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1.
Nature ; 612(7941): 701-706, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36450979

RESUMO

Salt marshes provide ecosystem services such as carbon sequestration1, coastal protection2, sea-level-rise (SLR) adaptation3 and recreation4. SLR5, storm events6, drainage7 and mangrove encroachment8 are known drivers of salt marsh loss. However, the global magnitude and location of changes in salt marsh extent remains uncertain. Here we conduct a global and systematic change analysis of Landsat satellite imagery from the years 2000-2019 to quantify the loss, gain and recovery of salt marsh ecosystems and then estimate the impact of these changes on blue carbon stocks. We show a net salt marsh loss globally, equivalent to an area double the size of Singapore (719 km2), with a loss rate of 0.28% year-1 from 2000 to 2019. Net global losses resulted in 16.3 (0.4-33.2, 90% confidence interval) Tg CO2e year-1 emissions from 2000 to 2019 and a 0.045 (-0.14-0.115) Tg CO2e year-1 reduction of carbon burial. Russia and the USA accounted for 64% of salt marsh losses, driven by hurricanes and coastal erosion. Our findings highlight the vulnerability of salt marsh systems to climatic changes such as SLR and intensification of storms and cyclones.


Assuntos
Sequestro de Carbono , Carbono , Mapeamento Geográfico , Internacionalidade , Áreas Alagadas , Carbono/análise , Elevação do Nível do Mar , Imagens de Satélites , Estados Unidos , Federação Russa , Tempestades Ciclônicas , Erosão do Solo
2.
Brief Bioinform ; 25(3)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38754407

RESUMO

Predicting cancer drug response using both genomics and drug features has shown some success compared to using genomics features alone. However, there has been limited research done on how best to combine or fuse the two types of features. Using a visible neural network with two deep learning branches for genes and drug features as the base architecture, we experimented with different fusion functions and fusion points. Our experiments show that injecting multiplicative relationships between gene and drug latent features into the original concatenation-based architecture DrugCell significantly improved the overall predictive performance and outperformed other baseline models. We also show that different fusion methods respond differently to different fusion points, indicating that the relationship between drug features and different hierarchical biological level of gene features is optimally captured using different methods. Considering both predictive performance and runtime speed, tensor product partial is the best-performing fusion function to combine late-stage representations of drug and gene features to predict cancer drug response.


Assuntos
Antineoplásicos , Genótipo , Neoplasias , Redes Neurais de Computação , Humanos , Neoplasias/genética , Neoplasias/tratamento farmacológico , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Aprendizado Profundo , Genômica/métodos , Biologia Computacional/métodos
3.
Conserv Biol ; : e14293, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38766900

RESUMO

Despite increasing efforts and investment in mangrove conservation, mangrove cover continues to decline globally. The extent to which protected area (PA) management effectively prevents mangrove loss globally across differing management objectives and governance types is not well understood. We combined remote sensing data with PA information to identify the extent and the drivers of mangrove loss across PAs with distinct governance types and protection levels based on categories developed by the International Union for Conservation of Nature (IUCN). Mangrove loss due to storms and erosion was prevalent across all governance types and most IUCN categories. However, the extent of human-driven loss differed across governance types and IUCN categories. Loss was highest in national government PAs. Private, local, shared arrangement, and subnational government agencies had low human-driven mangrove loss. Human-driven loss was highest in PAs with the highest level of restrictions on human activities (IUCN category I) due to mangrove conversion to areas for commodity production (e.g., aquaculture), whereas PAs that allowed sustainable resource use (e.g., category VI) experienced low levels of human-driven mangrove loss. Because category I PAs with high human-driven loss were primarily governed by national government agencies, conservation outcomes in highly PAs might depend not only on the level of restrictions, but also on the governance type. Mangrove loss across different governance types and IUCN categories varied regionally. Specific governance types and IUCN categories thus seemed more effective in preventing mangrove loss in certain regions. Overall, we found that natural drivers contributed to global mangrove loss across all PAs, whereas human-driven mangrove loss was lowest in PAs with subnational- to local-level governance and PAs with few restrictions on human activities.


Factores globales en la pérdida de manglares en las áreas protegidas Resumen A pesar del incremento en los esfuerzos e inversión de la conservación de los manglares, su cobertura sigue disminuyendo en todo el mundo. No se conoce muy bien el grado al que el manejo de las áreas protegidas (AP) previene eficientemente la pérdida mundial de los manglares en los diferentes objetivos de manejo y tipos de gestión. Combinamos los datos de teledetección con información de las AP para identificar el grado y los factores de la pérdida de manglares en las AP con tipos de gestión claros y niveles de protección basados en las categorías desarrolladas por la Unión Internacional para la Conservación de la Naturaleza (UICN). La pérdida por tormentas y erosión fue común en todos los tipos de gestión y en la mayoría de las categorías de la UICN. Sin embargo, el grado de pérdida antropogénica difirió entre los tipos de gestión y las categorías de la UICN. La pérdida fue mayor en las AP de gobiernos nacionales. Las agencias privadas, locales, de acuerdo compartido y las gubernamentales subnacionales tuvieron una pérdida antropogénica baja. La pérdida antropogénica fue mayor en la AP con el nivel más alto de restricción para las actividades humanas (categoría I de la UICN) debido a la conversión del manglar en áreas de producción de mercancía (p. ej.: acuacultura), mientras que las AP que permiten el uso sostenible de los recursos (p. ej.: categoría VI) tuvieron niveles bajos de pérdida antropogénica. Ya que las AP de categoría I con mayor pérdida antropogénica están gestionadas principalmente por agencias gubernamentales, puede que los resultados de conservación en las AP con mayor pérdida dependan no sólo del nivel de restricciones sino también del tipo de gestión. La pérdida del manglar en los diferentes tipos de gestión y en las categorías de la UICN varió en cada región. Por lo tanto, los tipos específicos de gestión y las categorías de la UICN parecen ser más eficientes en la prevención de la pérdida de manglares en ciertas regiones. En general, encontramos que los factores naturales contribuyen a la pérdida mundial del manglar en todas las AP, mientras que la pérdida antropogénica fue más baja en las AP con un nivel de subnacional a local de gestión y en las AP con pocas restricciones para la actividad humana.

6.
Ann Vasc Surg ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38582208

RESUMO

Educating trainees to treat Peripheral Artery Disease (PAD) carries specific contemporary challenges. The national increase of the prevalence of PAD combined with a significant shortage of vascular surgeons creates a need for concern for future management of this complex disease. Over the past 2 decades, traditional (5 + 2) and integrated (0 + 5) paradigms have fostered trainee annual growth and comparable case distribution and volumes in endovascular and open surgical treatment options have been maintained. Close evaluation into not only the absolute numbers of surgical cases, but the level of trainee involvement in each logged case is recommended. Future implementation of the Entrustable Professional Activity (EPA) modules will hopefully assist in ensuring linear development of surgical skill and judgment. Additionally, advances in individual and systems level techniques to enhance skill acquisition in the form of "off-the job training" and simulation-based training may provide an enhancement to traditional technical training methods. Finally, the possibility and role of artificial intelligence in vascular surgery skill training must not be ignored, but carefully explored and utilized to modernize cognitive and technical skill preparation for trainees in the and delivery of care for PAD patients. Overall, the training residents for the treatment of PAD patients will be associated with new challenges that vascular surgery must embrace and surmount to advance our specialty.

7.
Soc Sci Res ; 83: 102301, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31422839

RESUMO

Those with higher incomes tend to have better health outcomes, including healthy weight status. We use data from the 2003-2008 National Health and Nutrition Examination Survey (NHANES) to examine whether the association between higher weight status and social integration varies by income. We examine gender differences in weight status, measured by BMI and obesity, by social integration and income, and find evidence that high social integration is a risk factor for higher weight status among low-income men. The association between income and higher weight status operates differently for women and men and is dependent, in part, on their level of social integration. Income is negatively associated with weight status for men who are highly integrated, but is positively associated with weight status among men who have low integration. We conclude that higher numbers of close friends and family places low-income men at greater risk of higher weight status.


Assuntos
Peso Corporal , Renda/estatística & dados numéricos , Inquéritos Nutricionais/estatística & dados numéricos , Pobreza/estatística & dados numéricos , Classe Social , Integração Social , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Fatores de Risco , Estados Unidos/epidemiologia
8.
Health Commun ; 30(6): 557-65, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-24992003

RESUMO

This study examines the health-related content of Black megachurch websites in the southeastern United States. Data collection resulted in the identification of qualitative themes and frequencies of references to general health, specific health conditions, and corresponding general and specific health ministries. The most salient qualitative themes included holistic definitions of health, attention to racial health disparities, belief in divine health and protection from illness, emphasis on individual health responsibility, and belief in a religion-health connection. Nearly all websites referred to general health, and 74% mentioned a general health ministry. The most frequent references to specific health conditions included addiction, cancer, and HIV/AIDS, roughly corresponding to the top mentioned specific health ministries. This study provides baseline data on Black megachurch efforts to convey health information to their virtual congregations and communities. Findings support recent initiatives to involve megachurches in the provision of health messages within cultural frames to reach African Americans.


Assuntos
Negro ou Afro-Americano , Informação de Saúde ao Consumidor/estatística & dados numéricos , Comunicação em Saúde/métodos , Internet , Religião , Negro ou Afro-Americano/educação , Características Culturais , Humanos , Pesquisa Qualitativa , Sudeste dos Estados Unidos
10.
J Relig Spiritual Soc Work ; 40(4): 371-394, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35002549

RESUMO

This paper details findings from interviews with 32 faith leaders regarding their interest in and preferences for collaborative health partnerships with an academic center. Participants were willing to partner to develop equitable, sustainable, and trust-based relationships for the purpose of meeting the health needs of their congregations. We also describe the planning and early development of faith community-academic partnership focused on providing information and resources aimed at improving health. We apply a framework incorporating a socioecological perspective and social capital theory to discuss how establishing linkages between clergy and academic researchers is a beneficial and important task for social work.

11.
Soc Sci Med ; 284: 114197, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34274710

RESUMO

BACKGROUND: Survivors of gun violence in the United States (US) are twenty times more likely to be re-injured with a firearm and three times more likely to be arrested under a violence or a weapons-related charge. The mechanisms for these outcomes are multifactorial and remain largely understudied. We aimed to examine perspectives on both the police and guns among survivors of guns violence. METHODS: We conducted a secondary analysis of qualitative data from a study that examined the post-hospitalization recovery experience of survivors of firearm violence. Using a conceptual framework derived from sociology literature and a coding team made up of researchers, community members and former police officers, we used directed content analysis to construct themes. RESULTS: The data set included interviews with 20 survivors of gun violence that were all Black males, aged 20-51 years. The recurring themes around the police included: (1) Legal cynicism: "I don't like police, none of them"; (2) Interactions with the police in a medical setting: "The cops didn't make it any better" and (3) Ambivalence around police presence within the community: "That's their job to protect me, too." Themes related to guns in the community encompassed: (1) The availability of guns: "Getting a gun is about as easy as buying a pair of sneakers"; (2) Symbolic meaning: "Guns give them courage"; (3) Social meaning: "I just let them know: I have a gun, too." and (4) Strategic meaning: "It's just for protection." CONCLUSIONS: Survivors of gun violence describe distrust for the police and an ecology of guns that confers symbolic, social and strategic meaning to owning a gun. Interventions to decrease gun violence should address the cultural value of a gun as well as focus on improving police relations with the community.


Assuntos
Armas de Fogo , Violência com Arma de Fogo , Humanos , Masculino , Polícia , Sobreviventes , Estados Unidos , Violência
12.
PLoS One ; 15(2): e0229605, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32109951

RESUMO

Salt marshes provide a bulwark against sea-level rise (SLR), an interface between aquatic and terrestrial habitats, important nursery grounds for many species, a buffer against extreme storm impacts, and vast blue carbon repositories. However, salt marshes are at risk of loss from a variety of stressors such as SLR, nutrient enrichment, sediment deficits, herbivory, and anthropogenic disturbances. Determining the dynamics of salt marsh change with remote sensing requires high temporal resolution due to the spectral variability caused by disturbance, tides, and seasonality. Time series analysis of salt marshes can broaden our understanding of these changing environments. This study analyzed aboveground green biomass (AGB) in seven mid-Atlantic Hydrological Unit Code 8 (HUC-8) watersheds. The study revealed that the Eastern Lower Delmarva watershed had the highest average loss and the largest net reduction in salt marsh AGB from 1999-2018. The study developed a method that used Google Earth Engine (GEE) enabled time series of the Landsat archive for regional analysis of salt marsh change and identified at-risk watersheds and salt marshes providing insight into the resilience and management of these ecosystems. The time series were filtered by cloud cover and the Tidal Marsh Inundation Index (TMII). The combination of GEE enabled Landsat time series, and TMII filtering demonstrated a promising method for historic assessment and continued monitoring of salt marsh dynamics.


Assuntos
Biomassa , Ecossistema , Áreas Alagadas , Oceano Atlântico , Monitorização de Parâmetros Ecológicos
13.
Am J Physiol Cell Physiol ; 297(6): C1397-408, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19776394

RESUMO

The pharmacology of the large-conductance K(+) (BK) channel in human osteoblasts is not well defined, and its role in bone is speculative. Here we assess BK channel properties in MG63 cells and primary human osteoblasts and determine whether pharmacological modulation affects cell function. We used RT-PCR and patch-clamp methods to determine the expression of BK channel subunits and cell number assays in the absence and presence of BK channel modulators. RT-PCR showed the presence of KCNMA1, KCNMB1, KCNMB2, KCNMB3, and KCNMB4 subunits. The BK channel was voltage dependent, with a mean unitary conductance of 228.8 pS (n = 10) in cell-attached patches (140 mM K(+)/140 mM K(+)) and a conductance of 142.5 pS (n = 16) in excised outside-out and 155 pS (n = 6) in inside-out patches in 3 mM K(+)/140 mM K(+). The selectivity ratio (ratio of K(+) to Na(+) permeability) was 15:1. The channel was blocked by tetraethylammonium (TEA, 0.3 mM), iberiotoxin (5-60 nM), tetrandrine (5-30 microM), and paxilline (10 microM) and activated by isopimaric acid (20 microM). BK channel modulators affected MG63 cell numbers: TEA and tetrandrine significantly increased cell numbers at low concentrations (3 mM and 3 microM, respectively) and reduced cell numbers at higher concentrations (>10 mM and >10 microM, respectively). Neither iberiotoxin (20-300 nM) nor slotoxin (300 nM) affected cell numbers. The increase in cell numbers by TEA was blocked by isopimaric acid. TEA (0.1-3.0 mM) significantly increased mineralization in primary osteoblasts. In conclusion, the BK channel has a distinctive pharmacology and is thus a target for therapeutic strategies aimed at modulating osteoblast proliferation and function.


Assuntos
Calcificação Fisiológica/fisiologia , Divisão Celular/fisiologia , Canais de Potássio Ativados por Cálcio de Condutância Alta/fisiologia , Osteoblastos/citologia , Osteoblastos/metabolismo , Benzilisoquinolinas/farmacologia , Calcificação Fisiológica/efeitos dos fármacos , Ácidos Carboxílicos/farmacologia , Contagem de Células , Linhagem Celular , Corantes , Humanos , Indóis/farmacologia , Canais de Potássio Ativados por Cálcio de Condutância Alta/antagonistas & inibidores , Canais de Potássio Ativados por Cálcio de Condutância Alta/efeitos dos fármacos , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Técnicas de Patch-Clamp , Peptídeos/farmacologia , Permeabilidade/efeitos dos fármacos , Fenantrenos/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Isoformas de Proteínas/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tetraetilamônio/farmacologia , Azul Tripano
14.
Biochim Biophys Acta ; 1778(6): 1415-22, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18342619

RESUMO

The results here show for the first time that pH and monovalent cations can regulate cytosolic free Ca(2+) in E. coli through Ca(2+) influx and efflux, monitored using aequorin. At pH 7.5 the resting cytosolic free Ca(2+) was 0.2-0.5 microM. In the presence of external Ca(2+) (1 mM) at alkaline pH this rose to 4 microM, being reduced to 0.9 microM at acid pH. Removal of external Ca(2+) caused an immediate decrease in cytosolic free Ca(2+) at 50-100 nM s(-1). Efflux rates were the same at pH 5.5, 7.5 and 9.5. Thus, ChaA, a putative Ca(2+)/H(+)exchanger, appeared not to be a major Ca(2+)-efflux pathway. In the absence of added Na(+), but with 1 mM external Ca(2+), cytosolic free Ca(2+) rose to approximately 10 microM. The addition of Na(+)(half maximum 60 mM) largely blocked this increase and immediately stimulated Ca(2+) efflux. However, this effect was not specific, since K(+) also stimulated efflux. In contrast, an increase in osmotic pressure by addition of sucrose did not significantly stimulate Ca(2+) efflux. The results were consistent with H(+) and monovalent cations competing with Ca(2+) for a non-selective ion influx channel. Ca(2+) entry and efflux in chaA and yrbG knockouts were not significantly different from wild type, confirming that neither ChaA nor YrbG appear to play a major role in regulating cytosolic Ca(2+) in Escherichia coli. The number of Ca(2+) ions calculated to move per cell per second ranged from <1 to 100, depending on conditions. Yet a single eukaryote Ca(2+) channel, conductance 100 pS, should conduct >6 million ions per second. This raises fundamental questions about the nature and regulation of Ca(2+) transport in bacteria, and other small living systems such as mitochondria, requiring a new mathematical approach to describe such ion movements. The results have important significance in the adaptation of E. coli to different ionic environments such as the gut, fresh water and in sea water near sewage effluents.


Assuntos
Adaptação Fisiológica , Cálcio/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Potássio/metabolismo , Adaptação Fisiológica/genética , Cálcio/farmacologia , Proteínas de Transporte de Cátions/genética , Cátions Monovalentes/metabolismo , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Deleção de Genes , Concentração de Íons de Hidrogênio , Transporte de Íons/genética
15.
Sci Prog ; 92(Pt 3-4): 241-87, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19960866

RESUMO

A staggering 4000 million people cannot digest lactose, the sugar in milk, properly. All mammals, apart from white Northern Europeans and few tribes in Africa and Asia, lose most of their lactase, the enzyme that cleaves lactose into galactose and glucose, after weaning. Lactose intolerance causes gut and a range of systemic symptoms, though the threshold to lactose varies considerably between ethnic groups and individuals within a group. The molecular basis of inherited hypolactasia has yet to be identified, though two polymorphisms in the introns of a helicase upstream from the lactase gene correlate closely with hypolactasia, and thus lactose intolerance. The symptoms of lactose intolerance are caused by gases and toxins produced by anaerobic bacteria in the large intestine. Bacterial toxins may play a key role in several other diseases, such as diabetes, rheumatoid arthritis, multiple sclerosis and some cancers. The problem of lactose intolerance has been exacerbated because of the addition of products containing lactose to various foods and drinks without being on the label. Lactose intolerance fits exactly the illness that Charles Darwin suffered from for over 40 years, and yet was never diagnosed. Darwin missed something else--the key to our own evolution--the Rubicon some 300 million years ago that produced lactose and lactase in sufficient amounts to be susceptible to natural selection.


Assuntos
Enteropatias/metabolismo , Lactase/metabolismo , Intolerância à Lactose/metabolismo , Lactose/metabolismo , Sequência de Carboidratos , Humanos , Enteropatias/enzimologia , Enteropatias/genética , Lactase/genética , Intolerância à Lactose/enzimologia , Intolerância à Lactose/genética , Dados de Sequência Molecular
16.
Perspect Sex Reprod Health ; 51(3): 125-133, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31449728

RESUMO

CONTEXT: Unintended pregnancy is disproportionately reported by low-income individuals in the United States, and studies of men's roles in preventing pregnancy have largely focused on adolescents and young adults. Less is known about the pregnancy-related attitudes and behaviors among men older than 24, who are involved in the majority of pregnancies ending in a birth. METHODS: Between December 2015 and August 2016, in-depth interviews were conducted with 26 low-income men in Alabama who were aged 25-55, were sexually active and did not want more children. Interviews explored men's reasons for not wanting more children, their contraceptive knowledge and attitudes, and their involvement in contraceptive decision making. Transcripts were examined using content analysis to identify themes related to men's perspectives about preventing pregnancy and using contraceptives. RESULTS: Participants' motivations to prevent a pregnancy centered primarily on their age and financial circumstances. Most men had limited contraceptive knowledge and perceived their risk of causing a pregnancy to be low, regardless of method use. Few men engaged in decisions about contraceptive use, despite their beliefs that men and women had a shared responsibility to prevent pregnancy. Although some men were interested in vasectomy, a few were hesitant about undergoing the procedure because they might want to have children later if their life circumstances changed, and others worried that vasectomy might affect sexual performance. CONCLUSIONS: Some low-income adult men were uncertain about their pregnancy desires, and many lacked contraceptive knowledge that would help them avoid unwanted pregnancy. Research is needed to identify the types of programs that could effectively promote men's constructive engagement in preventing pregnancies over their reproductive life course.


Assuntos
Comportamento Contraceptivo/psicologia , Intenção , Homens/psicologia , Pobreza/psicologia , Comportamento Sexual/psicologia , Adulto , Alabama , Tomada de Decisões , Feminino , Fertilidade , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Gravidez não Planejada/psicologia , Pesquisa Qualitativa
17.
Surg Obes Relat Dis ; 15(1): 43-49, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30501957

RESUMO

BACKGROUND: Bariatric surgery has proven to be the most durable treatment for obesity, and it also provides improvement of obesity's associated co-morbidities. Although several mechanisms for its metabolic effects have been studied, the implications of the surgically constructed anatomy on its functioning physiology have not been elucidated. This leaves some uncertainty regarding the recommended limb lengths in Roux-en-Y gastric bypass. The alimentary limb length and function has been studied extensively, but few have studied the influences of the biliopancreatic limb length. OBJECTIVE: To present a systematic review of the literature comparing variations in length of BP limb and results in order to determine BP limb length influence. SETTING: Academic Hospital, United States. METHODS: We present a systematic review of all the articles comparing variations of the biliopancreatic limb length and their results. RESULTS: Thirteen articles were identified and analyzed. Most of the articles are prospective studies. Weight loss was superior in longer limbs. CONCLUSION: Based on our review of the subject, we can conclude that the release of enterohormones in response to a food load in the distal small bowel seems to play an important role in the remission of co-morbidities. Hence, the length of the biliopancreatic limb might affect this process.


Assuntos
Duodeno , Derivação Gástrica , Obesidade Mórbida/cirurgia , Duodeno/metabolismo , Duodeno/fisiologia , Duodeno/cirurgia , Humanos , Complicações Pós-Operatórias , Resultado do Tratamento , Redução de Peso/fisiologia
18.
Ann Clin Biochem ; 45(Pt 1): 50-8, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18275674

RESUMO

BACKGROUND: Currently, there is no 'gold standard' for detecting patients with sensitivity to lactose. Biochemical investigation by a breath hydrogen test alone detects <50% cases. Breath methane and symptoms are not recorded as standard practice. The clinical value of analysing C/T(13910) and G/A(22018) polymorphisms, strongly associated with lactose sensitivity, has not been established. METHODS: Two hundred and ten patients with unexplained gut and systemic symptoms and controls were challenged with 50 g lactose. Breath hydrogen and methane were measured and symptoms recorded. All were genotyped for two polymorphisms, C/T(13910) and G/A(22018). RESULTS: CC(13910)/GG(22018) in 14.5%, CT(13910)/GA(22018) in 39% and TT(13910)/AA(22018) in 46.5%. One hundred percent of CC(13910)/GG(22018) were lactose sensitive having a breath hydrogen >20 ppm within 6 h and symptoms. But the breath hydrogen test lacked sensitivity and specificity in the other groups. There was elevated breath hydrogen in 21% of CT(13910)/GA(22018) and 15% of TT(13910)/AA(22018) by 6 h, whereas 17 and 30.9% had elevated breath methane alone. Breath methane and breath hydrogen with clinical symptoms improved sensitivity and specificity, increasing detection of lactose sensitivity in genotypes CT/GA and TT/AA from <50 to >75%. CONCLUSIONS: The data presented define the current best practice for the clinical identification of lactose sensitivity. Patients were first genotyped. Those identified as CC with symptoms should immediately undertake a 12-week lactose-free diet. Those identified as CT or TT should undertake a breath hydrogen and methane test. Those positive for hydrogen or methane along with symptoms or with symptoms only, should also undertake a lactose-free diet. Those with high hydrogen without symptoms should be investigated for causes other than lactose sensitivity.


Assuntos
Hidrogênio/análise , Hidrogênio/metabolismo , Lactase/genética , Teste de Tolerância a Lactose/métodos , Metano/análise , Metano/metabolismo , Adolescente , Adulto , Idoso , Testes Respiratórios , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Lactase/metabolismo , Intolerância à Lactose/diagnóstico , Intolerância à Lactose/metabolismo , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético/genética , Sensibilidade e Especificidade
19.
Cell Calcium ; 41(2): 97-106, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16842848

RESUMO

The results here are the first demonstration of a physiological agonist opening Ca2+ channels in bacteria. Bacteria in the gut ferment glucose and other substrates, producing alcohols, diols, ketones and acids, that play a key role in lactose intolerance, through the activation of Ca2+ and other ion channels in host cells and neighbouring bacteria. Here we show butane 2,3-diol (5-200mM; half maximum 25mM) activates Ca2+ transients in E. coli, monitored by aequorin. Ca2+-transient magnitude depended on external Ca2+ (0.1-10mM). meso-Butane 2,3-diol was approximately twice as potent as 2R,3R (-) and 2S,3S (+) butane 2,3-diol. There were no detectable effects on cytosolic free Ca2+ of butane 1,3-diol, butane 1,4-diol and ethylene glycol. The glycerol fermentation product propane 1,3-diol only induced significant Ca2+ transients in 10mM external Ca2. Ca2+ butane 2,3-diol Ca2+ transients were due to activation of Ca2+ influx, followed by activation of Ca2+ efflux. The effect of butane 2,3-diol was abolished by La3+, and markedly reduced as a function of growth phase. These results were consistent with butane 2,3-diol activating a novel La3+-sensitive Ca2+ channel. They have important implications for the role of butane 2,3-diol and Ca2+ in bacterial-host cell signalling.


Assuntos
Butileno Glicóis/farmacologia , Canais de Cálcio/metabolismo , Cálcio/metabolismo , Fermentação , Lantânio/farmacologia , Sinalização do Cálcio , Citosol/metabolismo , Relação Dose-Resposta a Droga , Escherichia coli , Propano/farmacologia , Estereoisomerismo
20.
Arch Biochem Biophys ; 468(1): 107-13, 2007 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-17961498

RESUMO

The results here are the first demonstration of a family of carbohydrate fermentation products opening Ca2+ channels in bacteria. Methylglyoxal, acetoin (acetyl methyl carbinol), diacetyl (2,3 butane dione), and butane 2,3 diol induced Ca2+ transients in Escherichia coli, monitored by aequorin, apparently by opening Ca2+ channels. Methylglyoxal was most potent (K(1/2) = 1 mM, 50 mM for butane 2,3 diol). Ca2+ transients depended on external Ca2+ (0.1-10 mM), and were blocked by La3+ (5 mM). The metabolites affected growth, methylglyoxal being most potent, blocking growth completely up to 5 h without killing the cells. But there was no affect on the number of viable cells after 24 h. These results were consistent with carbohydrate products activating a La3+-sensitive Ca2+ channel, rises in cytosolic Ca2+ possibly protecting against certain toxins. They have important implications in bacterial-host cell signalling, and where numbers of different bacteria compete for the same substrates, e.g., the gut in lactose and food intolerance.


Assuntos
Acetais/administração & dosagem , Acetoína/administração & dosagem , Sinalização do Cálcio/fisiologia , Diacetil/administração & dosagem , Escherichia coli/fisiologia , Lantânio/administração & dosagem , Aldeído Pirúvico/administração & dosagem , Sinalização do Cálcio/efeitos dos fármacos , Metabolismo dos Carboidratos/efeitos dos fármacos , Metabolismo dos Carboidratos/fisiologia , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Interações Medicamentosas , Escherichia coli/efeitos dos fármacos
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