87 research outputs found
Riluzole But Not Melatonin Ameliorates Acute Motor Neuron Degeneration and Moderately Inhibits SOD1-Mediated Excitotoxicity Induced Disrupted Mitochondrial Ca2+ Signaling in Amyotrophic Lateral Sclerosis
Application of Handheld Tele-ECG for Health Care Delivery in Rural India
Telemonitoring is a medical practice that involves remotely monitoring patients who are not at the same location as the health care provider. The purpose of our study was to use handheld tele-electrocardiogram (ECG) developed by Bhabha Atomic Research Center (BARC) to identify heart conditions in the rural underserved population where the doctor-patient ratio is low and access to health care is difficult. The objective of our study was clinical validation of handheld tele-ECG as a screening tool for evaluation of cardiac diseases in the rural population. ECG was obtained in 450 individuals (mean age 31.49 ± 20.058) residing in the periphery of Chandigarh, India, from April 2011 to March 2013, using the handheld tele-ECG machine. The data were then transmitted to physicians in Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, for their expert opinion. ECG was interpreted as normal in 70% individuals. Left ventricular hypertrophy (9.3%) was the commonest abnormality followed closely by old myocardial infarction (5.3%). Patient satisfaction was reported to be ~95%. Thus, it can be safely concluded that tele-ECG is a portable, cost-effective, and convenient tool for diagnosis and monitoring of heart diseases and thus improves quality and accessibility, especially in rural areas
Effects of different plant growth regulators on in vitro callus induction in physic nut (Jatropha curcus L.)
Jatropha (Jatropha curcas L.) is an oil bearing crop growing in tropical and subtropical parts of the world. The present study was undertaken to investigate the effects of different plant growth regulators on in vitro callus induction in physic nut (J. curcus). In the present study, it was observed that all the explants viz., leaf lamina, petioles, nodal segments and cotyledonary nodes showed good callus induction responses on various culture media thus tried. Leaf lamina and petioles showed 100.0% callus induction responses on different MS media supplemented with auxins and cytokinins alone or in combinations whereas, nodal segments and cotyledonary nodes showed maximum 89.6% and 83.9% callus induction respectively. The presence of 2, 4-D in culture media with auxins or cytokinins was essential for good callus growth. Among different explants tried, leaf lamina was the best responding explants and MS-13 media supplemented with 5×10-6 M NAA and 10-5 M 2, 4-D is the best callusing and growth supporting medium. However, the regenerative competence of the callus tissues can differ depending on the type of explants used because certain types of plant tissues have more favorable regeneration responses than others. Callus induction rate from all explant types was highest than other reports. The results obtained in the present study would facilitate the high callus induction and regeneration responses in J. curcus for its improvement using biotechnological tools
Expression of a Cu,Zn superoxide dismutase typical for familial amyotrophic lateral sclerosis increases the vulnerability of neuroblastoma cells to infectious injury
<p>Abstract</p> <p>Background</p> <p>Infections can aggravate the course of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Mutations in the anti-oxidant enzyme Cu,Zn superoxide dismutase (EC 1.15.1.1, SOD1) are associated with familial ALS. Streptococcus pneumoniae, the most frequent respiratory pathogen, causes damage by the action of the cholesterol-binding virulence factor pneumolysin and by stimulation of the innate immune system, particularly via Toll-like-receptor 2.</p> <p>Methods</p> <p>SH-SY5Y neuroblastoma cells transfected with the G93A mutant of SOD1 typical for familial ALS (G93A-SOD1) and SH-SY5Y neuroblastoma cells transfected with wildtype SOD1 were both exposed to pneumolysin and in co-cultures with cultured human macrophages treated with the Toll like receptor 2 agonist N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-[R]-cysteinyl-[S]-seryl-[S]-lysyl-[S]-lysyl-[S]-lysyl-[S]-lysyl-[S]-lysine × 3 HCl (Pam<sub>3</sub>CSK<sub>4</sub>). Cell viability and apoptotic cell death were compared morphologically and by in-situ tailing. With the help of the WST-1 test, cell viability was quantified, and by measurement of neuron-specific enolase in the culture supernatant neuronal damage in co-cultures was investigated. Intracellular calcium levels were measured by fluorescence analysis using fura-2 AM.</p> <p>Results</p> <p>SH-SY5Y neuroblastoma cells transfected with the G93A mutant of SOD1 typical for familial ALS (G93A-SOD1) were more vulnerable to the neurotoxic action of pneumolysin and to the attack of monocytes stimulated by Pam<sub>3</sub>CSK<sub>4</sub> than SH-SY5Y cells transfected with wild-type human SOD1. The enhanced pneumolysin toxicity in G93A-SOD1 neuronal cells depended on the inability of these cells to cope with an increased calcium influx caused by pores formed by pneumolysin. This inability was caused by an impaired capacity of the mitochondria to remove cytoplasmic calcium. Treatment of G93A-SOD1 SH-SY5Y neuroblastoma cells with the antioxidant N-acetylcysteine reduced the toxicity of pneumolysin.</p> <p>Conclusion</p> <p>The particular vulnerability of G93A-SOD1 neuronal cells to hemolysins and inflammation may be partly responsible for the clinical deterioration of ALS patients during infections. These findings link infection and motor neuron disease and suggest early treatment of respiratory infections in ALS patients.</p
Impairment of mitochondrial calcium handling in a mtSOD1 cell culture model of motoneuron disease
<p>Abstract</p> <p>Background</p> <p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective loss of motor neurons (MN) in the brain stem and spinal cord. Intracellular disruptions of cytosolic and mitochondrial calcium have been associated with selective MN degeneration, but the underlying mechanisms are not well understood. The present evidence supports a hypothesis that mitochondria are a target of mutant SOD1-mediated toxicity in familial amyotrophic lateral sclerosis (fALS) and intracellular alterations of cytosolic and mitochondrial calcium might aggravate the course of this neurodegenerative disease. In this study, we used a fluorescence charged cool device (CCD) imaging system to separate and simultaneously monitor cytosolic and mitochondrial calcium concentrations in individual cells in an established cellular model of ALS.</p> <p>Results</p> <p>To gain insights into the molecular mechanisms of SOD1<sup>G93A </sup>associated motor neuron disease, we simultaneously monitored cytosolic and mitochondrial calcium concentrations in individual cells. Voltage – dependent cytosolic Ca<sup>2+ </sup>elevations and mitochondria – controlled calcium release mechanisms were monitored after loading cells with fluorescent dyes fura-2 and rhod-2. Interestingly, comparable voltage-dependent cytosolic Ca<sup>2+ </sup>elevations in WT (SH-SY5Y<sup>WT</sup>) and G93A (SH-SY5Y<sup>G93A</sup>) expressing cells were observed. In contrast, mitochondrial intracellular Ca<sup>2+ </sup>release responses evoked by bath application of the mitochondrial toxin FCCP were significantly smaller in G93A expressing cells, suggesting impaired calcium stores. Pharmacological experiments further supported the concept that the presence of G93A severely disrupts mitochondrial Ca<sup>2+ </sup>regulation.</p> <p>Conclusion</p> <p>In this study, by fluorescence measurement of cytosolic calcium and using simultaneous [Ca<sup>2+</sup>]i and [Ca<sup>2+</sup>]<sub>mito </sub>measurements, we are able to separate and simultaneously monitor cytosolic and mitochondrial calcium concentrations in individual cells an established cellular model of ALS. The primary goals of this paper are (1) method development, and (2) screening for deficits in mutant cells on the single cell level. On the technological level, our method promises to serve as a valuable tool to identify mitochondrial and Ca<sup>2+</sup>-related defects during G93A-mediated MN degeneration. In addition, our experiments support a model where a specialized interplay between cytosolic calcium profiles and mitochondrial mechanisms contribute to the selective degeneration of neurons in ALS.</p
Mid and Long Term Follow Up of 50 Pediatric Cardiac Chadians Operated in France from 2003 to 2012
Introduction
Cardiac valvular diseases (CVDs) are the major cause of cardiovascular morbidity and mortality globally, with predominance of rheumatic heart disease (RHD) in developing countries. Congenital heart defects (CHD) diagnoses are delayed due to socioeconomic factors. This study aims to evaluate the post-operative surgical outcomes of CHD and valvular RHD.
Methods
This study is conducted with 50 patients from Chad, operated on between 2003 and 2012. Post-operative outcomes are evaluated from 2010 to 2012.
Results
With the follow-up of 19 RHD patients who underwent plasty, 8 (42.1%) had no complications, 4 (21%) presented with mild regurgitation, 7 (36.8%) required re-operation due to 6 mitral stenosis (MS) cases (mitral surface range from 0.7 to 1.2 cm2) and 1 severe mitral regurgitation (MR) case. While those patients with valve replacement, 2 (50%) had no complications, 1 (25%) had mild regurgitation and 1 (25%) patient died. Two patients with aortic regurgitation (AR) that underwent annuloplasty presented with severe regurgitation. Regarding AR with valve replacement, 3 (60%) had no complications, and 2 (40%) had mild regurgitation. Among the tricuspid regurgitation (TR) patients who had plasty, 6 (85.7%) had no complications, and 1 (14.3%) had severe regurgitation. The surgical repair was curative in all CHD patients. The loss to follow-up rate was 13/50 (26%).
Conclusion
The annuloplasty on rheumatic valve disease (MR and AR) has proven to be disappointing. Plasty is debated without justified indication for AR. The Outcomes of CHD, mitral and aortic valve replacement are successful
Synergistic impact of nanomaterials and plant probiotics in agriculture: A tale of two-way strategy for long-term sustainability
Modern agriculture is primarily focused on the massive production of cereals and other food-based crops in a sustainable manner in order to fulfill the food demands of an ever-increasing global population. However, intensive agricultural practices, rampant use of agrochemicals, and other environmental factors result in soil fertility degradation, environmental pollution, disruption of soil biodiversity, pest resistance, and a decline in crop yields. Thus, experts are shifting their focus to other eco-friendly and safer methods of fertilization in order to ensure agricultural sustainability. Indeed, the importance of plant growth-promoting microorganisms, also determined as “plant probiotics (PPs),” has gained widespread recognition, and their usage as biofertilizers is being actively promoted as a means of mitigating the harmful effects of agrochemicals. As bio-elicitors, PPs promote plant growth and colonize soil or plant tissues when administered in soil, seeds, or plant surface and are used as an alternative means to avoid heavy use of agrochemicals. In the past few years, the use of nanotechnology has also brought a revolution in agriculture due to the application of various nanomaterials (NMs) or nano-based fertilizers to increase crop productivity. Given the beneficial properties of PPs and NMs, these two can be used in tandem to maximize benefits. However, the use of combinations of NMs and PPs, or their synergistic use, is in its infancy but has exhibited better crop-modulating effects in terms of improvement in crop productivity, mitigation of environmental stress (drought, salinity, etc.), restoration of soil fertility, and strengthening of the bioeconomy. In addition, a proper assessment of nanomaterials is necessary before their application, and a safer dose of NMs should be applicable without showing any toxic impact on the environment and soil microbial communities. The combo of NMs and PPs can also be encapsulated within a suitable carrier, and this method aids in the controlled and targeted delivery of entrapped components and also increases the shelf life of PPs. However, this review highlights the functional annotation of the combined impact of NMs and PPs on sustainable agricultural production in an eco-friendly manner
Superconductivity in single crystals of a quasi-one dimensional infinite chain cuprate SrCaCuO at 90 K
Although there is no complete theory of high temperature superconductivity,
the importance of CuO planes in cuprate superconductors is confirmed from
both theory and experiments. Strong Coulomb repulsion between electrons on the
CuO plane makes the resultant electron system highly correlated and a
difficult problem to solve since exact solutions of many-body Hamiltonian in
two dimensions do not exist. If however, superconductivity can arise in
structures having chains rather than planes and having a high critical
temperature, then the high temperature superconductivity problem could become
more tractable since exact solutions in one dimension do exist. In this paper,
we report the observation of bulk superconductivity in single crystals of a
cuprate SrCaCuO at very high critical temperature, T, of
90 K whose structure reveals the presence of infinite double chains of
Cu-O-Cu-O instead of CuO planes, thus, ensuring quasi-one dimensional
superconductivity. Bulk superconducting behaviour was observed in \textit{dc}
magnetisation, \textit{ac} susceptibility as well as resistance measurements.
The observation of bulk superconductivity in SrCaCuO having
chains of Cu-O-Cu-O rather than planes of CuO at a high T of 90 K is
expected to profoundly impact our understanding of high temperature
superconductivity.Comment: 15 pages, 4 figure
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Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021
BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation
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