Transmission dynamics, complications and mitigation strategies of the current mpox outbreak: A comprehensive review with bibliometric study.

As the mankind counters the ongoing COVID-19 pandemic by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), it simultaneously witnesses the emergence of mpox virus (MPXV) that signals at global spread and could potentially lead to another pandemic. Although MPXV has existed for more than 50 years now with most of the human cases being reported from the endemic West and Central African regions, the disease is recently being reported in non-endemic regions too that affect more than 50 countries. Controlling the spread of MPXV is important due to its potential danger of a global spread, causing severe morbidity and mortality. The article highlights the transmission dynamics, zoonosis potential, complication and mitigation strategies for MPXV infection, and concludes with suggested 'one health' approach for better management, control and prevention. Bibliometric analyses of the data extend the understanding and provide leads on the research trends, the global spread, and the need to revamp the critical research and healthcare interventions. Globally published mpox-related literature does not align well with endemic areas/regions of occurrence which should ideally have been the scenario. Such demographic and geographic gaps between the location of the research work and the endemic epicentres of the disease need to be bridged for greater and effective translation of the research outputs to pubic healthcare systems, it is suggested.

Inflammatory and vascular biomarkers in post-COVID-19 syndrome: A systematic review and meta-analysis of over 20 biomarkers.

Severe acute respiratory syndrome coronavirus 2 may inflict a post-viral condition known as post-COVID-19 syndrome (PCS) or long-COVID. Studies measuring levels of inflammatory and vascular biomarkers in blood, serum, or plasma of COVID-19 survivors with PCS versus non-PCS controls have produced mixed findings. Our review sought to meta-analyse those studies. A systematic literature search was performed across five databases until 25 June 2022, with an updated search on 1 November 2022. Data analyses were performed with Review Manager and R Studio statistical software. Twenty-four biomarkers from 23 studies were meta-analysed. Higher levels of C-reactive protein (Standardized mean difference (SMD) = 0.20; 95% CI: 0.02-0.39), D-dimer (SMD = 0.27; 95% CI: 0.09-0.46), lactate dehydrogenase (SMD = 0.30; 95% CI: 0.05-0.54), and leukocytes (SMD = 0.34; 95% CI: 0.02-0.66) were found in COVID-19 survivors with PCS than in those without PCS. After sensitivity analyses, lymphocytes (SMD = 0.30; 95% CI: 0.12-0.48) and interleukin-6 (SMD = 0.30; 95% CI: 0.12-0.49) were also significantly higher in PCS than non-PCS cases. No significant differences were noted in the remaining biomarkers investigated (e.g., ferritin, platelets, troponin, and fibrinogen). Subgroup analyses suggested the biomarker changes were mainly driven by PCS cases diagnosed via manifestation of organ abnormalities rather than symptomatic persistence, as well as PCS cases with duration of <6 than ≥6 months. In conclusion, our review pinpointed certain inflammatory and vascular biomarkers associated with PCS, which may shed light on potential new approaches to understanding, diagnosing, and treating PCS.

Immunotherapeutics in lung cancers: from mechanistic insight to clinical implications and synergistic perspectives.

BACKGROUND: Lung cancer is one of the highly lethal forms of cancer whose incidence has worldwide rapidly increased over the past few decades. About 80-85% of all lung cancer cases constitute non-small cell lung cancer (NSCLC), with adenocarcinoma, squamous cell carcinoma and large cell carcinoma as the main subtypes. Immune checkpoint inhibitors have led to significant advances in the treatment of a variety of solid tumors, significantly improving cancer patient survival rates. METHODS AND RESULTS: The cytotoxic drugs in combination with anti-PD-(L)1 antibodies is a new method that aims to reduce the activation of immunosuppressive and cancer cell prosurvival responses while also improving direct cancer cell death. The most commonly utilized immune checkpoint inhibitors for patients with non-small cell lung cancer are monoclonal antibodies (Atezolizumab, Cemiplimab, Ipilimumab, Pembrolizumab etc.) against PD-1, PD-L1, and CTLA-4. Among them, Atezolizumab (TECENTRIQ) and Cemiplimab (Libtayo) are engineered monoclonal anti programmed death ligand 1 (PD-L1) antibodies that inhibit binding of PD-L1 to PD-1 and B7.1. As a result, T-cell proliferation and cytokine synthesis are inhibited leading to restoring the immune homeostasis to fight cancer cells. CONCLUSIONS: In this review article, the path leading to the introduction of immunotherapeutic options in lung cancer treatment is described, with analyzing the benefits and shortages of the current immunotherapeutic drugs. In addition, possibilities to co-administer immunotherapeutic agents with standard cancer treatment modalities are also considered.

Anti-tubercular activity evaluation of natural compounds by targeting Mycobacterium tuberculosis resuscitation promoting factor B inhibition: An in silico study.

Tuberculosis (TB), an infectious disease caused by the Mycobacterium tuberculosis (Mtb), has been responsible for the deaths of millions of individuals around the globe. A vital protein in viral pathogenesis known as resuscitation promoting factor (RpfB) has been identified as a potential therapeutic target of anti-tuberculosis drugs. This study offered an in silico process to examine possible RpfB inhibitors employing a computational drug design pipeline. In this study, a total of 1228 phytomolecules were virtually tested against the RpfB of Mtb. These phytomolecules were sourced from the NP-lib database of the MTi-OpenScreen server, and five top hits (ZINC000044404209, ZINC000059779788, ZINC000001562130, ZINC000014766825, and ZINC000043552589) were prioritized for compute intensive docking with dock score ≤ - 8.5 kcal/mole. Later, molecular dynamics (MD) simulation and principal component analysis (PCA) were used to validate these top five hits. In the list of these top five hits, the ligands ZINC000044404209, ZINC000059779788, and ZINC000043552589 showed hydrogen bond formation with the functional residue Glu292 of the RpfB protein suggesting biological significance of the binding. The RMSD study showed stable protein-ligand complexes and higher conformational consistency for the ligands ZINC000014766825, and ZINC000043552589 with RMSD 3-4 Å during 100 ns MD simulation. The overall analysis performed in the study suggested promising binding of these compounds with the RpfB protein of the Mtb at its functional site, further experimental investigation is needed to validate the computational finding.

Challenges of the Omicron (B.1.1.529) Variant and Its Lineages: A Global Perspective.

The SARS-CoV-2 virus has shown increased ability to mutate over the past two years, especially in the regions of the spike protein and receptor binding sites. Omicron (B.1.1.529) is the fifth variant of concern (VOC) after the emergence of the Alpha, Beta, Gamma, and Delta VOCs of SARS-CoV-2. This new variant has now circulated in 128 countries and according to the Global Initiative on Sharing All Influenza Data (GISAID), these 128 countries have shared 650,657 Omicron genome sequences as of 26 January, 2022. In this article, we highlight the real challenges of Omicron and its different lineages.

Twin combination of Omicron and Delta variants triggering a tsunami wave of ever high surges in COVID-19 cases: A challenging global threat with a special focus on the Indian subcontinent.

The emergence of Omicron (B.1.1.529) variant of SARS-CoV-2 has resulted into a very massive surge in COVID-19 cases worldwide. Due to continuous emergence of multiple variants of SARS-CoV-2, the ongoing pandemic has caused severe morbidity and mortality in last two years. The rate of infectivity of Omicron variant is much higher than Delta variant and in a very quick time Omicron has displaced the Delta variant and now become a dominant variant across the globe. The twin combination of Omicron and Delta variant is triggering a Tsunami wave of ever high surges in COVID-19 cases worldwide. This article highlights the global threats and challenges posed by Omicron, and strategies to counter it with a particular focus on Indian sub-continent.

Recent Trends and Developments in Multifunctional Nanoparticles for Cancer Theranostics.

Conventional anticancer treatments, such as radiotherapy and chemotherapy, have significantly improved cancer therapy. Nevertheless, the existing traditional anticancer treatments have been reported to cause serious side effects and resistance to cancer and even to severely affect the quality of life of cancer survivors, which indicates the utmost urgency to develop effective and safe anticancer treatments. As the primary focus of cancer nanotheranostics, nanomaterials with unique surface chemistry and shape have been investigated for integrating cancer diagnostics with treatment techniques, including guiding a prompt diagnosis, precise imaging, treatment with an effective dose, and real-time supervision of therapeutic efficacy. Several theranostic nanosystems have been explored for cancer diagnosis and treatment in the past decade. However, metal-based nanotheranostics continue to be the most common types of nonentities. Consequently, the present review covers the physical characteristics of effective metallic, functionalized, and hybrid nanotheranostic systems. The scope of coverage also includes the clinical advantages and limitations of cancer nanotheranostics. In light of these viewpoints, future research directions exploring the robustness and clinical viability of cancer nanotheranostics through various strategies to enhance the biocompatibility of theranostic nanoparticles are summarised.

Immunological aspects and gender bias during respiratory viral infections including novel Coronavirus disease-19 (COVID-19): A scoping review.

The human immune system is not adequately equipped to eliminate new microbes and could result in serious damage on first exposure. This is primarily attributed to the exaggerated immune response (inflammatory disease), which may prove detrimental to the host, as evidenced by SARS-CoV-2 infection. From the experiences of Novel Coronavirus Disease-19 to date, male patients are likely to suffer from high-intensity inflammation and disease severity than the female population. Hormones are considered the significant pillars of sex differences responsible for the discrepancy in immune response exhibited by males and females. Females appear to be better equipped to counter invading respiratory viral pathogens, including the novel SARS-CoV-2, than males. It can be hypothesized that females are more shielded from disease severity, probably owing to the diverse action/influence of estrogen and other sex hormones on both cellular (thymus-derived T lymphocytes) and humoral immunity (antibodies).

Dengue fever coinfection in COVID-19 era: A public health concern.

Background and Aim: Dengue and SARS-CoV-2 coinfection is commonly encountered and constantly reported in particularly the dengue-endemic regions thus posing a co-epidemic threat. Coinfection is also significantly associated with morbidity and mortality. Comorbidity risk during a coinfection is of a greater concern. Although the pathophysiologies of the two infections vary, their identical clinical symptoms during coinfection result in diagnostic and therapeutic complexities. Methods: A literature search for the current relevant reports was carried out. The searched databases were Scopus, PubMed, Google Scholar and the Web of Science, with health agencies like the WHO. Based on the selection criteria, the most recent and pertinent reports published in English language were included for the ease of understanding, deciphering and analysing the secondary data. Results: A delay in proper diagnosis of coinfection could result in serious complications with poor patient outcome. Whether it is a standalone dengue or COVID-19 infection or a coinfection, specific biomarkers may be utilized for its foolproof diagnosis. This article highlights the various diagnostic techniques and immune responses from the perspective of prompt and appropriate public health management for patients suffering from COVID-19 and dengue viral coinfections, both being independently or collectively capable of damaging a human body. Conclusion: As coinfection poses significantly large burden on an already-fragile healthcare facility, constant monitoring of a coinfected patient is needed for prompt and suitable therapeutics. Also, to maintain high vigilance and invoke appropriate preventive measures particularly in dengue endemic regions, the government, healthcare authority and the general public need to collaborate and cooperate.

Global health concern on the rising dengue and chikungunya cases in the American regions: Countermeasures and preparedness.

Background and Aim: Severe morbidity and mortality due to seasonal infectious diseases are common global public health issues. Vector-borne viral illnesses like dengue and chikungunya overload the healthcare systems leading to critical financial burden to manage them. There is no effective drug or vaccine currently available to control these two diseases. Methods: The review was formulated by incorporating relevant reports on chikungunya and dengue in the Americas regions through a comprehensive search of literature that were available on dedicated scientific publication portals such as PubMed, ScienceDirect, and Web of Science. Results: The strategies of public health administrations to control largely the mosquito vectors during tropical monsoon seem to be effective. Yet, it seems practically impossible to completely eliminate them. The mosquito vector disseminates the virus via transovarian route thereby internalising the virus through generations, a reason behind reappearing and recurring outbreaks. The numerous factors associated with industrialisation, urbanisation, population density, and easy transboundary movements appear to have contributed to the spread of vectors from an endemic region to elsewhere. Conclusion: The article made a state-of-affair comprehensive analysis of the rising dengue and chikungunya cases in the tropics, particularly the tropical Americas, as a human health concern, the countermeasures undertaken and the overall preparedness. The viral transmission is a hard situation to tackle as the vector survives in diverse temperature and ecology, is resistant to insecticides, and the unavailability of drugs. Better vector-control measures and improved understanding of the reemerging arboviral infections could offer an extended reaction time to counter outbreaks, and minimise associated morbidity/mortality.

Current approaches in smart nano-inspired drug delivery: A narrative review.

Background and Aim: The traditional drug delivery approach involves systemic administration of a drug that could be nonspecific in targeting, low on efficacy, and with severe side-effects. To address such challenges, the field of smart drug delivery has emerged aiming at designing and developing delivery systems that can target specific cells, tissues, and organs and have minimal off-target side-effects. Methods: A literature search was done to collate papers and reports about the currently available various strategies for smart nano-inspired drug delivery. The databases searched were PubMed, Scopus, and Google Scholar. Based on selection criteria, the most pertinent and recent items were included. Results: Smart drug delivery is a cutting-edge revolutionary intervention in modern medicines to ensure effective and safe administration of therapeutics to target sites. These hold great promise for targeted and controlled delivery of therapeutic agents to improve the efficacy with reduced side-effects as compared to the conventional drug delivery approaches. Current smart drug delivery approaches include nanoparticles, liposomes, micelles, and hydrogels, each with its own advantages and limitations. The success of these delivery systems lies in engineering and designing them, and optimizing their pharmacokinetics and pharmacodynamics properties. Conclusion: Development of drug delivery systems that can get beyond various physiological and clinical barriers, as observed in conventionally administered chemotherapeutics, has been possible through recent advancements. Using multifunctional targeting methodologies, smart drug delivery tries to localize therapy to the target location, reduces cytotoxicity, and improves the therapeutic index. Rapid advancements in research and development in smart drug delivery provide wider and more promising avenues to guarantee a better healthcare system, improve patient outcomes, and achieve higher levels of effective medical interventions like personalized medicine.

Recurring food source-based Listeria outbreaks in the United States: An unsolved puzzle of concern?

Recurring Listeria outbreaks in the United States is a growing public healthcare concern. Although no associated reported death, 17 were hospitalized out of the 18 reported illnesses in the recent outbreak in 15 US states. The United States has experienced about 30 Listeria outbreaks in the last decade with 524 Listeriosis cases and 80 deaths. The identified origin were ice cream, leafy greens, mushroom, meat slice, dairy products like cheese, packaged salads, cooked chicken, hard-boiled egg, pork product, frozen vegetable, raw milk, packaged caramel apple, bean sprout and soya products. Although rare, Listeria may lead to serious illness (invasive listeriosis) or death. Listeriosis is critically harmful and medically complicated, especially in the pregnant, the old above 65 years and in the immunocompromised. It could cause premature birth, miscarriage or even neonatal death. Hospitalization is often necessary in the geriatric, being fatal at times. Among Listeria sp., Listeria monocytogenes is often human infection-associated. It is a gram-positive, non-sporulating, motile bacillus opportunistic pathogen. Food-borne listeriosis is often associated with frozen foods due to its ability to thrive at low temperatures. Hypervirulent strains of L. monocytogenes with an ability to infect the respiratory system (the lungs) was recently reported in the coronavirus disease-19 patients during the pandemic. L. monocytogenes seemed to have developed antimicrobial resistance to ciprofloxacin and meropenem, possibly acquired through the food chain. An early onset of listeriosis in the newborn is evident in the first 7 days postparturition. As the bacteria colonize the genitourinary tract, majority of such cases result from teratogenic transfer during vaginal delivery. Premature newborns, neonates born outside healthcare facilities and low-birth-weight babies were increasingly predisposed to an early onset of listeriosis. Listeria outbreaks were earlier reported in South Africa, Australia and Europe, with an unclear origin of the outbreaks. Social media updates about such outbreaks, the most likely food source, and measures to self-protect are suggested as preventive measures. The article deals on various such aspects related to listeriosis primarily originating from food, to ensure better public healthcare and human wellness.

Molecular dynamic analyses of the interaction of SARS-CoV-1 or 2 variants with various angiotensin-converting enzyme-2 species.

The transmembrane glycoprotein angiotensin-converting enzyme 2 (ACE2) is a key component of the renin-angiotensin system (RAS). It was shown to be the receptor of severe acute respiratory syndrome coronavirus 2 in the COVID-19 outbreak (SARS-COV-2). Furthermore, ACE2 aids in the transport of amino acids across the membrane. ACE2 is lost from the membrane, resulting in soluble ACE2 (sACE2). We aim to examine the structural conformation alterations between SARS-CoV-1 or 2 variants at various periods with ACE2 from various sources, particularly in the area where it interacts with the viral protein and the receptor. It is important to study the molecular dynamics of ACE2/SARS-COV RBD when the structure is available on the database. Here we analyzed the crystal structure of ACE2 from Human, Dog, Mus, Cat, and Bat ACE2 in complex with RBD from SARS-COV-1 and SARS-COV-2. The result shows, there is a variation in the type of residues, number of contact atoms and hydrogen bonds in ACE2 and RBD during the interaction interfaces. By using molecular dynamics simulation, we can measure RMSD, RMSF, SASA, Rg and the difference in the percentage of α helix and ß strand. As bat ACE2 & SARS-CoV-2 RBD found to have a high amount of ß strand compared to another structure complex, while hACE2 & SARS-CoV-1 RBD has fewer amounts of ß strand. Our study provides a deep view of the structure which is available and a summary of many works around ACE2/SARS-CoV RBD interaction.Communicated by Ramaswamy H. Sarma.

Surgical interventions for intractable migraine: a systematic review and meta-analysis.

BACKGROUND: Migraine affects approximately 14-15% of the global population, contributing to nearly 5% of the world's health burden. When drug treatments prove ineffective for intractable migraines, highly specific surgical interventions emerge as potential solutions. We aimed to analyze surgical approaches for these refractory or intractable migraines through a systematic review and meta-analysis. METHODS: We conducted a literature search across databases such as PubMed, Scopus, Web of Science, and Embase, focusing on studies related to migraines and surgical outcomes. We considered clinical trials or observational studies that included any surgical intervention for refractory or intractable migraines, emphasizing key outcomes such as reductions in migraine intensity, Migraine Disability Assessment scores (MIDAS), and 50% Migraine Headache Index (MHI) reduction rates. Statistical analyses were performed using R version 4.3. RESULTS: Eleven studies were included in the systematic review. A meta-analysis of four studies involving overall 95 patients showed a significant reduction in mean migraine intensity scores using ONS (-2.27, 95% CI: -3.92 to -0.63, P=0.021). Three studies with 85 patients showed an average MIDAS score reduction of -52.3, though this was not statistically significant (95% CI: -136.85 to 32.19, P=0.116). Two additional studies corroborated these reductions in MIDAS scores. Nerve decompression surgery showed a substantial decrease in the average migraine intensity (from 8.31 down to 4.06). Median MIDAS score dropped from 57 to 20. Two studies indicated a success rate of 40% and 82%, respectively, in achieving a 50% reduction in the Migraine MHI through nerve decompression. Findings from two studies suggest that septorhinoplasty and sinus surgery effectively decrease migraine intensity scores. CONCLUSION: The existing evidence emphasizes the potential advantages of surgical interventions as a promising approach to managing intractable or refractory migraines. However, robust and comprehensive research is crucial to refine and solidify the efficacy of these surgical methods, aiming for widespread benefits for patients, considering cost-effectiveness factors.

Photophysical properties of four-membered BN3 heterocyclic compounds: theoretical insights.

CONTEXT: Understanding the photochemistry of boron nitrogen (BN)-containing compounds is an important aspect to enhance the various optical and electronic applications. In this work, we have explored the structure, bonding, reactivity, electronic absorption (UV-Vis), and light harvesting efficiency (LHE) of a series of BN3 ring and open-chain systems. The frontier molecular orbitals (FMO) analysis found that ring systems have a low HOMO-LUMO energy gap as compared to the open-chain systems which insinuates the feasibility of ring systems in the optoelectronic materials. Also, the molecular electrostatic potential (MEP) maps have been computed to pursue the electrophilic and nucleophilic sites available at the surface of the compound. Interestingly, we have found that the open-chain compounds show more molecular charge distribution range rather than the ring compounds. The investigation of photophysical properties showed that the UV-Vis absorption significantly red-shifted in BN3 ring systems as compared to open-chain counterparts. Furthermore, light harvesting efficiency (LHE) was also found higher in the ring systems as compared to the BN3 open-chain systems. Moreover, the computed structural parameters are found well corroborated with the available X-ray data. METHODS: Structures of all compounds were optimized by using density functional theory (DFT) method, with M06-2X/6-31G(d,p) level. All the calculations in this work are carried out in Gaussian 16 program package. GaussView6.1 software was used for the modeling of initial geometries and for the plotting of MEP plots. To account the solvent effect on geometries the polarized continuum model (PCM) was used and tetrahydrofuran (THF) taken as solvent. The NBO6.0 program (incorporated in G16 software) was used for the exploration of bonding nature and stabilization energies of B-N bond. The absorption spectra were simulated by using ORCA 4.2 program.

SARS-CoV-2 Variants BA.2.86 and EG.5.1 Alongside Scrub Typhus and Nipah in India During the Ongoing Cricket World Cup 2023: Threat Perceptions and Countermeasures.

The United States (US), the United Kingdom (UK), and China witnessed rising cases of coronavirus disease 2019 (COVID-19) in 2023. Concerns about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) novel strains amid the sudden surge of COVID cases are growing. Recently, BA.2.86 (Pirola) poses a much greater risk due to its higher transmission rate and spreading across regions. Pirola variant has mutations that set it apart from all earlier known SARS-CoV-2 variants. This variant was designated a variant of interest by the World Health Organization (WHO). Another SARS-CoV-2 variant named "Eris" (EG.5.1) was detected in India and started picking up in the US and the UK. The WHO listed EG.5.1 (variant) as a variant under monitoring. Therefore, it is important to remain vigilant. Further, multiple Nipah virus infections and scrub typhus cases are spreading among humans in India currently. In this situation, the 13th edition of the International Cricket Council (ICC) Men's Cricket World Cup is being held in India this year. With global reach, this big sporting carnival attracts millions of cricket fans from several countries. In light of the multiple public health concerns encountered currently, this gala global sports event needs additional preventive measures.

Current Surge of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Variants in China Could Be Threatening as the Asian Games 2023 Flags Off in September: Foolproof Cautionary Measures Are Suggested.

Despite normalcy having almost returned in the lives of people throughout the world post-coronavirus disease-19 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the danger still looms over the fears of development and propagation of a newer SARS-CoV-2 variant. The movement of people globally has reached the pre-pandemic level, and this augmentation increased surveillance regarding the emergence of lethal SARS-CoV-2 variants. International sports events are among the potential avenues where the virus could cause serious impact. Therefore, the organization of such events should be planned and executed meticulously to avoid viral transmission and minimize the health effects of infections on the sportspersons and the local people. Additionally, there could be dissemination of the infections to the native countries of the participants and visitors while they return to their homes. Through this editorial, we prompt caution to the organizers and the event-hosting nation's administration regarding the potential threat and suggest measures to avoid any medical emergencies related to COVID-19.