Computational Screening of T-Muurolol for an Alternative Antibacterial Solution against Staphylococcus aureus Infections: An In Silico Approach for Phytochemical-Based Drug Discovery.

Staphylococcus aureus infections present a significant threat to the global healthcare system. The increasing resistance to existing antibiotics and their limited efficacy underscores the urgent need to identify new antibacterial agents with low toxicity to effectively combat various S. aureus infections. Hence, in this study, we have screened T-muurolol for possible interactions with several S. aureus-specific bacterial proteins to establish its potential as an alternative antibacterial agent. Based on its binding affinity and interactions with amino acids, T-muurolol was identified as a potential inhibitor of S. aureus lipase, dihydrofolate reductase, penicillin-binding protein 2a, D-Ala:D-Ala ligase, and ribosome protection proteins tetracycline resistance determinant (RPP TetM), which indicates its potentiality against S. aureus and its multi-drug-resistant strains. Also, T-muurolol exhibited good antioxidant and anti-inflammatory activity by showing strong binding interactions with flavin adenine dinucleotide (FAD)-dependent nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase, and cyclooxygenase-2. Consequently, molecular dynamics (MD) simulation and recalculating binding free energies elucidated its binding interaction stability with targeted proteins. Furthermore, quantum chemical structure analysis based on density functional theory (DFT) depicted a higher energy gap between the highest occupied molecular orbital and lowest unoccupied molecular orbital (EHOMO-LUMO) with a lower chemical potential index, and moderate electrophilicity suggests its chemical hardness and stability and less polarizability and reactivity. Additionally, pharmacological parameters based on ADMET, Lipinski's rules, and bioactivity score validated it as a promising drug candidate with high activity toward ion channel modulators, nuclear receptor ligands, and enzyme inhibitors. In conclusion, the current findings suggest T-muurolol as a promising alternative antibacterial agent that might be a potential phytochemical-based drug against S. aureus. This study also suggests further clinical research before human application.

E5 treatment showing improved health-span and lifespan in old Sprague Dawley rats.

Aging and, in particular, the emergence of age-related disorders is associated with tissue dysfunction and macromolecular damage, some of which can be attributable to accumulated oxidative damage. In the current study, we determine the potential of 'plasma-derived fraction (E5)' for cellular rejuvenation and extending the lifespan of Sprague Dawley (SD) rats. This is a unique study wherein we have used 24-month-old rats and monitored them until the end of their lifespan with and without E5 treatment. In the present investigation, the SD rats were separated into two groups old control group and the treatment group (n = 8). The treatment group received four injections of E5 every alternate day for 8 days, and eight injections every alternate day for 16 days. Body weight, grip strength, cytokines, and biochemical markers were measured for more than 400 days of the study. Clinical observation, necropsy, and histology were performed. The E5 treatment exhibited great potential by showing significantly improved grip strength, remarkably decreased pro-inflammatory markers of chronic inflammation and oxidative stress, as well as biomarkers for vital organs (BUN, SGPT, SGOT, and triglycerides), and increased anti-oxidant levels. Clinical examinations, necropsies, and histopathology revealed that the animals treated with the E5 had normal cellular structure and architecture. In conclusion, this unique 'plasma-derived exosome' treatment (E5) alone is adequate to improve the health-span and extend the lifespan of the old SD rats significantly.

Developing a process for assessing the safety of a digital mental health intervention and gaining regulatory approval: a case study and academic's guide.

BACKGROUND: The field of digital mental health has followed an exponential growth trajectory in recent years. While the evidence base has increased significantly, its adoption within health and care services has been slowed by several challenges, including a lack of knowledge from researchers regarding how to navigate the pathway for mandatory regulatory approval. This paper details the steps that a team must take to achieve the required approvals to carry out a research study using a novel digital mental health intervention. We used a randomised controlled trial of a digital mental health intervention called STOP (Successful Treatment of Paranoia) as a worked example. METHODS: The methods section explains the two main objectives that are required to achieve regulatory approval (MHRA Notification of No Objection) and the detailed steps involved within each, as carried out for the STOP trial. First, the existing safety of digital mental health interventions must be demonstrated. This can refer to literature reviews, any feasibility/pilot safety data, and requires a risk management plan. Second, a detailed plan to further evaluate the safety of the digital mental health intervention is needed. As part of this we describe the STOP study's development of a framework for categorising adverse events and based on this framework, a tool to collect adverse event data. RESULTS: We present literature review results, safety-related feasibility study findings and the full risk management plan for STOP, which addressed 26 possible hazards, and included the 6-point scales developed to quantify the probability and severity of typical risks involved when a psychiatric population receives a digital intervention without the direct support of a therapist. We also present an Adverse Event Category Framework for Digital Therapeutic Devices and the Adverse Events Checklist-which assesses 15 different categories of adverse events-that was constructed from this and used in the STOP trial. CONCLUSIONS: The example shared in this paper serves as a guide for academics and professionals working in the field of digital mental health. It provides insights into the safety assessment requirements of regulatory bodies when a clinical investigation of a digital mental health intervention is proposed. Methods, scales and tools that could easily be adapted for use in other similar research are presented, with the expectation that these will assist other researchers in the field seeking regulatory approval for digital mental health products.

Interventions promoting resilience through climate smart agricultural practices for women farmers: A systematic review.

Background: Climate change poses a significant threat to agricultural production worldwide, with developing countries being particularly vulnerable to its negative impacts. Agriculture, which is a crucial factor in ensuring food security and livelihoods, is particularly vulnerable to changes in climate patterns, such as increased temperatures, drought, and extreme weather events. One approach to addressing these challenges is by promoting the adoption of climate-smart agriculture (CSA) practices among farmers. CSA combines traditional agricultural practices with innovative techniques and technologies to adapt to and mitigate the impacts of climate change. infrastructure. By adopting CSA practices, farmers can enhance their resilience to climate variability and improve their productivity. Objectives: This review examines the effectiveness of interventions promoting CSA to enhance farmers' knowledge of the benefits of CSA approaches, subsequent adoption of CSA, and disadoption of harmful agricultural practices in low- and middle-income countries (LMICs). Search Methods: We searched 39 academic and online databases, websites, and repositories and screened over 19,000 experimental and quasi-experimental publications to identify studies promoting CSA practices to women farmers. We conducted a citation tracking process on included studies and contacted experts to ensure a thorough search. Selection Criteria: The review focused on studies that included interventions promoting climate-smart agricultural approaches. Using EPPI Reviewer 4, two review authors independently screened the impact evaluation using a standardized screening tool. Data Collection and Analysis: Information about participant characteristics, intervention characteristics, control conditions, research design, sample size, bias risk, outcomes, and results were gathered. Data collection and quantitative analysis were conducted using standard Campbell Collaboration methods. Main Results: Eight impact evaluations were found (two randomized controlled trials) evaluating the effects of CSA practices on farmer's knowledge gains of the benefits of CSA practices and subsequent adoption. Knowledge dissemination approaches such as Farmer Field Schools and weather and climate information services were found to positively impact farmers' knowledge and adoption of specific CSA practices. However, the evidence supporting this claim is uncertain as a high risk of bias was assessed for five of the eight included studies. However, we found no effects on the disadoption of harmful practices such as pesticide overuse. Authors' Conclusions: The evidence base for studies promoting climate-smart agricultural approaches (CSA) to farmers in LMICs is small, and there is a lack of studies reporting sex-disaggregated data and studies explicitly targeting women farmers. The review suggests that knowledge dissemination techniques are significantly effective in improving CSA knowledge and adoption, including integrated pest management techniques and their benefits, adoption of climate-resilient rice seed varieties (STRVs), and use of botanical pesticides by farmers. More and better confidence studies are needed to inform policy and programming, including those that look at a wider range of interventions, including changing norms, values, and institutional arrangements.

Kite String or Manja Cut Injury: A New Culprit.

Background Kite string injuries (manja cut injuries), particularly those caused by Chinese manja, are new culprit of emergencies especially in the month of January in Maharashtra region. These injuries commonly affect the neck, face, hands, and legs, especially among individuals traveling on two wheelers. The visibility challenge, where the kite's thread is difficult to see, further exacerbates the risk. Materials and Methods We have studied 10 cases of manja cut injuries presented to a tertiary care center in Nagpur during the last 2 years. Result A total of 10 patients reported kite string-related injuries to our department over a period of 2 years. All patients were male. The majority of patients presented in the younger age group with the mean age of presentation was 25 years. Majority of the patients had injuries in zone 2 of the hand. Conclusion Kite flying is a traditional festival celebrated in the month of January in Gujarat and Maharashtra for years. However, the introduction of Chinese or nylon manja has led to serious injuries and fate, affecting not only kite flyers but also bystanders, animals, and birds. This study seeks to highlight the harmful consequences of Chinese manja and deceptive appearance of manja giving false impression of simple lacerated wound which could be just a tip of the iceberg.

Value chain interventions for improving women's economic empowerment: A mixed-methods systematic review and meta-analysis: A systematic review.

Background: Value chain interventions have become widespread throughout the international development sector over the last 20 years, and there is a need to evaluate their effectiveness in improving women's welfare across multiple dimensions. Agricultural value chains are influenced by socio-cultural norms and gender dynamics that have an impact on the distribution of resources, benefits, and access to opportunities. While women play a critical role in agriculture, they are generally confined to the least-valued parts of the value chain with the lowest economic returns, depending on the local, social and institutional contexts. Objectives: The review assesses the effectiveness of approaches, strategies and interventions focused on women's engagement in agricultural value chains that lead to women's economic empowerment in low- and middle-income countries. It explores the contextual barriers and facilitators that determine women's participation in value chains and ultimately impact their effectiveness. Search Methods: We searched completed and on-going studies from Scopus, Web of Science Core Collection (Social Sciences Citation Index [SSCI], Science Citation Index Expanded [SCI-EXPANDED], Conference Proceedings Citation Index - Science [CPCI-S], Conference Proceedings Citation Index - Social Science & Humanities [CPCI-SSH], and Emerging Sources Citation Index [ESCI]), International Bibliography of the Social Sciences, EconLit, Business Source Premier, APA PsycInfo, Cochrane Central Register of Controlled Trials, Cochrane, Database of Systematic Reviews, CAB Abstracts and Sociological Abstracts. We also searched relevant websites such as Consortium of International Agricultural Research Centers (CGIAR); the International Fund for Agricultural Development (IFAD); AgriProFocus; the Bill & Melinda Gates Foundation (BMGF); Donor Committee for Enterprise Development; the UN Food and Agriculture Organisation (FAO); the International Labour Organisation (ILO); the Netherlands Development Organisation; USAID; the Swiss Agency for Development and Cooperation; the International Food Policy Research Institute; World Agroforestry; the International Livestock Research Institute; the Foreign, Commonwealth & Development Office; the British Library for Development Studies (BLDS); AGRIS; the IMMANA grant database; the 3ie impact evaluation database; Innovations for Poverty Action (IPA); The Abdul Latif Jameel Poverty Action Lab (J-PAL); the World Bank IEG evaluations; the USAID Development Data Library; Experience Clearinghouse; the proceedings of the Agriculture, Nutrition and Health Academy conference; the proceedings of the Centre for the Study of African Economies (CSAE) Conference; the proceedings of the North East Universities Development Consortium (NEUDC) Conference; and the World Bank Economic Review. The database search was conducted in March 2022, and the website search was completed in August 2022. Selection Criteria: The review includes value chain interventions evaluating the economic empowerment outcomes. The review includes effectiveness studies (experimental and non-experimental studies with a comparison group) and process evaluations. Data Collection and Analysis: Two review authors independently assessed studies for inclusion, extracted data, critically appraised the studies, and synthesised findings. Results: We found that value chain interventions are successful in improving the economic conditions of their intended beneficiaries. The interventions were found to improve women's economic outcomes such as income, assets holdings, productivity, and savings, but these effects were small in size and limited by low confidence in methodological quality. The meta-analysis suggests that this occurs more via the acquisition of skills and improved inputs, rather than through improvement in access to profitable markets. The qualitative evidence on interventions points to the persistence of cultural barriers and other constraints. Those interventions implemented in Sub-Saharan Africa and South Asia are consistently more successful for all outcomes considered, although there are few studies conducted in other areas of the world. Conclusions: The review concludes that value chain interventions empower women, but perhaps to a lesser extent than expected. Economic empowerment does not immediately translate into empowerment within families and communities. Interventions should either moderate their expectations of empowerment goals, or they should be implemented in a way that ensures higher rates of participation among women and the acquisition of greater decision-making power.

Electrocatalytic Hydrogen Generation by Ni-PN3P Pincer Complexes: Role of Phosphorus Substituents in Tuning the Reactivity.

Electrocatalytic hydrogen evolution reaction (eHER) is crucial in addressing the growing global energy demand. Although nickel-pincer-based molecular complexes, varying in donor atoms, were studied previously for eHER, the impact of variations in the substituents attached to the donor atoms was not investigated. Herein, three air-stable R1PN3PR2-based NiII-pincer complexes [R1=R2=Ph2 (7); R1=R2=tBu2 (9); R1= tBu2, R2=Ph2 (10)], varying solely in P-substituents, were studied in acetonitrile. While the redox potentials for NiII/I and NiI/0 couples underwent anodic shifts by ~100 mV upon progressively substituting tert-butyl by phenyl groups on each P-atom, the corresponding eHER reactivity with organic acids (acetic acid,  p-toluenesulfonic acid and trifluoromethanesulfonic acid) of different strengths followed different trends; likely influenced by the pKa of intermediate metal-hydride (M-H) species [pKa(M-H9) > pKa(M-H10) > pKa(M-H7)]. Depending on the acid strength, different oxidation states of the metal were activated to promote eHER. The catalytic rates for 9, 10, and 7 were calculated to be 85 s-1, 77 s-1 and 95 s-1 with Faradaic efficiencies of 88.5 ± 2%, 66.1 ± 1.4%, and 91.7 ± 1.5% respectively, in acetic acid. Electrochemical data supported by theoretical results reinforce a significant electronic influence of the anchoring P-substituents on the activity of these complexes.

Shoulder shake-up: Unveiling the unusual case of acute melioidosis.

Background: Melioidosis is one of the emerging infections in India and is often neglected due to lack of awareness among clinicians. The diseases usually present as multifocal or focal abscesses with bacteremia, yet the isolated septic monoarthritic complicated with septic venous thrombosis is a rare presentation. Case: This case report describes a 48-year-old male business executive with diabetes and alcoholism who developed septic arthritis caused by Burkholderia pseudomallei and no clear history of exposure to the organism. The patient initially experienced fever, chills, fatigue, reduced urine output, and signs of early sepsis. Despite initial improvement with fluid therapy and antibiotics, the patient's fever persisted. Meticulous clinical examination revealed signs of inflammation and movement restriction in the left shoulder which letter on became obvious and the main complaints of patient. Blood cultures confirmed the presence of B. pseudomallei. Imaging showed septic arthritis, osteomyelitis, lymphadenitis, and venous thrombosis in the left shoulder. Surgical debridement was performed, and the tissue cultures showed the growth of the same pathogen. This led to significant clinical improvement and with prolonged course of antibiotics, complete resolution of symptoms and normal joint function was achieved. Conclusion: This case report serves to highlight the rare and atypical presentation of Melioidosis and the importance of suspecting this infection in nonendemic regions underscoring the probable impact of climate change. Early diagnosis, effective source control measures and prolonged antibiotic therapy, emerges as pivotal factors contributing to favorable outcomes in such cases.

Nanoparticle-based immunosensors for enhanced DNA analysis in oral cancer: A systematic review.

To investigate the diagnostic and therapeutic potential of nanoparticle (NP)-based immunosensors in the field of oral cancer. PubMed, Embase, Scopus, Web of Science, and Google Scholar databases were explored for NP applications in oral cancer. Data extraction in terms and quality assessment of all the articles were done. Out of 147, 17 articles were included in this review. A majority of the studies showed improved sensitivity and specificity for saliva analysis using an enzyme-linked immunosorbent assay based on gold NPs, improving early identification. Additionally, novel therapeutic approaches, utilising NP-based immunosensors, demonstrated targeted drug delivery, coupled chemo-photothermal therapy, and gene silencing. Imaging methods have made it possible to distinguish between malignant and healthy states, such as surface-enhanced Raman scattering and optical coherence tomography. The reviews' findings highlight the transformational potential of NP-based immunosensors in addressing the difficulties associated with diagnosing and treating oral cancer. However, for an accurate interpretation and application of NP-based solutions in clinical practise, it is essential to be thoroughly aware of the intricacies involved, and the synthesised data in this review support the continued investigation and improvement of NP-based therapies in the ongoing effort to improve the management of oral cancer.

Oral habits among preschool Indian children at Durg-Bhilai city.

One of the major contributing causes to the development of malocclusion and other negative impacts on orofacial complexes is oral habits during and after preschool. Therefore, it is of interest to ascertain the prevalence of oral habits in preschoolers in Durg-Bhilai, Chhattisgarh, India. Using the cluster sampling technique, four schools two from each of Durg and Bhilai City were chosen to participate in the study. 400 LKG and UKG students, along with their mothers or caregivers, were chosen based on the inclusion/exclusion criteria. The Chi-square test was employed in the statistical study. Thus, preschoolers at durg-bhilai city, Chhattisgarh, India, had a high prevalence of oral habits.

Four Transformer-Based Deep Learning Classifiers Embedded with an Attention U-Net-Based Lung Segmenter and Layer-Wise Relevance Propagation-Based Heatmaps for COVID-19 X-ray Scans.

Background: Diagnosing lung diseases accurately is crucial for proper treatment. Convolutional neural networks (CNNs) have advanced medical image processing, but challenges remain in their accurate explainability and reliability. This study combines U-Net with attention and Vision Transformers (ViTs) to enhance lung disease segmentation and classification. We hypothesize that Attention U-Net will enhance segmentation accuracy and that ViTs will improve classification performance. The explainability methodologies will shed light on model decision-making processes, aiding in clinical acceptance. Methodology: A comparative approach was used to evaluate deep learning models for segmenting and classifying lung illnesses using chest X-rays. The Attention U-Net model is used for segmentation, and architectures consisting of four CNNs and four ViTs were investigated for classification. Methods like Gradient-weighted Class Activation Mapping plus plus (Grad-CAM++) and Layer-wise Relevance Propagation (LRP) provide explainability by identifying crucial areas influencing model decisions. Results: The results support the conclusion that ViTs are outstanding in identifying lung disorders. Attention U-Net obtained a Dice Coefficient of 98.54% and a Jaccard Index of 97.12%. ViTs outperformed CNNs in classification tasks by 9.26%, reaching an accuracy of 98.52% with MobileViT. An 8.3% increase in accuracy was seen while moving from raw data classification to segmented image classification. Techniques like Grad-CAM++ and LRP provided insights into the decision-making processes of the models. Conclusions: This study highlights the benefits of integrating Attention U-Net and ViTs for analyzing lung diseases, demonstrating their importance in clinical settings. Emphasizing explainability clarifies deep learning processes, enhancing confidence in AI solutions and perhaps enhancing clinical acceptance for improved healthcare results.

Cannabidiol and neurodegeneration: From molecular mechanisms to clinical benefits.

Neurodegenerative disorders (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis are severe and life-threatening conditions in which significant damage of functional neurons occurs to produce psycho-motor malfunctions. NDs are an important cause of death in the elderly population worldwide. These disorders are commonly associated with the progression of age, oxidative stress, and environmental pollutants, which are the major etiological factors. Abnormal aggregation of specific proteins such as α-synuclein, amyloid-ß, huntingtin, and tau, and accumulation of the associated oligomers in neurons are the hallmark pathological features of NDs. Existing therapeutic options for NDs are only symptomatic relief and do not address root-causing factors, such as protein aggregation, oxidative stress, and neuroinflammation. Cannabidiol (CBD) is a non-psychotic natural cannabinoid obtained from Cannabis sativa that possesses multiple pharmacological actions, including antioxidant, anti-inflammatory, and neuroprotective effects in various NDs and other neurological disorders both in vitro and in vivo. CBD has gained attention as a promising drug candidate for the management of neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, by inhibiting protein aggregation, free radicals, and neuroinflammation. In parallel, CBD has shown positive results in other neurological disorders, such as epilepsy, depression, schizophrenia, and anxiety, as well as adjuvant treatment with existing standard therapeutic agents. Hence, the present review focuses on exploring the possible molecular mechanisms in controlling various neurological disorders as well as the clinical applications of CBD in NDs including epilepsy, depression and anxiety. In this way, the current review will serve as a standalone reference for the researchers working in this area.

Specific CD4+ T cell phenotypes associate with bacterial control in people who 'resist' infection with Mycobacterium tuberculosis.

A subset of individuals exposed to Mycobacterium tuberculosis (Mtb) that we refer to as 'resisters' (RSTR) show evidence of IFN-γ- T cell responses to Mtb-specific antigens despite serially negative results on clinical testing. Here we found that Mtb-specific T cells in RSTR were clonally expanded, confirming the priming of adaptive immune responses following Mtb exposure. RSTR CD4+ T cells showed enrichment of TH17 and regulatory T cell-like functional programs compared to Mtb-specific T cells from individuals with latent Mtb infection. Using public datasets, we showed that these TH17 cell-like functional programs were associated with lack of progression to active tuberculosis among South African adolescents with latent Mtb infection and with bacterial control in nonhuman primates. Our findings suggested that RSTR may successfully control Mtb following exposure and immune priming and established a set of T cell biomarkers to facilitate further study of this clinical phenotype.

In silico exploration of 4(α-l-rhamnosyloxy)-benzyl isothiocyanate: A promising phytochemical-based drug discovery approach for combating multi-drug resistant Staphylococcus aureus.

Multidrug-resistant (MDR) Staphylococcus aureus infections significantly threaten global health. With rising resistance to current antibiotics and limited solutions, the urgent discovery of new, effective, and affordable antibacterials with low toxicity is imperative to combat diverse MDR S. aureus strains. Hence, in this study, we introduce an in silico phytochemical-based approach for discovering novel antibacterial agents, underscoring the potential of computational approaches in therapeutic discovery. Glucomoringin Isothiocyanate (GMG-ITC) from Moringa oleifera Lam. is one of the phytochemical compounds with several biological activities, including antimicrobial, anti-inflammatory, and antioxidant activities, and is also effective against S. aureus. This study focuses on screening GMG-ITC as a potential drug candidate to combat MDR S. aureus infections through a molecular docking approach. Moreover, interaction amino acid analysis, in silico pharmacokinetics, compound target prediction, pathway enrichment analysis and molecular dynamics (MD) simulations were conducted for further investigation. Molecular docking and interaction analysis showed strong binding affinity towards S. aureus lipase, dihydrofolate reductase, and other MDR S. aureus proteins, including penicillin-binding protein 2a, MepR, D-Ala:D-Ala ligase, and RPP TetM, through hydrophilic and hydrophobic interactions. GMG-ITC also showed a strong binding affinity to cyclooxygenase-2 and FAD-dependent NAD(P)H oxidase, suggesting that it is a potential anti-inflammatory and antioxidant candidate that may eliminate inflammation and oxidative stress associated with S. aureus infections. MD simulations validated the stability of the GMG-ITC molecular interactions determined by molecular docking. In silico pharmacokinetic analysis highlights its potency as a drug candidate, showing strong absorption, distribution, and excretion properties in combination with low toxicity. It acts as an active protease and enzyme inhibitor with moderate activity against GPCR ligands, ion channels, nuclear receptor ligands, and kinases. Enrichment analysis further elucidated its involvement in important biological, molecular, and cellular functions with potential therapeutic applications in diseases like cancer, hepatitis B, and influenza. Results suggest that GMG-ITC is an effective antibacterial agent that could treat MDR S. aureus-associated infections.

Anti-psoriatic potential of medicinal plants, Alstonia scholaris, Wrightia tinctoria, and Solanum xanthocarpum, using human HaCaT keratinocytes by multi-parametric analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis, a widespread skin condition impacting over 100 million individuals globally, is characterised by uncontrolled hyperproliferation of keratinocytes, abnormal apoptosis, and excessive secretion of inflammatory cytokines and angiogenic factors. Traditional use of Alstonia scholaris (L.) R.Br., Wrightia tinctoria (Roxb.) R.Br. and Solanum xanthocarpum Schrad. & Wendl. in Ayurveda and Siddha medicinal systems have shown promising anti-inflammatory and wound-healing properties. However, underlying mechanisms of their phytoactivity in addressing psoriasis-like skin inflammation on human keratinocytes remain largely unexplored. AIM OF THE STUDY: The study was aimed to investigate anti-psoriatic potential of ethyl acetate and ethanolic extracts of A. scholaris, W. tinctoria and S. xanthocarpum in human keratinocyte cell line (HaCaT). MATERIAL AND METHODS: Ethyl acetate and ethanolic extracts of A. scholaris (ASEA and ASE), W. tinctoria (WTEA and WTE) and S. xanthocarpum (SXEA and SXE) were first subjected to phytochemical screening through high-performance liquid chromatography (HPLC) using their marker compound loganin, kaempferol and chlorogenic acid, respectively. The proliferation inhibition efficiency of these extracts was measured using MTT assay on HaCaT cell line. Subsequently, the apoptotic effect of these extracts on HaCaT cell line was determined by JC-1 and Annexin V assays. Furthermore, IL-8 and RANTES levels were measured in TNF-alpha-induced HaCaT cell line post-treatment with these extracts to determine their anti-inflammatory properties. RESULTS: ASEA, ASE, WTEA, WTE, SXEA and SXE significantly inhibited proliferation of keratinocytes (HaCaT cells) and resulted in the induction of apoptotic markers (mitochondrial membrane potential and phosphatidyl serine externalization). Additionally, pro-inflammatory markers (IL-8 and RANTES levels) were downregulated in HaCaT cells. The anti-proliferative effects were particularly distinct at higher concentrations (200 µg/mL), with inhibition rates reaching over 85% for W. tinctoria and S. xanthocarpum extracts. In apoptotic assays, notable increases in late apoptotic or necrotic cell populations and significant losses in mitochondrial membrane potential were observed. All extracts markedly reduced the secretion of inflammatory mediators IL-8 and RANTES. CONCLUSION: All three plants exerted an anti-psoriatic effect at the cellular level via multiple parameters (anti-proliferative, pro-apoptotic, anti-inflammatory effect). This study provides insight into the mechanism of action of ASEA, ASE, WTEA, WTE, SXEA and SXE and highlights their promising potential for development as herbal therapeutic agents for psoriasis. It emphasizes the need for further pharmacological evaluation and toxicological studies of these extracts.

Interstitial cell of Cajal-like cells (ICC-LC) exhibit dynamic spontaneous activity but are not functionally innervated in mouse urethra.

Urethral smooth muscle cells (USMC) contract to occlude the internal urethral sphincter during bladder filling. Interstitial cells also exist in urethral smooth muscles and are hypothesized to influence USMC behaviours and neural responses. These cells are similar to Kit+ interstitial cells of Cajal (ICC), which are gastrointestinal pacemakers and neuroeffectors. Isolated urethral ICC-like cells (ICC-LC) exhibit spontaneous intracellular Ca2+ signalling behaviours that suggest these cells may serve as pacemakers or neuromodulators similar to ICC in the gut, although observation and direct stimulation of ICC-LC within intact urethral tissues is lacking. We used mice with cell-specific expression of the Ca2+ indicator, GCaMP6f, driven off the endogenous promoter for Kit (Kit-GCaMP6f mice) to identify ICC-LC in situ within urethra muscles and to characterize spontaneous and nerve-evoked Ca2+ signalling. ICC-LC generated Ca2+ waves spontaneously that propagated on average 40.1 ± 0.7 µm, with varying amplitudes, durations, and spatial spread. These events originated from multiple firing sites in cells and the activity between sites was not coordinated. ICC-LC in urethra formed clusters but not interconnected networks. No evidence for entrainment of Ca2+ signalling between ICC-LC was obtained. Ca2+ events in ICC-LC were unaffected by nifedipine but were abolished by cyclopiazonic acid and decreased by an antagonist of Orai Ca2+ channels (GSK-7975A). Phenylephrine increased Ca2+ event frequency but a nitric oxide donor (DEA-NONOate) had no effect. Electrical field stimulation (EFS, 10 Hz) of intrinsic nerves, which evoked contractions of urethral rings and increased Ca2+ event firing in USMC, failed to evoke responses in ICC-LC. Our data suggest that urethral ICC-LC are spontaneously active but are not regulated by autonomic neurons.

Intraoperative challenges and outcomes of pediatric cataract surgery following glaucoma filtering surgery.

PURPOSE: To analyze the intraoperative challenges of cataract surgery in children, following glaucoma filtering surgery. METHODS: This was a retrospective study to analyze intra-op challenges and outcomes of pediatric cataract surgery in post-glaucoma filtration surgery eyes, between January 2007 and December 2019. RESULTS: We included 20 eyes of 16 children. The most common glaucoma surgery performed was trabeculectomy and trabeculotomy (14 eyes). The median age at the time of cataract surgery was 74.5 months. The most common cataract surgery performed was lens aspiration with posterior chamber intraocular lens implantation (LA + PCIOL) (9/20). The most common intraoperative challenge faced was difficulty in capsulorrhexis (ten eyes), followed by extension of primary posterior capsulotomy (six eyes). At the final follow up eight eyes had improvement in visual acuity, five eyes had stable visual acuity and five eyes had a drop in visual acuity. In 12/20 eyes IOL was implanted, nine eyes in-the-bag and three eyes had in ciliary sulcus. None of the IOLs in the bag had decentration of IOL. The median postoperative IOP (p = 0.12) and median number of postoperative AGM (p = 0.13) at 2 years remained stable compared to the preoperative values. The IOP remained well controlled in 4 eyes without anti-glaucoma medications and in 14 eyes with anti-glaucoma medications and none needed additional surgery for IOP control. Two eyes developed retinal detachment postoperatively. CONCLUSION: Cataract surgery in pediatric eyes with prior glaucoma surgeries, have challenges with capsulorrhexis and IOL stability. The visual outcomes were reasonably good so was the IOP control.