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Nonalcoholic fatty liver disease (NAFLD) is characterized by low-circulating concentration of high-density lipoprotein cholesterol (HDL-C) and raised triacylglycerol (TAG). Exercise reduces hepatic fat content, improves insulin resistance and increases clearance of very-low-density lipoprotein-1 (VLDL1). However, the effect of exercise on TAG and HDL-C metabolism is unknown. We randomized male participants to 16 wk of supervised, moderate-intensity aerobic exercise (n = 15), or conventional lifestyle advice (n = 12). Apolipoprotein A-I (apoA-I) and VLDL-TAG and apolipoprotein B (apoB) kinetics were investigated using stable isotopes (1-[13C]-leucine and 1,1,2,3,3-2H5 glycerol) pre- and postintervention. Participants underwent MRI/spectroscopy to assess changes in visceral fat. Results are means ± SD. At baseline, there were no differences between exercise and control groups for age (52.4 ± 7.5 vs. 52.8 ± 10.3 yr), body mass index (BMI: 31.6 ± 3.2 vs. 31.7 ± 3.6 kg/m2), and waist circumference (109.3 ± 7.5 vs. 110.0 ± 13.6 cm). Percentage of liver fat was 23.8 (interquartile range 9.8-32.5%). Exercise reduced body weight (101.3 ± 10.2 to 97.9 ± 12.2 kg; P < 0.001) and hepatic fat content [from 19.6%, interquartile range (IQR) 14.6-36.1% to 8.9% (4.4-17.8%); P = 0.001] and increased the fraction HDL-C concentration (measured following ultracentrifugation) and apoA-I pool size with no change in the control group. However, plasma and VLDL1-TAG concentrations and HDL-apoA-I fractional catabolic rate (FCR) and production rate (PR) did not change significantly with exercise. Both at baseline (all participants) and after exercise there was an inverse correlation between apoA-I pool size and VLDL-TAG and -apoB pool size. The modest effect of exercise on HDL metabolism may be explained by the lack of effect on plasma and VLDL1-TAG.
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Apolipoproteína A-I/metabolismo , HDL-Colesterol/metabolismo , Ejercicio Físico , Grasa Intraabdominal/metabolismo , Lipoproteínas HDL/metabolismo , Lipoproteínas VLDL/metabolismo , Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Triglicéridos/metabolismo , Adulto , Humanos , Grasa Intraabdominal/diagnóstico por imagen , Cinética , Hígado/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/terapia , Resultado del Tratamiento , Pérdida de PesoRESUMEN
Background: Established procedures for mass casualty decontamination involve the deployment of equipment for showering with water (such as the ladder pipe system [LPS] and technical decontamination [TD]). This necessarily introduces a short, but critical delay. The incorporation of dry decontamination to the incident response process offers the potential to establish a more rapid and timely intervention. Objectives: To investigate the effectiveness of various dry (DD) and wet decontamination strategies for removing a chemical warfare simulant (methyl salicylate; MS) from the hair and skin of human volunteers. Methods: The simulant was applied to volunteers via whole body exposure to an aerosol. Three decontamination protocols (dry, LPS and technical decontamination) were applied, singly and in various combinations. The efficacy of the protocols was evaluated by fluorescent photography and analysis of residual MS from skin/hair swabs, decontamination materials and air samples. Results: Dry decontamination was effective, with the greatest reduction in skin and hair contamination arising from the "Triple Protocol" (DD+LPS+TD). Secondary hazards associated with contaminated individuals and equipment decreased as the number of decontamination procedures increased. In particular, dry decontamination reduced the potential contact and inhalation hazard arising from used washcloths, towels and vapor within the TD units. Discussion: The introduction of dry decontamination prior to wet forms of decontamination offers a simple strategy to initiate treatment at a much earlier opportunity, with a corresponding improvement in clinical outcomes and substantial reduction of secondary hazards associated with operational processes.
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Servicios Médicos de Urgencia , Socorristas , Humanos , Descontaminación/métodos , Lipopolisacáridos , CabelloRESUMEN
STUDY OBJECTIVE: The aim of this study was to evaluate the clinical and operational effectiveness of US federal government guidance (Primary Response Incident Scene Management [PRISM]) for the initial response phase to chemical incidents. METHODS: The study was performed as a large-scale exercise (Operation DOWNPOUR). Volunteers were dosed with a chemical warfare agent simulant to quantify the efficacy of different iterations of dry, ladder pipe system, or technical decontamination. RESULTS: The most effective process was a triple combination of dry, ladder pipe system, and technical decontamination, which attained an average decontamination efficiency of approximately 100% on exposed hair and skin sites. Both wet decontamination processes (ladder pipe system and technical decontamination, alone or in combination with dry decontamination) were also effective (decontamination efficiency >96%). In compliant individuals, dry decontamination was effective (decontamination efficiency approximately 99%), but noncompliance (tentatively attributed to suboptimal communication) resulted in significantly reduced efficacy (decontamination efficiency approximately 70%). At-risk volunteers (because of chronic illness, disability, or language barrier) were 3 to 8 times slower than ambulatory casualties in undergoing dry and ladder pipe system decontamination, a consequence of which may be a reduction in the overall rate at which casualties can be processed. CONCLUSION: The PRISM incident response protocols are fit for purpose for ambulatory casualties. However, a more effective communication strategy is required for first responders (particularly when guiding dry decontamination). There is a clear need to develop more appropriate decontamination procedures for at-risk casualties.
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Liberación de Peligros Químicos , Descontaminación , Planificación en Desastres/organización & administración , Socorristas/educación , Incidentes con Víctimas en Masa , Sustancias para la Guerra Química , Descontaminación/métodos , Guías como Asunto , HumanosRESUMEN
This report describes an approach to the simultaneous retention of a nasal prosthesis and an intraoral prosthesis for a patient who had undergone a total rhinectomy with resection of the upper lip and premaxilla. At the time of the nasal resection, 2 dental implants were placed adjacent to the resection margins in the first premolar positions. These were used to anchor an intraoral, milled titanium bar and overdenture to replace the missing anterior teeth and provide support for the upper lip, which had been reconstructed with a vascularized radial forearm free-flap. The titanium bar also incorporated a connection for a tissue-penetrating percutaneous nasal extension, which pierced the radial forearm flap near the junction with the hard palate. Magnetic attachments screwed to the nasal extension retained a nasal prosthesis. The predictable and straightforward implementation of this novel concept with digital design and manufacture of the titanium components and guided placement of the nasal extension was made possible with software planning.
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Prótesis Maxilofacial , Nariz/cirugía , Retención de la Prótesis/métodos , Anciano , Carcinoma de Células Escamosas/cirugía , Femenino , Humanos , Implantación de Prótesis Maxilofacial/métodos , Neoplasias Nasales/cirugíaRESUMEN
Non-alcoholic fatty liver disease (NAFLD) is associated with multi-organ (hepatic, skeletal muscle, adipose tissue) insulin resistance (IR). Exercise is an effective treatment for lowering liver fat but its effect on IR in NAFLD is unknown. We aimed to determine whether supervised exercise in NAFLD would reduce liver fat and improve hepatic and peripheral (skeletal muscle and adipose tissue) insulin sensitivity. Sixty nine NAFLD patients were randomized to 16 weeks exercise supervision (n=38) or counselling (n=31) without dietary modification. All participants underwent MRI/spectroscopy to assess changes in body fat and in liver and skeletal muscle triglyceride, before and following exercise/counselling. To quantify changes in hepatic and peripheral insulin sensitivity, a pre-determined subset (n=12 per group) underwent a two-stage hyperinsulinaemic euglycaemic clamp pre- and post-intervention. Results are shown as mean [95% confidence interval (CI)]. Fifty participants (30 exercise, 20 counselling), 51 years (IQR 40, 56), body mass index (BMI) 31 kg/m(2) (IQR 29, 35) with baseline liver fat/water % of 18.8% (IQR 10.7, 34.6) completed the study (12/12 exercise and 7/12 counselling completed the clamp studies). Supervised exercise mediated a greater reduction in liver fat/water percentage than counselling [Δ mean change 4.7% (0.01, 9.4); P<0.05], which correlated with the change in cardiorespiratory fitness (r=-0.34, P=0.0173). With exercise, peripheral insulin sensitivity significantly increased (following high-dose insulin) despite no significant change in hepatic glucose production (HGP; following low-dose insulin); no changes were observed in the control group. Although supervised exercise effectively reduced liver fat, improving peripheral IR in NAFLD, the reduction in liver fat was insufficient to improve hepatic IR.
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Ejercicio Físico/fisiología , Hígado/química , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Obesidad/metabolismo , Grasas/análisis , Grasas/metabolismo , Femenino , Técnica de Clampeo de la Glucosa , Homeostasis/fisiología , Humanos , Resistencia a la Insulina/fisiología , Hígado/fisiopatología , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Músculo Esquelético/química , Músculo Esquelético/fisiopatología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Obesidad/complicaciones , Obesidad/fisiopatología , Aptitud Física/fisiología , Triglicéridos/análisisRESUMEN
Energy used in dwellings is an important target for actions to avert climate change. Properly designed and implemented, such actions could have major co-benefits for public health. To investigate, we examined the effect of hypothetical strategies to improve energy efficiency in UK housing stock and to introduce 150 million low-emission household cookstoves in India. Methods similar to those of WHO's Comparative Risk Assessment exercise were applied to assess the effect on health that changes in the indoor environment could have. For UK housing, the magnitude and even direction of the changes in health depended on details of the intervention, but interventions were generally beneficial for health. For a strategy of combined fabric, ventilation, fuel switching, and behavioural changes, we estimated 850 fewer disability-adjusted life-years (DALYs), and a saving of 0.6 megatonnes of carbon dioxide (CO(2)), per million population in 1 year (on the basis of calculations comparing the health of the 2010 population with and without the specified outcome measures). The cookstove programme in India showed substantial benefits for acute lower respiratory infection in children, chronic obstructive pulmonary disease, and ischaemic heart disease. Calculated on a similar basis to the UK case study, the avoided burden of these outcomes was estimated to be 12 500 fewer DALYs and a saving of 0.1-0.2 megatonnes CO(2)-equivalent per million population in 1 year, mostly in short-lived greenhouse pollutants. Household energy interventions have potential for important co-benefits in pursuit of health and climate goals.
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Contaminación del Aire/prevención & control , Composición Familiar , Efecto Invernadero/prevención & control , Contaminantes Atmosféricos/efectos adversos , Conducta , Códigos de Edificación , Conservación de los Recursos Energéticos , Culinaria , Suministros de Energía Eléctrica , Combustibles Fósiles , Calefacción , Humanos , India , Salud Pública , Reino UnidoRESUMEN
This Series has examined the health implications of policies aimed at tackling climate change. Assessments of mitigation strategies in four domains-household energy, transport, food and agriculture, and electricity generation-suggest an important message: that actions to reduce greenhouse-gas emissions often, although not always, entail net benefits for health. In some cases, the potential benefits seem to be substantial. This evidence provides an additional and immediate rationale for reductions in greenhouse-gas emissions beyond that of climate change mitigation alone. Climate change is an increasing and evolving threat to the health of populations worldwide. At the same time, major public health burdens remain in many regions. Climate change therefore adds further urgency to the task of addressing international health priorities, such as the UN Millennium Development Goals. Recognition that mitigation strategies can have substantial benefits for both health and climate protection offers the possibility of policy choices that are potentially both more cost effective and socially attractive than are those that address these priorities independently.
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Salud Global , Efecto Invernadero/prevención & control , Prioridades en Salud , Cambio Climático , Salud PúblicaRESUMEN
This in vitro study evaluated the "triple protocol" of dry decontamination, the ladder pipe system (a method for gross decontamination), and technical decontamination for the decontamination of hair following chemical contamination. First, we assessed the efficacy of the 3 protocols, alone or in combination, on excised porcine skin and human hair contaminated with either methyl salicylate (MS), phorate (PHR), sodium fluoroacetate (SFA), or potassium cyanide (KCN). A second experiment investigated the residual hair contamination following decontamination with the triple protocol at different intervals postexposure. In a third experiment, hair decontaminated after exposure to MS or PHR was evaluated for off-gassing. Though skin decontamination was highly effective, a substantial proportion (20%-40%) of the lipophilic compounds (MS and PHR) remained within the hair. The more water-soluble contaminants (SFA and KCN) tended to form much smaller reservoirs within the hair. Interestingly, substantial off-gassing of MS, a medium volatility chemical, was detectable from triple-decontaminated hair up to 5 days postexposure. Overall, the decontamination strategies investigated were effective for the decontamination of skin, but less so for hair. These findings highlight the importance of contaminated hair serving as a source of potential secondary contamination by contact or inhalation. Therefore, consideration should be given to the removal of contaminated hair following exposure to toxic chemicals.
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Five carrier media with different shapes (spherical and cylindrical), sizes, voidage and protected surface areas (112-610â¯m2/m3) were studied in a pilot scale moving bed biofilm reactor (MBBR). This study aimed at assessing start-up duration using biofilm formation rates. Results indicated that the spherical media required shorter periods to achieve stable biofilm formation rates associated with chemical oxygen demand (COD) (15-17â¯days), compared to cylindrical high surface area media (23-24â¯days). Protected surface area presented weaker correlations with the biofilm formation rate for COD (R2â¯=â¯0.83) and ammonia removal (R2â¯=â¯0.76). However, good correlations were observed with a combination of the media physical factors: dimensionality (Di), voidage (Voi), and hydraulic efficiency (HE) strongly correlated with biofilm formation rates for heterotrophic (R2â¯=â¯0.95) and nitrifying bacteria (R2â¯=â¯0.92). This study proposes that the media physical properties can contribute to shortening start-up, contributing to improved removal rates and fast commissioning of MBBRs.
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Biopelículas , Reactores Biológicos , Amoníaco , Análisis de la Demanda Biológica de Oxígeno , Eliminación de Residuos LíquidosRESUMEN
A fed-batch process for the high cell density cultivation of E. coli TG1 and the production of the recombinant protein phenylalanine dehydrogenase (PheDH) was developed. A model based on Monod kinetics with overflow metabolism and incorporating acetate utilization kinetics was used to generate simulations that describe cell growth, acetate production and reconsumption, and glucose consumption during fed-batch cultivation. Using these simulations a predetermined feeding profile was elaborated that would maintain carbon-limited growth at a growth rate below the critical growth rate for acetate formation (mu < mu(crit)). Two starvation periods are incorporated into the feed profile in order to induce acetate utilization. Cell concentrations of 53 g dry cell weight (DCW)/L were obtained with a final intracellular product concentration of recombinant protein corresponding to approximately 38% of the total cell protein. The yield of PheDH was 129 U/mL with a specific activity of 1.2 U/mg DCW and a maximum product formation rate of 0.41 U/mg DCW x h. The concentration of aectate was maintained below growth inhibitory levels until 3 h before the end of the fermentation when the concentration reached a maximum of 10.7 g/L due to IPTG induction of the recombinant protein.
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Aminoácido Oxidorreductasas/biosíntesis , Escherichia coli/enzimología , Escherichia coli/crecimiento & desarrollo , Aminoácido Oxidorreductasas/efectos de los fármacos , Técnicas Bacteriológicas/métodos , Biomasa , Medios de Cultivo Condicionados/farmacología , Escherichia coli/efectos de los fármacos , Fermentación , Modelos Biológicos , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/efectos de los fármacos , Factores de TiempoRESUMEN
Oral rehabilitation of missing teeth in cleft patients has acceptable success rates. A two-stage approach is indicated; however, timing of implant placement in the grafted maxilla varies within existing protocols. This case highlights successful implant osseointegration and esthetic oral rehabilitation following placement of two implants at 5 months after maxillary grafting (alveolar bone grafting) with a corticocancellous block obtained from the iliac crest. A 31-year-old male patient had already undergone repair of his bilateral cleft lip and soft palate according to established guidelines for cleft patients. Initial closure of his alveolar clefts and further correction of the maxillary hypoplasia with a bi-maxillary osteotomy were completed in 2002. However, bone resorption due to infection in 2003 necessitated removal of all maxillary incisors. The patient was not satisfied with the removable partial denture provided. In 2007, he did undergo anterior maxillary augmentation under general anesthesia, and 5 months later two implants were placed. A 3-unit bridge did replace functional and esthetic demands. Postoperative recovery was uneventful, and overall bone loss, and oral health remain within standards 28 months following implant placement. Optimal outcome is achievable when replacing missing teeth in cleft patients when timing does not exceed approximately a 6-month interval from bone grafting to implant placement. This article demonstrates that overall esthetic and functional rehabilitation is feasible in cleft lip and palate patients. In this patient, overall oral treatment was achieved with an implant prosthesis.
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BACKGROUND: Falls in older adults are a significant public health issue. Interventions have been developed and proven effective to reduce falls in older adults, but these programs typically last several months and can be resource intensive. Virtual rehabilitation technologies may offer a solution to bring these programs to scale. Off-the-shelf and custom exergames have demonstrated to be a feasible adjunct to rehabilitation with older adults. However, it is not known if older adults will be able or willing to use a virtual rehabilitation technology to participate in an evidence-based fall prevention program. To have the greatest impact, virtual rehabilitation technologies need to be acceptable to older adults from different backgrounds and level of fall risk. If these technologies prove to be a feasible option, they offer a new distribution channel to disseminate fall prevention programs. OBJECTIVE: Stand Tall (ST) is a virtual translation of the Otago Exercise Program (OEP), an evidence-based fall prevention program. Stand Tall was developed using the Virtual Exercise Rehabilitation Assistant (VERA) software, which uses a Kinect camera and a laptop to deliver physical therapy exercise programs. Our purpose in this pilot study was to explore if ST could be a feasible platform to deliver the OEP to older adults from a variety of fall risk levels, education backgrounds, and self-described level of computer expertise. METHODS: Adults age 60 and over were recruited to participate in a one-time usability study. The study included orientation to the program, navigation to exercises, and completion of a series of strength and balance exercises. Quantitative analysis described participants and the user experience. RESULTS: A diverse group of individuals participated in the study. Twenty-one potential participants (14 women, 7 men) met the inclusion criteria. The mean age was 69.2 (± 5.8) years, 38% had a high school education, 24% had a graduate degree, and 66% classified as "at risk for falls". Eighteen participants agreed they would like to use ST to help improve their balance, and 17 agreed or strongly agreed they would feel confident using the system in either the senior center or the home. Thirteen participants felt confident they could actually set up the system in their home. The mean System Usability Scale (SUS) score was 65.5 ± 21.2 with a range of 32.5 to 97.5. Ten participants scored ST as an above average usability experience compared to other technologies and 5 participants scored a less than optimal experience. Exploratory analysis revealed no significant relationships between user experience, education background, self-described computer experience, and fall risk. CONCLUSIONS: Results support the virtual delivery of the OEP by a Kinect camera and an avatar may be acceptable to older adults from a variety of backgrounds. Virtual technologies, like Stand Tall, could offer an efficient and effective approach to bring evidence-based fall prevention programs to scale to address the problem of falls and fall-related injuries. Next steps include determining if similar or better outcomes are achieved by older adults using the virtual OEP, Stand Tall, compared to the standard of care.
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Graves' disease is a thyroid-specific autoimmune disorder in which the body makes antibodies to the thyroid-stimulating hormone receptor leading to hyperthyroidism. Therapeutic options for the treatment of Graves' disease include medication, radioactive iodine ablation, and surgery. Radioactive iodine is absolutely contraindicated in pregnancy as exposure to I-131 to the fetal thyroid can result in fetal hypothyroidism and cretinism. Here we describe a case of a female patient with recurrent Graves' disease, who inadvertently received I-131 therapy when she was estimated to be eight days pregnant. This was despite the obtaining of a negative history of pregnancy and a negative urine pregnancy test less than 24 hours prior to ablation. At birth, the infant was found to have neonatal Graves' disease. The neonatal Graves' disease resolved spontaneously. It was suspected that the fetal thyroid did not trap any I-131 as it does not concentrate iodine until 10 weeks of gestation.
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Particles of spent antifouling paint collected from a marine boatyard were ground and subsequently administered to the filter-feeding bivalve, Mytilus edulis, maintained in static aquaria. Concentrations of Cu and Zn were measured in seawater throughout a 16 h feeding phase and a 24 h depuration phase, in rejected and egested particles collected during the respective phases, and in the organisms themselves at the end of the experiments. Concentrations and distributions of Cu and Zn in processed particles indicated that M. edulis was able to ingest paint particles, regardless of whether nutritionally viable silt was present, and no mechanism of particle discrimination was evident. Enrichment of Cu and Zn in the visceral mass of individuals and in the aqueous phase during depuration supported these assertions, although elevated concentrations in other compartments of the organism (e.g. shell, gill) suggested that biotic and abiotic uptake of aqueous metal was also important.
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Desinfectantes/metabolismo , Mytilus edulis/metabolismo , Pintura , Contaminantes Químicos del Agua/metabolismo , Animales , Cobre/análisis , Desinfectantes/análisis , Ecología/métodos , Mytilus edulis/química , Material Particulado , Contaminantes Químicos del Agua/análisis , Zinc/análisisRESUMEN
Rusticyanin from the extremophile Thiobacillus ferrooxidans is a blue copper protein with unusually high redox potential and acid stability. We present the crystal structures of native rusticyanin and of its Cu site mutant His143Met at 1.27 and 1.10 A, respectively. The very high resolution of these structures allows a direct comparison with EXAFS data and with quantum chemical models of the oxidized and reduced forms of the proteins, based upon both isolated and embedded clusters and density functional theory (DFT) methods. We further predict the structure of the Cu(II) form of the His143Met mutant which has been experimentally inaccessible due to its very high redox potential. We also present metrical EXAFS data and quantum chemical calculations for the oxidized and reduced states of the Met148Gln mutant, this protein having the lowest redox potential of all currently characterized mutants of rusticyanin. These data offer new insights into the structural factors which affect the redox potential in this important class of proteins. Calculations successfully predict the structure and the order of redox potentials for the three proteins. The calculated redox potential of H143M ( approximately 400 mV greater than native rusticyanin) is consistent with the failure of readily available chemical oxidants to restore a Cu(II) species of this mutant. The structural and energetic effects of mutating the equatorial cysteine to serine, yet to be studied experimentally, are predicted to be considerable by our calculations.
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Azurina/química , Azurina/genética , Computadores Moleculares , Cobre/química , Cobre/metabolismo , Cristalización , Cristalografía por Rayos X , Histidina/genética , Histidina/metabolismo , Metaloproteínas/química , Metionina/genética , Metionina/metabolismo , Modelos Moleculares , Oxidación-Reducción , Mutación Puntual , Solventes , Relación Estructura-Actividad , Thiobacillus/metabolismoRESUMEN
OBJECTIVE: We conducted a survey to compare condom use and its associated factors between foreign Asian and local clients of female sex workers in Singapore. STUDY: A survey was conducted between 2001 and 2002 on a random sample of 810 clients (677 foreign Asian workers and 133 locals) recruited from the streets and outside the brothels in Singapore. RESULTS: Foreign clients were more likely than locals to be inconsistent condom users with sex workers. Clients from China reported the highest percentage of inconsistent condom use (29.2%) and sexually transmitted infections (16.7%) compared with 8.3% (P < 0.003) and 2.3% (P < 0.005), respectively, among locals. On multivariate analysis, inconsistent condom use among foreign clients increased significantly with the number of freelance sex workers. The reverse trend was found for local clients. CONCLUSION: There is a need to design separate condom-promotion programs for foreign Asian and local clients of sex workers in Singapore.
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Condones , Enfermedades Profesionales/epidemiología , Sexo Seguro , Trabajo Sexual , Enfermedades de Transmisión Sexual/epidemiología , Adolescente , Adulto , Estudios Transversales , Emigración e Inmigración , Humanos , Masculino , Persona de Mediana Edad , Grupos de Población , Singapur/epidemiología , Clase SocialRESUMEN
A study was conducted in 31 Karen tribal villages in Northern Thailand in 1999-2000 to address the question of why some villages have a relatively high prevalence of illicit drug use compared with others? Data were gathered from village leaders, residents, and through observations by field workers and the researchers, and included demographic, economic, and infrastructure development, and social and acculturation measures. Overall, few village-level variables were related significantly to drug use in the villages; those that were included: 1) better access to elementary education reported by "high drug" villages (81%) in comparison with "low drug" villages (29%) and 2) high drug villages reported having more alcoholic residents than low drug villages. The findings provide some support for the hypothesis that illicit drug use is positively associated with socioeconomic development, acculturation, and socialization into mainstream attitudes, values, and behaviors.
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Alcoholismo/epidemiología , Países en Desarrollo , Drogas Ilícitas , Población Rural/estadística & datos numéricos , Trastornos Relacionados con Sustancias/epidemiología , Aculturación , Adolescente , Adulto , Anciano , Alcoholismo/etiología , Causalidad , Escolaridad , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Metanfetamina , Persona de Mediana Edad , Trastornos Relacionados con Opioides/epidemiología , Trastornos Relacionados con Opioides/etiología , Opio , Medio Social , Factores Socioeconómicos , Trastornos Relacionados con Sustancias/etiología , TailandiaRESUMEN
Dissimilatory nitrite reductase catalyses the reduction of nitrite to nitric oxide within the key biological process of denitrification. We present biochemical and structural results on two key mutants, one postulated to be important for the interaction with the partner protein and the other for substrate entry. Trp138, adjacent to one of the type-1 Cu ligands, is one of the residues surrounding a small depression speculated to be important in complex formation with the physiological redox partners, azurin I and II. Our data reveal that the Trp138His mutant is fully active using methyl viologen as an artificial electron donor, but there is a large decrease in activity using azurin I. These observations together with its crystal structure at a high resolution of 1.6 A confirm the importance of Trp138 in electron transfer and thus in productive interaction with azurin. A "hydrophobic pocket" on the protein surface has been identified as the channel through which nitrite may be guided to the catalytic type-2 Cu site. Glu133 and His313 at the opening of the pocket are conserved among most blue and green copper nitrite reductases (CuNiRs). The failure to soak the substrate into our high-resolution crystal form of native and mutant CuNiRs has been linked to the observation of an extraneous poly(ethylene glycol) (PEG) molecule interacting with His313. We present the crystal structure of His313Gln and the substrate-bound mutant at high resolutions of 1.65 and 1.72 A, respectively. The observation of the substrate-bound structure for the His313Gln mutant and inhibitory studies with PEG establishes the role of the hydrophobic pocket as the port of substrate entry.