An Overview of SARS-CoV-2 Potential Targets, Inhibitors, and Computational Insights to Enrich the Promising Treatment Strategies.

The rapid spread of the SARS-CoV-2 virus has emphasized the urgent need for effective therapies to combat COVID-19. Investigating the potential targets, inhibitors, and in silico approaches pertinent to COVID-19 are of utmost need to develop novel therapeutic agents and reprofiling of existing FDA-approved drugs. This article reviews the viral enzymes and their counter receptors involved in the entry of SARS-CoV-2 into host cells, replication of genomic RNA, and controlling the host cell physiology. In addition, the study provides an overview of the computational techniques such as docking simulations, molecular dynamics, QSAR modeling, and homology modeling that have been used to find the FDA-approved drugs and other inhibitors against SARS-CoV-2. Furthermore, a comprehensive overview of virus-based and host-based druggable targets from a structural point of view, together with the reported therapeutic compounds against SARS-CoV-2 have also been presented. The current study offers future perspectives for research in the field of network pharmacology investigating the large unexplored molecular libraries. Overall, the present in-depth review aims to expedite the process of identifying and repurposing drugs for researchers involved in the field of COVID-19 drug discovery.

Use of free jejunal flap as a salvage procedure in the management of high corrosive esophageal re-strictures: an institutional experience and review of literature.

BACKGROUND: High pharyngo-esophageal strictures following corrosive ingestion continue to pose a challenge to the surgeon, particularly in the developing world. With the advancements and increased experience with microsurgical techniques, free jejunal flaps offer a viable reconstruction option in patients with high corrosive strictures with previous failed reconstruction. We review our experience with free jejunal flap in three cases with high pharyngo-esophageal stricture following corrosive ingestion, with previous failed reconstruction. MATERIALS AND METHODS: A total of three patients underwent salvage free jejunal flap after failed reconstruction for high pharyngo-esophageal strictures following corrosive acid ingestion. All the three patients developed anastomotic leak and subsequent stricture, two following a pharyngo-gastric anastomosis and one following a pharyngo-colic anastomosis. The strictured segment was bridged using a free jejunal graft with microvascular anastomosis to the lingual artery and common facial vein. All patients were followed-up at regular intervals. RESULTS AND CONCLUSIONS: The strictured pharyngeal anastomotic segment was successfully reconstructed with free jejunal flap in all the three patients. Patients were able to take food orally and maintain nutrition without the need of jejunostomy feeding. On long-term follow-up (median: 5 years), there was no recurrence of dysphagia and all the patients had good health-related quality of life.

Paradigms of actinorhizal symbiosis under the regime of global climatic changes: New insights and perspectives.

Nitrogen occurs as inert and inaccessible dinitrogen gaseous form (N2 ) in the atmosphere. Biological nitrogen fixation is a chief process that makes this dinitrogen (N2 ) accessible and bioavailable in the form of ammonium (NH4 + ) ions. The key organisms to fix nitrogen are certain prokaryotes, called diazotrophs either in the free-living form or establishing significant mutual relationships with a variety of plants. On such examples is ~95-100 MY old incomparable symbiosis between dicotyledonous trees and a unique actinobacterial diazotroph in diverse ecosystems. In this association, the root of the certain dicotyledonous tree (~25 genera and 225 species) belonging to three different taxonomic orders, Fagales, Cucurbitales, and Rosales (FaCuRo) known as actinorhizal trees can host a diazotroph, Frankia of order Frankiales. Frankia is gram-positive, branched, filamentous, sporulating, and free-living soil actinobacterium. It resides in the specialized, multilobed, and coralloid organs (lateral roots but without caps), the root nodules of actinorhizal tress. This review aims to provide systematic information on the distribution and the phylogenetic diversity of hosts from FaCuRo and their micro-endosymbionts (Frankia spp.), colonization mechanisms, and signaling pathways. We also aim to provide details on developmental and physiological imperatives for gene regulation and functional genomics of symbiosis, phenomenal restoration ecology, influences of contemporary global climatic changes, and anthropogenic impacts on plant-Frankia interactions for the functioning of ecosystems and the biosphere.

Immediate and Long-Term Outcomes of Percutaneous Radiological Interventions for Hemorrhagic Complications in Acute and Chronic Pancreatitis.

PURPOSE: To evaluate and compare the immediate and long-term outcomes of radiological interventions for hemorrhagic complications in patients with acute and chronic pancreatitis. MATERIALS AND METHODS: This retrospective study, conducted between January 2014 and June 2020, included all patients with acute and chronic pancreatitis presenting with hemorrhagic complications who underwent angiography and/or embolization. Their clinical, angiographic, and embolization details were evaluated and correlated with procedure success, complications, recurrence, and mortality. The patients were subgrouped into groups A (acute pancreatitis) and C (chronic pancreatitis), and comparisons were made. RESULTS: The study included 141 patients (mean age, 36.3 ± 11.2 years; 124 men), of whom 106 patients had abnormal angiography findings and underwent embolization. Of them, group A had 50 patients (56 lesions) and group C had 56 patients (61 lesions). All the patients in group A had severe acute pancreatitis, with a mean computed tomography severity index of 7.6. The technical and clinical success rates of embolization, complications, recurrence, and long-term outcomes were not significantly different between the groups. Group A had significantly higher mortality due to sepsis and organ failure. Embolic agents did not have any significant association with complications, recurrence, and mortality. After a mean follow-up of 2 years, 72.5% of the patients were asymptomatic, and none had symptoms attributable to embolization. CONCLUSIONS: Success, complications, and recurrence after embolization for hemorrhagic complications were comparable between acute and chronic pancreatitis. Acute pancreatitis was associated with significantly higher mortality. Embolic agents did not significantly influence the outcomes. None had long-term adverse effects attributable to embolization.

FibroScan-aspartate aminotransferase score in an Asian cohort of non-alcoholic fatty liver disease and its utility in predicting histological resolution with bariatric surgery.

BACKGROUND AND AIM: The FibroScan-aspartate aminotransferase (FAST) score was developed for identifying patients with non-alcoholic steatohepatitis, who also have an elevated non-alcoholic fatty liver disease (NAFLD) activity score (NAS) ≥ 4 and significant fibrosis (F ≥ 2). We aimed to validate it in our NAFLD cohort and assess if it correlates with the histological changes after bariatric surgery. METHODS: Patients with NAFLD, including those undergoing bariatric surgery, were included. The FAST score was calculated using liver stiffness measure, controlled attenuation parameter, and aspartate aminotransferase. Calibration and discrimination of the model were assessed by calibration plots and area under the receiver operating characteristic curve, respectively. Sensitivity and specificity were assessed at the rule-out and rule-in cutoffs (≤0.35 and ≥0.67), respectively. Changes in the NAS and FAST scores were compared in the bariatric cohort 1 year after surgery. RESULTS: The cohort composed of 309 patients, of which 48 patients underwent repeat liver biopsy at 1 year. The model showed good discrimination with area under the receiver operating characteristic curve of 0.79 (0.74-0.84); however, it was not satisfactorily calibrated (Hosmer-Lemeshow test, P = 0.008). The sensitivity and specificity at the rule-out and rule-in cutoffs were 0.90 and 0.84, respectively. A significant correlation was seen between the 1-year reduction in the NAS and FAST scores (r = 0.38, P = 0.009). A significant reduction in the median FAST score was seen in patients who had ≥2-point reduction in NAS after bariatric surgery. CONCLUSION: FibroScan-aspartate aminotransferase score demonstrated good discrimination for fibrotic non-alcoholic steatohepatitis in our cohort. However, a miscalibration resulted in overprediction. The score correlated well with the histological response to interventions for NAFLD.

Single-Center Randomized Trial Comparing Feeding Jejunostomy with Nasojejunal Tube Placement in Patients Undergoing Transhiatal Esophagectomy Post-Neoadjuvant Therapy for Esophageal Cancer.

BACKGROUND: Enteral nutrition is the preferred mode of nutrition following esophagectomy. However, the preferred mode of enteral nutrition (feeding jejunostomy (FJ) vs. nasojejunal (NJ) tube) remains contentious. In this randomized controlled trial (RCT), we compared FJ with NJ tube feeding in terms of safety, feasibility, efficacy, and quality-of-life (QOL) parameters in Indian patients undergoing trans-hiatal esophagectomy (THE) for carcinoma esophagus. MATERIALS AND METHODS: This single-center, two-armed (FJ and NJ tube), non-inferiority RCT was conducted from March 2020 to January 2024. Forty-eight patients underwent THE with posterior-mediastinal-gastric pull-up and were randomized to NJ and FJ arms (24 in each group). The postoperative complications, catheter efficacy, and QOL parameters were compared between the two groups till the 6-week follow-up. RESULTS: In this RCT, we found no significant difference in the occurrence of catheter-related complications, postoperative complication rate, catheter efficacy, and visual analog pain scores between patients with NJ tube and FJ, following THE for esophageal cancer. There was a significantly better self-reported physical domain QOL score noted in the NJ group, both at the time of discharge (44.7 ± 6.2 vs 39.8 + 5.6; p value, 0.005) and at the 6-week follow-up (55.4 ± 5.2 vs 48.6 ± 4.5; p value, < 0.001). CONCLUSION: Based on the findings of our RCT, we conclude that both enteral access methods (NJ vs. FJ) exhibit comparable incidences of catheter-related complications. The use of NJ tube is a viable alternative to a surgical FJ, has the benefit of early removal, and saves the distress associated with a tube per abdomen.

Impact of nasogastric tube exclusion after minimally invasive esophagectomy for esophageal cancer: a single-center retrospective study in India.

Purpose: This study examines the impacts of omitting nasogastric tube (NGT) placement following cervical esophagogastric anastomosis (CEGA) in Enhanced Recovery After Surgery (ERAS) protocols, comparing outcomes to those from early NGT removal. Methods: In a retrospective cohort of esophagectomy patients treated for esophageal cancer, participants were divided into two groups: group 1 had the NGT inserted post-CEGA and removed by postoperative day 3, while group 2 underwent the procedure without NGT placement. We primarily investigated anastomotic leak rates, also analyzing hospital stay duration, pulmonary complications, and NGT reinsertion. Results: Among 50 esophageal squamous cell carcinoma patients, 30 in group I were compared with 20 in group II. The baseline demographic and tumor characteristics were similar between both groups. The overall incidence of anastomotic leak was 14.0%, comparable in both groups (16.7% vs. 10.0%, p = 0.63). The postoperative hospital stay was significantly shorter in the no NGT group (median of 7 days vs. 6 days, p = 0.03) with similar major morbidity (Clavien-Dindo grade ≥IIIa; 13.3% vs. 5.0%, p = 0.63). There was no 30-day mortality, and one patient in each group had reinsertion of NGT for conduit dilatation. Conclusion: The exclusion of an NGT across CEGA after esophagectomy did not influence the anastomotic leak rate with comparable complications and a shorter hospital stay.

Green route to fabrication of Semal-ZnO nanoparticles for efficient solar-driven catalysis of noxious dyes in diverse aquatic environments.

This work successfully demonstrates a sustainable and environmentally friendly approach for synthesizing Semal-ZnO nanoparticles (NPs) using the aqueous leaf extract of Bombax ceiba L. These NPs exhibit an absorption peak at approximately 390 nm in the UV-visible spectrum and an energy gap (Eg) of 3.11 eV. Detailed analyses of the morphology and particle size using various spectroscopic and microscopic techniques, XRD, FE-SEM with EDS, and HR-TEM reveal crystallographic peaks attributable to the hexagonal phase, with an average crystal size of 17 nm. The Semal-ZnO NPs also exhibit a notable photocatalytic efficiency for degrading methylene blue (MB) and methyl orange (MO) under sunlight in different water samples collected from diverse natural sources, indicating that they are promising photocatalysts for environmental remediation. The photocatalytic efficiency of the biofabricated Semal-ZnO NPs is impressive, exhibiting a photodegradation rate of up to 99% for MB and 79% for MO in different water samples under exposure to sunlight. The novel phytofabricated Semal-ZnO NPs are thus a beacon of hope for the environment, with their desirable photocatalytic efficiency, pseudo-first-order kinetics, and ability to break down noxious dye pollutants in various aquatic environments.

Pattern of Aorto-coeliac Calcification Correlating Cervical Esophago-gastric Anastomotic Leak After Esophagectomy for Cancer: a Retrospective Study.

PURPOSE: Cervical esophagogastric anastomotic leak (CEGAL) is a troublesome complication after esophagectomy and gastric pull-up. The aim of the study was to identify the preoperative clinical and radiological factors associated with increased risk of CEGAL. METHODS: Consecutive patients whose clinical and imaging data were available and who underwent cervical esophago-gastric anastomosis following esophagectomy and gastric pull-up for esophageal cancer, between January 2013 and January 2021, were included. The patient details were collected from a prospectively maintained database. The demographic, clinical, and laboratory data including preoperative hemoglobin and serum albumin levels were recorded. Preoperative computed tomographic (CT) images were reviewed by two independent radiologists to assign vascular calcification scores for proximal aorta, distal aorta, aortic bifurcation, celiac trunk, and celiac artery branches. The primary outcome evaluated was clinically evident neck leak. Univariate and multivariate analysis of the clinical and radiological factors was performed to identify significant predictors. RESULTS: A total of 100 patients (mean age: 54.7 years; 60 males, 40 females) were included in the study and of them, 27 developed CEGAL. Compared to the group without CEGAL, the patient group with CEGAL had significantly higher mean age (60.3 vs. 52.7 years, p < 0.01), and higher incidences of diabetes mellitus (25.9% vs 10.9%, p = 0.03), major proximal aortic calcification (29.6% vs. 6.3%, p < 0.01), and major celiac trunk calcification (22.2% vs. 6.3%, p = 0.02). Multivariate regression analysis identified age and presence of major proximal aortic calcification as independent risk factors for the development of CEGAL. CONCLUSION: Major calcification of the proximal aorta and advanced age are independent risk factors for CEGAL after esophagectomy.

Carcinosarcoma of the Esophagus-A Diagnostic Challenge.

Background: Esophageal carcinosarcoma is an uncommon histologic variant of esophageal malignancy, occurring in approximately 0.5% to 2.8% of patients. Esophageal carcinosarcoma usually involves the middle and lower esophagus and consists of both epithelial and mesenchymal components. Case Report: A 54-year-old male presented with painless progressive dysphagia associated with loss of weight for 2 months. Esophagogastroduodenoscopy suggested an ulceroproliferative polypoidal growth in the lower thoracic esophagus. Biopsies from the growth showed leiomyosarcoma with tumor cells immunopositive for vimentin, h-Caldesmon, and smooth muscle actin and negative for pan-cytokeratin. Imaging suggested a heterogeneously enhancing polypoidal growth arising in the lower third of the esophagus. Thoracoscopic-assisted McKeown esophagectomy with gastric pull-up and standard 2-field lymphadenectomy was performed. A minor epithelial component was identified on final pathologic examination in addition to the leiomyosarcoma found on the preoperative biopsy. This epithelial component was invasive squamous cell carcinoma and was positive for pan-cytokeratin and p40, both of which were negative in the sarcomatous component. The patient received 4 cycles of adjuvant chemotherapy (carboplatin and paclitaxel). However, he developed a recurrence in the left cervical lymph node 4 months after adjuvant treatment and died 2 months after the diagnosis of recurrence. Conclusion: Carcinosarcoma can be easily missed in the presence of predominantly sarcomatous components even on immunohistochemical analysis. These tumors may be associated with poor prognosis and may have early recurrence despite surgery and adjuvant treatment.

Thoracoscopy-Assisted Esophagectomy for Esophageal Leiomyomatosis.

INTRODUCTION: Diffuse esophageal leiomyomatosis is a rare esophageal tumor characterized by circumferential thickening of smooth muscle layers of the entire esophagus. CLINICAL CASE: Herein, we describe the case of a 19-year-old girl, who presented with a history of long-standing dysphagia. On evaluation she was found to have diffuse esophageal leiomyomatosis and was managed successfully by thoracoscopy-assisted esophagectomy with intra-nodal indocyanine green injection. DISCUSSION: In this report, we discuss the pre-operative workup and our surgical approach to managing this rare entity. We also discuss the available literature on the subject and the lessons learnt in managing this complex condition.

Laparoscopic Witzel feeding jejunostomy: a procedure overlooked!

Purpose: Feeding jejunostomy (FJ) is a critical procedure to establish a source of enteral nutrition for upper gastrointestinal disorders. Minimally invasive surgery has the inherent benefit of better patient outcomes, less postoperative pain, and early discharge. This study aims to describe our total laparoscopic technique of Witzel FJ and to compare its outcome with its open counterpart. Methods: A retrospective database analysis was performed in patients who underwent laparoscopic (n = 20) and open (n = 21) FJ as a stand-alone procedure from July 2018 to July 2022. A readily available nasogastric tube (Ryles tube) and routine laparoscopic instruments were used to perform laparoscopic FJ. Perioperative data and postoperative outcomes were analyzed. Results: Baseline preoperative variables were comparable in both groups. The median operative duration in the laparoscopic FJ group was 180 minutes vs. 60 minutes in the open FJ group (p = 0.01). Postoperative length of hospital stay was 3 days vs. 4 days in the laparoscopic and open FJ groups, respectively (p = 0.08). Four patients in the open FJ group suffered from an immediate postoperative complication (none in the laparoscopic FJ group). After a median follow-up of 10 months, fewer patients in the laparoscopic FJ group had complications such as tube clogging, tube dislodgement, surgical-site infection, and small bowel obstruction. Conclusion: Laparoscopic FJ with the Witzel technique is a safe and feasible procedure with a comparable outcome to the open technique. Patient selection is vital to overcome the initial learning curve.

Duplicated extrahepatic bile duct (type Vb): An important rare anomaly.

Congenital duplication of the extrahepatic bile duct (DEBD) is an unusual anomaly of the biliary system. It occurs due to inability of the embryological duplex biliary system to regress. DEBD has various subtypes depending on the morphology and opening of the aberrant common bile duct. It can have distinct complications. We encountered a 38-year-old lady who experienced pain in the right upper abdomen along with a low-grade fever. Magnetic resonance cholangiopancreatography revealed DEBD with multiple calculi in the right hepatic duct (ductolithiasis) and joining of the right hepatic duct with the left hepatic duct in the intrapancreatic region. Endoscopic retrograde cholangiography failed to clear the calculi from the right duct. They were then managed by common bile duct exploration and roux-en-Y right hepaticojejunostomy for biliary drainage. Her postoperative period was uneventful. She is currently doing well after three months of follow-up. Hence, a proper preoperative delineation of such rare anomalies is essential. It could avoid inadvertent injury to the bile duct and operative complications.

Spontaneous hepatic arterioportal fistula in extrahepatic portal vein obstruction: Combined endovascular and surgical management.

Hepatic arterioportal fistulae are abnormal communications between the hepatic artery and portal vein. They are reported to be congenital or acquired secondary to trauma, iatrogenic procedures, hepatic cirrhosis, and hepatocellular carcinoma, but less likely to occur spontaneously. Extrahepatic portal venous obstruction (EHPVO) can lead to pre-hepatic portal hypertension. A spontaneous superimposed hepatic arterioportal fistula can lead to pre-sinusoidal portal hypertension, further exacerbating its physiology. This report describes a young woman with long-standing EHPVO presenting with repeated upper gastrointestinal variceal bleeding and symptomatic hypersplenism. Computed tomography scan demonstrated a cavernous transformation of the portal vein and a macroscopic hepatic arterioportal fistula between the left hepatic artery and portal vein collateral in the central liver. The hepatic arterioportal fistula was associated with a flow-related left hepatic artery aneurysm and a portal venous collateral aneurysm proximal and distal to the fistula, respectively. Endovascular coiling was performed for the hepatic arterioportal fistula, followed by proximal splenorenal shunt procedure. This case illustrates an uncommon association of a spontaneous hepatic arterioportal fistula with EHPVO and the utility of a combined endovascular and surgical approach for managing multifactorial non-cirrhotic portal hypertension in such patients.

Advances in the synthetic strategies of benzoxazoles using 2-aminophenol as a precursor: an up-to-date review.

Benzoxazole is a resourceful and important member of the heteroarenes that connects synthetic organic chemistry to medicinal, pharmaceutical, and industrial areas. It is a bicyclic planar molecule and is the most favorable moiety for researchers because it has been extensively used as a starting material for different mechanistic approaches in drug discovery. The motif exhibits a high possibility of broad substrate scope and functionalization to offer several biological activities like anti-microbial, anti-fungal, anti-cancer, anti-oxidant, anti-inflammatory effects, and so on. There has been a large upsurge in the synthesis of benzoxazole via different pathways. The present article presents recent advances in synthetic strategies for benzoxazole derivatives since 2018. A variety of well-organized synthetic methodologies for benzoxazole using 2-aminophenol with aldehydes, ketones, acids, alcohols, isothiocyanates, ortho-esters, and alkynones under different reaction conditions and catalysts, viz. nanocatalysts, metal catalysts, and ionic liquid catalysts, with other miscellaneous techniques has been summarized.

Amelioration of the physio-biochemical responses to salinity stress and computing the primary germination index components in cauliflower on seed priming.

The significant horticultural crop, cauliflower (Brassica oleracea L. var. botrytis) is vulnerable to the excessive salt concentration in the soil, which contributes to its scaled-down growth and productivity, among other indices. The current study examines the efficacy of hydropriming, halopriming, and osmopriming on the physio-biochemical attributes and tolerance to salinity (100 mM NaCl) in cauliflower under controlled conditions. The results showed that the salinity (100 mM NaCl) has significant deleterious impacts on cauliflower seed germination, seedling growth, and photosynthetic attributes, and provoked the production of reactive oxygen species. In contrast, different priming approaches proved beneficial in mitigating the negative effects of salinity and boosted the germination, vigor indices, seedling growth, and physio-biochemical attributes like photosynthetic pigments, protein, and proline content while suppressing oxidative damage and MDA content in cauliflower seedlings in treatment- and dose-dependent manner. PCA revealed 61% (PC1) and 15% (PC2) of the total variance with substantial positive relationships and high loading conditions on all germination attributes on PC1 with greater PC1 scores for PEG treatments showing the increased germination indices in PEG-treated seeds among all the priming treatments tested. All 13 distinct priming treatments tried clustered into three groups as per Ward's approach of systematic categorization, clustering the third group showing relatively poor germination performances. Most germination traits exhibited statistically significant associations at the p < 0.01 level. Overall, the results established the usefulness of the different priming approaches facilitating better germination, survival, and resistance against salinity in the cauliflower to be used further before sowing in the salt-affected agro-ecosystems.

Gangliocytic Paraganglioma of the Duodenum: A Masquerader.

Background: Gangliocytic paraganglioma (GP) is a rare tumor that most commonly arises from the duodenum and is characterized pathologically by 3 cell types: epithelioid, spindle, and ganglion cells. GP is often difficult to differentiate from a neuroendocrine tumor on the basis of preoperative imaging, and the diagnosis is based on final histopathologic and immunohistochemical analysis. Case Report: We report the case of a 28-year-old male who presented with pain in the abdomen, bilious vomiting, and weight loss. Imaging showed a mass involving the first and second part of the duodenum that was likely a neuroendocrine or gastrointestinal stromal tumor. He underwent robotic-assisted pancreatoduodenectomy, and the final pathology report identified GP with lymph node metastasis. The patient was doing well at 1-year follow-up. Conclusion: GP is often a histologic surprise as most cases are diagnosed in postoperative histopathology. While GP has a more benign course than a neuroendocrine tumor, radical surgical resection is warranted in cases of diagnostic dilemma, suspicion of malignancy, or lymph node metastasis. Robotic-assisted pancreatoduodenectomy is a feasible option.

Open injury, robotic repair-moving ahead! Total robotic Roux-en-Y hepaticojejunostomy for post-open cholecystectomy Bismuth type 2 biliary stricture using indocyanine green dye.

Hepaticojejunostomy is currently the best treatment for post-cholecystectomy biliary strictures. Laparoscopic repair has not gained popularity due to difficult reconstruction. We present case of 43-year-old-female with Bismuth type 2 stricture following laparoscopic converted open cholecystectomy with bile duct injury done elsewhere. Position was modified Llyod-Davis position and four 8-mm robotic ports (including camera) and 12-mm assistant port were placed. The procedure included noticeable steps such as adhesiolysis, identification of gallbladder fossa, identification of common hepatic duct, lowering of hilar plate etc. Operating and console time were 420 and 350 minutes and blood loss was 100 mL. Patient was discharged on postoperative day 4. Robotic repair (hepaticojejunostomy) of biliary tract stricture after cholecystectomy is safe and feasible with good outcomes.