Circular economical approach of extracting nanocarbons from waste pea peel for sensing of p-nitrophenol and its conversion into paracetamol.

An important paradigm shift towards the circular economy is to prioritize waste prevention, reuse, recycling, and recovery before disposal is necessary. In this context, a sustainable protocol of converting waste pea peel (wPP) into low-cost carbon nanomaterials for sensing and conversion of p-nitrophenol (p-NP) into value-added paracetamol is being reported. Two fractions of the carbonaceous nanomaterials were obtained after the hydrothermal treatment (HT) of wPP, firstly an aqueous portion containing water-soluble carbon dots (wPP-CDs) and a solid residue, which was converted into carbonized biochar (wPP-BC). Blue-colored fluorescent wPP-CDs displayed excitation-dependent and pH-independent properties with a quantum yield (QY) of 8.82 %, which were exploited for the fluorescence sensing of p-NP with 4.20 µM limit of detection. Pyrolyzed biochar acting as an efficient catalyst effectively reduces p-NP to p-aminophenol (p-AP) in just 16 min with a 0.237 min-1 rate of conversion. Furthermore, the produced p-AP was converted into paracetamol, an analgesic and antipyretic drug, to achieve zero waste theory. Thus, this study provides the execution of sustainable approaches based on the integral valorization of biowaste that can be further recycled and reused, offering an effective way to attain a profitable circular economy.

Upper Esophageal Sphincter and Esophageal Motility Pathology on Manometry in Retrograde Cricopharyngeal Dysfunction.

OBJECTIVE: There exists a paucity of data regarding the mechanism and manometric findings in retrograde cricopharyngeal dysfunction (RCPD). In this study, we aimed to compare esophageal physiologic findings between patients with RCPD compared to an asymptomatic cohort. STUDY DESIGN: Case-control study. SETTING: Tertiary Care Center. METHODS: Esophageal high-resolution impedance manometry was completed preoperatively in patients diagnosed with RCPD. Manometric data were compared between the RCPD and asymptomatic cohorts. A 2:1 age-sex-matched asymptomatic cohort was used as the control group. Treatment response was assessed among the RCPD cohort. RESULTS: Thirty-nine patients are included: 13 RCPD [mean age: 31.1 (SD: 12.6) years, female sex: 11 (85%)] and 26 asymptomatic [mean age: 32.1 (SD: 1.5) years, female sex: 22 (85%)]. The RCPD cohort, compared to the asymptomatic cohort, exhibited significantly greater upper esophageal sphincter (UES) length [4.5 (SD: 0.7) vs 3.7 (0.9) cm, P = .01] and higher UES basal pressures [91.9 (35.0) vs 49.7 (25.5) mm Hg, P = .002]. Patients with RCPD demonstrated higher rates of ineffective swallows [70.0% (31.6%) vs 15.4% (21.6%), P < .001] and incomplete bolus clearance [81% (22.0%) vs 21.8% (30.0%), P < .001]. All patients who underwent cricopharyngeal botulinum injections experienced initial improvement of symptoms with 3 patients requiring repeat intervention. CONCLUSION: RCPD is associated with a longer UES, elevated UES basal pressures, and an increased incidence of ineffective esophageal motility. This study is the first to compare preoperative manometry results among patients with RCPD to those of an asymptomatic cohort, providing insights into the mechanism of RCPD.

Meta-QTL and ortho analysis unravels the genetic architecture and key candidate genes for cold tolerance at seedling stage in rice.

Rice, a critical cereal crop, grapples with productivity challenges due to its inherent sensitivity to low temperatures, primarily during the seedling and booting stages. Recognizing the polygenic complexity of cold stress signaling in rice, a meta-analysis was undertaken, focusing on 20 physiological traits integral to cold tolerance. This initiative allowed the consolidation of genetic data from 242 QTLs into 58 meta-QTLs, thereby significantly constricting the genetic and physical intervals, with 84% of meta-QTLs (MQTLs) being reduced to less than 2 Mb. The list of 10,505 genes within these MQTLs, was further refined utilizing expression datasets to pinpoint 46 pivotal genes exhibiting noteworthy differential regulation during cold stress. The study underscored the presence of several TFs such as WRKY, NAC, CBF/DREB, MYB, and bHLH, known for their roles in cold stress response. Further, ortho-analysis involving maize, barley, and Arabidopsis identified OsWRKY71, among others, as a prospective candidate for enhancing cold tolerance in diverse crop plants. In conclusion, our study delineates the intricate genetic architecture underpinning cold tolerance in rice and propounds significant candidate genes, offering crucial insights for further research and breeding strategies focused on fortifying crops against cold stress, thereby bolstering global food resilience. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01412-1.

Genome-wide association study (GWAS) identified PCOS susceptibility variants and replicates reported risk variants.

BACKGROUND: Genetic predisposition and environmental factors are considered risk factors for polycystic ovary syndrome (PCOS). Genome-wide association studies (GWAS) have been reported from various subpopulations to evaluate SNPs associated with PCOS risk. No PCOS-associated GWAS study has been reported from India so far. PURPOSE: The current study was conducted to identify the PCOS-susceptible loci among the North Indian population and to validate the significant loci reported by previous GWAS studies. METHODS: A total of 272 participants with 134 PCOS patients and 138 age-matched healthy controls were recruited. Genomic DNA was isolated and genotyped by using Infinium Global Screening Array v3.0 microchip considering HWE 10e-5 statistically significant. RESULTS: A total of fifteen markers have been identified as candidate PCOS risk factors. Only two SNPs, namely rs17186366 and rs11171739 have been identified through replication analysis while comparing the previously reported PCOS GWAS data. In-silico analysis was performed to study the functional impact of identified significant genes for gene ontology, pathways related to gene set, and cluster analysis to determine protein-protein interaction among genes or gene products. CONCLUSION: The study suggests that multiple variants play an important role in PCOS pathogenesis and emphasizes the importance of further genetic studies among Indian subpopulations. The study also validates two previously reported SNPs in the Indian population. What this study adds to clinical work Study summarizes the importance of candidate gene markers validated by replication and in-silico functional study, significantly involved in PCOS pathogenesis in the studied population. These markers can be used in the future as diagnostic markers for clinical phenotype identification.

Monitoring thyroid function during amiodarone use.

Amiodarone is an antiarrhythmic drug used to treat cardiac tachyarrhythmias. It has many adverse effects, with thyroid dysfunction one of the most notable. Through various mechanisms, both thyrotoxicosis and hypothyroidism can occur secondary to amiodarone therapy. There are two types of amiodarone-induced thyrotoxicosis: type 1 occurs in those with pre-existing thyroid disease and is treated with thionamide, whereas type 2 occurs in those without and is treated with glucocorticoids. Patients with amiodarone-induced hypothyroidism may be given levothyroxine to replace thyroid hormone, but in some cases, the appropriate management may be cessation of amiodarone.

An assessment of radiology resident competency in identifying suppurative retropharyngeal lymphadenitis: an examination using the WIDI SIM platform.

BACKGROUND AND PURPOSE: Suppurative retropharyngeal lymphadenitis is a retropharyngeal space infection almost exclusively seen in the young (4-8 years old) pediatric population. It can be misdiagnosed as a retropharyngeal abscess, leading to unnecessary invasive treatment procedures. This retrospective study aims to assess radiology residents' ability to independently identify CT imaging findings and make a definitive diagnosis of suppurative retropharyngeal lymphadenitis in a simulated call environment. MATERIALS AND METHODS: The Wisdom in Diagnostic Imaging Emergent/Critical Care Radiology Simulation (WIDI SIM) is a computer-aided emergency imaging simulation proven to be a reliable method for assessing resident preparedness for independent radiology call. The simulation included 65 cases across various imaging modalities of varying complexity, including normal studies, with one case specifically targeting suppurative retropharyngeal adenitis identification. Residents' free text responses were manually scored by faculty members using a standardized grading rubric, with errors subsequently classified by type. RESULTS: A total of 543 radiology residents were tested in three separate years on the imaging findings of suppurative retropharyngeal lymphadenitis using the Wisdom in Diagnostic Imaging simulation web-based testing platform. Suppurative retropharyngeal lymphadenitis was consistently underdiagnosed by radiology residents being tested for call readiness irrespective of the numbers of years in training. On average, only 3.5% of radiology residents were able to correctly identify suppurative retropharyngeal lymphadenitis on a contrast-enhanced computed tomography (CT). CONCLUSIONS: Our findings underscore a potential gap in radiology residency training related to the accurate identification of suppurative retropharyngeal lymphadenitis, highlighting the potential need for enhanced educational efforts in this area.

Metabolomic and Immunologic Discriminators of MIS-C at Emergency Room Presentation.

Multisystem Inflammatory Syndrome in Childhood (MIS-C) follows SARS-CoV-2 infection and frequently leads to intensive care unit admission. The inability to rapidly discriminate MIS-C from similar febrile illnesses delays treatment and leads to misdiagnosis. To identify diagnostic discriminators at the time of emergency department presentation, we enrolled 104 children who met MIS-C screening criteria, 14 of whom were eventually diagnosed with MIS-C. Before treatment, we collected breath samples for volatiles and peripheral blood for measurement of plasma proteins and immune cell features. Clinical and laboratory features were used as inputs for a machine learning model to determine diagnostic importance. MIS-C was associated with significant changes in breath volatile organic compound (VOC) composition as well as increased plasma levels of secretory phospholipase A2 (PLA2G2A) and lipopolysaccharide binding protein (LBP). In an integrated model of all analytes, the proportion of TCRVß21.3+ non-naive CD4 T cells expressing Ki-67 had a high sensitivity and specificity for MIS-C, with diagnostic accuracy further enhanced by low sodium and high PLA2G2A. We anticipate that accurate diagnosis will become increasingly difficult as MIS-C becomes less common. Clinical validation and application of this diagnostic model may improve outcomes in children presenting with multisystem febrile illnesses.

Maternal body mass index and necrotizing enterocolitis: A case-control study.

INTRODUCTION: Our aim was to determine if maternal body mass index (BMI) is associated with necrotizing enterocolitis (NEC) in a large urban delivery center. METHODS: This single center retrospective case-control study included 291 infants under gestational age of 33 weeks admitted to the neonatal intensive care unit (NICU) during a 10-year period. Cases of stage 2 and 3 NEC were matched at a ratio of 2 controls (n = 194) to 1 case (n = 97). Maternal BMI was categorized as normal (≤24.9), overweight (25-29.9) and obese (≥30). Chi-square and stepwise logistic regression were used for analysis. A power analysis was performed to determine if sample size was sufficient to detect an association. RESULTS: Stepwise logistic regression demonstrated no association between NEC and maternal obesity. Maternal hypertension, pre-eclampsia, premature rupture of membranes, maternal exposure to antibiotics, placental abruption and gestational diabetes were not associated with NEC. Power analysis showed the sample size was sufficient to detect an association of NEC with maternal BMI in three groups analyzed. In this case-control study, there was an association between NEC and maternal overweight but not obesity at delivery. DISCUSSION: Our results did not show a significant association of NEC with maternal obesity. The percent of overweight and obese mothers prior to pregnancy and at delivery was significantly higher in our population than the national average and may be responsible for the limited ability to reveal any association between maternal obesity and NEC.

Development of a Prediction Model for Surgery or Early Mortality at the Time of Initial Assessment for Necrotizing Enterocolitis.

OBJECTIVE: No available scale, at the time of initial evaluation for necrotizing enterocolitis (NEC), accurately predicts, that is, with an area under the curve (AUC) ≥0.9, which preterm infants will undergo surgery for NEC stage III or die within a week. STUDY DESIGN: This is a retrospective cohort study (n = 261) of preterm infants with <33 weeks' gestation or <1,500 g birthweight with either suspected or with definite NEC born at Parkland Hospital between 2009 and 2021. A prediction model using the new HASOFA SCORE (H: yperglycemia, H: yperkalemia, use of inotropes for H: ypotension during the prior week, A: cidemia, Neonatal S: equential O: rgan F: ailure A: ssessment [nSOFA: ] score) was compared with a similar model using the nSOFA score. RESULTS: Among 261 infants, 112 infants had NEC stage I, 68 with NEC stage II, and 81 with NEC stage III based on modified Bell's classification. The primary outcome, surgery for NEC stage III or death within a week, occurred in 81 infants (surgery in 66 infants and death in 38 infants). All infants with pneumoperitoneum or abdominal compartment syndrome either died or had surgery. The HASOFA and the nSOFA scores were evaluated in 254 and 253 infants, respectively, at the time of the initial workup for NEC. Both models were internally validated. The HASOFA model was a better predictor of surgery for NEC stage III or death within a week than the nSOFA model, with greater AUC 0.909 versus 0.825, respectively, p < 0.001. Combining HASOFA at initial assessment with concurrent or later presence of abdominal wall erythema or portal gas improved the prediction surgery for NEC stage III or death with AUC 0.942 or 0.956, respectively. CONCLUSION: Using this new internally validated prediction model, surgery for NEC stage III or death within a week can be accurately predicted at the time of initial assessment for NEC. KEY POINTS: · No available scale, at initial evaluation, accurately predicts which preterm infants will undergo surgery for NEC stage III or die within a week.. · In this retrospective cohort study of 261 preterm infants with either suspected or definite NEC we developed a new prediction model (HASOFA score).. · The HASOFA-model had high discrimination (AUC 0.909) and excellent calibration and was internally validated..

Genetic Determinants of Selenium Availability, Selenium-Response, and Risk of Polycystic Ovary Syndrome.

Selenium is a trace element and its deficiency has been associated with the risk of PCOS, a multifactorial syndrome that affects a large number of women worldwide. Several databases and literature were searched to find out genetic variants of the genes involved in selenium uptake, metabolism, and regulation which may be significantly associated with the risk of PCOS through Se-related pathways. Genes that require selenium for their biological actions to perform were also shortlisted. A total of eighteen significantly associated genes with forty-four variants were identified as candidate variants that could play a potential role in the modulation of PCOS risk among the study population. The genetic variant distribution data was available in-house and was obtained through a GWAS study of the North India population. In silico tools were applied to understand the functional impact of these variants. Three variants namely LDLR (rs2228671), TNF (rs1041981), and SAA2 (rs2468844) are strongly associated with PCOS risk and have a functional impact on encoded protein. Certain variants of Se uptake genes such as DIO1, GPX2, TXNRD1, DIO2 and GPX3 are also significantly associated with the risk of PCOS development. "C" allele of the Se transporter gene SELENOP (rs9686343) significantly increases PCOS risk. Other potential genes require selenium for their biological actions and are involved in the inflammatory, antioxidant response, and energy homeostasis signaling pathways. Thus, genetic variants of the population may affect the Se availability in the body. Also, deficiency of Se effects may get modulated due to underlying genetic polymorphism of Se-associated genes. This information may be helpful in dosage adjustment of Se supplementation for a population in order to get maximum benefits.

Psychological Distress During COVID-19 Pandemic in School-age Children of Health Care Professionals.

BACKGROUND: COVID-19 pandemic had a profound impact on the psychosocial well-being of societies across nations. METHODS: This prospective interventional study assessed the psychological distress in children, aged 6-19 years, whose parents were health care professionals. Parents were interviewed with a set of questionnaires based on signs of psychological distress given in the UNICEF and Childline's manual "Psychosocial Support for Children during COVID-19". Reassessment with same questionnaire was done after 15 days of intervention in the form of counseling and use of toolkits provided in the manual. RESULTS: The mean (SD) score was highest in children whose both parents were healthcare professionals. A significant reduction in psychological distress was seen after parents were provided with knowledge about UNICEF and Childline's manual (P < 0.001). CONCLUSION: Counseling activities and toolkits provided in the manual were effective in reduction of psychological distress in children during COVID-19 pandemic.

Translation and Psychometric Evaluation of the Hindi Language Version of the Pediatric Nausea Assessment Tool (PeNAT) in the Indian Population.

OBJECTIVES: To translate the Pediatric Nausea Assessment Tool (PeNAT) into Hindi and validate it in Indian pediatric cancer patients and survivors. METHODS: The PeNAT-Hindi was finalized by forward and backward translations, and pilot testing. The PeNAT-Hindi was administered to 200 Hindi-speaking pediatric (4-18 y) cancer patients/survivors, in three groups. These included pediatric cancer patients who had recently received chemotherapy (n = 150); who received no chemotherapy within 5 d (n = 25) and survivors (n = 25). Construct validity was tested by comparing scores among the three groups. Test-retest reliability and criterion validity were estimated by the correlation of the first PeNAT score with the second (taken 1 h later) PeNAT score and the number of vomiting/retching episodes, respectively. Convergent validity and discriminant validity were estimated by correlating PeNAT scores with parent-assessed nausea severity, and pain, respectively. The responsiveness was tested by comparing second PeNAT scores with subsequent divergent PeNAT scores among patients reporting subjective change (improvement and worsening, respectively) in nausea severity. RESULTS: Test-retest reliability of PeNAT-Hindi was good (intraclass correlation = 0.791). The initial PeNAT score had moderate correlation with the number of vomiting/retching episodes (Spearman ρ = 0.401). Median PeNAT scores in group 1 versus groups 2 and 3 were significantly different (p < 0.001). Initial PeNAT scores showed a moderate correlation with parent-assessed nausea (Spearman ρ = 0.657) and a weak correlation with parent-assessed pain (Spearman ρ = 0.319). The responsiveness (standardized response mean) of PeNAT-Hindi to the change in nausea severity was -1.79 (improvement) and 2.19 (worsening), respectively. CONCLUSION: PeNAT-Hindi showed good reliability and acceptable validity. It may be used among Hindi-speaking children for measuring nausea. The responsiveness of PeNAT-Hindi needs further evaluation.

Investigation of the Association of Serum Trace Elements Concentrations and Serum Biochemical Parameters with the Risk of Polycystic Ovary Syndrome: a Case-Control Study.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrinological syndrome characterized by hyperandrogenism of ovarian origin and is often considered a predisposing factor for metabolic disorders. The objective of the study was to investigate serum levels of (a) trace elements (copper (Cu), zinc (Zn), magnesium (Mg), selenium (Se), iron (Fe), chromium (Cr), and manganese (Mn)); and (b) biochemical parameters (glucose, cholesterol, triglycerides, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), albumin, total protein, creatinine, and C-reactive protein (CRP) with risk of PCOS. Another objective was to explore the relationship between serum trace elements and biochemical variables. Serum trace elements were estimated by inductively coupled plasma mass spectrometry (ICP-MS) and biochemical parameters were estimated by colorimetric methods in 99 PCOS cases and 82 controls. Linear and non-linear associations of serum variables with PCOS risk were studied under logistic, probit, GAM, and BKMR model. Statistical analyses were performed using IBM SPSS 22.0 and R package version 4.2.1. All studied serum trace elements (except Zn) are significantly associated with PCOS. Combined effect analysis revealed Mg-Se and Fe-Cu association with PCOS risk. A significant association of cholesterol, HDL-C, LDL-C, CRP, and albumin was observed. Furthermore, linear regression analysis suggests an association between Mg-Cu and Mg-Fe-Mn with HDL-C; Fe and Cr-Cu with albumin; and Cu-Se with cholesterol and LDL-C both.

Radiology resident competency in detecting basilar artery occlusion: a simulation-based assessment.

PURPOSE: Basilar artery strokes are rare but can have characteristic imaging findings that can often be overlooked. This retrospective study aims to assess radiology residents' ability to identify CT imaging findings of basilar artery occlusion in a simulated call environment. METHODS: The Wisdom in Diagnostic Imaging Emergent/Critical Care Radiology Simulation (WIDI SIM)-a tested and reliable computer-aided emergency imaging simulation-was employed to assess resident readiness for independent radiology call. The simulations include 65 cases of varying complexity, including normal studies, with one case specifically assessing basilar artery stroke. Residents were presented with a single, unique case of basilar artery occlusion in two separate years of testing and were only provided with non-contrast CT images. Residents' free text responses were manually scored by faculty members using a standardized grading rubric, with errors subsequently classified by type. RESULTS: A total of 454 radiology residents were tested in two separate years on the imaging findings of basilar artery occlusion using the Wisdom in Diagnostic Imaging simulation web-based testing platform. Basilar artery occlusion was consistently underdiagnosed by radiology residents being tested for call readiness irrespective of the numbers of years in training. On average, only 14% of radiology residents were able to correctly identify basilar artery occlusion on non-contrast CT. CONCLUSIONS: Our findings underscore a potential gap in radiology residency training related to the detection of basilar artery occlusion, highlighting the potential need for increased educational efforts in this area.

Genetic Variants of Steroidogenesis and Gonadotropin Pathways and Polycystic Ovary Syndrome Susceptibility: A Systematic Review and Meta-analysis.

Genetic variants are predisposing factors to polycystic ovary syndrome (PCOS), a multifactorial condition that often gets triggered due to various environmental factors. The study investigates the association of the variants of genes that are involved in the steroidogenesis pathway or gonadotropin pathway with the risk of PCOS. Appropriate keywords for predetermined genes were used to search in PubMed, Google Scholar, Science Direct, and Central Cochrane Library up to January 11, 2023. PROSPERO (CRD42022275425). Inclusion criteria: (a) case-control study; (b) genotype or allelic data. Exclusion criteria were: (a) duplicate studies; (b) clinical trials, systematic reviews, meta-analysis or conference abstract, case reports; (c) other than the English language; (d) having insufficient data; e) genetic variants for which meta-analysis has been reported recently and does not have a scope of the update. Various genetic models were applied as per data availability. Overall 12 variants of 7 genes were selected for the analysis. Relevant data were extracted from 47 studies which include 10,584 PCOS subjects and 16,150 healthy controls. Meta-analysis indicates a significant association between TOX3 rs4784165 [ORs = 1.08, 95% CI (1.00-1.16)], HMGA2 rs2272046 [ORs = 2.73, 95% CI (1.97-3.78)], YAP1 rs1894116 [OR = 1.22, 95% CI (1.13-1.33)] and increased risk of PCOS. Whereas FSHR rs2268361 [ORs = 0.84, 95% CI (0.78-0.89)] is associated with decreased PCOS risk. When sensitivity analysis was carried out, the association became significant for CYP19 rs700519 and FSHR rs6165 under an additive model. In addition, C9Orf3 rs3802457 became significantly associated with decreased PCOS risk with the removal of one study. Insignificant association was observed for CYP19A (rs2470152), FSHR (rs2349415, rs6166), C9Orf3 (rs4385527), GnRH1 (rs6185) and risk of PCOS. Our findings suggest association of CYP19A (rs700519), TOX3 (rs4784165), HMGA2 (rs2272046), FSHR (rs6165, rs2268361), C9orf3 (rs3802457), and YAP1 (rs1894116) with risk for PCOS.

Evaluation of Adsorptive Capture and Release Efficiency of MNPs-SA@Cu MOF Composite Beads Toward U(VI) and Th(IV) Ions from an Aqueous Media.

Effluent from nuclear power plants, rocks, and minerals contains hazardous radionuclides that adversely affect human health and seriously threaten the environment. To address this issue, simple, economic, and sustainable magnetite nanoparticle loaded sodium alginate copper metal-organic framework composite beads (MNPs-SA@Cu MOF composite beads) have been designed, and their performance has been evaluated under varying conditions of pH, time, adsorbent dose, and initial concentration and have been studied by batch adsorption studies for optimizing the adsorption conditions. In this work, MNPs-SA@Cu MOF composite beads have been prepared in situ for the adsorptive removal of uranium [U(VI)] and thorium [Th(IV)] ions from an aqueous solution. The synthesized MNPs-SA@Cu MOF composite beads were characterized by model analytical techniques like Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, field emission scanning electron microscopy, Brunauer-Emmett-Teller, and thermal gravimetric analysis. Here, 6 mg of adsorbent with 10 mL of 50 mg/L uranium and thorium ion solution at pH 5 was capable of removing the U(VI) and Th(IV) ions with 99.9 and 97.7% removal efficiencies, respectively. The obtained results showed that the adsorption behavior of the adsorbent for U(VI) and Th(IV) follows pseudo-second-order kinetics, and Langmuir isotherm fitted well with a maximum adsorption capacity of 454.54 and 434.78 mg/g, respectively. The adsorption mechanism indicated that electrostatic interaction and hydrogen bonding are the main driving forces for removing the U(VI) and Th(IV) ions. It can be reused for up to 10 adsorption-desorption cycles with minimal loss of removal efficiency. The easy synthesis method of MNPs-SA@Cu MOF composite beads and the high removal efficiency of U(VI) and Th(IV) ions reveal that they can potentially treat radionuclide waste effectively.

Palliative Care in Drug Resistance Tuberculosis: An Overlooked Component in Management.

Palliative care should be an important component in the management of drug resistant tuberculosis (DRTB); however, it is not given much importance. Even in the current scenario, many patients and their caregivers consider multidrug-resistant and extensively drug-resistant tuberculosis (TB) as a terminal illness and considering it almost as a death sentence, this group of patients also require palliative care. There is a misconception about considering palliative care as a treatment component in the terminal stage of an illness where curative treatment has no role in improving the survival of the patient. However, the real meaning of palliative care is to relieve suffering in all stages of the disease and is not limited to end-of-life care only. Palliative care in DRTB aims to improve the quality of life, intractable symptoms and physical, psychosocial and spiritual suffering of patients as well as their caregivers. There is an imminent need to train all TB healthcare workers regarding basic palliative care and integrate palliative care into the TB healthcare system.

A mitochondrial quality control mechanism reverses the phagosome maturation arrest caused by Mycobacterium tuberculosis.

Phagosome maturation arrest (PMA) imposed by Mycobacterium tuberculosis ( Mtb ) is a classic tool that helps Mtb evade macrophage anti-bacterial responses. The exclusion of RAB7, a small GTPase, from Mtb -phagosomes underscores PMA. Here we report an unexpected mechanism that triggers crosstalk between the mitochondrial quality control (MQC) and the phagosome maturation pathways that reverses the PMA. CRISPR-mediated p62/SQSTM1 depletion ( p62 KD ) blocks mitophagy flux without impacting mitochondrial quality. In p62 KD cells, Mtb growth and survival are diminished, mainly through witnessing an increasingly oxidative environment and increased lysosomal targeting. The lysosomal targeting of Mtb is facilitated by enhanced TOM20 + mitochondria-derived vesicles (MDVs) biogenesis, a key MQC mechanism. In p62 KD cells, TOM20 + -MDVs biogenesis is MIRO1/MIRO2-dependent and delivered to lysosomes for degradation in a RAB7-dependent manner. Upon infection in p62 KD cells, TOM20 + -MDVs get extensively targeted to Mtb -phagosomes, inadvertently facilitating RAB7 recruitment, PMA reversal and lysosomal targeting of Mtb . Triggering MQC collapse in p62 KD cells further diminishes Mtb survival signifying cooperation between redox- and lysosome-mediated mechanisms. The MQC-anti-bacterial pathway crosstalk could be exploited for host-directed anti-tuberculosis therapies.

Meta-QTL analysis in wheat: progress, challenges and opportunities.

Wheat, an important cereal crop globally, faces major challenges due to increasing global population and changing climates. The production and productivity are challenged by several biotic and abiotic stresses. There is also a pressing demand to enhance grain yield and quality/nutrition to ensure global food and nutritional security. To address these multifaceted concerns, researchers have conducted numerous meta-QTL (MQTL) studies in wheat, resulting in the identification of candidate genes that govern these complex quantitative traits. MQTL analysis has successfully unraveled the complex genetic architecture of polygenic quantitative traits in wheat. Candidate genes associated with stress adaptation have been pinpointed for abiotic and biotic traits, facilitating targeted breeding efforts to enhance stress tolerance. Furthermore, high-confidence candidate genes (CGs) and flanking markers to MQTLs will help in marker-assisted breeding programs aimed at enhancing stress tolerance, yield, quality and nutrition. Functional analysis of these CGs can enhance our understanding of intricate trait-related genetics. The discovery of orthologous MQTLs shared between wheat and other crops sheds light on common evolutionary pathways governing these traits. Breeders can leverage the most promising MQTLs and CGs associated with multiple traits to develop superior next-generation wheat cultivars with improved trait performance. This review provides a comprehensive overview of MQTL analysis in wheat, highlighting progress, challenges, validation methods and future opportunities in wheat genetics and breeding, contributing to global food security and sustainable agriculture.