Few studies have assessed the burden of Chagas disease in non-endemic countries and most of them are based on prevalence estimates from Latin American (LA) countries that likely differ from the ...prevalence in migrants living in Europe. The aim of this study was to systematically review the existing data informing current understanding of the prevalence of Chagas disease in LA migrants living in European countries.
We conducted a systematic review and meta-analysis of studies reporting prevalence of Chagas disease in European countries belonging to the European Union (EU) before 2004 in accordance with the MOOSE guidelines and based on the database sources MEDLINE and Global Health. No restrictions were placed on study date, study design or language of publication. The pooled prevalence was estimated using random effect models based on DerSimonian & Laird method.
We identified 18 studies conducted in five European countries. The random effect pooled prevalence was 4.2% (95%CI:2.2-6.7%); and the heterogeneity of Chagas disease prevalence among studies was high (I2 = 97%,p<0.001). Migrants from Bolivia had the highest prevalence of Chagas disease (18.1%, 95%CI:13.9-22.7%).
Prevalence of Chagas in LA migrants living in Europe is high, particularly in migrants from Bolivia and Paraguay. Data are highly heterogeneous dependent upon country of origin and within studies of migrants from the same country of origin. Country-specific prevalence differs from the estimates available from LA countries. Our meta-analysis provides prevalence estimates of Chagas disease that should be used to estimate the burden of disease in European countries.
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In this trial, a 24-week regimen of bedaquiline, pretomanid, linezolid, and moxifloxacin was noninferior to standard care for rifampin-resistant tuberculosis.
Hepatic glucose release into the circulation is vital for brain function and survival during periods of fasting and is modulated by an array of hormones that precisely regulate plasma glucose levels. ...We have identified a fasting-induced protein hormone that modulates hepatic glucose release. It is the C-terminal cleavage product of profibrillin, and we name it Asprosin. Asprosin is secreted by white adipose, circulates at nanomolar levels, and is recruited to the liver, where it activates the G protein-cAMP-PKA pathway, resulting in rapid glucose release into the circulation. Humans and mice with insulin resistance show pathologically elevated plasma asprosin, and its loss of function via immunologic or genetic means has a profound glucose- and insulin-lowering effect secondary to reduced hepatic glucose release. Asprosin represents a glucogenic protein hormone, and therapeutically targeting it may be beneficial in type II diabetes and metabolic syndrome.
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•Asprosin discovered as a fasting-induced glucogenic protein hormone•Asprosin induces hepatic glucose production by using cAMP as a second messenger•Asprosin is pathologically elevated with human and mouse insulin resistance•Reduction of asprosin protects against metabolic-syndrome-associated hyperinsulinism
Circulating asprosin, a protein hormone, responds to low dietary glucose by triggering the release of liver glucose stores, and the reduction of asprosin protects against the hyperinsulinism associated with metabolic syndrome.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
These parameters were developed by the Joint Task Force on Practice Parameters (JTFPP), representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, ...Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma & Immunology. The AAAAI and ACAAI have jointly accepted responsibility for establishing “The diagnosis and management of acute and chronic urticaria: 2014 update.” This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the JTFPP, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. The JTFPP understands that the cost of diagnostic tests and therapeutic agents is an important concern that might appropriately influence the work-up and treatment chosen for a given patient. The JTFPP recognizes that the emphasis of our primary recommendations regarding a medication might vary, for example, depending on third-party payer issues and product patent expiration dates. However, because a given test or agent's cost is so widely variable and there is a paucity of pharmacoeconomic data, the JTFPP generally does not consider cost when formulating practice parameter recommendations. In extraordinary circumstances, when the cost/benefit ratio of an intervention is prohibitive, as supported by pharmacoeconomic data, commentary might be provided. These parameters are not designed for use by pharmaceutical companies in drug promotion. The JTFPP is committed to ensuring that the practice parameters are based on the best scientific evidence that is free of commercial bias. To this end, the parameter development process includes multiple layers of rigorous review. These layers include the workgroup convened to draft the parameter, the task force reviewers, and peer review by members of each sponsoring society. Although the task force has the final responsibility for the content of the documents submitted for publication, each reviewer comment will be discussed, and reviewers will receive written responses to comments, when appropriate. To preserve the greatest transparency regarding potential conflicts of interest, all members of the JTFPP and the practice parameter workgroups will complete a standard potential conflict of interest disclosure form, which will be available for external review by the sponsoring organization and any other interested individual. In addition, before confirming the selection of a Work Group chairperson, the Joint Task Force will discuss and resolve all relevant potential conflicts of interest associated with this selection. Finally, all members of parameter workgroups will be provided a written statement regarding the importance of ensuring that the parameter development process is free of commercial bias. Practice parameters are available online at www.jcaai.org and www.allergyparameters.org.
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The transition from medical school to residency is a critical step in the careers of physicians. Because of the standardized application process-wherein schools submit summative Medical Student ...Performance Evaluations (MSPE's)-it also represents a unique opportunity to assess the possible prevalence of racial and gender disparities, as shown elsewhere in medicine.
The authors conducted textual analysis of MSPE's from 6,000 US students applying to 16 residency programs at a single institution in 2014-15. They used custom software to extract demographic data and keyword frequency from each MSPE. The main outcome measure was the proportion of applicants described using 24 pre-determined words from four thematic categories ("standout traits", "ability", "grindstone habits", and "compassion").
The data showed significant differences based on race and gender. White applicants were more likely to be described using "standout" or "ability" keywords (including "exceptional", "best", and "outstanding") while Black applicants were more likely to be described as "competent". These differences remained significant after controlling for United States Medical Licensing Examination Step 1 scores. Female applicants were more frequently described as "caring", "compassionate", and "empathic" or "empathetic". Women were also more frequently described as "bright" and "organized".
While the MSPE is intended to reflect an objective, summative assessment of students' qualifications, these data demonstrate for the first time systematic differences in how candidates are described based on racial/ethnic and gender group membership. Recognizing possible implicit biases and their potential impact is important for faculty who strive to create a more egalitarian medical community.
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More than half of breast cancers express low levels of HER2. In a phase 3 trial, the antibody–drug conjugate trastuzumab deruxtecan resulted in longer survival than the physician’s choice of ...chemotherapy among patients with HER2-low breast cancer.
We conducted a model-based assessment of changes in permafrost area and carbon storage for simulations driven by RCP4.5 and RCP8.5 projections between 2010 and 2299 for the northern permafrost ...region. All models simulating carbon represented soil with depth, a critical structural feature needed to represent the permafrost carbon–climate feedback, but that is not a universal feature of all climate models. Between 2010 and 2299, simulations indicated losses of permafrost between 3 and 5 million km² for the RCP4.5 climate and between 6 and 16 million km² for the RCP8.5 climate. For the RCP4.5 projection, cumulative change in soil carbon varied between 66-Pg C (1015-g carbon) loss to 70-Pg C gain. For the RCP8.5 projection, losses in soil carbon varied between 74 and 652 Pg C (mean loss, 341 Pg C). For the RCP4.5 projection, gains in vegetation carbon were largely responsible for the overall projected net gains in ecosystem carbon by 2299 (8- to 244-Pg C gains). In contrast, for the RCP8.5 projection, gains in vegetation carbon were not great enough to compensate for the losses of carbon projected by four of the five models; changes in ecosystem carbon ranged from a 641-Pg C loss to a 167-Pg C gain (mean, 208-Pg C loss). The models indicate that substantial net losses of ecosystem carbon would not occur until after 2100. This assessment suggests that effective mitigation efforts during the remainder of this century could attenuate the negative consequences of the permafrost carbon–climate feedback.
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The growing burden of diabetes worldwide is a threat to tuberculosis (TB) control. Drug-induced liver injury (DILI) due to TB drugs is a significant concern and there is currently limited evidence on ...the effect of diabetes on TB DILI. This study sought to investigate the effect of diabetes as a risk factor for DILI and to further study any potential co-factors.
An unmatched case-control study. Cases were TB patients on 2RHZE/4RH presenting with DILI from 2013-2017 in Porto Alegre, Brazil. Controls were contemporaneous TB patients without DILI being treated in any one of the same five Porto Alegre TB clinics. The exposure variables were diabetes (main exposure variable), age, sex, alcohol misuse, human immunodeficiency virus (HIV), hepatitis C (HCV) and B (HBV) viruses, concomitant hepatotoxic drugs, other liver diseases and TB site. The outcome variable was the occurrence of DILI.
Odds of DILI were increased by: older age group 51-60, 61-70 and 71-93 years (adjusted OR 2.39, 95%CI 1.30-4,38; adjusted OR 4.37, 2.28-8,35; adjusted OR 12.91, 5.81-28,66, respectively), HIV positive status (adjusted OR 3.59, 95%CI 2.25-5.73), HCV positive status (adjusted OR 3.49, 95%CI 1.96-6.21) and having concurrent pulmonary and extrapulmonary TB (adjusted OR 3.16, 95%CI 1.93-5.19). Diabetes, gender, and other hepatotoxic drugs were not associated with DILI.
This study confirms the association between TB DILI and well-known risk factors but did not demonstrate increased odds of TB DILI in patients with diabetes.
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The mechanical properties of a cell determine many aspects of its behavior, and these mechanics are largely determined by the cytoskeleton. Although the contribution of actin filaments and ...microtubules to the mechanics of cells has been investigated in great detail, relatively little is known about the contribution of the third major cytoskeletal component, intermediate filaments (IFs). To determine the role of vimentin IF (VIF) in modulating intracellular and cortical mechanics, we carried out studies using mouse embryonic fibroblasts (mEFs) derived from wild-type or vimentin−/− mice. The VIFs contribute little to cortical stiffness but are critical for regulating intracellular mechanics. Active microrheology measurements using optical tweezers in living cells reveal that the presence of VIFs doubles the value of the cytoplasmic shear modulus to ∼10 Pa. The higher levels of cytoplasmic stiffness appear to stabilize organelles in the cell, as measured by tracking endogenous vesicle movement. These studies show that VIFs both increase the mechanical integrity of cells and localize intracellular components.
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Molecular motors in cells typically produce highly directed motion; however, the aggregate, incoherent effect of all active processes also creates randomly fluctuating forces, which drive ...diffusive-like, nonthermal motion. Here, we introduce force-spectrum-microscopy (FSM) to directly quantify random forces within the cytoplasm of cells and thereby probe stochastic motor activity. This technique combines measurements of the random motion of probe particles with independent micromechanical measurements of the cytoplasm to quantify the spectrum of force fluctuations. Using FSM, we show that force fluctuations substantially enhance intracellular movement of small and large components. The fluctuations are three times larger in malignant cells than in their benign counterparts. We further demonstrate that vimentin acts globally to anchor organelles against randomly fluctuating forces in the cytoplasm, with no effect on their magnitude. Thus, FSM has broad applications for understanding the cytoplasm and its intracellular processes in relation to cell physiology in healthy and diseased states.
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•Random intracellular motion is driven by active force fluctuations in the cytoplasm•The aggregate random forces enhance motion of small proteins and large organelles•We develop force spectrum microscopy to probe aggregate random cytoplasmic forces•The aggregate random forces are larger in malignant cancer cells than benign cells
A new technique called force spectrum microscopy allows probing random active force fluctuations in the cytoplasm of living cells. These forces drive a diffusive-like mechanism of transport of organelles and proteins in the cytoplasm and are more active in cancer than in normal cells.
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