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1.
JNMA J Nepal Med Assoc ; 59(238): 542-546, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34508411

RESUMO

INTRODUCTION: The world is facing the pandemic of COVID-19 caused by the corona virus since December 2019 and has caused millions of death throughout the world. Exposure of nursing students in clinical placement during pandemic is fearful and stressful with high risk of infection which can cause anxiety and different levels of psychological crisis to individuals. The main objective of the study is to find out the prevalence of anxiety among nursing students during clinical placement in the pandemic of COVID-19. METHODS: A descriptive cross-sectional study was conducted among 144 nursing students enrolled in different clinical placement of a tertiary hospital of Nepal from 20th January 2021 to 2nd February 2021. Ethical approval was received from the Institutional Review Committee. Demographic, COVID-19 related and Beck Anxiety Inventory questionnaires was used for assessing anxiety. Whole sampling was done. Descriptive statistics was conducted using Statistical Package for the Social Sciences 2016 version. RESULTS: Out of 144 females enrolled in the study, all the nursing students 144 (100%) having clinical placement had anxiety. Among them, 117 (81%) had mild anxiety and 27 (19%) had moderate level of anxiety. All the students used coping strategies for the anxiety. The most commonly used strategy to cope with anxiety was religion (5.03±1.78). CONCLUSIONS: All the nursing students had anxiety during the clinical placement and all the students used the coping strategies for the anxiety. Majority of the nursing students had mild anxiety. Religion was most common method of strategy to cope with anxiety.


Assuntos
COVID-19 , Estudantes de Enfermagem , Ansiedade/epidemiologia , Estudos Transversais , Feminino , Humanos , Nepal/epidemiologia , SARS-CoV-2 , Centros de Atenção Terciária
2.
Ecotoxicol Environ Saf ; 223: 112572, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34352571

RESUMO

Epidemiological studies have associated chronic exposure to arsenic (As) from drinking water with increased risk of hypertension. However, evidence of an association between As exposure from food and hypertension risks is sparse. To quantify the association between daily As intake from both food (rice, wheat and potatoes) and drinking water (Aswater) along with total exposure (Astotal) and hypertension risks in a study population in Bihar, India, we conducted an individual level cross-sectional analysis between 2017 and 2019 involving 150 participants. Arsenic intake variables and three indicators of hypertension risks (general hypertension, low-density lipoprotein (LDL) and high-density lipoprotein (HDL)) were derived, and any relationship was quantified using a series of crude and multivariable log-linear or logistic regression models. The prevalence of general hypertension was 40% for the studied population. The median level of HDL was 45 mg/dL while median value of LDL was 114 mg/dL. Apart from a marginally significant positive relationship between As intake from rice and the changes of LDL (p-value = 0.032), no significant positive association between As intake and hypertension risks could be ascertained. In fact, Astotal was found to be associated with lower risks of general hypertension and higher levels of HDL (p-value = 0.020 and 0.010 respectively) whilst general hypertension was marginally associated with lower Aswater (p-value = 0.043). Due to limitations regarding study design and residual confounding, all observed marginal associations should be treated with caution.


Assuntos
Arsênio , Água Potável , Hipertensão , Poluentes Químicos da Água , Arsênio/análise , Arsênio/toxicidade , Estudos Transversais , Água Potável/análise , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Contaminação de Alimentos/análise , Humanos , Hipertensão/induzido quimicamente , Hipertensão/epidemiologia , Índia/epidemiologia , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
3.
Exp Brain Res ; 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34324019

RESUMO

Traumatic brain injury (TBI) is one of the main causes of death and disability in both civilian and military population. TBI may occur via a variety of etiologies, all of which involve trauma to the head. However, the neuroprotective drugs which were found to be very effective in animal TBI models failed in phase II or phase III clinical trials, emphasizing a compelling need to review the current status of animal TBI models and therapeutic strategies. No single animal model can adequately mimic all aspects of human TBI owing to the heterogeneity of clinical TBI. However, due to the ethical limitations, it is difficult to precisely emulate the TBI mechanisms that occur in humans. Therefore, many animal models with varying severity and mechanisms of brain injury have been developed, and each model has its own pros and cons in its implementation for TBI research. These challenges pose a need for study of continued TBI mechanisms, brain injury severity, duration, treatment strategies, and optimization of animal models across the neurotrauma research community. The aim of this review is to discuss (1) causes of TBI, (2) its prevalence in military and civilian population, (3) classification and pathophysiology of TBI, (4) biomarkers and detection methods, (5) animal models of TBI, and (6) the advantages and disadvantages of each model and the species used, as well as possible treatments.

4.
Sci Total Environ ; 754: 142082, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32919317

RESUMO

Extensive evidence of elevated arsenic (As) in the food-chain, mainly rice, wheat and vegetables exists. Nevertheless, the importance of exposure from food towards total As exposure and associated health risks in areas with natural occurring As in drinking water is still often neglected, and accordingly mitigations are largely focused on drinking water only. In this study, the contribution of food over drinking water to overall As exposure was estimated for As exposed populations in Bihar, India. Increased lifetime cancer risk was predicted using probabilistic methods with input parameters based on detailed dietary assessment and estimation of As in drinking water, cooked rice, wheat flour and potato collected from 91 households covering 19 villages. Median total exposure was 0.83 µg/kgBW/day (5th and 95th percentiles were 0.21 and 11.1 µg/kgBW/day) and contribution of food (median = 49%) to overall exposure was almost equal to that from drinking water (median = 51%). More importantly and contrary to previous studies, food was found to contribute more than drinking water to As exposure, even when drinking water As was above the WHO provisional guide value of 10 µg/L. Median and 95th percentile excess lifetime cancer risks from food intake were 1.89 × 10-4 and 7.32 × 10-4 respectively when drinking water As was below 10 µg/L and 4.00 × 10-4 and 1.83 × 10-3 respectively when drinking water As was above 10 µg/L. Our results emphasise the importance of food related exposure in As-endemic areas, and, perhaps surprisingly, particularly in areas with high As concentrations in drinking water - this being partly ascribed to increases in food As due to cooking in high As water. These findings are timely to stress the importance of removing As from the food chain and not just drinking water in endemic areas.


Assuntos
Arsênio , Água Potável , Oryza , Poluentes Químicos da Água , Arsênio/análise , Exposição Ambiental/análise , Farinha , Contaminação de Alimentos/análise , Índia/epidemiologia , Triticum , Poluentes Químicos da Água/efeitos adversos , Poluentes Químicos da Água/análise
5.
Shock ; 54(4): 438-450, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32649367

RESUMO

The world is currently embroiled in a pandemic of coronavirus disease 2019 (COVID-19), a respiratory illness caused by the novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The severity of COVID-19 disease ranges from asymptomatic to fatal acute respiratory distress syndrome. In few patients, the disease undergoes phenotypic differentiation between 7 and 14 days of acute illness, either resulting in full recovery or symptom escalation. However, the mechanism of such variation is not clear, but the facts suggest that patient's immune status, comorbidities, and the systemic effects of the viral infection (potentially depending on the SARS-CoV-2 strain involved) play a key role. Subsequently, patients with the most severe symptoms tend to have poor outcomes, manifest severe hypoxia, and possess elevated levels of pro-inflammatory cytokines (including IL-1ß, IL-6, IFN-γ, and TNF-α) along with elevated levels of the anti-inflammatory cytokine IL-10, marked lymphopenia, and elevated neutrophil-to-lymphocyte ratios. Based on the available evidence, we propose a mechanism wherein SARS-CoV-2 infection induces direct organ damage while also fueling an IL-6-mediated cytokine release syndrome (CRS) and hypoxia, resulting in escalating systemic inflammation, multi-organ damage, and end-organ failure. Elevated IL-6 and hypoxia together predisposes patients to pulmonary hypertension, and the presence of asymptomatic hypoxia in COVID-19 further compounds this problem. Due to the similar downstream mediators, we discuss the potential synergistic effects and systemic ramifications of SARS-CoV-2 and influenza virus during co-infection, a phenomenon we have termed "COVI-Flu." Additionally, the differences between CRS and cytokine storm are highlighted. Finally, novel management approaches, clinical trials, and therapeutic strategies toward both SARS-CoV-2 and COVI-Flu infection are discussed, highlighting host response optimization and systemic inflammation reduction.


Assuntos
Betacoronavirus , Coinfecção/terapia , Infecções por Coronavirus/complicações , Hipóxia/terapia , Imunoterapia , Influenza Humana/complicações , Pneumonia Viral/complicações , COVID-19 , Coinfecção/diagnóstico , Coinfecção/virologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/terapia , Humanos , Hipóxia/virologia , Influenza Humana/diagnóstico , Influenza Humana/terapia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , SARS-CoV-2
6.
Sci Total Environ ; 703: 134774, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31734495

RESUMO

In arsenic (As) endemic areas of south-east Asia, where a subsistence rice-based diet is prevalent, As exposure from food is mainly focused on rice intake. However, consumption of wheat is substantial and increasing. We present a probabilistic assessment of increased cancer risk from wheat-based food intake in a study population of rural Bihar, India where As exposure is endemic. Total As in wheat grains (43.64 ±â€¯48.19 µg/kg, n = 72) collected from 77 households across 19 villages was found to be lower than reported As in wheat grains from other south-east Asian countries but higher than a previous study from Bihar. This is the first study where As concentration in wheat flour was used for risk estimation, bearing in mind that it was the flour obtained after indigenous household processing of the grains that was used for making the home-made bread (chapati) which contributed 95% of wheat intake for the studied population. Interestingly, while 78% of the surveyed participants (n = 154) consumed rice every day, chapati was consumed every day by 99.5% of the participants. In contrast to previous studies, where As concentration in wheat grains was found to be lower than the flour due to the removal of the bran on grinding, we did not find any appreciable lowering of arsenic in the wheat flour (49.80 ±â€¯74.08 µg/kg, n = 58), most likely due to external contamination during processing and grinding. Estimated gender adjusted excess lifetime cancer risk of 1.23 × 10-4 for the studied rural population of Bihar indicated risk higher than the 10-4-10-6 range, typically used by the USEPA as a threshold to guide regulatory values. Hence, our findings suggest As exposure from wheat-based food intake to be of concern not only in As endemic areas of rural Bihar but also in non-endemic areas with similar wheat-based diet due to public distribution of the wheat across India.


Assuntos
Triticum , Arsênio , Farinha , Contaminação de Alimentos , Humanos , Índia , Oryza
7.
Neurol India ; 65(6): 1304-1311, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29133706

RESUMO

OBJECTIVE: Among newer neuroprotectant modalities, hypothermia and progesterone have shown a beneficial role in preliminary studies enrolling patients with severe traumatic brain injury (sTBI). The primary objective of this study was to evaluate the efficacy of progesterone with or without prophylactic hypothermia in acute sTBI patients. MATERIALS AND METHODS: This is a prospective, outcome assessor, statistician blinded, randomized, and placebo-controlled phase II trial of progesterone with or without hypothermia (factorial design). All adult patients (18-65 years) with acute sTBI (Glasgow coma score of 4-8) and presenting to trauma center within 8 h after injury were included in the trial. Computer-generated randomization was done after exclusion; sequentially numbered, opaque, sealed envelope technique was used for allocation concealment. The enrollment duration was from January 2012 to October 2014. The primary endpoint was dichotomized Glasgow outcome score (GOS) [poor recovery = GOS 1-3; good recovery = GOS 4-5], and secondary endpoints were functional independence measure (FIM) score and mortality rate at 6 and 12 months follow-up after recruitment. RESULTS: A total of 107 patients were randomized into four groups (placebo [n = 27], progesterone [n = 26], hypothermia alone [n = 27], and progesterone + hypothermia [n = 27]). The study groups were comparable in baseline parameters except for a higher incidence of decompressive craniectomy in the placebo group (P = 0.001). The analysis of GOS at 6 months revealed statistically significant better outcome in the hypothermia group (82%; P = 0.01) and a weaker evidence for progesterone group (74%; P = 0.07) as compared with the placebo group (44%). However, the outcome benefit was marginal at 1-year follow-up for the hypothermia group (82% vs. 58%, P = 0.17). The adjusted odds ratio of poor recovery at 6 months in the hypothermia group was 0.21 (confidence interval = 0.05-0.84, P = 0.03), as compared with the placebo group. Although mean FIM scores at 6 and 12 months respectively were marginally higher in the hypothermia and progesterone groups compared with the placebo group (P = 0.06 and 0.27), the proportion of functionally independent individuals were similar in all the groups (P = 0.79 and 0.51). The mortality rates were similar in all the groups at 6 and 12 months (P = 0.78 and 0.52 respectively). CONCLUSIONS: A strong evidence for prophylactic hypothermia and a weak evidence for progesterone therapy was observed for a better primary outcome at 6 months as compared to the placebo. A similar trend was observed at a 1-year follow-up. Contrary to our hypothesis, prophylactic hypothermia therapy suppressed the beneficial effects of progesterone therapy in sTBI patients. The complex cascades of factors responsible for such interactions are still unknown and need to be further determined.


Assuntos
Lesões Encefálicas Traumáticas/tratamento farmacológico , Hipotermia/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Progesterona/uso terapêutico , Adulto , Lesões Encefálicas/complicações , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas Traumáticas/complicações , Craniectomia Descompressiva/métodos , Feminino , Escala de Coma de Glasgow , Humanos , Hipotermia/complicações , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
8.
J Clin Neurosci ; 30: 31-38, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27262871

RESUMO

Recent studies have observed the central role of mitochondrial dysfunction in severe traumatic brain injury (sTBI). One hundred and seven sTBI patients (18-65years old, presenting within 8hours of injury) were randomised for a placebo controlled phase II trial of progesterone with or without hypothermia. We serially analysed blood mitochondrial enzymes (Complex I [C1], Complex IV [C4] and pyruvate dehydrogenase complex [PDH]) using a dipstick assay at admission and 7days later for 37 patients, irrespective of assigned group. Favorable Glasgow Outcome Scale (GOS) at 1year was associated with admission C1 levels above 0.19µg, admission C4 levels above 0.19µg and day 7 C1 levels above 0.17µg, all per 25µl of blood. Unfavorable GOS at 1year was associated with admission serum PDH levels above 0.23µg/25µl of blood. Survivors at 1year had significantly higher admission serum C1 levels above 0.19µg/25µl and day 7 C1 levels above 0.17µg/25µl. To our knowledge this is the first clinical trial associating blood mitochondrial enzymes with long-term outcome in sTBI. Serial monitoring and optimisation of blood C1, C4 and PDH levels could aid in prognostication and potentially guide in using mitochondrial targeted therapies. Blood mitochondrial enzymatic assay might suggest global reduction-oxidation status.


Assuntos
Biomarcadores/sangue , Lesões Encefálicas Traumáticas/sangue , Complexo IV da Cadeia de Transporte de Elétrons/sangue , Complexo I de Transporte de Elétrons/sangue , Complexo Piruvato Desidrogenase/sangue , Adulto , Lesões Encefálicas Traumáticas/terapia , Ensaios Enzimáticos , Feminino , Escala de Coma de Glasgow , Escala de Resultado de Glasgow , Humanos , Hipotermia Induzida/métodos , Masculino , Pessoa de Meia-Idade , Progesterona/uso terapêutico
9.
J Neurosurg ; 125(3): 631-41, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26722854

RESUMO

OBJECTIVE There has been increased interest in the potential importance of biochemical parameters as predictors of outcome in severe traumatic brain injury (sTBI). METHODS Of 107 patients with sTBI (age 18-65 years with a Glasgow Coma Scale score of 4-8 presenting within 8 hours after injury) who were randomized for a placebo-controlled Phase II trial of progesterone with or without hypothermia, the authors serially analyzed serum biomarkers (S100-B, glial fibrillary acidic protein [GFAP], neuron-specific enolase [NSE], tumor necrosis factor-α, interleukin-6 [IL-6], estrogen [Eg], and progesterone [Pg]). This analysis was performed using the sandwich enzyme-linked immunosorbent assay technique at admission and 7 days later for 86 patients, irrespective of assigned group. The long-term predictive values of serum biomarkers for dichotomized Glasgow Outcome Scale (GOS) score, functional independence measure, and survival status at 6 and 12 months were analyzed using an adjusted binary logistic regression model and receiver operating characteristic curve. RESULTS A favorable GOS score (4-5) at 1 year was predicted by higher admission IL-6 (above 108.36 pg/ml; area under the curve [AUC] 0.69, sensitivity 52%, and specificity 78.6%) and Day 7 Pg levels (above 3.15 ng/ml; AUC 0.79, sensitivity 70%, and specificity 92.9%). An unfavorable GOS score (1-3) at 1 year was predicted by higher Day 7 GFAP levels (above 9.50 ng/ml; AUC 0.82, sensitivity 78.6%, and specificity 82.4%). Survivors at 1 year had significantly higher Day 7 Pg levels (above 3.15 ng/ml; AUC 0.78, sensitivity 66.7%, and specificity 90.9%). Nonsurvivors at 1 year had significantly higher Day 7 GFAP serum levels (above 11.14 ng/ml; AUC 0.81, sensitivity 81.8%, and specificity 88.9%) and Day 7 IL-6 serum levels (above 71.26 pg/ml; AUC 0.87, sensitivity 81.8%, and specificity 87%). In multivariate logistic regression analysis, independent predictors of outcome at 1 year were serum levels of Day 7 Pg (favorable GOS-OR 3.24, CI 1.5-7, p = 0.003; and favorable survival-OR 2, CI 1.2-3.5, p = 0.01); admission IL-6 (favorable GOS-OR 1.04, CI 1.00-1.08, p = 0.04); and Day 7 GFAP (unfavorable GOS-OR 0.79, CI 0.65-0.95, p = 0.01; and unfavorable survival-OR 0.80, CI 0.66-0.96, p = 0.01). CONCLUSIONS Serial Pg, GFAP, and IL-6 monitoring could aid in prognosticating outcomes in patients with acute sTBI. A cause and effect relationship or a mere association of these biomarkers to outcome needs to be further studied for better understanding of the pathophysiology of sTBI and for choosing potential therapeutic targets. Clinical trial registration no.: CTRI/2009/091/000893 ( http://www.ctri.nic.in ).


Assuntos
Lesões Encefálicas Traumáticas/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Feminino , Escala de Resultado de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Método Simples-Cego , Fatores de Tempo , Adulto Jovem
10.
BMC Pediatr ; 15: 115, 2015 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-26357896

RESUMO

BACKGROUND: To Assess the efficacy of nebulised hypertonic saline (HS) (3%) among children with mild to moderately severe bronchiolitis. METHODS: Infants aged 6 weeks to 24 months, with a first episode of wheezing and Clinical Severity scores (Arch Dis Child 67:289-93, 1992) between 1 and 8, were enrolled over 4 months duration. Those with severe disease, co-morbidities, prior wheezing, recent bronchodilator and steroid use were excluded. Patients were randomized in a double-blind fashion, to receive two doses of nebulized 3% HS (Group 1) or 0.9% normal saline (Group 2) with 1.5 mg of L-Epineprine, delivered 30 min apart. Parents were contacted at 24 h and 7 days. The principal outcome measure was the mean change in clinical severity score at the end of 2 h of observation. RESULTS: A total of 100 infants (mean age 9.6 months, range 2-23 months; 61 % males) were enrolled. Patients in both groups had mild to moderately severe disease at presentation. On an intention-to-treat basis, the infants in the HS group had a significant reduction (3.57 ± 1.41) in the mean clinical severity score compared to those in the NS group (2.26 ± 1.15); [p < 0.001; CI: 0.78-1.82]. More children in the HS group (n = 35/50; 70.0%) were eligible for ER/OPD discharge at the end of 2 h than those in the NS group (n = 15/50; 30%; p < 0.001), and less likely to need a hospital re-visit (n = 5/50; 10.0%) in the next 24 h as compared to the NS group (n = 15/50, 30.0%; p < 0.001). The treatment was well tolerated, with no adverse effects. CONCLUSIONS: Nebulized 3% HS is effective, safe and superior to normal saline for outpatient management of infants with mild to moderately severe viral bronchiolitis in improving Clinical Severity Scores, facilitating early Out-Patient Department discharge and preventing hospital re-visits and admissions in the 24 h of presentation. TRIAL REGISTRATION: Clinicaltrials.gov NCTID012766821. Registered on January 12, 2011.


Assuntos
Bronquiolite Viral/tratamento farmacológico , Broncodilatadores/administração & dosagem , Epinefrina/administração & dosagem , Solução Salina Hipertônica/administração & dosagem , Administração por Inalação , Método Duplo-Cego , Quimioterapia Combinada , Serviço Hospitalar de Emergência , Feminino , Humanos , Lactente , Masculino , Nebulizadores e Vaporizadores , Índice de Gravidade de Doença , Resultado do Tratamento
11.
J Emerg Trauma Shock ; 8(3): 159-66, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26229300

RESUMO

OBJECTIVES: To determine the optimal effective dose of sodium pyruvate in maintaining the vital signs following hemorrhagic shock (HS) in rats. MATERIALS AND METHODS: Anesthetized, male Sprague-Dawley rats underwent computer-controlled HS for 30 minute followed by fluid resuscitation with either hypertonic saline, or sodium pyruvate solutions of 0.5 M, 1.0 M, 2.0 M, and 4.0 M at a rate of 5ml/kg/h (60 minute) and subsequent blood infusion (60 minute). The results were compared with sham and non- resuscitated groups. The animals were continuously monitored for mean arterial pressure, systolic and diastolic pressure, heart rate, pulse pressure, temperature, shock index and Kerdo index (KI). RESULTS: The Sham group remained stable throughout the experiment. Non-resuscitated HS animals did not survive for the entire experiment due to non-viable vital signs and poor shock and KI. All fluids were effective in normalizing the vital signs when shed blood was used adjunctively. Sodium pyruvate 2.0 M was most effective, and 4.0 M solution was least effective in improving the vital signs after HS. CONCLUSIONS: Future studies should be directed to use 2.0 M sodium pyruvate adjuvant for resuscitation on multiorgan failure and survival rate in HS.

12.
Antioxidants (Basel) ; 4(1): 134-52, 2015 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-26785342

RESUMO

The biological effects of high-dose total body ionizing irradiation [(thereafter, irradiation (IR)] are attributed to primary oxidative breakage of biomolecule targets, mitotic, apoptotic and necrotic cell death in the dose-limiting tissues, clastogenic and epigenetic effects, and cascades of functional and reactive responses leading to radiation sickness defined as the acute radiation syndrome (ARS). The range of remaining and protracted injuries at any given radiation dose as well as the dynamics of post-IR alterations is tissue-specific. Therefore, functional integrity of the homeostatic tissue barriers may decline gradually within weeks in the post-IR period culminating with sepsis and failure of organs and systems. Multiple organ failure (MOF) leading to moribundity is a common sequela of the hemotapoietic form of ARS (hARS). Onset of MOF in hARS can be presented as "two-hit phenomenon" where the "first hit" is the underlying consequences of the IR-induced radiolysis in cells and biofluids, non-septic inflammation, metabolic up-regulation of pro-oxidative metabolic reactions, suppression of the radiosensitive hematopoietic and lymphoid tissues and the damage to gut mucosa and vascular endothelium. While the "second hit" derives from bacterial translocation and spread of the bacterial pathogens and inflammagens through the vascular system leading to septic inflammatory, metabolic responses and a cascade of redox pro-oxidative and adaptive reactions. This sequence of events can create a ground for development of prolonged metabolic, inflammatory, oxidative, nitrative, and carbonyl, electrophilic stress in crucial tissues and thus exacerbate the hARS outcomes. With this perspective, the redox mechanisms, which can mediate the IR-induced protracted oxidative post-translational modification of proteins, oxidation of lipids and carbohydrates and their countermeasures in hARS are subjects of the current review. Potential role of ubiquitous, radioresistant mesenchymal stromal cells in the protracted responses to IR and IR-related septicemia is also discussed.

13.
PLoS One ; 9(3): e90079, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24594935

RESUMO

BACKGROUND: Cobalamin and folate are essential micronutrients and are important in DNA and RNA synthesis, cell proliferation, growth, hematopoiesis, and cognitive function. However, data on cobalamin and folate status are lacking particularly from young children residing in low and middle income countries. OBJECTIVE: To measure cobalamin and folate status and identifies their predictors among 6 to 35 months old children presenting with acute diarrhea. DESIGN: This was a cross-sectional study in 823 children presenting with acute diarrhea. We measured plasma cobalamin, folate, methylmalonic acid and total homocysteine who sought treatment for acute diarrhea between June 1998 and August 2000. RESULTS: The mean (SD) plasma concentrations of cobalamin, folate, total homocysteine and methylmalonic acid were 206 (124) pmol/L, 55 (32) nmol/L, 11.4 (5.6) µmol/L and 0.79 (1.2) µmol/L, respectively. The prevalence of low plasma cobalamin (<150 pmol/L) was 41% but less than 2% (15) children had low folate concentration (<10 nmol/L). Plasma homocysteine and methylmalonic acid concentrations were negatively associated with cobalamin concentration but not associated with folate status. The prevalence of cobalamin deficiency was higher in breastfed than non-breastfed children (44% vs 24%; p = <0.001). The prevalence of hyperhomocysteinemia (>10 µmol/L) and elevated methylmalonic acid (>0.28 µmol/L) were 73% and 52%, respectively. In the regression analyses, the plasma cobalamin concentration was positively associated with age, and introduction of animal or formula milk. CONCLUSIONS: Our study indicated that poor cobalamin status was common particularly among breastfed children. Folate deficiency was virtually none existent. Possible consequences of cobalamin deficiency in young children need to be explored.


Assuntos
Diarreia/sangue , Ácido Fólico/sangue , Vitamina B 12/sangue , Doença Aguda , Pré-Escolar , Estudos Transversais , Diarreia/epidemiologia , Feminino , Humanos , Lactente , Masculino , Nepal/epidemiologia
14.
Front Neurol ; 4: 196, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24376434

RESUMO

A significant proportion of the military personnel returning from Iraq and Afghanistan conflicts have suffered from both mild traumatic brain injury (mTBI) and post-traumatic stress disorder. The mechanisms are unknown. We used a rat model of repeated stress and mTBI to examine brain activity and behavioral function. Adult male Sprague-Dawley rats were divided into four groups: Naïve; 3 days repeated tail-shock stress; lateral fluid percussion mTBI; and repeated stress followed by mTBI (S-mTBI). Open field activity, sensorimotor responses, and acoustic startle responses (ASRs) were measured at various time points after mTBI. The protein expression of mitochondrial electron transport chain (ETC) complex subunits (CI-V) and pyruvate dehydrogenase (PDHE1α1) were determined in four brain regions at day 7-post mTBI. Compared to Naïves, repeated stress decreased horizontal activity; repeated stress and mTBI both decreased vertical activity; and the mTBI and S-mTBI groups were impaired in sensorimotor and ASRs. Repeated stress significantly increased CI, CII, and CIII protein levels in the prefrontal cortex (PFC), but decreased PDHE1α1 protein in the PFC and cerebellum, and decreased CIV protein in the hippocampus. The mTBI treatment decreased CV protein levels in the ipsilateral hippocampus. The S-mTBI treatment resulted in increased CII, CIII, CIV, and CV protein levels in the PFC, increased CI level in the cerebellum, and increased CIII and CV levels in the cerebral cortex, but decreased CI, CII, CIV, and PDHE1α1 protein levels in the hippocampus. Thus, repeated stress or mTBI alone differentially altered ETC expression in heterogeneous brain regions. Repeated stress followed by mTBI had synergistic effects on brain ETC expression, and resulted in more severe behavioral deficits. These results suggest that repeated stress could have contributed to the high incidence of long-term neurologic and neuropsychiatric morbidity in military personnel with or without mTBI.

15.
JNMA J Nepal Med Assoc ; 52(190): 322-31, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24362654

RESUMO

INTRODUCTION: Medical students tend to have a neutral or negative attitude to Psychiatry as a discipline. This study was initiated to explore the attitude towards mental illness and Psychiatry among the medical students and interns in Kathmandu University School of Medical Sciences. METHODS: A cross-sectional questionnaire based study was conducted among the medical students and interns at Dhulikhel Hospital.Two self-rating scales; Attitudes towards Psychiatry-30 and Attitudes to Mental Illnesswere used to assess attitudes towards mental illness and Psychiatryamong the total 159 subjects. Descriptive statistics and independent sample t-test were applied using SPSS- 16 for analysis. RESULTS: Among the total 159 subjects, 44 (27.7%) were interns. Comparison of means of each item in Attitudes towards Psychiatry-30 and Attitudes to Mental Illnesswas done between males and females, medical students and interns, fi rst semester and ninth semester students. Most of the subjects showed neutral attitude towards all the scoring items; though there were a few signifi cant differences in mean scores of some items in group wise comparison. CONCLUSIONS: Overall attitudes towards mental illness and psychiatry among the medical students and interns in our medical school were positive or neutral. A further study with medical students from different institutions is needed to get a detail nationwide picture. KEYWORDS: attitude; interns; medical students; mental illness; psychiatry.


Assuntos
Atitude do Pessoal de Saúde , Atitude Frente a Saúde , Internato e Residência , Médicos/psicologia , Estudantes de Medicina/psicologia , Estudos Transversais , Feminino , Humanos , Masculino , Transtornos Mentais , Nepal , Psiquiatria , Faculdades de Medicina
16.
JNMA J Nepal Med Assoc ; 52(189): 238-44, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23591303

RESUMO

INTRODUCTION: Consultation-liaison psychiatry is an upcoming field dealing with interdepartmental collaboration heading into multidisciplinary and holistic care. In general hospital setting, psychiatrists need to be involved in evaluation of patients referred from other specialties. This study analyzed the psychiatric morbidity among the inpatients referred to Psychiatry Department from different wards in a Tertiary care University Teaching Hospital. METHODS: Total 385 subjects were referred to the Department of Psychiatry from different wards during a period of one year. Each of them underwent a detailed psychiatric evaluation by a consultant psychiatrist once they were medically stable. Psychiatric diagnosis was considered as per International Classification of Disease-10 criteria. RESULTS: The mean age of the subjects evaluated was 37.26 (±1.86); most of them were females 216 (56.4%), married 287 (74.5%), and homemaker 159 (41.3%). Maximum 271 (70.4%) referral was from Medical ward, and most of them 292 (75.8%) were admitted in general bed. The most common medical diagnosis was self-poisoning 115 (30.6%) followed by alcoholic liver disease 49 (12.7%); while the commonest 123 (31.9%) psychiatric diagnosis was depression (including Dysthymia and Adjustment disorder). Depression remained the commonest diagnosis among those referred from medical ward 131 (34.7%); while anxiety was mostly found in the emergency referral 94 (24.5%). Significant Correlation (P <0.05) was seen between the source of referral and Psychiatric diagnosis. CONCLUSIONS: Psychiatric consultation was sought mostly by medical ward that had maximum number of patients presenting with self-poisoning. The commonest diagnosis seen in the referred in-patients was depression and anxiety disorder.


Assuntos
Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , Unidade Hospitalar de Psiquiatria , Encaminhamento e Consulta , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Cuidados Críticos , Estudos Transversais , Serviço Hospitalar de Emergência , Feminino , Hospitalização , Humanos , Masculino , Transtornos Mentais/terapia , Pessoa de Meia-Idade , Nepal , Adulto Jovem
17.
J Emerg Trauma Shock ; 5(4): 309-15, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23248499

RESUMO

OBJECTIVES: To evaluate the effectiveness of normal saline, hypertonic saline, and Ringer's lactate solution followed by blood infusion in ameliorating the physiological, biochemical, and organ functions following hemorrhagic shock (HS) in rats. MATERIALS AND METHODS: Anesthetized, male Sprague-Dawley rats underwent computer-controlled HS, and were randomly divided into five groups consisting of (1) sham, (2) HS without resuscitation, (3) resuscitation with normal saline, (4) resuscitation with hypertonic saline, and (5) resuscitation with Ringer's lactate solution. All resuscitated animals were infused with subsequent infusion of shed blood. Animals were continuously monitored for physiological, hemodynamic, biochemical parameters, and organ dysfunctions. RESULTS: Non-resuscitated animals were unable to survive due to hypotension, poor oxygen metabolism, and lactic acidosis. Although these HS related parameters were corrected by all the fluids used in this study, additional blood infusion was more effective than fluid resuscitation alone. Also, hypertonic saline was more effective than Ringer's lactate solution, and normal saline was the least effective in preserving the liver and kidney functions and muscle damage. CONCLUSIONS: All crystalloid fluids were significantly more effective in reversing the HS outcome when used with blood infusion, but hypertonic salinewith blood was more effective in preventing the organ damage than Lactated Ringers solutions or normal saline in the treatment of HS.

18.
Int J Crit Illn Inj Sci ; 2(3): 172-9, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23181213

RESUMO

CONTEXT: Mild traumatic brain injury (mTBI) represents a major health problem in civilian populations as well as among the military service members due to (1) lack of effective treatments, and (2) our incomplete understanding about the progression of secondary cell injury cascades resulting in neuronal cell death due to deficient cellular energy metabolism and damaged mitochondria. AIMS: The aim of this study was to identify and delineate the mitochondrial targeted genes responsible for altered brain energy metabolism in the injured brain. SETTINGS AND DESIGN: Rats were either grouped into naïve controls or received lateral fluid percussion brain injury (2-2.5 atm) and followed up for 7 days. MATERIALS AND METHODS: Rats were either grouped into naïve controls or received lateral fluid percussion brain injury (2-2.5 atm) and followed for 7 days. The severity of brain injury was evaluated by the neurological severity scale-revised (NSS-R) at 3 and 5 days post TBI and immunohistochemical analyses at 7 days post TBI. The expression profiles of mitochondrial-targeted genes across the hippocampus from TBI and naïe rats were also examined by oligo-DNA microarrays. RESULTS: NSS-R scores of TBI rats (5.4 ± 0.5) in comparison to naïe rats (3.9 ± 0.5) and H and E staining of brain sections suggested a mild brain injury. Bioinformatics and systems biology analyses showed 31 dysregulated genes, 10 affected canonical molecular pathways including a number of genes involved in mitochondrial enzymes for oxidative phosphorylation, mitogen-activated protein Kinase (MAP), peroxisome proliferator-activated protein (PPAP), apoptosis signaling, and genes responsible for long-term potentiation of Alzheimer's and Parkinson's diseases. CONCLUSIONS: Our results suggest that dysregulated mitochondrial-focused genes in injured brains may have a clinical utility for the development of future therapeutic strategies aimed at the treatment of TBI.

19.
Neurosci Lett ; 525(2): 140-5, 2012 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-22884618

RESUMO

Cerebral pyruvate depletion and lactate acidosis are common metabolic characteristics of patients with traumatic brain injury (TBI) and are associated with poor prognosis. Pyruvate dehydrogenase (PDH) is the rate-limiting enzyme coupling glycolysis to mitochondrial tricarboxylic acid (TCA) cycle. Brain PDH activity is regulated by its phosphorylation status and other effectors. Phosphorylation of PDH E1α1 subunit by PDH kinase inhibits PDH activity while dephosphorylation of phosphorylated PDHE1α1 by PDH phosphatase (PDP1) restores PDH activity. In situ hybridization showed that PDP1 mRNA is highly expressed in the cerebral cortex, hippocampus and thalamus of rat. Controlled cortical impact (CCI) induced a significant increase in PDP1 mRNA expression in ipsilateral cerebral cortex at 4 h (P<0.05) and 24 h post CCI (P<0.01) that returned to basal level 72 h post CCI. PDP1 mRNA level increased transiently in ipsilateral hippocampal dentate gyrus and CA1-3 subfields 4 h post CCI (P<0.01) but decreased significantly 24 h and 72 h (P<0.01) post CCI, coinciding with a marked increase in neuronal apoptosis in ipsilateral hippocampus 24 h post CCI. PDP1 mRNA expression in thalamus and other subcortical regions decreased persistently post CCI. Contralateral CCI and craniotomy showed similar effects on PDP1 mRNA expression as ipsilateral CCI. Because GFAP mRNA expression was induced in brain regions where PDP1 expression was altered, further study should determine the potential relationship between astrocyte activation, PDP1 alteration, and pyruvate metabolism following TBI.


Assuntos
Lesões Encefálicas/enzimologia , Córtex Cerebral/enzimologia , Hipocampo/enzimologia , Hiperglicemia/enzimologia , Hipoglicemia/enzimologia , Neurônios/enzimologia , Piruvato Desidrogenase (Lipoamida)-Fosfatase/metabolismo , RNA Mensageiro/metabolismo , Tálamo/enzimologia , Animais , Apoptose , Biomarcadores/metabolismo , Lesões Encefálicas/complicações , Lesões Encefálicas/patologia , Hipocampo/patologia , Hiperglicemia/etiologia , Hipoglicemia/etiologia , Hibridização In Situ , Masculino , Neurônios/patologia , Piruvato Desidrogenase (Lipoamida)-Fosfatase/genética , Ratos , Ratos Sprague-Dawley
20.
PLoS One ; 7(5): e36436, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22590543

RESUMO

OBJECTIVE AND BACKGROUND: We sought to identify predictors of extended duration of diarrhea in young children, which contributes substantially to the nearly 1 1/2 million annual diarrheal deaths globally. METHODS: We followed 6-35 month old Nepalese children enrolled in the placebo-arm of a randomized controlled trial with 391 episodes of acute diarrhea from the day they were diagnosed until cessation of the episode. Using multiple logistic regression analysis, we identified independent risk factors for having diarrhea for more than 7 days after diagnosis. RESULTS: Infants had a 17 (95% CI 3.5, 83)-fold and toddlers (12 to 23 month olds) a 9.9 (95% CI 2.1, 47)-fold higher odds of having such illness duration compared to the older children. Not being breastfed was associated with a 9.3 (95% CI 2.4, 35.7)-fold increase in the odds for this outcome. The odds also increased with increasing stool frequency. Furthermore, having diarrhea in the monsoon season also increased the risk of prolonged illness. CONCLUSION: We found that high stool frequency, not being breastfed, young age and acquiring diarrhea in the rainy season were risk factors for prolonged diarrhea. In populations such as ours, breastfeeding may be the most important modifiable risk factor for extended duration of diarrhea.


Assuntos
Diarreia/etiologia , Doença Aguda , Fatores Etários , Aleitamento Materno , Pré-Escolar , Diarreia/metabolismo , Feminino , Seguimentos , Humanos , Lactente , Masculino , Nepal/epidemiologia , Fatores de Risco , Estações do Ano
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