Meleney's Gangrene of the Abdomen Managed With Serial Debridement and Negative Pressure Wound Therapy: A Case Report.

Meleney's gangrene (necrotizing fasciitis (NF)), also known as progressive bacterial synergistic gangrene, is a potentially fatal subcutaneous tissue infection with abdominal wall necrosis that progresses rapidly and systematically. It has been observed to exhibit the cultural characteristics of a symbiotic organism. Due to its rarity and high mortality rate, this infection needs to be diagnosed promptly and treated aggressively with antibiotics and rigorous debridement. There are several approaches to management, which include intravenous antibiotics, aggressive debridement, and dressings, along with the application of negative pressure wound therapy (NPWT). Herein, we report the case of a 45-year-old male patient with type 2 diabetes mellitus who presented to our facility after being bitten by an insect and exhibiting symptoms of Meleney's gangrene of the abdomen.

Adenocarcinoma of Sacrococcygeal Pilonidal Disease: A Report of a Rare Case.

A recurring abscess or draining sinus overlying the sacrococcygeal area is the hallmark of the chronic, well-known condition known as sacrococcygeal pilonidal disease. It is among the most difficult surgical challenges. Rarely, recurrent illness, persistent infection, and associated inflammation result in malignant transformation, most frequently in the form of squamous cell carcinoma (SCC). We report a similar case of an 84-year-old man who presented to our outpatient clinic and had a persistent, recurring sacrococcygeal pilonidal sinus for 28 years. He had already undergone several surgical excisions for the same and now developed an ulceroproliferative growth on his right gluteal cleft since his previous resection when he first appeared.

Pathogenic Huntingtin aggregates alter actin organization and cellular stiffness resulting in stalled clathrin mediated endocytosis.

Aggregation of mutant forms of Huntingtin is the underlying feature of neurodegeneration observed in Huntington's disorder. In addition to neurons, cellular processes in non-neuronal cell types are also shown to be affected. Cells expressing neurodegeneration-associated mutant proteins show altered uptake of ligands, suggestive of impaired endocytosis, in a manner as yet unknown. Using live cell imaging, we show that clathrin-mediated endocytosis (CME) is affected in Drosophila hemocytes and mammalian cells containing Huntingtin aggregates. This is also accompanied by alterations in the organization of the actin cytoskeleton resulting in increased cellular stiffness. Further, we find that Huntingtin aggregates sequester actin and actin-modifying proteins. Overexpression of Hip1 or Arp3 (actin-interacting proteins) could restore CME and cellular stiffness in cells containing Huntingtin aggregates. Neurodegeneration driven by pathogenic Huntingtin was also rescued upon overexpression of either Hip1 or Arp3 in Drosophila. Examination of other pathogenic aggregates revealed that TDP-43 also displayed defective CME, altered actin organization and increased stiffness, similar to pathogenic Huntingtin. Together, our results point to an intimate connection between dysfunctional CME, actin misorganization and increased cellular stiffness caused by alteration in the local intracellular environment by pathogenic aggregates.

Epidemiological Profile of Chronic Wounds in an Indian Population: A Community-Based Cross-Sectional Observational Study.

Introduction A wound that has not healed in a timely and organized manner to maintain its anatomical and functional integrity is considered chronic. It can last anywhere from four weeks to over three months and could be caused by trauma, diabetes, vascular disease, infection, or pressure. The primary objective of the study was to determine the prevalence of wounds in a rural and urban community in India, and the secondary objective was to evaluate the effect of various chronic wounds on quality of life (QoL) as assessed by the Short-Form Health Survey-36 (SF-36) questionnaire. Materials and methods The present study is a cross-sectional analytical study done between June 2022 and December 2023, and a total of 10,003 sample population was screened in Varanasi district, Uttar Pradesh, India. The study involved conducting a door-to-door survey of the population sample under interest based on a stratified sampling technique. During the survey, the epidemiological profile of the sample population, a detailed history, and clinical examination findings were recorded in a proforma. The reports of relevant diagnostic investigations were also recorded.  Results The overall prevalence of chronic wounds was 1.89 per 1000 (19/10003) population. The prevalence of wounds in urban areas was 1.57 per 1000 (11/6984) population, while that in rural communities was 2.64 per 1000 (8/3019) population. Of the total 19 patients with chronic wounds, the majority of the patients, i.e., seven each (36.8%), had diabetic foot ulcers (DFUs) and neglected/uncared trauma as the etiology for chronic wounds. The remaining five (5.3%) patients were equally divided between cellulitis, venous ulcers, trophic ulcers, tubercular ulcers, and malignancy as the etiology for chronic wounds. The QoL data suggested that 11 (57.9%) patients reported their general health status as fair with wounds, followed by five (26.3%) reporting their general health status as poor. Only three (15.8%) of the patients with wounds reported their general health condition as good. There was no significant difference between the QoL of rural and urban patients with chronic wounds. The overall prevalence of wounds has decreased from 15.03 to 1.89 per 1000 people in the survey locality. The switch from opting for home-based remedies to supervised care under the clinician (be it in a private or public setting) clearly indicates raised awareness regarding the management of wounds, and with time, people have shown an increased interest in healthcare facility treatment under supervision over adopting home remedies for wound treatment. The same domain may be attributed to the prompt management and efficacy of the management protocols by the treating physicians in India. Conclusion  The findings of the present study regarding the incidence and prevalence of chronic wounds in connection to demographic factors are important when allocating resources and making healthcare plans. The present study conveys a clear message to healthcare practitioners about the necessity of carrying out large-scale epidemiological research on this topic and offers a solid foundation for future studies.

Epigallocatechin-3-gallate Synergistically Inhibits the Proliferation of Lung Cancer Cells with Gemcitabine by Induction of Apoptosis Mediated by ROS Generation.

The present study focused on the formulation, characterization, and evaluation of solid lipid nanoparticles (SLNs) loaded with gemcitabine (GEM) and epigallocatechin-3-gallate (EGCG) for lung cancer treatment. A 2-level, 3-factor factorial design was used to optimize various process parameters in the preparation of SLNs. The average particle size and polydispersity index (PDI) of GEM-EGCG SLNs were found to be 122.8 ± 8.02 and 0.1738 ± 0.02, respectively. Drug loading and release studies indicated a sustained release behavior for GEM-EGCG SLNs, with release kinetics confirmed by the Higuchi model. Cell viability and anticancer activities were assessed using the MTT assay, which determined an IC50 value of 12.5 µg/mL for GEM-EGCG SLNs against A549 cell lines (lung carcinoma epithelial cells). The SLNs were able to internalize into the nuclei of cells, likely due to their small particle size, and were effective in killing cancer cells. Additionally, a study of ROS production-mediated apoptosis of A549 cells was performed through FACS. GEM-EGCG SLNs were found to be stable for 3 months. In vivo studies revealed better drug distribution in the lungs and improved pharmacokinetic profile compared with pure drugs. Overall, the results suggest that combining GEM and EGCG in biocompatible SLNs has resulted in synergistic antitumor potential and improved bioavailability for both drugs, making it a promising anticancer therapeutic regimen against lung cancer.

Translation stalling induced mitochondrial entrapment of ribosomal quality control related proteins offers cancer cell vulnerability.

Ribosome-associated quality control (RQC) monitors ribosomes for aberrant translation. While the role of RQC in neurodegenerative disease is beginning to be appreciated, its involvement in cancer is understudied. Here, we show a positive correlation between RQC proteins ABCE1 and ZNF598 and high-grade muscle-invasive bladder cancer. Translational stalling by the inhibitor emetine (EME) leads to increased mitochondrial localization of RQC factors including ABCE1, ZNF598, and NEMF, which are continuously imported into mitochondria facilitated by increased mitochondrial membrane potential caused by EME. This reduces the availability of these factors in the cytosol, compromising the effectiveness of RQC in handling stalled ribosomes in the cytosol and those associated with the mitochondrial outer membrane (MOM). Imported RQC factors form aggregates inside the mitochondria in a process we term stalling-induced mitochondrial stress (SIMS). ABCE1 plays a crucial role in maintaining mitochondrial health during SIMS. Notably, cancer stem cells (CSCs) exhibit increased expression of ABCE1 and consequently are more resistant to EME-induced mitochondrial dysfunction. This points to a potential mechanism of drug resistance by CSCs. Our study highlights the significance of mitochondrial entrapment of RQC factors such as ABCE1 in determining the fate of cancer cells versus CSCs. Targeting ABCE1 or other RQC factors in translational inhibition cancer therapy may help overcome drug resistance.

Powassan Virus Encephalitis after Tick Bite, Manitoba, Canada.

A case of Powassan encephalitis occurred in Manitoba, Canada, after the bite of a black-legged tick. Awareness of this emerging tickborne illness is needed because the number of vector tick species is growing. No specific treatment options exist, and cases with illness and death are high. Prevention is crucial.

NAFLD-associated hepatocellular carcinoma (HCC) - A compelling case for repositioning of existing mTORc1 inhibitors.

The increasing prevalence of non-alcoholic fatty liver disease (NAFLD) is a growing concern for the high incidence rate of hepatocellular carcinoma (HCC) globally. The progression of NAFLD to HCC is heterogeneous and non-linear, involving intermediate stages of non-alcoholic steatohepatitis (NASH), liver fibrosis, and cirrhosis. There is a high unmet clinical need for appropriate diagnostic, prognostic, and therapeutic options to tackle this emerging epidemic. Unfortunately, at present, there is no validated marker to identify the risk of developing HCC in patients suffering from NAFLD or NASH. Additionally, the current treatment protocols for HCC don't differentiate between viral infection or NAFLD-specific etiology of the HCC and have a limited success rate. The mammalian target of rapamycin complex 1 (mTORc1) is an important protein involved in many vital cellular processes like lipid metabolism, glucose homeostasis, and inflammation. These cellular processes are highly implicated in NAFLD and its progression to severe liver manifestations. Additionally, hyperactivation of mTORc1 is known to promote cell proliferation, which can contribute to the genesis and progression of tumors. Many mTORc1 inhibitors are being evaluated for different types of cancers under various phases of clinical trials. This paper deliberates on the strong pathological implication of the mTORc1 signaling pathway in NAFLD and its progression to NASH and HCC and advocates for a systematic investigation of known mTORc1 inhibitors in suitable pre-clinical models of HCC having NAFLD/NASH-specific etiology.

Comprehensive assessment of per and polyfluoroalkyl substances (PFAS) contamination in groundwater of Kamrup, Assam, India: occurrence, health risks, and metabolomic insights.

Per-and polyfluoroalkyl substances (PFAS) are synthetic chemicals that are known for their environmental persistence and adverse health effects. This study comprehensively assessed PFAS contamination in the Kamrup region of Assam, India, focusing on its presence in groundwater and associated health risks. The analysis detected 12 PFAS in groundwater samples from both the Kamrup Metro and Rural regions. In Kamrup Rural, Perfluorohexanoic acid (PFHxA), perfluorononanoic acid (PFNA), and perfluorooctanesulfonic acid (PFOS) were prevalent, whereas in Kamrup Metro, PFNA and PFOS were dominant, based on detection frequencies. These findings are noteworthy, as they demonstrate the widespread presence of PFAS in groundwater, a vital source of drinking water in the region. The assessment of PFAS health risks in India involved hazard quotient calculations for different age groups. Perfluorobutanesulfonic acid (PFBS) posed the highest risk, ranking children > boys > men > girls > women. Overall, ∑PFAS had low hazard (HQ: 0.27-0.41). Further, this study assessed PFBS and PFOS toxicity in human kidney epithelial cell lines (HEK293T) cells, revealing that PFBS was more cytotoxic than PFOS. The study examined the metabolomics of HEK293T cells after PFBS exposure, revealing significant alterations in lipid metabolism, particularly glycerophospholipids, potentially affecting cellular function and health. These findings underscore the importance of monitoring PFAS contamination in drinking water sources, especially in regions such as Kamrup, where groundwater is a primary source. Our metabolomics results show significant health effects at the cellular level, raising concerns about the impact of PFAS exposure on human health. This study highlights PFAS contamination in Kamrup, Assam's groundwater and its health risks, providing valuable insights for policymakers and public health management.

Fabrication of Na and K based MnO2 nanocomposites for supercapacitive applications.

α-Na0.5Mn0.93O2@Na0.91MnO2 (NaMnO) and K0.48Mn1.94O5@Na0.91MnO2 (KNaMnO) nanocomposites have been synthesized using solid-state reaction method. FESEM results convey the formation of column-shaped morphology. FTIR exhibited a shift in the vibration frequency upon potassium loading. Cyclic voltammetric curves are scanned (0 V-0.8 V) at different scan rates (5 mV/s to 100 mV/s) in 1M KOH electrolyte. Galvanostatic charge-discharge characteristics, for different current densities, have shown non-linear or pseudocapacitive characteristics of the prepared electrodes. High specific capacitance of ∼361 F/g and ∼143 F/g, at a current density of 1A/g, has been achieved for KNaMnO and NaMnO samples, respectively. KNaMnO sample exhibited higher capacitive retention (116 %), up to 2000 cycles, and obeys lower series resistance, charge transfer resistance, and Warburg impedance parameters, thus, convey higher efficiency of this compound for supercapacitor applications.

Evaluation of adapted parent training for challenging behaviour in pre-school children with moderate to severe intellectual developmental disabilities: A randomised controlled trial.

OBJECTIVES: There is limited evidence on the effectiveness of parenting interventions to improve disruptive behaviour in children with intellectual developmental disabilities. This clinical trial evaluated whether an adapted group parenting intervention for preschool children with intellectual developmental disabilities who display challenging behaviour is superior to treatment as usual in England. STUDY DESIGN: 261 children aged 30-59 months with moderate to severe intellectual developmental disabilities and challenging behaviour were randomised to either the intervention (Stepping Stones Triple P) and treatment as usual or treatment as usual alone. The primary outcome was the parent-rated Child Behaviour Checklist at 52 weeks after randomisation. A health economic evaluation was also completed. RESULTS: We found no significant difference between arms on the primary outcome (mean difference -4.23; 95% CI: -9.99 to 1.53; p = 0.147). However, a subgroup analysis suggests the intervention was effective for participants randomised before the COVID-19 pandemic (mean difference -7.12; 95% CI: -13.44 to -0.81; p = 0.046). Furthermore, a complier average causal effects analysis (mean difference -11.53; 95% CI: -26.97 to 3.91; p = 0.143) suggests the intervention requires participants to receive a sufficient intervention dose. The intervention generated statistically significant cost savings (-£1,057.88; 95% CI -£3,218.6 to -£46.67) but the mean point estimate in Quality Adjusted Life Years was similar in both groups. CONCLUSION: This study did not find an effect of the intervention on reducing challenging behaviour, but this may have been influenced by problems with engagement. The intervention could be considered by services as an early intervention if families are supported to attend, especially given its low cost.

A case series analysis of spigelian hernia: A diagnostic dilemma and its successful laparoscopic repair.

ABSTRACT: A Spigelian hernia is an uncommon, atypical protrusion of the peritoneum or abdominal contents via a defect (Spigelian fascia), consisting of the internal oblique aponeuroses and the transversus abdominis. With a frequency ranging from 0.12% to 2% of all abdominal wall hernias, Spigelian hernias are extremely rare. It usually arises from a condition that increases intra-abdominal pressure, the degeneration of the abdominal aponeurotic layers or trauma to the abdominal wall. Herein, we present a case series of patients with varying presentations of Spigelian hernia who presented, who were promptly diagnosed and who were managed successfully with laparoscopic surgical repair.

Coping strategies in young people during the COVID-19 pandemic: rapid review.

AIMS AND METHOD: To better understand factors supporting young people's (age <18 years) mental health during pandemic-type conditions, we aimed to identify whether coping strategies adopted during the COVID-19 pandemic could be dichotomised according to manifesting positive or negative psychological outcomes. Medline, EMBASE, CINAHL, PsycINFO, Scopus and ASSIA databases were used to identify empirical studies that examined coping strategies used by young people experiencing psychological challenges during COVID-19. RESULTS: Twenty-five international studies were included, identifying that coping strategies adopted could be significantly dichotomised according to reducing or exacerbating psychological challenges. Positive coping strategies were proactive and solutions-oriented, whereas negative coping strategies were more avoidant and emotion-oriented. CLINICAL IMPLICATIONS: An internal locus of control may account for why adolescents exercised more proactive coping compared with their younger counterparts, although parents of younger children may offset the impact of stressors by drawing on a proposed coping framework emphasising proactivity and engagement. This would be an invaluable addition to future pandemic preparedness planning cycles.

Phantom Hernia: A Rare Sequela of Herpes Zoster Infection.

The herpes zoster (HZ) virus first manifests as varicella, or chickenpox, in children and remains dormant in the dorsal root ganglia of the nerves. The vesicular eruptions that might be painful develop along a dermatome when the virus is reactivated. While postherpetic neuralgia is a well-known side effect of herpes simplex, there are well-reported motor consequences as well. Segmental zoster paresis is an uncommon motor consequence of herpes zoster that resembles an anterior abdominal wall hernia but does not require surgery in contrast to an actual abdominal wall hernia. We present a similar case of a 46-year-old male who presented with classic herpes zoster rash and phantom hernia as a rare sequela of this condition.

Evaluation of Gemcitabine and Epigallocatechin-3-Gallate Loaded Solid Lipid Nanoparticles on Benzopyrene Induced Lung Cancer Model Via Intranasal Route: Improved Pharmacokinetics and Safety Profile.

The objective of this study was to create a new treatment for lung cancer using solid lipid nanoparticles (SLNs) loaded with gemcitabine (GEM) and epigallocatechin-3-gallate (EGCG) that can be administered through the nose. We analyzed the formulation for its effectiveness in terms of micromeritics, drug release, and anti-cancer activity in the benzopyrene-induced Swiss albino mice lung cancer model. We also assessed the pharmacokinetics, biodistribution, biocompatibility, and hemocompatibility of GEM-EGCG SLNs. The GEM-EGCG SLNs had an average particle size of 93.54 ± 11.02 nm, a polydispersity index of 0.146 ± 0.05, and a zeta potential of -34.7 ± 0.4 mV. The entrapment efficiency of GEM and EGCG was 93.39 ± 4.2% and 89.49 ± 5.1%, respectively, with a sustained release profile for both drugs. GEM-EGCG SLNs had better pharmacokinetics than other treatments, and a high drug targeting index value of 17.605 for GEM and 2.118 for EGCG, indicating their effectiveness in targeting the lungs. Blank SLNs showed no pathological lesions in the liver, kidney, and nasal region validating the safety of SLNs. GEM-EGCG SLNs also showed fewer pathological lesions than other treatments and a lower hemolysis rate of 1.62 ± 0.10%. These results suggest that GEM-EGCG SLNs could effectively treat lung cancer.

An Incidental Finding of Unilateral Winged Scapula in a Patient Presenting With Acute Abdomen: A Case Report.

The primary cause of scapular winging, also known as scapula alata, is typically a malfunction of the serratus anterior, trapezius, and rhomboids, the three major scapular stabilizers. Scapular winging is often caused by injuries to the long thoracic nerve, which weakens the serratus anterior muscle. The long thoracic nerve is particularly vulnerable to both acute and nontraumatic damage due to its longer and superficial course. There are very few documented cases of isolated scapula winging. Here, we present the case of a 15-year-old Asian female who initially presented with right hypochondrium pain, and during a general physical examination, an incidental finding of a left-winged scapula was noted.