COX-2 targeted therapy for diabetic foot ulcers using T7-enhanced CS-PVA membranes.

Diabetic foot ulcers can lead to severe complications, including infection, gangrene, and even amputation, significantly impacting patients' quality of life. The application of anti-inflammatory compounds loaded into chitosan membranes offers targeted therapeutic effects, reducing inflammation and promoting tissue regeneration. This study evaluates the therapeutic efficacy of T7, a selective COX-2 inhibitor, incorporated into chitosan-polyvinylalcohol (CS-PVA) membranes for diabetic wound treatment. Cytotoxicity analysis showed high cell viability across various T7 concentrations, indicating minimal cytotoxicity. In silico pharmacology identified 98 potential inflammation-related targets for T7, further supported by GO and KEGG enrichment analyses. Developmental toxicity tests on zebrafish embryos indicated no significant toxicity up to 100 µM concentration. SEM and FTIR analyses confirmed the successful incorporation of T7 into the CS-PVA membrane, while XRD analysis indicated structural stability. The drug release assay demonstrated a sustained release profile, crucial for prolonged therapeutic efficacy. Antibacterial activity assays revealed significant inhibition of common pathogens. In vivo wound healing assays showed accelerated wound closure and enhanced collagen deposition, with histological and immunohistochemistry analyses supporting improved tissue architecture and reduced inflammation. Gene expression analysis confirmed reduced inflammatory markers. These findings suggest that T7-loaded CS-PVA membranes offer a promising, multifaceted approach to diabetic wound treatment, combining anti-inflammatory, antimicrobial, and collagen-promoting properties for effective wound healing.

Intrabiliary pressure in the pathophysiology of extra hepatic biliary obstruction.

Background and Aim: The aim of this study was to evaluate the role of intrabiliary pressure (IBP) in the pathophysiology of extrahepatic biliary obstruction (EHBO) during percutaneous transhepatic biliary drainage (PTBD). Materials and Methods: Adult patients with EHBO who underwent PTBD were prospectively enrolled. IBP was recorded during primary PTBD. The parameters of interest were age, gender, etiology of EHBO, baseline and post-PTBD liver function tests, duration for resolution of jaundice (decrease in total serum bilirubin ≥30% of baseline or <2 mg/dL), cholangitis, bile cultures, and serum albumin levels. The level of EHBO was divided into three types: Type 1 - secondary biliary confluence involved; Type 2 - primary biliary confluence involved; Type 3 - mid and distal common bile duct obstruction. Results: IBP was measured in 102 patients, and finally, 87 patients, including 52 (59.77%) females, were analyzed. The mean age of the patients was 56.1±11.6 years. The most common etiology of EHBO was carcinoma of the gallbladder in 44 (50.6%) patients. The mean IBP was 18.41±3.91 mmHg. IBP was significantly higher in Type 3 EHBO compared to Type 1 and 2 (p=0.012). A significant correlation was seen between IBP and baseline total serum bilirubin (p<0.01). There was a negative correlation between IBP and baseline serum albumin (p=0.017). In 56.3% of patients, resolution of jaundice was observed by day 3, but this was not significantly associated with IBP (p=0.19). There was no correlation between IBP and cholangitis (p=0.97) or bacterial cultures (p=0.21). Conclusion: IBP was significantly associated with the type of EHBO, baseline serum bilirubin, and albumin levels. IBP could not predict cholangitis or the resolution of jaundice after PTBD.

Exploring the Impact of In Situ-Formed Solid-Electrolyte Interphase on the Cycling Performance of Aluminum Metal Anodes.

Unwanted processes in metal anode batteries, e.g., non-uniform metal electrodeposition, electrolyte decomposition, and/or short-circuiting, are not fully captured by the electrolyte bulk solvation structure but rather defined by the electrode-electrolyte interface and its changes induced by cycling conditions. Specifically, for aluminum-ion batteries (AIBs), the role of the solid-electrolyte interphase (SEI) on the Al0 electrodeposition mechanism and associated changes during resting or cycling remain unclear. Here, we investigated the current-dependent changes at the electrified aluminum anode/ionic liquid electrolyte interface to reveal the conditions of the SEI formation leading to irreversible cycling in the AIBs. We identified that the mechanism of anode failure depends on the nature of the counter electrode, where the areal capacity and cycling current for Al0 electrodeposition dictates the number of successful cycles. Notwithstanding the differences behind unstable aluminum anode cycling in symmetrical cells and AIBs, the uniform removal of electrochemically inactive SEI components, e.g., oxide-rich or solvent-derived organic-rich interphases, leads to more efficient cycling behavior. These understandings raise the importance of using specific conditioning protocols for efficient cycling of the aluminum anode in conjugation with different cathode materials.

Nordihydroguaiaretic acid microparticles are effective in the treatment of osteoarthritis.

Several disease-modifying osteoarthritis (OA) drugs have emerged, but none have been approved for clinical use due to their systemic side effects, short half-life, and rapid clearance from the joints. Nordihydroguaiaretic acid (NDGA), a reactive oxygen species (ROS) scavenger and autophagy inducer, could be a potential treatment for OA. In this report, we show for the first time that sustained delivery of NDGA through polymeric microparticles maintains therapeutic concentrations of drug in the joint and ameliorates post-traumatic OA (PTOA) in a mouse model. In vitro treatment of oxidatively stressed primary chondrocytes from OA patients using NDGA-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles (NDGA-MP) inhibited 15-lipoxygenase, induced autophagy, prevented chondrosenescence, and sustained matrix production. In vivo intra-articular delivery of NDGA-MP was non-toxic and had prolonged retention time (up to 35 days) in murine knee joints. Intra-articular therapy using NDGA-MP effectively reduced cartilage damage and reduced pain in the surgery-induced PTOA mouse model. Our studies open new avenues to modulate the immune environment and treat post-traumatic OA using ROS quenchers and autophagy inducers.

Estimates of the burden of human rabies deaths and animal bites in India, 2022-23: a community-based cross-sectional survey and probability decision-tree modelling study.

BACKGROUND: Reliable and recent data of human rabies deaths and animal bites are not available in India, where a third of global cases occur. Since there is a global target of eliminating dog-mediated human rabies by 2030, understanding whether the country is on track is essential. We aimed to estimate the animal-bite burden and the number of human rabies deaths in India. METHODS: We conducted a community-based nationwide cross-sectional survey with a multistage cluster-sampling design from March 2, 2022 to Aug 26, 2023, covering 60 districts in 15 Indian states. The head of the household or an adult family member was interviewed to collect information about animal-bite history in family members, receipt of anti-rabies vaccination (ARV), and death following animal bite in the family. Annual animal-bite incidence along with 95% CIs were estimated after applying the sampling weights and adjusting for clustering. We estimated annual human rabies deaths using a decision-tree probability model with parameters from the community survey and laboratory data on rabies positivity among suspected rabid dogs. FINDINGS: Of the 337 808 individuals residing in the 78 807 households surveyed, 2052 gave a history of animal bite, mostly (1576 [76·8%]) due to dogs in the past 1 year. The weighted and adjusted annual incidence of animal bite was 6·6 (95% CI 5·7-7·6) per 1000 population, translating into 9·1 million bites nationally. Annual dog-bite incidence was 5·6 (4·8-6·6) per 1000. Among people who had been bitten by a dog, 323 (20·5%) did not receive ARV, and 1043 (66·2%) received at least three doses. Nearly half (615 [49·1%]) of the 1253 individuals who received one dose did not complete their full course of vaccination. We estimated 5726 (95% uncertainty interval 3967-7350) human rabies deaths occurring annually in India. INTERPRETATION: Although there was a substantial decline in human rabies deaths over the past two decades, to eliminate dog-mediated human rabies by 2030, India needs to fast-track its actions by adopting a focused one-health approach. Integrating human and animal surveillance, ensuring timely administration of full course of post-exposure prophylaxis, and accelerating dog vaccination across the country are crucial steps towards this goal. FUNDING: Indian Council of Medical Research.

Recent developments in intranasal drug delivery of nanomedicines for the treatment of neuropsychiatric disorders.

Neuropsychiatric disorders are multifaceted syndromes with confounding neurological explanations. It includes anxiety, depression, autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia, Tourette's syndrome, delirium, dementia, vascular cognitive impairment, and apathy etc. Globally, these disorders occupy 15% of all diseases. As per the WHO, India has one of the largest populations of people with mental illnesses worldwide. The blood-brain barrier (BBB) makes it extremely difficult to distribute medicine to target cells in the brain tissues. However, it is possible through novel advancements in nanotechnology, molecular biology, and neurosciences. One such cutting-edge delivery method, nose-to-brain (N2B) drug delivery using nanoformulation (NF), overcomes traditional drug formulation and delivery limitations. Later offers more controlled drug release, better bioavailability, improved patient acceptance, reduced biological interference, and circumvention of BBB. When medicines are delivered via the intranasal (IN) route, they enter the nasal cavity and go to the brain via connections between the olfactory and trigeminal nerves and the nasal mucosa in N2B. Delivering phytochemical, bioactive and synthetic NF is being investigated with the N2B delivery strategy. The mucociliary clearance, enzyme degradation, and drug translocations by efflux mechanisms are significant issues associated with N2B delivery. This review article discusses the types of neuropsychiatric disorders and their treatment with plant-derived as well as synthetic drug-loaded NFs administered via the IN-delivery system. In conclusion, this review provided a comprehensive and critical overview of the IN applicability of plant-derived NFs for psychiatric disorders.

Complete Correction following Temporary Hemiepiphysiodesis using 2-hole Reconstruction Plates among Skeletally Immature Patients with Angular Deformities around Knees: A Descriptive Cross-sectional Study.

INTRODUCTION: Studies have shown that 2-hole reconstruction plates can be used effectively as tension band plates for temporary hemiepiphysiodesis. However, limited data is available regarding the effectiveness of such plates in terms of complete correction rates. This study was aimed to find out the prevalence of complete correction following temporary hemiepiphysiodesis using 2-hole reconstruction plates among skeletally immature patients with angular deformities around knees. METHODS: A descriptive cross-sectional study was carried out among skeletally immature patients with angular deformities around knees undergoing temporary hemiepiphysiodesis after getting approval from the Institutional Review Committee (Reference number: B&BIRC-23-05). The data were collected between 1 January 2012 to 31 December 2018. All skeletally immature patients with angular deformities around knees undergoing temporary hemiepiphysiodesis using 2-hole reconstruction plates were included. Patients who required additional procedures or implants for deformity correction and those who did not provide consent were excluded. Convenience sampling method was used. Point estimate at 95% Confidence Interval was calculated. RESULTS: Among 102 patients, 66 (64.70%) patients achieved complete correction (59.97-69.43 at 95% Confidence Interval). Mean age of the patients was 8.21±3.11 years and 43 (65.15%) were males and 23 (34.84%) were females. CONCLUSIONS: The prevalence of complete correction following temporary hemiepiphysiodesis using 2-hole reconstruction plate among skeletally immature patients with angular deformities around knees was lower than that reported in other international studies.

Dual Toxidrome of Anti-cholinergic Storm and Neuroleptic Malignant Syndrome: A Therapeutic Challenge Overcome by Intrathecal Neostigmine.

Anticholinergic toxicity and neuroleptic malignant syndrome (NMS) are common toxidromes in medical emergencies. However, their co-occurrence, resulting in a dual toxidrome, is rare and presents significant diagnostic and therapeutic challenges. We present the case of a 23-year-old young male with polysubstance dependence, admitted following combined trihexyphenidyl and risperidone toxicity. He was diagnosed with a dual toxidrome of anticholinergic storm and NMS. Treatment of NMS included lorazepam and bromocriptine. Due to the unavailability of physostigmine, the preferred antidote for anticholinergic syndrome, intrathecal neostigmine was administered. The patient subsequently recovered and was discharged. This case highlights the complexity of managing dual toxidromes and the need for alternative therapeutic strategies in resource-limited settings.

A Case Report on the Trilogy of Yellow Nail Syndrome: Yellow Nails, Pleural Effusion, and Lymphedema.

Yellow nail syndrome is a rare medical syndrome characterized by the combination of a triad of yellow nails, recurrent pulmonary manifestations, and lymphedema. All three features of the triad may not be present synchronously. The diagnosis is made clinically once other causes have been excluded. Typically, it occurs in individuals who are 50 years old and above. We report a case of yellow nail syndrome in a 62-year-old male who presented with recurrent episodes of difficulty breathing due to pleural effusion. Further examination revealed pitting edema of the bilateral lower extremities. In the later encounter, his nail was found to be yellowish. Excluding other diagnoses like heart failure, fungal infections, autoimmune diseases, and lung cancer, with a typical triad, a diagnosis of yellow nail syndrome was made. He was managed with pleural fluid tapping for pleural effusion, compression stockings for leg edema, and vitamin E for nail changes. The study also intends to highlight current treatment options and alert physicians of this syndrome with such typical findings.

Preliminary Investigation and Therapeutic Efficacy Determination of a Novel Anti-IL-17A Antibody, Indikizumab.

Purpose: The study aimed to develop and characterize Indikizumab, a novel humanized anti-IL-17A monoclonal antibody (mAb), for potential therapeutic use in inflammatory indications such as psoriasis, psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis. Methods: The research involved the purification of IL-17 isoforms, epitope mapping, affinity ranking, and comparative binding assessment of anti-IL-17 antibodies. The study also included cell-based neutralization assays and in vivo studies using mouse models to evaluate the efficacy of Indikizumab. Results: Indikizumab demonstrated a high binding affinity (KD=27.2 pM) and specificity for IL-17A, with comparable potency to Secukinumab. In cell-based neutralization assays, Indikizumab effectively neutralized the effects of IL-17A and demonstrated a statistically significant reduction in plasma KC (Keratinocyte) levels in a mouse model. In imiquimod-induced psoriasis mouse model, Indikizumab showed potential in reducing the psoriasis index. Conclusion: Indikizumab represents a promising therapeutic option for inflammatory indications with its high binding affinity, specificity for IL-17A, and effectiveness in neutralizing IL-17A effects in vivo.