RESUMO
BACKGROUND: The physical literacy (PL) concept integrates different personal (e.g., physical, cognitive, psychological/affective, social) determinants of physical activity and has received growing attention recently. Although practical efforts increasingly adopt PL as a guiding concept, latest evidence has shown that PL interventions often lack specification of important theoretical foundations and basic delivery information. Therefore, the goal of the present study was to develop an expert-based template that supports researchers and practitioners in planning and reporting PL interventions. METHODS: The development process was informed by Moher et al.'s guidance for the development of research reporting guidelines. We composed a group of ten distinguished experts on PL. In two face-to-face meetings, the group first discussed a literature-driven draft of reporting items. In the second stage, the experts anonymously voted and commented on the items in two rounds (each leading to revisions) until consensus was reached. RESULTS: The panel recommended that stakeholders of PL initiatives should tightly interlock interventional aspects with PL theory while ensuring consistency throughout all stages of intervention development. The Physical Literacy Interventions Reporting Template (PLIRT) encompasses a total of 14 items (two additional items for mixed-methods studies) in six different sections: title (one item), background and definition (three items), assessment (one item each for quantitative and qualitative studies), design and content (five items), evaluation (one item plus one item each for quantitative and qualitative studies), discussion and conclusion (two items). CONCLUSION: The PLIRT was designed to facilitate improved transparency and interpretability in reports on PL interventions. The template has the potential to close gaps between theory and practice, thereby contributing to more holistic interventions for the fields of physical education, sport, and health.
Assuntos
Exercício Físico , Alfabetização , Humanos , Consenso , Educação Física e Treinamento , Pesquisa QualitativaRESUMO
BACKGROUND: The Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) was developed to incorporate the patient's perspective into evaluation of clinical benefit in advanced non-small cell lung cancer trials and meet regulatory expectations for doing so. Qualitative evidence supported 7 items covering 5 symptom concepts. OBJECTIVE: This study evaluated measurement properties of the NSCLC-SAQ's items, overall scale, and total score. METHODS: In this observational cross-sectional study, a purposive sample of patients with clinician-diagnosed advanced non-small cell lung cancer, initiating or undergoing treatment, provided sociodemographic information and completed the NSCLC-SAQ, National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Lung Symptom Index (FLSI-17), and a Patient Global Impression of Severity item. Rasch analyses, factor analyses, and assessments of construct validity and reliability were completed. RESULTS: The 152 participants had a mean age of 64 years, 57% were women, and 87% where White. The majority were Stage IV (83%), 51% had an Eastern Cooperative Oncology Group performance status of 1 (32% performance status 0 and 17% performance status 2), and 33% were treatment naïve. Rasch analyses showed ordered thresholds for response options. Factor analyses demonstrated that items could be combined for a total score. Internal consistency (Cronbach αâ¯=â¯0.78) and test-retest reliability (intraclass correlation coefficientâ¯=â¯0.87) were quite satisfactory. NSCLC-SAQ total score correlation was 0.83 with the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Lung Symptom Index-17. The NSCLC-SAQ was able to differentiate between symptom severity levels and performance status (both P values < .001). CONCLUSIONS: The NSCLC-SAQ generated highly reliable scores with substantial evidence of construct validity. The Food and Drug Administration's qualification supports the NSCLC-SAQ as a measure of symptoms in drug development. Further evaluation is needed on its longitudinal measurement properties and interepretation of meaningful within-patient score change. (Curr Ther Res Clin Exp. 2021; 82:XXX-XXX).
RESUMO
Our interprofessional team examined the mental health effects of a pilot mindfulness meditation workshop for college students (n = 39) from 4 health professions. A mixed-methods survey examined students' self-compassion (short form; SCS-sf), perceived stress (PSS-10), and self-reported mindfulness behaviors pre-workshop and at 2 months. The survey captured attitudes, beliefs, and intentions to continue mindfulness practices over time and perceived barriers to mindfulness practice. Participants (69%; 27/39) indicated significantly improved SCS-sf (p=0.016) and significantly reduced PSS (p=0.009) at 2 months post-workshop. Students reported improved mental health after 2 months, but the small sample size limits generalizability of findings. Interprofessional education promoting mindfulness skills may help prevent burnout and empathy fatigue for health professionals entering the workplace.
Assuntos
Atenção Plena , Estudantes de Ciências da Saúde , Ocupações em Saúde , Humanos , Saúde Mental , Estresse Psicológico/prevenção & controleRESUMO
PURPOSE: To determine the effectiveness of telephone motivational coaching delivered by veteran peers to improve mental health (MH) treatment engagement among veterans. METHODS: Veterans receiving primary care from primarily rural VA community-based outpatient clinics were enrolled. Veterans not engaged in MH treatment screening positive for ≥1 MH problem(s) were randomized to receive veteran peer-delivered feedback on MH screen results and referrals plus 4 sessions of telephone motivational coaching (intervention) versus veteran peer-delivered MH results and referrals without motivational coaching (control). Blinded telephone assessments were conducted at baseline, 8, 16, and 32 weeks. Cox proportional hazard models compared MH clinician-directed treatment initiation between groups; descriptive analyses compared MH treatment retention, changes in MH symptoms, quality of life, and self-care. FINDINGS: Among 272 veterans screening positive for ≥1 MH problem(s), 45% who received veteran peer telephone motivational coaching versus 46% of control participants initiated MH treatment (primary outcome) (hazard ratio: 1.09, 95% CI: 0.76-1.57), representing no between-group differences. In contrast, veterans receiving veteran peer motivational coaching achieved significantly greater improvements in depression, posttraumatic stress disorder and cannabis use scores, quality of life domains, and adoption of some self-care strategies than controls (secondary outcomes). Qualitative data revealed that veterans who received veteran peer motivational coaching may no longer have perceived a need for MH treatment. CONCLUSIONS: Among veterans with MH problems using predominantly rural VA community clinics, telephone peer motivational coaching did not enhance MH treatment engagement, but instead had positive effects on MH symptoms, quality of life indicators, and use of self-care strategies.
Assuntos
Tutoria , Veteranos , Humanos , Saúde Mental , Qualidade de Vida , TelefoneRESUMO
Millions of people worldwide use nutritional and dietary supplements, such as vitamins and minerals. These and other performance-enhancing substances are also used by high school, college, and professional athletes, bodybuilders, and amateur sports enthusiasts. The constituents of these supplements and their metabolites may be harmful and not listed on the product label. We present a case report of a 32-year-old bodybuilder using myriad nutritional, performance-enhancing, and weight-loss supplements with life-threatening encephalopathy, hepatic failure, rhabdomyolysis, and copper toxicity mimicking Wilson's disease. Emergency physicians and nurses should be aware of these potential deleterious effects and inquire about supplement use by patients with unexplained multiorgan failure. Family, friends, or acquaintances should be asked to bring the actual products to the hospital for analysis.
Assuntos
Fármacos Antiobesidade/intoxicação , Encefalopatias/induzido quimicamente , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Cobre/intoxicação , Suplementos Nutricionais/intoxicação , Falência Hepática Aguda/induzido quimicamente , Substâncias para Melhoria do Desempenho/intoxicação , Rabdomiólise/induzido quimicamente , Oligoelementos/intoxicação , Adulto , Creatina Quinase/metabolismo , Diagnóstico Diferencial , Degeneração Hepatolenticular/diagnóstico , Humanos , Falência Hepática Aguda/metabolismo , Testes de Função Hepática , Masculino , Rabdomiólise/metabolismo , Levantamento de PesoRESUMO
OBJECTIVES: Low grip strength is a marker of frailty and a risk factor for mortality among HIV patients and other populations. We investigated factors associated with grip strength in malnourished HIV patients at referral to ART, and at 12 weeks and 2-3 years after starting ART. METHODS: The study involved HIV-infected Zambian and Tanzanian participants recruited to the NUSTART trial when malnourished (body mass index <18.5 kg/m2 ) and requiring ART. The relationship of grip strength to nutritional, infectious and demographic factors was assessed by multivariable linear regression at referral for ART (n = 1742) and after 12 weeks (n = 778) and 2-3 years of ART (n = 273). RESULTS: In analyses controlled only for sex, age and height, most nutrition and infection-related variables were associated with grip strength. However, in multivariable analyses, consistent associations were seen for fat-free mass index, mid-upper arm circumference, haemoglobin and systolic blood pressure, and a variable association with fat mass index in men. C-reactive protein and CD4 count had limited independent effects on grip strength, while receiving tuberculosis treatment was associated with weaker grip strength. CONCLUSIONS: In this population of originally malnourished HIV patients, poor grip strength was more strongly and independently associated with nutritional than with infection and inflammation variables. Programmes to improve health and survival of HIV patients should incorporate nutritional assessment and management and could use grip strength as a functional indicator of improving nutrition.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/complicações , Força da Mão/fisiologia , Estado Nutricional/fisiologia , Adolescente , Adulto , Fármacos Anti-HIV/farmacologia , Índice de Massa Corporal , Proteína C-Reativa/análise , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/fisiopatologia , Síndrome de Emaciação por Infecção pelo HIV/complicações , Síndrome de Emaciação por Infecção pelo HIV/diagnóstico , Síndrome de Emaciação por Infecção pelo HIV/etiologia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Dinamômetro de Força Muscular , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Tanzânia , Adulto Jovem , ZâmbiaRESUMO
We have observed previously that micronutrient supplementation ameliorated suppression of α-defensin expression during diarrhoea. However, how interactions between anti-microbial peptide (AMP) expression and diarrhoeal disease are altered by micronutrient supplementation remain unclear. Using oral vaccination as a model of intestinal infection, we measured changes in AMP expression during multiple micronutrient supplementation. In the first part, volunteers underwent duodenal jejunal biopsy before and at 1, 2, 4 or 7 days after administration of one of three live, attenuated oral vaccines against rotavirus, typhoid and enterotoxigenic Escherichia coli. In the second part, participants were randomized to receive a multiple micronutrient supplement or placebo for 6 weeks before undergoing intestinal biopsy, vaccination against typhoid and rebiopsy after 14 days. Expression of human alpha-defensin (HD)5, HD6, hBD1, hBD2 and LL-37 was measured by quantitative reverse transcription-polymerase chain reaction. Taken together, the bacterial vaccines, but not rotavirus vaccine, reduced HD5 expression (P = 0·02, signed-rank test) and reduced LL-37 expression in seven of the eight individuals whose biopsies had expression prevaccination (P = 0·03). hBD2 was not detected. In the controlled trial, HD5 and HD6 expression after vaccination was lower [median ratio 0·5, interquartile range (IQR) = 0·07-2·2 and 0·58, IQR = 0·13-2·3, respectively] than before vaccination. There was no significant effect detected of micronutrient supplementation on expression of HD5, HD6, hBD1 or LL-37. We conclude that live attenuated bacterial vaccines, but not rotavirus vaccine, can reduce intestinal α-defensins, and typhoid vaccine reduced LL-37 expression. We found no evidence that micronutrient supplementation in the short term had any impact on anti-microbial peptide expression.
RESUMO
BACKGROUND & AIMS: Advanced HIV infection combined with undernutrition and antiretroviral therapy (ART) places HIV/AIDS patients at high risk of electrolyte abnormalities and increased morbidity and mortality. Here, in a sub-study of a large published randomized trial, we evaluated if nutritional supplements will help curtail renal electrolyte loss in HIV/AIDS patients starting ART. METHODS: 130 malnourished HIV-positive patients referred for ART received lipid-based nutrient supplements alone (LNS, n = 63) or together with vitamins and minerals (LNS-VM, n = 67). Serum and spot urine samples were collected and assayed for creatinine, potassium, magnesium and phosphate concentrations at baseline and after 12 weeks of ART, and fractional excretion and reabsorption were calculated using standard equations. RESULTS: Eighteen (28.6%) patients from the LNS and 16 (23.9%) from LNS-VM groups died, most during the referral interval before starting ART. Phosphate excretion at baseline, was high in both LNS (mean ± SD: 1.2 ± 0.6 mg/mg creatinine) and LNS-VM (1.1 ± 0.8 mg/mg creatinine) groups relative to normal physiological ranges. Phosphate excretion remained high in the LNS group (1.1 ± 0.41 mg/mg creatinine) but significantly decreased in the LNS-VM group (0.6 ± 0.28 mg/mg creatinine; p < 0.001) after 12 weeks of ART. This difference is probably explained by increased renal tubular reabsorption of phosphate in the LNS-VM group (88.3 ± 5.7%) compared to the LNS group (76.6 ± 8.9%). The fractional excretion of potassium (FEK) was not significantly different at baseline between the two groups (p = 0.69) but the values were above normal physiological ranges (i.e. >6.4%) reflecting renal potassium wasting. However, FEK was significantly lowered in the LNS-VM group (6.2 ± 3.4%) but not in the LNS group (12.8 ± 4.7%) after 12 weeks of ART (p < 0.001). Finally, the fractional excretion of magnesium was not significantly different between the two groups at baseline (p = 0.68) and remained unchanged within normal physiological ranges at 12 weeks of ART (p = 0.82) in both groups. CONCLUSIONS: The LNS-VM regimen appeared to offer protection against phosphate and potassium loss during HIV/AIDS treatment. This offers potential opportunities to improve care and support of poorly nourished HIV-infected patients in resource-limited settings. TRIAL REGISTRATION: www.pactr.org ID number: PACTR201106000300631.
Assuntos
Suplementos Nutricionais , Eletrólitos/urina , Infecções por HIV/urina , Lipídeos , Desnutrição/urina , Minerais/urina , Vitaminas/urina , Síndrome da Imunodeficiência Adquirida/sangue , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/urina , Adolescente , Adulto , Antirretrovirais/uso terapêutico , Gorduras na Dieta , Eletrólitos/sangue , Feminino , Infecções por HIV/sangue , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Magnésio/sangue , Magnésio/urina , Masculino , Desnutrição/sangue , Desnutrição/complicações , Pessoa de Meia-Idade , Minerais/sangue , Estado Nutricional , Fosfatos/sangue , Fosfatos/urina , Eliminação Renal , Vitaminas/sangue , Equilíbrio Hidroeletrolítico , Adulto Jovem , ZâmbiaRESUMO
INTRODUCTION: The aims of the present study were to develop an optimized microfluidic method for the production of the selective nicotinic acetylcholine α4ß2 receptor radiotracer [(18)F]-(-)-NCFHEB ([(18)F]-Flubatine) and to investigate its receptor binding profile and pharmacokinetic properties in rhesus monkeys in vivo. METHODS: [(18)F]-(-)-NCFHEB was prepared in two steps, a nucleophilic fluorination followed by N-Boc deprotection. PET measurements were performed in rhesus monkeys including baseline and preblocking experiments with nicotine (0.24 mg/kg). Radiometabolites in plasma were measured using HPLC. RESULTS: [(18)F]-(-)-NCFHEB was prepared in a total synthesis time of 140 min. The radiochemical purity in its final formulation was >98% and the mean specific radioactivity was 97.3 ± 16.1 GBq/µmol (n = 6) at end of synthesis (EOS). In the monkey brain, radioactivity concentration was high in the thalamus, moderate in the putamen, hippocampus, frontal cortex, and lower in the cerebellum. Nicotine blocked 98-100% of [(18)F]-(-)-NCFHEB specific binding, and the non-displaceable distribution volume (VND) was estimated at 5.9 ± 1.0 mL/cm(3) (n = 2), or 6.6 ± 1.1 mL/cm(3) after normalization by the plasma free fraction fP. Imaging data are amenable to kinetic modeling analysis using the multilinear analysis (MA1) method, and model-derived binding parameters display good test-retest reproducibility. In rhesus monkeys, [(18)F]-(-)-NCFHEB can yield robust regional binding potential (BPND) values (thalamus = 4.1 ± 1.5, frontal cortex = 1.2 ± 0.2, putamen = 0.96 ± 0.45, and cerebellum = 0.10 ± 0.29). CONCLUSION: An efficient microfluidic synthetic method was developed for preparation of [(18)F]-(-)-NCFHEB. PET examination in rhesus monkeys showed that [(18)F]-(-)-NCFHEB entered the brain readily and its regional radioactivity uptake pattern was in accordance with the known distribution of α4ß2 receptors. Estimated non-displaceable binding potential (BPND) values in brain regions were better than those of [(18)F]2-FA and comparable to [(18)F]AZAN. These results confirm previous findings and support further examination of [(18)F]-(-)-NCFHEB in humans.
Assuntos
Benzamidas/farmacocinética , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/farmacocinética , Radioisótopos de Flúor/farmacocinética , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/farmacocinética , Receptores Nicotínicos/metabolismo , Animais , Avaliação Pré-Clínica de Medicamentos , Humanos , Macaca mulatta , Radioquímica , Distribuição TecidualRESUMO
Advances in the spatial resolution of modern analytical techniques have tremendously augmented the scientific insight gained from the analysis of natural samples. Yet, while techniques for the elemental and structural characterization of samples have achieved sub-nanometre spatial resolution, infrared spectral mapping of geochemical samples at vibrational 'fingerprint' wavelengths has remained restricted to spatial scales >10 µm. Nevertheless, infrared spectroscopy remains an invaluable contactless probe of chemical structure, details of which offer clues to the formation history of minerals. Here we report on the successful implementation of infrared near-field imaging, spectroscopy and analysis techniques capable of sub-micron scale mineral identification within natural samples, including a chondrule from the Murchison meteorite and a cometary dust grain (Iris) from NASA's Stardust mission. Complementary to scanning electron microscopy, energy-dispersive X-ray spectroscopy and transmission electron microscopy probes, this work evidences a similarity between chondritic and cometary materials, and inaugurates a new era of infrared nano-spectroscopy applied to small and invaluable extraterrestrial samples.
RESUMO
Educational campaigns and legislative actions may have led to an overall decrease in the prevalence of volatile substance misuse (VSM) in many countries; however, it is still a common practice throughout the world. Studies currently suggest that girls are misusing volatile substances more than before and at a prevalence rate equal to or exceeding that of boys in several countries. Products that may be misused are ubiquitous and relatively easy to acquire. The most commonly misused substances in recent studies are fuels such as butane or petrol and compressed gas dusters and deodorants that may contain fluorocarbons and/or butane. Detection of VSM is challenging, therefore physicians must maintain a high level of suspicion based on history and clinical presentation. Clues to misuse are often subtle and may include the patient's proximity to a volatile substance or paraphernalia when found intoxicated, dermal burns, blisters, pigments, or rashes, and chemical odors. The primary targets of toxicity are the brain and the heart. The leading cause of death from VSM is from ventricular dysrhythmias. Treatment of toxicity begins with support of airway, breathing, and circulation. Exogenous catecholamines should be avoided if possible due to the theoretical "sensitized" and irritable myocardium. In the case of ventricular dysrhythmias, direct current defibrillation and/or beta-adrenergic receptor antagonism should be used. New evidence demonstrates the addictive potential of VSM yet effective therapy remains uncertain. Further research is needed in developing methods for preventing, detecting, and treating the harmful effects of VSM.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Arritmias Cardíacas/diagnóstico , Butanos/toxicidade , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Disfunção Ventricular/diagnóstico , Adolescente , Adulto , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/terapia , Encéfalo/efeitos dos fármacos , Cardioversão Elétrica , Fluorocarbonos/toxicidade , Coração/efeitos dos fármacos , Humanos , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/terapia , Disfunção Ventricular/etiologia , Disfunção Ventricular/terapia , Compostos Orgânicos Voláteis , Adulto JovemRESUMO
There is an urgent need to identify ways of enhancing the mucosal immune response to oral vaccines. Rotavirus vaccine protection is much lower in Africa and Asia than in industrialized countries, and no oral vaccine has efficacy approaching the best systemic vaccines. All-trans retinoic acid (ATRA) up-regulates expression of α4ß7 integrin and CCR9 on lymphocytes in laboratory animals, increasing their gut tropism. The aim of this study was to establish the feasibility of using ATRA as an oral adjuvant for oral typhoid vaccination. In order to establish that standard doses of oral ATRA can achieve serum concentrations greater than 10 nmol/l, we measured ATRA, 9-cis and 13-cis retinoic acid in serum of 14 male volunteers before and 3 h after 10 mg ATRA. We then evaluated the effect of 10 mg ATRA given 1 h before, and for 7 days following, oral typhoid vaccine in eight men, and in 24 men given various control interventions. We measured immunoglobulin (Ig)A directed against lipopolysaccharide (LPS)and protein preparations of vaccine antigens in whole gut lavage fluid (WGLF) and both IgA and IgG in serum, 1 day prior to vaccination and on day 14. Median [interquartile range (IQR)] C(max) was 26·2 (11·7-39·5) nmol/l, with no evidence of cumulation over 8 days. No adverse events were observed. Specific IgA responses to LPS (P = 0·02) and protein (P = 0·04) were enhanced in WGLF, but no effect was seen on IgA or IgG in serum. ATRA was well absorbed, well tolerated and may be a promising candidate oral adjuvant.
Assuntos
Adjuvantes Imunológicos , Imunidade nas Mucosas/imunologia , Tretinoína/imunologia , Vacinas Tíficas-Paratíficas/imunologia , Administração Oral , Adulto , Anticorpos Antibacterianos/imunologia , Humanos , Imunoglobulina A Secretora/imunologia , Mucosa Intestinal/imunologia , Masculino , Pessoa de Meia-Idade , Tretinoína/administração & dosagem , Tretinoína/farmacocinética , Vacinas Tíficas-Paratíficas/administração & dosagem , Adulto Jovem , ZâmbiaRESUMO
BACKGROUND/OBJECTIVE: Low birthweight (LBW) and intrauterine growth restriction are linked with maternal nutritional status during pregnancy, and maternal supplementation with multiple micronutrients (MMNs) is reported to increase birthweight. Responses to MMN, however, might be modified by maternal nutrition. SUBJECTS/METHODS: To examine the differential effects of maternal nutritional status on birthweight responses to prenatal MMN supplementation, data from the Supplementation with Multiple Micronutrient Intervention Trial, a cluster-randomized trial in Indonesia was analyzed. Birthweight outcomes of 7001 infants whose mothers received iron/folic acid were compared with 7292 infants whose mothers received MMN. The modifying effects of maternal short-term nutritional status (mid-upper arm circumference (MUAC) and long-term nutritional status (height) on the birthweight response to MMN supplementation were assessed. RESULTS: For women with higher MUAC (≥23.5 cm), MMN increased mean birthweight by 33 g (95% confidence interval (CI): -1 to 66, P=0.06) and significantly reduced LBW by 21% (relative risk: 0.79, 95% CI: 0.64-0.99, P=0.04). The modifying effect of MUAC on mean birthweight, LBW and small for gestational age was significant. There was no evidence of a modifying effect of maternal height on the response to MMN. CONCLUSIONS: Supplementation with MMN in pregnancy increased birthweight, but maternal nutritional status modified this response, with infants born to women with better short-term nutrition having greater birthweight response.
Assuntos
Peso ao Nascer , Suplementos Nutricionais , Fenômenos Fisiológicos da Nutrição Materna , Micronutrientes/administração & dosagem , Estado Nutricional , Adulto , Análise por Conglomerados , Feminino , Retardo do Crescimento Fetal , Seguimentos , Humanos , Indonésia , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Ferro da Dieta/administração & dosagem , Modelos Lineares , Masculino , Gravidez , Fatores Socioeconômicos , Adulto JovemRESUMO
The trout heart is 10-fold more sensitive to Ca(2+) than the mammalian heart. This difference is due, in part, to cardiac troponin C (cTnC) from trout having a greater Ca(2+) affinity than human cTnC. To determine what other proteins are involved, we cloned cardiac troponin I (cTnI) from the trout heart and determined how it alters the Ca(2+) affinity of a cTn complex containing all mammalian components (mammalian cTn). Ca(2+) activation of the complex was characterized using a human cTnC mutant that contains anilinonapthalenesulfote iodoacetamide attached to Cys53. When the cTn complex containing labeled human cTnC was titrated with Ca(2+), its fluorescence changed, reaching an asymptote upon saturation. Our results reveal that trout cTnI lacks the N-terminal extension found in cTnI from all other vertebrate groups. This protein domain contains two targets (Ser23 and Ser24) for protein kinase A (PKA) and protein kinase C. When these are phosphorylated, the rate of cardiomyocyte relaxation increases. When rat cTnI in the mammalian cTn complex was replaced with trout cTnI, the Ca(2+) affinity was increased â¼1.8-fold. This suggests that trout cTnI contributes to the high Ca(2+) sensitivity of the trout heart. Treatment of the two cTn complexes with PKA decreased the Ca(2+) affinity of both complexes. However, the change for the complex containing rat cTnI was 2.2-fold that of the complex containing trout cTnI. This suggests that the phosphorylation of trout cTnI does not play as significant a role in regulating cTn function in trout.
Assuntos
Cálcio/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Miocárdio/metabolismo , Oncorhynchus mykiss/metabolismo , Citoesqueleto de Actina/metabolismo , Sequência de Aminoácidos , Animais , DNA Complementar , Humanos , Dados de Sequência Molecular , Miócitos Cardíacos/metabolismo , Fosforilação , Estrutura Terciária de Proteína , Ratos , Troponina C/metabolismo , Troponina T/metabolismoRESUMO
This paper reviews evidence suggesting that nicotine and tobacco smoke profoundly modulate the effects of alcohol on γ-aminobutyric acid (GABA) neuronal function, specifically at the GABA(A)-benzodiazepine receptor (GABA(A)-BZR). The focus of this paper is on recent neuroimaging evidence in preclinical models as well as clinical experiments. First, we review findings implicating the role of alcohol at the GABA(A)-BZR and discuss the changes in GABA(A)-BZR availability during acute and prolonged alcohol withdrawal. Second, we discuss preclinical evidence that suggests nicotine affects GABA neuronal function indirectly by a primary action at neuronal nicotinic acetylcholine receptors. Third, we show how this evidence converges in studies that examine GABA levels and GABA(A)-BZRs in alcohol-dependent smokers and nonsmokers, suggesting that tobacco smoking attenuates the chemical changes that occur during alcohol withdrawal. Based on a comprehensive review of literature, we hypothesize that tobacco smoking minimizes the changes in GABA levels that typically occur during the acute cycles of drinking in alcohol-dependent individuals. Thus, during alcohol withdrawal, the continued tobacco smoking decreases the severity of the withdrawal-related changes in GABA chemistry. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.
Assuntos
Alcoolismo/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Ácido gama-Aminobutírico/metabolismo , Alcoolismo/metabolismo , Alcoolismo/reabilitação , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Humanos , Cintilografia , Receptores de GABA-A/metabolismo , FumarRESUMO
BACKGROUND: Recent studies in noise-induced and idiopathic sensorineural hearing loss have suggested that magnesium supplementation may lessen both hearing loss and the severity of tinnitus in patients. Further epidemiological evidence indicates that all age groups of Americans fall short of the recommended daily allowance for magnesium by 100 mg daily. PURPOSE: The purpose of this study was to examine any potential benefit in lessening the severity of tinnitus in patients taking supplemental magnesium. RESEARCH DESIGN: The study was a single-arm, open-label, before-and-after study of oral magnesium (532 mg per day) in 26 patients for 3 months. Tinnitus severity was evaluated and recorded daily by the patient using the Tinnitus Distress Rating (TDR) scale of 0 (no tinnitus) to 10 (worst possible tinnitus). The Tinnitus Handicap Inventory (THI) was administered before and at the end of the study, and scores were converted to the grades of the 5-item Tinnitus Severity Scale (TSS). The purpose of this phase 2 study was to investigate whether the treatment was effective at all, and, as such, a placebo control was not performed. All data were collected at Mayo Clinic in Scottsdale, Arizona, between March 6 and December 10, 2008. STUDY SAMPLE: Patients with moderate to very severe tinnitus (TDR score of 3 through 8). INTERVENTION: Daily magnesium supplementation, 532 mg; patient completion of the THI; and daily self-report of TDR. DATA COLLECTION AND ANALYSIS: The main outcome measures were mean TDR scale scores and THI scores as converted to TSS grades. The primary analysis was done on the basis of intention to treat. RESULTS: Twenty-six patients were enrolled; 19 completed the study. The extent of handicap, as measured by THI/TSS, for subjects with slight or greater impairment was significantly decreased (P=.03). Patients who ranked slight or greater on the THI/TSS before intervention showed a significant decrease in the severity of their tinnitus at post-testing (P=.008). CONCLUSION: The results suggest that magnesium may have a beneficial effect on perception of tinnitus-related handicap when scored with the THI.
Assuntos
Deficiência de Magnésio/complicações , Deficiência de Magnésio/tratamento farmacológico , Magnésio/administração & dosagem , Zumbido/tratamento farmacológico , Zumbido/etiologia , Adulto , Idoso , Avaliação da Deficiência , Feminino , Seguimentos , Humanos , Magnésio/efeitos adversos , Deficiência de Magnésio/psicologia , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Índice de Gravidade de Doença , Inquéritos e Questionários , Zumbido/psicologia , Resultado do TratamentoRESUMO
Lead poisoning has been reportedly linked to a high risk of learning disabilities, aggression and criminal offenses. To study the association between lead exposure and antisocial/delinquent behavior, a cross-sectional study was conducted with 173 Brazilian youths aged 14-18 and their parents (n=93), living in impoverished neighborhoods of Bauru-SP, with high criminality indices. Self-Reported Delinquency (SRD) and Child Behavior Checklist (CBCL) questionnaires were used to evaluate delinquent/antisocial behavior. Body lead burdens were evaluated in surface dental enamel acid microbiopsies. The dental enamel lead levels (DELL) were quantified by graphite furnace atomic absorption spectrometry (GFAAS) and phosphorus content was measured using inductively coupled plasma optical emission spectrometry (ICP-OES). Logistic regression was used to identify associations between DELL and each scale defined by CBCL and SRD scores. Odd ratios adjusted for familial and social covariates, considering a group of youths exposed to high lead levels (>or=75 percentile), indicated that high DELL is associated with increased risk of exceeding the clinical score for somatic complaints, social problems, rule-breaking behavior and externalizing problems (CI 95%). High DELL was not found to be associated with elevated SRD scores. In conclusion, our data support the hypothesis that high-level lead exposure can trigger antisocial behavior, which calls for public policies to prevent lead poisoning.
Assuntos
Transtorno da Personalidade Antissocial/induzido quimicamente , Transtorno da Personalidade Antissocial/epidemiologia , Esmalte Dentário/metabolismo , Exposição Ambiental/efeitos adversos , Intoxicação do Sistema Nervoso por Chumbo/epidemiologia , Chumbo/metabolismo , Adolescente , Transtorno da Personalidade Antissocial/fisiopatologia , Biomarcadores/análise , Biomarcadores/metabolismo , Brasil/epidemiologia , Comorbidade , Psicologia Criminal , Estudos Transversais , Esmalte Dentário/química , Feminino , Humanos , Chumbo/análise , Intoxicação do Sistema Nervoso por Chumbo/diagnóstico , Intoxicação do Sistema Nervoso por Chumbo/fisiopatologia , Masculino , Fósforo/análise , Fósforo/metabolismo , Áreas de Pobreza , Fatores Socioeconômicos , Espectrofotometria Atômica , Inquéritos e QuestionáriosRESUMO
Nutrient limitation is an environmental stress that may reduce the effectiveness of bioremediation strategies, especially when the contaminants are organic compounds or when organic compounds are added to promote microbial activities such as metal reduction. Genes indicative of phosphate-limitation were identified by microarray analysis of chemostat cultures of Geobacter sulfureducens. This analysis revealed that genes in the pst-pho operon, which is associated with a high-affinity phosphate uptake system in other microorganisms, had significantly higher transcript abundance under phosphate-limiting conditions, with the genes pstB and phoU upregulated the most. Quantitative PCR analysis of pstB and phoU transcript levels in G. sulfurreducens grown in chemostats demonstrated that the expression of these genes increased when phosphate was removed from the culture medium. Transcripts of pstB and phoU within the subsurface Geobacter species predominating during an in situ uranium-bioremediation field experiment were more abundant than in chemostat cultures of G. sulfurreducens that were not limited for phosphate. Addition of phosphate to incubations of subsurface sediments did not stimulate dissimilatory metal reduction. The added phosphate was rapidly adsorbed onto the sediments. The results demonstrate that Geobacter species can effectively reduce U(VI) even when experiencing suboptimal phosphate concentrations and that increasing phosphate availability with phosphate additions is difficult to achieve because of the high reactivity of this compound. This transcript-based approach developed for diagnosing phosphate limitation should be applicable to assessing the potential need for additional phosphate in other bioremediation processes.
Assuntos
Água Doce/microbiologia , Geobacter/genética , Geobacter/metabolismo , Fosfatos/metabolismo , Urânio/metabolismo , Poluentes da Água/metabolismo , Biodegradação Ambiental , Água Doce/química , Regulação Bacteriana da Expressão Gênica , Geobacter/crescimento & desenvolvimentoRESUMO
BACKGROUND: While manually-assisted body-weight supported treadmill training (BWSTT) has revealed improved locomotor function in persons with post-stroke hemiparesis, outcomes are inconsistent and it is very labor intensive. Thus an alternate treatment approach is desirable. Objectives of this pilot study were to: 1) compare the efficacy of body-weight supported treadmill training (BWSTT) combined with the Lokomat robotic gait orthosis versus manually-assisted BWSTT for locomotor training post-stroke, and 2) assess effects of fast versus slow treadmill training speed. METHODS: Sixteen volunteers with chronic hemiparetic gait (0.62 +/- 0.30 m/s) post-stroke were randomly allocated to Lokomat (n = 8) or manual-BWSTT (n = 8) 3x/wk for 4 weeks. Groups were also stratified by fast (mean 0.92 +/- 0.15 m/s) or slow (0.58 +/- 0.12 m/s) training speeds. The primary outcomes were self-selected overground walking speed and paretic step length ratio. Secondary outcomes included: fast overground walking speed, 6-minute walk test, and a battery of clinical measures. RESULTS: No significant differences in primary outcomes were revealed between Lokomat and manual groups as a result of training. However, within the Lokomat group, self-selected walk speed, paretic step length ratio, and four of the six secondary measures improved (p = 0.04-0.05, effect sizes = 0.19-0.60). Within the manual group, only balance scores improved (p = 0.02, effect size = 0.57). Group differences between fast and slow training groups were not revealed (p > or = 0.28). CONCLUSION: Results suggest that Lokomat training may have advantages over manual-BWSTT following a modest intervention dose in chronic hemiparetic persons and further, that our training speeds produce similar gait improvements. Suggestions for a larger randomized controlled trial with optimal study parameters are provided.