Pemigatinib for metastatic or surgically unresectable urothelial carcinoma with FGF/FGFR genomic alterations: final results from FIGHT-201.

BACKGROUND: Fibroblast growth factor receptor 3 (FGFR3) alterations are oncogenic drivers of urothelial carcinoma (UC). Pemigatinib is a selective, oral inhibitor of FGFR1-3 with antitumor activity. We report the efficacy and safety of pemigatinib in the open-label, single-arm, phase II study of previously treated, unresectable or metastatic UC with FGFR3 alterations (FIGHT-201; NCT02872714). PATIENTS AND METHODS: Patients ≥18 years old with FGFR3 mutations or fusions/rearrangements (cohort A) and other FGF/FGFR alterations (cohort B) were included. Patients received pemigatinib 13.5 mg once daily continuously (CD) or intermittently (ID) until disease progression or unacceptable toxicity. The primary endpoint was centrally confirmed objective response rate (ORR) as per RECIST v1.1 in cohort A-CD. Secondary endpoints included ORR in cohorts A-ID and B, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Overall, 260 patients were enrolled and treated (A-CD, n = 101; A-ID, n = 103; B, n = 44; unconfirmed FGF/FGFR status, n = 12). All discontinued treatment, most commonly due to progressive disease (68.5%). ORR [95% confidence interval (CI)] in cohorts A-CD and A-ID was 17.8% (10.9% to 26.7%) and 23.3% (15.5% to 32.7%), respectively. Among patients with the most common FGFR3 mutation (S249C; n = 107), ORR was similar between cohorts (A-CD, 23.9%; A-ID, 24.6%). In cohorts A-CD/A-ID, median (95% CI) DOR was 6.2 (4.1-8.3)/6.2 (4.6-8.0) months, PFS was 4.0 (3.5-4.2)/4.3 (3.9-6.1) months, and OS was 6.8 (5.3-9.1)/8.9 (7.5-15.2) months. Pemigatinib had limited clinical activity among patients in cohort B. Of 36 patients with samples available at progression, 6 patients had 8 acquired FGFR3 secondary resistance mutations (V555M/L, n = 3; V553M, n = 1; N540K/S, n = 2; M528I, n = 2). The most common treatment-emergent adverse events overall were diarrhea (44.6%) and alopecia, stomatitis, and hyperphosphatemia (42.7% each). CONCLUSIONS: Pemigatinib was generally well tolerated and demonstrated clinical activity in previously treated, unresectable or metastatic UC with FGFR3 mutations or fusions/rearrangements.

TROPHY-U-01, a phase II open-label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors: updated safety and efficacy outcomes.

BACKGROUND: Sacituzumab govitecan (SG) is a Trop-2-directed antibody-drug conjugate containing cytotoxic SN-38, the active metabolite of irinotecan. SG received accelerated US Food and Drug Administration approval for locally advanced (LA) or metastatic urothelial carcinoma (mUC) previously treated with platinum-based chemotherapy and a checkpoint inhibitor, based on cohort 1 of the TROPHY-U-01 study. Mutations in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene are associated with increased adverse events (AEs) with irinotecan-based therapies. Whether UGT1A1 status could impact SG toxicity and efficacy remains unclear. PATIENTS AND METHODS: TROPHY-U-01 (NCT03547973) is a multicohort, open-label, phase II registrational study. Cohort 1 includes patients with LA or mUC who progressed after platinum- and checkpoint inhibitor-based therapies. SG was administered at 10 mg/kg intravenously on days 1 and 8 of 21-day cycles. The primary endpoint was objective response rate (ORR) per central review; secondary endpoints included progression-free survival, overall survival, and safety. Post hoc safety analyses were exploratory with descriptive statistics. Updated analyses include longer follow-up. RESULTS: Cohort 1 included 113 patients. At a median follow-up of 10.5 months, ORR was 28% (95% CI 20.2% to 37.6%). Median progression-free survival and overall survival were 5.4 months (95% CI 3.5-6.9 months) and 10.9 months (95% CI 8.9-13.8 months), respectively. Occurrence of grade ≥3 treatment-related AEs and treatment-related discontinuation were consistent with prior reports. UGT1A1 status was wildtype (∗1|∗1) in 40%, heterozygous (∗1|∗28) in 42%, homozygous (∗28|∗28) in 12%, and missing in 6% of patients. In patients with ∗1|∗1, ∗1|∗28, and ∗28|∗28 genotypes, any grade treatment-related AEs occurred in 93%, 94%, and 100% of patients, respectively, and were managed similarly regardless of UGT1A1 status. CONCLUSIONS: With longer follow-up, the ORR remains high in patients with heavily pretreated LA or mUC. Safety data were consistent with the known SG toxicity profile. AE incidence varied across UGT1A1 subgroups; however, discontinuation rates remained relatively low for all groups.

Evidence of a Hardening in the Cosmic Ray Proton Spectrum at around 166 TeV Observed by the GRAPES-3 Experiment.

We present the measurement of the cosmic ray proton spectrum from 50 TeV to 1.3 PeV using 7.81×10^{6} extensive air shower events recorded by the ground-based GRAPES-3 experiment between 1 January 2014 and 26 October 2015 with a live time of 460 day. Our measurements provide an overlap with direct observations by satellite and balloon-based experiments. The electromagnetic and muon components in the shower were measured by a dense array of plastic scintillator detectors and a tracking muon telescope, respectively. The relative composition of the proton primary from the air shower data containing all primary particles was extracted using the multiplicity distribution of muons which is a sensitive observable for mass composition. The observed proton spectrum suggests a spectral hardening at ∼166 TeV and disfavors a single power law description of the spectrum up to the Knee energy (∼3 PeV).

Clinical and health care utilization variables can predict 90-day hospital re-admission in adults with Crohn's disease for point of care risk evaluation.

BACKGROUND: Hospital re-admission for persons with Crohn's disease (CD) is a significant contributor to morbidity and healthcare costs. We derived prediction models of risk of 90-day re-hospitalization among persons with CD that could be applied at hospital discharge to target outpatient interventions mitigating this risk. METHODS: We performed a retrospective study in persons with CD admitted between 2009 and 2016 for an acute CD-related indication. Demographic, clinical, and health services predictor variables were ascertained through chart review and linkage to administrative health databases. We derived and internally validated a multivariable logistic regression model of 90-day CD-related re-hospitalization. We selected the optimal probability cut-point to maximize Youden's index. RESULTS: There were 524 CD hospitalizations and 57 (10.9%) CD re-hospitalizations within 90 days of discharge. Our final model included hospitalization within the prior year (adjusted odds ratio [aOR] 3.27, 95% confidence interval [CI] 1.76-6.08), gastroenterologist consultation within the prior year (aOR 0.185, 95% CI 0.0950-0.360), intra-abdominal surgery during index hospitalization (aOR 0.216, 95% CI 0.0500-0.934), and new diagnosis of CD during index hospitalization (aOR 0.327, 95% CI 0.0950-1.13). The model demonstrated good discrimination (optimism-corrected c-statistic value 0.726) and excellent calibration (Hosmer-Lemeshow goodness-of-fit p-value 0.990). The optimal model probability cut point allowed for a sensitivity of 71.9% and specificity of 70.9% for identifying 90-day re-hospitalization, at a false positivity rate of 29.1% and false negativity rate of 28.1%. CONCLUSIONS: Demographic, clinical, and health services variables can help discriminate persons with CD at risk of early re-hospitalization, which could permit targeted post-discharge intervention.

Multi-omics analysis identifies potential microbial and metabolite diagnostic biomarkers of bacterial vaginosis.

BACKGROUND: Bacterial vaginosis (BV) is a common clinical manifestation of a perturbed vaginal ecology associated with adverse sexual and reproductive health outcomes if left untreated. The existing diagnostic modalities are either cumbersome or require skilled expertise, warranting alternate tests. Application of machine-learning tools to heterogeneous and high-dimensional multi-omics datasets finds promising potential in data integration and may aid biomarker discovery. OBJECTIVES: The present study aimed to evaluate the potential of the microbiome and metabolome-derived biomarkers in BV diagnosis. Interpretable machine-learning algorithms were used to evaluate the utility of an integrated-omics-derived classification model. METHODS: Vaginal samples obtained from reproductive-age group women with (n = 40) and without BV (n = 40) were subjected to 16S rRNA amplicon sequencing and LC-MS-based metabolomics. The vaginal microbiome and metabolome were characterized, and machine-learning analysis was performed to build a classification model using biomarkers with the highest diagnostic accuracy. RESULTS: Microbiome-based diagnostic model exhibited a ROC-AUC (10-fold CV) of 0.84 ± 0.21 and accuracy of 0.79 ± 0.18, and important features were Aerococcus spp., Mycoplasma hominis, Sneathia spp., Lactobacillus spp., Prevotella spp., Gardnerella spp. and Fannyhessea vaginae. The metabolome-derived model displayed superior performance with a ROC-AUC of 0.97 ± 0.07 and an accuracy of 0.92 ± 0.08. Beta-leucine, methylimidazole acetaldehyde, dimethylethanolamine, L-arginine and beta cortol were among key predictive metabolites for BV. A predictive model combining both microbial and metabolite features exhibited a high ROC-AUC of 0.97 ± 0.07 and accuracy of 0.94 ± 0.08 with diagnostic performance only slightly superior to the metabolite-based model. CONCLUSION: Application of machine-learning tools to multi-omics datasets aid biomarker discovery with high predictive performance. Metabolome-derived classification models were observed to have superior diagnostic performance in predicting BV than microbiome-based biomarkers.

Assessment of clinical validity of KPG index for 3D classification of impacted maxillary canines by cone beam computed tomography in patients.

OBJECTIVES: The primary objective of this study was to assess the validity of the KPG index in predicting the difficulty of treatment involving impacted maxillary canines. The secondary objective was to assess the reliability and reproducibility of the index. MATERIALS AND METHODS: A retrospective study was conducted on 96 maxillary impacted canines (MIC) in 60 patients aged 13-35 years. Cone-beam computed tomography (CBCT) scans were used to predict the treatment difficulty of MIC using the KPG index. Patient case files were assessed for the actual difficulty encountered in treating MIC. Cohen's kappa correlation coefficient was used for intra-observer reliability and Kendell's W test was used for inter-observer reliability. Spearman's correlation coefficient test was used to assess the correlation between predicted and actual treatment. RESULTS: Easy and moderately difficult cases exhibited a moderate correlation between actual and predicted treatment outcomes, whereas difficult cases displayed a weak correlation. The perfect correlation was observed exclusively in extremely difficult cases. The intra-observer reliability for assessing CBCT scans using the KPG guide was found to be 0.88, and the inter-rater reliability was 0.94. CONCLUSION: The KPG index displayed 87%, 71%, 50% and 100% validity in easy, moderately difficult, difficult, and extremely difficult cases, respectively. This index showed good reliability and reproducibility. However, it is imperative to consider a multitude of other factors, including the patient's age, presence of associated root resorption in adjacent teeth, and duration of treatment, to make an informed decision between surgical exposure and extraction.

Surgical anatomy of the cerebellar tonsils: A cadaveric study.

BACKGROUND: Knowledge of the normal anatomy of the cerebellar tonsils is a prerequisite in various surgeries of the posterior cranial fossa Clinical conditions, as the Chiari I malformations (CIM) alter the normal position of the cerebellar tonsils. OBJECTIVE: Therefore, we aim to better elucidate the surgical anatomy of and around the cerebellar tonsils in regard to the CIM. METHODS: Fifty formalin-fixed adult cadavers injected with colored latex through vertebral arteries underwent craniotomy and durotomy to expose the cerebellar tonsils and related structures. The tonsils and their surrounding anatomy were then studied. RESULTS: Forty cerebellar tonsils were at or above the foramen magnum. Five specimens presented with CIM with the tonsils below (3-5 mm) the FM with a mean tonsillar decent of 7.9 ± 2.3 mm. Of the cadavers without CIM, in forty-two cases, the thickness of the dura mater was within ±3SD ranges. In three cases, the dura mater was thinner at the CVJ and one case; the dura adhered tightly to the inner aspect of the occipital squama. In five CIM cadavers, the dura mater was markedly thicker at the CVJ. The PICA caudal loop was 5.9 ± 1.6 mm long. In CIM cases, the PICA loop was longer, nearer the dura, 1 mm below the superior border of the C1 posterior arch. The distances from the PICA loop were markedly reduced by 3 mm from the spinal accessory nerve and 2 mm from the first spinal nerve. The DN was significantly closer to the tonsillar peduncle in CIM cases. CONCLUSION: These data are important for better understanding the intrinsic and extrinsic anatomy of the cerebellar tonsils in patients with and without CIM. Importantly, tonsillectomy/tonsillar coagulation must consider the close relationship of the dentate nucleus to the base of the cerebellar tonsil to avoid iatrogenic injury.

Recycling air conditioner-generated condensate water for microalgal biomass production and carbon dioxide sequestration.

Air conditioners alleviate the discomfort of human beings from heat waves that are consequences of climate change caused by anthropogenic activities. With each passing year, the effects of global warming worsen, increasing the growth of air conditioning industry. Air conditioning units produce substantial amounts of non-nutritive and (generally) neglected condensate water and greenhouse gases. Considering this, the study explored the potential of using air conditioner condensate water (ACW) to cultivate Chlorella sorokiniana, producing biomass, and sequestering carbon dioxide (CO2). The maximum biomass production was obtained in the BG11 medium (1.45 g L-1), followed by ACW-50 (1.3 g L-1). Similarly, the highest chlorophyll-a content was observed in the BG11 medium (11 µg mL-1), followed by ACW-50 (9.11 µg mL-1). The ACW-50 cultures proved to be better adapted to physiological stress (Fv/Fm > 0.5) and can be suitable for achieving maximum biomass with adequate lipid, protein, and carbohydrate production. Moreover, C. sorokiniana demonstrated higher lipid and carbohydrate yields in the ACW-50 medium, while biomass production and protein yields were comparable to the BG11 medium. The lipid, protein, and carbohydrate productivity were 23.43, 32.9, and 23.19 mg L-1 d-1, respectively for ACW-50. Estimation of carbon capture potential through this approach equals to 9.5% of the total emissions which is an added advantage The results indicated that ACW could be effectively utilized for microalgae cultivation, reducing the reliance on freshwater for large-scale microalgal biomass production and reduce the carbon footprints of the air conditioning industry.

Unmet Surgical Need among Adults in A Mixed Urban-Rural Community in Nigeria: A Survey of 1,993 Adults Using the Sosas Survey Tool.

INTRODUCTION: Community-based prevalence studies are known to be more accurate than hospital-based records. However, such community-based prevalence studies are uncommon in low- and middle-income countries including Nigeria. Allocation of resources and prioritization of health care needs by policy makers require data from such community-based studies to be meaningful and sustainable. This study aims to assess the prevalence of common surgical conditions amongst adults in Nigeria. METHODS: A descriptive cross-sectional community-based study to determine the prevalence of congenital and acquired surgical conditions in adults in a mixed rural-urban area of Lagos was conducted. The study population comprised resident members in the Ikorodu Local Government Area (LGA) of Lagos State. Data was collected using a modified version of the interviewer-administered questionnaire, the Surgeons OverSeas Assessment of Surgical Need (SOSAS) survey tool. Data was analysed using the REDCap analytic tool. RESULTS: Eight hundred and fifty-six households were surveyed with a yield of 1,992 adults. There were 95 adults who complained of surgical conditions giving a prevalence rate of 5%. Vast majority of reported conditions were acquired deformities (n=94) while only 1 congenital deformity was reported. Others included breast lumps, anterior neck swelling, and groin swellings. CONCLUSION: The most common surgical complaints in our setting among adults were acquired conditions of the extremities and open wounds/sores. With an estimated population of 90 million adults and approximately 1,200 orthopaedic and general surgeons respectively, the surgeon-to-affected population ratio is 1:10,000. There is a large gap to be filled in terms of surgical manpower development.

INTRODUCTION: Les études de prévalence communautaires sont connues pour être plus précises que les dossiers hospitaliers. Cependant, de telles études de prévalence communautaires sont rares dans les pays à revenu faible et intermédiaire, y compris le Nigeria. L'allocation des ressources et la priorisation des besoins de santé par les décideurs nécessitent des données issues de telles études communautaires pour être significatives et durables. Cette étude vise à évaluer la prévalence des affections chirurgicales courantes chez les adultes au Nigeria. MÉTHODES: Une étude descriptive transversale basée sur la communauté pour déterminer la prévalence des conditions chirurgicales congénitales et acquises chez les adultes dans une zone rurale-urbaine mixte de Lagos a été menée. La population étudiée comprenait des membres résidents de la zone de gouvernement local (LGA) d'Ikorodu, dans l'État de Lagos. Les données ont été collectées à l'aide d'une version modifiée du questionnaire administré par un enquêteur, l'outil d'enquête Surgeons OverSeas Assessment of Surgical Need (SOSAS). Les données ont été analysées à l'aide de l'outil analytique REDCap. RÉSULTATS: Huit cent cinquante-six ménages ont été enquêtés, ce qui a donné 1 992 adultes. Quatre-vingt-quinze adultes se sont plaints de conditions chirurgicales, donnant un taux de prévalence de 5 %. La grande majorité des conditions rapportées étaient des déformations acquises (n=94) tandis qu'une seule déformation congénitale a été signalée. Les autres incluaient des nodules mammaires, des gonflements antérieurs du cou et des gonflements inguinaux. CONCLUSION: Les plaintes chirurgicales les plus courantes dans notre cadre parmi les adultes étaient des conditions acquises des extrémités et des plaies ouvertes/ulcères. Avec une population estimée à 90 millions d'adultes et environ 1 200 chirurgiens orthopédiques et généralistes respectivement, le ratio chirurgien-population affectée est de 1:10,000. Il y a un grand écart à combler en termes de développement de la main-d'œuvre chirurgicale. MOTS CLÉS: Prévalence, Charge de morbidité, Chirurgie, Plaies.

Chemical aspects of polyphenol-protein interactions and their antibacterial activity.

The hunt for novel antibiotics has become a global public health imperative due to the rise in multidrug-resistant microorganisms, untreatable infection cases, overuse, and inefficacy of modern antibiotics. Polyphenols are getting much attention in research due to their multiple biological effects; their use as antimicrobial agents is attributed to their activity and that microbes have a hard time developing resistance to these natural compounds. Polyphenols are secondary metabolites produced in higher plants. They are known to possess various functional properties in the human body. Polyphenols also exhibit antibacterial activities against foodborne pathogens. Their antibacterial mechanism is based on inhibiting bacterial biofilm formation or inactivating enzymes. This review focused on polyphenol-protein interactions and the creation of this complex as a possible antibacterial agent. Also, different phenolic interactions on bacterial proteins, efflux pump, cell membrane, bacterial adhesion, toxins, and other bacterial proteins will be explored; these interactions can work in a synergic combination with antibiotics or act alone to assure bacterial inhibition. Additionally, our review will focus on polyphenol-protein interaction as a possible strategy to eradicate bacteria because polyphenols have shown a robust enzyme-inhibitory characteristic and a high tendency to complex with proteins, a response that neutralizes any bactericidal potential.

Outcomes of complex colorectal polyps managed by multi-disciplinary team strategies-a multi-centre observational study.

PURPOSE: Team management strategies for complex colorectal polyps are recommended by professional guidelines. Multi-disciplinary meetings are used across the UK with limited information regarding their impact. The aim of this multi-centre observational study was to assess procedures and outcomes of patients managed using these approaches. METHOD: This was a retrospective, observational study of patients managed by six UK sites. Information was collected regarding procedures and outcomes including length of stay, adverse events, readmissions and cancers. RESULTS: Two thousand one hundred ninety-two complex polyps in 2109 patients were analysed with increasing referrals annually. Most presented symptomatically and the mean polyp size was 32.1 mm. Primary interventions included endoscopic therapy (75.6%), conservative management (8.3%), colonic resection (8.1%), trans-anal surgery (6.8%) or combined procedures (1.1%). The number of primary colonic resections decreased over the study period without a reciprocal increase in secondary procedures or recurrence. Secondary procedures were required in 7.8%. The median length of stay for endoscopic procedures was 0 days with 77.5% completed as day cases. Median length of stay was 5 days for colonic resections. Overall adverse event and 30-day readmission rates were 9.0% and 3.3% respectively. Malignancy was identified in 8.8%. Benign polyp recurrence occurred in 13.1% with a median follow up of 30.4 months. Screening detected lesions were more likely to undergo bowel resection. Colonic resection was associated with longer stays, higher adverse events and more cancers on final histology. CONCLUSION: Multi-disciplinary team management of complex polyps is safe and effective. Standardisation of organisation and quality monitoring is needed to continue positive effects on outcomes and services.

Peri-operative tobacco cessation interventions: a systematic review and meta-analysis.

Tobacco smoking is associated with a substantially increased risk of postoperative complications. The peri-operative period offers a unique opportunity to support patients to stop tobacco smoking, avoid complications and improve long-term health. This systematic review provides an up-to-date summary of the evidence for tobacco cessation interventions in surgical patients. We conducted a systematic search of randomised controlled trials of tobacco cessation interventions in the peri-operative period. Quantitative synthesis of the abstinence outcomes data was by random-effects meta-analysis. The primary outcome of the meta-analysis was abstinence at the time of surgery, and the secondary outcome was abstinence at 12 months. Thirty-eight studies are included in the review (7310 randomised participants) and 26 studies are included in the meta-analysis (5969 randomised participants). Studies were pooled for subgroup analysis in two ways: by the timing of intervention delivery within the peri-operative period and by the intensity of the intervention protocol. We judged the quality of evidence as moderate, reflecting the degree of heterogeneity and the high risk of bias. Overall, peri-operative tobacco cessation interventions increased successful abstinence both at the time of surgery, risk ratio (95%CI) 1.48 (1.20-1.83), number needed to treat 7; and 12 months after surgery, risk ratio (95%CI) 1.62 (1.29-2.03), number needed to treat 9. More work is needed to inform the design and optimal delivery of interventions that are acceptable to patients and that can be incorporated into contemporary elective and urgent surgical pathways. Future trials should use standardised outcome measures.

Occurrence and antimicrobial resistance of Campylobacter isolates from broiler chicken and slaughter house environment in India.

Campylobacteriosis is among the most frequently reported foodborne zoonoses. A total of 848 samples were screened for Campylobacter spp. and occurrence was found to be 8.7%, 2.3% and 1.65% in broiler cecum samples, chicken meat samples and slaughter house environment swabs, respectively. High level of antimicrobial resistance was found against tetracycline (64.1%), doxycycline (54.4%), ampicillin (46.6%), nalidixic acid (42.7%), kanamycin (35.9%), and ciprofloxacin (33.33%). Resistance to co-amoxiclav (19.4%) and erythromycin (21.4%) was less common. The MAR index of the isolates was in the range of 0.11-0.78. Multi-drug resistance was observed in 54.4% of the isolates, with 53.2% C. jejuni and 55.3% C. coli isolates found resistant against three or more classes of antimicrobials. Presence of mutations in gyrA and 23S rRNA genes was investigated, which revealed that all the fluoroquinolone resistant isolates possessed Thr-86-Ile point mutation, whereas only 68% of erythromycin resistant isolates had A2075G mutation. The tetO gene was present in 91.7% tetracycline resistant isolates and blaOXA-61 gene was detected in 97.9% of the ampicillin resistant isolates. The occurrence of antimicrobial resistant Campylobacter spp. in broiler chicken samples and slaughter house settings is a public health risk and calls for judicial use of antimicrobials.

Gender differences in workplace violence against physicians and nurses in Latin America: a survey from the Interamerican Society of Cardiology.

OBJECTIVES: To evaluate gender differences in workplace violence (WPV) against physicians and nurses in Latin America. STUDY DESIGN: Cross-sectional study. METHODS: A cross-sectional electronic survey was conducted between January 11 and February 28, 2022. A prespecified gender analysis was performed. RESULTS: Among the 3056 responses to the electronic survey, 57% were women, 81.6% were physicians, and 18.4% were nurses. At least one act of violence was experienced by 59.2% of respondents, with verbal violence being the most common (97.5%). Women experienced more WPV than men (65.8% vs 50.4%; P < 0.001; odds ratio [OR]: 1.89; 95% confidence interval [CI]: 1.63-2.19). Women were more likely to report at least one episode of WPV per week (19.2% vs 11.9%, P < 0.001), to request for psychological help (14.5% vs 9%, P = 0.001) and to experience more psychosomatic symptoms. In addition, women were more likely to report having considered changing their job after an aggression (57.6% vs 51.3%, P = 0.011) and even leaving their job (33% vs 25.7%, P = 0.001). In a multivariate analysis, being a woman (OR: 1.76), working in emergency departments (OR: 1.99), and with COVID-19 patients (OR: 3.3) were independently associated with more aggressive interactions, while older age (OR: 0.95) and working in a private setting (OR: 0.62) implied lower risk. CONCLUSIONS: Women are more likely to experience WPV and to report more psychosomatic symptoms after the event. Preventive measures are urgently needed, with a special focus on high-risk groups such as women.

Analysis of distribution and localization of proteins of the reelin signalling pathway in mesial temporal lobe epilepsy.

INTRODUCTION: Granule cell dispersion (GCD) is pathognomonic of hippocampal sclerosis seen in the mesial temporal lobe epilepsy (MTLE). Current animal studies indicate deficiency of Reelin is associated with abnormal granule cell migration leading to GCD. The present study aimed to evaluate complete Reelin signalling pathway to assess whether Reelin deficiency is related to MTLE. MATERIALS AND METHODS: Hippocampal sclerosis was confirmed by H and E stain. To explore the amount and cellular location of the Reelin cascade molecules, the hippocampal tissues from MTLE surgery and controls (n = 15 each) were studied using Immuno-histochemistry (IHC). Additionally, confocal imaging was used to validate the IHC findings by co-localization of different proteins. Quantification of IHC images was performed using histo-score and confocal images by Image J software. RESULTS: Immune expression of active Reelin was significantly reduced in patients. Reelin receptors were deranged, apolipoprotein E receptor 2 was increased while very low-density lipoprotein receptor was reduced. Disabled-1, a downstream molecule was significantly reduced in MTLE. Its ultimate target, cofilin was thus disinhibited and expressed more in MTLE. Reelin cleaving protease, matrix metalloprotease-9 (MMP-9) and MMP-9 inhibitor, tissue inhibitor of matrix protease-1, showed reduced expression in extracellular matrix. Semi-quantification of immunohistochemistry was done using Histo (H) score. H score of Reelin in diseased patients was 15 against 125 for control patients. These results were validated by confocal fluorescence microscopy. CONCLUSIONS: Reelin signalling cascade was deranged in chronic MTLE. Pharmacological manipulation of Reelin cascade can be done at various levels and it may provide novel treatment options for MTLE.

The Comparative Accuracy of BISAP and PANC3 Scoring System for the Disease Severity and Outcome in Acute Pancreatitis in Tertiary Care Hospital from North India.

Background Acute pancreatitis has local and systemic manifestations, so it's important to assess the severity by various scoring system. Among them bed side index for severity of acute pancreatitis and pancreatitis three score have been considered to be more predictive and easier. Objective To determine the comparative prognostic value of bed side index for severity of acute pancreatitis and pancreatitis 3 score and its correlation with the outcome. Method A prospective observational study was conducted on 50 cases of acute pancreatitis. The patients were assessed clinically, radiologically and biochemically and were categorised into mild, moderate and severe category as per Atlanta Classification. Bed side index for severity of acute pancreatitis and pancreatitis 3 score was calculated at the time of admission and followed till the time of discharge or they had mortality. Result Receiver operating characteristic curve, showed bed side Index for severity of acute pancreatitis score had sensitivity (66.67%), specificity (84.09%), diagnostic accuracy (84%) while pancreatitis 3 score had sensitivity (50%), specificity (81.82%), diagnostic accuracy (80%) for the severity of acute pancreatitis. Bed side index for severity of acute pancreatitis had sensitivity (100%), specificity (66.67%) and Pancreatitis 3 score had sensitivity (66.67%), specificity (80.85%) for predicting the mortality in acute pancreatitis. Conclusion Bed side index for severity of acute pancreatitis and pancreatitis 3 score are both simple, bedside tool for assessing the severity and mortality but bed side index for severity of acute pancreatitis score had better sensitivity, specificity for assessing the severity and mortality as compared to pancreatitis three score.

Cross-cultural Adaptation and Psychometric Properties of Nepali Version of Developmental Coordination Disorder Questionnaire.

Background Revised developmental coordination disorder questionnaire (DCDQ'07) is the best available population-based screening tool to identify developmental coordination disorder and being a parent reported tool, it needs to be available in Nepali language for its application in Nepali population. Objective The objective of this study was to cross-culturally adapt developmental coordination disorder questionnaire into Nepali (DCDQ-NP). The psychometric properties of Nepali version of Developmental coordination disorder questionnaire were established. Method The adaptation was done following Beaton's guideline and the psychometric properties was studied in the community sample of 165 parents of school going children of 5-15 years. Fifty parents were asked to refill the questionnaire after the two weeks period. The study determines internal consistency, test retest reliability, floor and ceiling effect and construct validity. Result Significant cultural adaptation was required to obtain relevant Nepali version. The Nepali version of Developmental coordination disorder questionnaire demonstrates high internal consistency (α = 0.912), excellent test-retest reliability (IC = 0.901) and the floor and ceiling effect were acceptable. Principal component analysis showed three factor structure accounting 62% of variance. Conclusion The developmental coordination disorder questionnaire into Nepali were successfully translated and culturally adapted preserving its original concept. It showed good psychometric properties in a Nepali population. The adapted questionnaire shall be of significance in carry out further research in developmental coordination disorder in Nepal.

THE IMPACT OF CLIMATE CHANGE ON INFECTIOUS DISEASES: A COMPREHENSIVE ANALYSIS OF VECTOR-BORNE DISEASES, WATER-BORNE DISEASES, AND PUBLIC HEALTH STRATEGIES.

Climate change is long-term modifications to weather patterns and a rise in extreme weather events. It might modify the hazard to human health and exacerbate current problems. The article explores the scientific data in a description of the effects of Infectious diseases in humans and climate change. It identifies scientific advancements and gaps in potential responses from human civilization and how it might prepare for the changes that come with it by adjusting to them. The impact reflects three aspects, such as climate variables, selected infectious diseases, and infectious disease components. This study demonstrates how vulnerable people are to any ill consequences that climate change may have on their health. Humans can actively influence controllable correlated health impacts by taking proactive measures, such as increasing our understanding of the detrimental effects associated with specific diseases and the patterns in climate change. We can also carefully distribute technology and resources, encouraging exercise and public awareness. It is advised to take the following adaption measures: Considering how infectious diseases and climate change are not the only things that science has discovered and create locally efficient early warning systems for those effects to produce more scientific justifications and go beyond scientific reports. Improve prediction of the spatiotemporal processes behind climate change and changes in infectious illnesses connected at different temporal and spatial scales.

Meta-analyses of the quantitative computed tomography data in dialysis patients show differential impacts of renal failure on the trabecular and cortical bones.

Dialysis patients have compromised bone health that increases their fracture risk due to low bone mass and deterioration in bone microarchitecture. Through meta-analyses of published studies, we conclude that dialysis patients suffer from impaired compartmental bone parameters compared with healthy controls. INTRODUCTION: We performed meta-analyses to determine the effect of chronic kidney disease (CKD) patients under dialysis on the trabecular and cortical parameters of radius and tibia. METHODS: This is a meta-analysis of cross-sectional and prospective clinical studies. PubMed, Web of Science, Google Scholar, and Scopus were searched using various permutation combinations. Dialysis patients were compared with non-CKD healthy controls using quantitative computed tomography. High-resolution peripheral quantitative computed tomography (HR-pQCT) and pQCT data of dialysis patients were dissected from eligible studies for pooled analysis of each parameter. RESULTS: Ten studies met the inclusion criteria that included data from 457 dialysis patients and 2134 controls. Pooled analysis showed a significant decrease (a) in total vBMD at distal radius [standard deviation of the mean (SDM) = -0.842, p = 0.000] and tibia (SMD = -0.705, p = 0.000) and (b) in cortical vBMD (SDM = -1.037, p = 0.000) at radius of dialysis patients compared with control. There were strong correlations between total vBMD and microarchitecture parameters at tibia in dialysis patients. CONCLUSIONS: At radius and tibia, bone mass, microarchitecture, and geometry at trabecular and cortical envelopes displayed impairments in dialysis patients compared with control. Tibial vBMD may have diagnostic value in dialysis. HR-pQCT and pQCT may be used to further understand the compartmental bones response to CKD-induced loss at different stages of CKD.

Letter to editor: Emerging public health challenge in UK: perception and belief on increased COVID19 death among BAME healthcare workers.

A cross-sectional survey of Black Asian and minority ethnic (BAME) health care workers evaluating their perception and belief on increased Coronavirus disease-19 (COVID-19) death among BAME health care workers was conducted in Leicester. They found that 72% of respondents had some form of impact on their mental health but the majority were satisfied with the overall support they received from local health care providers. In conclusion, adequate culturally competent mental health support is necessary as the BAME workforce is routinely involved in frontline work.