Antigenic epitope analysis of Pakistani G3 and G9 rotavirus strains compared to vaccine strains revealed multiple amino acid differences.

Rotaviruses belong to genotype VP4-P[8] are a significant cause of severe loose diarrhea in infants and young children. In the present study, we characterised the complete genome of three of the Pakistani P[8]b RVA strains by Illumina HiSeq sequencing technology to determine the complete genotype constellation providing insight into the evolutionary dynamics of their genes using maximum likelihood analysis. The maximum genomic sequences of our study strains were similar to more recent human Wa-Like G1P[8]a, G3P[8]a, G4P[6], G4P[8], G9P[4], G9P[8]a, G11P[25],G12P[8]a and G12P[6] strains circulating around the world. Therefore, strains PAK274, PAK439 and PAK624 carry natively distinctive VP4 gene with universally common human Wa-Like genetic backbone. Comparing our study P[8]b strains with vaccines strains RotarixTM and RotaTeqTM, multiple amino acid differences were examined between vaccine virus antigenic epitopes and Pakistani isolates. Over time, these differences may result in the selection for strains that will escape the vaccine-induced RVA-neutralizing-antibody effect.

Nivolumab with or without ipilimumab in patients with recurrent or metastatic cervical cancer (CheckMate 358): a phase 1-2, open-label, multicohort trial.

BACKGROUND: In preliminary findings from the recurrent or metastatic cervical cancer cohort of CheckMate 358, nivolumab showed durable anti-tumour responses, and the combination of nivolumab plus ipilimumab showed promising clinical activity. Here, we report long-term outcomes from this cohort. METHODS: CheckMate 358 was a phase 1-2, open-label, multicohort trial. The metastatic cervical cancer cohort enrolled patients from 30 hospitals and cancer centres across ten countries. Female patients aged 18 years or older with a histologically confirmed diagnosis of squamous cell carcinoma of the cervix with recurrent or metastatic disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, and up to two previous systemic therapies were enrolled into the nivolumab 240 mg every 2 weeks group, the randomised groups (nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks [NIVO3 plus IPI1] or nivolumab 1 mg/kg every 3 weeks plus ipilimumab 3 mg/kg every 3 weeks for four cycles then nivolumab 240 mg every 2 weeks [NIVO1 plus IPI3]), or the NIVO1 plus IPI3 expansion group. All doses were given intravenously. Patients were randomly assigned (1:1) to NIVO3 plus IPI1 or NIVO1 plus IPI3 via an interactive voice response system. Treatment continued until disease progression, unacceptable toxicity, or consent withdrawal, or for up to 24 months. The primary endpoint was investigator-assessed objective response rate. Anti-tumour activity and safety were analysed in all treated patients. This study is registered with ClinicalTrials.gov (NCT02488759) and is now completed. FINDINGS: Between October, 2015, and March, 2020, 193 patients were recruited in the recurrent or metastatic cervical cancer cohort of CheckMate 358, of whom 176 were treated. 19 patients received nivolumab monotherapy, 45 received NIVO3 plus IPI1, and 112 received NIVO1 plus IPI3 (45 in the randomised group and 67 in the expansion group). Median follow-up times were 19·9 months (IQR 8·2-44·8) with nivolumab, 12·6 months (7·8-37·1) with NIVO3 plus IPI1, and 16·7 months (7·2-27·5) with pooled NIVO1 plus IPI3. Objective response rates were 26% (95% CI 9-51; five of 19 patients) with nivolumab, 31% (18-47; 14 of 45 patients) with NIVO3 plus IPI1, 40% (26-56; 18 of 45 patients) with randomised NIVO1 plus IPI3, and 38% (29-48; 43 of 112 patients) with pooled NIVO1 plus IPI3. The most common grade 3-4 treatment-related adverse events were diarrhoea, hepatic cytolysis, hyponatraemia, pneumonitis, and syncope (one [5%] patient each; nivolumab group), diarrhoea, increased gamma-glutamyl transferase, increased lipase, and vomiting (two [4%] patients each; NIVO3 plus IPI1 group), and increased lipase (nine [8%] patients) and anaemia (seven [6%] patients; pooled NIVO1 plus IPI3 group). Serious treatment-related adverse events were reported in three (16%) patients in the nivolumab group, 12 (27%) patients in the NIVO3 plus IPI1 group, and 47 (42%) patients in the pooled NIVO1 plus IPI3 group. There was one treatment-related death due to immune-mediated colitis in the NIVO1 plus IPI3 group. INTERPRETATION: Nivolumab monotherapy and nivolumab plus ipilimumab combination therapy showed promise in the CheckMate 358 study as potential treatment options for recurrent or metastatic cervical cancer. Future randomised controlled trials of nivolumab plus ipilimumab or other dual immunotherapy regimens are warranted to confirm treatment benefit in this patient population. FUNDING: Bristol Myers Squibb and Ono Pharmaceutical.

Phytochemicals for Cancer Treatment: An Update on Plant-Derived Anti-Cancer Compounds and their Mechanisms of Action.

Cancer remains one of the major causes of morbidity and mortality worldwide. Scientists from different fields are working to devise an efficient treatment strategy in order to reduce the global burden of cancer. Commonly used treatment approaches for cancer treatment include chemotherapy, immunotherapy, photodynamic therapy, radiation, surgery, etc. These treatment procedures have several pitfalls, such as toxicity, limited bioavailability, rapid elimination, poor specificity, and high cost. On the other side, plant-derived anticancer compounds exhibit several advantages and can overcome these shortcomings. Plant-based anticancer compounds are safer, potent, easily available, and comparatively cost-effective. The current review discusses pure plant- based compounds that are used as a therapeutic remedy for anticancer application. The proposed mechanisms of action, through which these compounds inhibit cancer cell growth, tumor growth, angiogenesis, instigate apoptosis, cytotoxicity, mitochondrial membrane degradation, and reduce cell viability as well as cell cycle progression, are also reviewed. These naturally occurring compounds exhibit great therapeutic potential and could be used as candidate drugs in clinical applications.

Achieving Surgical, Obstetric, Trauma, and Anesthesia (SOTA) care for all in South Asia.

South Asia is a demographically crucial, economically aspiring, and socio-culturally diverse region in the world. The region contributes to a large burden of surgically-treatable disease conditions. A large number of people in South Asia cannot access safe and affordable surgical, obstetric, trauma, and anesthesia (SOTA) care when in need. Yet, attention to the region in Global Surgery and Global Health is limited. Here, we assess the status of SOTA care in South Asia. We summarize the evidence on SOTA care indicators and planning. Region-wide, as well as country-specific challenges are highlighted. We also discuss potential directions-initiatives and innovations-toward addressing these challenges. Local partnerships, sustained research and advocacy efforts, and politics can be aligned with evidence-based policymaking and health planning to achieve equitable SOTA care access in the South Asian region under the South Asian Association for Regional Cooperation (SAARC).

Low profile high gain RHCP antenna for L-Band and S-Band using rectangular ring metasurface with backlobe suppression.

In this reported work a single feed, miniaturized, dual layer, and low profile antenna is presented for 1.575GHz frequency band. The proposed antenna offers high gain, lower noise bandwidth, with better sensitivity and range. The ground choke technique is used for back lobe suppression. The prototype is fabricated on FR 4 substrate using manual fabrication technique. This offers an inexpensive and readily available fabrication. Therefore, fabricated antenna is small size, low cost, easily fabricated and tested for satellite communication. The antenna comprises of two layers, containing a patch radiator and a Metasurface layer with 3x3 rectangular ring resonators. The layers are separated using foam with a 12mm width. The proposed prototype is radiating at 1.575GHz and 2.33GHz with an overall dimension of 85.6 x 68.4 x 15.204 mm. The developed antenna provides a gain of 5.9 dBi. The simulated results are verified using VNA and anechoic chamber testing. Moreover, the developed antenna has been successfully tested for L-Band Satellite communication in real time scenario without any LNA. Higher Gain due to Metasurface increase the efficiency of the system. The promising results indicate the aptness of the developed antenna for real-world applications of L-Band and S-Band.

Structural vaccinology, molecular simulation and immune simulation approaches to design multi-epitopes vaccine against John Cunningham virus.

The JCV (John Cunningham Virus) is known to cause progressive multifocal leukoencephalopathy, a condition that results in the formation of tumors. Symptoms of this condition such as sensory defects, cognitive dysfunction, muscle weakness, homonosapobia, difficulties with coordination, and aphasia. To date, there is no specific and effective treatment to completely cure or prevent John Cunningham polyomavirus infections. Since the best way to control the disease is vaccination. In this study, the immunoinformatic tools were used to predict the high immunogenic and non-allergenic B cells, helper T cells (HTL), and cytotoxic T cells (CTL) epitopes from capsid, major capsid, and T antigen proteins of JC virus to design the highly efficient subunit vaccines. The specific immunogenic linkers were used to link together the predicted epitopes and subjected to 3D modeling by using the Robetta server. MD simulation was used to confirm that the newly constructed vaccines are stable and properly fold. Additionally, the molecular docking approach revealed that the vaccines have a strong binding affinity with human TLR-7. The codon adaptation index (CAI) and GC content values verified that the constructed vaccines would be highly expressed in E. coli pET28a (+) plasmid. The immune simulation analysis indicated that the human immune system would have a strong response to the vaccines, with a high titer of IgM and IgG antibodies being produced. In conclusion, this study will provide a pre-clinical concept to construct an effective, highly antigenic, non-allergenic, and thermostable vaccine to combat the infection of the John Cunningham virus.

Global Neurosurgery at the 76th World Health Assembly (2023): First Neurosurgery-Driven Resolution Calls for Micronutrient Fortification to Prevent Spina Bifida.

Since 2018, a neurosurgery delegation has been actively engaged and consistently present at the World Health Assembly. Recognizing the growing impact of neurosurgical diseases, the neurosurgery delegation participated in the 76th World Health Assembly in May 2023, advocating for timely, safe, and affordable global neurosurgical care. The delegation focused on forging new collaborations, strengthening the World Health Organization-World Federation of Neurosurgical Societies official relations, and actively supporting resolutions that impact the neurosurgical patients. However, there is a long advocacy journey ahead to address unmet neurosurgical needs. Patient-centered advocacy is an inherent task of our profession and the essence of the Global Neurosurgery Bogota Declaration of 2016. The highlight of the 76th World Health Assembly was the adoption of the first neurosurgery-driven resolution calling for micronutrient fortification to prevent spina bifida and other micronutrient deficiencies. For the last 4 years, the Global Alliance for Prevention of Spina Bifida, a group spearheaded by neurosurgeons, advocated for spina bifida prevention. This Alliance collaborated with many stakeholders, notably, the Colombian government to promote the resolution: "Accelerating efforts for preventing micronutrient deficiencies and their consequences, including spina bifida and other neural tube defects, through safe and effective food fortification." This is a proud milestone for the neurosurgical profession. There are many strategies available for neurosurgeons, when working together with elected leaders, other stakeholders, and allied professionals, to implement initiatives that can prevent future cases of spina bifida and other neurological disorders and reduce the burden of neurosurgical disease.

Consensus-Based Development of a Global Registry for Traumatic Brain Injury: Establishment, Protocol, and Implementation.

BACKGROUND AND OBJECTIVES: Global disparity exists in the demographics, pathology, management, and outcomes of surgically treated traumatic brain injury (TBI). However, the factors underlying these differences, including intervention effectiveness, remain unclear. Establishing a more accurate global picture of the burden of TBI represents a challenging task requiring systematic and ongoing data collection of patients with TBI across all management modalities. The objective of this study was to establish a global registry that would enable local service benchmarking against a global standard, identification of unmet need in TBI management, and its evidence-based prioritization in policymaking. METHODS: The registry was developed in an iterative consensus-based manner by a panel of neurotrauma professionals. Proposed registry objectives, structure, and data points were established in 2 international multidisciplinary neurotrauma meetings, after which a survey consisting of the same data points was circulated within the global neurotrauma community. The survey results were disseminated in a final meeting to reach a consensus on the most pertinent registry variables. RESULTS: A total of 156 professionals from 53 countries, including both high-income countries and low- and middle-income countries, responded to the survey. The final consensus-based registry includes patients with TBI who required neurosurgical admission, a neurosurgical procedure, or a critical care admission. The data set comprised clinically pertinent information on demographics, injury characteristics, imaging, treatments, and short-term outcomes. Based on the consensus, the Global Epidemiology and Outcomes following Traumatic Brain Injury (GEO-TBI) registry was established. CONCLUSION: The GEO-TBI registry will enable high-quality data collection, clinical auditing, and research activity, and it is supported by the World Federation of Neurosurgical Societies and the National Institute of Health Research Global Health Program. The GEO-TBI registry ( https://geotbi.org ) is now open for participant site recruitment. Any center involved in TBI management is welcome to join the collaboration to access the registry.

Two-Stage Self-Supervised Contrastive Learning Aided Transformer for Real-Time Medical Image Segmentation.

The availability of large, high-quality annotated datasets in the medical domain poses a substantial challenge in segmentation tasks. To mitigate the reliance on annotated training data, self-supervised pre-training strategies have emerged, particularly employing contrastive learning methods on dense pixel-level representations. In this work, we proposed to capitalize on intrinsic anatomical similarities within medical image data and develop a semantic segmentation framework through a self-supervised fusion network, where the availability of annotated volumes is limited. In a unified training phase, we combine segmentation loss with contrastive loss, enhancing the distinction between significant anatomical regions that adhere to the available annotations. To further improve the segmentation performance, we introduce an efficient parallel transformer module that leverages Multiview multiscale feature fusion and depth-wise features. The proposed transformer architecture, based on multiple encoders, is trained in a self-supervised manner using contrastive loss. Initially, the transformer is trained using an unlabeled dataset. We then fine-tune one encoder using data from the first stage and another encoder using a small set of annotated segmentation masks. These encoder features are subsequently concatenated for the purpose of brain tumor segmentation. The multiencoder-based transformer model yields significantly better outcomes across three medical image segmentation tasks. We validated our proposed solution by fusing images across diverse medical image segmentation challenge datasets, demonstrating its efficacy by outperforming state-of-the-art methodologies.

Heterologous expression of bacterial dehydrin gene in Arabidopsis thaliana promotes abiotic stress tolerance.

Salinity, low temperature, and drought are major environmental factors in agriculture leading to reduced crop yield. Dehydrins (DHNs) are induced transcriptionally during cellular dehydration and accumulate in different tissues during abiotic stresses. Here we isolated and characterized a bacterial gene BG757 in Arabidopsis, encoding a putative dehydrin type protein. ABA induces the expression of various dehydrins in plants, therefore, to elucidate the potential role, ABA sensitivity was examined in Arabidopsis transgenic lines expressing BG757. Interestingly, BG757-expressing plants showed hypersensitivity towards NaCl and ABA during seed germination. In addition to germination, BG757-expressing plants also showed root growth retardation in the presence of ABA and NaCl when compared with wild type (WT), suggesting that BG757 positively regulate salt stress and ABA response. Furthermore, BG757-expressing plants showed significant drought tolerance compared with WT. Consistent with drought tolerance, expression levels of stress inducible genes (DREB2A, RD22, RD26, LEA7 and SOS1) were strongly upregulated in transgenic plants compared with WT. All together these results suggest that heterologous expression of bacterial gene, BG757 in plants promotes resistance to environmental stresses. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01358-w.

Radial Artery Harvesting With Skin Bridge Technique Among Patients Undergoing Coronary Artery Bypass Grafting: An Approach For Developing Countries.

The risk of wound dehiscence and sternal infections remains high after coronary artery bypass grafting, especially in patients with diabetes. Radial artery is a potential alternative which has shown good post-operative outcomes with least complications. Open and endoscopic techniques for harvesting have been used till now. We propose an interrupted or bridging technique, for harvesting the radial artery. This report describes 25 patients undergoing CABG, using radial artery graft, harvested via skin bridge technique, at South City Hospital, Karachi. It has a better cosmetic outcome, reduced postoperative pain, shortened hospital stay and increased level of satisfaction. The interrupted technique offers less invasive cost-effective approach compared to open and endoscopic techniques for radial artery harvesting.

Reactive oxygen species induced oxidative damage to DNA, lipids, and proteins of antibiotic-resistant bacteria by plant-based silver nanoparticles.

This study assesses the mechanism of action of plant-based silver nanoparticles (AgNPs) against antibiotic-resistant bacteria. We compared AgNPs synthesized through Salvia moorcroftiana and Origanum vulgare extracts and their conjugates with the antibiotic Ceftriaxone for their capacity to cause oxidative damage through reactive oxygen species (ROS). We quantified ROS in the cells of two bacterial strains after treating them with all AgNP types and observed that AgNPs were most effective in K. pneumoniae as they resulted in the highest ChS1 count (44,675), while in P. aeruginosa, Cfx-AgNPs induced the highest levels of ROS with ChS1 count of 56,865. DNA analysis showed that both plant-based AgNPs (O-AgNPs = 0.192 and S-AgNPs = 0.152) were most effective in K. pneumoniae and S-AgNPs (abs = 0.174) and O-Cfx-AgNPs (abs = 0.261) in P. aeruginosa. We observed a significant increase in the levels of conjugated dienes (86.4 µM) and malondialdehyde (172.25 nM) in the bacterial strains after treatment with AgNPs, compared to the control (71.65 µM and 18.064 nM, respectively, in K. pneumoniae and P. aeruginosa). These results indicate lipid peroxidation. AgNPs also increased the levels of protein thiols (0.672 nM) compared to the control (0.441 nM) in K. pneumoniae, except for Chem-AgNPs (0.21 nM). These results suggest that plant-based AgNPs are more effective in oxidizing bacterial DNA, protein, and lipids than Chem-AgNPs. Furthermore, protein oxidation varied between AgNPs alone and AgNPs-antibiotic conjugates. The highest levels of protein thiols were found in the samples treated with O-Cfx-AgNPs (0.672 nM and 0.525 nM in K. pneumoniae and P. aeruginosa, respectively). The results demonstrated that AgNPs kill bacteria by altering bacterial macromolecules such as DNA, lipids, and proteins.

LDMRes-Net: A Lightweight Neural Network for Efficient Medical Image Segmentation on IoT and Edge Devices.

In this study, we propose LDMRes-Net, a lightweight dual-multiscale residual block-based convolutional neural network tailored for medical image segmentation on IoT and edge platforms. Conventional U-Net-based models face challenges in meeting the speed and efficiency demands of real-time clinical applications, such as disease monitoring, radiation therapy, and image-guided surgery. In this study, we present the Lightweight Dual Multiscale Residual Block-based Convolutional Neural Network (LDMRes-Net), which is specifically designed to overcome these difficulties. LDMRes-Net overcomes these limitations with its remarkably low number of learnable parameters (0.072M), making it highly suitable for resource-constrained devices. The model's key innovation lies in its dual multiscale residual block architecture, which enables the extraction of refined features on multiple scales, enhancing overall segmentation performance. To further optimize efficiency, the number of filters is carefully selected to prevent overlap, reduce training time, and improve computational efficiency. The study includes comprehensive evaluations, focusing on the segmentation of the retinal image of vessels and hard exudates crucial for the diagnosis and treatment of ophthalmology. The results demonstrate the robustness, generalizability, and high segmentation accuracy of LDMRes-Net, positioning it as an efficient tool for accurate and rapid medical image segmentation in diverse clinical applications, particularly on IoT and edge platforms. Such advances hold significant promise for improving healthcare outcomes and enabling real-time medical image analysis in resource-limited settings.

Efficient green silver nanoparticles-antibiotic combinations against antibiotic-resistant bacteria.

Antibiotic-resistant bacterial strains and the consequent surge in infections caused by them have become major public health concerns. Silver nanoparticles (AgNPs) exhibit antibacterial properties and have wide applications in biomedical sciences. In this study, AgNPs were synthesized in the presence of antibiotics: Ceftazidime (Cft), Cefotaxime (Cef), Ceftriaxone (Cfx), and Cefepime (Cpm), along with the extract of Mentha longifolia. Mentha longifolia-based AgNPs were kept as the control for all experiments. The associated metabolites, structural properties, surface charges, and antibacterial activity of the AgNPs were also evaluated. Overall, a blue-shift of SPR peaks was observed for control AgNPs (λmax = 421 nm, 422 nm, 426 nm, and 406 nm for Cft-AgNPs, Cef-AgNPs, Cfx-AgNPs, and Cpm-AgNPs, respectively), compared to the control (λmax = 438 nm). Fourier-transform infrared spectroscopy showed that antibiotic-based AgNPs had distinct peaks that corresponded to the respective antibiotics, which were not observed in the control. XRD analysis showed that there were observed changes in crystallinity in antibiotic-based AgNPs compared to the control. TEM images revealed that all samples had spherical nanoparticles with different sizes and distributions compared to the control. The Zeta potential for extract-based AgNPs was - 33.6 mV, compared to -19.6 mV for Cft-AgNPs, -2 mV for Cef-AgNPs, -21.1 mV for Cfx-AgNPs, and - 24.2 mV for Cpm-AgNPs. The increase in the PDI value for antibiotic-based AgNPs also showed a highly polydisperse distribution. However, the antibiotic-AgNPs conjugates showed significantly higher activity against pathogenic bacteria. The addition of antibiotics to AgNPs brought significant changes in structural properties and antibacterial activities.

An international, prospective observational study on traumatic brain injury epidemiology study protocol: GEO-TBI: Incidence.

Background: The epidemiology of traumatic brain injury (TBI) is unclear - it is estimated to affect 27-69 million individuals yearly with the bulk of the TBI burden in low-to-middle income countries (LMICs). Research has highlighted significant between-hospital variability in TBI outcomes following emergency surgery, but the overall incidence and epidemiology of TBI remains unclear. To address this need, we established the Global Epidemiology and Outcomes following Traumatic Brain Injury (GEO-TBI) registry, enabling recording of all TBI cases requiring admission irrespective of surgical treatment. Objective: The GEO-TBI: Incidence study aims to describe TBI epidemiology and outcomes according to development indices, and to highlight best practices to facilitate further comparative research. Design: Multi-centre, international, registry-based, prospective cohort study. Subjects: Any unit managing TBI and participating in the GEO-TBI registry will be eligible to join the study. Each unit will select a 90-day study period. All TBI patients meeting the registry inclusion criteria (neurosurgical/ICU admission or neurosurgical operation) during the selected study period will be included in the GEO-TBI: Incidence. Methods: All units will form a study team, that will gain local approval, identify eligible patients and input data. Data will be collected via the secure registry platform and validated after collection. Identifiers may be collected if required for local utility in accordance with the GEO-TBI protocol. Data: Data related to initial presentation, interventions and short-term outcomes will be collected in line with the GEO-TBI core dataset, developed following consensus from an iterative survey and feedback process. Patient demographics, injury details, timing and nature of interventions and post-injury care will be collected alongside associated complications. The primary outcome measures for the study will be the Glasgow Outcome at Discharge Scale (GODS) and 14-day mortality. Secondary outcome measures will be mortality and extended Glasgow Outcome Scale (GOSE) at the most recent follow-up timepoint.

Traumatic brain injury (TBI) is a significant global health problem, which affects 27­69 million people every year. After-effects of TBI commonly affect the injured individuals for years. Most patients who sustain a TBI are from developing countries. Research has shown that there are differences in patients' recovery after TBI between countries and hospitals. The causes of these differences are unclear and tackling them could improve TBI treatment worldwide. To address this need, we have recently established the Global Epidemiology and Outcomes Following Traumatic Brain Injury (GEO-TBI) registry. The international collaborative registry aims to collect data related to the causes, treatments and outcomes related to TBI patients. This data will hopefully enable future research to elucidate the causes of the recovery differences between hospitals, which could lead to improved patient outcomes. The GEO-TBI: Incidence study collects data from all TBI patients that are admitted to participating hospitals or undergo a neurosurgical operation due to TBI during a 90-day period. This study looks at the patient's recovery at discharge using the Glasgow Outcome at Discharge Scale (GODS), and at the 2-week mortality. In addition, the study also evaluates recovery at the most recent follow-up timepoint. We hope that this information will enhance our understanding on the causes, treatments, and commonness of TBI. The study results will also help local hospitals compare their treatment results to an international standard.

Solvent based fractional biosynthesis, phytochemical analysis, and biological activity of silver nanoparticles obtained from the extract of Salvia moorcroftiana.

Multi-drug resistant bacteria sometimes known as "superbugs" developed through overuse and misuse of antibiotics are determined to be sensitive to small concentrations of silver nanoparticles. Various methods and sources are under investigation for the safe and efficient synthesis of silver nanoparticles having effective antibacterial activity even at low concentrations. We used a medicinal plant named Salvia moorcroftiana to extract phytochemicals with antibacterial, antioxidant, and reducing properties. Three types of solvents; from polar to nonpolar, i.e., water, dimethyl sulfoxide (DMSO), and hexane, were used to extract the plant as a whole and as well as in fractions. The biosynthesized silver nanoparticles in all extracts (except hexane-based extract) were spherical, smaller than 20 nm, polydispersed (PDI ranging between 0.2 and 0.5), and stable with repulsive force of action (average zeta value = -18.55±1.17). The tested bacterial strains i.e., Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis were found to be sensitive to even small concentrations of Ag-NPs, especially P. aeruginosa. The antibacterial effect of these Ag-NPs was associated with their ability to generate reactive oxygen species. DMSO (in fraction) could efficiently extract antibacterial phytochemicals and showed activity against MDR bacteria (inhibition zone = 11-12 mm). Thus, the antibacterial activity of fractionated DMSO extract was comparable to that of Ag-NPs because it contained phytochemicals having solid antibacterial potential. Furthermore, Ag-NPs synthesized from this extract owned superior antibacterial activity. However, whole aqueous extract-based Ag-NPs MIC was least (7-32 µg/mL) as compared to others.

Nanomedicine as a potential novel therapeutic approach against the dengue virus.

Dengue is an arbovirus infection which is transmitted by Aedes mosquitoes. Its prompt detection and effective treatment is a global health challenge. Various nanoparticle-based vaccines have been formulated to present immunogen (antigens) to instigate an immune response or prevent virus spread, but no specific treatment has been devised. This review explores the role of nanomedicine-based therapeutic agents against dengue virus, taking into consideration the applicable dengue virus assays that are sensitive, specific, have a short turnaround time and are inexpensive. Various kinds of metallic, polymeric and lipid nanoparticles with safe and effective profiles present an alternative strategy that could provide a better remedy for eradicating the dengue virus.

Red light enhances the antibacterial properties, biofabrication, and stability of Fagonia indica callus-based silver nanoparticles.

Plant-based nanoparticles can be tuned through the frequency of light for efficient synthesis, structural properties, and antibacterial applications. This research assessed the effect of material type (callus and whole-plant extract) and the interaction with a specific range of light wavelength on AgNP synthesis. All types of AgNPs were characterized by their size, shape, associated functional groups, and surface charge. Interestingly, the size of red light and callus-based AgNPs (RC-AgNPs) was smaller (6.32 nm) compared to 14.59 nm for Ultraviolet light and callus-based AgNPs (UV-C-AgNPs). Zeta potential analysis showed that RC-AgNPs had higher stability (-29.2 mV) compared to UV-C-AgNPs (-16.7 mV). Similarly, red light-based AgNPs had higher Oxidation reduction potential in both whole-plant-based and callus-based AgNPs, indicating a more oxidizing nature compared to those synthesized under UV light. This was confirmed by the lower total phenolic and flavonoid content associated with them and their lower antioxidant activity. The higher antibacterial activities and lower minimum inhibitory concentrations of red light-based AgNPs against highly resistant pathogenic bacteria demonstrated the role of red light in enhancing antibacterial activity. These results indicate that AgNPs synthesized in red light and callus extract are more active compared to those synthesized under other wavelengths and/or in whole-plant extracts.

Conceptual Understanding of Preventive Strategies for Metabolic Disorders in Unani Medicine: A Narrative Review.

Background: The global burden of metabolic disorders is increasing at an alarming rate. These disorders have a huge impact in terms of human suffering and economic implications. There is an urgent need for effective strategies, including the use of traditional systems of medicine, to reduce the burden of these diseases. Objective: The objective of this article is to compile information on preventive strategies for metabolic disorders found in Unani medicine. Methods: A literature survey of classical Unani texts was conducted to understand the conceptual framework in Unani medicine underlying preventive strategies for metabolic disorders. Electronic databases such as PubMed, ScienceDirect, and Google Scholar were searched to obtain the evidence needed to validate the Unani medicine viewpoint. Results: Unani scholars have described a set of clinical conditions caused by the insufficiency of the nutritive faculty. These conditions correlate in many ways with metabolic disorders. Cold dystemperament of the liver is considered to be the cause of insufficiency of nutritive faculty. Therefore, care and protection of the liver is considered as the main preventive approach for metabolic disorders in Unani medicine. Several epidemiological studies have also reported a strong relationship between non-alcoholic fatty liver disease and metabolic syndrome. Conclusion: The broad set of approaches (based on its theoretical foundations) used by Unani scholars to maintain the nutritive faculty in its optimal functional state seems to be an effective measure for the prevention of metabolic disorders.

Copper-Catalyzed Asymmetric Hydroboration Reaction of Novel Methylene Isoindolinone Compounds through Microwave Irradiation and Their Antileishmanial and Antitoxoplasma Activities.

The aim of this study was devoted into molecular docking calculations to discover the potential antileishmania and antitoxoplasma activities of newly synthesized compounds obtained by applying a practical and simple method under microwave irradiation. All these compounds were tested in vitro for their biological activity against Leishmania major promastigotes, amastigotes, and Toxoplasma gondii tachyzoites. Compounds 2a, 5a, and 5e were the most active against both L. major promastigotes and amastigotes, with IC50 values of less than 0.4 µM mL-1. Compounds 2c, 2e, 2h, and 5d had a strong antitoxoplasma activity of less than 2.1 µM mL-1 against T. gondii. We can conclude that aromatic methyleneisoindolinones are potently active against both L. major and T. gondii. Further studies for mode of action evaluation are recommended. Compounds 5c and 5b are the best drug candidates for antileishmania and antitoxoplasma due to their SI values being over 13. The docking studies of compounds 2a-h and 5a-e against pteridine reductase 1 and T. gondii enoyl acyl carrier protein reductase reveal that compound 5e may be an effective antileishmanial and antitoxoplasma drug discovery initiative.