Timing is everything: outcomes of 30,259 delayed cholecystectomies in New York State.

BACKGROUND: The timing of cholecystectomy in relation to outcomes has been debated. To our knowledge, there are no large population-based studies looking at outcomes and complications of delayed cholecystectomy [DC] (> 72 h after presentation). This study utilizes a statewide database to determine whether there are differences in patient outcomes for DC performed at 3-4 days, 5-6 days, and ≥ 7 days after presentation. METHODS: The New York SPARCS database was used to identify adult patients presenting with a diagnosis of acute cholecystitis from 2005 to 2017. Patients aged < 18, those with missing identifier or procedure-date information, those who underwent early cholecystectomy < 72 h or upon readmission, were excluded. Patients undergoing DC at 3-4 days, 5-6 days, and ≥ 7 days were compared in terms of overall complications, hospital length of stay (LOS), 30-day readmissions/emergency department (ED) visits, and 30-day mortality. RESULTS: 30,259 patients were identified. DCs were performed within 3-4 days (n = 19,845, 65.6%), 5-6 days (n = 6432, 21.3%), and ≥ 7 days (n = 3982, 13.2%). There was a stepwise deterioration in outcomes with increased delay to surgery (Fig. 1). When comparing 3-4 and ≥ 7 days, overall complications (OR = 0.418, 95% CI: 0.387-0.452), 30-day readmissions (OR = 0.609, 95% CI: 0.549-0.674), 30-day ED visits (OR = 0.697, 95% CI: 0.637-0.763), 30-day mortality (OR = 0.601, 95% CI: 0.400-0.904), and LOS (OR = 0.729, 95% CI: 0.710-0.748) were lower in the 3-4 day cohort. CONCLUSIONS: DC within 3-4 days is associated with fewer complications, readmissions and ED visits, and reduced LOS compared to DC at 5-6 or ≥ 7 days after presentation. In addition, 30-day mortality was also significantly different comparing 3-4 with ≥ 7-day cohorts. These data are important for guiding patients in the consent process and may point to choosing an earlier interval cholecystectomy for high-risk patients.

Total pancreatectomy, splenectomy and remnant gastrectomy for invasive intraductal papillary mucinous neoplasm (IPMN) after prior Roux-en-Y gastric bypass.

A female patient in her 50s presented with abdominal pain, nausea and jaundice. She had a history of prior Roux-en-Y gastric bypass and her body mass index was 52.5 kg/m2 Biochemical testing revealed a total bilirubin level of 14.3 mg/dL (normal<1.2 mg/dL) and carbohydrate antigen 19-9 of 38.3 units/mL (normal<36.0 units/mL). CT demonstrated a 3.2 cm pancreatic head mass, biliary and pancreatic duct dilation and cystic replacement of the pancreas. The findings were consistent with a diagnosis of mixed-type intraductal papillary mucinous neoplasm (IPMN) with invasive malignancy. The patient's Roux-en-Y anatomy precluded endoscopic biopsy, and she underwent upfront resection with diagnostic laparoscopy, open total pancreatectomy, splenectomy and remnant gastrectomy with reconstruction. Pathology confirmed T2N1 pancreatic adenocarcinoma, 1/29 lymph nodes positive and diffuse IPMN. She completed adjuvant chemotherapy. IPMNs have malignant potential and upfront surgical resection should be considered without biopsy in the appropriate clinical setting.

Quantification and characterization of microplastics in coastal environments: Insights from laser direct infrared imaging.

The study identified and quantified nine plastic polymers frequently detected in the environment by collecting sediment and seawater samples from coastal areas in Auckland, New Zealand. Polymer types, size distributions, and number of microplastics (MPs) were analyzed using a laser direct infrared (LDIR) imaging technique. Compared to conventional spectroscopic or microscopic methods, LDIR enabled capturing and quantifying MPs in much lower size ranges (20-5000 µm). The results demonstrated the widespread occurrence of MPs in the Auckland coastal environment, with polyethylene terephthalate (PET) being the most frequently detected plastic polymer. MP contamination levels ranged from 13 to 83 particles per liter of coastal water and from 1200 to 3400 particles/kg of dry sand in beach sediments. Six additional locations were investigated to assess the contribution of MPs from stormwater drains to the coastal environment. The total count of identified MPs extracted from sediments near stormwater drains reached a maximum of 18,000 particles/kg of dry sand, representing an order of magnitude increase compared to MP levels found in beach sediments at the same location. In contrast to the prevalence of PET and polyamide observed in beach sediments and coastal waters, polyurethane and polyethylene emerged as the predominant plastic polymers in the vicinity of stormwater drain sediments, implying that the variation could potentially stem from distinct sources of plastics. This significant disparity in quality and quantity underscored the potential link between urban runoff and MP pollution in marine ecosystems. A sample preparation method using 100 g sediment samples was developed and used to assess and compare MPs detection in sediment samples. The commonly used 5 g sample method showed higher extraction efficiency and better detection of the most abundant MPs, but the new 100 g method enabled the detection of previously missed, less abundant plastics.

Potential inhibitors of VEGFR1, VEGFR2, and VEGFR3 developed through Deep Learning for the treatment of Cervical Cancer.

Cervical cancer stands as a prevalent gynaecologic malignancy affecting women globally, often linked to persistent human papillomavirus infection. Biomarkers associated with cervical cancer, including VEGF-A, VEGF-B, VEGF-C, VEGF-D, and VEGF-E, show upregulation and are linked to angiogenesis and lymphangiogenesis. This research aims to employ in-silico methods to target tyrosine kinase receptor proteins-VEGFR-1, VEGFR-2, and VEGFR-3, and identify novel inhibitors for Vascular Endothelial Growth Factors receptors (VEGFRs). A comprehensive literary study was conducted which identified 26 established inhibitors for VEGFR-1, VEGFR-2, and VEGFR-3 receptor proteins. Compounds with high-affinity scores, including PubChem ID-25102847, 369976, and 208908 were chosen from pre-existing compounds for creating Deep Learning-based models. RD-Kit, a Deep learning algorithm, was used to generate 43 million compounds for VEGFR-1, VEGFR-2, and VEGFR-3 targets. Molecular docking studies were conducted on the top 10 molecules for each target to validate the receptor-ligand binding affinity. The results of Molecular Docking indicated that PubChem IDs-71465,645 and 11152946 exhibited strong affinity, designating them as the most efficient molecules. To further investigate their potential, a Molecular Dynamics Simulation was performed to assess conformational stability, and a pharmacophore analysis was also conducted for indoctrinating interactions.

Determinants of initiation, continuation and cessation of smokeless tobacco use among pregnant and lactating women: a qualitative study from low-income communities in urban India.

Smokeless tobacco (SLT) consumption increases the risk of cardiovascular diseases and cancer and leads to adverse reproductive health outcomes among women and newborns. This study examines the factors associated with initiation, continuation and cessation of SLT use among women in the reproductive age so as to formulate and include prevention and cessation interventions from its inception. The study was conducted in urban low-income communities in India. Using snowball and purposive sampling techniques, in-depth interviews were conducted with 20 pregnant and 22 lactating women who currently used SLT products. Data were analysed using thematic analysis with the help of QSR NVivo software. Findings revealed that factors such as people influencing usage change with different life stages including pre-marital and post-marital periods. Perceived health benefits, altered taste preferences during pregnancy and social influences were also studied. Women were found to be more aware of the harmful effects of tobacco during pregnancy than during breastfeeding. Social stigma around women consuming tobacco acted as a major driving factor for cessation. Most of the participants were willing to quit but were not aware of any technique or programme for cessation. The findings of the study highlight the need to develop behavioural change intervention tools, which are culturally and locally appropriate and have a gender-sensitive approach. Different socio-cultural factors associated with initiation/cessation at different life stages should also be taken into consideration while developing these tools.

Unveiling the ESR1 Conformational Stability and Screening Potent Inhibitors for Breast Cancer Treatment

BACKGROUND: The current study recognizes the significance of estrogen receptor alpha (ERα) as a member of the nuclear receptor protein family, which holds a central role in the pathophysiology of breast cancer. ERα serves as a valuable prognostic marker, with its established relevance in predicting disease outcomes and treatment responses. METHOD: In this study, computational methods are utilized to search for suitable drug-like compounds that demonstrate analogous ligand binding kinetics to ERα. RESULTS: Docking-based simulation screened out the top 5 compounds - ZINC13377936, NCI35753, ZINC35465238, ZINC14726791, and NCI663569 against the targeted protein. Further, their dynamics studies reveal that the compounds ZINC13377936 and NCI35753 exhibit the highest binding stability and affinity. CONCLUSION: Anticipating the competitive inhibition of ERα protein expression in breast cancer, we envision that both ZINC13377936 and NCI35753 compounds hold substantial promise as potential therapeutic agents. These candidates warrant thorough consideration for rigorous In vitro and In vivo evaluations within the context of clinical trials. The findings from this current investigation carry significant implications for the advancement of future diagnostic and therapeutic approaches for breast cancer.

Characterization of Microbial Inactivation Using Plasma-Activated Water and Plasma-Activated Acidified Buffer.

This work investigates the efficacy of plasma-activated water (PAW) and plasma-activated acidified buffer (PAAB) on Enterobacter aerogenes in aqueous system and fruit systems. Reactive oxygen and nitrogen species in PAW have been suggested to provide antimicrobial and acidifying effects, causing the pH of treated water to drop. To isolate the effect of pH in microbial inactivation and to study the interactive effects of pH and reactive species on microbial inactivation, a citrate-phosphate buffer (pH 3.1) and PAAB (citrate-phosphate) were studied. A 1.92 ± 0.70 log CFU/mL reduction in E. aerogenes was observed in PAW, while no reduction was achieved in the buffer, suggesting that the inactivation was due to the reactive species in PAW and not the acidic pH. PAAB achieved a 5.11 ± 0.63 log CFU/mL reduction, suggesting an interactive effect of reactive species and low pH. Electrical conductivity and oxidation-reduction potential measurements suggest potential mechanisms for the greater antimicrobial efficacy of PAAB over PAW. Four surfaces of increasing roughness (glass slides, grape tomatoes, limes, and spiny gourds) were spot inoculated and washed with distilled water, PAW, buffer, and PAAB for 3 min. The smoothest surface (glass) showed the highest reduction (6.32 ± 0.43 log CFU per surface), while the roughest surface (spiny gourd) showed a significantly lower reduction (2.52 ± 0.46 log CFU per surface) when treated with PAAB. For treatment with PAW, no significant differences were observed between glass slides, limes, and spiny gourds. With PAW treatment, significantly lower reduction was observed on spiny gourds (1.70 ± 0.21 log CFU per surface) than on grape tomatoes (4.65 ± 1.34 log CFU per surface). PAW and PAAB both showed potential for their use in fresh produce sanitation.