An Analysis of the Impact of Intra-abdominal Pressure on Surgical Outcomes in Cases of Intestinal Obstruction: A Prospective Observational Study.

BACKGROUND: The decision and timing of surgical exploration of intestinal obstruction depend on the clinical findings and probable etiology of the symptoms. Patients with intestinal obstruction often have intra-abdominal hypertension (IAH), which is associated with a poor prognosis. PURPOSE OF THE STUDY: The purpose of the study is to evaluate the surgical outcomes in patients with intestinal obstruction in relation to intra-abdominal pressure (IAP). MATERIALS AND METHODS: The study was conducted on 50 patients with intestinal obstruction undergoing surgery. Preoperatively, IAP was measured in all the patients and was allocated into two groups based on the presence or absence of IAP. Patients were assessed for the postoperative length of hospital or ICU stay, surgical site infection, wound dehiscence, and recovery following surgery. RESULTS: The patients with preoperative IAH had significantly longer postoperative stays, with a median stay of eight days in these patients compared to four days in patients without IAH (p=0.009). A significantly higher number of patients (24%) had gangrenous changes on the bowel wall (p=0.042) and fascial dehiscence (p=0.018) in the group associated with raised IAP. A total of 75% of patients who required ventilator support belonged to the raised IAP group. The mean IAP in patients admitted to the ICU was significantly higher than in patients not admitted to the ICU (p=0.027). CONCLUSION: Preoperative IAH in intestinal obstruction is a significant factor in predicting the possibility of bowel ischemia with gangrene, perforation, intra-abdominal sepsis, surgical site infections, and prolonged hospital stay. Early surgical exploration and abdominal decompression must be considered in such cases.

Low-Cost System for Maintaining Low Atmospheric CO2 Levels During Arabidopsis Cultivation.

Photosynthesis requires CO2 as the carbon source, and the levels of ambient CO2 determine the oxygenation or carboxylation of Ribulose-1,5-bisphosphate (RuBP) by RuBP carboxylase/oxygenase (Rubisco). Low CO2 levels lead to oxygenation and result in photorespiration, which ultimately causes a reduction in net carbon assimilation through photosynthesis. Therefore, an increased understanding of plant responses to low CO2 contributes to the knowledge of how plants circumvent the harmful effects of photorespiration. Methods for elevating CO2 above ambient concentrations are often achieved by external sources of CO2, but reducing CO2 below the ambient value is much more difficult as CO2 gas needs to be scrubbed from the atmosphere rather than added to it. Here, we describe a low-cost method of achieving low CO2 conditions for Arabidopsis growth.

Gallbladder perforation: Diagnostic accuracy of new CT difficulty score in predicting complicated laparoscopic cholecystectomy.

PURPOSE: To formulate and evaluate the diagnostic performance and utility of a new CT difficulty score in predicting difficult laparoscopic surgery in cases of gallbladder (GB) perforation. METHODS: This prospective single centre study included a total of 48 diagnosed cases of GB perforation on CT between December 2021 and June 2023, out of which 24 patients were operated. A new 6-point CT difficulty scoring system was devised to predict difficult laparoscopic approach, based on patterns of inflammation around the perforated GB that were found to be surgically relevant. The pre-operative imaging findings on CT were studied in detail and correlation coefficients of various imaging findings were calculated to predict difficult surgery. RESULTS: On CECT, the type of perforation, according to the revised Niemeier's classification could be exactly delineated in all 48 patients. A CT difficulty score of ≥ 3 was found to a good predictor difficult laparoscopic approach, with statistical significance (p = 0.001), sensitivity of 94.44%, specificity of 83.33%, PPV of 94.44% and NPV of 83.33%. Inflammatory changes around duodenum showed maximum correlation coefficient of 0.744 (p = 0.0001), around colon showed a correlation coefficient of 0.657 (p = 0.0005), and in the omentum had a correlation coefficient of 0.5 (p = 0.013)). Inter-observer agreement was also calculated for various findings and it was found to have moderate to strong agreement (κ value 0.5-1.0). CONCLUSION: The CT difficulty scoring system can be an effective tool in predicting difficult laparoscopic surgery in cases of GB perforation in an emergency setting which can help in decision making and improved patient outcome.

Enhancing grid resiliency in distributed energy systems through a comprehensive review and comparative analysis of islanding detection methods.

Reduction of fossil fuel usage, clean energy supply, and dependability are all major benefits of integrating distributed energy resources (DER) with electrical utility grid (UG). Nevertheless, there are difficulties with this integration, most notably accidental islanding that puts worker and equipment safety at risk. Islanding detection methods (IDMs) play a critical role in resolving this problem. All IDMs are thoroughly evaluated in this work, which divides them into two categories: local approaches that rely on distributed generation (DG) side monitoring and remote approaches that make use of communication infrastructure. The study offers a comparative evaluation to help choose the most efficient and applicable IDM, supporting well-informed decision-making for the safe and dependable operation of distributed energy systems within electrical distribution networks. IDMs are evaluated based on NDZ outcomes, detection duration, power quality impact, multi-DG operation, suitability, X/R ratio reliance, and efficient functioning.

Effects of transcutaneous electrical nerve stimulation on recovery of gastrointestinal motility after laparotomy: A randomized controlled trial.

INTRODUCTION: Postoperative Ileus (POI) negatively impacts patient outcomes and increases healthcare costs. Transcutaneous electrical nerve stimulation (TENS) has been found to improve gastrointestinal (GI) motility following abdominal surgery. However, its effectiveness in this context is not well-established. This study was designed to evaluate the role of TENS on the recovery of GI motility after exploratory laparotomy. METHODS: Patients undergoing exploratory laparotomy were randomized in a 1:1 ratio into control (standard treatment alone) and experimental (standard treatment + TENS) arms. TENS was terminated after 6 days or after the passage of stool or stoma movement. The primary outcome was time for the first passage of stool/functioning stoma. Non-passage of stool or nonfunctioning stoma beyond 6 days was labeled as prolonged POI. Patients were monitored until discharge. RESULTS: Median (interquartile range) time to first passage of stool/functioning stoma was 82.6 (49-115) hours in the standard treatment group and 50 (22-70.6) hours in the TENS group [p < 0.001]. Prolonged POI was noted in 11 patients in the standard treatment group (35.5%) and one in the TENS group (3.2%) [p = 0.003]. Postoperative hospital stay was similar in the two groups. CONCLUSION: TENS resulted in early recovery of GI motility by shortening the duration of POI without any improvement in postoperative hospital stay. TRIAL REGISTRATION NUMBER: CTRI/2021/10/037054.

Ginsenoside Re protects against kainate-induced neurotoxicity in mice by attenuating mitochondrial dysfunction through activation of the signal transducers and activators of transcription 3 signaling.

It was demonstrated that ginsenosides exert anti-convulsive potentials and interleukin-6 (IL-6) is protective from excitotoxicity induced by kainate (KA), a model of temporal lobe epilepsy. Ginsenosides-mediated mitochondrial recovery is essential for attenuating KA-induced neurotoxicity, however, little is known about the effects of ginsenoside Re (GRe), one of the major ginsenosides. In this study, GRe significantly attenuated KA-induced seizures in mice. KA-induced redox changes were more evident in mitochondrial fraction than in cytosolic fraction in the hippocampus of mice. GRe significantly attenuated KA-induced mitochondrial oxidative stress (i.e. increases in reactive oxygen species, 4-hydroxynonenal, and protein carbonyl) and mitochondrial dysfunction (i.e. the increase in intra-mitochondrial Ca2+ and the decrease in mitochondrial membrane potential). GRe or mitochondrial protectant cyclosporin A restored phospho-signal transducers and activators of transcription 3 (STAT3) and IL-6 levels reduced by KA, and the effects of GRe were reversed by the JAK2 inhibitor AG490 and the mitochondrial toxin 3-nitropropionic acid (3-NP). Thus, we used IL-6 knockout (KO) mice to investigate whether the interaction between STAT3 and IL-6 is involved in the GRe effects. Importantly, KA-induced reduction of manganese superoxide dismutase (SOD-2) levels and neurodegeneration (i.e. astroglial inhibition, microglial activation, and neuronal loss) were more prominent in IL-6 KO than in wild-type (WT) mice. These KA-induced detrimental effects were attenuated by GRe in WT and, unexpectedly, IL-6 KO mice, which were counteracted by AG490 and 3-NP. Our results suggest that GRe attenuates KA-induced neurodegeneration via modulating mitochondrial oxidative burden, mitochondrial dysfunction, and STAT3 signaling in mice.

The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.

The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.

ICOS costimulation in combination with CTLA-4 blockade remodels tumor-associated macrophages toward an antitumor phenotype.

We have previously demonstrated synergy between ICOS costimulation (IVAX; ICOSL-transduced B16-F10 cellular vaccine) and CTLA-4 blockade in antitumor therapy. In this study, we employed CyTOF and single-cell RNA sequencing and observed significant remodeling of the lymphoid and myeloid compartments in combination therapy. Compared with anti-CTLA-4 monotherapy, the combination therapy enriched Th1 CD4 T cells, effector CD8 T cells, and M1-like antitumor proinflammatory macrophages. These macrophages were critical to the therapeutic efficacy of anti-CTLA-4 combined with IVAX or anti-PD-1. Macrophage depletion with clodronate reduced the tumor-infiltrating effector CD4 and CD8 T cells, impairing their antitumor functions. Furthermore, the recruitment and polarization of M1-like macrophages required IFN-γ. Therefore, in this study, we show that there is a positive feedback loop between intratumoral effector T cells and tumor-associated macrophages (TAMs), in which the IFN-γ produced by the T cells polarizes the TAMs into M1-like phenotype, and the TAMs, in turn, reshape the tumor microenvironment to facilitate T cell infiltration, immune function, and tumor rejection.

Apple (Malus × domestica Borkh.) production and quality in response to anti-hail nets.

Anti-hail nets are the best way to mitigate the effects of hailstorms in the orchards. Apple trees covered with nets may exhibit a variety of vegetative and reproductive responses, inclusive of changes in tree vigour, cropping, sugar contents, and fruit colour. The present study was conducted to assess the effect of timing of installation and colour of anti-hail net on cropping and fruit quality in high-density apple orchard for two consecutive seasons (2021 and 2022). White and blue colour nets of size (9 m × 30 m) 80 GSM (square mesh with non-sliding threaded, leno weave, and < 30% shading factor) were installed at three different time intervals (15 days before estimated full bloom, at full bloom, and 15 days after full bloom) on apple cultivar 'Jeromine'. The installation at different time and colour of anti-hail nets significantly exhibit variability in cropping, fruit quality, and bio-chemical metrics. The significant highest cropping (fruit yield, productivity, and yield efficiency) and fruit biochemical parameters (total soluble solids) were recorded in T3C2 (15 days after full bloom + white colour anti-hail net) followed by T2C2 (installed at full bloom + white colour anti-hail net). Hence, white colour anti-hail nets installed 15 days after full bloom increased fruit production and improved quality in comparison to blue colour anti-hail net in apple under high-density plantations.

KRAS Pathways: A Potential Gateway for Cancer Therapeutics and Diagnostics.

One of the major disturbing pathways within cancer is "The Kirsten rat sarcoma viral oncogene homolog (KRAS) pathway", and it has recently been demonstrated to be the most crucial in therapies and diagnostics. KRAS pathway includes numerous genes. This multi-component signaling system promotes cell growth, division, survival, and death by transferring signals from outside the cell to its interior. KRAS regulates the activation of a variety of signaling molecules. The KRAS oncogene is a key player in advancing a wide range of malignancies, and the mutation rank of this gene is a key feature of several tumors. For some malignancies, the mutation type of the gene may offer information about prognostic, clinical, and predictive. KRAS belongs to the RAS oncogene family, which consists of a compilation of minor GTP-binding proteins that assimilate environmental inputs and trigger internal signaling pathways that control survival, cell differentiation, and proliferation. This review aims to examine the recent and fascinating breakthroughs in the identification of new therapies that target KRAS, including the ever-expanding experimental approaches for reducing KRAS activity and signaling as well as direct targeting of KRAS. A literature survey was performed. All the relevant articles and patents related to the KRAS pathway, the mutation in the KRAS gene, cancer treatment, and diagnostics were found on PubMed and Google Patents. One of the most prevalent causes of cancer in humans is a mutation in the K-RAS protein. It is extremely difficult to decipher KRAS-mediated signaling. It allows transducing signals to go from the cell's outer surface to its nucleus, having an influence on a variety of crucial cellular functions including cell chemotaxis, division, dissemination, and cell death. Other involved signaling pathways are RAF, and the phosphatidylinositol 3 kinase also known as AKT. The EGFR pathway is incomplete without KRAS. The activation of PI3K significantly contributes to acquiring resistance to a mixture of MEK inhibitors and anti-EGFR in colorectal cancer cell lines which are mutated by KRAS. A series of recent patent studies towards cancer diagnostics and therapeutics reveals the paramount importance of mutated protein KRAS as an extensive driver in human tumors. For the prognosis, diagnosis, and treatment of colorectal cancer, KRAS plays a critical role. This review concludes the latest and vowing developments in the discovery of novel techniques for diagnosis and drugs that target KRAS, the advancements in experimental techniques for signaling and inhibiting KRAS function, and the direct targeting of KRAS for cancer therapeutics.

Prediction of mortality in secondary peritonitis: a prospective study comparing p-POSSUM, Mannheim Peritonitis Index, and Jabalpur Peritonitis Index.

BACKGROUND: Risk scoring systems are required to allow accurate prognostication, compare outcomes of surgery, and allow patients to make informed decisions about their health. This prospective study compares the p-POSSUM (Portsmouth Modification to Physiological and Operative Severity Score for Enumeration of Mortality), Mannheim Peritonitis Index, and Jabalpur Peritonitis Index for their utility in predicting mortality in patients with peritonitis. METHODS: Perioperative data was collected from 235 patients with secondary peritonitis and used to calculate p-POSSUM, MPI, and JPI scores. The accuracy of the 3 scores was compared using receiver operator characteristic curves. RESULTS: p-POSSUM and Mannheim Peritonitis Index were similar in their accuracy with area under the curve (AUC) values of 0.756 and 0.757. Jabalpur Peritonitis Index had an AUC of 0.665. CONCLUSION: p-POSSUM and Mannheim Peritonitis Index can be used to predict mortality in patients with secondary peritonitis. Jabalpur Peritonitis Index is not suited for this purpose. Further studies are required to improve the diagnostic performance of p-POSSUM and MPI in patients with secondary peritonitis.

Insight into Structure Activity Relationship of DPP-4 Inhibitors for Development of Antidiabetic Agents.

This article sheds light on the various scaffolds that can be used in the designing and development of novel synthetic compounds to create DPP-4 inhibitors for the treatment of type 2 diabetes mellitus (T2DM). This review highlights a variety of scaffolds with high DPP-4 inhibition activity, such as pyrazolopyrimidine, tetrahydro pyridopyrimidine, uracil-based benzoic acid and esters, triazole-based, fluorophenyl-based, glycinamide, glycolamide, ß-carbonyl 1,2,4-triazole, and quinazoline motifs. The article further explains that the potential of the compounds can be increased by substituting atoms such as fluorine, chlorine, and bromine. Docking of existing drugs like sitagliptin, saxagliptin, and vildagliptin was done using Maestro 12.5, and the interaction with specific residues was studied to gain a better understanding of the active sites of DPP-4. The structural activities of the various scaffolds against DPP-4 were further illustrated by their inhibitory concentration (IC50) values. Additionally, various synthesis schemes were developed to make several commercially available DPP4 inhibitors such as vildagliptin, sitagliptin and omarigliptin. In conclusion, the use of halogenated scaffolds for the development of DPP-4 inhibitors is likely to be an area of increasing interest in the future.

Mountain-cultivated ginseng protects against cognitive impairments in aged GPx-1 knockout mice via activation of Nrf2/ChAT/ERK signaling pathway.

Background: Escalating evidence shows that ginseng possesses an antiaging potential with cognitive enhancing activity. As mountain cultivated ginseng (MCG) is cultivated without agricultural chemicals, MCG has emerged as a popular herb medicine. However, little is known about the MCG-mediated pharmacological mechanism on brain aging. Methods: As we demonstrated that glutathione peroxidase (GPx) is important for enhancing memory function in the animal model of aging, we investigated the role of MCG as a GPx inducer using GPx-1 (a major type of GPx) knockout (KO) mice. We assessed whether MCG modulates redox and cholinergic parameters, and memory function in aged GPx-1 knockout KOmice. Results: Redox burden of aged GPx-1 KO mice was more evident than that of aged wild-type (WT) mice. Alteration of Nrf2 DNA binding activity appeared to be more evident than that of NFκB DNA binding activity in aged GPx-1 KO mice. Alteration in choline acetyltransferase (ChAT) activity was more evident than that in acetylcholine esterase activity. MCG significantly attenuated reductions in Nrf2 system and ChAT level. MCG significantly enhanced the co-localization of Nrf2-immunoreactivity and ChAT-immunoreactivity in the same cell population. Nrf2 inhibitor brusatol significantly counteracted MCG-mediated up-regulation in ChAT level and ChAT inhibition (by k252a) significantly reduced ERK phosphorylation by MCG, suggesting that MCG might require signal cascade of Nrf2/ChAT/ERK to enhance cognition. Conclusion: GPx-1 depletion might be a prerequisite for cognitive impairment in aged animals. MCG-mediated cognition enhancement might be associated with the activations of Nrf2, ChAT, and ERK signaling cascade.

Current Trends in the Management of Port-Site Infections: A Case Series and a Review of Published Work.

Introduction Laparoscopic techniques have become standard for many surgeries, offering benefits such as quicker recovery and less pain. However, port-site infections (PSIs) can occur and pose challenges. PSIs can be early (within seven days) or delayed (after three to four weeks), with delayed PSIs often caused by non-tuberculous mycobacteria (NTMs). NTMs are difficult to treat and do not respond well to antibiotics, leading to prolonged and recurrent infections. Guidelines for PSI management are limited. This summary highlights a case series of 10 patients with PSIs, discussing their treatment experience and presenting a treatment algorithm used at our institute. Methods This is a retrospective study (2015-2020) on chronic port-site infections (PSIs) in laparoscopic surgeries. Data were collected on patient demographics, surgery type, prior treatment, and management at the institute. Results The study analyzed 10 patients with chronic PSIs following laparoscopic surgery between 2015 and 2020. Laparoscopic cholecystectomy was the most frequent index surgery. Three patients had a history of treatment with varying durations of anti-tubercular therapy, one of whom had completed anti-tubercular treatment prior to presentation. Complete surgical excision with histopathological examination and fungal, bacterial and mycobacterial cultures were performed. Seven of the 10 patients were treated with oral ciprofloxacin and clarithromycin combination therapy for three months, two were treated with culture-based antibiotics and one was treated with anti-tubercular therapy. All patients improved on treatment. The mean follow-up period was 52 ± 9.65 months, with no relapses being reported.  Conclusion Port-site infections (PSIs) are troublesome complications of laparoscopic surgery that can erode the benefits of the procedure. Delayed PSIs caused by drug-resistant mycobacteria are difficult to treat. Improved sterilization methods and thorough microbiological work-up are crucial. Radical excision and prolonged oral antibiotics are effective treatments. Clinicians should avoid empirical antibiotic therapy to prevent antimicrobial resistance.

Region-wise severity analysis of diabetic plantar foot thermograms.

OBJECTIVES: Diabetic foot ulcers (DFU) can be avoided if symptoms of diabetic foot complications are detected early and treated promptly. Early detection requires regular examination, which might be limited for many reasons. To identify affected or potentially affected regions in the diabetic plantar foot, the region-wise severity of the plantar foot must be known. METHODS: A novel thermal diabetic foot dataset of 104 subjects was developed that is suitable for Indian healthcare conditions. The entire plantar foot thermogram is divided into three parts, i.e., forefoot, midfoot, and hindfoot. The division of plantar foot is based on the prevalence of foot ulcers and the load on the foot. To classify the severity levels, conventional machine learning (CML) techniques like logistic regression, decision tree, KNN, SVM, random forest, etc., and convolutional neural networks (CNN), such as EfficientNetB1, VGG-16, VGG-19, AlexNet, InceptionV3, etc., were applied and compared for robust outcomes. RESULTS: The study successfully developed a thermal diabetic foot dataset, allowing for effective classification of diabetic foot ulcer severity using the CML and CNN techniques. The comparison of different methods revealed variations in performance, with certain approaches outperforming others. CONCLUSIONS: The region-based severity analysis offers valuable insights for targeted interventions and preventive measures, contributing to a comprehensive assessment of diabetic foot ulcer severity. Further research and development in these techniques can enhance the detection and management of diabetic foot complications, ultimately improving patient outcomes.

Ginsenoside Re blocks Bay k-8644-induced neurotoxicity via attenuating mitochondrial dysfunction and PKCδ activation in the hippocampus of mice: Involvement of antioxidant potential.

Although the anticonvulsant effects of ginsenosides are recognized, little is known about their effects on the convulsive behaviors induced by the activation of L-type Ca2+ channels. Here, we investigated whether ginsenoside Re (GRe) modulates excitotoxicity induced by the L-type Ca2+ channel activator Bay k-8644. GRe significantly attenuated Bay k-8644-induced convulsive behaviors and hippocampal oxidative stress in mice. GRe-mediated antioxidant potential was more pronounced in the mitochondrial fraction than cytosolic fraction. As L-type Ca2+ channels are thought to be targets of protein kinase C (PKC), we investigated the role of PKC under excitotoxic conditions. GRe attenuated Bay k-8644-induced mitochondrial dysfunction, PKCδ activation, and neuronal loss. The PKCδ inhibition and neuroprotection mediated by GRe were comparable to those by the ROS inhibitor N-acetylcysteine, the mitochondrial protectant cyclosporin A, the microglial inhibitor minocycline, or the PKCδ inhibitor rottlerin. Consistently, the GRe-mediated PKCδ inhibition and neuroprotection were counteracted by the mitochondrial toxin 3-nitropropionic acid or the PKC activator bryostatin-1. GRe treatment did not have additional effects on PKCδ gene knockout-mediated neuroprotection, suggesting that PKCδ is a molecular target of GRe. Collectively, our results suggest that GRe-mediated anticonvulsive/neuroprotective effects require the attenuation of mitochondrial dysfunction and altered redox status and inactivation of PKCδ.