Acute Care Surgery: Navigating Recent Developments, Protocols, and Challenges in the Comprehensive Management of Surgical Emergencies.

Acute care surgery (ACS) is a crucial medical field that specifically deals with the rapid treatment of surgical emergencies. This investigation encompasses the most recent progress, procedures, and obstacles in ACS, utilizing various sources such as scholarly articles, clinical trials, and expert statements. The development of ACS as a specialized field is a significant area of concentration, particularly emphasizing its contribution to improving patient care. An examination is conducted on the efficacy of contemporary triage systems and prompt response mechanisms, specifically in diminishing the incidence of illness and death rates associated with illnesses such as trauma, acute appendicitis, and obstructed viscera. The emphasis is placed on the surgical protocols and principles that form the basis of ACS. Examining regional and international approaches provides insight into the distinctions and commonalities in surgical techniques. An assessment is conducted to determine the effects of the transition to minimally invasive procedures on patient outcomes, recuperation periods, and healthcare expenses. The assessment also examines the logistical obstacles that ACS encounters, such as resource allocation and managing diverse teams. The examination focuses on the delicate equilibrium between prompt decision-making and care grounded in evidence. It also evaluates the possible contribution of technical breakthroughs such as telemedicine and AI to improving patient care and overcoming current obstacles. The topic of training and education for surgeons in ACS is of utmost importance and requires careful consideration. The evaluation evaluates the sufficiency of existing educational frameworks and the necessity of specific training to equip surgeons for the requirements of ACS. This analysis explores the current discourse surrounding the standardization of ACS training, considering its potential ramifications for the future of surgical procedures. Exploring ethical and legal problems in ACS also includes situations when prompt decision-making may clash with patient autonomy and informed consent. The significance of proficient communication with patients and their families during emergency surgical scenarios is underscored, emphasizing the necessity for ethical awareness and interpersonal aptitude. The investigation of ACS demonstrates its dynamic character, signifying notable advancements while recognizing enduring obstacles. Continual research, interdisciplinary collaboration, and policy adjustments are necessary to improve ACS procedures. This thorough investigation offers valuable insights for professionals and researchers, facilitating future progress in managing surgical crises.

Protein-Aided Synthesis of Copper-Integrated Polyaniline Nanocomposite Encapsulated with Reduced Graphene Oxide for Highly Sensitive Electrochemical Detection of Dimetridazole in Real Samples.

Dimetridazole (DMZ) is a derivative of nitroimidazole and is a veterinary drug used as an antibiotic to treat bacterial or protozoal infections in poultry. The residues of DMZ cause harmful side effects in human beings. Thus, we have constructed a superior electrocatalyst for DMZ detection. A copper (Cu)-integrated poly(aniline) (PANI) electrocatalyst (PANI-Cu@BSA) was prepared by using a one-step method of biomimetic mineralization and polymerization using bovine serum albumin (BSA) as a stabilizer. Then, the synthesized PANI-Cu@BSA was encapsulated with reduced graphene oxide (rGO) using an ultrasonication method. The PANI-Cu@BSA/rGO nanocomposite had superior water dispersibility, high electrical conductivity, and nanoscale particles. Moreover, a PANI-Cu@BSA/rGO nanocomposite-modified, screen-printed carbon electrode was used for the sensitive electrochemical detection of DMZ. In phosphate buffer solution, the PANI-Cu@BSA/rGO/SPCE displayed a current intensity greater than PANI-Cu@BSA/SPCE, rGO/SPCE, and bare SPCE. This is because PANI-Cu@BSA combined with rGO increases fast electron transfer between the electrode and analyte, and this synergy results in analyte-electrode junctions with extraordinary conductivity and active surface areas. PANI-Cu@BSA/rGO/SPCE had a low detection limit, a high sensitivity, and a linear range of 1.78 nM, 5.96 µA µM-1 cm-2, and 0.79 to 2057 µM, respectively. The selective examination of DMZ was achieved with interfering molecules, and the PANI-Cu@BSA/rGO/SPCE showed excellent selectivity, stability, repeatability, and practicability.

Microfluidics-Based Nanobiosensors for Healthcare Monitoring.

Efficient healthcare management demands prompt decision-making based on fast diagnostics tools, astute data analysis, and informatics analysis. The rapid detection of analytes at the point of care is ensured using microfluidics in synergy with nanotechnology and biotechnology. The nanobiosensors use nanotechnology for testing, rapid disease diagnosis, monitoring, and management. In essence, nanobiosensors detect biomolecules through bioreceptors by modulating the physicochemical signals generating an optical and electrical signal as an outcome of the binding of a biomolecule with the help of a transducer. The nanobiosensors are sensitive and selective and play a significant role in the early identification of diseases. This article reviews the detection method used with the microfluidics platform for nanobiosensors and illustrates the benefits of combining microfluidics and nanobiosensing techniques by various examples. The fundamental aspects, and their application are discussed to illustrate the advancement in the development of microfluidics-based nanobiosensors and the current trends of these nano-sized sensors for point-of-care diagnosis of various diseases and their function in healthcare monitoring.

Mechanism of hydrophobic gating in the acetylcholine receptor channel pore.

Neuromuscular acetylcholine receptors (AChRs) are hetero-pentameric, ligand-gated ion channels. The binding of the neurotransmitter acetylcholine (ACh) to two target sites promotes a global conformational change of the receptor that opens the channel and allows ion conduction through the channel pore. Here, by measuring free-energy changes from single-channel current recordings and using molecular dynamics simulations, we elucidate how a constricted hydrophobic region acts as a "gate" to regulate the channel opening in the pore of AChRs. Mutations of gate residues, including those implicated in congenital myasthenia syndrome, lower the permeation barrier of the channel substantially and increase the unliganded gating equilibrium constant (constitutive channel openings). Correlations between hydrophobicity and the observed free-energy changes, supported by calculations of water densities in the wild-type versus mutant channel pores, provide evidence for hydrophobic wetting-dewetting transition at the gate. The analysis of a coupled interaction network provides insight into the molecular mechanism of closed- versus open-state conformational changes at the gate. Studies of the transition state by "phi"(φ)-value analysis indicate that agonist binding serves to stabilize both the transition and the open state. Intersubunit interaction energy measurements and molecular dynamics simulations suggest that channel opening involves tilting of the pore-lining M2 helices, asymmetric outward rotation of amino acid side chains, and wetting transition of the gate region that lowers the barrier to ion permeation and stabilizes the channel open conformation. Our work provides new insight into the hydrophobic gate opening and shows why the gate mutations result in constitutive AChR channel activity.

Combating Staphylococcus aureus biofilm formation: the inhibitory potential of tormentic acid and 23-hydroxycorosolic acid.

Plant extracts have been used to treat microbiological diseases for centuries. This study examined plant triterpenoids tormentic acid (TA) and 23-hydroxycorosolic acid (HCA) for their antibiofilm effects on Staphylococcus aureus strains (MTCC-96 and MTCC-7405). Biofilms are bacterial colonies bound by a matrix of polysaccharides, proteins, and DNA, primarily impacting healthcare. As a result, ongoing research is being conducted worldwide to control and prevent biofilm formation. Our research showed that TA and HCA inhibit S. aureus planktonic growth by depolarizing the bacterial membrane. In addition, zone of inhibition studies confirmed their effectiveness, and crystal violet staining and biofilm protein quantification confirmed their ability to prevent biofilm formation. TA and HCA exhibited substantial reductions in biofilm formation for S. aureus (MTCC-96) by 54.85% and 48.6% and for S. aureus (MTCC-7405) by 47.07% and 56.01%, respectively. Exopolysaccharide levels in S. aureus biofilm reduced significantly by TA (25 µg/mL) and HCA (20 µg/mL). Microscopy, bacterial motility, and protease quantification studies revealed their ability to reduce motility and pathogenicity. Furthermore, TA and HCA treatment reduced the mRNA expression of S. aureus virulence genes. In silico analysis depicted a high binding affinity of triterpenoids for biofilm and quorum-sensing associated proteins in S. aureus, with TA having the strongest affinity for TarO (- 7.8 kcal/mol) and HCA for AgrA (- 7.6 kcal/mol). TA and HCA treatment reduced bacterial load in S. aureus-infected peritoneal macrophages and RAW264.7 cells. Our research indicates that TA and HCA can effectively combat S. aureus by inhibiting its growth and suppressing biofilm formation.

Assessment of Oral Health-Related Quality of Life Using the Oral Impact on Daily Performance (OIDP) Instrument Among Secondary School Teachers of Modinagar, Uttar Pradesh: A Cross-Sectional Study.

Introduction Oral health has an impact on a person's general health, well-being, and quality of life. Due to their expertise and interactions with people, school staff members can actively contribute to the promotion of children's health if provided with the proper training. Methodology A cross-sectional survey was conducted to assess the "oral health-related quality of life" using the Oral Impact on Daily Performance (OIDP) instrument among the secondary school teachers of Modinagar, Uttar Pradesh. The study included a sample of 400 government secondary school teachers and 400 private secondary school teachers. The independent sample t-test was performed to assess the relationship between the mean of OIDP dimensions and the prevalence of dental caries. Any p-value less than 0.05 was considered significant. The data was analyzed using the SPSS version 20.0 software package (IBM Corp., Armonk, NY). Results In the present study, most of the participants (174 (43.5%) government teachers and 197 (49.2%) private teachers) were in the age group of 41-50 years. According to the Decayed, Missing, and Filled Teeth (DMFT) index, the mean decayed teeth present for government and private school teachers were 0.45 ± 0.503 and 0.41 ± 0.493, respectively, and the mean DMF scores for government and private teachers were 1.27 ± 0.736 and 1.03 ± 0.757, respectively. There was a positive correlation between the DMFT scores and the mean scores for the dimensions of the OIDP among both government and private secondary school teachers. Conclusion The poor dental health status of teachers' has a bad impact on everyday performance and academic work. The findings of the study highlight the need for oral health education and good oral health maintenance among school teachers since they are the ones who can easily influence the behavior of the children.

mRNA-based vaccines and therapeutics: an in-depth survey of current and upcoming clinical applications.

mRNA-based drugs have tremendous potential as clinical treatments, however, a major challenge in realizing this drug class will promise to develop methods for safely delivering the bioactive agents with high efficiency and without activating the immune system. With regard to mRNA vaccines, researchers have modified the mRNA structure to enhance its stability and promote systemic tolerance of antigenic presentation in non-inflammatory contexts. Still, delivery of naked modified mRNAs is inefficient and results in low levels of antigen protein production. As such, lipid nanoparticles have been utilized to improve delivery and protect the mRNA cargo from extracellular degradation. This advance was a major milestone in the development of mRNA vaccines and dispelled skepticism about the potential of this technology to yield clinically approved medicines. Following the resounding success of mRNA vaccines for COVID-19, many other mRNA-based drugs have been proposed for the treatment of a variety of diseases. This review begins with a discussion of mRNA modifications and delivery vehicles, as well as the factors that influence administration routes. Then, we summarize the potential applications of mRNA-based drugs and discuss further key points pertaining to preclinical and clinical development of mRNA drugs targeting a wide range of diseases. Finally, we discuss the latest market trends and future applications of mRNA-based drugs.

Evaluation of Dental Professionals' Knowledge and Attitude Regarding the Diagnosis of Oral Cancer Through Histopathological Examination of Granulation Tissue.

INTRODUCTION: The current cancer trend in India has reported an alarming increase in cancer of the lip, throat, and oral cavity. Few dentists are aware that malignant neoplasms can also occur in the form of granulation tissue and periapical granulomas. However, most dentists agree that biopsies are essential to diagnose oral cancer. This makes the timely diagnosis of oral cancer dependent upon the histopathological examination of the granulation tissue by the dentist. AIM:  The main aim of this study was to evaluate the knowledge and attitudes of dentists regarding the diagnosis of oral cancer through histopathological analysis of granulation tissue. METHOD: A cross-sectional study was conducted on dentists who were residents of Uttar Pradesh, India. Two hundred and fifty study participants enrolled to complete a self-structured questionnaire containing 15 closed-ended questions. The study was conducted over a period of three months, from June to August 2020. Descriptive statistics were analyzed using IBM SPSS Statistics for Windows, Version 21.0 (Released 2012; IBM Corp., Armonk, New York, United States, and the t-test was performed. A significance level of P ≤ 0.05 was used to determine the statistical significance of quantitative variables. RESULTS: The study findings revealed that only a small percentage of dentists (47.2%) were aware of the importance of biopsies in diagnosing oral cancer. Moreover, a minority (14.4%) had conducted biopsies and submitted samples for histopathological analysis. Of them, 10% were aware that in clinical practice, malignant tumors can also manifest as periapical granulomas, granulation tissue, gingivitis, and other conditions. CONCLUSION: Dentists should proactively submit any granulation tissue for histopathological examination. Oral healthcare providers must maintain a high level of suspicion, develop a range of potential or differential diagnoses for oral cancer, and take necessary measures to attain a definitive diagnosis. This may include considering a referral to a specialist for the treatment of oral cancer.

A Questionnaire Study to Assess the Belief and Barrier to Blood Donation and the Influence of Educational Intervention on Urban and Rural Patients.

OBJECTIVE:  Blood transfusion services are an essential part of any healthcare delivery system in today's clinical world with advanced medicines because blood is in high demand during various medical emergencies. Improving knowledge and hastening the development of a positive attitude toward blood donation in society should be the goal of developing an efficient strategy for sustaining a safe and adequate blood supply. AIM:  The study aims to explore the knowledge, attitude, and motivation toward blood donation among urban and rural patients attending the outreach program. MATERIALS AND METHODS:  Patients who attended the outreach program held by the Dental College of Uttar Pradesh were subjected to a questionnaire survey to determine their level of knowledge regarding blood donation. Further, an education-based intervention was done among the camp patients to assess the change in their learning after the intervention. The difference between the individual responses prior to and following the intervention was analyzed using the chi-square test. p≤0.05 was considered statistically significant. RESULTS:  Urban patients comprise 186 males (44.28%) and 234 females (55.72%). Among the rural patients, 205 (45.55%) were males and 245 were females (54.45%). About 48.80% of the urban patients and 48.88% of the rural patients were Hindus while the remaining were Muslims. Only 22.14% of urban patients and 16.88% of rural patients had donated blood till now. The comparison after the intervention for rural patients showed a significant improvement in the level of knowledge and awareness. CONCLUSION:  Although it is quite common knowledge that rural people require more awareness and education related to health, after the conduction of our study, we have resolute evidence that demands thorough IEC and health information activities for the welfare of rural people and to diminish the divide.

Metatranscriptomic insight into the possible role of clay microbiome in skin disease management.

Even though the scientific documentation is limited, microbiome of healing clay is gradually gaining attention of the scientific community, as a therapeutic force playing an indispensable role in skin disease management. The present study explores the metatranscriptome profile of the Chamliyal clay, widely known for its efficacy in managing various skin problems, using Illumina NextSeq sequencing technology. The gene expression profile of the clay microbial community was analyzed through SEED subsystems of the MG-RAST server. Due to the unavailability of metatranscriptomic data on other therapeutic clays, Chamliyal's profile was compared to non-therapeutic soils, as well as healthy and diseased human skin microbiomes. The study identified Firmicutes, Proteobacteria, and Actinobacteria as the primary active microbial phyla in Chamliyal clay. These resemble those abundant in a healthy human skin microbiome. This is significant as lower levels of these phyla in the skin are linked to inflammatory skin conditions like psoriasis. Interestingly, pathogenic microbes actively metabolizing in the clay were absent. Importantly, 6% of the transcripts annotated to sulfur and iron metabolism, which are known to play a major role in skin disease management. This study provides the most comprehensive and a novel overview of the metatranscriptome of any of the healing clay available worldwide. The findings offer valuable insights into the clay microbiome's potential in managing skin disorders, inspiring future endeavors to harness these insights for medical applications.

Antibiotic resistance, biofilm formation, and virulence genes of Streptococcus agalactiae serotypes of Indian origin.

BACKGROUND: Group B Streptococcus (GBS) is a causative agent of various infections in newborns, immunocompromised (especially diabetic) non-pregnant adults, and pregnant women. Antibiotic resistance profiling can provide insights into the use of antibiotic prophylaxis against potential GBS infections. Virulence factors are responsible for host-bacteria interactions, pathogenesis, and biofilm development strategies. The aim of this study was to determine the biofilm formation capacity, presence of virulence genes, and antibiotic susceptibility patterns of clinical GBS isolates. RESULTS: The resistance rate was highest for penicillin (27%; n = 8 strains) among all the tested antibiotics, which indicates the emergence of penicillin resistance among GBS strains. The susceptibility rate was highest for ofloxacin (93%; n = 28), followed by azithromycin (90%; n = 27). Most GBS strains (70%; n = 21) were strong biofilm producers and the rest (30%; n = 9) were moderate biofilm producers. The most common virulence genes were cylE (97%), pavA (97%), cfb (93%), and lmb (90%). There was a negative association between having a strong biofilm formation phenotype and penicillin susceptibility, according to Spearman's rank correlation analysis. CONCLUSION: About a third of GBS strains exhibited penicillin resistance and there was a negative association between having a strong biofilm formation phenotype and penicillin susceptibility. Further, both the strong and moderate biofilm producers carried most of the virulence genes tested for, and the strong biofilm formation phenotype was not associated with the presence of any virulence genes.

Bivalent mRNA vaccine effectiveness against SARS-CoV-2 variants of concern.

BACKGROUND: Sequential infections with SARS-CoV-2 variants such as Alpha, Delta, Omicron and its sublineages may cause high morbidity, so it is necessary to develop vaccines that can protect against both wild-type (WT) virus and its variants. Mutations in SARS-CoV-2's spike protein can easily alter viral transmission and vaccination effectiveness. METHODS: In this study, we designed full-length spike mRNAs for WT, Alpha, Delta, and BA.5 variants and integrated each into monovalent or bivalent mRNA-lipid nanoparticle vaccines. A pseudovirus neutralization assay was conducted on immunized mouse sera in order to examine the neutralizing potential of each vaccine. RESULTS: Monovalent mRNA vaccines were only effective against the same type of virus. Interestingly, monovalent BA.5 vaccination could neutralize BF.7 and BQ.1.1. Moreover, WT, Alpha, Delta, BA.5, and BF.7 pseudoviruses were broadly neutralized by bivalent mRNA vaccinations, such as BA.5 + WT, BA.5 + Alpha, and BA.5 + Delta. In particular, BA.5 + WT exhibited high neutralization against most variants of concern (VOCs) in a pseudovirus neutralization assay. CONCLUSIONS: Our results show that combining two mRNA sequences may be an effective way to develop a broadly protective SARS-CoV-2 vaccine against a wide range of variant types. Importantly, we provide the optimal combination regimen and propose a strategy that may prove useful in combating future VOCs.

Correction to: Parent's Perspective on Teletherapy of Pediatric Population with Speech and Language Disorder During Covid-19 Lockdown in India.

[This corrects the article DOI: 10.1007/s12070-022-03310-y.].

Quaternary Pullulan-Functionalized 2D MoS2 Glycosheets: A Potent Bactericidal Nanoplatform for Efficient Wound Disinfection and Healing.

Rapid emergence of multidrug-resistant bacterial strains has posed a global threat to public health. Hospital-acquired infections, especially in diabetic and burn patients, severely impede the process of wound healing, thereby causing high mortality. This calls for developing a new biomaterial that synergistically destroys pathogenic strains and also helps in promoting wound healing without causing any resistance generation. A new and highly potent antibacterial agent has been developed by integrating the bactericidal and wound healing properties of MoS2 nanosheets and a recently developed quaternized polysaccharide, pullulan (CP), into a single nanoplatform for accelerated wound therapy. MoS2 nanosheets are noncovalently functionalized with quaternized pullulan to yield glycosheets (MCP) that efficiently eradicate both Gram-negative Escherichia coli (5 µg/mL) and Gram-positive Staphylococcus aureus (10 µg/mL) within a short period of 4 h, through a synergistic action of membrane damage and chemical oxidation. MoS2 nanosheets coupled with CP exert a membrane-directed bactericidal action through distinct mechanisms of "pore-forming" and "non-pore-forming" pathways, respectively, whereas oxidative stress is induced by MoS2 nanosheets alone to collectively kill the pathogens. The MCP glycosheets have good biocompatibility and are also capable of disrupting and eradicating mature biofilms. Rapid and highly efficient in vivo wound disinfection and healing occurred upon MCP treatment through the reduction of inflammation and promotion of cellular proliferation and tissue remodeling. Thus, MCP glycosheets can emerge as a safe and potential biomaterial for better wound care management.

Graphitic carbon nitride (g-C3N4)-assisted materials for the detection and remediation of hazardous gases and VOCs.

Graphitic carbon nitride (g-C3N4)-based materials are attracting attention for their unique properties, such as low-cost, chemical stability, facile synthesis, adjustable electronic structure, and optical properties. These facilitate the use of g-C3N4 to design better photocatalytic and sensing materials. Environmental pollution by hazardous gases and volatile organic compounds (VOCs) can be monitored and controlled using eco-friendly g-C3N4- photocatalysts. Firstly, this review introduces the structure, optical and electronic properties of C3N4 and C3N4 assisted materials, followed by various synthesis strategies. In continuation, binary and ternary nanocomposites of C3N4 with metal oxides, sulfides, noble metals, and graphene are elaborated. g-C3N4/metal oxide composites exhibited better charge separation that leads to enhancement in photocatalytic properties. g-C3N4/noble metal composites possess higher photocatalytic activities due to the surface plasmon effects of metals. Ternary composites by the presence of dual heterojunctions improve properties of g-C3N4 for enhanced photocatalytic application. In the later part, we have summarised the application of g-C3N4 and its assisted materials for sensing toxic gases and VOCs and decontaminating NOx and VOCs by photocatalysis. Composites of g-C3N4 with metal and metal oxide give comparatively better results. This review is expected to bring a new sketch for developing g-C3N4-based photocatalysts and sensors with practical applications.

Wrapping-Trapping versus Extraction Mechanism of Bactericidal Activity of MoS2 Nanosheets against Staphylococcus aureus Bacterial Membrane.

The promising broad-spectrum antibacterial activity of two-dimensional molybdenum disulfide (2D MoS2) has been widely recognized in the past decade. However, a comprehensive understanding of how the antibacterial pathways opted by the MoS2 nanosheets varies with change in lipid compositions of different bacterial strains is imperative to harness their full antibacterial potential and remains unexplored thus far. Herein, we present an atomistic molecular dynamics (MD) study to investigate the distinct modes of antibacterial action of MoS2 nanosheets against Staphylococcus aureus (S. aureus) under varying conditions. We observed that the freely dispersed nanosheets readily adhered to the bacterial membrane outer surface and opted for an unconventional surface directed "wrapping-trapping" mechanism at physiological temperature (i.e., 310 K). The adsorbed nanosheets mildly influenced the membrane structure by originating a compact packing of the lipid molecules present in its direct contact. Interestingly, these surface adsorbed nanosheets exhibited extensive phospholipid extraction to their surface, thereby inducing transmembrane water passage analogous to the cellular leakage, even at a slight increment of 20 K in the temperature. The strong van der Waals interactions between lipid fatty acyl tails and MoS2 basal planes were primarily responsible for this destructive phospholipid extraction. In addition, the MoS2 nanosheets bound to an imaginary substrate, controlling their vertical alignment, demonstrated a "nano-knives" action by spontaneously piercing inside the membrane core through their sharp corner, subsequently causing localized lipid ordering in their vicinity. The larger nanosheet produced a more profound deteriorating impact in all of the observed mechanisms. Keeping the existing knowledge about the bactericidal activity of 2D MoS2 in view, our study concludes that their antibacterial activity is strongly governed by the lipid composition of the bacterial membrane and can be intensified either by controlling the nanosheet vertical alignment or by moderately warming up the systems.

Broadly neutralizing antibodies against Omicron variants of SARS-CoV-2 derived from mRNA-lipid nanoparticle-immunized mice.

The COVID-19 pandemic continues to threaten human health worldwide as new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerge. Currently, the predominant circulating strains around the world are Omicron variants, which can evade many therapeutic antibodies. Thus, the development of new broadly neutralizing antibodies remains an urgent need. In this work, we address this need by using the mRNA-lipid nanoparticle immunization method to generate a set of Omicron-targeting monoclonal antibodies. Five of our novel K-RBD-mAbs show strong binding and neutralizing activities toward all SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, Delta and Omicron). Notably, the epitopes of these five K-RBD-mAbs are overlapping and localized around Y453 and F486 of the spike protein receptor binding domain (RBD). Chimeric derivatives of the five antibodies (K-RBD-chAbs) neutralize Omicron sublineages BA.1 and BA.2 with low IC50 values ranging from 5.7 to 12.9 ng/mL. Additionally, we performed antibody humanization on broadly neutralizing chimeric antibodies to create K-RBD-hAb-60 and -62, which still retain excellent neutralizing activity against Omicron. Our results collectively suggest that these five therapeutic antibodies may effectively combat current and emerging SARS-CoV-2 variants, including Omicron BA.1 and BA.2. Therefore, the antibodies can potentially be used as universal neutralizing antibodies against SARS-CoV-2.

Assessment of sub-chronic oral toxicity of Nityanand Rasa: An ayurvedic herbo-metallic formulation.

ETHNOPHARMACOLOGICAL RELEVANCE: Nityananda Rasa (NR) is an ayurvedic herbo-metallic formulation used to treat gout, obesity, hypothyroidism, elephantiasis, and other diseases. However, its safety is a concern owing to the use of heavy metals like mercury and arsenic. AIM OF THE STUDY: To study the sub-chronic oral toxicity of NR on albino wistar rats for safety evaluation. MATERIALS AND METHODS: The male and female albino wistar rats were administered a daily dose of 30 (low), 300 (medium) and 600 (high) mg/kg BW/day of NR for 90-day period. The body weight and feed consumption were monitored once a week. After 90 days, blood and vital organs were harvested for genotoxicity, hematology, biochemistry, histopathology, gene expression and the biodistribution analysis. RESULTS: There was no mortality or severe behavioural changes observed in rats. Significant changes in biochemical enzyme levels were seen at medium and high doses of NR i. e. 300 and 600 mg/kg BW/day respectively. No hematological changes were observed. Mild histopathological changes seen at high dose of NR which were found in concurrence with the biochemical alterations in liver and brain. There was mild genotoxicity and no detectable level of mercury but significant arsenic level in blood at high dose. Gene expression was mildly affected. CONCLUSIONS: NR induced moderate toxic effects at high dose but can be considered safe at therapeutic doses.

Screening of potential antiplasmodial agents targeting cysteine protease-Falcipain 2: a computational pipeline.

The spread of antimalarial drug resistance is a substantial challenge in achieving global malaria elimination. Consequently, the identification of novel therapeutic candidates is a global health priority. Malaria parasite necessitates hemoglobin degradation for its survival, which is mediated by Falcipain 2 (FP2), a promising antimalarial target. In particular, FP2 is a key enzyme in the erythrocytic stage of the parasite's life cycle. Here, we report the screening of approved drugs listed in DrugBank using a computational pipeline that includes drug-likeness, toxicity assessments, oral toxicity evaluation, oral bioavailability, docking analysis, maximum common substructure (MCS) and molecular dynamics (MD) Simulations analysis to identify capable FP2 inhibitors, which are hence potential antiplasmodial agents. A total of 45 drugs were identified, which have positive drug-likeness, no toxic features and good bioavailability. Among these, six drugs showed good binding affinity towards FP2 compared to E64, an epoxide known to inhibit FP2. Notably, two of them, Cefalotin and Cefoxitin, shared the highest MCS with E64, which suggests that they possess similar biological activity as E64. In an investigation using MD for 100 ns, Cefalotin and Cefoxitin showed adequate protein compactness as well as satisfactory complex stability. Overall, these computational approach findings can be applied for designing and developing specific inhibitors or new antimalarial agents for the treatment of malaria infections.Communicated by Ramaswamy H. Sarma.

Artificial intelligence-based prediction of lycopene content in raw tomatoes using physicochemical attributes.

INTRODUCTION: Lycopene consumption reduces risk and incidence of cancer and cardiovascular diseases. Tomatoes are a rich source of phytochemical compounds including lycopene as a major constituent. Lycopene estimation using high-performance liquid chromatography is time-consuming and expensive. OBJECTIVE: To develop artificial intelligence models for prediction of lycopene in raw tomatoes using 14 different physicochemical parameters including salinity, total dissolved solids (TDS), electrical conductivity (EC), firmness, pH, total soluble solids (TSS), titratable acidity (TA), colour values on Hunter scale (L, a, b), total phenolic content (TPC), total flavonoid content (TFC) and antioxidant activity (AOA). MATERIAL AND METHODS: The post-harvest data acquisition was collected through investigation for more than 100 raw tomatoes stored for 15 days. Linear multivariate regression (LMVR), principal component regression (PCR) and partial least squares regression (PLSR) models were developed by splitting data set into train and test datasets. The training of models was performed using 10-fold cross validation (CV). RESULTS: Principal component analysis showed strong positive association between lycopene, colour value 'a', TPC, TFC and AOA. The R2 (CV), root mean square error (RMSE) (CV) and RMSE (Test) for best LMVR model was observed to be at 0.70, 8.48 and 9.69 respectively. The PCR model revealed R2 (CV) at 0.59, RMSE (CV) at 8.91 and RMSE (Test) at 10.17 while PLSR model revealed R2 (CV) at 0.60, RMSE (CV) at 9.10 and RMSE (Test) at 10.11. CONCLUSION: Results of the present study show that epidemiological studies suggest fully ripened tomatoes are most beneficial for consumption to ensure recommended daily intake of lycopene content.