Design and computational evaluation of a novel multi-epitope hybrid vaccine against monkeypox virus: Potential targets and immunogenicity assessment for pandemic preparedness.

Monkeypox is a type of DNA-enveloped virus that belongs to the orthopoxvirus family, closely related to the smallpox virus. It can cause an infectious disease in humans known as monkeypox disease. Although there are multiple drugs and vaccines designed to combat orthopoxvirus infections, with a primary focus on smallpox, the recent spread of the monkeypox virus to over 50 countries have ignited a mounting global concern. This unchecked viral proliferation has raised apprehensions about the potential for a pandemic corresponding to the catastrophic impact of COVID-19. This investigation explored the structural proteins of monkeypox virus as potential candidates for designing a novel hybrid multi-epitope vaccine. The epitopes obtained from the selected proteins were screened to ensure their non-allergenicity, non-toxicity, and antigenicity to trigger T and B-cell responses. The interaction of the vaccine with toll-like receptor-3 (TLR-3) and major histocompatibility complexes (MHCs) was assessed using Cluspro 2.0. To establish the reliability of the docked complexes, a comprehensive evaluation was conducted using Immune and MD Simulations and Normal Mode Analysis. However, to validate the computational results of this study, additional in-vitro and in-vivo research is essential.

Systemic Bacillus Calmette-Guerin Infection One Year After Intravesical Immunotherapy Mimicking Sarcoidosis.

A patient presented with pancytopenia and hypercalcemia after intravesical immunotherapy with Bacillus Calmette-Guerin (BCG) for bladder cancer. Bone marrow biopsy performed six months later revealed noncaseating granulomas with negative stains for AFB. He was diagnosed with sarcoidosis and treated with prednisone. Hypercalcemia resolved, but mild pancytopenia persisted. One year later, he developed sepsis. Blood cultures six weeks later grew Mycobacterium tuberculosis complex, ultimately identified as Mycobacterium bovis. Despite triple antibiotic therapy, the patient progressively declined and expired.

System level modeling and analysis of TNF-α mediated sphingolipid signaling pathway in neurological disorders for the prediction of therapeutic targets.

Sphingomyelin (SM) belongs to a class of lipids termed sphingolipids. The disruption in the sphingomyelin signaling pathway is associated with various neurodegenerative disorders. TNF-α, a potent pro-inflammatory cytokine generated in response to various neurological disorders like Alzheimer's disease (AD), Parkinson's disease (PD), and Multiple Sclerosis (MS), is an eminent regulator of the sphingomyelin metabolic pathway. The immune-triggered regulation of the sphingomyelin metabolic pathway via TNF-α constitutes the sphingomyelin signaling pathway. In this pathway, sphingomyelin and its downstream sphingolipids activate various signaling cascades like PI3K/AKT and MAPK/ERK pathways, thus, controlling diverse processes coupled with neuronal viability, survival, and death. The holistic analysis of the immune-triggered sphingomyelin signaling pathway is imperative to make necessary predictions about its pivotal components and for the formulation of disease-related therapeutics. The current work offers a comprehensive in silico systems analysis of TNF-α mediated sphingomyelin and downstream signaling cascades via a model-based quantitative approach. We incorporated the intensity values of genes from the microarray data of control individuals from the AD study in the input entities of the pathway model. Computational modeling and simulation of the inflammatory pathway enabled the comprehensive study of the system dynamics. Network and sensitivity analysis of the model unveiled essential interaction parameters and entities during neuroinflammation. Scanning of the key entities and parameters allowed us to determine their ultimate impact on neuronal apoptosis and survival. Moreover, the efficacy and potency of the FDA-approved drugs, namely Etanercept, Nivocasan, and Scyphostatin allowed us to study the model's response towards inhibition of the respective proteins/enzymes. The network analysis revealed the pivotal model entities with high betweenness and closeness centrality values including recruit FADD, TNFR_TRADD, act CASP2, actCASP8, actCASP3 and 9, cytochrome C, and RIP_RAIDD which profoundly impacted the neuronal apoptosis. Whereas some of the entities with high betweenness and closeness centrality values like Gi-coupled receptor, actS1PR, Sphingosine, S1P, actAKT, and actERK produced a high influence on neuronal survival. However, the current study inferred the dual role of ceramide, both on neuronal survival and apoptosis. Moreover, the drug Nivocasan effectively reduces neuronal apoptosis via its inhibitory mechanism on the caspases.

Anesthetic Exposure During Childhood and Neurodevelopmental Outcomes: A Systematic Review and Meta-analysis.

Importance: Clinical studies of neurodevelopmental outcomes after anesthetic exposure have evaluated a range of outcomes with mixed results. Objective: To examine via meta-analyses the associations between exposure to general anesthesia and domain-specific neurodevelopmental outcomes in children. Data Sources: PubMed/MEDLINE, Embase, CINAHL, Web of Science and the Cochrane Library were searched from inception to August 31, 2021. Study Selection: Inclusion criteria were exposures to procedures requiring general anesthesia at younger than 18 years and evaluation of long-term neurodevelopmental function after exposure. Studies lacking unexposed controls or focused on children with major underlying comorbidities were excluded. Data Extraction and Synthesis: Extracted variables included effect size; hazard, risk, or odds ratio; number of exposures; procedure type; major comorbidities; age of exposure and assessment; presence of unexposed controls; and study design. Studies were independently reviewed by 2 coders, and review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were pooled using a random-effects model. Main Outcomes and Measures: The main outcomes were standardized mean differences (SMD) for scores in the neurodevelopmental domains of academics, behavioral problems, cognition, executive function, general development, language, motor function, nonverbal reasoning, social cognition, and hazard and risk of neurodevelopmental disorder diagnoses. Results: A total of 31 studies contributed data for meta-analysis. For each of the assessed neurodevelopmental domains, the numbers of children evaluated ranged from 571 to 63 315 exposed and 802 to 311 610 unexposed. Children with any exposure (single or multiple) had significantly worse behavioral problems scores, indicating more behavioral problems (SMD, -0.10; 95% CI, -0.18 to -0.02; P = .02), and worse scores in academics (SMD, -0.07; 95% CI -0.12 to -0.01; P = .02), cognition (SMD, -0.03; 95% CI, -0.05 to 0.00; P = .03), executive function (SMD, -0.20; 95% CI, -0.32 to -0.09; P < .001), general development (SMD, -0.08; 95% CI, -0.13 to -0.02; P = .01), language (SMD, -0.08; 95% CI, -0.14 to -0.02; P = .01), motor function (SMD, -0.11; 95% CI, -0.21 to -0.02; P = .02), and nonverbal reasoning (SMD, -0.15; 95% CI, -0.27 to -0.02; P = .02). Higher incidences of neurodevelopmental disorder diagnoses were also reported (hazard ratio, 1.19; 95% CI, 1.09 to 1.30; P < .001; risk ratio, 1.81; 95% CI, 1.25 to 2.61; P = .002). Conclusions and Relevance: These findings support the hypothesis that associations between anesthetic exposure during childhood and subsequent neurodevelopmental deficits differ based on neurodevelopmental domain.

Efficient Recovery of Lithium Cobaltate from Spent Lithium-Ion Batteries for Oxygen Evolution Reaction.

Owing to technological advancements and the ever-increasing population, the search for renewable energy resources has increased. One such attempt at finding effective renewable energy is recycling of lithium-ion batteries and using the recycled material as an electrocatalyst for the oxygen evolution reaction (OER) step in water splitting reactions. In electrocatalysis, the OER plays a crucial role and several electrocatalysts have been investigated to improve the efficiency of O2 gas evolution. Present research involves the use of citric acid coupled with lemon peel extracts for efficient recovery of lithium cobaltate from waste lithium-ion batteries and subsequent use of the recovered cathode material for OER in water splitting. Optimum recovery was achieved at 90 °C within 3 h of treatment with 1.5 M citric acid and 1.5% extract volume. The consequent electrode materials were calcined at 600, 700 and 800 °C and compared to the untreated waste material calcined at 600 °C for OER activity. The treated material recovered and calcined at 600 °C was the best among all of the samples for OER activity. Its average particle size was estimated to be within the 20-100 nm range and required a low overpotential of 0.55 V vs. RHE for the current density to reach 10 mA/cm2 with a Tafel value of 128 mV/dec.

Surface-enhanced Raman spectroscopy for comparison of serum samples of typhoid and tuberculosis patients of different stages.

BACKGROUND: Surface-enhanced Raman spectroscopy (SERS) is a reliable tool for the identification and differentiation of two different human pathological conditions sharing the same symptomology, typhoid and tuberculosis (TB). OBJECTIVES: To explore the potential of surface-enhanced Raman spectroscopy for differentiation of two different diseases showing the same symptoms and analysis by principal component analysis (PCA) and partial least square discriminate analysis (PLS-DA). METHODS: Serum samples of clinically diagnosed typhoid and tuberculosis infected individuals were analyzed and differentiated by SERS using silver nanoparticles (Ag NPs) as a SERS substrate. For this purpose, the collected serum samples were analyzed under the SERS instrument and unique SERS spectra of typhoid and tuberculosis were compared showing notable spectral differences in protein, lipid and carbohydrates features. Different stages of the diseased class of typhoid (Early acute and late acute stage) and tuberculosis (Pulmonary and extra-pulmonary stage) were compared with each other and with healthy human serum samples, which were significantly separated. Moreover, SERS data was analyzed using multivariate data analysis techniques including principal component analysis (PCA) and partial least square discriminate analysis (PLS-DA) and differences were so prominent to observe. RESULTS: SERS Spectral data of typhoid and tuberculosis showed clear differences and were significantly separated using PCA. SERS spectral data of both stages of typhoid and tuberculosis were separated according to 1st principle component. Moreover, by analyzing data using partial least square discriminate analysis, differentiation of two disease classes were considered more valid with a 100% value of sensitivity, specificity and accuracy. CONCLUSION: SERS can be employed for identification and comparison of two different human pathological conditions sharing same symptomology.

Phytochemical relationship of Euphorbia helioscopia and Euphorbia pulcherrima with Lactuca sativa.

Allelopathy is an important phenomenon that modifies the ecosystem. A plant can enhance or reduce the growth of other plant due to the presence of a number of allelochemicals in its different parts. Euphorbia helioscopia and Euphorbia pulcherrima are medicinal plant species. Both these species are collected from wild resources for various purposes. To reduce the pressure on wild population, it is important to bring them into cultivation. Therefore, the allelopathic effects of E. helioscopia and E. pulcherrima on the growth of lettuce seeds were studied. Three different concentrations (2%, 4% and 6%) of five different solvents (methanol, acetone, ethyl acetate, n-hexane and distilled water) were used to estimate the allelopathic potential of the above-mentioned Euphorbia species. Results indicated a non-significant growth inhibitory effect of both plants on lettuce seeds. Different extracts reduced the growth of test plant to some extent but this inhibition was not significant. From the observed results, it was concluded that the studied Euphorbia species, being medicinally important crops, can be introduced as intercrop with other cash crops.

Idiopathic primary ovarian insufficiency: a study of serial hormonal profiles to assess ovarian follicular activity.

BACKGROUND: Ovarian follicular activity in serial hormone profiles has been reported in up to 86% of patients with primary ovarian insufficiency (POI). In most of these studies, patients had a short duration of amenorrhea or irregular menstrual cycles which could influence the occurrence of spontaneous follicular activity. The aim was to study the incidence of follicular activity in serial hormonal profiles of women with spontaneous POI and amenorrhea of 1 year duration. METHODS: This observational study involved 20 patients with spontaneous POI, amenorrhea of >1 year duration and normal karyotype. Serum measurements of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), progesterone, free T3, free T4, thyroid-stimulating hormone and anti-thyroperoxidase antibodies, taken in the absence of estrogen replacement, were followed by weekly measurements of serum E2, FSH, LH and progesterone for 1 month then monthly measurements for 2 months. Increases in serum E2 >184 pmol/l and serum progesterone >10 nmol/l were taken as evidence of follicular activity and ovulation, respectively. RESULTS: A rise in serum E2 >184 pmol/l was noted in 2/18 subjects [11.1%; 95% confidence interval (CI): 1.4-34.7%]. Though the corresponding serum FSH levels showed a decline, the values remained >40 IU/l. None of the subjects had serum progesterone levels >10 nmol/l, return of menses or pregnancy. CONCLUSION: Endogenous ovarian follicular function is intermittently present in only 11.1% of Asian Indian women with POI. However, the 95% CI (1.4-34.7%) was large due to a small sample size.