Genetic dissection of value-added quality traits and agronomic parameters through genome-wide association mapping in bread wheat (T. aestivum L.).

Bread wheat (T. aestivum) is one of the world's most widely consumed cereals. Since micronutrient deficiencies are becoming more common among people who primarily depend upon cereal-based diets, a need for better-quality wheat varieties has been felt. An association panel of 154 T. aestivum lines was evaluated for the following quality traits: grain appearance (GA) score, grain hardness (GH), phenol reaction (PR) score, protein percent, sodium dodecyl sulfate (SDS) sedimentation value, and test weight (TWt). In addition, the panel was also phenotyped for grain yield and related traits such as days to heading, days to maturity, plant height, and thousand kernel weight for the year 2017-18 at the Borlaug Institute for South Asia (BISA) Ludhiana and Jabalpur sites. We performed a genome-wide association analysis on this panel using 18,351 genotyping-by-sequencing (GBS) markers to find marker-trait associations for quality and grain yield-related traits. We detected 55 single nucleotide polymorphism (SNP) marker trait associations (MTAs) for quality-related traits on chromosomes 7B (10), 1A (9), 2A (8), 3B (6), 2B (5), 7A (4), and 1B (3), with 3A, 4A, and 6D, having two and the rest, 4B, 5A, 5B, and 1D, having one each. Additionally, 20 SNP MTAs were detected for yield-related traits based on a field experiment conducted in Ludhiana on 7D (4) and 4D (3) chromosomes, while 44 SNP MTAs were reported for Jabalpur on chromosomes 2D (6), 7A (5), 2A (4), and 4A (4). Utilizing these loci in marker-assisted selection will benefit from further validation studies for these loci to improve hexaploid wheat for better yield and grain quality.

Outcome of COVID-19 infection in patients on antihypertensives: A cross-sectional study.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) infection frequently have hypertension as a co-morbidity, which is linked to adverse outcomes. Antihypertensives may affect the outcome of COVID-19 infection. AIM: To assess the effects of antihypertensive agents on the outcomes of COVID-19 infection. METHODS: A total of 260 patients were included, and their demographic data and clinical profile were documented. The patients were categorized into nonhypertensive, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB), calcium channel blocker (CCB), a combination of ACEI/ARB and CCB, and beta-blocker groups. Biochemical, hematological, and inflammatory markers were measured. The severity of infection, intensive care unit (ICU) intervention, and outcome were recorded. RESULTS: The mean age of patients was approximately 60-years-old in all groups, except the nonhypertensive group. Men were predominant in all groups. Fever was the most common presenting symptom. Acute respiratory distress syndrome was the most common complication, and was mostly found in the CCB group. Critical cases, ICU intervention, and mortality were also higher in the CCB group. Multivariable logistic regression analysis revealed that age, duration of antihypertensive therapy, erythrocyte sedimentation rate, high-sensitivity C-reactive protein, and interleukin 6 were significantly associated with mortality. The duration of antihypertensive therapy exhibited a sensitivity of 70.8% and specificity of 55.7%, with a cut-off value of 4.5 years and an area under the curve of 0.670 (0.574-0.767; 95% confidence interval) for COVID-19 outcome. CONCLUSION: The type of antihypertensive medication has no impact on the clinical sequence or mortality of patients with COVID-19 infection. However, the duration of antihypertensive therapy is associated with poor outcomes.

Transmethylation and Oxidative Biomarkers in Children with Autism Spectrum Disorder: A Cross Sectional Study.

We aimed to investigate the potential role of biomarkers of transmethylation, oxidative stress, and mitochondrial dysfunction in children with Autism Spectrum Disorder (ASD) by comparing them with that of typically developing children (TDC) controls. We also tried to correlate them with severity of autism, sensory issues, behavioural comorbidities and developmental quotients 119 with ASD and 52 age and sex matched typically developing children (TDC) controls were enrolled excluding those with chronic-illness or on any antioxidant therapy/multivitamins/anti-epileptic drugs. Median levels of biomarkers - serum homocysteine, cysteine, methionine, urine uric acid-to-creatinine ratio, arterial lactate, serum vitamin E, vitamin B12, folate, Nε-carboxymethyllysine, Nω- carboxymethylarginine (CMA), dityrosine and MTHFR C677T polymorphism were calculated. Children with ASD were further characterised using Childhood Autism Rating Scale-2, Childhood behavioural checklist, child sensory profile 2 caregiver questionnaire, Developmental Profile 3 for any correlation with the various biomarker levels. The median level of serum homocysteine in ASD group was 9 µmol/L(Range, 7- 16µmol/L), which was significantly higher than controls 7 µmol/L(Range, 4- 11µmol/L)(p=0.01). The prevalence of hyper-homocystinemia(>15µmol/L) was 13.4% in ASD as compared to 3.8% in controls with a significant difference(p=0.04). Dityrosine level was higher among ASD children when compared to TDC (9.8 vs 2.2 counts per second(cps), p<0.001). No significant correlation was found between prevalence of hyperhomocysteinemia and severity of autism/DQ/behavioural issues. No significant difference was found between the median levels of other biomarkers. Results support possible role of transmethylation defects and oxidative stress in ASD pathogenesis. Further studies are warranted for a better understanding of ASD pathogenesis.

Thanatin: A Promising Antimicrobial Peptide Targeting the Achilles' Heel of Multidrug-Resistant Bacteria.

Antimicrobial resistance poses an escalating threat to human health, necessitating the development of novel antimicrobial agents capable of addressing challenges posed by antibiotic-resistant bacteria. Thanatin, a 21-amino acid ß-hairpin insect antimicrobial peptide featuring a single disulfide bond, exhibits broad-spectrum antibacterial activity, particularly effective against multidrug-resistant strains. The outer membrane biosynthesis system is recognized as a critical vulnerability in antibiotic-resistant bacteria, which thanatin targets to exert its antimicrobial effects. This peptide holds significant promise for diverse applications. This review begins with an examination of the structure-activity relationship and synthesis methods of thanatin. Subsequently, it explores thanatin's antimicrobial activity, detailing its various mechanisms of action. Finally, it discusses prospective clinical, environmental, food, and agricultural applications of thanatin, offering valuable insights for future research endeavors.

SCN1A rs6732655A/T polymorphism: Diagnostic and therapeutic insights for drug-resistant epilepsy.

BACKGROUND: A significant subset of individuals with epilepsy fails to respond to currently available antiepileptic drugs, resulting in heightened mortality rates, psychosocial challenges, and a diminished quality of life. Genetic factors, particularly within the SCN1A gene, and the pro-inflammatory cytokine response is important in intricating the drug resistance in idiopathic epilepsy cases. In this extended study, we determined the correlation of rs6732655A/T single nucleotide polymorphism to understand the causative association of SCN1A gene with epilepsy drug resistance and inflammatory response. AIM: To find the correlation of SCN1A gene rs6732655A/T polymorphism with the drug-resistant epilepsy and inflammatory response. METHODS: The study enrolled 100 age and sex-matched patients of both drug-resistant and drug-responsive epilepsy cases. We analysed the rs6732655A/T polymorphism to study its association and causative role in drug-resistant epilepsy cases using restriction fragment length polymorphism technique. The diagnostic performance of interleukin (IL)-1ß, IL-6, and high mobility group box 1 (HMGB1) protein levels was evaluated in conjunction with genotypic outcome receiver operating characteristic analysis. RESULTS: AT and AA genotypes of rs6732655 SCN1A gene polymorphism were associated with higher risk of drug resistance epilepsy. Serum biomarkers IL-6, IL1ß and HMGB1 demonstrated diagnostic potential, with cutoff values of 4.63 pg/mL, 59.52 pg/mL and 7.99 ng/mL, respectively, offering valuable tools for epilepsy management. Moreover, specific genotypes (AA and AT) were found to be linked to the elevated levels of IL-1ß and IL-6 and potentially reflecting increased oxidative stress and neuro-inflammation in drug-resistant cases supporting the previous reported outcome of high inflammatory markers response in drug resistance epilepsy. CONCLUSION: SCN1A genotypes AA and AT are linked to higher drug-resistant epilepsy risk. These findings underscore the potential influence of inflammation and genetics on epilepsy treatment resistance.

Urinary biomarkers NG AL and beta-2 microglobulin in children with type 1 diabetes mellitus.

OBJECTIVES: To study the urinary neutrophil gelatinase-associated lipocalin (NGAL) and beta-2-microglobulin (ß2M) levels as markers of tubular damage in children with type 1 diabetes (T1DM). METHODS: Forty T1DM children and 40 age-matched controls were enrolled. Subjects with coexisting kidney disorder, intake of oral glucose lowering drugs and syndromic diabetes mellitus were excluded. Fasting plasma glucose, glycated hemoglobin (HbA1c), kidney function, urinary albumin-creatinine ratio (UACR), NGAL and ß2M were measured and compared in cases and controls. RESULTS: The median (IQR) age of cases and controls was 10.6 (8, 14.2) and 10.7 (8.4, 13.7) years, respectively. Cases had disease duration of 4 (3, 6.8) years and HbA1c 10.9 (9, 13.1) %. Microalbuminuria was seen in 14 (35 %). Median (IQR) levels of UACR were higher in cases than controls [19.38 (10.27, 35.26) and 6.49 (3.10, 11.65) µg/mg; p<0.001], similarly NGAL/creatinine [352.21 (191.49, 572.45) and 190.54 (125.91, 322.83) ng/mg; p=0.006], unlike ß2M/creatinine [1.7 (0.43, 6.02) and 2.12 (1.05, 4.47) µg/mg; p=0.637]. Children with higher HbA1c (≥10 %) had higher urinary ACR and tubular biomarkers than HbA1c<10 % (p>0.05). Urinary ACR showed positive correlation with NGAL/creatinine (r=0.38, p=0.019) and ß2M/creatinine (r=0.42, p=0.009). CONCLUSIONS: Urinary biomarkers NGAL and ß2M were elevated in the presence of normal urinary microalbumin levels suggestive of early tubular damage in T1DM.

Association between seated trunk control and cortical sensorimotor white matter brain changes in patients with chronic low back pain.

Trunk control involves integration of sensorimotor information in the brain. Individuals with chronic low back pain (cLBP) have impaired trunk control and show differences in brain structure and function in sensorimotor areas compared with healthy controls (HC). However, the relationship between brain structure and trunk control in this group is not well understood. This cross-sectional study aimed to compare seated trunk control and sensorimotor white matter (WM) structure in people with cLBP and HC and explore relationships between WM properties and trunk control in each group. Thirty-two people with cLBP and 35 HC were tested sitting on an unstable chair to isolate trunk control; performance was measured using the 95% confidence ellipse area (CEA95) of center-of-pressure tracing. A WM network between cortical sensorimotor regions of interest was derived using probabilistic tractography. WM microstructure and anatomical connectivity between cortical sensorimotor regions were assessed. A mixed-model ANOVA showed that people with cLBP had worse trunk control than HC (F = 12.96; p < .001; ηp2 = .091). There were no differences in WM microstructure or anatomical connectivity between groups (p = 0.564 to 0.940). In the cLBP group, WM microstructure was moderately correlated (|r| = .456 to .565; p ≤ .009) with trunk control. Additionally, the cLBP group demonstrated stronger relationships between anatomical connectivity and trunk control (|r| = .377 to .618 p < .034) compared to the HC group. Unique to the cLBP group, WM connectivity between right somatosensory and left motor areas highlights the importance of interhemispheric information exchange for trunk control. Parietal areas associated with attention and spatial reference frames were also relevant to trunk control. These findings suggest that people with cLBP adopt a more cortically driven sensorimotor integration strategy for trunk control. Future research should replicate these findings and identify interventions to effectively modulate this strategy.

Emerging Role of Functional Magnetic Resonance Spectroscopy (MRS) to Monitor Response to Kinase Inhibitors in Cancer.

Inhibitors of kinases involved in signaling and other intracellular pathways, have revolutionized cancer treatment by providing highly targeted and effective therapies. However, timely monitoring treatment response remains a considerable challenge since conventional methods such as assessing changes in tumor volume do not adequately capture early responses or resistance development, due to the predominantly cytostatic rather than cytotoxic effect of kinase inhibitors. Magnetic resonance spectroscopy (MRS) is a non-invasive imaging technique that can provide insights into cellular metabolism by detecting changes in metabolite concentrations. By measuring metabolite levels, MRS offers a means to assess treatment response in real-time, providing earlier indications of efficacy or resistance compared to conventional imaging modalities. Bruton's Tyrosine Kinase (BTK) is a critical enzyme involved in B-cell receptor signaling. BTK inhibitors have been approved for the treatment of Mantle Cell Lymphoma (MCL) and other B-cell malignancies. Recent studies involving genome-scale gene expression, metabolomic, and fluxomic analyses have demonstrated that ibrutinib, an index BTK inhibitor, profoundly affects the key metabolic pathways in MCL cells., including glycolysis, glutaminolysis, pentose shunt, TCA cycle and phospholipid metabolism. Importantly, the effects of ibrutinib on MCL cells directly and proportionately correlates with their sensitivity to the drug. Consequently, changes in specific metabolite concentrations detectable non-invasively by MRS such as lactate and alanine reflecting mostly the status of cellular glycolysis and glutaminolysis, respectively, have emerged as potential biomarkers for predicting response and resistance of MCL cells to BTK inhibition, both in vitro and in vivo. Preparations to validate the utility of these biomarkers in clinical setting are under way. These studies may pave the way to monitor therapeutic response to kinase inhibitors also in other types of cancer.

Advances in microbial based bio-inoculum for amelioration of soil health and sustainable crop production.

The adoption of sustainable agricultural practices is increasingly imperative in addressing global food security and environmental concerns, with microbial based bio-inoculums emerging as a promising approach for nurturing soil health and fostering sustainable crop production.This review article explores the potential of microbial based bio-inoculumsor biofertilizers as a transformative approach toenhance plant disease resistance and growth. It explores the commercial prospects of biofertilizers, highlighting their role in addressing environmental concerns associated with conventional fertilizers while meeting the growing demand for eco-friendly agricultural practices. Additionally, this review discusses the future prospects of biofertilizers, emphasizing the ongoing advancements in biotechnology and formulation techniques that are expected to enhance their efficacy and applicability. Furthermore, this article provides insights into strategies for the successful acceptance of biofertilizers among farmers, including the importance of quality control, assurance, and education initiatives to raise awareness about their benefits and overcome barriers to adoption. By synthesizing the current research findings and industrial developments, this review offers valuable guidance for stakeholders seeking to exploit the potential of biofertilizers or beneficial microbes to promote soil health, ensure sustainable crop production, and addressing the challenges of modern agriculture.

Mining and multifaceted applications of phage lysin for combatting Vibrio parahaemolyticus.

Vibrio parahaemolyticus, a prevalent foodborne pathogen found in both water and seafood, poses substantial risks to public health. The conventional countermeasure, antibiotics, has exacerbated the issue of antibiotic resistance, increasing the difficulty of controlling this bacterium. Phage lysins, as naturally occurring active proteins, offer a safe and reliable strategy to mitigate the impact of V. parahaemolyticus on public health. However, there is currently a research gap concerning bacteriophage lysins specific to Vibrio species. To address this, our study innovatively and systematically evaluates 37 phage lysins sourced from the NCBI database, revealing a diverse array of conserved domains and notable variations in similarity among Vibrio phage lysins. Three lysins, including Lyz_V_pgrp, Lyz_V_prgp60, and Lyz_V_zlis, were successfully expressed and purified. Optimal enzymatic activity was observed at 45℃, 800 mM NaCl, and pH 8-10, with significant enhancements noted in the presence of 1 mM membrane permeabilizers such as EDTA or organic acids. These lysins demonstrated effective inhibition against 63 V. parahaemolyticus isolates from clinical, food, and environmental sources, including the reversal of partial resistance, synergistic interactions with antibiotics, and disruption of biofilms. Flow cytometry analyses revealed that the combination of Lyz_V_pgp60 and gentamicin markedly increased bacterial killing rates. Notably, Lyz_V_pgrp, Lyz_V_pgp60, and Lyz_V_zlis exhibited highly efficient biofilm hydrolysis, clearing over 90 % of preformed V. parahaemolyticus biofilms within 48 h. Moreover, these lysins significantly reduced bacterial loads in various food samples and environmental sources, with reductions averaging between 1.06 and 1.29 Log CFU/cm2 on surfaces such as stainless-steel and bamboo cutting boards and approximately 0.87 CFU/mL in lake water and sediment samples. These findings underscore the exceptional efficacy and versatile application potential of phage lysins, offering a promising avenue for controlling V. parahaemolyticus contamination in both food and environmental contexts.

A rare biofilm dispersion strategy demonstrated by Staphylococcus aureus under oxacillin stress.

Staphylococcus aureus (S. aureus), a versatile Gram-positive bacterium, is implicated in a spectrum of infections, and its resilience is often attributed to biofilm formation. This study investigates the effect of sub-inhibitory doses of oxacillin on biofilm formation by methicillin-resistant S. aureus (MRSA). Specifically, it examines how these doses influence biofilms' development, maturation, and dispersal. The biofilm's zenith reached 48 h of incubation, followed by a noteworthy decline at 96 h and a distinctive clearance zone around biofilm-positive cells exposed to oxacillin. Scanning electron micrographs unveiled an intriguing active biofilm dispersal mechanism, a rarity in this species. Among 180 isolates, only three carrying the elusive icaD gene exhibited this phenomenon. icaD gene was absent in their counterparts. Notably, the icaD gene emerges as a distinctive marker, crucial in regulating biofilm dispersion and setting these isolates apart. The captivating interplay of oxacillin, biofilm dynamics, and genetic signatures disintegrate novel dimensions in understanding MRSA's adaptive strategies and underscores the importance of the icaD gene in engineering biofilm resilience.

Successful Kidney Transplant from Donors with Sickle Cell Disease: A Case Series of Six Transplants.

People with sickle cell disease experience a high incidence of chronic kidney disease and end-stage kidney disease, secondary to tubular and glomerular effects of vaso-occlusion-induced hypoxia. Because of concerns of suboptimal kidney function, sickle cell donors are usually not considered for kidney donation, even if the rest of the parameters are acceptable for organ donation. A significant gap exists between the number of organ donors and the number of candidates waiting for a kidney transplant in the United States. To bridge the gap, we need to consider using nontraditional donors. We report kidney transplant outcomes in 6 recipients from 4 sickle cell kidney donors. Intracranial hemorrhage and sepsis were the causes of the death in donors, and no donor was in sickle cell crisis at the time of donation. None of the recipients experienced delayed graft function, and all recipients achieved excellent allograft function. The earliest allograft failure was at 27 months in a recipient who developed early acute rejection, while the longest follow-up was 10 years with adequate kidney function. In conclusion, given the shortage of kidneys for transplantation and demonstrated good outcomes, we propose that kidneys from sickle cell donors can be safely used.

RT-PCR Result of SARS-CoV-2 Viral RNA in Cadavers and Viral Transmission Risk to Handlers.

During the onset of the pandemic, a common research question was asked by the hospital staff, and family members who were handling COVID-19-infected cadavers, "does COVID-19-positive dead body harbor SARS-CoV-2 viral RNA?" Several research findings were reported but due to the lack of proper research findings, the question remained unanswered. The present study was planned to observe the virus transmission risk from cadavers to the handlers. A pilot study was conducted on 54 cadavers who died in COVID-ICU (SARS-CoV-2-positive diagnosed by RT-PCR) during 2021-2022. Skin swab sample from 54 dead bodies and 54 glove samples of handlers were taken within 1 hour of death for the RT-PCR test. Viability results from RT-PCR show that the infection risk was 50% in cadavers, whereas the transmission risk to handlers while handling was 7%, which is minimal. The SARS-CoV-2 viability was high in cases of those died after a long time of infection. Based on the RT-PCR result and data analysis the interpretation of the study was that the SARS-CoV-2 transmission risk from dead bodies to the handlers is minimal but the SARS-CoV-2 viability persists in the cadavers. This fact is helpful for the people who will conduct funeral activities, autopsy staff, and hospital staff handling dead bodies. How to cite this article: Panda B, Singh N, Singh G, Patro ARK, Mohanty AP, Patnaik PK, et al. RT-PCR Result of SARS-CoV-2 Viral RNA in Cadavers and Viral Transmission Risk to Handlers. Indian J Crit Care Med 2024;28(6):614-616.

Author Response: Beyond the Nasal Prongs: A Joust of Oxygen Delivery Methods in Post-op Hypoxemia.

How to cite this article: Mishra S, Kothari N, Sharma A, Goyal S, Rathod DK, Meshram T, et al. Author Response: Beyond the Nasal Prongs: A Joust of Oxygen Delivery Methods in Post-op Hypoxemia. Indian J Crit Care Med 2024;28(6):626-627.

Current Applications of Artificial Intelligence in Billing Practices and Clinical Plastic Surgery.

Integration of artificial intelligence (AI), specifically with natural language processing and machine learning, holds tremendous potential to enhance both clinical practices and administrative workflows within plastic surgery. AI has been applied to various aspects of patient care in plastic surgery, including postoperative free flap monitoring, evaluating preoperative risk assessments, and analyzing clinical documentation. Previous studies have demonstrated the ability to interpret current procedural terminology codes from clinical documentation using natural language processing. Various automated medical billing companies have used AI to improve the revenue management cycle at hospitals nationwide. Additionally, AI has been piloted by insurance companies to streamline the prior authorization process. AI implementation holds potential to enhance billing practices and maximize healthcare revenue for practicing physicians.

Impact of therapeutic inhibition of oncogenic cell signaling tyrosine kinase on cell metabolism: in vivo-detectable metabolic biomarkers of inhibition.

BACKGROUND: Inhibition of kinases is the ever-expanding therapeutic approach to various types of cancer. Typically, assessment of the treatment response is accomplished by standard, volumetric imaging procedures, performed weeks to months after the onset of treatment, given the predominantly cytostatic nature of the kinase inhibitors, at least when used as single agents. Therefore, there is a great clinical need to develop new monitoring approaches to detect the response to kinase inhibition much more promptly. Noninvasive 1H magnetic resonance spectroscopy (MRS) can measure in vitro and in vivo concentration of key metabolites which may potentially serve as biomarkers of response to kinase inhibition. METHODS: We employed mantle cell lymphoma (MCL) cell lines demonstrating markedly diverse sensitivity of inhibition of Bruton's tyrosine kinase (BTK) regarding their growth and studied in-depth effects of the inhibition on various aspects of cell metabolism including metabolite synthesis using metabolomics, glucose and oxidative metabolism by Seahorse XF technology, and concentration of index metabolites lactate, alanine, total choline and taurine by 1H MRS. RESULTS: Effective BTK inhibition profoundly suppressed key cell metabolic pathways, foremost pyrimidine and purine synthesis, the citrate (TCA) cycle, glycolysis, and pyruvate and glutamine/alanine metabolism. It also inhibited glycolysis and amino acid-related oxidative metabolism. Finally, it profoundly and quickly decreased concentration of lactate (a product of mainly glycolysis) and alanine (an indicator of amino acid metabolism) and, less universally total choline both in vitro and in vivo, in the MCL xenotransplant model. The decrease correlated directly with the degree of inhibition of lymphoma cell expansion and tumor growth. CONCLUSIONS: Our results indicate that BTK inhibition exerts a broad and profound suppressive effect on cell metabolism and that the affected index metabolites such as lactate, alanine may serve as early, sensitive, and reliable biomarkers of inhibition in lymphoma patients detectable by noninvasive MRS-based imaging method. This kind of imaging-based detection may also be applicable to other kinase inhibitors, as well as diverse lymphoid and non-lymphoid malignancies.

Structural Heart Imaging Using 3-Dimensional Intracardiac Echocardiography: JACC Cardiovascular Imaging Position Statement.

3-dimensional (3D) intracardiac echocardiography (ICE) is emerging as a promising complement and potential alternative to transesophageal echocardiography for imaging guidance in structural heart interventions. To establish standardized practices, our multidisciplinary expert position statement serves as a comprehensive guide for the appropriate indications and utilization of 3D-ICE in various structural heart procedures. The paper covers essential aspects such as the fundamentals of 3D-ICE imaging, basic views, and workflow recommendations specifically tailored for ICE-guided structural heart procedures, such as transeptal puncture, device closure of intracardiac structures, and transcatheter mitral and tricuspid valve interventions. Current challenges, future directions, and training requirements to ensure operator proficiency are also discussed, thereby promoting the safety and efficacy of this innovative imaging modality to support expanding its future clinical applications.