Healing the diabetic wound: Unlocking the secrets of genes and pathways.

Diabetic wounds (DWs) are open sores that can occur anywhere on a diabetic patient's body. They are often complicated by infections, hypoxia, oxidative stress, hyperglycemia, and reduced growth factors and nucleic acids. The healing process involves four phases: homeostasis, inflammation, proliferation, and remodeling, regulated by various cellular and molecular events. Numerous genes and signaling pathways such as VEGF, TGF-ß, NF-κB, PPAR-γ, MMPs, IGF, FGF, PDGF, EGF, NOX, TLR, JAK-STAT, PI3K-Akt, MAPK, ERK, JNK, p38, Wnt/ß-catenin, Hedgehog, Notch, Hippo, FAK, Integrin, and Src pathways are involved in these events. These pathways and genes are often dysregulated in DWs leading to impaired healing. The present review sheds light on the pathogenesis, healing process, signaling pathways, and genes involved in DW. Further, various therapeutic strategies that target these pathways and genes via nanotechnology are also discussed. Additionally, clinical trials on DW related to gene therapy are also covered in the present review.

Polypharmacy in Psychiatry: An In-depth Examination of Drug-drug Interactions and Treatment Challenges.

Polypharmacy in psychiatry is an in-depth examination of drug-drug interactions and treatment challenges that explores the intricate landscape of psychiatric polypharmacy, a practice involving the prescription of multiple medications to individuals with mental health disorders. This review is based on the critical aspects of drug-drug interactions and the associated treatment challenges. Psychiatric polypharmacy is motivated by the complexity of mental health conditions, where monotherapy may be insufficient. While it offers potential benefits, the practice raises concerns related to drug interactions that can compromise safety and efficacy. The review delves into the prevalence and clinical indications for psychiatric polypharmacy, thoroughly analyzing drug interactions, treatment challenges, and strategies for mitigation. Real-world case studies illustrate the complexities and outcomes of managing complex medication regimens, while emerging trends in personalized medicine, advancements in psychopharmacology, multidisciplinary approaches, and digital health solutions offer a glimpse into the future of psychiatric polypharmacy. This examination underscores the importance of a patient-centered, evidence-based approach in optimizing psychiatric polypharmacy to achieve therapeutic benefits while minimizing risks.

A Comprehensive Guide to the Development, Evaluation, and Future Prospects of Self-nanoemulsifying Drug Delivery Systems for Poorly Water-soluble Drugs.

Self-Nano Emulsifying Drug Delivery Systems (SNEDDS) are novel formulations that can enhance the solubility and bioavailability of poorly water-soluble drugs. SNEDDS are composed of lipids, surfactants, co-solvents, and drugs and can spontaneously form nanoemulsions when mixed with water under mild agitation. SNEDDS can be formulated as liquid or solid dosage forms and can improve drug absorption by increasing the interfacial area, protecting the drug from degradation, and facilitating lymphatic transport. SNEDDS is characterized by various parameters such as particle size, zeta potential, droplet morphology, emulsification efficiency, drug solubility, and stability. SNEDDS offers several advantages over conventional dosage forms, such as dose reduction, faster onset of action, reduced variability, versatility, and ease of formulation. However, SNEDDS also face some limitations and challenges, such as drug precipitation, cost-effectiveness, compatibility with capsule shells, and lack of predictive in vitro models. SNEDDS has a promising future in the field of pharmaceuticals, especially for personalized medicine and targeted drug delivery.

Investigating flock-associated mimicry: examining the evidence for, and drivers of, plumage mimicry in the greater and lesser necklaced laughingthrush.

Visual mimicry is less understood in birds than in other taxa. The interspecific social dominance mimicry (ISDM) hypothesis asserts that subordinate species resemble dominant ones to reduce aggression. Plumage mimicry has also been consistently noted in mixed-species flocks (MSFs), suggesting a connection to grouping behaviour, although it is unclear whether this is linked to ISDM. We studied greater necklaced laughingthrush (GNLT, Pterorhinus pectoralis) and lesser necklaced laughingthrush (LNLT, Garrulax monileger), which were recently placed in different genera. Measurements of 162 museum specimens showed LNLT converging in sympatry with GNLT in necklace colour, but diverging in necklace to body ratio, with proportionally smaller necklaces. The species were closely associated in six of seven MSF systems from Nepal to China. In a study of foraging behaviour in Nepal, aggression was rare between the species, LNLT followed GNLT and had lower foraging rates when further from GNLT. Our data suggest a link between this MSF-associated mimicry and ISDM, and that the subordinate LNLT may be the mimic and gain more from the resemblance. The species spend much time together in dense and poorly lit vegetation, where the LNLTs resemblance to GNLTs potentially allows them to forage closer to GNLTs than would be otherwise possible.

The Risk of Crimean Congo Haemorrhagic Fever in India as a Growing Health Concern.

Every year witnesses an outbreak of some or the other zoonotic disease that causes the unparalled loss of human life. The year 2022 presented the outbreak of Crimean Congo haemorrhagic fever (CCHF), which brought unprecedented challenges to individuals as well as to the healthcare system all around the world, making it a serious health concern. Rising health concerns have highlighted the importance of managing and decreasing the further transmission of the CCHF virus. CCHF is one of tick-borne viral diseases, which spreads due to various reasons like changes in global warming, environmental influences, and other ecological factors. All these factors somehow impact the disease prevalence. This disease has a negative impact on both humans and livestock. The diverse climate and significant livestock population of India make it susceptible to the prevalence of CCHF. Therefore, it is the need of the hour to develop some strategies in order to tackle the challenges posed by CCHF. This article includes all the cases of CCHF that have occurred in India from the year 2011, along with the fatality rates associated with this disease. Also this study discusses the need to explore some specific drugs for the management and prevention of such diseases. In addition, the pathogenesis of the disease progression, along with some protective measures suggested by the government has been described for prevention of CCHF. Subsequently, this article attempted to draw attention towards the risk that may be posed by CCHF in the coming scenario, emphasizing the importance of taking proactive measures in anticipation of such risks.

Modelling Cross Talk in the Spatiotemporal System Dynamics of Calcium, IP3 and Nitric Oxide in Neuron Cells.

The bioenergetic system of calcium ([Ca2+]), inositol 1, 4, 5-trisphophate (IP3) and nitric oxide (NO) regulate the diverse mechanisms in neurons. The dysregulation in any or all of the calcium, IP3 and nitric oxide dynamics may cause neurotoxicity and cell death. Few studies are noted in the literature on the interactions of two systems like [Ca2+] with IP3 and [Ca2+] with nitric oxide in neuron cells, which gives limited insights into regulatory and dysregulatory processes in neuron cells. But, no study is available on the cross talk in dynamics of three systems [Ca2+], IP3 and NO in neurons. Thus, the cross talk in the system dynamics of [Ca2+], IP3 and NO regulation processes in neurons have been studied using mathematical model. The two-way feedback process between [Ca2+] and IP3 and two-way feedback process between [Ca2+] and NO through cyclic guanosine monophosphate (cGMP) with plasmalemmal [Ca2+]-ATPase (PMCA) have been incorporated in the proposed model. This coupling handles the indirect two-way feedback process between IP3 and nitric oxide in neuronal cells automatically. The numerical outcomes were acquired by employing the finite element method (FEM) with the Crank-Nicholson scheme (CNS). The present model incorporating the sodium-calcium exchanger (NCX) and voltage-gated calcium channel (VGCC) provides novel insights into the various regulatory and dysregulatory processes due to buffer, IP3-receptor, ryanodine receptor, cGMP kinetics through PMCA channel, etc. and their impacts on the interactive spatiotemporal system dynamics of [Ca2+], IP3 and NO in neurons. It is concluded that the behavior of different crucial mechanisms is quite different for interactions of two systems of [Ca2+] and NO and the interactions of three systems of [Ca2+], IP3 and nitric oxide in neuronal cell due to mutual regulatory adjustments. The association of several neurological disorders with the alterations in calcium, IP3 and NO has been explored in neurons.

Assessment of Carbon Sequestration in Private Forests across Two Different Physiographic Regions of Nepal: Implications for Conservation and Climate Change Mitigation.

Private forests offer diverse ecosystem services, including carbon sequestration and biodiversity conservation, which are crucial for Nepal. However, there is a notable absence of comprehensive research on these services. Assessing carbon sequestration in private forests can have economic advantages for forest owners by promoting resource conservation and contributing to greenhouse gas reduction. This study aims to estimate and compare carbon stocks in private forests located in two distinct physiographic regions of Nepal while also identifying the factors influencing these carbon stocks. The analysis focuses on 16 private forests (with 0.1 to 0.5 hectares) each from Chitwan district (Terai region) and Kavrepalanchok district (Hilly region). Field data collection involved direct measurements of tree and sapling diameter at breast height (DBH), as well as height and class of trees and poles, utilizing a total enumeration method. These collected values were utilized to calculate aboveground biomass (AGTB), aboveground sapling biomass (AGSB), belowground biomass, and carbon stock. Private forests of Terai region were dominated by Shorea borneensis, Tectona grandis, and Dalbergia sissoo, whereas the Hilly region was dominated by Pinus patula, Alnus nepalensis, Schima wallichii, and Quercus leucotrichophora. The aboveground biomass carbon in the Terai region's private forests was estimated to be 83.53 t·ha-1, while in the Hilly region, it was 37.32 t·ha-1. The belowground biomass carbon in the Terai region's private forests was found to be 21.72 t·ha-1, compared to 9.70 t·ha-1 in the Hilly region. Consequently, the estimated total carbon stock in the Terai and Hilly regions' private forests was 105.25 t·ha-1 (386.26 t·ha-1 CO2-eq) and 47.02 t·ha-1 (172.57 t·ha-1 CO2-eq), respectively. Carbon sequestration in the Terai region's private forests was discovered to be 2.24 times higher than that in the Hilly region. These findings underscore the significant potential of private forests, which can generate economic benefits through carbon trading and leverage mechanisms such as REDD+/CDM to promote sustainable conservation practices.

Study of disorders in regulatory spatiotemporal neurodynamics of calcium and nitric oxide.

Experimental studies have reported the dependence of nitric oxide (NO) on the regulation of neuronal calcium ([Ca2+]) dynamics in neurons. But, there is no model available to estimate the disorders caused by various parameters in their regulatory dynamics leading to various neuronal disorders. A mathematical model to analyze the impacts due to alterations in various parameters like buffer, ryanodine receptor, serca pump, source influx, etc. leading to regulation and dysregulation of the spatiotemporal calcium and NO dynamics in neuron cells is constructed using a system of reaction-diffusion equations. The numerical simulation is performed with the finite element approach. The disturbances in the different constitutive processes of [Ca2+] and nitric oxide including source influx, buffer mechanism, ryanodine receptor, serca pump, IP3 receptor, etc. can be responsible for the dysregulation in the [Ca2+] and NO dynamics in neurons. Also, the results reveal novel information about the magnitude and intensity of disorders in response to a range of alterations in various parameters of this neuronal dynamics, which can cause dysregulation leading to neuronal diseases like Parkinson's, cerebral ischemia, trauma, etc.

TWEAK Progress in Dermatology: A Review.

Tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a member of the TNF superfamily (TNFSF). It acts through its receptor fibroblast growth factor-inducible 14 (Fn14). Studies have indicated that TWEAK/Fn14 pathway activation controls multiple cellular responses, including proliferation, angiogenesis and induction of inflammatory cytokines. TWEAK/Fn14 is manifested in many tissues of our body and most importantly in the skin causing inflammation and many autoimmune and neoplastic cutaneous disorders. Evidence suggests that the TWEAK/Fn14 axis, the downstream signalling pathway and its inflammatory molecular expressions are involved in the pathogenesis of many cutaneous disorders such as psoriasis, atopic dermatitis (AD) vitiligo and melanoma. So, this literature review describes a brief introduction of TWEAK and TWEAK/Fn14 pathway and summarises the case-series and open-label studies performed in the field of dermatology and its potential therapeutic benefit.

Seasonal Prey Abundance and Food Plasticity of the Vulnerable Snow Leopard (Panthera uncia) in the Lapchi Valley, Nepal Himalayas.

Conservation strategies for apex predators, like the snow leopard (Panthera uncia), depend on a robust understanding of their dietary preferences, prey abundance, and adaptability to changing ecological conditions. To address these critical conservation concerns, this study presents a comprehensive evidence on prey availability and preferences for snow leopards in the Lapchi Valley in the Nepal Himalayas from November 2021 to March 2023. Field data were collected through the installation of twenty-six camera traps at 16 strategically chosen locations, resulting in the recording of 1228 events of 19 mammalian species, including domesticated livestock. Simultaneously, the collection of twenty snow leopard scat samples over 3800 m above sea level allowed for a detailed dietary analysis. Photo capture rate index and biomass composition analysis were carried out and seasonal prey availability and consumption were statistically analyzed. A total of 16 potential prey species for the snow leopard were documented during the study period. Himalayan musk deer (Moschus leucogaster) was the most abundant prey species, but infrequent in the diet suggesting that are not the best bet prey for the snow leopards. Snow leopards were found to exhibit a diverse diet, consuming eleven prey species, with blue sheep (Pseudois nayaur) being their most consumed wild prey and horses as their preferred livestock. The Pianka's index of dietary niche overlap between the summer and winter seasons were 0.576, suggesting a pronounced seasonal variation in food preference corroborating with the prey availability. The scarcity of larger preys in winter is compensated by small and meso-mammals in the diet, highlighting the snow leopard's capacity for dietary plasticity in response to the variation in resource availability. This research suggests for the utilization of genetic tools to further explore snow leopard diet composition. Additionally, understanding transboundary movements and conducting population assessments will be imperative for the formulation of effective conservation strategies.

Modelling the transmission of dengue, zika and chikungunya: a scoping review protocol.

INTRODUCTION: Aedes mosquitoes are the primary vectors for the spread of viruses like dengue (DENV), zika (ZIKV) and chikungunya (CHIKV), all of which affect humans. Those diseases contribute to global public health issues because of their great dispersion in rural and urban areas. Mathematical and statistical models have become helpful in understanding these diseases' epidemiological dynamics. However, modelling the complexity of a real phenomenon, such as a viral disease, should consider several factors. This scoping review aims to document, identify and classify the most important factors as well as the modelling strategies for the spread of DENV, ZIKV and CHIKV. METHODS AND ANALYSIS: We will conduct searches in electronic bibliographic databases such as PubMed, MathSciNet and the Web of Science for full-text peer-reviewed articles written in English, French and Spanish. These articles should use mathematical and statistical modelling frameworks to study dengue, zika and chikungunya, and their cocirculation/coinfection with other diseases, with a publication date between 1 January 2011 and 31 July 2023. Eligible studies should employ deterministic, stochastic or statistical modelling approaches, consider control measures and incorporate parameters' estimation or considering calibration/validation approaches. We will exclude articles focusing on clinical/laboratory experiments or theoretical articles that do not include any case study. Two reviewers specialised in zoonotic diseases and mathematical/statistical modelling will independently screen and retain relevant studies. Data extraction will be performed using a structured form, and the findings of the study will be summarised through classification and descriptive analysis. Three scoping reviews will be published, each focusing on one disease and its cocirculation/co-infection with other diseases. ETHICS AND DISSEMINATION: This protocol is exempt from ethics approval because it is carried out on published manuscripts and without the participation of humans and/or animals. The results will be disseminated through peer-reviewed publications and presentations in conferences.

Preparation of a Pt(II)-3-Hydroxy-2-tolyl-4H-chromen-4-one Complex Having Antimicrobial, Anticancerous, and Radical Scavenging Activities with Related Computational Studies.

A novel benzopyran-based platinum (II)-3-hydroxy-2-tolyl-4H-chromen-4-one (HToC) complex has been prepared and studied by UV-visible spectrophotometry. The study is based on the colored complexation between Pt(II) and HToC in the pH range of 8.92-9.21, resulting in the formation of a stable binary yellow complex exhibiting λmax at 509-525 nm. The formed complex maintains linearity between 0.0 and 1.8 µg Pt(II) mL-1. The well-known qualitative analytical methods, including Job's method of continuous variations and the mole ratio approach, have both proven that the stoichiometry of the complex is 1:2 [Pt(II)/HToC]. Hence, the analytical results suggest that the formed platinum complex exhibits a square planar geometry. The values of various attributes corresponding to spectrophotometric studies and statistical calculations, such as the molar extinction coefficient (6.790 × 104 L mol-1 cm-1), Sandell's sensitivity (0.0029 µg Pt(II) cm-2), standard deviation (± 0.0011), RSD (0.317%), limit of detection (0.0147 µg mL-1) and correlation coefficient (0.9999), show that the performed study satisfies all of the criteria for good sensitivity, versatility, and cost-effectiveness. In order to have an apprehension of the molecular geometry and other structural specifics of the complex, DFT studies have been carried out. The in vitro anticancer potential of the ligand and its platinum complex in the human breast cancer cell line (T-27D), as determined by the MTT assay, reveals that the complex has better antiproliferative potential than the ligand. The antimicrobial potential of the complex has been successfully tested against both Gram-positive and -negative bacteria. Antioxidant capacity results suggest the better radical scavenging capacity of the complex than that of the ligand.

Multifunctional chromone-incorporated poly(hydroxybutyrate) luminescent film for active and intelligent food packaging.

The major objective of present work was to fabricate poly(hydroxybutyrate) based luminescent films for genuine food packaging applications. These films were synthesized by incorporating varying Chromone (CH) concentrations (5, 10, 15, 20, and 25 wt%) into poly(hydroxybutyrate) (PHB) matrix through solvent-casting. Different characteristics of prepared films were examined using Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM), Thermogravimetric analysis (TGA), Mechanical testing, and Time-resolved photoluminescence (TRPL). UV-blocking properties and water vapor permeation were also examined. FTIR spectra indicated the occurrence of hydrogen bonding between PHB and CH. Among all prepared film samples, PHB/CH15 showed maximum tensile strength (22.5 MPa) with enhanced barrier ability against water vapor and UV rays, thermal stability, and luminescent performance. After overall analysis, PHB/CH15 film was selected to investigate its X-ray diffraction, release behavior, DPPH scavenging, and antimicrobial potential. Release kinetics revealed that the cumulative release percentage of CH was higher in fatty acid stimulant. Moreover, results suggested that this film demonstrated antioxidant activity (>55 %) and superior antimicrobial potential against Aspergillus niger, Staphylococcus aureus, and Escherichia coli. Furthermore, packaging of bread samples using PHB/CH15 film demonstrated the complete inhibition of microbial growth in bread up to 10 days of storage and ensure the safety of genuine food products.

Sex-Based Differences in Clinical Profile and Complications among Individuals with Type 2 Diabetes Seen at a Private Tertiary Diabetes Care Centre in India.

This study aimed to compare the clinical and biochemical profiles as well as the complications in males and females with type 2 diabetes (T2DM) presenting to a private tertiary diabetes care centre in India. This is a retrospective study, conducted between 1 January 2017 and 31 December 2019, and included 72,980 individuals with T2DM, aged ≥ 18 years (age and sex-matched-males-36,490; females-36,490). Anthropometric measurements, blood pressure, fasting plasma glucose (FPG), post-prandial plasma glucose (PPPG), glycated haemoglobin (HbA1c), lipids, urea, and creatinine were measured. Retinopathy was screened using retinal photography, neuropathy using biothesiometry, nephropathy measuring urinary albumin excretion, peripheral vascular disease (PVD) using Doppler, and coronary artery disease (CAD) based on the history of myocardial infarction and/or drug treatment for CAD and/or electrocardiographic changes. Obesity (73.6% vs. 59.0%) rates were significantly higher in females compared to males. FPG, PPPG, and HbA1c were higher among younger age groups among both sexes, with males having higher values compared to females. However, after the age of 44 years, control of diabetes was worse among females. In addition, only 18.8% of the females achieved glycemic control (HbA1c < 7%) compared to 19.9% in males (p < 0.001). Males had higher prevalence of neuropathy (42.9% vs. 36.9%), retinopathy (36.0% vs. 26.3%), and nephropathy (25.0% vs. 23.3%) compared to females. Males had 1.8- and 1.6-times higher risk of developing CAD and retinopathy compared to females. Hypothyroidism (12.5% vs. 3.5%) and cancers (1.3% vs. 0.6%) were significantly higher in females compared to males. In this large sample of T2DM seen at a chain of private tertiary diabetes centres, females had higher prevalence of metabolic risk factors and poorer diabetes control compared to males, emphasizing the need for better control of diabetes in females. However, males had higher prevalence of neuropathy, retinopathy, nephropathy, and CAD compared to females.

Mechanistic insights of neuronal calcium and IP3 signaling system regulating ATP release during ischemia in progression of Alzheimer's disease.

The mechanisms of calcium ([Ca2+]) signaling in various human cells have been widely analyzed by scientists due to its crucial role in human organs like the heartbeat, muscle contractions, bone activity, brain functionality, etc. No study is reported for interdependent [Ca2+] and IP3 mechanics regulating the release of ATP in neuron cells during Ischemia in Alzheimer's disease advancement. In the present investigation, a finite element method (FEM) is framed to explore the interdependence of spatiotemporal [Ca2+] and IP3 signaling mechanics and its role in ATP release during Ischemia as well as in the advancement of Alzheimer's disorder in neuron cells. The results provide us insights of the mutual spatiotemporal impacts of [Ca2+] and IP3 mechanics as well as their contributions to ATP release during Ischemia in neuron cells. The results obtained for the mechanics of interdependent systems differ significantly from the results of simple independent system mechanics and provide new information about the processes of the two systems. From this study, it is concluded that neuronal disorders cannot only be simply attributed to the disturbance caused directly in the processes of calcium signaling mechanics, but also to the disturbances caused in IP3 regulation mechanisms impacting the calcium regulation in the neuron cell and ATP release.

A comparison of the quality of images of chest X-ray between handheld portable digital X-ray & routinely used digital X-ray machine.

Background & objectives: Chest X-ray (CXR) is an important screening tool for pulmonary tuberculosis (TB). Accessibility to CXR facilities in difficult-to-reach and underserved populations is a challenge. This can potentially be overcome by deploying digital X-ray machines that are portable. However, these portable X-ray machines need to be validated before their deployment in the field. Here, we compare the image quality of CXR taken by a newly developed handheld X-ray machine with routinely used reference digital X-ray machine through the conduct of a feasibility study. Methods: A total of 100 participants with suspected pulmonary TB were recruited from the outpatient departments of a medical college and a community health centre in Agra. Each participant underwent CXR twice, once with each machine. Both sets of de-identified images were independently read by two radiologists, who were blinded to the type of X-ray machine used. The primary outcome was agreement between image qualities produced by these two machines. Results: The intra-observer (radiologist) agreements regarding the status of the 15 CXR parameters ranged between 74 per cent and 100 per cent, with an unweighted mean of 87.2 per cent (95% confidence interval: 71.5-100). The median Cohen's kappa values for intra-observer agreement were 0.62 and 0.67 for radiologists 1 and 2, respectively. In addition, on comparison of the overall median score of quality of the image, the handheld machine images had a higher score for image quality. Interpretation & conclusions: The current study shows that a handheld X-ray machine, which is easy to use and can potentially be carried to any area, produces X-ray images with quality that is comparable to digital X-ray machines routinely used in health facilities.