasters. Aim: The aim of the present study was to evaluate the orbital aperture dimensions along with interorbital distance as observed on posteroanterior (PA) cephalograms for personal and gender identification. Materials and Methods: The present retrospective study was conducted to evaluate the morphometric dimensions of orbital aperture seen on PA cephalogram taken using PLANMECA digital machine and ROMEXIS software. The height and width of the orbits along with the interorbital distance were measured using measuring tools in the accompanying software. Data were analyzed using SPSS software version 21.0. Results: All the linear measurements such as orbital height, orbital width, and interorbital distance were significantly greater in males than females in the North Indian population with P = 0.001. The present study found 84.8% accuracy after subjecting the obtained value to discriminant function analysis. Conclusion: The morphometric analysis of the orbital aperture using postero-anterior cephalogram can be used as an adjuvant for personal and gender identification in forensic anthropology.

Morton's toe: Prevalence and inheritance pattern among Nigerians Eric Osamudiamwen Aigbogun, Ade Stephen Alabi, Blessing Chimezie Didia, Kenneth Shelu Ordu International Journal of Applied and Basic Medical Research 2019 9(2):89-94 Background: Anatomical variations have been genetically linked and the difference in the length of the big toe relative to the second toe (Morton's toe) is not an exception; however, its prevalence and inheritance pattern has been a scientific debate. Therefore, this study investigated the prevalence and inheritance pattern of Morton's toe among Nigerians in Rivers State. Materials and Methods: A total of 101 families comprising of 101 parents (fathers and mothers) and 135 offspring were conveniently sampled for this study. The observed big toe pattern was described as “LBT” and “SBT” representing big toe longer than the second toe and big toe shorter or equal to the second toe, respectively. The offspring trait was tabulated alongside the parental combination patterns (i.e., when both parents had LBT, both parents SBTand a combination of LBTand SBT). XLSTAT 2012 (version 4.2.2) Chi-square analysis tested the association between sex and Morton's toe. Mendelian Chi-square gene distribution model evaluated the conformance to simple dominance-recessive pattern, while the Hardy–Weinberg (H-W) equation for allele frequency compared the parental allele frequency to that of the offspring. Results: LBT(218; 64.7%) was more in the studied population than SBT(119; 35.3%); with males (63; 18.7%) having slightly higher proportion of SBT (Morton's toe) than females (56; 16.6%), which was without sexual preference (χ2 = 0.141, P > 0.932). The test of offspring gene distribution in conformance to Mendelian simple dominant-recessive monohybrid cross had rather weak result. The H-W equation showed a deviation of offspring allele distribution (1:3:2.5 [2:6:5]) from the parents (1:3:2). Conclusion: Morton's toe could be said to be genetically linked, however, its inheritance pattern does not conform to the simple dominant-recessive model, but a more complex pattern. It should be noted that the large frequency of a trait in a population does not make it dominant.

Rate of forced expiratory volume in one second and forced expiratory volume in one second/forced vital capacity decline among Indonesian patients with chronic obstructive pulmonary disease after a year of treatment Wily Pandu Ariawan, Faisal Yunus, Triya Damayanti, Fariz Nurwidya International Journal of Applied and Basic Medical Research 2019 9(2):95-99 Background: The rate of decline in lung function in chronic obstructive pulmonary disease (COPD) patients showed more profound decline than normal individuals. However, a 1-year lung function among Indonesian patients with COPD has not been elucidated. Aim: This study attempted to determine the rate of lung function decline in terms of obstruction variable among COPD patients after a 1-year of treatment. Materials and Methods: This retrospective cohort study measures the rate of decline in forced expiratory volume in 1 s (FEV1) and ratio of FEV1 to forced vital capacity (FEV1/FVC) in COPD patients at COPD Outpatient Clinic Persahabatan Hospital after 1-year of treatment. Results: There were 31 COPD patients with the prevalence of 1-year declined FEV1 and FEV1/FVC which were 83.9% and 51.6%, respectively. Among 1-year declined lung function group, there were significant (P < 0.05) decline in FEV1 (121.53 ± 120 ml/year) and in FEV1/FVC (2.75 ± 0.47%). The rate of decline in FEV1 was more prevalent in Group D, while the rate of decline in FEV1/FVC was more prevalent in Group B. No significant associations were found between sex, age, respiratory complaints, smoking history, Brinkman index, type of cigarette, comorbid, educational level, diagnosed age, body mass index, symptoms-based COPD classification, and risk-based COPD classification, with the rate of decline in FEV1 and FEV1/FVC. Conclusions: Most patients had statistically significant rate of decline in FEV1 and FEV1/FVC within 1-year of COPD treatment. This study recognized an unfavorable prognosis in terms of irreversible deteriorating lung function of COPD patients despite therapeutic management.

Effect of Boswellia serrata extract on acute inflammatory parameters and tumor necrosis factor-α in complete Freund's adjuvant-induced animal model of rheumatoid arthritis Rajendra Kumar, Sarvesh Singh, Anil Kumar Saksena, Rishi Pal, Riddhi Jaiswal, Rahul Kumar International Journal of Applied and Basic Medical Research 2019 9(2):100-106 Context: The worldwide prevalence of rheumatoid arthritis (RA) is about 1%, whereas in India, it is approximately 0.75%. The current therapy for RA includes nonsteroidal anti-inflammatory drugs corticosteroids, disease-modifying anti-rheumatic drugs and some recently developed biologic agents, but all of these are associated with adverse effects. Some herbal drugs, such as Boswellia serrata, have been reported to possess anti-inflammatory activity. Aims: The aim of this study is to evaluate the anti-arthritic activity of Boswellia serrata extract (BSE) in complete Freund's adjuvant (CFA)-induced arthritis in rats. Materials and Methods: Thirty-six Wistar rats were divided into six equal groups. RA was induced by intradermal injection of 0.1 ml CFA in hind paw. Body weight, ankle diameter, paw volume, arthritic index, tumor necrosis factor-α (TNF-α), and histopathological examination were assessed. The experimental data were statistically assessed by one-way analysis of variance (ANOVA). Statistical Analysis Used: The recorded data were analyzed using paired t-test and ANOVA test using SPSS. The data were analyzed and represented as mean difference. Value of P < 0.05 was considered statistically significant. Results: BSE at dose 180 mg/kg showed statistically significant improvement in body weight and decrease in ankle diameter and arthritic index (P < 0.05); however, there was insignificant change in paw volume (P = 0.056). This improvement was comparable with Indomethacin. The level of TNF-α did not show any statistically significant change (P = 0.076). Histopathological results also exhibited a reduction in inflammatory parameters. Conclusions: BSE might have usefulness as an adjunct to conventional therapy of RA.

Pitfalls in fine-needle aspiration cytology diagnosis of ductal carcinoma in a lactating breast Hajra K Mehdi, Kalyani Raju, C SBR Prasad, Manan B Shah International Journal of Applied and Basic Medical Research 2019 9(2):107-110 Breast undergoes hormonal changes, especially during pregnancy and postpartum period and may be associated with benign and malignant lesions. These lesions can arise either de novo or can be an exacerbated change occurring in a preexisting breast lesion. The benign lesion in the lactating breast can show some degree of atypia due to the high levels of progesterone and prolactin which can mimic malignant features microscopically and can be overdiagnosed with breast cancer. On the other hand, breast cancer in the lactating breast can be underdiagnosed when the atypical cytological features are considered as hormonal changes. A few case reports are published in the literature regarding lactating adenoma undergoing malignant transformation. We present a case in 23 years postpartum lactating female with mass in bilateral breasts. Initially, the lesions were diagnosed with hormonal changes on cytology. On follow-up by fine-needle aspiration cytology and biopsy, it was diagnosed with infiltrating ductal carcinoma in both breasts. As far as our knowledge goes, this is the first-case report in the English literature of ductal carcinoma in the bilateral lactating breast arising de novo.

Cardiovascular & Thoracic Surgery

African-American surgeons: A legacy of excellence Mark Walker Nigerian Journal of Cardiovascular & Thoracic Surgery 2018 3(2):21-22

History of pioneer black surgeons in American medicine – Part 2 Arthur Brown Lee, Mark Walker, Jonathan Nwiloh Nigerian Journal of Cardiovascular & Thoracic Surgery 2018 3(2):23-30 Little information was acknowledged by the American medical establishment on the contributions of Black Americans to medicine in the United States till after the civil rights revolution of the 1960s. This review is an attempt to recount some of the small corps of Black surgeons' trailblazers who helped establish the black identity in American surgery, thereby paving the way for succeeding generations.

Pharmacologic management of chronic heart failure Obiora Egbuche, Jo Ann Cross, Anekwe Onwuanyi Nigerian Journal of Cardiovascular & Thoracic Surgery 2018 3(2):31-35 Heart failure (HF) is a complex progressive clinical syndrome that is associated with high morbidity and mortality. Although several pharmacologic therapy have become available for treatment of certain HF phenotypes, HF still is characterized by recurrent hospitalizations and need for advanced therapy resulting in huge economic burden. The optimal management of HF includes modifying risk factors, identifying and treating reversible causes, address socioeconomic barriers to care and instituting appropriate pharmacologic and device treatments. In this brief review, we summarize the pharmacologic treatment of chronic heart failure and highlight a few major landmark trials that provide the basis for specific therapy in clinical practice.

Lung metastasectomy in renal cell carcinoma: Evaluation of 20 cases Aynur Bas, Anil Gökçe, Merve Satir Turk, Muhammet Sayan, Ali Çelik, İsmail Cüneyt Kurul, Abdullah İrfan Taştepe Nigerian Journal of Cardiovascular & Thoracic Surgery 2018 3(2):36-39 Aim: About 90% of kidney cancers are renal cell carcinoma (RCC), and one-third of them are metastatic at the time of diagnosis. Most RCC metastases are to the lung. In this article, we present the results of a series of pulmonary metastasectomies for RCC in our institute. Materials and Methods: Twenty cases who underwent pulmonary metastasectomy for RCC between 2007 and 2017 were retrospectively reviewed. Patients were classified according to the age, sex, smoking history, duration of disease-free survival, number of metastatic lesions, median survival time, survival time after metastasectomy, type of surgery, and whether they received immunotherapy. Results: Fifteen of the patients were male and five were female. The mean age was 60-year-old (range: 28–86-year-old). Nineteen of the 20 patients had a history of nephrectomy. The median disease-free survival time was found to be 16.5 months while the median survival time after nephrectomy was 43.3 months. The number of detected metastatic lesions ranged from one to eight, and the location of the majority of them was intraparenchymal. Survival time after metastasectomy was found to be 20.6 months. Surgical approaches included bilateral metastasectomy through median sternotomy, unilateral wedge resection, and lobectomy through video-assisted thoracoscopic surgery or thoracotomy. Conclusion: The results of a combination of pulmonary metastasectomy and immunotherapy treatment were found to be better than immunotherapy or surgery alone. However, further study is needed with a larger series to support this argument.

Chronic mitral regurgitation: Does atrial fibrillation impact outcome in patients managed with medical therapy only? Jonathan Nwiloh, Uzoma Okechukwu, Kenneth Adiele, Newton Orumwense, Uche Oriaku, Victor Ezenwajiaku Nigerian Journal of Cardiovascular & Thoracic Surgery 2018 3(2):40-45 Background: The AHA/ACC guideline recommends surgery for symptomatic chronic severe mitral regurgitation or percutaneous mitral valve repair for high surgical risk or inoperable patients. Although atrial fibrillation (AF) is a known predictor of survival after either of these interventional procedures, its impact on the outcome of patients treated only medically is less well defined. Materials and Methods: This was a retrospective review of adult patients with chronic mitral regurgitation seen at our heart center from August 2014 to December 2017. Results: There were 102 patients, with a mean age of 58.4 ± 15.8 years and 51% were males. Major comorbidities were AF (58.8%), hypertension (HTN) (53.9%), pulmonary HTN (18.6%), and diabetes mellitus (10.8%). Sixty-seven (65.7%) patients had primary and 35 (34.3%) had secondary mitral regurgitation. Eighty-eight (86.3%) patients were in New York Heart Association Class 3/4, 92 (90.2%) in AHA/ACC Stages C/D, and 70 (68.6%) had left ventricular (LV) dysfunction with ejection fraction (EF) <60. Patients were subdivided into Group 1 – 60 (58.8%) patients with AF and Group 2 – 42 (41.2%) patients without AF. AF frequency was higher with primary or degenerative mitral regurgitation (PMR) versus secondary mitral regurgitation (SMR), 75% versus 25%, P = 0.031, whereas HTN was higher in SMR versus PMR, 77.1% versus 41.8%, P = 0.001. Four patients underwent mitral valve replacement and two patients implantable cardioverter defibrillator. All patients were treated with the AHA/ACC guideline-directed medical therapy (GDMT). All-cause mortality for Groups 1 and 2 was 25% and 14.3%, respectively, odds ratio was 2.0, and 95% confidence interval was 0.705–5.677, P = 0.285. Overall, Kaplan–Meier survival at 30 months was 63%, and log-rank analysis survival was 56% and 79% for Groups 1 and 2, respectively, P = 0.345. Conclusion: In a cohort of patients with chronic mitral regurgitation treated only medically with GDMT in a low-resource country, all-cause mortality and intermediate survival were comparable between AF and non AF patients.

Ophthalmology

Read, learn, and grow VA Bastin Kerala Journal of Ophthalmology 2019 31(1):1-1

Medical education in India - General Profile Alex Joseph Kerala Journal of Ophthalmology 2019 31(1):2-3

Atropine in the treatment of childhood myopia Sanitha Sathyan Kerala Journal of Ophthalmology 2019 31(1):4-10 The practice of using topical atropine to prevent the progression of myopia in children has been going on for decades in some Asian populations. The encouraging results obtained from Atropine for the treatment of childhood myopia (ATOM) studies and animal studies have created much interest among the practitioners regarding the use of atropine in preventing myopic progression. This review aims to summarize the major research works done on the subject and its implications in clinical practice.

Ptosis: Evaluation and management Marian Pauly, R Sruthi Kerala Journal of Ophthalmology 2019 31(1):11-16 Blepharoptosis, or ptosis of the eyelid, refers to drooping of the upper eyelid that usually results from a congenital or acquired abnormality of the muscles that elevate the eyelid. Ptosis may be the presenting sign or symptom of a serious neurologic disease. Regardless of the etiology, when ptosis obstructs vision, it is disabling. The appropriate management requires recognition of the underlying cause. This review article highlights the various aspects of ptosis evaluation and management.

Optical coherence tomography in the evaluation of disc edema Deepa Gaur, H Vijaya Pai Kerala Journal of Ophthalmology 2019 31(1):17-23 Optic disc oedema is a common clinical problem where the ophthalmologist plays an important role in the diagnosis, management. Many optic nerve diseases can cause disc oedema like papilloedema, papillitis, anterior ischaemic optic neuropathy, central retinal vein occlusion, optic nerve head drusen etc. It is important to differentiate pseudoneuritis as in hypermetropia from true disc oedema. The clinical features, fundus examination sometimes may not give the correct diagnosis. Fundus fluorescein angiogram helps to differentiate pseudo from true disc oedema. However it is an invasive procedure. With newer technologies like optical coherence tomography which helps to image the optic disc, it is possible to differentiate pseudo from true disc oedema, also to recognise the aetiology of disc oedema. In this review article we are highlighting the OCT findings in various causes of disc oedema.

The use of atropine in childhood myopia: Experience in Indian eyes Sanitha Sathyan Kerala Journal of Ophthalmology 2019 31(1):24-27 This clinical query section discusses the use of topical atropine in childhood myopia among Indian children. Experts from across the country share their viewpoints, clinical experience, and concerns on the subject.

Correlation between ocular axial length and anterior chamber depth and a differential analysis in same-sized eyes Rakesh Maggon, Sumit Kumar Singh, Maneesh Jha, Avinash Mishra, Sandeep Gupta, Vivek Sharma Kerala Journal of Ophthalmology 2019 31(1):28-32 Purpose: To study correlation between ocular axial length and anterior chamber depth in eyes and to differentially analyse strength of this correlation in eyes with near-equal axial length. Materials and Methods: We conducted an observational study where keratometry and optical biometry records of 872 patients reporting for cataract surgery were taken. A comparative analysis using Optical Biometry (Zeiss IOL master) for pre-operative measurement of Axial length (AL), Anterior chamber depth (ACD) and calculated IOL power was done. Statistical Analysis: Data was analysed to determine overall correlation between two parameters. Patients were then classified into various groups of near-equal AL for a differential comparison within the group. Kendall-Pearson product-moment correlation test was used to assess relationship between AL and ACD, overall and within each subgroup. A P-value < 0.05 was considered as statistically significant. Results: 872 eyes were analysed and it was seen that as the mean AL (23.28mm), increased, mean ACD (2.97mm) also increased in overall analysis. In group analysis correlation between AL and ACD varied widely from 0.86 (AL-17-21 mm) to a negative -0.14 (AL 21-22mm). Conclusions: As mean AL increases ACD also increases. In eyes with near-equal AL there is wide variability in ACD which is either due to variable lens thickness or lens location in different eyes. Since lens thickness variability was obviated by taking age-matched eyes, location of lens is the probable cause. Therefore, Effective Lens Position (ELP) based formulae (Haigis & Holladay II) have an inherent unpredictability and may result in post-operative refractive surprises.

Acute acquired comitant esotropia in children: A benign entity or an ominous sign? R Neena, Anantharaman Giridhar Kerala Journal of Ophthalmology 2019 31(1):33-38 Purpose: The purpose is to study the clinical features of acute acquired comitant esotropia (AACE) in children and analyze the course and outcome. Materials and Methods: A retrospective, clinical study of all patients under the age of 18 years with acute onset, nonaccommodative comitant esotropia in a tertiary eye care center from September 2013 to December 2016. Parameters studied were age, sex, visual acuity, eye involved, age of onset, precipitating event, amount of deviation, presence or absence of amblyopia, cycloplegic refraction, systemic involvement, surgical or nonsurgical intervention, course, and outcome. All patients underwent magnetic resonance imaging of brain and orbits, and systemic evaluation was done in suspicious cases. Minimum follow-up period was 6 months. Results: Out of 12 patients, 8 were male. Average age of the patients was 7.9 years. The mean esodeviation was 33.75 PD, and mean age of onset was 6.14 years (range: 2&#8211;15 years). There was left eye preponderance. Three patients (25&#37;) had a history of a precipitating event. Cycloplegic refraction ranged from &#43;0.50 DS to &#8722;6.75 DS, with majority having <&#43;2.00 DS. Amblyopia was noted in 8 (66.6&#37;) patients. Systemic involvement was seen in three patients in the form of ocular myasthenia, central nervous system glioma, and viral fever, respectively. Esotropia disappeared in one patient with overcorrected, high myopia following atropinization, and change of glass. Eight patients (66.6&#37;) underwent strabismus surgery with good postoperative alignment, and the rest were managed conservatively. Conclusion: AACE is an unusual ocular alignment disorder characterized by a nonaccommodative esodeviation which can occur in older children, adults, and even the elderly. Although most children with this form of esotropia are otherwise healthy, systemic diseases must be considered and ruled out before planning surgery. Prompt amblyopia therapy and timely surgery can result in a satisfactory outcome in those without systemic involvement.

Outcomes of multifocal intraocular lens implantation in pediatric eyes Minnu Parakal, Swapna Nair Kerala Journal of Ophthalmology 2019 31(1):39-44 Objective: To study the pre operative profile and postoperative visual, quality of life outcomes and complications in pediatric eyes with multifocal intraocular lens implants. Methods: All children requiring primary or secondary intraocular lens implantation where the IOL could be placed in the capsular bag were assigned to this prospective study. The cause for cataract, laterality, preoperative and postoperative corrected and uncorrected distance and near visual acuity, slit lamp observations, intraocular pressures, type of surgery, postoperative IOL positioning, intra and post operative complications and quality of life estimates were recorded. SPSS ver21 was used for data analysis and the outcomes were documented. Results: 21 eyes of 14 pediatric patients were included in this study, 7 of them underwent bilateral surgery. The age range was 1 to 14 years. The logmar best corrected visual acuity for distance and near improved in 100&#37; of eyes. The average corrected distant visual acuity was 0.3 (6/12p) and average near vision was 0.38 (N6-N8) without near addition. The average residual spherical power was 0.26DS and astigmatism was -0.22DC. 9 eyes had raised IOP immediate post procedure. The average IOP after 1 month was 13.71 mm of Hg. The quality of life questionnaire indicated satisfactory levels of performance at school and play. Conclusions: Multifocals IOLs are an effective and safe implant to impart instant near vision correction, thereby bypassing the need to wear or be compliant with bifocals, thus aiding in overcoming amblyogenic influences.

Posterior chamber phakic intraocular lenses in refractive surgery: Preoperative profile and postoperative outcomes VL Divya, Swapna Nair Kerala Journal of Ophthalmology 2019 31(1):45-50 Objective: To assess the pre operative visual, refractive and topographic profile and to analyse postoperative vision, contrast and complications of patients undergoing phakic intraocular lens implantation. Methods: This prospective study enrolled patients that underwent phakic intraocular lens implantation after refractive surgery work up. The corrected pre op and uncorrected post op distance visual acuity, pachymetry, keratometry, topography, white to white, anterior chamber depth, and specular microscopy, along with postoperative anterior chamber angles, corneal and lens status and vaulting of the phakic IOL were recorded at 1 month. Results: 59 eyes of 32 patients with myopia, simple and compound myopic astigmatism underwent posterior chamber phakic IOL. The average sphere corrected was -8.4 D and the average cylinder was -1.5 D with 45.8 &#43;/- 2.2 being the average steep k values. The mean central corneal thickness, WTW and ACD in these patients were 511.9 &#43;/-42,11.44 &#43;/- 0.65 mm, 3.24 &#43;/- 0.33 mm respectively. The average post op UCDVA was 0.1 logmar with most eyes gaining more lines than preop CDVA. The average post op phakic IOL vault wrt the natural lens was 455 micron and average IOP 13.74 &#43;/- 2.8 mmHg. Conclusion: Posterior chamber phakic IOLs are a safe and predictable means of providing good vision especially in high myopes with borderline corneae. Accurate preoperative sizing of the lens is key to optimum results.