Pioneering Nit Gene Exploitation to Develop Molecular Diagnostic Assay for Rapid Detection of Cotton Root Rot Incitant, Macrophomina phaseolina (Tassi) Goid, in Field Soil.

Cotton root rot caused by Macrophomina phaseolina pose a significant threat to cotton production, leading to substantial yield and quality losses. Early and accurate diagnosis of this pathogen in soil is crucial for effective disease management. This study presents a pioneering investigation into the utilization of the nit gene encoding nitrilase for the development of a molecular diagnostic assay aimed at the rapid detection of M. phaseolina in field soils. The methodology involved the design and validation of primers targeting the Nit gene sequence, followed by the optimization of PCR conditions for efficient amplification. Leveraging state-of-the-art molecular techniques, the assay offers a novel protocol to accurately identify the presence of M. phaseolina in soil with high sensitivity and specificity. The specificity of the designed primers was confirmed through PCR amplification using DNA from M. phaseolina and other related fungi. Sensitivity tests demonstrated that the PCR assay reliably detected M. phaseolina DNA at concentrations as low as 1 ng. Furthermore, the performance of the diagnostic assay was rigorously evaluated using field soil samples with a known status of M. phaseolina infection, demonstrating its reliability and efficacy in real-world scenarios. This study introduces a novel molecular marker for the detection of M. phaseolina and offers a rapid and efficient means for screening M. phaseolina in large soil samples with minimal time and manpower.

Beyond the classic players: Mas-related G protein-coupled receptor member X2 role in pruritus and skin diseases.

Chronic spontaneous urticaria (CSU), atopic dermatitis (AD), psoriasis and rosacea are highly prevalent inflammatory skin conditions which impose a significant burden on patients' quality of life. Their pathophysiology is likely multifactorial, involving genetic, immune and environmental factors. Recent advancements in the field have demonstrated the key role of mast cells (MC) in the pathophysiology of these conditions. The Mas-related G protein-coupled receptor X2 (MRGPRX2) has emerged as a promising non-IgE-mediated MC activation receptor. MRGPRX2 is predominately expressed on MC and activated by endogenous and exogenous ligands, leading to MC degranulation and release of various pro-inflammatory mediators. Mounting evidence on the presence of endogenous MRGPRX2 agonists (substance P, cortistatin-14, LL37, PAMP-12 and VIP) and its high expression among patients with CSU, AD, rosacea, psoriasis and chronic pruritus emphasizes the pathogenic role of MRGPRX2 in these conditions. Despite the currently available treatments, there remains a pressing need for novel drug targets and treatment options for these chronic inflammatory skin conditions. Here, we reviewed the pathogenic role of MRGPRX2 and its potential as a novel therapeutic target and provided an update on future research directions.

Mirror, Mirror on the Wall; He Had a "Bypass" After All!

How to cite this article: Magoon R, Jose J, Kumar M. Mirror, Mirror on the Wall; He Had a "Bypass" After All! Indian J Crit Care Med 2024;28(7):706-707.

Film Coating of Phosphorylated Mandua Starch on Matrix Tablets for pH-Sensitive Release of Mesalamine.

Chemically modified mandua starch was successfully synthesized and applied to coat mesalamine-loaded matrix tablets. The coating material was an aqueous dispersion of mandua starch modified by sodium trimetaphosphate and sodium tripolyphosphate. To investigate the colon-targeting release competence, chemically modified mandua starch film-coated mesalamine tablets were produced using the wet granulation method followed by dip coating. The effect of the coating on the colon-targeted release of the resultant delivery system was inspected in healthy human volunteers and rabbits using roentgenography. The results show that drug release was controlled when the coating level was 10% w/w. The release percentage in the upper gastric phase (pH 1.2, simulated gastric fluid) was less than 6% and reached up to 59.51% w/w after 14 h in simulated colonic fluid. In addition to in vivo roentgenographic studies in healthy rabbits, human volunteer studies proved the colon targeting efficiency of the formulation. These results clearly demonstrated that chemically modified mandua starch has high effectiveness as a novel aqueous coating material for controlled release or colon targeting.

Indicator metrics and temporal aggregations introduce ambiguities in water scarcity estimates.

Water scarcity is a global challenge affecting billions of people worldwide. This study systematically assesses differences in the estimation of the global population exposed to water scarcity based on 7 water scarcity indicators and 11 Environmental Flow Requirements (EFR) evaluated at various spatial and temporal resolutions. All indicators show an increase in water scarcity since 1901. However, considering monthly average water scarcity estimates spatially aggregated at the basin scale found 35% less population exposed than estimates based on a distributed grid over the landscape. Estimates temporally disaggregated to consider water scarcity for at least one month a year found 50% (tenfold) larger population exposed compared to average monthly (annual) estimates. The study illustrates that estimates of the impacts of water scarcity are an artifact of how water scarcity is defined and calculated. This suggests caution is needed when relying on a single method and emphasizes the importance of considering the diversity of factors that can influence estimates of impact when assessing water scarcity.

Prevalence and correlates of cognitive impairment among an urban geriatric population of Haryana.

Background: Severe Cognitive Impairment (CI) is a major cause of disability and dependency among the elderly worldwide, and it has a significant impact not only on individuals but also on families, communities, and societies. Early identification and management of CI are critical in geriatric medicine. Prevalence data is often scarce, and this hinders the ground-level implementation of preventive health programs. Objectives: The objective was to find the prevalence of CI and its covariates among the urban geriatric population of Haryana. Materials and Methods: This was a community-based cross-sectional study conducted among 300 geriatric participants residing in an urban area of Rohtak district, Haryana. Hindi Mental State Examination (HMSE) tool was used to assess CI. Data were analyzed using IBM Corp, released 2020, IBM SPSS statistics for windows Ver 20, Armonk, NY. Results: The prevalence of geriatric CI was found to be 27.3% and was found to be significantly associated with age, female gender, scheduled and backward caste (BC), widowhood, and low educational status and is not engaged in any occupation, low socioeconomic status, teetotalism, economic dependency, physical dependency on others, and chronic morbidity. Conclusion: Age, female gender, scheduled and backward caste, widowhood, low educational status, nil employment status, low socioeconomic status, teetotalism, economic dependency, physical dependency on others, and chronic morbidity were found to be important correlates of CI. Further analytical studies can focus on these aspects for an early targeted preventive approach.

Can site-specific nutrient management improve the productivity and resource use efficiency of climate-resilient finger millet in calcareous soils in India?

Finger millet, an important 'Nutri-Cereal' and climate-resilient crop, is cultivated as a marginal crop in calcareous soils. Calcareous soils have low organic carbon content, high pH levels, and poor structure. Such a situation leads to poor productivity of the crop. Site-specific nutrient management (SSNM), which focuses on supplying optimum nutrients when a crop is needed, can ensure optimum production and improve the nutrient and energy use efficiency of crops. Moreover, developing an appropriate SSNM technique for this crop could offer new insights into nutrient management practices, particularly for calcareous soils. A field experiment was conducted during the rainy seasons of 2020 and 2021 in calcareous soil at Dr. Rajendra Prasad Central Agricultural University, Pusa, India. The experiment consisted of 8 treatments, viz. control, nitrogen (N)/phosphorus (P)/potassium (K)-omission, 75 %, 100 %, and 125 % recommended fertilizer dose (RFD), and 100 % recommended P and K + 30 kg ha-1 N as basal + rest N as per GreenSeeker readings. From this study, it was observed that the GreenSeeker-based SSNM resulted in the maximum grain yield (2873 kg ha-1), net output energy (96.3 GJ ha-1), and agronomic efficiency of N (30.6 kg kg-1), P (68.9 kg kg-1), and K (68.9 kg kg-1). The application of 125 % RFD resulted in ∼7 % lower yield than that under GreenSeeker-based nutrient management. Approximately 12 % greater energy use efficiency and 21-36 % greater nutrient use efficiency were recorded under GreenSeeker-based nutrient management than under 125 % RDF. The indigenous supplies of N, P, and K were found to be 14.31, 3.00, and 18.51 kg ha-1, respectively. Thus, 100 % of the recommended P and K + 30 kg ha-1 N as basal + rest N according to GreenSeeker readings can improve the yield, nutrient use efficiency, and energy balance of finger millet in calcareous soils.

A systematic review of risk factors and adverse outcomes associated with anterior cervical discectomy and fusion surgery over the past decade.

Background: Anterior cervical discectomy and fusion (ACDF) is one of the most frequently performed cervical surgeries in the world, yet there have been several reported complications. Objective: To determine the actual incidence of complications related to ACDF as well as any risk variables that may have been identified in earlier research. Methods: To evaluate the origin, presentation, natural history, and management of the risks and the complications, we conducted a thorough assessment of the pertinent literature. An evaluation of clinical trials and case studies of patients who experienced one or more complications following ACDF surgery was done using a PubMed, Cochrane Library, and Google Scholar search. Studies involving adult human subjects that were written in the English language and published between 2012 and 2022 were included in the search. The search yielded 79 studies meeting our criteria. Results: The overall rates of complications were as follows: Dysphagia 7.9%, psudarthrosis 5.8%, adjacent segment disease (ASD) 8.8%, esophageal perforations (EPs) 0.5%, graft or hardware failure 2.2%, infection 0.3%, recurrent laryngeal nerve palsy 1.7%, cerebrospinal fluid leak 0.8%, Horner syndrome 0.5%, hematoma 0.8%, and C5 palsy 1.9%. Conclusion: Results showed that dysphagia was a common postoperative sequelae with bone morphogenetic protein use and a higher number of surgical levels being the major risk factors. Pseudarthrosis rates varied depending on the factors such as asymptomatic radiographic graft sinking, neck pain, or radiculopathy necessitating revision surgery. The incidence of ASD indicated no data to support anterior cervical plating as more effective than standalone ACDF. EP was rare but frequently fatal, with no correlation found between patient age, sex, body mass index, operation time, or number of levels.

Upregulation of Neuroinflammation-Associated Genes in the Brain of SARS-CoV-2-Infected Mice.

Neurological manifestations are a significant complication of coronavirus disease 2019 (COVID-19), but the underlying mechanisms are yet to be understood. Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced neuroinvasion and encephalitis were observed in K18-hACE2 mice, leading to mortality. Our goal in this study was to gain insights into the molecular pathogenesis of neurological manifestations in this mouse model. To analyze differentially expressed genes (DEGs) in the brains of mice following SARS-CoV-2 infection, we performed NanoString gene expression analysis using three individual animal samples at 1, 3, and 6 days post-infection. We identified the DEGs by comparing them to animals that were not infected with the virus. We found that genes upregulated at day 6 post-infection were mainly associated with Toll-like receptor (TLR) signaling, RIG-I-like receptor (RLR) signaling, and cell death pathways. However, downregulated genes were associated with neurodegeneration and synaptic signaling pathways. In correlation with gene expression profiles, a multiplexed immunoassay showed the upregulation of multiple cytokines and chemokines involved in inflammation and cell death in SARS-CoV-2-infected brains. Furthermore, the pathway analysis of DEGs indicated a possible link between TLR2-mediated signaling pathways and neuroinflammation, as well as pyroptosis and necroptosis in the brain. In conclusion, our work demonstrates neuroinflammation-associated gene expression profiles, which can provide key insight into the severe disease observed in COVID-19 patients.

Steroid-Responsive Seronegative Immune-Mediated Necrotizing Myopathy Likely Triggered by Coxsackie B Virus: A Case Report.

Viral myositis can be mistaken for other types of myopathies, and the main causes of muscle damage are direct myotoxic effect and immune-mediated mechanisms. The biochemical parameters, electromyography (EMG), and muscle biopsy findings can be similar in viral myositis and idiopathic inflammatory myopathies. Viruses are rarely isolated from muscle biopsy specimens, so clinical evaluation and ancillary tests are necessary for a definitive diagnosis. Viral etiology is suspected when weakness occurs after a respiratory or gastrointestinal infection. Coxsackieviruses, particularly A9 and B5, can cause myositis and muscle necrosis. This is a case of a 47-year-old female with a history of alcoholic cirrhosis and a recent coxsackie B virus infection presented with weakness, numbness, and body pain. Creatine kinase levels were elevated but tests for extended myositis panel and antibodies were negative. A muscle biopsy revealed immune-mediated inflammatory myopathy. After a week without improvement, the patient received IV methylprednisolone followed by prednisone taper leading to improvement in symptoms. Prolonged myalgia has been observed in patients recovering from coxsackie A infections. The role of coxsackie B in causing myositis is still disputed and requires more reported data and guidelines. Clinicians should consider testing for coxsackie B as a potential cause of weakness. Awareness of potential complications like myositis can aid in effective patient management. More cases are needed to determine the significance of steroid use in managing coxsackie B-related muscle weakness.

Causality, Severity, Preventability and Predictability Assessments Scales for Adverse Drug Reactions: A Review.

The pharmacovigilance program of India (PvPI), after its inception, has been reliably acquiring force in bringing issues to light among the masses, healthcare professionals, the pharma industry, and clinical staff at hospitals. Adverse drug reactions are unintended events that occur after exposure to a drug, biological product, or medical device, and they may result in morbidity and mortality. It is critical to monitor the safety of drugs during the post-marketing phase to find long-term and rare ADRs, as well as ADRs in special populations and patients with co-morbidities that are not usually included during clinical trials. The definitive objective of pharmacovigilance is to collate data and analyze it. Assessing the causality between ADRs and drugs is necessary to decrease the occurrence of ADRs and to reduce the risk of drug-related ADRs. ADRs may lead to increased morbidity, increased hospital stays, and increased cost of treatment, resulting in compromised patient safety. Causality assessment is the evaluation of the likelihood that a particular treatment is the cause of an observed adverse event and establishing a causal association between a drug and a drug reaction is necessary to prevent further recurrences. Numerous methods available for establishing a causal association between the drug and adverse events have been broadly classified into clinical judgment or global introspection, algorithms, and probabilistic methods. These include the Swedish method, World Health Organization-Uppsala Monitoring Centre (WHO-UMC) scale, Naranjo's algorithm, Kramer algorithm, Jones algorithm, Karch algorithm, Bégaud algorithm, Adverse Drug Reactions Advisory Committee guidelines, Bayesian Adverse Reaction Diagnostic Instrument, and so on. Despite various methods available, none of the causality assessment tools have been universally accepted as the gold standard. Naranjo's algorithm and WHO-UMC scales are, however, the most commonly used. Similarly, for preventability and severity assessment of ADRs, the Schumock and Thornton scale and Hartwig and Siegel's scale are most commonly used. Hence, we reviewed different tools and methods available to assess the causality, preventability, and severity of ADRs.

mRNA-encoded Cas13 can be used to treat dengue infections in mice.

Dengue is a major global health threat, and there are no approved antiviral agents. Prior research using Cas13 only demonstrated dengue mitigation in vitro. Here we demonstrate that systemic delivery of mRNA-encoded Cas13a and guide RNAs formulated in lipid nanoparticles can be used to treat dengue virus (DENV) 2 and 3 in mice. First, we identified guides against DENV 2 and 3 that demonstrated in vitro efficacy. Next, we confirmed that Cas13 enzymatic activity is necessary for DENV 2 or DENV 3 mitigation in vitro. Last, we show that a single dose of lipid-nanoparticle-formulated mRNA-encoded Cas13a and guide RNA, administered 1 day post-infection, promotes survival of all infected animals and serum viral titre decreases on days 2 and 3 post-infection after lethal challenge in mice. Off-target analysis in mice using RNA sequencing showed no collateral cleavage. Overall, these data demonstrate the potential of mRNA-encoded Cas13 as a pan-DENV drug.

Incidence, management and outcomes in hepatic artery complications after paediatric liver transplantation: protocol of the retrospective, international, multicentre HEPATIC Registry.

INTRODUCTION: Hepatic artery complications (HACs), such as a thrombosis or stenosis, are serious causes of morbidity and mortality after paediatric liver transplantation (LT). This study will investigate the incidence, current management practices and outcomes in paediatric patients with HAC after LT, including early and late complications. METHODS AND ANALYSIS: The HEPatic Artery stenosis and Thrombosis after liver transplantation In Children (HEPATIC) Registry is an international, retrospective, multicentre, observational study. Any paediatric patient diagnosed with HAC and treated for HAC (at age <18 years) after paediatric LT within a 20-year time period will be included. The primary outcomes are graft and patient survivals. The secondary outcomes are technical success of the intervention, primary and secondary patency after HAC intervention, intraprocedural and postprocedural complications, description of current management practices, and incidence of HAC. ETHICS AND DISSEMINATION: All participating sites will obtain local ethical approval and (waiver of) informed consent following the regulations on the conduct of observational clinical studies. The results will be disseminated through scientific presentations at conferences and through publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: The HEPATIC registry is registered at the ClinicalTrials.gov website; Registry Identifier: NCT05818644.

High performance Pt-anchored MoS2based chemiresistive ascorbic acid sensor.

Ascorbic acid (AA), known as vitamin C, is a vital bioactive compound that plays a crucial role in several metabolic processes, including the synthesis of collagen and neurotransmitters, the removal of harmful free radicals, and the uptake of iron by cells in the human intestines. As a result, there is an absolute need for a highly selective, sensitive, and economically viable sensing platform for AA detection. Herein, we demonstrate a Pt-decorated MoS2for efficient detection of an AA biosensor. MoS2hollow rectangular structures were synthesized using an easy and inexpensive chemical vapor deposition approach to meet the increasing need for a reliable detection platform. The synthesized MoS2hollow rectangular structures are characterized through field effect scanning electron microscopy (FESEM), energy-dispersive spectroscopy elemental mapping, Raman spectroscopy, and x-ray photoelectron spectroscopy. We fabricate a chemiresistive biosensor based on Pt-decorated MoS2that measures AA with great precision and high sensitivity. The experiments were designed to evaluate the response of the Pt-decorated MoS2biosensor in the presence and absence of AA, and selectivity was evaluated for a variety of biomolecules, and it was observed to be very selective towards AA. The Pt-MoS2device had a higher response of 125% against 1 mM concentration of AA biomolecules, when compared to that of all other devices and 2.2 times higher than that of the pristine MoS2device. The outcomes of this study demonstrate the efficacy of Pt-decorated MoS2as a promising material for AA detection. This research contributes to the ongoing efforts to enhance our capabilities in monitoring and detecting AA, fostering advancements in environmental, biomedical, and industrial applications.

Hot Carrier Nanowire Transistors at the Ballistic Limit.

We demonstrate experimentally nonequilibrium transport in unipolar quasi-1D hot electron devices reaching the ballistic limit at room temperature. The devices are realized with heterostructure engineering in nanowires to obtain dopant- and dislocation-free 1D-epitaxy and flexible bandgap engineering. We show experimentally the control of hot electron injection with a graded conduction band profile and the subsequent filtering of hot and relaxed electrons with rectangular energy barriers. The number of electrons passing the barrier depends exponentially on the transport length with a mean-free path of 200-260 nm, and the electrons reach the ballistic transport regime for the shortest devices with 70% of the electrons flying freely through the base electrode and the barrier reflections limiting the transport to the collector.