Nitric oxide: Potential therapeutic target in Heat Stress-induced Multiple Organ Dysfunction.

As climate change intensifies, urgent action is needed to address global warming and its associated health risks, particularly in vulnerable regions. Rising global temperature and increasing frequency of heatwaves present a hidden health risk, disrupting the body's temperature regulation and leading to severe consequences such as heat stress-induced multiple organ dysfunction (HS-MOD). Multiple organ injury triggered by heat stress involves complex molecular pathways such as nitric oxide dysregulation, inflammation, oxidative stress, mitochondrial dysfunction, calcium homeostasis disruption, and autophagy impairment that contribute to cellular damage. Understanding these molecular pathways is crucial for developing targeted therapeutic interventions to alleviate the impact of heat stress (HS). As we explore numerous therapeutic strategies, a remarkable molecule captures our attention: nitric oxide (NO). This colorless gas, mainly produced by nitric oxide synthase (NOS) enzymes, plays crucial roles in various body functions. From promoting vasodilation and neurotransmission to regulating the immune response, platelet function, cell signaling, and reproductive health, NO stands out for its versatility. Exploring it as a promising treatment for heat stress-induced multiple organ injury highlights its distinctive features in the journey towards effective therapeutic interventions. This involves exploring both pharmacological avenues, considering the use of NO donors and antioxidants, and non-pharmacological strategies, such as adopting nitrate-rich diets and engaging in exercise regimens. This review highlights the concept of heat stress, the molecular framework of the disease, and treatment options based upon some new interventions.

A fluorescent probe with serum albumin as a signal amplifier for real-time sensing of HSO3- in solution, mitochondria of animal cells and rice roots.

Endogenous release of HSO3- during the enzymatic oxidation of sulfur containing amino acids in mitochondria or insufficiency of sulfite oxidase results in the accumulation of sulfite and thiosulfate in biological fluids affecting mitochondrial homeostasis of brain mitochondria associated with serious clinical symptoms related to neurological disorders. The red fluorescent probe MGQ undergoes self-assembly in water and reveals aggregation induced quenching of fluorescence. MGQ reveals 143-fold and 179-fold increases in fluorescence intensity at 645 nm, respectively, in the presence of HSA and BSA and does not significantly differentiate between two albumins. The detailed studies of MGQ have been performed in the presence of BSA. The presence of other enzymes/proteins and amino acids, viz. pepsin, trypsin, lysozyme, Bromelain, lysine, histidine, hemoglobin, etc., does not affect the fluorescence of MGQ or MGQ-BSA solutions and points to high selectivity towards BSA. The limit of detection for BSA is 10 nM. In PBS buffer, MGQ in the absence of BSA does not react with HSO3- and sluggishly in a 1 : 1 ethanol-water mixture. However, in the confined space of BSA/HSA, MGQ displays a signal amplification, undergoes instantaneous Michael type addition of HSO3- and results in a ratiometric change in fluorescence intensity in ≤1.5 min with the decrease of red fluorescence at 645 nm and emergence of green fluorescence at 515 nm. The LOD for the detection of HSO3- is 4 nM.

Candidaemia and Central Line-Associated Candidaemia in a Network of Indian ICUs: Impact of COVID-19 Pandemic.

BACKGROUND AND OBJECTIVES: Candidaemia is a potentially life-threatening emergency in the intensive care units (ICUs). Surveillance using common protocols in a large network of hospitals would give meaningful estimates of the burden of candidaemia and central line associated candidaemia in low resource settings. We undertook this study to understand the burden and epidemiology of candidaemia in multiple ICUs of India, leveraging the previously established healthcare-associated infections (HAI) surveillance network. Our aim was also to assess the impact that the pandemic of COVID-19 had on the rates and associated mortality of candidaemia. METHODS: This study included adult patients from 67 Indian ICUs in the AIIMS-HAI surveillance network that conducted BSI surveillance in COVID-19 and non-COVID-19 ICUs during and before the COVID-19 pandemic periods. Hospitals identified healthcare-associated candidaemia and central line associated candidaemia and reported clinical and microbiological data to the network as per established and previously published protocols. RESULTS: A total of 401,601 patient days and 126,051 central line days were reported during the study period. A total of 377 events of candidaemia were recorded. The overall rate of candidaemia in our network was 0.93/1000 patient days. The rate of candidaemia in COVID-19 ICUs (2.52/1000 patient days) was significantly higher than in non-COVID-19 ICUs (1.05/patient days) during the pandemic period. The rate of central line associated candidaemia in COVID-19 ICUs (4.53/1000 central line days) was also significantly higher than in non-COVID-19 ICUs (1.73/1000 central line days) during the pandemic period. Mortality in COVID-19 ICUs associated with candidaemia (61%) was higher than that in non-COVID-19 ICUs (41%). A total of 435 Candida spp. were isolated. C. tropicalis (26.7%) was the most common species. C. auris accounted for 17.5% of all isolates and had a high mortality. CONCLUSION: Patients in ICUs with COVID-19 infections have a much higher risk of candidaemia, CLAC and its associated mortality. Network level data helps in understanding the true burden of candidaemia and will help in framing infection control policies for the country.

A Network Meta-Analysis of Randomized Controlled Trials on the Comparative Efficacy of Stem Cells Therapy for Diabetic Foot Ulcer Healing.

Stem cell therapy in diabetic foot ulcer has emerged as a promising treatment option to promote ulcer healing. This network meta-analysis was undertaken to evaluate how they compete with each other and their ranking with respect to chances of ulcer healing. A systematic search strategy to retrieve data from five databases, were used to identify potential studies. Randomized controlled trial or clinical controlled trial, published in English, using any type of stem cells as intervention in individuals aged over 18 years diagnosed with diabetic foot ulcers were included. This network meta-analysis was performed using frequentist method using R version 4.2.1. Eighteen clinical trials were included in the study which included 13 interventions. The study found that most of the stem cells were significantly promoting ulcer healing chances with human viable wound matrix (hVWM) [RR 2.91; CI: 1.28, 6.64], peripheral blood mononuclear cells (PBMNC) [RR 2.35; CI: 1.21, 4.55], bone marrow mesenchymal stem cells (BMMSCs) [RR 2.20; CI: 1.34, 3.60], were top three stem cell options among all. P score also suggested the same. Risk of bias study suggested that there was "some concern or "high risk'' among majority of studies. It is evident from this study that bone marrow mononuclear cells were found to be most effective in wound healing in cases of diabetic foot ulcer in that order. Though there was no significant difference between these and more studies were required to ascertain whether they differ in term of efficacy for the clinical outcome of ulcer healing.

A brief review on the lessons learned from COVID-19 on drug discovery and research.

COVID-19 pandemic has taught many lessons regarding drug discovery and development. This review covers these aspects of drug discovery and research for COVID-19 which might be used as a tool for future. It summarizes the positives such as progresses in antiviral drug discovery, drug repurposing, adaptations of clinical trial and its regulations, as well as the negative points such as the need to develop more collaboration among stakeholders and future directions. It also discusses the benefits and limitations of finding new indications for existing drugs, and the lessons learned regarding rigorous and robust clinical trials, pharmacokinetic/pharmacodynamic modelling, as well as combination therapy. The pandemic has also revealed some gaps regarding global collaboration and coordination, data sharing and transparency and equitable distribution. Finally, the review enumerates the future directions and implications of drug discovery and research for COVID-19 and other infectious diseases such as preparedness and resilience, interdisciplinary and integrative approaches, diversity and inclusion, and personalized and precision medicine.

STAT3 Protein-Protein Interaction Analysis Finds P300 as a Regulator of STAT3 and Histone 3 Lysine 27 Acetylation in Pericytes.

BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) is a member of the cytoplasmic inducible transcription factors and plays an important role in mediating signals from cytokines, chemokines, and growth factors. We and others have found that STAT3 directly regulates pro-fibrotic signaling in the kidney. The STAT3 protein-protein interaction plays an important role in activating its transcriptional activity. It is necessary to identify these interactions to investigate their function in kidney disease. Here, we investigated the protein-protein interaction among three species to find crucial interactions that can be targeted to alleviate kidney disease. METHOD: In this study, we examined common protein-protein interactions leading to the activation or downregulation of STAT3 among three different species: humans (Homo sapiens), mice (Mus musculus), and rabbits (Oryctolagus cuniculus). Further, we chose to investigate the P300 and STAT3 interaction and performed studies of the activation of STAT3 using IL-6 and inhibition of the P300 by its specific inhibitor A-485 in pericytes. Next, we performed immunoprecipitation to confirm whether A-485 inhibits the binding of P300 to STAT3. RESULTS: Using the STRING application from ExPASy, we found that six proteins, including PIAS3, JAK1, JAK2, EGFR, SRC, and EP300, showed highly confident interactions with STAT3 in humans, mice, and rabbits. We also found that IL-6 treatment increased the acetylation of STAT3 and increased histone 3 lysine acetylation (H3K27ac). Furthermore, we found that the disruption of STAT3 and P300 interaction by the P300 inhibitor A-485 decreased STAT3 acetylation and H3K27ac. Finally, we confirmed that the P300 inhibitor A-485 inhibited the binding of STAT3 with P300, which inhibited its transcriptional activity by reducing the expression of Ccnd1 (Cyclin D1). CONCLUSIONS: Targeting the P300 protein interaction with STAT3 may alleviate STAT3-mediated fibrotic signaling in humans and other species.

Protective effect of rutin on acrylamide induced ovarian inflammation, oxidative stress, DNA damage, and hormonal changes: Based on in silico and in vivo study.

Acrylamide (AA) is a carcinogenic compound that affects people due to its frequent use in laboratories and industry as well as the high-temperature cooking of foods with high hydrocarbon content. AA is known to cause severe reproductive abnormalities. The main aim of this study is to evaluate the protective effect of rutin (RU), a phytoactive compound, against AA-induced reproductive toxicity in female rats. Initially, rats were exposed to AA (40 mg/kg for 10 days). Therapy of RU was given after AA intoxication consecutively for 3 days. After 24 h of the last treatment, all the animals were sacrificed. The study evaluated reproductive hormones, oxidative stress markers, membrane-bound enzymes, DNA damage, histological findings, and an in silico approach to determine the protective efficacy of RU. The results indicated that RU significantly protected against inflammation, oxidative stress, and DNA damage induced by AA, likely due to its antioxidant properties.

Genetic mapping of stripe rust resistance in a geographically diverse barley collection and selected biparental populations.

Barley stripe or yellow rust (BYR) caused by Puccinia striiformis f. sp. hordei (Psh) is a significant constraint to barley production. The disease is best controlled by genetic resistance, which is considered the most economical and sustainable component of integrated disease management. In this study, we assessed the diversity of resistance to Psh in a panel of international barley genotypes (n = 266) under multiple disease environments (Ecuador, India, and Mexico) using genome-wide association studies (GWASs). Four quantitative trait loci (QTLs) (three on chromosome 1H and one on 7H) associated with resistance to Psh were identified. The QTLs were validated by mapping resistance to Psh in five biparental populations, which detected key genomic regions on chromosomes 1H (populations Pompadour/Zhoungdamei, Pompadour/Zug161, and CI9214/Baudin), 3H (Ricardo/Gus), and 7H (Fumai8/Baronesse). The QTL RpshQ.GWA.1H.1 detected by GWAS and RpshQ.Bau.1H detected using biparental mapping populations co-located were the most consistent and stable across environments and are likely the same resistance region. RpshQ.Bau.1H was saturated using population CI9214/Baudin by enriching the target region, which placed the resistance locus between 7.9 and 8.1 Mbp (flanked by markers sun_B1H_03, 0.7 cM proximal to Rpsh_1H and sun_B1H_KASP_02, 3.2 cM distal on 1HS) in the Morex reference genome v.2. A Kompetitive Allele Specific PCR (KASP) marker sun_B1H_KASP_01 that co-segregated for RpshQ.Bau.1H was developed. The marker was validated on 50 Australian barley cultivars, showing well-defined allelic discrimination and presence in six genotypes (Baudin, Fathom, Flagship, Grout, Sakurastar, and Shepherd). This marker can be used for reliable marker-assisted selection and pyramiding of resistance to Psh and in diversifying the genetic base of resistance to stripe rust.

Surgical Cholecystectomy Score (SCS) for grading the difficulty of laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy (LC) is the standard of care for symptomatic gall stone disease. A good scoring system is necessary to standardize the reporting. Our aim was to develop and validate an objective scoring system, the Surgical Cholecystectomy Score (SCS) to grade the difficulty of LC. METHODS: The study was conducted in a single surgical unit at a tertiary care hospital in two phases from January 2017 to April 2021. Retrospective data was analysed and the difficulty of each procedure was graded according to the modified Nassar's scoring system. Significant preoperative and intraoperative data obtained was given a weightage score. In phase II, these scores were validated on a prospective cohort. Each procedure was classified either as easy, moderately difficult or difficult. STATISTICAL ANALYSIS: A univariate analysis was performed on the data followed by a multivariate regression analysis. Bidirectional stepwise selection was done to select the most significant variables. The Beta /Schneeweiss scoring system was used to generate a rounded risk score. RESULTS: Data of 800 patients was retrieved and graded. 10 intraoperative parameters were found to be significant. Each variable was assigned a rounded risk score. The final SCS range for intraoperative parameters was 0-15. The scoring system was validated on a cohort of 249 LC. In the final scoring, cut off SCS of > 8 was found to correlate with difficult procedures. Score of < 2 was equivalent to easy LC. A score between 2 and 8 indicated moderate difficulty. The area under ROC curve was 0.98 and 0.92 for the intraoperative score indicating that the score was an excellent measure of the difficulty level of LCs. CONCLUSION: The scoring system developed in this study has shown an excellent correlation with the difficulty of LC. It needs to be validated in different cohorts and across multiple centers further.

Outcomes of Video-assisted Thoracic Surgery-guided Early Evacuation of Traumatic Hemothorax: A Randomized Pilot Study at Level I Trauma Center.

Introduction: Traumatic hemothorax is accounted for about 20% of traumatic chest injuries. Although majority can be managed with the timely placement of intercostal tube (ICT) drainage, the remaining pose a challenge owing to high complication rates associated with retained hemothorax. Although various treatment modalities including intrapleural instillation of fibrinolytics, radioimage guided drainage, VATS guided evacuation and thoractomy do exist to address the retained hemothorax, but indications along with timing to employ a specific treatment option is still unclear and ambiguous. Methods: Patient with residual hemothorax (>200 mL) on ultrasonography after 48 h of indwelling ICT was randomized into either early video-assisted thoracic surgery (VATS) or conventional approach cohort. Early VATS cohort was subjected to video-assisted thoracoscopic evacuation of undrained blood along with normal saline irrigation and ICT placement. The conventional cohort underwent intrapleural thrombolytic instillation for 3 consecutive days. The outcome measures were the duration of indwelling ICT, removal rate of tube thoracostomy, length of hospital stay, duration of intensive care unit (ICU) monitoring, need for mechanical ventilation, incidence of pulmonary and pleural complications, and requirement of additional intervention to address undrained hemothorax and mortality rate. Results: The early VATS cohort had shorter length of hospital stay (7.50 ± 0.85 vs. 9.50 ± 3.03, P = 0.060), reduced duration of indwelling ICT (6.70 ± 1.25 vs. 8.30 ± 2.91, P = 0.127) with higher rate of tube thoracostomy removal (70% vs. 30%, P = 0.003) and lesser need of additional interventions (0% vs. 30%, P = 0.105). Thoracotomy (3 patients) and image-guided drainage (4 patients) were additional interventions to address retained hemothorax in the conventional cohort. However, similar length of ventilator assistance (0.7 ± 0.48 vs. 0.60 ± 1.08, P = 0.791) and prolonged ICU monitoring (1.30 ± 1.06 vs. 0.90 ± 1.45, P = 0.490) was observed in early VATS cohort. Both the cohorts had no mortality. Conclusion: VATS-guided early evacuation of traumatic hemothorax is associated with shorter length of hospital stay along with abbreviated indwelling ICT duration, reduced incidence of complications, lesser readmissions, and improved rate of tube thoracostomy removal. However, the duration of ventilator requirement, ICU stay, and mortality remain unchanged.

Recombinant YopE and LcrV vaccine candidates protect mice against plague and yersiniosis.

No licensed vaccine exists for the lethal plague and yersiniosis. Therefore, a combination of recombinant YopE and LcrV antigens of Yersinia pestis was evaluated for its vaccine potential in a mouse model. YopE and LcrV in formulation with alum imparted a robust humoral immune response, with isotyping profiles leaning towards the IgG1 and IgG2b subclasses. It was also observed that a significantly enhanced expression of IFN-γ, TNF-α, IL-6, IL-2, and IL-1ß from the splenic cells of vaccinated mice, as well as YopE and LcrV-explicit IFN-γ eliciting T-cells. The cocktail of YopE + LcrV formulation conferred complete protection against 100 LD50Y. pestis infection, while individually, LcrV and YopE provided 80 % and 60 % protection, respectively. Similarly, the YopE + LcrV vaccinated animal group had significantly lower colony forming unit (CFU) counts in the spleen and blood compared to the groups administered with YopE or LcrV alone when challenged with Yersinia pseudotuberculosis and Yersinia enterocolitica. Histopathologic evidence reinforces these results, indicating the YopE + LcrV formulation provided superior protection against acute lung injury as early as day 3 post-challenge. In conclusion, the alum-adjuvanted YopE + LcrV is a promising vaccine formulation, eliciting a robust antibody response including a milieu of pro-inflammatory cytokines and T-cell effector functions that contribute to the protective immunity against Yersinia infections. YopE and LcrV, conserved across all three human-pathogenic Yersinia species, provide cross-protection. Therefore, our current vaccine (YopE + LcrV) targets all three pathogens: Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica. However, the efficacy should be tested in other higher mammalian models.

Role of low-pressure negative pleural suction in patients with thoracic trauma - a randomized controlled trial.

BACKGROUND: Thoracic trauma frequently includes a pneumothorax, hemothorax, or hemopneumothorax, which may necessitate an Intercostal drainage (ICD) for air and fluid evacuation to improve breathing and circulatory function. It is a simple and life-saving procedure; nevertheless, it carries morbidity, even after its removal. Efforts have been made continuously to shorten the duration of ICD, but mostly in non-trauma patients. In this study, we evaluated the impact of negative pleural suction over the duration of ICD. METHODS: This study was a prospective randomized controlled interventional trial conducted at Level 1 Trauma Centre. Thoracic trauma patients with ICD, who met the inclusion criteria (sample size 70) were randomized into two groups, the first group with negative pleural suction up to -20 cm H2O, and the second group as conventional, i.e. ICD connected to underwater seal container only. The primary objective was to compare the duration of ICDs and the secondary objectives were the length of hospital stay and various complications of thoracic trauma. RESULTS: Duration of ICD was measured in median days with minimum & maximum days. For the negative suction group, it was 4 days (2-16 days); for the conventional group, it was also 4 days (2-17 days). There was also no significant difference among both groups in length of hospital stay. CONCLUSION: The beneficial effect of negative pleural suction to ICD could not be demonstrated over the duration of ICD and hospital stay. In both groups, there was no significant difference in complication rates like recurrent pneumothorax, retained hemothorax, persistent air leak, and empyema. LEVEL OF EVIDENCE: Therapeutic Study, Level II TRIAL REGISTRATION: This trial was registered with the Clinical Trial Registry of India (CTRI) with registration no. REF/2020/11/038403.

Self-Healable Interfaces with Improved Mechanical Properties Induced by Dynamic Network Reconfiguration in Carbon Fiber-Reinforced Epoxy Laminates.

Interfacial failure in carbon fiber-reinforced epoxy (CFRE) laminates is a prominent mode of failure, attracting significant research attention. The large surface-energy mismatch between carbon fiber (CF) and epoxy results in a weaker interface. This study presents a facile yet effective method for enhancing the interfacial adhesion between CF and epoxy with self-healable interfaces. Two variants of a designer sizing agent, poly(ether imide) (PEI), were synthesized, one without a self-healing property termed BO, and the second one by incorporating disulfide metathesis in one of its monomers that renders self-healing properties at the interface-mediated by network reconfiguration, termed BA. 0.25 wt % of CF was found to be the optimum amount of BO and BA sizing agents. The surface free energy of CF drastically increased and became quite close to the surface energy of epoxy after the deposition of both sizing agents and the higher surface roughness. The improved surface wettability, presence of functional groups, and mechanical interlocking worked in tandem to strengthen the interface. The interlaminar shear strength (ILSS) and flexural strength (FS) of CFRE laminate sized with BO consequently increased by 35% and 22% and of CFRE laminate sized with BA increased by 26% and 19%, respectively. Fractography analysis revealed outstanding bonding between epoxy and PEI-CF, indicating that matrix fracture is the predominant mode of failure. The self-healable interfaces due to the preinstalled disulfide metathesis in the sizing agent resulted in 51% self-healing efficiency in ILSS for BA-sized CFRE laminate. Interestingly, the functional properties, deicing, and EMI shielding effectiveness were not compromised by modification of the interface with this designer sizing agent. This study opens new avenues for interfacial modification to improve the mechanical properties while retaining the key functional properties of the laminates.

MicroRNAs and synapse turnover in Alzheimer's disease.

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-beta plaques and neurofibrillary tangles in the brain, leading to synaptic dysfunction and cognitive decline. Healthy synapses are the crucial for normal brain function, memory restoration and other neurophysiological function. Synapse loss and synaptic dysfunction are two primary events that occur during AD initiation. Synapse lifecycle and/or synapse turnover is divided into five key stages and several sub-stages such as synapse formation, synapse assembly, synapse maturation, synapse transmission and synapse termination. In normal state, the synapse turnover is regulated by various biological and molecular factors for a healthy neurotransmission. In AD, the different stages of synapse turnover are affected by AD-related toxic proteins. MicroRNAs (miRNAs) have emerged as critical regulators of gene expression and have been implicated in various neurological diseases, including AD. Deregulation of miRNAs modulate the synaptic proteins and affect the synapse turnover at different stages. In this review, we discussed the key milestones of synapse turnover and how they are affected in AD. Further, we discussed the involvement of miRNAs in synaptic turnover, focusing specifically on their role in AD pathogenesis. We also emphasized the regulatory mechanisms by which miRNAs modulate the synaptic turnover stages in AD. Current studies will help to understand the synaptic life-cycle and role of miRNAs in each stage that is deregulated in AD, further allowing for a better understanding of the pathogenesis of devastating disease.

Mitochondria-Associated MicroRNAs and Parkinson's Disease.

Parkinson's Disease (PD) occurs as a result of the progressive loss of dopaminergic neurons within the substantia nigra causing motor and non-motor symptoms and has become more prevalent within the last several decades. With mitochondria being essential to cellular survival, mitochondrial dysfunction contributes to the disease progression by increasing neuron loss through (1) insufficient ATP production and (2) reactive oxygen species generation. MicroRNAs (miRNAs) are small molecules located throughout cells that regulate gene expression, particularly mitochondrial function. Through their own dysregulation, miRNAs offset the delicate balance of mitochondrial function by altering or dysregulating the expression of proteins, increasing neuroinflammation, increasing retention of toxic substances, limiting the removal of reactive oxygen species, and preventing mitophagy. Improper mitochondrial function places cells at increased risk of apoptosis, a major concern in individuals with PD due to their reduced number of dopaminergic neurons. This article has identified the 17 most promising mitochondrial associated miRNAs within PD: hsa-miR-4639-5p, miR-376a, miR-205, miR-421, miR-34b/c, miR-150, miR-7, miR-132, miR-17-5p, miR-20a, miR-93, miR-106, miR-181, miR-193b, miR-128, miR-181a, and miR-124-3p. These miRNAs alter mitochondrial function and synaptic energy by impeding normal gene expression when up or downregulated. However, there is limited research regarding mitochondria-localized miRNAs that are typically seen in other diseases. Mitochondria-localized miRNA may have a greater impact on mitochondrial dysfunction due to their proximity. Further research is needed to determine the location of these miRNAs and to better understand their regulatory capabilities on mitochondrial and synaptic function within PD.

Vaccine Designing Technology against Leishmaniasis: Current Challenges and Implication.

Leishmaniasis, a debilitating disease caused by protozoan parasites of the genus Leishmania and transmitted by the bite of a female sandfly, continues to present significant challenges despite ongoing research and collaboration in vaccine development. The intricate interaction between the parasite's life cycle stages and the host's immunological response, namely the promastigote and amastigote forms, adds complexity to vaccine design. The quest for a potent vaccine against Leishmaniasis demands a comprehensive understanding of the immune mechanisms that confer long-lasting protection, which necessitates extensive research efforts. In this pursuit, innovative approaches such as reverse vaccinology and computer-aided design offer promising avenues for unraveling the intricacies of host-pathogen interactions and identifying effective vaccine candidates. However, numerous obstacles, including limited treatment options, the need for sustained antigenic presence, and the prevalence of co-infections, particularly with HIV, impede progress. Nevertheless, through persistent research endeavours and collaborative initiatives, the goal of developing a highly efficacious vaccine against Leishmaniasis can be achieved, offering hope through the latest Omics data development with immunoinformatics approaches for effective vaccine design for the prevention of this disease.

Benefits of Rib Fixation Utilizing Low-Cost Materials: A Randomized Pilot Trial.

INTRODUCTION: Surgical stabilization of rib fractures (SSRF) using standard rib plating systems has become a norm in developed countries. However, the procedure has not garnered much interest in low-middle-income countries, primarily because of the cost. METHODS: This was a single-center pilot randomized trial. Patients with severe rib fractures were randomized into two groups: SSRF and nonoperative management. SSRF arm patients underwent surgical fixation in addition to the tenets of nonoperative management. Low-cost materials like stainless steel wires and braided polyester sutures were used for fracture fixation. The primary outcome was to assess the duration of hospital stay. RESULTS: Twenty-two patients were randomized, 11 in each arm. Per-protocol analysis showed that the SSRF arm had significantly reduced duration of hospital stay (22.6 ± 19.1 d versus 7.9 ± 5.7 d, P value 0.031), serial pain scores at 48 h and 5 d (median score 5, IQR (3-6) versus median score 7, IQR (6.5-8), P value 0.004 at 48 h and median score 2 IQR (2-3) versus median score 7 IQR (4.5-7) P value 0.0005 at 5 d), significantly reduced need for injectable opioids (9.9 ± 3.8 mg versus 4.4 ± 3.4 mg, P value 0.003) and significantly more ventilator-free days (19.9 ± 8.7 d versus 26.4 ± 3.2 d, P value 0.04). There were no statistically significant differences in the total duration of ICU stay (median number of days 2, IQR 1-4.5 versus median number of days 7, IQR 1-14, P value 0.958), need for tracheostomy (36.4% versus 0%, P value 0.155), and pulmonary and pleural complications. CONCLUSIONS: SSRF with low-cost materials may provide benefits similar to standard rib plating systems and can be used safely in resource-poor settings.

MicroRNA-502-3p regulates GABAergic synapse function in hippocampal neurons.

JOURNAL/nrgr/04.03/01300535-202412000-00026/figure1/v/2024-04-08T165401Z/r/image-tiff Gamma-aminobutyric acid (GABA)ergic neurons, the most abundant inhibitory neurons in the human brain, have been found to be reduced in many neurological disorders, including Alzheimer's disease and Alzheimer's disease-related dementia. Our previous study identified the upregulation of microRNA-502-3p (miR-502-3p) and downregulation of GABA type A receptor subunit α-1 in Alzheimer's disease synapses. This study investigated a new molecular relationship between miR-502-3p and GABAergic synapse function. In vitro studies were performed using the mouse hippocampal neuronal cell line HT22 and miR-502-3p agomiRs and antagomiRs. In silico analysis identified multiple binding sites of miR-502-3p at GABA type A receptor subunit α-1 mRNA. Luciferase assay confirmed that miR-502-3p targets the GABA type A receptor subunit α-1 gene and suppresses the luciferase activity. Furthermore, quantitative reverse transcription-polymerase chain reaction, miRNA in situ hybridization, immunoblotting, and immunostaining analysis confirmed that overexpression of miR-502-3p reduced the GABA type A receptor subunit α-1 level, while suppression of miR-502-3p increased the level of GABA type A receptor subunit α-1 protein. Notably, as a result of the overexpression of miR-502-3p, cell viability was found to be reduced, and the population of necrotic cells was found to be increased. The whole cell patch-clamp analysis of human-GABA receptor A-α1/ß3/γ2L human embryonic kidney (HEK) recombinant cell line also showed that overexpression of miR-502-3p reduced the GABA current and overall GABA function, suggesting a negative correlation between miR-502-3p levels and GABAergic synapse function. Additionally, the levels of proteins associated with Alzheimer's disease were high with miR-502-3p overexpression and reduced with miR-502-3p suppression. The present study provides insight into the molecular mechanism of regulation of GABAergic synapses by miR-502-3p. We propose that micro-RNA, in particular miR-502-3p, could be a potential therapeutic target to modulate GABAergic synapse function in neurological disorders, including Alzheimer's disease and Alzheimer's disease-related dementia.

A Narrative Review on 3-Dimensional Visualization Techniques in Neurosurgical Education, Simulation, and Planning.

BACKGROUND: High-fidelity visualization of anatomical organs is crucial for neurosurgical education, simulation, and planning. This becomes much more important for minimally invasive neurosurgical procedures. Realistic anatomical visualization can allow resident surgeons to learn visual cues and orient themselves with the complex 3-dimensional (3D) anatomy. Achieving full fidelity in 3D medical visualization is an active area of research; however, the prior reviews focus on the application area and lack the underlying technical principles. Accordingly, the present study attempts to bridge this gap by providing a narrative review of the techniques used for 3D visualization. METHODS: We conducted a literature review on 3D medical visualization technology from 2018 to 2023 using the PubMed and Google Scholar search engines. The cross-referenced manuscripts were extensively studied to find literature that discusses technology relevant to 3D medical visualization. We also compiled and ran software applications that were accessible to us in order to better understand them. RESULTS: We present the underlying fundamental technology used in 3D medical visualization in the context of neurosurgical education, simulation, and planning. Further, we discuss and categorize a few important applications based on the 3D visualization techniques they use. CONCLUSIONS: The visualization of virtual human organs has not yet achieved a level of realism close to reality. This gap is largely due to the interdisciplinary nature of this research, population diversity, and validation complexities. With the advancements in computational resources and automation of 3D visualization pipelines, next-gen applications may offer enhanced medical 3D visualization fidelity.

GO-tagged PEI sizing agent imparts self-healing and excellent mechanical properties to carbon fiber reinforced epoxy laminates.

Carbon fiber-reinforced epoxy (CFRE) laminates have attracted significant attention as a structural material specifically in the aerospace industry. In recent times, various strategies have been developed to modify the carbon fiber (CF) surface as the interface between the epoxy matrix and CFs plays a pivotal role in determining the overall performance of CFRE laminates. In the present work, graphene oxide (GO) was used to tag a polyetherimide (PEI, termed BA) containing exchangeable bonds and was employed as a sizing agent to improve the interfacial adhesion between CFs and epoxy. This unique GO-tagged-BA sizing agent termed BAGO significantly enhanced the mechanical properties of CFRE laminates by promoting stronger interactions between CFs and the epoxy matrix. The successful synthesis of BAGO was verified by Fourier-transform infrared spectroscopy. Additionally, the partial reduction of GO owing to this tagging with BA was further confirmed by X-ray diffraction and Raman spectroscopy, and the thermal stability of this unique sizing agent was evaluated using thermogravimetric analysis. The amount of GO in BAGO was optimized as 0.25 wt% of BA termed 0.25-BAGO. The 0.25-BAGO sizing agent resulted in a significant increase in surface roughness, from 15 nm to 140 nm, and surface energy, from 13.2 to 34.7 mN m-1 of CF. The laminates prepared from 0.25-BAGO exhibited a remarkable 40% increase in flexural strength (FS) and a 35% increase in interlaminar shear strength (ILSS) due to interfacial strengthening between epoxy and CFs. In addition, these laminates exhibited a self-healing efficiency of 51% in ILSS due to the presence of dynamic disulfide bonds in BAGO. Interestingly, the laminates with 0.25-BAGO exhibited enhanced Joule heating and enhanced deicing, though the EMI shielding efficiency slightly declined.