Impact of multidisciplinary management via special clinic for the outcome of diabetic foot disease: A prospective observational study.

Introduction: Diabetic foot is a common complication of diabetes mellitus, affecting approximately 15-20% of individuals with diabetes. It is a comorbid condition that significantly impacts the routine life of patients. This study aimed to assess multidisciplinary management strategies and their impact on the outcomes of patients with diabetic foot. Methods: A prospective observational study was conducted on 56 patients with diabetic foot. Outcome measures included the type of surgery, frequency of surgery, morbidity, mortality, patient satisfaction, return to work, and the number of patients using prostheses. Results: The majority of the patients (87%) received surgical treatment. The most common type of surgery performed was debridement (55%), followed by minor amputations (toes amputation/forefoot amputation) (28%) and major amputations (below-knee (B/K) or above-knee (A/K)) (15%). More than 70% of patients had multiple surgeries. The mortality rate was low (7%), and 71% of surviving patients were satisfied with their treatment. Sixty-seven percent of patients had an early return to work. The number of patients using prostheses was also high (73% of major amputation cases). Conclusion: Multidisciplinary management is the most effective approach for diabetic foot patients. These patients may experience less morbidity and an early return to work. A specialized care clinic for diabetic foot patients is essential to prevent treatment failure, loss of follow-up records, permanent limb loss, and economic burdens on society.

A quilting sutures technique for flap closure in patients undergoing modified radical mastectomy for the prevention of seroma: A single-center, randomized controlled trial.

Seroma formation is a common adverse event following modified radical mastectomy, and it leads to delayed wound healing and increased post-operative pain and increases overall morbidity of patients. The quilting sutures as a newer technique for the skin flap closure is done to reduce incidence of seroma formation. Although it has controversy in the literature for the satisfactory outcome, the study has aimed to compare the Quilting suture technique with the conventional closure method to evaluate the efficacy of the quilting technique. The primary objective of the study was to access and compare the frequency of seroma formation following the quilting suture technique with standard flap closure in MRM. The secondary objectives were to compare drain output, post-operative complications, and the requirement of additional procedures for management of related complications. The 72 female participants in this randomized control trial had modified radical mastectomy after being diagnosed with breast cancer. The quilting suture technique was applied in the 36 patients and conventional technique applied in 36 patients for skin flap closure. The frequency of seroma formation and other complications were reported. Between the two groups, there was no statistically significant difference in the frequency of seroma production (P = 0.233). Total drainage volume (P = 0.213), drainage duration (P = 0.652), and post-operative complications (P = 0.641) did not substantially differ between the two groups. The study concludes that the quilting sutures technique does not decrease the incidence of seroma formation, total drain output, and total duration of drainage. There is no significant difference in complications and requirement of additional procedures compared to the standard technique.

Tau proteins and senescent Cells: Targeting aging pathways in Alzheimer's disease.

Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by abnormal accumulation of tau proteins and amyloid-ß, leading to neuronal death and cognitive impairment. Recent studies have implicated aging pathways, including dysregulation of tau and cellular senescence in AD pathogenesis. In AD brains, tau protein, which normally stabilizes microtubules, becomes hyperphosphorylated and forms insoluble neurofibrillary tangles. These tau aggregates impair neuronal function and are propagated across the brain's neurocircuitry. Meanwhile, the number of senescent cells accumulating in the aging brain is rising, releasing a pro-inflammatory SASP responsible for neuroinflammation and neurodegeneration. This review explores potential therapeutic interventions for AD targeting tau protein and senescent cells, and tau -directed compounds, senolytics, eliminating senescent cells, and agents that modulate the SASP-senomodulators. Ultimately, a combined approach that incorporates tau-directed medications and targeted senescent cell-based therapies holds promise for reducing the harmful impact of AD's shared aging pathways.

Characterization of Clinical Presentation, Etiology, and Antibiotic Sensitivity Patterns in Neonatal Septicemia: A Comprehensive Analysis of Bacterial Isolates.

BACKGROUND: Neonatal septicemia remains a significant healthcare challenge, particularly in resource-limited settings, with both early-onset neonatal septicemia (EONS) and late-onset neonatal septicemia (LONS) presentations contributing to morbidity and mortality. This study aimed to characterize the clinico-etiological profile and antibiotic susceptibility patterns of neonatal septicemia in a tertiary care setting in north India. METHODOLOGY: An analytical cross-sectional study was conducted from March 2021 to February 2022, encompassing neonates admitted to the Department of Pediatrics with suspected neonatal septicemia, confirmed by positive blood cultures. RESULTS: A total of 96 neonates were included, predominantly male (71.9%). Gram-negative bacteria constituted 61.6% of isolates, and the most common organism isolated was non-lactose fermenter group (38.4%) followed by coagulase-negative staphylococci (CoNS) (33.4%). Non-lactose fermenter group bacteria were prominent in EONS cases (44.6%), while CoNS predominated in LONS cases (51.6%). Birthplace, birth weight, and perinatal score were significantly associated with both EONS and LONS. Linezolid exhibited high efficacy against gram-positive bacteria, while ciprofloxacin and meropenem demonstrated effectiveness against various gram-negative pathogens. Methicillin-resistant Staphylococcus aureus (MRSA) strains exhibited resistance to all the antibiotics used in the study except for linezolid. CONCLUSION: These findings underscore the importance of tailored empirical therapy guided by local epidemiological data to optimize clinical outcomes and mitigate antimicrobial resistance.

Neoantigen-specific cytotoxic Tr1 CD4 T cells suppress cancer immunotherapy.

CD4+ T cells can either enhance or inhibit tumour immunity. Although regulatory T cells have long been known to impede antitumour responses1-5, other CD4+ T cells have recently been implicated in inhibiting this response6,7. Yet, the nature and function of the latter remain unclear. Here, using vaccines containing MHC class I (MHC-I) neoantigens (neoAgs) and different doses of tumour-derived MHC-II neoAgs, we discovered that whereas the inclusion of vaccines with low doses of MHC-II-restricted peptides (LDVax) promoted tumour rejection, vaccines containing high doses of the same MHC-II neoAgs (HDVax) inhibited rejection. Characterization of the inhibitory cells induced by HDVax identified them as type 1 regulatory T (Tr1) cells expressing IL-10, granzyme B, perforin, CCL5 and LILRB4. Tumour-specific Tr1 cells suppressed tumour rejection induced by anti-PD1, LDVax or adoptively transferred tumour-specific effector T cells. Mechanistically, HDVax-induced Tr1 cells selectively killed MHC-II tumour antigen-presenting type 1 conventional dendritic cells (cDC1s), leading to low numbers of cDC1s in tumours. We then documented modalities to overcome this inhibition, specifically via anti-LILRB4 blockade, using a CD8-directed IL-2 mutein, or targeted loss of cDC2/monocytes. Collectively, these data show that cytotoxic Tr1 cells, which maintain peripheral tolerance, also inhibit antitumour responses and thereby function to impede immune control of cancer.

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.

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.

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.

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.

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.