Narratives of childhood sexual abuse: healing through music in Ian McEwan's On Chesil Beach.

Narratives of survivors or by survivors offer useful and compelling insights into the experiences of abuse and its consequent effect on health. Reading such narratives can help a physician or clinician to understand the complexities of abuse. Furthermore, the critical study of narratives can open multiple therapeutic options for survivors of abuse to cater both their mental health and medical problems. In this article, we deal with the genre of childhood sexual abuse survivor's narrative and its clinical application adding to the discourse of medical humanities and then critically examine one such narrative (On Chesil Beach by Ian McEwan) in particular and explore the therapeutics of music in abused victim's clinical care.

Internal student migration in India: Impact of the COVID-19 crisis.

The education sector in India was among the most affected sectors during the COVID-19 pandemic. While considerable attention has been paid to informal workers' return or reverse migration to their home communities, not much has been reported about the challenges faced by migrant students. Using a mixed-method approach, the current study presents an overview of internal student migration in India prior to the COVID-19 pandemic using data from the 2001 and 2011 Census of India and the 2007-2008 National Sample Survey Organization, and discusses challenges faced by selected migrant learners during the COVID-19 pandemic based on primary research. Based on the census data, nearly 3.3 million migrants in India move for study reasons with 2.9 million migrating within the state (with the duration of residence less than five years) from their last residence within India. The pattern of female student migration suggests an increasingly localized interdistrict migration. Findings from the qualitative data indicate that during the pandemic, students had compromised learning and placement experience, inadequate digital resources and pressure to repay loans. Student migrants experienced varying degrees of the impact of the COVID-19 pandemic based on their destination and migration stream.

An Insight into Efflux-Mediated Arsenic Resistance and Biotransformation Potential of Enterobacter Cloacae RSC3 from Arsenic Polluted Area.

Indiscriminate discharge of heavy metals/metalloids from different sources into the sustainable agro-ecosystem is a major global concern for food security and human health. Arsenic (As), categorized as group one human carcinogen is a quintessential toxic metalloid that alters the microbial compositions and functions, induce physiological and metabolic changes in plants and contaminate surface/ground water. The management of arsenic toxicity, therefore, becomes imminent. Acknowledging the arsenic threat, the study was aimed at identifying arsenic resistant bacteria and evaluating its arsenic removal/detoxification potential. Of the total 118 bacterial isolates recovered from arsenic rich environment, the bacterial strain RSC3 demonstrating highest As tolerance was identified as Enterobacter cloacae by 16S rRNA gene sequence analysis. Enterobacter cloacae tolerated high concentration (6000 ppm) of As and exhibited 0.55 h-1 of specific growth rate as calculated from growth kinetics data. Strain RSC3 also displayed varying level of resistance to other heavy metals and many antibacterial drugs in plate bioassay. The bacterial strain RSC3 possessed gene (arsC) which causes transformation of arsenate to arsenite. The arsenate uptake and efflux of the bacterial cells was revealed by high throughput techniques such as AAS, SEM/TEM and EDX. The simultaneous As reducing ability, and multi metal/multi-antibiotics resistance potentials of E. cloacae provides a promising option in the microbes based remediation of As contaminated environments.

Role of genetic variants of Vitamin D receptor, Toll-like receptor 2 and Toll-like receptor 4 in extrapulmonary tuberculosis.

BACKGROUND: Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (MTB). Vitamin D deficiency and vitamin D receptor (VDR) gene abnormalities confer susceptibility to tuberculosis. Toll-like receptors (TLRs), such as TLR-2, are also important mediators of inflammatory response against Mycobacterium tuberculosis. We evaluated VDR, TLR-2 and TLR-4 gene polymorphisms in patients with extrapulmonary tuberculosis (EPTB). OBJECTIVES: To find out a possible association of Vitamin D receptor (VDR) (rs731236), TLR-2 (196-174 Ins > Del) and TLR-4 (Thr399Ile) gene polymorphisms with extrapulmonary tuberculosis in ethnic Kashmiri population. METHODS: A total of 100 extrapulmunary tuberculosis cases and 102 healthy controls were analyzed for Vitamin D receptor (VDR) (rs731236), TLR-2 (196-174 ins > del) and TLR-4 (Thr399Ile) gene polymorphisms using PCR-RFLP and Allele-Specific PCR methods. RESULTS: We found increased frequency of TLR-4 Thr/Ile heterozygous genotype in cases as compared with healthy controls (22% vs 5.8%). Thus acting as a risk factor for extrapulmonary tuberculosis, as was elucidated from statistical analysis [OR, 4.5; 95% CI (1.74-11.68); P < 0.001]. In case of TLR-2 (196-174 ins > del) we observed significant differences in the homozygous variant (Del/Del) genotype of cases and controls (28% in cases & 2.94% in controls). Thus, TLR-2 (Del/Del) genotype acts as a strong risk factor for extrapulmonary tuberculosis predisposition [OR, 12.2; 95% CI (3.5-42.69); P < 0.001]. We did not find any significant differences in the genotypic distribution of (VDR) (rs731236) T > C SNP between cases and controls (P > 0.05). CONCLUSION: TLR-4 (Thr/Ile) and TLR-2 (Del/Del) act as significant risk factors for extrapulmonary tuberculosis predisposition in ethnic Kashmiri population.

Concrete Crack Restoration Using Bacterially Induced Calcium Metabolism.

Concrete structures are prone to develop cracks and cause devastation. Repair and renovation are not enough to ensure complete eradication of crack development. The entire process is costly and laborious. The microbiologically induced calcium carbonated precipitation can be effective in restoring the cracks. The calcium-based nutrients along with specific bacterial strain have been used in the present investigation. The pellets of calcium as per Fourier transform infrared spectroscopy and energy-dispersive X-ray spectroscopy are deposited in the cracks of the concrete over a period of 7 days of incubation. The presence of bacteria in the calcium precipitates as demonstrated by scanning electron microscope provides adequate strength and adhering quality to the pellets. The effective filling of cracks is confirmed with the help ultrasonic pulse velocity test also. Since, elephantine heritage and high sky buildings have high maintenance costs, the use of present technique will cut down the cost and duration of restoration. SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s12088-020-00916-0) contains supplementary material, which is available to authorized users.

European Association of Cardiothoracic Anesthesiology (EACTA) Cardiothoracic and Vascular Anesthesia Fellowship Curriculum: First Edition.

This special article summarizes the design and certification process of the European Association of Cardiothoracic Anesthesiology (EACTA) Cardiothoracic and Vascular Anesthesia (CTVA) Fellowship Program. The CTVA fellowship training includes a two-year curriculum at an EACTA-accredited educational facility. Before fellows are accepted into the program, they must meet a number of requirements, including evidence of a valid license to practice medicine, a specialist degree examination in anesthesiology, and appropriate language skills as required in the host centers. The CVTA Fellowship Program has 2 sequential and complementary levels of training-both with a modular structure that allows for individual planning and also takes into account the differing national healthcare needs and requirements of the 36 countries represented in EACTA. The basic training period focuses on the anesthetic management of patients undergoing cardiac, thoracic, and vascular surgery and related procedures. The advanced training period is intended to deepen and to extend the clinical and nontechnical skills that fellows have acquired during the basic training. The goal of the EACTA fellowship is to produce highly trained and competent perioperative physicians who are able to care for patients undergoing cardiac, thoracic, and vascular anesthesia.

Flower Shaped Gold Nanoparticles: Biogenic Synthesis Strategies and Characterization.

Microbes can serve as mediators for the fabrication of complicated nano-structures, obviating the tedious and time-consuming methods of synthesis. The shape of a nanoparticle has a very prominent role in defining the functionality in prospective arenas. So, the flower shaped nanoparticles are in focus nowadays due to their enhanced electrocatalytic and optical properties as compared to the spherical ones. We present the biosynthesis of flower shaped gold nanoparticles by Bacillus subtilis RSB64 and process parameters optimization using central composite design. The two well-separated scattering spectra showing absorption peaks at 540 nm and 750 nm indicate the presence of anisotropic gold nanoparticles and the results were corroborated by transmission electron microscopy analysis. The presence of gold nanoparticles was further confirmed by energy dispersive X-ray studies. The functional groups responsible for the stability of gold nanoparticles were predicted by Fourier transform infrared spectroscopy. The gold nanoparticles biosynthesis were collective effects of three experimental process parameters viz pH, temperature and precursor concentration. These three parameters were statistically optimized wherein pH 11.0, substrate concentration 1:1 (v/v) and temperature of 50 °C resulted in the synthesis of stable flower shaped gold nanoparticles of 50 nm size. The results indicated the tailored biosynthesis of gold nanoparticles with a flower like morphology by multi process parameter analysis to finalize robust conditions for the synthesis using B. subtilis RSB64. These gold nanoflowers demonstrate increased surface area efficiency/reactivity and could be employed for sustained and controlled delivery of drugs.

Molecular Modeling of Cloned Bacillus subtilis Keratinase and Its Insinuation in Psoriasis Treatment Using Docking Studies.

Present study demonstrated the expression of cloned Bacillus subtilis RSE163 keratinase gene and in silico binding affinities of deduced protein with psoriasis topical drugs for systemic absorption and permeation through skin. The ker gene expressed in E. coli showed significantly higher keratinase activity 450 ± 10.43 U representing 1342 bp nucleotides encoding 447 amino acids with molecular weight of 46 kDa. The modeled structure was validated using ramachandran's plot showing 305 residues (84.3%) in most favoured region. Docking studies using extra precision (XP) method of Glide showed optimum binding affinities with the drugs Acitretin (- 39.62 kcal/mol), Clobetasol propionate (- 37.90 kcal/mol), Fluticasone (- 38.53 kcal/mol), Desonide (- 32.23 kcal/mol), Anthralin (- 38.04 kcal/mol), Calcipotreine (- 21.55 kcal/mol) and Mometasone (- 28.40 kcal/mol) in comparison to other psoriasis drugs. The results can further be correlated with in vitro enzymatic experiments using keratinase as an effective drug mediator through skin to serve the unmet need of industries.

Cloning of merA Gene from Methylotenera Mobilis for Mercury Biotransformation.

Mercury (Hg) is one of the most toxic heavy metal and is extremely harmful for the environment. The permissible limit of mercury in industrial effluents is 0.001 ppm, whereas there are various sites having very high levels of mercury contamination. In the present study, 10 different mercury (Hg) resistant bacterial strains were isolated from Ulhas Estuary, Mumbai (Hg concentration of 107 ppm). All the strains were subsequently grown on higher concentration of mercuric chloride (HgCl2), one of the isolate (USP5) showed significant growth at high concentration of Hg (40 ppm) and 16S rRNA gene sequencing revealed the identity of the bacterium as Methylotenera mobilis, (Accession no. KT714144). The mer operon was isolated and cloned in E.coli and checked for its ability to tolerate higher concentration of Hg. It has shown growth up to 70 ppm of Hg, also presence of merA gene indicated its ability to detoxify Hg into less toxic volatile form. The atomic absorption spectrophotometry confirmed the ability of clone to efficiently detoxify 60-90 % of the Hg (10-70 ppm) within 48-72 h. This clone can be used for effective volatilization of Hg from contaminated areas.

The role of nanotechnology in combating multi-drug resistant bacteria.

The development of antibiotics has played a significant role in combating the dreaded infectious disease such as tuberculosis, pneumonia, typhoid fever and meningitis in 20th century. However, the improper use of antibiotics led to the development of multidrug resistance (MDR) in microbial flora raising a global public health concern of 21st century. This unforeseen threat demands the development of new drugs and strategies for combating antibiotic resistance shown by many microbial species. Recent developments in nanotechnology to engineer nanoparticles with desired physicochemical properties have been projected as a new line of defense against MDR micro-organism. In this review, we summarized and discussed the recent development demonstrating the potential of nanomaterials to evade the MDR. Nanoparticles have shown effective antimicrobial activity against MDR bacteria, such as Acinetobacter baumanii, Pseudomonas aeruginosa, Klebsiella pneumoniae, Mycobacterium tuberculosis, vancomycin resistant enterococci, methicillin-resistant Staphylococcus aureus and others. Furthermore, new strategies like combination of radiation and drugs with nanoparticle that are being explored to potentiate the effectiveness against MDR bacteria have also been summarized.

Hydrolyzing proficiency of keratinases in feather degradation.

The keratinase degrade highly rigid, cross linked structural polypeptides with different efficiency depending on the type of source. Two newly isolated strains of Bacillus subtilis (RSE163 and RSE165; NCBI Accession no JQ887983 and JQ887982) were found to be efficient keratinase producers with unusual catalytic activity result in different morphological changes in degradation pattern of feather, confirmed by their scanned electron micrographs. Maximum keratinolytic activity of both the strains B. subtilis RSE163 and RSE165 were found to be 366 ± 15.79 and 194 ± 7.26 U after 72 h of incubation. While the disulphide reductase activity of RSE163 and RSE165 estimated 0.24 ± 0.05 and 0.15 ± 0.03 U/ml of enzyme after 24 h of incubation. A total of 16 free amino acids of variable concentration were also analyzed in the cell free supernatant of hydrolyzed feather from two strains. Present study demonstrates the action of two different keratinases in feather degradation.

Chasmophyte associated stress tolerant bacteria confer drought resilience to chickpea through efficient nutrient mining and modulation of stress response.

In the present study, ten (10) selected bacteria isolated from chasmophytic wild Chenopodium were evaluated for alleviation of drought stress in chickpea. All the bacterial cultures were potential P, K and Zn solubilizer. About 50% of the bacteria could produce Indole-3-acetic acid (IAA) and 1-aminocyclopropane-1-carboxylate (ACC) deaminase. The bacteria showed wide range of tolerance towards pH, salinity, temperature and osmotic stress. Bacillus paralicheniformis L38, Pseudomonas sp. LN75, Enterobacter hormachei subsp. xiangfengensis LJ89, B. paramycoides L17 and Micrococcus luteus LA9 significantly improved growth and nutrient (N, P, K, Fe and Zn) content in chickpea under water stress during a green house experiment conducted following a completely randomized design (CRD). Application of Microbacterium imperiale LJ10, B. stercoris LN74, Pseudomonas sp. LN75, B. paralicheniformis L38 and E. hormachei subsp. xiangfengensis LJ89 reduced the antioxidant enzymes under water stress. During field experiments conducted following randomized block design (RBD), all the bacterial inoculations improved chickpea yield under water stress. Highest yield (1363 kg ha-1) was obtained in plants inoculated with Pseudomonas sp. LN75. Pseudomonas sp. LN75, B. paralicheniformis L38 and E. hormachei subsp. xiangfengensis LJ89 have potential as microbial stimulants to alleviate the water stress in chickpea. To the best of our knowledge this is the first report of using chasmophyte associated bacteria for alleviation of water stress in a crop plant.

Comparison of local versus intramuscular steroid injection in patients with carpal tunnel syndrome: A prospective open label randomized clinical trial.

AIM: This study compared the efficacy and safety of local corticosteroid injection (LCI) vs intramuscular (IM) corticosteroid injection in mild to moderate carpal tunnel syndrome (CTS). METHODS: This is an open labeled, randomized controlled trial conducted during December 2021 to August 2023. Eighty-six patients with CTS were randomized in 1:1 ratio to receive either single 40 mg methylprednisolone (MP) injection at the wrist (LCI arm), or single 40 mg MP intramuscular injection (IM arm) in the deltoid. Primary outcome was absolute Symptom Severity Scale (SSS) at 3 months. Secondary outcomes were SSS score at 1-month, Functional Status Scale (FSS) score at 1 and 3 months, and recurrence at 3 months and injection site pain assessed on visual analog (VAS) scale. RESULTS: Median age was 45 (range 22 - 80) years, and 86 % were females. Baseline characteristics were comparable between groups. Mean SSS score at 3 months was similar in two arms (1.72 ± 0.71 vs 2.0 ± 0.93) with mean difference (MD) -0.03 (-0.31 to 0.25, p = 0.83) after adjusting for baseline SSS scores. LCI, however, resulted in significantly better SSS (1.48 ± 0.51 vs 1.88 ± 0.69, adjusted p = 0.04), and FSS scores (1.57 ± 0.44 vs 1.80 ± 0.66, adjusted p = 0.03) at 1 month compared to IM arm. Response rate (67.4 % vs 55.8 %; p = 0.30) and recurrence rate (17.1 % vs 22.6 %, p = 0.74) at 3 months were similar. Injection site pain was severe in LCI arm[median 5 (range 3 - 8) vs median 3 (range 2 - 6)]. CONCLUSIONS: In patients with mild to moderate CTS, LCI resulted in better improvement in the BCTQ scores at 1 month compared to IM steroid. However, 3-month's outcome was similar. Intramuscular steroid injection was better tolerated.

Green synthesis of zinc oxide nanoparticles using lychee peel and its application in anti-bacterial properties and CR dye removal from wastewater.

In nanoscience and nanobiotechnology, using plant extracts in synthesizing metal nanoparticles (NPs) has recently come to light as an exciting opportunity with several benefits over traditional physicochemical methods. In the present work, zinc oxide (ZnO) based nanoparticles (NPs) were synthesized by green chemistry route using lychee peel extract to capture hazardous congo red dye from wastewater and illustrate their antimicrobial behavior. The X-Ray Diffraction (XRD) spectra confirm the wurtzite crystal structure, and Fourier Transform Infrared (FTIR) spectra confirm the functional group in ZnO, which is suitable for dye adsorption. It was found that the NPs were spherical and had a size of <10 nm. The synthesized ZnO NPs could effectively remove >98% of CR dye from wastewater within 120 min of contact time at a wide pH range from 2 to 10. The primary mechanism involved in removing dye was the electrostatic interaction between ZnO adsorbent and CR dye. The antimicrobial performance of synthesized ZnO NPs was found to show 34% inhibition against Bacillus subtilis (ATCC 6538), 52% against Escherichia coli (ATCC 11103), 58% against Pseudomonas aeruginosa (ATCC 25668) and 32% against Staphylococcus aureus (ATCC 25923) using well diffusion assay. ZnO demonstrates a suitable anti-bacterial property over both gram-positive and gram-negative pathogenic bacteria. Overall, the green synthesized method for developing ZnO NPs shows promising and significant anti-bacterial performance and is a highly potential adsorbent for removing CR dye from wastewater.

Microbial lipopeptides: Properties, mechanics and engineering for novel lipopeptides.

Microorganisms produce active surface agents called lipopeptides (LPs) which are amphiphilic in nature. They are cyclic or linear compounds and are predominantly isolated from Bacillus and Pseudomonas species. LPs show antimicrobial activity towards various plant pathogens and act by inhibiting the growth of these organisms. Several mechanisms are exhibited by LPs, such as cell membrane disruption, biofilm production, induced systematic resistance, improving plant growth, inhibition of spores, etc., making them suitable as biocontrol agents and highly advantageous for industrial utilization. The biosynthesis of lipopeptides involves large multimodular enzymes referred to as non-ribosomal peptide synthases. These enzymes unveil a broad range of engineering approaches through which lipopeptides can be overproduced and new LPs can be generated asserting high efficacy. Such approaches involve several synthetic biology systems and metabolic engineering techniques such as promotor engineering, enhanced precursor availability, condensation domain engineering, and adenylation domain engineering. Finally, this review provides an update of the applications of lipopeptides in various fields.

Fibrin and Fibrinolytic Enzyme Cascade in Thrombosis: Unravelling the Role.

Blood clot formation in blood vessels (thrombosis) is a major cause of life-threatening cardiovascular diseases. These clots are formed by αA-, ßB-, and ϒ-peptide chains of fibrinogen joined together by isopeptide bonds with the help of blood coagulation factor XIIIa. These clot structures are altered by various factors such as thrombin, platelets, transglutaminase, DNA, histones, and red blood cells. Various factors are used to dissolve the blood clot, such as anticoagulant agents, antiplatelets drugs, fibrinolytic enzymes, and surgical operations. Fibrinolytic enzymes are produced by microorganisms (bacteria, fungi, etc.): streptokinase of Streptococcus hemolyticus, nattokinase of Bacillus subtilis YF 38, bafibrinase of Bacillus sp. AS-S20-I, longolytin of Arthrobotrys longa, versiase of Aspergillus versicolor ZLH-1, etc. They act as a thrombolytic agent by either enhancing the production of plasminogen activators (tissue or urokinase types), which convert inactive plasminogen to active plasmin, or acting as plasmin-like proteins themselves, forming fibrin degradation products which cause normal blood flow again in blood vessels. Fibrinolytic enzymes may be classified in two groups, as serine proteases and metalloproteases, based on their catalytic properties, consisting of a catalytic triad responsible for their fibrinolytic activity having different physiochemical properties (such as molecular weight, pH, and temperature). The analysis of fibrinolysis helps to detect hyperfibrinolysis (menorrhagia, renal failure, etc.) and hypofibrinolysis (diabetes, obesity, etc.) with the help of various fibrinolytic assays such as a fibrin plate assay, fibrin microplate assay, the viscoelastic method, etc. These fibrinolytic activities serve as a key aspect in the recognition of numerous cardiovascular diseases and can be easily produced on a large scale with a short generation time by microbes and are less expensive.

Dose-Effect Relationship of Motor Nerve Inexcitability on Outcome in Guillain-Barré Syndrome: A Prospective Cohort Study.

Objective: One or more inexcitable motor (IM) nerves are common during electrodiagnostic (EDx) study in Guillain-Barré syndrome (GBS). This study assessed the dose-effect relationship of IM nerves on outcome in patients with acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor and/or sensory axonal neuropathy (AMAN and AMSAN). Materials and Methods: Eighty-eight GBS patients admitted during May 2018-June 2023 underwent detailed clinical evaluation and EDx study. Admission and follow-up disability were assessed on a 0-10 Clinical Grading Scale (CGS). Outcome was recovery at 6 months, defined as good (CGS <3) and poor (CGS ≥3). Binary multivariate logistic regression with backward elimination was used to calculate independent predictors of outcome. Results: Proportion of patients with complete recovery decreased significantly with increasing numbers of IM nerves (P < 0.01). Seventy-six patients were followed for 6 months. Among patients with IM nerves (n = 28), complete recovery was similar between AIDP and axonal GBS (70% vs. 50%, respectively; P = 0.40). However, in patients with recordable compound muscle action potentials (CMAPs) in all the motor nerves (n = 26), axonal GBS had significantly poor recovery compared to AIDP (75% vs. 9.1%; P = 0.01). Among patients receiving intravenous immunoglobulin (IVIg; n = 42), poor recovery was seen in 53.6% with IM nerves compared to 35.7% without (P = 0.28), while it was 37.5% versus 5.6% (P = 0.04), respectively, in those who did not receive IVIg (n = 34). However, only admission disability (odds ratio [OR] 0.88, 95% confidence interval [CI] 0.81-0.97; P = 0.007) was found to be an independent predictor of outcome. Conclusion: Although increasing numbers of IM nerves were associated with poor outcome on univariate analysis, they did not predict 6 months' outcome independently. Outcome did not differ between axonal GBS and AIDP among those with IM nerves. IVIg improved outcome in patients with IM nerves.

Structural-functional analysis and molecular characterization of arsenate reductase from Enterobacter cloacae RSC3 for arsenic biotransformation.

Enterobacter cloacae RSC3 isolated from an industrial pesticide site transformed arsenate into arsenite. The arsenate is transported by membrane-bound phosphate transporter and transformed to arsenite by arsenate reductase (arsC). E. cloacae RSC3 produced an arsenate reductase enzyme with a maximum activity of 354 U after 72 h of incubation. Arsenate reductase was found to be active and stable at a wide range of temperatures (20 and 45 °C) and pH (5-10), with maximum activity at 35 °C and pH 7.0. The arsenate reductase protein was further characterised molecularly using different bioinformatics tools. The 3D structure of ArsC protein was predicted by homology modelling and validated by the Ramachandran plot with 91.9% residues in the most favoured region. ArsC protein of E. cloacae RSC3 revealed structural homology with ArsC from PDB ID: 1S3C. The gene ontology results also showed that the ArsC protein had a molecular functionality of the arsenate reductase (glutaredoxin) activity and the biological function of cellular response to DNA damage stimulus. Molecular docking analysis of 3D structures using AutoDock vina-1.5.7 server predicted four ligand binding active site residues at Gln70, Asp68, Leu68, and Leu63. Strong ArsC-arsenate ion interaction was observed with binding energy -1.03 kcal/mol, indicating significant arsenate reductase activity and specificity of ArsC protein. On the basis of molecular dynamics simulation analysis, the RMSD and RMSF values revealed the stability of ArsC protein from E. cloacae RSC3. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03730-9.

Comparison of Human Epididymis Protein 4, Cancer Antigen 125, and Ultrasound Prediction Model in Differentiating Benign from Malignant Adnexal Masses.

Background: This study aimed to compare the diagnostic performance of carcinogenic antigen (CA) 125, (HE)-4 (Human epididymis protein 4), and ultrasound (International Ovarian Tumor Analysis [IOTA]) Simple Rules individually and to derive a composite score in the differentiating ovarian cancer from benign ovarian mass. Subjects and Methods: Consecutive patients (n = 100) with pelvic mass admitted during February 2018-August 2019 were included prospectively. Patients with either known case of epithelial ovarian cancer (EOC) or metastatic EOC were excluded. The primary outcome was to assess the sensitivity and specificity of CA-125, HE-4, and IOTA Simple Rules in predicting benign from malignant mass independently, while secondary outcome was derivation of a new model incorporating these variables using multivariate logistic regression analysis to predict benign from malignant lesions. Receiver operator curve (ROC) was drawn to redefine the best-performing cutoff values and difference between area under the ROC (AUROC) were compared by DeLong's method. Results: Out of 100 cases of adnexal mass selected, the sensitivity and specificity of CA-125 were 73.8% and 77.6%, HE-4 were 90.5% and 87.9%, and IOTA Simple Rules were 92.9% and 81.0%. CA-125, HE-4, and IOTA Simple Rules were independently associated with the likelihood of malignancy/borderline (P < 0.001). The area under the curve for the "composite score" (AUC = 0.93) was the highest and was significantly better than that of CA-125 (AUC = 0.786) (P = 0.004 using DeLong's test) and comparable with HE-4 (AUROC = 0.90; P = 0.128 using DeLong's Test). Conclusion: The sensitivity and specificity of HE-4 and IOTA Simple Rules for predicting malignant ovarian tumor was better than those of CA-125. The diagnostic performance of "composite score" was comparable to those of either HE-4 or IOTA Simple Rules and significantly better than CA-125.

Haploid insufficiency of suppressor enhancer Lin12 1-like (SEL1L) protein predisposes mice to high fat diet-induced hyperglycemia.

Increasing evidence suggests that endoplasmic reticulum (ER) stress plays an important role in the pathogenesis of type 2 diabetes mellitus. SEL1L is an ER membrane protein that is highly expressed in the pancreatic islet and acinar cells. We have recently reported that a deficiency of SEL1L causes systemic ER stress and leads to embryonic lethality in mice. Here we show that mice with one functional allele of Sel1l (Sel1l(+/-)) are more susceptible to high fat diet (HFD)-induced hyperglycemia. Sel1l(+/-) mice have a markedly reduced ß-cell mass as a result of decreased ß-cell proliferation. Consequently, Sel1l(+/-) mice are severely glucose-intolerant and exhibit significantly retarded glucose-stimulated insulin secretion. Pancreatic islets from Sel1l(+/-) mice stimulated with a high concentration of glucose in vitro express significantly higher levels of unfolded protein response genes than those from wild-type control mice. Furthermore, dominant-negative interference of SEL1L function in insulinoma cell lines severely impairs, whereas overexpression of SEL1L efficiently improves protein secretion. Taken together, our results indicate that haploid insufficiency of SEL1L predispose mice to high fat diet-induced hyperglycemia. Our findings highlight a critical and previously unknown function for SEL1L in regulating adult ß-cell function and growth.