"Naringenin: A Promising Immunomodulator for Anti-Inflammatory, Neuroprotective, and Anti-Cancer Applications".

BACKGROUND: Inflammatory, immune, and neurodegenerative diseases constitute a category of persistent and debilitating conditions affecting millions worldwide, with inter-twined pathophysiological pathways. Recent research has spotlighted naturally occurring compounds like naringenin for potential therapeutic applications across multiple ailments. OBJECTIVE: This review offers an encompassing exploration of naringenin's anti-inflamma-tory, immune-protective, and neuroprotective mechanisms, elucidating its pharmacological targets, signal transduction pathways, safety profile, and insights from clinical investigations. METHODS: Data for this review were amassed through the scrutiny of various published studies via search engines such as PubMed and Google Scholar. Content from reputable publishers including Bentham Science, Taylor and Francis, Nature, PLOS ONE, among others, was referenced. RESULTS: Naringenin exhibits substantial anti-inflammatory effects by restraining the NF-κB signaling pathway. It activates Nrf2, renowned for its anti-inflammatory properties, inducing the release of hemeoxynase-1 by macrophages. Furthermore, naringenin treatment downregulates the expression of Th1 cytokines and inflammatory mediators. It also impedes xanthine oxidase, counteracts reactive oxygen species (ROS), scavenges superoxide radicals, mitigates the accessibility of oxygen-induced K+ erythrocytes, and reduces lipid peroxidation. Naringenin's antioxidant prowess holds promise for addressing neurological conditions. CONCLUSION: Extensive research has been undertaken to establish the anti-inflammatory, immunomodulatory, and neuroprotective attributes of naringenin across various medical domains, lending credence to its pharmacological utility. The principal obstacle to naringenin's adoption as a therapeutic agent remains the dearth of in vivo data. Efforts should focus on rendering naringenin delivery patient-friendly, economically viable, and technologically advanced.

Learning points about myalgic encephalomyelitis/chronic fatigue syndrome: Bridging the gap between research, clinical practice and awareness.

This essay examines the complex landscape of myalgic encephalomyelitis, commonly known as chronic fatigue syndrome, highlighting its chronic and multisystemic nature with elusive causative factors. It discusses clinical challenges in diagnosis and management, emphasising the importance of increased education and awareness among healthcare professionals. The role of empathic, person-centred care in improving patient outcomes is underscored, urging for a paradigm shift towards understanding and addressing the profound impact of myalgic encephalitis/chronic fatigue syndrome on patients' lives.

Intra-abdominal Inflammatory Myofibroblastic Tumour (IMFT)-Uncommon Entity.

IMFT (inflammatory myofibroblastic tumour) is an uncommon tumour predominantly affecting the lungs and mediastinum. Most of the published literature supports that it affects children and young individuals. IMFT involving the gastrointestinal tract is rare. We report a case of multifocal IMFT affecting the GI tract which was managed with gross total excision followed by chemotherapy. Surgical resection remains the treatment of choice. The role of chemotherapy and radiation therapy remains limited. The aetiology of these tumours remains unclear and is mostly ALK-positive that could be targeted. Local recurrences are common and hence require close follow-up. The risk of recurrences and metastasis is increased in cases with TP53 positivity, aneuploidy and recurrent lesions.

Nephrotic Syndrome and Posterior Reversible Encephalopathy Syndrome as Clinical Presentations of Gemcitabine-Induced Thrombotic Micro-Angiopathy.

Gemcitabine-induced thrombotic micro-angiopathy (GiTMA) is a very rare pathology of micro-vascular occlusion with a poor prognosis. In this case report, we present a young male with pancreatic carcinoma who received gemcitabine as adjuvant chemotherapy and developed thrombotic micro-angiopathy (TMA) manifesting as nephrotic syndrome with renal dysfunction and posterior reversible encephalopathy syndrome (PRES). The case was successfully managed with discontinuation of the drug and conservative management. The pathogenesis of GiTMA might be direct endothelial dysfunction with consequent activation of the clotting system. The role of plasma exchanges and monoclonal antibodies is unclear in drug-induced TMA.

Global disease burden of and risk factors for acute lower respiratory infections caused by respiratory syncytial virus in preterm infants and young children in 2019: a systematic review and meta-analysis of aggregated and individual participant data.

BACKGROUND: Infants and young children born prematurely are at high risk of severe acute lower respiratory infection (ALRI) caused by respiratory syncytial virus (RSV). In this study, we aimed to assess the global disease burden of and risk factors for RSV-associated ALRI in infants and young children born before 37 weeks of gestation. METHODS: We conducted a systematic review and meta-analysis of aggregated data from studies published between Jan 1, 1995, and Dec 31, 2021, identified from MEDLINE, Embase, and Global Health, and individual participant data shared by the Respiratory Virus Global Epidemiology Network on respiratory infectious diseases. We estimated RSV-associated ALRI incidence in community, hospital admission, in-hospital mortality, and overall mortality among children younger than 2 years born prematurely. We conducted two-stage random-effects meta-regression analyses accounting for chronological age groups, gestational age bands (early preterm, <32 weeks gestational age [wGA], and late preterm, 32 to <37 wGA), and changes over 5-year intervals from 2000 to 2019. Using individual participant data, we assessed perinatal, sociodemographic, and household factors, and underlying medical conditions for RSV-associated ALRI incidence, hospital admission, and three severity outcome groups (longer hospital stay [>4 days], use of supplemental oxygen and mechanical ventilation, or intensive care unit admission) by estimating pooled odds ratios (ORs) through a two-stage meta-analysis (multivariate logistic regression and random-effects meta-analysis). This study is registered with PROSPERO, CRD42021269742. FINDINGS: We included 47 studies from the literature and 17 studies with individual participant-level data contributed by the participating investigators. We estimated that, in 2019, 1 650 000 (95% uncertainty range [UR] 1 350 000-1 990 000) RSV-associated ALRI episodes, 533 000 (385 000-730 000) RSV-associated hospital admissions, 3050 (1080-8620) RSV-associated in-hospital deaths, and 26 760 (11 190-46 240) RSV-attributable deaths occurred in preterm infants worldwide. Among early preterm infants, the RSV-associated ALRI incidence rate and hospitalisation rate were significantly higher (rate ratio [RR] ranging from 1·69 to 3·87 across different age groups and outcomes) than for all infants born at any gestational age. In the second year of life, early preterm infants and young children had a similar incidence rate but still a significantly higher hospitalisation rate (RR 2·26 [95% UR 1·27-3·98]) compared with all infants and young children. Although late preterm infants had RSV-associated ALRI incidence rates similar to that of all infants younger than 1 year, they had higher RSV-associated ALRI hospitalisation rate in the first 6 months (RR 1·93 [1·11-3·26]). Overall, preterm infants accounted for 25% (95% UR 16-37) of RSV-associated ALRI hospitalisations in all infants of any gestational age. RSV-associated ALRI in-hospital case fatality ratio in preterm infants was similar to all infants. The factors identified to be associated with RSV-associated ALRI incidence were mainly perinatal and sociodemographic characteristics, and factors associated with severe outcomes from infection were mainly underlying medical conditions including congenital heart disease, tracheostomy, bronchopulmonary dysplasia, chronic lung disease, or Down syndrome (with ORs ranging from 1·40 to 4·23). INTERPRETATION: Preterm infants face a disproportionately high burden of RSV-associated disease, accounting for 25% of RSV hospitalisation burden. Early preterm infants have a substantial RSV hospitalisation burden persisting into the second year of life. Preventive products for RSV can have a substantial public health impact by preventing RSV-associated ALRI and severe outcomes from infection in preterm infants. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe.

Utility of "Acanthosis Nigricans" and "Skin Tags" as a screening tool for risk of developing noncommunicable diseases: A cross-sectional study at a health facility in Lucknow (India).

Context: Over the past three decades, there has been a significant rise in the prevalence of noncommunicable diseases (NCDs) globally, accompanied by a relative decline in communicable diseases. Aims: With this background, the research was planned to determine the prevalence of acanthosis nigricans (AN) or skin tags (STs) in the study population and to examine the relationship between the presence of AN and ST with commonly used indicators such as waist-to-height ratio (W/Ht.), Indian Diabetes Risk Score (IDRS), and body mass index for predicting the risk of NCDs. Settings and Design: This cross-sectional study was done at a health facility in Lucknow (India). Methodology: Consecutive sampling was employed to select 152 apparently healthy adults as the participants. Data collection involved administering a questionnaire and conducting anthropometry using standardized methods. Visual inspection was conducted to identify AN or ST on the common sites. Statistical Analysis Used: Data entry was done in Microsoft Office Excel, followed by data analysis using SPSS. To test the association between variables "significance of difference of mean," Chi-square test, logistic regression analysis, and estimation of Kohen's kappa were used. A "P" value was considered statistically significant at <0.05 level. The sensitivity and specificity of AN and ST were also estimated in predicting the risk of NCDs. Results: The prevalence of AN was 19.08% (95% confidence interval [CI] = 12.76%-25.40%), while the prevalence of STs was 28.29% (95% CI = 21.05%-35.53%). AN showed a sensitivity of 22.4% and specificity of 96.3% with W/Ht. ratio as the standard, and a sensitivity of 26.44% and specificity of 90.77% with IDRS as the standard. ST exhibited a sensitivity of 32.0% and specificity of 88.89% with W/Ht. ratio as the standard, and a sensitivity of 37.93% and specificity of 84.62% with IDRS as the standard. Conclusion: AN and ST can be used as simple and time-saving tools in screening protocols for (NCDs). Further research is desirable to validate the findings.

Résumé Contexte: Au cours des trois dernières décennies, il y a eu une augmentation significative de la prévalence des maladies non transmissibles (MNT) à l'échelle mondiale, accompagnée d'un déclin relatif des maladies transmissibles. Objectifs: Dans ce contexte, la recherche était prévue pour déterminer la prévalence de l'acanthose nigricans (AN) ou des acrochordons (ST) dans la population étudiée et pour examiner la relation entre la présence d'AN et de ST avec des indicateurs couramment utilisés tels que la taille. rapport taille (W/Ht.), score de risque de diabète indien (IDRS) et indice de masse corporelle pour prédire le risque de MNT. Paramètres et conception: cette étude transversale a été réalisée dans un établissement de santé à Lucknow (Inde). Méthodologie: Un échantillonnage consécutif a été utilisé pour sélectionner 152 adultes apparemment en bonne santé comme participants. La collecte de données impliquait l'administration d'un questionnaire et la réalisation d'anthropométries à l'aide de méthodes standardisées. Une inspection visuelle a été réalisée pour identifier AN ou ST sur les sites communs. Analyse statistique utilisée: La saisie des données a été effectuée dans Microsoft Office Excel, suivie d'une analyse des données à l'aide de SPSS. Pour tester l'association entre les variables " signification de la différence de moyenne ", le test du chi carré, l'analyse de régression logistique et l'estimation du kappa de Kohen ont été utilisés. Une valeur " P " a été considérée comme statistiquement significative au niveau < 0,05. La sensibilité et la spécificité de l'AN et du ST ont également été estimées pour prédire le risque de MNT. Résultats: La prévalence de l'AN était de 19,08 % (intervalle de confiance à 95 % [IC] = 12,76 % à 25,40 %), tandis que la prévalence des ST était de 28,29 % (IC à 95 % = 21,05 % à 35,53 %). AN a montré une sensibilité de 22,4 % et une spécificité de 96,3 % avec W/Ht. ratio comme standard, et une sensibilité de 26,44 % et une spécificité de 90,77 % avec IDRS comme standard. ST présentait une sensibilité de 32,0 % et une spécificité de 88,89 % avec W/Ht. ratio comme standard, et une sensibilité de 37,93 % et une spécificité de 84,62 % avec IDRS comme standard. Conclusion: AN et ST peuvent être utilisés comme des outils simples et permettant de gagner du temps dans les protocoles de dépistage des (MNT). Des recherches plus approfondies sont souhaitables pour valider les résultats. Mots-clés: diagnostic d'Acanthosis nigricans, dépistage des maladies non transmissibles, diagnostic des acrochordons.

Lipid-induced polymorphic amyloid fibril formation by α-synuclein.

Many proteins that self-assemble into amyloid and amyloid-like fibers can adopt diverse polymorphic forms. These forms have been observed both in vitro and in vivo and can arise through variations in the steric-zipper interactions between ß-sheets, variations in the arrangements between protofilaments, and differences in the number of protofilaments that make up a given fiber class. Different polymorphs arising from the same precursor molecule not only exhibit different levels of toxicity, but importantly can contribute to different disease conditions. However, the factors which contribute to formation of polymorphic forms of amyloid fibrils are not known. In this work, we show that in the presence of 1,2-dimyristoyl-sn-glycero-3-phospho-L-serine, a highly abundant lipid in the plasma membrane of neurons, the aggregation of α-synuclein is markedly accelerated and yields a diversity of polymorphic forms under identical experimental conditions. This morphological diversity includes thin and curly fibrils, helical ribbons, twisted ribbons, nanotubes, and flat sheets. Furthermore, the amyloid fibrils formed incorporate lipids into their structures, which corroborates the previous report of the presence of α-synuclein fibrils with high lipid content in Lewy bodies. Thus, the present study demonstrates that an interface, such as that provided by a lipid membrane, can not only modulate the kinetics of α-synuclein amyloid aggregation but also plays an important role in the formation of morphological variants by incorporating lipid molecules in the process of amyloid fibril formation.

One Anastomosis Gastric Bypass (OAGB) vs Roux en Y Gastric Bypass (RYGB) for Remission of T2DM in Patients with Morbid Obesity: a Randomized Controlled Trial.

INTRODUCTION: Majority of the studies comparing Roux en Y gastric bypass (RYGB) and one anastomosis gastric bypass (OAGB) are non-randomized. Moreover, few randomized studies have focussed on weight loss as the primary outcome rather than the impact on type 2 diabetes mellitus (T2DM). This randomized trial compared OABG over RYGB with the hypothesis that OAGB is not inferior to RYGB in terms of remission of T2DM. METHODS: This was an open-labelled, randomized trial in which patients having a BMI greater than 30 kg/m2 with T2DM were included. The primary outcome was the remission of T2DM. RESULTS: In the study, 25 and 24 patients were recruited in OAGB and RYGB groups respectively. The remission rates of T2DM were similar at all timelines. The highest rate was achieved at 1 year (86.36% vs 85.71%) for both the groups and a 4-year remission rate of (72.22% vs 71.43%), for OAGB vs RYGB respectively. The % EWL was also comparable with the highest rate achieved again at 1 year (69.23% vs 66.67%) and a 4-year rate of (58.33% vs 53.33%), for OAGB vs RYGB respectively. Remission of other co-morbidities, major and minor complication rate, re-admission rate, and nutritional issues were similar in both groups. CONCLUSION: OAGB is non-inferior to RYGB in terms of remission of type 2 diabetes mellitus, weight loss, and early and late complications with a shorter operating time.

Identification of metabolic fingerprints in severe obstructive sleep apnea using gas chromatography-Mass spectrometry.

Objective: Obstructive sleep apnea (OSA) is considered a major sleep-related breathing problem with an increasing prevalence rate. Retrospective studies have revealed the risk of various comorbidities associated with increased severity of OSA. This study aims to identify novel metabolic biomarkers associated with severe OSA. Methods: In total, 50 cases of OSA patients (49.74 ± 11.87 years) and 30 controls (39.20 ± 3.29 years) were included in the study. According to the polysomnography reports and questionnaire-based assessment, only patients with an apnea-hypopnea index (AHI >30 events/hour) exceeding the threshold representing severe OSA patients were considered for metabolite analysis. Plasma metabolites were analyzed using gas chromatography-mass spectrometry (GC-MS). Results: A total of 92 metabolites were identified in the OSA group compared with the control group after metabolic profiling. Metabolites and their correlated metabolic pathways were significantly altered in OSA patients with respect to controls. The fold-change analysis revealed markers of chronic kidney disease, cardiovascular risk, and oxidative stress-like indoxyl sulfate, 5-hydroxytryptamine, and 5-aminolevulenic acid, respectively, which were significantly upregulated in OSA patients. Conclusion: Identifying these metabolic signatures paves the way to monitor comorbid disease progression due to OSA. Results of this study suggest that blood plasma-based biomarkers may have the potential for disease management.

A Rare Presentation of Sarcomatoid Carcinoma of Duodenum: A Case Report.

Sarcomatoid tumors are very rare biphasic tumors characterized by a mixture of malignant epithelial and mesenchymal cells that have been usually identified in the lungs with other documented cases in skin, bone, thyroid gland, salivary glands, breast, and genitourinary and gastrointestinal systems. They have an incidence estimated to be 0.5 to 0.8 per 100 000 per year. Three classic features include the presence of a genuine sarcomatous component, no transitional zone between carcinomatous and sarcomatous components, and immunohistochemistry of the sarcomatous component that is positive for mesenchymal markers and negative for epithelial markers. Sarcomatoid carcinoma of the gastrointestinal tract is rare but more commonly found within the stomach, gallbladder, and esophagus. Small bowel involvement is very rare.

Tracheostomy in Pediatric Intensive Care Unit-A Two Decades of Experience.

AIM AND OBJECTIVE: To study the profile, indications, related complications, and predictors of decannulation and mortality in patients who underwent tracheostomy in the pediatric intensive care unit (PICU). MATERIALS AND METHODS: Retrospective analysis of prospectively collected data of tracheostomies was done on patients admitted at PICU. Demographics, primary diagnosis, indication of tracheostomy, and durations of endotracheal intubation, mechanical ventilation, and tracheostomy cannulation were recorded. The indication was recorded in one of the four categories-upper airway obstruction (UAO), central neurological impairment (CNI), prolonged mechanical ventilation, and peripheral neuromuscular disorders). RESULTS: Two hundred ninety cases were analyzed. UAO (42%) and CNI (48.2%) were main indications in the halves of the study period, respectively. Decannulation was successful in 188 (64.8%) patients. Seventy-seven percentage UAO patients were decannulated successfully [OR (odds ratio); 95% CI (confidence interval), 2.647; 1.182-5.924, p = 0.018]. Age <1 year (0.378; 0.187-0.764; p = 0.007), nontraumatic, noninfectious central neurological diseases (0.398; 0.186-0.855; p = 0.018), and malignancy (0.078; 0.021-0.298; p <0.001), durations of posttracheostomy ventilation (0.937; 0.893-0.983; p = 0.008), and stay in the PICU (0.989; 0.979-0.999; p = 0.029) were predictors of unsuccessful decannulation. There were 91 (31.4%) deaths. Age <1 year (2.39 (1.13-5.05; p = 0.02), malignancy (17.55; 4.10-75.11; p <0.001), durations of posttracheostomy ventilation (1.06; 1.006-1.10; p = 0.028), and hospital stay (1.007; 1.0-1.013; p = 0.043) were independent predictors of mortality. Indication of UAO favored survivor (0.24; 0.09-0.57; p <0.001). CONCLUSION: The indications for tracheostomy in children had changed over the years. Infancy, primary diagnosis, length of posttracheostomy ventilation, and stay in the PICU and hospital were independent predictors of decannulation and mortality. WHAT THIS ADDS: Similar to developed countries, the age at the time of tracheostomy and indication are changing. Inability to decannulate and mortality were associated with the age of a child at the time of tracheostomy, indication, medical diagnosis, and duration of postprocedure mechanical ventilation and stay in the hospital. HOW TO CITE THIS ARTICLE: Sachdev A, Chaudhari ND, Singh BP, Sharma N, Gupta D, Gupta N, et al. Tracheostomy in Pediatric Intensive Care Unit-A Two Decades of Experience. Indian J Crit Care Med 2021;25(7):803-811.

Recent trends in gas sensing via carbon nanomaterials: outlook and challenges.

The presence of harmful and poisonous gases in the environment can have dangerous effects on human health, and therefore portable, flexible, and highly sensitive gas sensors are in high demand for environmental monitoring, pollution control, and medical diagnosis. Currently, the commercialized sensors are based on metal oxides, which generally operate at high temperatures. Additionally, the desorption of chemisorbed gas molecules is also challenging. Hence, due to the large surface area, high flexibility, and good electrical properties of carbon nanomaterials (CNMs) such as carbon nanotubes, graphene and their derivatives (graphene oxide, reduced graphene oxide, and graphene quantum dots), they are considered to be the most promising chemiresistive sensing materials, where their electrical resistance is affected by their interaction with the analyte. Further, to increase their selectivity, nanocomposites of CNMs with metal oxides, metallic nanoparticles, chalcogenides, and polymers have been studied, which exhibit better sensing capabilities even at room temperature. This review summarizes the state-of-the-art progress in research related to CNMs-based sensors. Moreover, to better understand the analyte adsorption on the surface of CNMs, various sensing mechanisms and dependent sensing parameters are discussed. Further, several existing challenges related to CNMs-based gas sensors are elucidated herein, which can pave the way for future research in this area.

Acoustic Reflexes in Individuals Having Hyperacusis of the Auditory Origin.

Functional role of the acoustic reflex in preventing over stimulation of the inner auditory system by decreasing sound intensity along with the previous reports of acoustic reflex abnormalities in individuals having hyperacusis point towards the involvement of acoustic reflex deficit in the origin of hyperacusis especially when any medical condition leading to hyperacusis is not associated. However this issue remains contradictory owing to limited comprehensive investigation. This study was undertaken to ascertain the relationship between hyperacusis and the acoustic reflex. Threshold, amplitude and latency of the acoustic reflex were measured in two different groups of individuals having hyperacusis; Group 1: 14 individuals having hyperacusis with hearing loss (HwHL) and Group 2: 17 individuals having hyperacusis without hearing loss (HwoHL). Control group (Group 3) consisted of 15 normal hearing individuals who never experienced hyperacusis. Result showed a significant group effect on all the measured characteristics of the acoustic reflex. ARTs were found to be significantly higher in HwHL and HwoHL when compared to NHwoH. ARTs were statistically similar for HwoHL and NHwoH. HwoHL's ARAs and ARLs were significantly smaller and prolonged, respectively, when compared to HwHL and NHwoH. HwHL and NHwoH had statistically similar ARAs and ARLs. This study confirms acoustic reflex abnormalities in some individuals having hyperacusis with or without hearing loss. It further highlight the importance of involving acoustic reflex testing in the assessment of hyperacusis especially when hyperacusis is not associated with hearing loss or any other medical condition that may lead to hyperacusis.

Fluoresceinated Aminohexanol Tethered Inositol Hexakisphosphate: Studies on Arabidopsis thaliana and Drosophila melanogaster and Docking with 2P1M Receptor.

Inositol hexakisphosphate (InsP6; phytic acid) is considered as the second messenger and plays a very important role in plants, animals, and human beings. It is the principal storage form of phosphorus in many plant tissues, especially in dry fruits, bran, and seeds. The resulting anion is a colorless species that plays a critical role in nutrition and is believed to cure many diseases. A fluoresceinated aminohexanol tethered inositol hexakisphosphate (III) had been synthesized earlier involving many complicated steps. We describe here a simple two-step synthesis of (III) and its characterization using different techniques such as matrix-assisted laser desorption ionization mass spectrometry, tandem mass spectrometry, and Fourier transform infrared, ultraviolet-visible, ultraviolet-fluorescence, 1H nuclear magnetic resonance (NMR), and two-dimensional NMR spectroscopies. The effect of (III) has been investigated in the model systems, Arabidopsis thaliana and Drosophila melanogaster. Using Schrodinger software, computational studies on the binding of (III) with the protein 2P1M (Auxin-receptor TIR1-adaptor ASK1 complex) has revealed strong binding propensity with this compound. These studies on the fluoresceinated tethered phytic acid could have far reaching implications on its efficacy for human health and treatment of diseases (cancer/tumor and glioblastoma) and for understanding phosphorous recycling in the environment, especially for plant systems.

Giant pressure sensitivity in piezo/ferro-electric ceramics.

We report the fabrication of single-phase polycrystalline Pb0.85Bi0.10(Zr0.52Ti0.48)O3 (PBiZT) ceramic which shows large polarization, i.e., ∼40 µC cm-2 and piezoelectric coefficients ∼130 pC N-1 and giant linear change in capacitive reactance and dielectric properties with increasing and decreasing pressure in the range of 1 kHz to 5 MHz. Nearly 70% change in dielectric constant and 56% change in capacitive reactance were obtained in the pressure range of 20-200 MPa, which makes it suitable for applications as a capacitive pressure sensor/gauge. The sensitivity of the device is calculated as 0.66 MPa-1 and 18.2 MPa-1 at 1 MHz and 5 MHz, respectively, which is the highest ever reported value so far for any bulk polycrystalline ceramic. The compressive stress of the device was tested according to the standard test method as a function of linear and volumetric strain, which yields the Young's modulus, Bulk modulus, and Poisson's ratio of the device. These values were further utilized to calculate actual stress in the sample and energy density using ANSYS software, which indicates at least four orders smaller pressure in the sample compared to the applied pressure.

Incidental Carcinoma Gallbladder: Incidence, Risk Factors, and Factors Affecting Survival-5-Year Experience from a Tertiary Care Institute.

INTRODUCTION: Carcinoma gallbladder is a very lethal disease. It can get detected incidentally after laparoscopic cholecystectomy. The overall outcome of incidentally detected carcinoma gallbladder is a matter of debate in literature. AIM: To estimate the overall incidence of the incidental gallbladder carcinoma, the various risk factors associated with it and factors affecting overall survival in patients who underwent laparoscopic cholecystectomy with eventual histology turning out to be carcinoma gallbladder. METHODS: Data of all the patients undergoing laparoscopic cholecystectomies in one surgical unit under the Department of Surgery at All India Institute of Medical Sciences, New Delhi, India, between January 2014 and December 2018 was retrospectively analyzed. All patients with incidental carcinoma gallbladder were followed up and completion radical cholecystectomy was performed. The demographic profile, preoperative imaging, intra-operative finding, histopathology of primary surgery, and median interval between two surgeries were analyzed to look for various risk factors associated with incidental carcinoma gallbladder and factors affecting overall survival. RESULTS: Incidence of the incidental carcinoma gallbladder was 0.51% with a female/male ratio of 4:1 and mean age of 47.2 years. Preoperative imaging of most of them was suggestive of chronic cholecystitis; however, one patient had multiple gallbladder polyps. Six patients had uneventful laparoscopic cholecystectomy, while four had bile spillages intraoperatively. All the patients had adenocarcinoma on histopathology. Pathological staging of four patients was pT1b and six patients had pT2 tumor. The median interval between cholecystectomy and completion radical cholecystectomy in this series was 8 weeks. At the end of 19-month median follow-up, overall survival was 55.5%. CONCLUSION: Incidence of incidental carcinoma gallbladder is 0.51%, most commonly affecting middle-aged females. Risk factors associated with incidental carcinoma gallbladder were found to be multiple gallbladder calculi, single large stone, and gallbladder polyps. Survival is better in males, young patients with uneventful primary surgery and better-differentiated pathology.

Glycosylation differentially modulates membranolytic and chaperone-like activities of PDC-109, the major protein of bovine seminal plasma.

The major bovine seminal plasma protein, PDC-109, is a mixture of glycosylated (BSP-A1) and non-glycosylated (BSP-A2) isoforms of a 109-residue long polypeptide. It binds to spermatozoa by specifically recognizing choline phospholipids on the plasma membrane and destabilizes it by penetrating the hydrophobic interior, resulting in lipid efflux, which is necessary for sperm capacitation and successful fertilization. PDC-109 also acts as a molecular chaperone and protects target proteins from denaturation and aggregation induced by various types of stress. In order to investigate the role of glycosylation in these activities, we have separated BSP-A1 and BSP-A2 from PDC-109, and also cloned and expressed BSP-A2 in E. coli and purified the recombinant BSP-A2 (rBSP-A2) to homogeneity. Employing biophysical and biochemical approaches we have investigated the membrane-perturbing and chaperone-like activities (CLA) of PDC-109, BSP-A1, BSP-A2 and recombinant BSP-A2 (rBSP-A2). The results obtained demonstrate that glycan-lacking wild-type BSP-A2 and rBSP-A2 exhibit higher membrane-perturbing activity but decreased CLA as compared to PDC-109. In contrast, BSP-A1 exhibits significantly higher CLA than PDC-109, but its ability to destabilize membranes is considerably lower. This differential modulation of the membrane-perturbing and chaperone-like activities has been explained on the basis of higher membrane-penetrating ability and lower solubility of glycan-lacking BSP-A2 as compared to the glycosylated BSP-A1.

Outcomes in Super Obese Patients Undergoing One Anastomosis Gastric Bypass or Laparoscopic Sleeve Gastrectomy.

INTRODUCTION: The data on the role of OAGB in super obese patients and its direct comparison with LSG in super obese patients is scarce. OBJECTIVES: To compare weight loss, impact on comorbidities and nutritional parameters between LSG and OAGB in super obese patients. METHODS: Prospectively collected data of 75 matched patients with BMI > 50, who underwent either laparoscopic sleeve gastrectomy (LSG) or one anastomosis gastric bypass (OAGB), was analyzed retrospectively. Percentage excess weight loss at 1 year and impact on comorbidities were compared in both the groups. RESULTS: Both the groups were comparable for age, sex, BMI, and presence or absence of diabetes mellitus. Mean TWL% ± 2SD at 1 year was 30.09% ± 19.76 in patients undergoing LSG, while it was 39.9% ± 12.78 in patients undergoing OAGB (p < 0.001). In the LSG group, 85.7% and 66.67% of patients had remission of diabetes mellitus and hypertension, respectively, as compared to 77.77% and 78.5%, respectively, in the OAGB group. All the patients with OSA had a resolution of their symptoms in both the groups. Patients in the OAGB group became more folate deficient despite regular supplementation. CONCLUSION: Weight loss following OAGB was found to be better than LSG in the super obese patients in our study. There was a similar resolution of comorbidities and a lesser rate of major complications in the OAGB group.

Proceedings of the 2018 National Toxicology Program Satellite Symposium.

The 2018 annual National Toxicology Program Satellite Symposium, entitled "Pathology Potpourri," was held in Indianapolis, Indiana, at the Society of Toxicologic Pathology's 37th annual meeting. The goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. This article presents summaries of the speakers' talks along with select images that were used by the audience for voting and discussion. Various lesions and other topics covered during the symposium included seminiferous tubule dysgenesis in rats, ameloblast and odontoblast degeneration/necrosis in a Sprague Dawley rat, intestinal leiomyositis in a beagle dog, gallbladder mucinous hyperplasia, focus of hepatocellular alteration and bile duct alteration in otters, renal tubule cytoplasmic vacuolation with basophilic granules in mice treated swith antisense oligonucleotide therapy, a uterine choriocarcinoma in a rhesus macaque, and rete ovarii proliferative ovarian lesions in various aged rat strains. One particularly provocative lesion was a malignant neoplastic proliferation in the renal pelvic region of a cynomolgus macaque from a 21-day study. Additional challenging lesions included thyroid proliferative lesions in zebra fish and gross findings in fish larvae during routine chemical screening. The Rabbit and Minipig International Harmonization of Nomenclature and Diagnostic Criteria Organ Working Groups also presented a series of challenging lesions.

Fasiglifam (TAK-875): Mechanistic Investigation and Retrospective Identification of Hazards for Drug Induced Liver Injury.

TAK-875, a GPR40 agonist, was withdrawn from Phase III clinical trials due to drug-induced liver injury (DILI). Mechanistic studies were conducted to identify potential DILI hazards (covalent binding burden (CVB), hepatic transporter inhibition, mitochondrial toxicity, and liver toxicity in rats) associated with TAK-875. Treatment of hepatocytes with radiolabeled TAK-875 resulted in a CVB of 2.0 mg/day, which is above the threshold of 1 mg/day considered to be a risk for DILI. Covalent binding to hepatocytes was due to formation of a reactive acyl glucuronide (AG) and, possibly, an acyl-CoA thioester intermediate. Formation of TAK-875AG in hepatocytes and/or in vivo was in the order of non-rodents > human (in vitro only) > rat. These data suggest that non-rodents, and presumably humans, form TAK-875AG more efficiently than rats, and that AG-mediated toxicities in rats may only occur at high doses. TAK-875 (1000 mg/kg/day) formed significant amounts of AG metabolite (≤32.7 µM) in rat liver that was associated with increases in ALT (×4), bilirubin (×9), and bile acids (×3.4), and microscopic findings of hepatocellular hypertrophy and single cell necrosis. TAK-875 and TAK-875AG had similar potencies (within 3-fold) for human multi-drug resistant associated protein 2/4 (MRP2/4) and bile salt export pump, but TAK-875AG was exceptionally potent against MRP3 (0.21 µM). Inhibition of MRPs may contribute to liver accumulation of TAK-875AG. TAK-875 also inhibited mitochondrial respiration in HepG2 cells, and mitochondrial Complex 1 and 2 activities in isolated rat mitochondria. In summary, formation of TAK-875AG, and possibly TAK-875CoA in hepatocytes, coupled with inhibition of hepatic transporters and mitochondrial respiration may be key contributors to TAK-875-mediated DILI.