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Vaccination will likely be a key component of strategies to curtail or prevent future sarbecovirus pandemics and to reduce the prevalence of infection and disease by future SARS-CoV-2 variants. A "pan-sarbecovirus" vaccine, that provides maximum possible mitigation of human disease, should elicit neutralizing antibodies with maximum possible breadth. By positioning multiple different receptor binding domain (RBD) antigens in close proximity on a single immunogen, it is postulated that cross-reactive B cell receptors might be selectively engaged. Heteromultimeric vaccines could therefore elicit individual antibodies that neutralize a broad range of viral species. Here, we use model systems to investigate the ability of multimeric sarbecovirus RBD immunogens to expand cross-reactive B cells and elicit broadly reactive antibodies. Homomultimeric RBD immunogens generated higher serum neutralizing antibody titers than the equivalent monomeric immunogens, while heteromultimeric RBD immunogens generated neutralizing antibodies recognizing each RBD component. Moreover, RBD heterodimers elicited a greater fraction of cross-reactive germinal center B cells and cross-reactive RBD binding antibodies than did homodimers. However, when serum antibodies from RBD heterodimer-immunized mice were depleted using one RBD component, neutralization activity against the homologous viral pseudotype was removed, but neutralization activity against pseudotypes corresponding to the other RBD component was unaffected. Overall, simply combining divergent RBDs in a single immunogen generates largely separate sets of individual RBD-specific neutralizing serum antibodies that are mostly incapable of neutralizing viruses that diverge from the immunogen components.
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Anticuerpos Neutralizantes , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo , Animales , Ratones , Humanos , Anticuerpos Antivirales , Pruebas de Neutralización , Vacunación , Glicoproteína de la Espiga del Coronavirus/químicaRESUMEN
Acute myeloid leukemia (AML) is a genetically heterogeneous clonal disorder characterized by the accumulation of acquired somatic genetic alterations in hematopoietic progenitor cells, which alter the normal mechanisms of self-renewal, proliferation, and differentiation. Due to significant technological advancements in sequencing technologies in the last 2 decades, classification and prognostic scoring of AML has been refined, and multiple guidelines are now available for the same. The authors have tried to summarize, latest guidelines for AML diagnosis, important markers associated, epigenetics markers, various AML fusions and their importance, etc. Review of literature suggests lack of study or comprehensive information about current NGS panels for AML diagnosis, genes and fusions covered, their technical know-how, etc. To solve this issue, the authors have tried to present detailed review about currently in use next-generation sequencing myeloid panels and their offerings.
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Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Pronóstico , Secuenciación de Nucleótidos de Alto Rendimiento , MutaciónRESUMEN
OBJECTIVE: Subclinical life style disease can cause endothelial dysfunction associated with perfusion abnormalities and reduced vascular compliance. Subclinical elevated beta type natriuretic peptide (BNP) has been associated with altered fluid shift from extra to intracellular space during acute hypoxia. Therefore we measured vascular response and BNP levels during acute hypoxia to study endothelial functions among healthy individuals. METHODS: Individuals were exposed to acute normobaric hypoxia of FiO2 = 0.15 for one hour in supine position and their pulmonary and systemic vascular response to hypoxia was compared. Individuals were divided into two groups based on either no response (Group 1) or rise in systolic pulmonary artery pressure to hypoxia (Group 2) and their BNP levels were compared. RESULTS: BNP was raised after hypoxia exposure in group 2 only from 18.52 ± 7 to 21.56 ± 10.82 picogram/ml, p < 0.05. Group 2 also showed an increase in mean arterial pressure and no fall in total body water in response to acute hypoxia indicating decreased endothelial function compared to Group 1. CONCLUSION: Rise in pulmonary artery pressure and BNP level in response to acute normobaric hypoxia indicates reduced endothelial function and can be used to screen subclinical lifestyle disease among healthy population.
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Hipoxia , Péptido Natriurético Encefálico , Humanos , Hipoxia/diagnóstico , Pulmón/irrigación sanguínea , Vasodilatadores , Estilo de Vida , Arteria PulmonarRESUMEN
Herein, we report the synthesis of two-dimensional chiral ZnII Salen covalent organic frameworks (COFs) (2) via rapid microwave-promoted condensation of C3-symmetric 1,3,5-tris[(5-tert-butyl-3-formyl-4-hydroxyphenyl)ethynyl]benzene 1 with (1R,2R)-1,2-diaminocyclohexane in excellent yields. The synthesized chiral ZnII Salen COF (2) showed a 454 m2 g-1 BET surface area with excellent crystallinity and thermal stability. Further, the post-synthetic metal exchange reaction was performed for chiral ZnII Salen COFs (2) with Mn(OAc)2·4H2O to synthesize chiral MnIII Salen COFs (3) and utilized as an effective heterogeneous catalyst for the enantioselective epoxidation of styrenes and chromenes to afford chiral epoxides up to 72% ee. Chiral MnIII Salen COF (3) could easily be separated by centrifugation and reused up to four recycles with an observable loss in activity without impairing enantioselectivity.
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Second-generation bioenergy, a carbon neutral or negative renewable resource, is crucial to achieving India's net-zero emission targets. Crop residues are being targeted as a bioenergy resource as they are otherwise burned on-field, leading to significant pollutant emissions. But estimating their bioenergy potential is problematic because of broad assumptions about their surplus fractions. Here, we use comprehensive surveys and multivariate regression models to estimate the bioenergy potential of surplus crop residues in India. These are with high sub-national and crop disaggregation that can facilitate the development of efficient supply chain mechanisms for its widespread usage. The estimated potential for 2019 of 1313 PJ can increase the present bioenergy installed capacity by 82% but is likely insufficient alone to meet India's bioenergy targets. The shortage of crop residue for bioenergy, combined with the sustainability concerns raised by previous studies, imply a need to reassess the strategy for the use of this resource.
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Agricultura , Contaminantes Ambientales , India , CarbonoRESUMEN
INTRODUCTION: Collusion is the non-disclosure of information about diagnosis or prognosis, frequently encountered in cancer care and palliative services. Unraveling collusion is a skill and differences among communication techniques by Health Care Workers have maintained the process of non-disclosure to patients and caregivers. Identifying the prevalence of collusion in cancer care is required to improve the existing strategies across the world. METHODS: A systematic review of the literature from 1991 to 2020 in the English language was conducted with the protocol registration on PROSPERO ID (CRD 42021249216.) to identify the pooled prevalence of collusion. RESULTS: By using random effect model, the pooled prevalence estimate among patients for the diagnostic and prognostic collusion was 24.15, (95% CI [17.09; 32.96], Tou2 = 1.0801, I2 = 97.9%, Cochran's Q = 1058.22, df = 21, p-value < 0.001) and 37.92, (95% CI [22.46; 56.30], Tou2 = 1.9641, I2 = 98.6%, Cochran's Q = 944.26, df = 13, p-value < 0.001) respectively. There was no difference across subgroups with different types of setting for the interview, WHO regions and trend over the years. CONCLUSIONS: Substantial prevalence of collusion goes unnoticed in cancer care. A meaningful understanding of such a large prevalence requires inquiry into the existing communication paradigm in cancer care across the world. The findings also question the need of formulating uniform interview techniques and structured assessment tools or questionnaires in cancer care to improve the disclosure rates.
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Neoplasias , Cuidados Paliativos , Comunicación , Revelación , Humanos , Neoplasias/epidemiología , Neoplasias/terapia , Cuidados Paliativos/métodos , PrevalenciaRESUMEN
New DABCO-based chiral ionic liquids were synthesized and evaluated in asymmetric Diels-Alder reaction of cyclopentadiene with α,ß-unsaturated aldehydes or 4-phenyl-3-buten-2-one. Chiral ionic liquid of modified MacMillan catalyst having a DABCO cation and hexafluorophosphate anion acts as organocatalyst (5 mol%) for the Diels-Alder reaction of crotonaldehyde and cyclopentadiene producing 98% of the product and 87% ee (endo) in CH3 CN/H2 O (95/5) at 25°C in 2 h. The scope and limitations of the catalysis were also studied by using cyclopentadiene and α,ß-unsaturated aldehydes, and the Diels-Alder products were obtained in 18%-92% yields with 68%-93% ee. The catalyst was recycled and reused up to 6 cycles with a slight drop in ee and conversion of the product.
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Líquidos Iónicos , Reacción de Cicloadición , Estructura Molecular , Piperazinas , EstereoisomerismoRESUMEN
Imidazolidin-4-one is used as a recoverable organocatalyst for the asymmetric Diels-Alder reaction in the presence of catalytic amount of dicationic ionic liquid and trifluoroacetic acid as a co-catalyst. The Diels-Alder reaction between model substrate cyclopentadiene and crotonaldehyde gave the product in 95% conversion and 87% ee of the endo-product. The catalyst was shown better reusability when the 20 mol% of dicationic ionic liquid was used and catalyst was reused upto 5 cycles, conversion remains upto 3 recycles but ee of endo-9 was slightly droped.
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BACKGROUND: Physicians routinely encounter diagnostic uncertainty in practice. Despite its impact on health care utilization, costs and error, measurement of diagnostic uncertainty is poorly understood. We conducted a systematic review to describe how diagnostic uncertainty is defined and measured in medical practice. METHODS: We searched OVID Medline and PsycINFO databases from inception until May 2017 using a combination of keywords and Medical Subject Headings (MeSH). Additional search strategies included manual review of references identified in the primary search, use of a topic-specific database (AHRQ-PSNet) and expert input. We specifically focused on articles that (1) defined diagnostic uncertainty; (2) conceptualized diagnostic uncertainty in terms of its sources, complexity of its attributes or strategies for managing it; or (3) attempted to measure diagnostic uncertainty. KEY RESULTS: We identified 123 articles for full review, none of which defined diagnostic uncertainty. Three attributes of diagnostic uncertainty were relevant for measurement: (1) it is a subjective perception experienced by the clinician; (2) it has the potential to impact diagnostic evaluation-for example, when inappropriately managed, it can lead to diagnostic delays; and (3) it is dynamic in nature, changing with time. Current methods for measuring diagnostic uncertainty in medical practice include: (1) asking clinicians about their perception of uncertainty (surveys and qualitative interviews), (2) evaluating the patient-clinician encounter (such as by reviews of medical records, transcripts of patient-clinician communication and observation), and (3) experimental techniques (patient vignette studies). CONCLUSIONS: The term "diagnostic uncertainty" lacks a clear definition, and there is no comprehensive framework for its measurement in medical practice. Based on review findings, we propose that diagnostic uncertainty be defined as a "subjective perception of an inability to provide an accurate explanation of the patient's health problem." Methodological advancements in measuring diagnostic uncertainty can improve our understanding of diagnostic decision-making and inform interventions to reduce diagnostic errors and overuse of health care resources.
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Toma de Decisiones Clínicas , Atención a la Salud/normas , Medicina/normas , Incertidumbre , Toma de Decisiones Clínicas/métodos , Atención a la Salud/métodos , Humanos , Medicina/métodosRESUMEN
The effects of methyl jasmonate (MeJA), an elicitor of plant defense mechanisms, on the biosynthesis of diosgenin, a steroidal saponin, were investigated in six fenugreek (Trigonella foenum-graecum) varieties (Gujarat Methi-2, Kasuri-1, Kasuri-2, Pusa Early Branching, Rajasthan Methi and Maharashtra Methi-5). Treatment with 0.01% MeJA increased diosgenin levels, in 12 days old seedlings, from 0.5%-0.9% to 1.1%-1.8%. In addition, MeJA upregulated the expression of two pivotal genes of the mevalonate pathway, the metabolic route leading to diosgenin: 3-hydroxy-3-methylglutaryl-CoA reductase (HMG) and sterol-3-ß-glucosyl transferase (STRL). In particular, MeJA increased the expression of HMG and STRL genes by 3.2- and 22.2-fold, respectively, in the Gujarat Methi-2 variety, and by 25.4- and 28.4-fold, respectively, in the Kasuri-2 variety. Therefore, MeJA may be considered a promising elicitor for diosgenin production by fenugreek plants.
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Acetatos/farmacología , Ciclopentanos/farmacología , Diosgenina/metabolismo , Oxilipinas/farmacología , Plantones/metabolismo , Trigonella/metabolismo , Biomasa , Vías Biosintéticas/efectos de los fármacos , Vías Biosintéticas/genética , Electroforesis en Gel de Agar , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Genes Esenciales , Genes de Plantas , Plantones/anatomía & histología , Plantones/efectos de los fármacos , Trigonella/efectos de los fármacos , Trigonella/genéticaRESUMEN
This work involves fluorescent probe which is composed of carbon dots (CD) and cadmium sulfide quantum dots (CdS QD) for the sensitive and selective fluorescence detection of chromium(vi) ions. The blue fluorescent carbon dots were synthesized by hydrothermal method from natural precursor apricot. The carbon dots-cadmium sulfide quantum dots (CD-CdS QD) nanocomposite was synthesized and all as-synthesized products were characterized using different characterization techniques. It showed white fluorescence under UV light which was quenched selectively in the presence of chromium(vi) ions due to the inner filter effect (IFE). The linear decrease in the white fluorescence was observed in the concentration range 2-120 µM of chromium(vi) ions with the limit of detection 2.07 µM. This is novel probe for the sensitive, selective and rapid detection of chromium(vi) ions.
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Dietary exposure risks of 39 multi-class Endocrine Disrupting Chemicals (EDCs) to the threatened Gangetic dolphins (Platanista gangetica) were investigated in a conservation-priority segment of the Ganga River. Elevated EDCs bioaccumulation was observed across prey fish species, with di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DnBP) significantly contributing to the EDC burden. The concentrations of persistent organochlorines in prey revealed a shift from dioxin-like polychlorinated biphenyls (PCBs) to non-dioxin-like PCBs. The prevalence of regulated p,p' DDT (Dichlorodiphenyltrichloroethane) and γ-HCH (Lindane) residues suggests regional non-compliance with regulatory standards. The concentration of some EDCs is dependent on the habitat, foraging behavior, trophic level and fish growth. The potential drivers of EDCs contamination in catchment includes agriculture, vehicular emissions, poor solid waste management, textile industry, and high tourist influx. Risk quotients (RQs) based on toxicity reference value were generally below 1, while the RQ derived from the reference dose highlighted a high risk to Gangetic dolphins from DEHP, DDT, DnBP, arsenic, PCBs, mercury, and cadmium, emphasizing the need for their prioritization within monitoring programs. The study also proposes a monitoring framework to provide guidance on monitoring and assessment of chemical contamination in Gangetic dolphin and habitats.
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The efficacy and treatment outcome of a CML patient are heavily dependent on BCR::ABL1 kinase domain (KD) mutation status. Next-generation sequencing technology is a bright alternative to the previously used sanger sequencing method due to its global presence in diagnostic setups, massive parallel sequencing ability, and far better sensitivity. In the present study, we have demonstrated a new protocol for kinase domain mutation analysis using the next-generation sequencing (NGS) method using the ion torrent sequencing platform. This protocol uses RNA as the starting material, followed by nested PCR to amplify the fusion transcript, which is subsequently used as a template for NGS. Initial validation and comparison of this assay with the sanger sequencing (SS) method yielded 95.23% agreement. CML samples (n = 121) with a failure to TKI response were subjected to this newly developed NGS-based assay to detect KD mutations, from which samples were found to have mutations with a sensitivity ranging from 2.32 to 93.41%. A total of 34.71% of samples (n = 42) were found to be positive for one or more KD mutations, whereas 65.29% of samples (n = 81) were found to be negative. Nine samples out of 42 positive samples, i.e., 21.42%, were found to have compound mutations. This is one of the first studies from India, which includes more than 160 samples and is analyzed by the NGS approach for KD mutation analysis.
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Proteínas de Fusión bcr-abl , Secuenciación de Nucleótidos de Alto Rendimiento , Leucemia Mielógena Crónica BCR-ABL Positiva , Mutación , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Estudios de Cohortes , Análisis Mutacional de ADN/métodos , Proteínas de Fusión bcr-abl/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , India , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
The threatened Gangetic dolphin (Platanista gangetica) and smooth-coated otter (Lutrogale perspicillata) occuring in the Ganga River Basin (GRB), are experiencing a decline in their population and distribution range owing to multiple anthropogenic pressures, including pollution by Potentially Toxic Elements (PTEs). Apex predators primarily encounter contaminants through dietary exposure. Yet, notable gaps persist in our understanding of the risks associated with the ingestion of PTE-contaminated prey for Gangetic dolphins and smooth-coated otters. In this study, we examined the occurrence and spatial variation of PTEs in the prey (fish) of both these riverine mammals across three major rivers of the Basin, while also evaluating the associated risk of ingesting contaminated prey. Our assessment revealed no statistical variation in bioaccumulation profiles of PTEs across the three rivers, attributable to comparable land use patterns and PTE consumption within the catchment. Zn and Cu were the most dominant PTEs in the prey species. The major potential sources of pollution identified in the catchment include agricultural settlements, vehicular emissions, and the presence of metal-based additives in plastics. Zn, As and Hg accumulation vary with the trophic level whereas some PTEs show concentration (Hg) and dilution (As, Cr, Pb and Zn) with fish growth. The Risk Quotient (RQ), based on the dietary intake of contaminated prey calculated using Toxicity Reference Value was consistently below 1 indicating no significant risk to these riverine mammals. Conversely, with the exception of Co and Ni, the Reference Dose-based RQs for all other PTEs indicated a substantial risk for Gangetic dolphins and smooth-coated otters through dietary exposure. This study serves as a pivotal first step in assessing the risk of PTEs for two threatened riverine mammals in a densely populated river basin, highlighting the importance of their prioritization in regular monitoring to reinforce the ongoing conservation efforts.
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Exposición Dietética , Monitoreo del Ambiente , Nutrias , Ríos , Contaminantes Químicos del Agua , Animales , Ríos/química , India , Exposición Dietética/estadística & datos numéricos , Contaminantes Químicos del Agua/análisis , Peces , Delfines , Cadena AlimentariaRESUMEN
The majority of preclinical research has shown that Mycobacterium tuberculosis can modify host lipids in various ways. To boost its intramacrophage survival, M. tuberculosis causes host lipids to build up, resulting in the development of lipid-laden foam cells. M. tuberculosis binds to and enters the macrophage via the cell membrane cholesterol. Aggregation of cholesterol in the cell wall of M. tuberculosis and an increase in vascularity at the granuloma site reduce the permeability of rifampicin and isoniazid concentrations. However, very few studies have assessed the effect of statins on drug penetration. Here, we used atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, to observe its effect on the bacterial burden by increasing the drug concentration at the infection site. We looked into how atorvastatin could be used in conjunction with first-line drugs to promote drug permeation. In this study, we detected an accumulation of drugs at the peripheral sites of the lungs and impaired drug distribution to the diseased sites. The efficacy of antituberculosis drugs, with atorvastatin as an adjunct, on the viability of M. tuberculosis cells was demonstrated. A nontoxic statin dosage established phenotypic and normal granuloma vasculature and showed an additive effect with rifampicin and isoniazid. Our data show that statins help to reduce the tuberculosis bacterial burden. Our findings reveal that the bacterial load is connected with impaired drug permeability resulting from lipid accumulation in the bacterial cell wall. Statin therapy combined with antituberculosis medications have the potential to improve treatment in tuberculosis patients. IMPORTANCE Mycobacterium tuberculosis binds to and enters the macrophage via the cell membrane cholesterol. M. tuberculosis limits phagosomal maturation and activation without engaging in phagocytosis. Aggregation of cholesterol in the cell wall of M. tuberculosis and an increase in the vascularity at the granuloma site reduce the permeability of rifampicin and isoniazid concentrations. However, very few studies have assessed the effect of statins on drug penetration, which can be increased through a reduction in cholesterol and vascularity. Herein, we used atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, to observe its effect on bacterial burden through increasing the drug concentration at the infection site. Our main research goal is to diminish mycobacterial dissemination and attenuate bacterial growth by increasing drug permeability.
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Elucidation of the genetic basis of drought tolerance is vital for genomics-assisted breeding of drought tolerant crop varieties. Here, we used genotyping-by-sequencing (GBS) to identify single nucleotide polymorphisms (SNPs) in recombinant inbred lines (RILs) derived from a cross between a drought tolerant chickpea variety, Pusa 362 and a drought sensitive variety, SBD 377. The GBS identified a total of 35,502 SNPs and subsequent filtering of these resulted in 3237 high-quality SNPs included in the eight linkage groups. Fifty-one percent of these SNPs were located in the genic regions distributed throughout the genome. The high density linkage map has total map length of 1069 cm with an average marker interval of 0.33 cm. The linkage map was used to identify 9 robust and consistent QTLs for four drought related traits viz. membrane stability index, relative water content, seed weight and yield under drought, with percent variance explained within the range of 6.29%-90.68% and LOD scores of 2.64 to 6.38, which were located on five of the eight linkage groups. A genomic region on LG 7 harbors quantitative trait loci (QTLs) explaining > 90% phenotypic variance for membrane stability index, and > 10% PVE for yield. This study also provides the first report of major QTLs for physiological traits such as membrane stability index and relative water content for drought stress in chickpea. A total of 369 putative candidate genes were identified in the 6.6 Mb genomic region spanning these QTLs. In-silico expression profiling based on the available transcriptome data revealed that 326 of these genes were differentially expressed under drought stress. KEGG analysis resulted in reduction of candidate genes from 369 to 99, revealing enrichment in various signaling pathways. Haplotype analysis confirmed 5 QTLs among the initially identified 9 QTLs. Two QTLs, qRWC1.1 and qYLD7.1, were chosen based on high SNP density. Candidate gene-based analysis revealed distinct haplotypes in qYLD7.1 associated with significant phenotypic differences, potentially linked to pathways for secondary metabolite biosynthesis. These identified candidate genes bolster defenses through flavonoids and phenylalanine-derived compounds, aiding UV protection, pathogen resistance, and plant structure.The study provides novel genomic regions and candidate genes which can be utilized in genomics-assisted breeding of superior drought tolerant chickpea cultivars.
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Cicer , Sitios de Carácter Cuantitativo , Cicer/genética , Resistencia a la Sequía , Genoma de Planta , Fitomejoramiento , Polimorfismo de Nucleótido Simple , Agua , Ligamiento GenéticoRESUMEN
The most frequently reported symptom of exposure to high altitude is loss of body mass and decreased performance which has been attributed to altered protein metabolism affecting skeletal muscles mass. The present study explores the mechanism of chronic hypobaric hypoxia mediated skeletal muscle wasting by evaluating changes in protein turnover and various proteolytic pathways. Male Sprague-Dawley rats weighing about 200 g were exposed to hypobaric hypoxia (7,620 m) for different durations of exposure. Physical performance of rats was measured by treadmill running experiments. Protein synthesis, protein degradation rates were determined by (14)C-Leucine incorporation and tyrosine release, respectively. Chymotrypsin-like enzyme activity of the ubiquitin-proteasome pathway and calpains were studied fluorimetrically as well as using western blots. Declined physical performance by more than 20%, in terms of time taken in exhaustion on treadmill, following chronic hypobaric hypoxia was observed. Compared to 1.5-fold increase in protein synthesis, the increase in protein degradation was much higher (five-folds), which consequently resulted in skeletal muscle mass loss. Myofibrillar protein level declined from 46.79 ± 1.49 mg/g tissue at sea level to 37.36 ± 1.153 (P < 0.05) at high altitude. However, the reduction in sarcoplasmic proteins was less as compared to myofibrillar protein. Upregulation of Ub-proteasome pathway (five-fold over control) and calpains (three-fold) has been found to be important factors for the enhanced protein degradation rate. The study provided strong evidences suggesting that elevated protein turnover rate lead to skeletal muscle atrophy under chronic hypobaric hypoxia via ubiquitin-proteasome pathway and calpains.
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Atrofia/fisiopatología , Hipoxia/fisiopatología , Músculo Esquelético/metabolismo , Proteínas/metabolismo , Proteolisis , Animales , Calpaína/metabolismo , Radioisótopos de Carbono , Masculino , Actividad Motora , Músculo Esquelético/fisiopatología , Miofibrillas/metabolismo , Presión/efectos adversos , Complejo de la Endopetidasa Proteasomal/metabolismo , Ratas , Ratas Sprague-Dawley , Ubiquitina/metabolismoRESUMEN
BACKGROUND: The hypothesis of the present study is that the occurrence of oxidative stress with exposure to chronic hypobaric hypoxia will be different in the gastrocnemius and soleus muscles as these two muscles differ in their fiber types. METHODS: Male Sprague-Dawley rats were divided into seven groups (I, II, III, IV, V, VI, VII). Groups I-V were exposed to an altitude of 25,000 ft (7620 m) for 0, 3, 7, 14, and 21 d, respectively. Group VI and VII were given curcumin orally and exposed to an altitude of 25,000 ft (7620 m) for 0 and 14 d, respectively. On completion of exposure, the soleus and gastrocnemius muscle were removed and used for various estimations. RESULTS: Maximum changes were observed in 14-d exposed gastrocnemius muscle (GM) as compared to soleus muscle (SM). Lipid peroxidation (nmol x g(-1) of muscle) was higher in GM than SM in 14-d exposed rats (43.05 +/- 2.96 vs. 27.4 +/- 2.35, respectively). Similarly significant increases were observed in free radicals and protein carbonyl on exposure to hypobaric hypoxia. We also observed depletion of the antioxidant, reduced glutathione, in the exposed rats as compared to the control group. A significant reduction of 26% was observed in total protein of the GM as compared to a reduction of 13% in the SM. Myofibrillar proteins were also significantly decreased in the exposed groups. DISCUSSION: Hypobaric hypoxia affects different hind limb muscles differentially and the response of each muscle varies as a function of time. Gastrocnemius muscle is more vulnerable to hypobaric hypoxia-induced oxidative stress in comparison to soleus muscle.
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Mal de Altura/metabolismo , Músculo Esquelético/metabolismo , Animales , Antioxidantes/metabolismo , Creatina Quinasa/metabolismo , Glutatión/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Peroxidación de Lípido , Masculino , Modelos Animales , Proteínas Musculares/metabolismo , Estrés Oxidativo/fisiología , Carbonilación Proteica , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Background: Collusion in cancer care is the diplomatic concealment of information between a triad of the health care professional (HCP), patient, and caregiver. Free and expressive communication is determined by multiple factors, which establishes a healthy balance between 'patient-centric' and 'family-centric' decision making. The lack of a universal approach to prognostic disclosure techniques emphasizes the need for a systematic review of contemporary practice. Methods: A systematic review of the literature was conducted till June 2020 using themes based on cancer, communication, prognostic disclosure, and collusion by using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Fifty-three studies involving 10,569 subjects were studied for their utility on prognostic disclosure using different communication methods and interfaces. Twenty-three studies used a face-to-face interview with subjects while in-person telephonic interviews were conducted in two studies, 16 studies implicated semi-structured questionnaires, and 6 studies mentioned the development of a new technique/tool for disclosure. The duration of a session for prognosis-disclosure ranged from 22 min to 1 h. The involvement of palliative care specialists and mental health professionals was limited during the disclosure of the prognosis. Conclusion: The findings of the review indicate that patients in cancer care are aware of their diagnosis and to a certain extent of prognosis despite nondisclosure by their family members and treating teams. This review emphasizes the assessment of 'disclosure wishes' among patients and caregivers in separate interviews rather than simply relying on one specific method of interviewing. The nonconfrontational approach and training among HCPs are of utmost importance to build therapeutic resilience among the treating team involved in cancer care. Since many factors such as family wishes, cultural dissonance, medical model, and patient perception could become barriers to prognostic disclosure, there is a need to develop a universal approach to prognostic disclosure and handling associated collusion.
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A rapid and simple protocol for the determination of enantiopurity of primary and secondary amines was developed by using (S)-BINOL/(S)-BINOL derivatives/(R)-1,1'-binaphthyl-2,2'-diyl hydrogenphosphate as chiral solvating agents via 1H- and 19F-NMR spectroscopic analysis. In this protocol, the analyte and chiral solvating agent were directly mixed in an NMR tube in chloroform-d and after shaking for 30 seconds the 1H- and 19F-NMR spectra were recorded, which affords well-resolved resonance peaks for both the enantiomers present in an analyte. The enantiomeric excess of 1,2-diphenylethylenediamine was determined and linear relationship with coefficient of R 2 = 0.9995 was observed. The binding constant and associated ΔG values were also calculated for diastereomeric complexes formed between both the enantiomers of analyte 5 with CSA (S)-3a by using UV-visible spectroscopy.