bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simultaneous cell growth and ethanol production from cellulose by an engineered yeast consortium displaying a functional mini-cellulosome
Authors: Goyal Garima , Tsai Shen-Long , Madan Bhawna , DaSilva Nancy A , Chen Wilfred 
Published: November 2011

Abstract

Background
The recalcitrant nature of cellulosic materials and the high cost of enzymes required for efficient hydrolysis are the major impeding steps to their practical usage for ethanol production. Ideally, a recombinant microorganism, possessing the capability to utilize cellulose for simultaneous growth and ethanol production, is of great interest. We have reported recently the use of a yeast consortium for the functional presentation of a mini-cellulosome structure onto the yeast surface by exploiting the specific interaction of different cohesin-dockerin pairs. In this study, we engineered a yeast consortium capable of displaying a functional mini-cellulosome for the simultaneous growth and ethanol production on phosphoric acid swollen cellulose (PASC).

Results
A yeast consortium composed of four different populations was engineered to display a functional mini-cellulosome containing an endoglucanase, an exoglucanase and a β-glucosidase. The resulting consortium was demonstrated to utilize PASC for growth and ethanol production. The final ethanol production of 1.25 g/L corresponded to 87% of the theoretical value and was 3-fold higher than a similar yeast consortium secreting only the three cellulases. Quantitative PCR was used to enumerate the dynamics of each individual yeast population for the two consortia. Results indicated that the slight difference in cell growth cannot explain the 3-fold increase in PASC hydrolysis and ethanol production. Instead, the substantial increase in ethanol production is consistent with the reported synergistic effect on cellulose hydrolysis using the displayed mini-cellulosome.

Conclusions
This report represents a significant step towards the goal of cellulosic ethanol production. This engineered yeast consortium displaying a functional mini-cellulosome demonstrated not only the ability to grow on the released sugars from PASC but also a 3-fold higher ethanol production than a similar yeast consortium secreting only the three cellulases. The use of more complex cellulosomal structures may further improve the overall efficiency for ethanol production.
Accessibility, availability and affordability of anti-malarials in a rural district in Kenya after implementation of a national subsidy scheme
Authors: Smith Nathan , Obala Andrew , Simiyu Chrispinus , Menya Diana , Khwa-Otsyula Barasa , O'Meara Wendy Prudhomme 
Published: November 2011

Abstract

Background
Poor access to prompt and effective treatment for malaria contributes to high mortality and severe morbidity. In Kenya, it is estimated that only 12% of children receive anti-malarials for their fever within 24 hours. The first point of care for many fevers is a local medicine retailer, such as a pharmacy or chemist. The role of the medicine retailer as an important distribution point for malaria medicines has been recognized and several different strategies have been used to improve the services that these retailers provide. Despite these efforts, many mothers still purchase ineffective drugs because they are less expensive than effective artemisinin combination therapy (ACT). One strategy that is being piloted in several countries is an international subsidy targeted at anti-malarials supplied through the retail sector. The goal of this strategy is to make ACT as affordable as ineffective alternatives. The programme, called the Affordable Medicines Facility - malaria was rolled out in Kenya in August 2010.

Methods
In December 2010, the affordability and accessibility of malaria medicines in a rural district in Kenya were evaluated using a complete census of all public and private facilities, chemists, pharmacists, and other malaria medicine retailers within the Webuye Demographic Surveillance Area. Availability, types, and prices of anti-malarials were assessed. There are 13 public or mission facilities and 97 medicine retailers (registered and unregistered).

Results
The average distance from a home to the nearest public health facility is 2 km, but the average distance to the nearest medicine retailer is half that. Quinine is the most frequently stocked anti-malarial (61% of retailers). More medicine retailers stocked sulphadoxine-pyramethamine (SP; 57%) than ACT (44%). Eleven percent of retailers stocked AMFm subsidized artemether-lumefantrine (AL). No retailers had chloroquine in stock and only five were selling artemisinin monotherapy. The mean price of any brand of AL, the recommended first-line drug in Kenya, was $2.7 USD. Brands purchased under the AMFm programme cost 40% less than non-AMFm brands. Artemisinin monotherapies cost on average more than twice as much as AMFm-brand AL. SP cost only $0.5, a fraction of the price of ACT.

Conclusions
AMFm-subsidized anti-malarials are considerably less expensive than unsubsidized AL, but the price difference between effective and ineffective therapies is still large.
TO901317 regulating apolipoprotein M expression mediates via the farnesoid X receptor pathway in Caco-2 cells
Authors: Zhu Chunhua , Di Dongmei , Zhang Xiaoying , Luo Guanghua , Wang Zongchun , Wei Jiang , Shi Yuanping , Berggren-Söderlund Maria , Nilsson-Ehle Peter , Xu Ning 
Published: November 2011

Abstract

Background
Apolipoprotein M (apoM) may have potential antiatherosclerotic properties. It has been reported that apoM expression could be regulated by many intracellar and extracellar factors. In the present study we further investigated regulation of apoM expression in Caco-2 cells stimulated by a liver X receptor (LXR) agonist, TO901317.

Materials and methods
Caco-2 cells were cultured in the presence of either TO901317, farnesoid X receptor (FXR) antagonist guggulsterone or TO901317 together with guggulsterone at different concentrations for 24 hrs. The mRNA levels of ATP-binding cassette transporter A1 (ABCA1), apoA1, apoM, liver receptor homologue-1 (LRH-1) and short heterodimer partner 1 (SHP1) were determined by real-time RT-PCR.

Results
When Caco-2 cell cultured with TO901317 alone, the mRNA levels of ABCA1, apoA1, apoM, LRH-1 and SHP1 were significantly increased with dose-dependent manners (p < 0.05), whereas when the cells cultured with guggulsterone alone, the mRNA levels of apoM, SHP1 and LRH-1 (p < 0.05) were strongly inhibited. Moreover, guggulsterone could abolish the TO901317 enhanced mRNA levels of apoA1 apoM, SHP1 and LRH-1.

Conclusion
The present study demonstrated that LXR agonist TO901317 induced apoM expression in Caco-2 cells might be mediated via the LXR/FXR pathway.
A multi-tissue type genome-scale metabolic network for analysis of whole-body systems physiology
Authors: Bordbar Aarash , Feist Adam M , Usaite-Black Renata , Woodcock Joseph , Palsson Bernhard O , Famili Iman 
Published: November 2011

Abstract

Background
Genome-scale metabolic reconstructions provide a biologically meaningful mechanistic basis for the genotype-phenotype relationship. The global human metabolic network, termed Recon 1, has recently been reconstructed allowing the systems analysis of human metabolic physiology and pathology. Utilizing high-throughput data, Recon 1 has recently been tailored to different cells and tissues, including the liver, kidney, brain, and alveolar macrophage. These models have shown utility in the study of systems medicine. However, no integrated analysis between human tissues has been done.

Results
To describe tissue-specific functions, Recon 1 was tailored to describe metabolism in three human cells: adipocytes, hepatocytes, and myocytes. These cell-specific networks were manually curated and validated based on known cellular metabolic functions. To study intercellular interactions, a novel multi-tissue type modeling approach was developed to integrate the metabolic functions for the three cell types, and subsequently used to simulate known integrated metabolic cycles. In addition, the multi-tissue model was used to study diabetes: a pathology with systemic properties. High-throughput data was integrated with the network to determine differential metabolic activity between obese and type II obese gastric bypass patients in a whole-body context.

Conclusion
The multi-tissue type modeling approach presented provides a platform to study integrated metabolic states. As more cell and tissue-specific models are released, it is critical to develop a framework in which to study their interdependencies.
Current parathyroid hormone immunoassays do not adequately meet the needs of patients with chronic kidney disease
Authors: Almond Alison , Ellis Andrew R , Walker Simon W 
Published: November 2011

Background There are significant differences in plasma parathyroid hormone (PTH) results obtained by current immunoassay methods. However, many clinical guidelines relevant to patients with chronic kidney disease (CKD) that recommend PTH target values do not take account of these differences. This raises major questions about the validity of the evidence underpinning current use of PTH measurements in the management of CKD as well as of published relevant audit data. Methods PTH was measured in plasma from patients with CKD in six commercially available immunoassays. The initial pilot study included 19 patients while 98 patients were included in a second extended study. Data from the second study were analysed by regression analysis to obtain assay-specific targets for each immunoassay. Results Although similar PTH reference intervals are provided by most manufacturers, both studies confirmed substantial between-method differences in observed PTH for all patients, with results varying by as much as 4.2-fold between the lowest and highest reading methods. These differences were sufficient to have treatment implications for 79% of the patients in the pilot study. Applying the assay-specific targets derived here to results from the extended study decreased treatment misclassifications from 53% to 12%. Conclusions Existing between-method differences in PTH measurements clearly have treatment implications. International initiatives to address these differences are in progress and will require support and input from all stakeholders. Adoption of assay-specific target values such as those reported here provides a convenient and practical interim solution that should lead to significant improvement in patient management, while also enabling meaningful audit.
Effectiveness and Acceptability of Delivery of Antiretroviral Treatment in Health Centres by Health Officers and Nurses in Ethiopia
Authors: Assefa Yibeltal , Kiflie Abiyou , Tekle Betru , Mariam Damen Haile , Laga Marie , Van Damme Wim 
Published: November 2011

Objective The World Health Organization (WHO) recommends shifting tasks from physicians to lower cadres for the delivery of antiretroviral treatment (ART) for countries short of physicians. Our objective was to evaluate the effectiveness and acceptability of ART delivery by health officers and nurses in Ethiopia. Methods A retrospective cohort study to evaluate outcomes of ART services in 25 health centresstaffed with health officers and/or nurses and 30 hospitals staffed with physicians in 2009. Median CD4-cell counts, mortality, loss to follow-up and retention were the primary outcomes. Interviews and focus group discussions were conducted with people living with HIV/AIDS, AIDS programme managers and health care providers to identify the types and acceptability of the tasks conducted by the health officers, nurses and community health workers. Results Health officers and nurses were providing ART, including ART prescription, for non-severe cases. The management of severe cases was exclusively the task of physicians. Community health workers were involved in adherence counselling and defaulter tracing. The baseline median CD4-cell counts per micro-liter of blood were 117 (interquartiles [IQ] 64,188) and 119 (IQ 67,190) at health centres and hospitals respectively. After 24 months on ART, the median CD4-cell counts per micro-literof blood increased to 321 (IQ 242, 414) and 301 (IQ 217, 411) at health centres and hospitals respectively. Retention in care was higher in health centres (76%, 95% confidence interval [CI] [73%-79%]) than hospitals (67%, 95% CI [66%-68%]). This difference is mainly due to the higher loss to follow-up rate in hospitals (25% versus 13%). Mortality was higher in health centres than hospitals (11% versus 8%), but the difference is not statistically significant. Service delivery by non-physicians was accepted by patients, health care providers and programme managers. However, the absence of a regulatory framework for task shifting, the lack of extra remuneration for the additional roles assumed by nurses and health officers, and the high cost for training and mentorship were identified as weaknesses. Conclusion ART delivery in health centres, based on health officers and nurses is feasible, effective and acceptable in Ethiopia. However, issues related to regulation, remuneration and cost need to be addressed for the sustainable implementation of these delivery models.
Influence of Population Selection on the 99th Percentile Reference Value for Cardiac Troponin Assays
Authors: Collinson Paul O , Heung Yen Ming , Gaze David , Boa Frances , Senior Roxy , Christenson Robert , Apple Fred S 
Published: November 2011

Abstract

OBJECTIVE
We sought to determine the effect of patient selection on the 99th reference percentile of 2 sensitive and 1 high-sensitivity (hs) cardiac troponin assays in a well-defined reference population.

METHODS
Individuals &gt;45 years old were randomly selected from 7 representative local community practices. Detailed information regarding the participants was collected via questionnaires. The healthy reference population was defined as individuals who had no history of vascular disease, hypertension, or heavy alcohol intake; were not receiving cardiac medication; and had blood pressure &lt;140/90 mmHg, fasting blood glucose &lt;110 mg/dL (approximately 6 mmol/L), estimated creatinine clearance &gt;60 mL · min−1 · (1.73 m2)−1, and normal cardiac function according to results of echocardiography. Samples were stored at −70 °C until analysis for cardiac troponin I (cTnI) and cardiac troponin T (cTnT) and N-terminal pro-B–type natriuretic peptide.

RESULTS
Application of progressively more stringent population selection strategies to the initial baseline population of 545 participants until the only individuals who remained were completely healthy according to the study criteria reduced the number of outliers seen and led to a progressive decrease in the 99th-percentile value obtained for the Roche hs-cTnT assay and the sensitive Beckman cTnI assay but not for the sensitive Siemens Ultra cTnI assay. Furthermore, a sex difference found in the baseline population for the hs-cTnT (P = 0.0018) and Beckman cTnI assays (P &lt; 0.0001) progressively decreased with more stringent population selection criteria.

CONCLUSIONS
The reference population selection strategy significantly influenced the 99th percentile reference values determined for troponin assays and the observed sex differences in troponin concentrations.
Impaired aerobic exercise adaptation in children and adolescents with craniopharyngioma is associated with hypothalamic involvement
Authors: Piguel Xavier , Abraham Pierre , Bouhours-Nouet Natacha , Gatelais Frédérique , Dufresne Sylvie , Rouleau Stéphanie , Coutant Régis 
Published: November 2011

ObjectiveMany patients treated for craniopharyngioma (CP) complain of a relative incapacity for physical activity. Whether this is due to an objective decrease in adaptation to exercise is unclear. We assessed exercise tolerance in children with surgically treated CP and appropriate pituitary hormone replacement therapy compared with healthy controls and we examined the potential relationships with hypothalamic involvement, GH replacement, and the catecholamine deficiency frequently observed in these subjects.Design and methodsSeventeen subjects (12 males and five females) with CP and 22 healthy controls (14 males and eight females) aged 15.3±2.5 years (7.3–18 years) underwent a standardized cycle ergometer test. Maximum aerobic capacity was expressed as the ratio of VO2maxto fat-free mass (VO2max/FFM), a measure independent of age and fat mass in children.ResultsVO2max/FFM was 20% lower in children with CP compared with controls (P<0.05), even after adjustment for gender. Children with hypothalamic involvement (n=10) had a higher percentage of fat mass (P<0.05) than those without hypothalamic involvement (n=7) and lower VO2max/FFM (P<0.05), whereas children without hypothalamic involvement had VO2max/FFM close to that of controls (P>0.05). GH treatment was associated with a significant positive effect on aerobic capacity (P<0.05) only in the absence of hypothalamic involvement. No relationship was found between exercise capacity parameters and daily urine epinephrine excretion or epinephrine peak response to insulin-induced hypoglycemia.ConclusionsChildren with CP have a decrease in aerobic capacity mainly related to hypothalamic involvement. The hypothalamic factors altering aerobic capacity remain to be determined.
Promoting Transparency in Pharmaceutical Industry–Sponsored Research
Authors: Ross Joseph S. , Gross Cary P. , Krumholz Harlan M. 
Published: November 2011

Strong, evidence-based practice requires that objective, unbiased research be available to inform individual clinical decisions, systematic reviews, meta-analyses, and expert guideline recommendations. Industry has used seeding trials, publication planning, messaging, ghostwriting, and selective publication and reporting of trial outcomes to distort the medical literature and undermine clinical trial research by obscuring information relevant to patients and physicians. Policies that promote transparency in the clinical trial research process, through improved and expanded disclosure of investigator contributions and funding, comprehensive publicly available trial registration, and independent analysis of clinical trial data analysis may address these subversive practices by improving accountability among industry and investigators. Minimizing marketing's impact on clinical trial research and strengthening the science will protect medical literature's integrity and the public's health.
Sexual Compulsivity, Co-Occurring Psychosocial Health Problems, and HIV Risk Among Gay and Bisexual Men: Further Evidence of a Syndemic
Authors: Parsons Jeffrey T. , Grov Christian , Golub Sarit A. 
Published: November 2011

Objectives. We evaluated whether sexual compulsivity fits into a syndemic framework, in which sexual compulsivity is one of a number of co-occurring psychosocial health problems that increase HIV risk among men who have sex with men (MSM). Methods. In 2003 and 2004, we conducted an anonymous cross-sectional survey of MSM in New York City (n = 669) by approaching attendees at gay, lesbian, and bisexual community events. We analyzed data by bivariate and multivariate logistic regression. Results. We found strong positive interrelationships among syndemic factors including sexual compulsivity, depression, childhood sexual abuse, intimate partner violence, and polydrug use. In bivariate analyses, all syndemic health problems except for childhood sexual abuse were positively related to HIV seropositivity and high-risk sexual behavior. Our multivariate models revealed an array of interrelationships among psychosocial health problems. We found amplified effects of these problems on HIV seropositivity and on the likelihood of engaging in high-risk sexual behavior. Conclusions. Our findings support the conclusion that sexual compulsivity is a component of a syndemic framework for HIV risk among MSM. HIV prevention interventions should consider the overlapping and compounding effects of psychosocial problems, including sexual compulsivity.
Inventing Conflicts of Interest: A History of Tobacco Industry Tactics
Authors: Brandt Allan M. 
Published: November 2011

Confronted by compelling peer-reviewed scientific evidence of the harms of smoking, the tobacco industry, beginning in the 1950s, used sophisticated public relations approaches to undermine and distort the emerging science.The industry campaign worked to create a scientific controversy through a program that depended on the creation of industry–academic conflicts of interest. This strategy of producing scientific uncertainty undercut public health efforts and regulatory interventions designed to reduce the harms of smoking.A number of industries have subsequently followed this approach to disrupting normative science. Claims of scientific uncertainty and lack of proof also lead to the assertion of individual responsibility for industrially produced health risks.
Ethical Justification for Conducting Public Health Surveillance Without Patient Consent
Authors: Lee Lisa M. , Heilig Charles M. , White Angela 
Published: November 2011

Public health surveillance by necessity occurs without explicit patient consent. There is strong legal and scientific support for maintaining name-based reporting of infectious diseases and other types of public health surveillance. We present conditions under which surveillance without explicit patient consent is ethically justifiable using principles of contemporary clinical and public health ethics. Overriding individual autonomy must be justified in terms of the obligation of public health to improve population health, reduce inequities, attend to the health of vulnerable and systematically disadvantaged persons, and prevent harm. In addition, data elements collected without consent must represent the minimal necessary interference, lead to effective public health action, and be maintained securely.
Household Food Insufficiency, Financial Strain, Work–Family Spillover, and Depressive Symptoms in the Working Class: The Work, Family, and Health Network Study
Authors: Okechukwu Cassandra A. , El Ayadi Alison M. , Tamers Sara L. , Sabbath Erika L. , Berkman Lisa 
Published: November 2011

Objectives. We evaluated the association of household-level stressors with depressive symptoms among low-wage nursing home employees. Methods. Data were collected in 2006 and 2007 from 452 multiethnic primary and nonprimary wage earners in 4 facilities in Massachusetts. We used logistic regression to estimate the association of depressive symptoms with household financial strain, food insufficiency, and work–family spillover (preoccupation with work-related concerns while at home and vice versa). Results. Depressive symptoms were significantly associated with household financial strain (odds ratio [OR] = 1.82; 95% confidence interval [CI] = 1.03, 3.21) and food insufficiency (OR = 2.10; 95% CI = 1.10, 4.18). Among primary earners, stratified analyses showed that food insufficiency was associated with depressive symptoms (OR = 3.60; 95% CI = 1.42, 9.11) but financial strain was not. Among nonprimary wage earners, depressive symptoms correlated with financial strain (OR = 3.65; 95% CI = 1.48, 9.01) and work–family spillover (OR = 3.22; 95% CI = 1.11, 9.35). Conclusions. Household financial strain, food insufficiency, and work–family spillover are pervasive problems for working populations, but associations vary by primary wage earner status. The prevalence of food insufficiency among full-time employees was striking and might have a detrimental influence on depressive symptoms and the health of working-class families.