bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxidative Phosphorylation as a Target Space for Tuberculosis: Success, Caution, and Future Directions
Authors: Cook Gregory M. , Hards Kiel , Dunn Elyse , Heikal Adam , Nakatani Yoshio , Greening Chris , Crick Dean C. , Fontes Fabio L. , Pethe Kevin , Hasenoehrl Erik , Berney Michael 
Published: June 2017

ABSTRACT

The emergence and spread of drug-resistant pathogens, and our inability to develop new antimicrobials to combat resistance, have inspired scientists to seek out new targets for drug development. The
Mycobacterium tuberculosis
complex is a group of obligately aerobic bacteria that have specialized for inhabiting a wide range of intracellular and extracellular environments. Two fundamental features in this adaptation are the flexible utilization of energy sources and continued metabolism in the absence of growth.
M. tuberculosis
is an obligately aerobic heterotroph that depends on oxidative phosphorylation for growth and survival. However, several studies are redefining the metabolic breadth of the genus. Alternative electron donors and acceptors may provide the maintenance energy for the pathogen to maintain viability in hypoxic, nonreplicating states relevant to latent infection. This hidden metabolic flexibility may ultimately decrease the efficacy of drugs targeted against primary dehydrogenases and terminal oxidases. However, it may also open up opportunities to develop novel antimycobacterials targeting persister cells. In this review, we discuss the progress in understanding the role of energetic targets in mycobacterial physiology and pathogenesis and the opportunities for drug discovery.
Mycobacterial Biofilms: Revisiting Tuberculosis Bacilli in Extracellular Necrotizing Lesions
Authors: Basaraba Randall J. , Ojha Anil K. 
Published: June 2017

ABSTRACT

Under detergent-free
in vitro
conditions,
Mycobacterium tuberculosis
, the etiological agent of tuberculosis in humans, spontaneously forms organized multicellular structures called biofilms. Moreover,
in vitro
biofilms of
M. tuberculosis
are more persistent against antibiotics than their single-cell planktonic counterparts, thereby raising questions about the occurrence of biofilms in the host tissues and their significance in persistence during chemotherapy of tuberculosis. In this article, we present arguments that extracellular
M. tuberculosis
in necrotizing lesions likely grows as biofilms.
KillingMycobacterium tuberculosis In Vitro: What Model Systems Can Teach Us
Authors: Keiser Tracy L. , Purdy Georgiana E. 
Published: June 2017

ABSTRACTTuberculosis is one of the most successful human diseases in our history due in large part to the multitude of virulence factors exhibited by the causative agent,Mycobacterium tuberculosis. Understanding the pathogenic nuances of this organism in the context of its human host is an ongoing topic of study facilitated by isolating cells from model organisms such as mice and non-human primates. However,M. tuberculosisis an obligate intracellular human pathogen, and disease progression and outcome in these model systems can differ from that of human disease. Currentin vitromodels of infection include primary macrophages and macrophage-like immortalized cell lines as well as the induced pluripotent stem cell-derived cell types. This article will discuss thesein vitromodel systems in general, what we have learned so far about utilizing them to answer questions about pathogenesis, the potential role of other cell types in innate control ofM. tuberculosisinfection, and the development of new coculture systems with multiple cell types. As we continue to expand currentin vitrosystems and institute new ones, the knowledge gained will improve our understanding of not only tuberculosis but all infectious diseases.
Incidence and prevalence of uveitis in South Korea: a nationwide cohort study
Authors: Rim Tyler Hyungtaek , Kim Sung Soo , Ham Don-Il , Yu Seung-Young , Chung Eun Jee , Lee Sung Chul 
Published: June 2017

AimTo evaluate the incidence and prevalence of uveitis and associated risk factors in South Korea.MethodsFor this retrospective national cohort study, approximately 1 000 000 Korean residents were randomly selected from the Korean National Health Insurance Service database. Uveitis was defined according to the Korean Classification of Diseases. The uveitis incidence and prevalence were calculated. Sociodemographic factors and comorbidities associated with uveitis were evaluated via Cox proportional regression models.ResultsA total of 1 094 440 subjects were evaluated over 7 051 346 person-years (mean follow-up: 6.44 years). Overall, 7447 newly developed uveitis cases were identified during the period of 2007–2013; the average incidence of uveitis was 10.6 per 10 000 person-years (95% CI 10.3 to 10.8). The average incidences of anterior and non-anterior uveitis were 9.0 and 1.5 per 10 000 person-years, respectively. The prevalence rates of uveitis, anterior uveitis and non-anterior uveitis were 17.3, 15.0 and 2.3 per 10 000 persons, respectively, during the period of 2007–2013. Increasing age, male sex, residing in a relatively rural area and high income were associated with uveitis, along with Behçet’s disease, juvenile idiopathic arthritis, ankylosing spondylitis, systemic lupus erythematous, ulcerative colitis and tuberculosis.ConclusionsThe overall incidence of uveitis in Korea was similar to those reported in Taiwan and the USA. Despite a potentially inaccurate disease definition, claims data may be useful for monitoring the substantial uveitis burden in South Korea.
Should exercises be painful in the management of chronic musculoskeletal pain? A systematic review and meta-analysis
Authors: Smith Benjamin E , Hendrick Paul , Smith Toby O , Bateman Marcus , Moffatt Fiona , Rathleff Michael S , Selfe James , Logan Pip 
Published: June 2017

BackgroundChronic musculoskeletal disorders are a prevalent and costly global health issue. A new form of exercise therapy focused on loading and resistance programmes that temporarily aggravates a patient’s pain has been proposed. The object of this review was to compare the effect of exercises where pain is allowed/encouraged compared with non-painful exercises on pain, function or disability in patients with chronic musculoskeletal pain within randomised controlled trials.MethodsTwo authors independently selected studies and appraised risk of bias. Methodological quality was evaluated using the Cochrane risk of bias tool, and the Grading of Recommendations Assessment system was used to evaluate the quality of evidence.ResultsThe literature search identified 9081 potentially eligible studies. Nine papers (from seven trials) with 385 participants met the inclusion criteria. There was short- term significant difference in pain, with moderate quality evidence for a small effect size of −0.27 (−0.54 to −0.05) in favour of painful exercises. For pain in the medium and long term, and function and disability in the short, medium and long term, there was no significant difference.ConclusionProtocols using painful exercises offer a small but significant benefit over pain-free exercises in the short term, with moderate quality of evidence. In the medium and long term there is no clear superiority of one treatment over another. Pain during therapeutic exercise for chronic musculoskeletal pain need not be a barrier to successful outcomes. Further research is warranted to fully evaluate the effectiveness of loading and resistance programmes into pain for chronic musculoskeletal disorders.PROSPERO registrationCRD42016038882.
Psychometric validation of the Hypoglycemia Fear Survey-II (HFS-II) in Singapore
Authors: Lam Amanda Yun Rui , Xin Xiaohui , Tan Wee Boon , Gardner Daphne Su-Lyn , Goh Su-Yen 
Published: June 2017

ObjectiveWe conducted a cross-sectional study to adapt and validate the Hypoglycemia Fear Survey-II (HFS-II) for use in Singapore among persons with type 1 and 2 diabetes mellitus.Research design and methodsA total of 144 patients with type 1 or 2 diabetes on insulin therapy for at least a year completed the HFS-II between September and December 2013 in the Diabetes Center at Singapore General Hospital. We examined the validity (content, concurrent and discriminant validity, and construct validity) and reliability (internal consistency and test–retest reliability) of the instrument. Content validity was established using cognitive interviews. Construct validity was assessed using confirmatory factor analysis (CFA) followed by exploratory factor analysis (EFA) after the hypothesized two-factor structure was not confirmed by CFA. Measures of anxiety (Generalized Anxiety Disorder-7 (GAD-7)) and depression (Patient Health Questionnaire-9 (PHQ-9)) were used to establish concurrent validity; history of severe hypoglycemia and status of glycemic control were used to establish discriminant validity. Internal consistency was measured by Cronbach's α; test–retest reliability was measured by intracluster correlation coefficient (ICC).ResultsScores of the adapted HFS-II had moderate positive correlations with measures of anxiety and depression scores (ranxiety=0.41, p<0.01; rdepression=0.37, p<0.01). Patients with a recent history of severe hypoglycemia had higher HFS-II scores than those without (mean difference=9, p<0.01). Patients with poor glycemic control had higher HFS-II scores than those with good control (p<0.05). The original two-factor structure was not confirmed in our sample. EFA results suggested a three-factor solution with the original Behavior subscale splitting into two dimensions. The adapted HFS-II displayed good internal consistency (Cronbach's α=0.93) and test–retest reliability (ICC=0.75).ConclusionsThe adapted HFS-II has good content, concurrent and discriminant validity, and reliability, but its constructvalidity was not proven with the Behavior subscale turning out to be non-unidimensional.
Weight cycling and the subsequent onset of type 2 diabetes mellitus: 10-year cohort studies in urban and rural Japan
Authors: Yokomichi Hiroshi , Ohde Sachiko , Takahashi Osamu , Mochizuki Mie , Takahashi Atsunori , Yoda Yoshioki , Tsuji Masahiro , Akiyama Yuka , Yamagata Zentaro 
Published: June 2017

ObjectiveTo investigate how weight cycling (gaining and losing weight) affects the risk of diabetes.DesignCohort studies.SettingPrimary healthcare in urban and rural Japan.Participants20 708 urban and 9670 rural residents.Primary outcome measuresORs for diabetes in those with weight loss, weight loss-gain, stable weight, weight gain-loss and weight gain over 10 years. Weight gain and loss were defined as a change of more than ±4% from baseline weight.ResultsIn the urban region, the ORs relative to the stable group for the loss-gain and gain-loss groups were 0.63 (95% CI 0.45 to 0.89) and 0.51 (95% CI 0.32 to 0.82) for men and 0.72 (95% CI 0.39 to 1.34) and 1.05 (95% CI 0.57 to 1.95) for women. In the rural region, they were 1.58 (95% CI 0.78 to 3.17) and 0.44 (95% CI 0.15 to 1.29) in men and 0.41 (95% CI 0.12 to 1.44) and 0.77 (95% CI 0.28 to 2.14) in women. The ORs for an increase in weight between 5 and 10 kg from the age of 20 years were 1.54 (95% CI 1.03 to 2.30) in men and 0.96 (95% CI 0.55 to 1.65) in women.ConclusionsIn Japan, weight cycling was associated with a significant reduction in the risk of diabetes for men from urban regions. The associations were unclear for women from urban regions and both men and women from rural regions. These results differ from those in Western studies, probably because of differences in diet, insulin secretion and sensitivity and weight-consciousness.
General practitioners’ views of clinically led commissioning: cross-sectional survey in England
Authors: Moran Valerie , Checkland Kath , Coleman Anna , Spooner Sharon , Gibson Jonathan , Sutton Matt 
Published: June 2017

ObjectivesInvolving general practitioners (GPs) in the commissioning/purchasing of services has been an important element in English health policy for many years. The Health and Social Care Act 2012 handed responsibility for commissioning of the majority of care for local populations to GP-led Clinical Commissioning Groups (CCGs). In this paper, we explore GP attitudes to involvement in commissioning and future intentions for engagement.Design and settingSurvey of a random sample of GPs across England in 2015.MethodThe Eighth National GP Worklife Survey was distributed to GPs in spring 2015. Responses were received from 2611 respondents (response rate = 46%). We compared responses across different GP characteristics and conducted two sample tests of proportions to identify statistically significant differences in responses across groups. We also used multivariate logistic regression to identify the characteristics associated with wanting a formal CCG role in the future.ResultsWhile GPs generally agree that they can add value to aspects of commissioning, only a minority feel that this is an important part of their role. Many current leaders intend to quit in the next 5 years, and there is limited appetite among those not currently in a formal role to take up such a role in the future. CCGs were set up as ‘membership organisations’ but only a minority of respondents reported feeling that they had ‘ownership’ of their local CCG and these were often GPs with formal CCG roles. However, respondents generally agree that the CCG has a legitimate role in influencing the work that they do.ConclusionCCGs need to engage in active succession planning to find the next generation of GP leaders. GPs believe that CCGs have a legitimate role in influencing their work, suggesting that there may be scope for CCGs to involve GPs more fully in roles short of formal leadership.
Permian rugose corals of the world
Authors: Wang Xiangdong , Yao Le , Lin Wei 
Published: June 2017

Abstract
Permian rugose corals underwent evolutionary episodes of assemblage changeover, biogeographical separation and extinction, which are closely related to geological events during this time. Two coral realms were recognized, the Tethyan Realm and the Cordilleran–Arctic–Uralian Realm. These are characterized by the families Kepingophyllidae and Waagenophyllidae during the Cisuralian, Waagenophyllidae in the Guadalupian and the subfamily Waagenophyllinae in the Lopingian, and the families Durhaminidae and Kleopatrinidae during the Cisuralian and major disappearance of colonial and dissepimented solitary rugose corals from the Guadalupian to the Lopingian, respectively. The development of these coral realms is controlled by the geographical barrier resulting from the Pangaea formation. According to the changes in the composition and diversity of the Permian rugose corals, a changeover event might have occurred at the end-Sakmarian and is characterized by the mixed Pennsylvanian and Permian faunas to typical Permian faunas, probably related to a global regression. In addition, three extinction events are present at the end-Kungurian, the end-Guadalupian and the end-Permian, which are respectively triggered by the northward movement of Pangaea, the Emeishan volcanic eruptions and subsequent global regression, and the global climate warming induced by the Siberian Traps eruption.
Pretreatment with indomethacin results in increased heat stroke severity during recovery in a rodent model of heat stroke
Authors: Audet Gerald N. , Dineen Shauna M. , Stewart Delisha A. , Plamper Mark L. , Pathmasiri Wimal W. , McRitchie Susan L. , Sumner Susan J. , Leon Lisa R. 
Published: June 2017

It has been suggested that medications can increase heat stroke (HS) susceptibility/severity. We investigated whether the nonsteroidal anti-inflammatory drug (NSAID) indomethacin (INDO) increases HS severity in a rodent model. Core temperature (Tc) of male, C57BL/6J mice ( n = 45) was monitored continuously, and mice were given a dose of INDO [low dose (LO) 1 mg/kg or high dose (HI) 5 mg/kg in flavored treat] or vehicle (flavored treat) before heating. HS animals were heated to 42.4°C and euthanized at three time points for histological, molecular, and metabolic analysis: onset of HS [maximal core temperature (Tc,Max)], 3 h of recovery [minimal core temperature or hypothermia depth (HYPO)], and 24 h of recovery (24 h). Nonheated (control) animals underwent identical treatment in the absence of heat. INDO (LO or HI) had no effect on physiological indicators of performance (e.g., time to Tc,Max, thermal area, or cooling time) during heating or recovery. HI INDO resulted in 45% mortality rate by 24 h (HI INDO + HS group). The gut showed dramatic increases in gross morphological hemorrhage in HI INDO + HS in both survivors and nonsurvivors. HI INDO + HS survivors had significantly lower red blood cell counts and hematocrit suggesting significant hemorrhage. In the liver, HS induced cell death at HYPO and increased inflammation at Tc,Max, HYPO, and 24 h; however, there was additional effect with INDO + HS group. Furthermore, the metabolic profile of the liver was disturbed by heat, but there was no additive effect of INDO + HS. This suggests that there is an increase in morbidity risk with INDO + HS, likely resulting from significant gut injury.NEW & NOTEWORTHY This paper suggests that in a translational mouse model, NSAIDs may be counterindicated in situations that put an individual at risk of heat injury. We show here that a small, single dose of the NSAID indomethacin before heat stroke has a dramatic and highly damaging effect on the gut, which ultimately leads to increased systemic morbidity.
Marcadores inflamatórios como fatores preditivos para o efeito antidepressivo dos inibidores seletivos da recaptura de serotonina (ISRS)
Authors: Corradi Mariana de Antonio , Lisboa Amanda Barbosa , Fráguas Junior Renerio 
Published: June 2017

A influência da inflamação na fisiopatologia da depressão e o papel da depressão no desenvolvimento de um estado pró-inflamatório têm sido apoiados por diversos estudos. O transtorno depressivo maior (TDM), principal diagnóstico de depressão, tem os inibidores seletivos da recaptação de serotonina (ISRS) como tratamento farmacológico de primeira linha. Esforços têm sido feitos para identificar fatores preditivos da responsividade ao tratamento antidepressivo os ISRS. Portanto, esta revisão tem como objetivo avaliar a hipótese de que níveis basais de marcadores inflamatórios predizem a responsividade do TDM ao tratamento com ISRS. Métodos: Pesquisamos o banco de dados PubMed, incluindo as palavras-chave (“ISRS” ou “sertralina” ou “citalopram” ou “fluvoxamina” ou “escitalopram” ou “fluoxetina” ou “paroxetina”) e (“citocinas” ou “CRP” ou “TNF” ou “inflamatório”) e (“transtorno depressivo maior” ou “depressão maior”). Resultados: A pesquisa identificou 245 manuscritos, dos quais 12 satisfizeram os critérios de inclusão e exclusão e foram incluídos nesta revisão. A análise destes manuscritos sugeriu que níveis elevados de interleucina 6 (IL-6), interleucina 1β (IL-1β), fator de necrose tumoral – alfa (TNF-α) e proteína C-reativa (PCR) na avaliação basal podem prever baixa responsividade da depressão ao tratamento com ISRS. Fatores de confusão como deficiência cognitiva, cronicidade e gravidade da depressão, subtipo melancólico, idade e sexo, não foram sistematicamente incluídos nos estudos. Conclusão: Os achados desta revisão sugerem que níveis elevados de marcadores pró-inflamatórios na avaliação basal podem predizer baixa responsividade do TDM ao tratamento com ISRS. Estudos com controle adequado para fatores de confusão são necessários.
Entre Israel e a Palestina poderia haver um Mandela
Authors: Paganelli Magno 
Published: June 2017

O presente ensaio pretende indicar a necessidade do diálogo e de abordagens conciliatórias em contextos diversos, tomando como modelo o processo de pacificação étnica ocorrido na África do Sul. A opção do presente autor contempla a situação de Apartheid no conflito Israel-Palestina como objeto e destaca apenas um dos seus inúmeros aspectos, a ocupação, propondo como paradigma no caminho para a paz a atuação de Nelson Rolihlahla Mandela, Prêmio Nobel da Paz em 1993, em sua luta contra a segregação racial naquele país
Serum Insulin-Like Growth Factor 1 and the Risk of Ischemic Stroke
Authors: Saber Hamidreza , Himali Jayandra J. , Beiser Alexa S. , Shoamanesh Ashkan , Pikula Aleksandra , Roubenoff Ronenn , Romero Jose R. , Kase Carlos S. , Vasan Ramachandran S. , Seshadri Sudha 
Published: June 2017

Background and Purpose—
Low insulin-like growth factor 1 (IGF-1) has been associated with increased risk of atherosclerosis and atrial fibrillation in cross-sectional studies. Yet, prospective data linking IGF-1 levels to the development of ischemic stroke remain inconclusive. We examined prospectively the association between serum IGF-1 levels and incident ischemic stroke.

Methods—
We measured serum IGF-1 levels in 757 elderly individuals (mean age 79±5, 62% women), free of prevalent stroke, from the Framingham original cohort participants at the 22nd examination cycle (1990–1994) and were followed up for the development of ischemic stroke. Cox models were used to relate IGF-1 levels to the risk for incident ischemic stroke, adjusted for potential confounders.

Results—

During a mean follow-up of 10.2 years, 99 individuals developed ischemic stroke. After adjustment for age, sex, and potential confounders, higher IGF-1 levels were associated with a lower risk of incident ischemic stroke, with subjects in the lowest quintile of IGF-1 levels having a 2.3-fold higher risk of incident ischemic stroke (95% confidence interval, 1.09–5.06;
P
=0.03) as compared with those in the top quintile. We observed an effect modification by diabetes mellitus and waist–hip ratio for the association between IGF-1 and ischemic stroke (
P
<0.1). In subgroup analyses, the effects were restricted to subjects with diabetics and those in top waist–hip ratio quartile, in whom each standard deviation increase in IGF-1 was associated with a 61% (hazard ratio, 0.39; 95% confidence interval, 0.20–0.78;
P
=0.007) and 41% (hazard ratio, 0.59; 95% confidence interval, 0.37–0.95;
P
=0.031) lower risk of incident ischemic stroke, respectively.

Conclusions—
IGF-1 levels were inversely associated with ischemic stroke, especially among persons with insulin resistance.
Association Between Previous Use of Antiplatelet Therapy and Intracerebral Hemorrhage Outcomes
Authors: Khan Nadeem I. , Siddiqui Fazeel M. , Goldstein Joshua N. , Cox Margueritte , Xian Ying , Matsouaka Roland A. , Heidenreich Paul A. , Peterson Eric D. , Bhatt Deepak L. , Fonarow Gregg C. , Schwamm Lee H. , Smith Eric E. 
Published: June 2017

Background and Purpose—
Although the use of antiplatelet therapy (APT) is associated with the risk of intracerebral hemorrhage (ICH), there are limited data on prestroke APT and outcomes, particularly among patients on combination APT (CAPT). We hypothesized that the previous use of antiplatelet agents is associated with increased mortality in ICH.

Methods—
We analyzed data of 82 576 patients with ICH who were not on oral anticoagulant therapy from 1574 Get with the Guidelines-Stroke hospitals between October 2012 and March 2016. Patients were categorized as not on APT, on single-APT (SAPT), and CAPT before hospital presentation with ICH. We described baseline characteristics, comorbidities, hospital characteristics and outcomes, overall and stratified by APT use.

Results—
Before the diagnosis of ICH, 65.8% patients were not on APT, 29.5% patients were on SAPT, and 4.8% patients were on CAPT. There was an overall modest increased in-hospital mortality in the APT group versus no APT group (24% versus 23%; adjusted odds ratio, 1.05; 95% confidence interval, 1.01–1.10). Although patients on SAPT and CAPT were older and had higher risk profiles in terms of comorbidities, there was no significant difference in the in-hospital mortality among patients on SAPT versus those not on any APT (23% versus 23%; adjusted odds ratio, 1.01; 95% confidence interval, 0.97–1.05). However, in-hospital mortality was higher among those on CAPT versus those not on APT (30% versus 23%; adjusted odds ratio, 1.50; 95% confidence interval, 1.39–1.63).

Conclusions—
Our study suggests that among patients with ICH, previous use of CAPT, but not SAPT, was associated with higher risk for in-hospital mortality.