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Despite great advances in our knowledge of the consequences of Zika virus to human health, many questions remain unanswered, and results are often inconsistent. The small sample size of individual studies has limited inference about the spectrum of congenital Zika manifestations and the prognosis of affected children. The Brazilian Zika Cohorts Consortium addresses these limitations by bringing together and harmonizing epidemiological data from a series of prospective cohort studies of pregnant women with rash and of children with microcephaly and/or other manifestations of congenital Zika. The objective is to estimate the absolute risk of congenital Zika manifestations and to characterize the full spectrum and natural history of the manifestations of congenital Zika in children with and without microcephaly. This protocol describes the assembly of the Consortium and protocol for the Individual Participant Data Meta-analyses (IPD Meta-analyses). The findings will address knowledge gaps and inform public policies related to Zika virus. The large harmonized dataset and joint analyses will facilitate more precise estimates of the absolute risk of congenital Zika manifestations among Zika virus-infected pregnancies and more complete descriptions of its full spectrum, including rare manifestations. It will enable sensitivity analyses using different definitions of exposure and outcomes, and the investigation of the sources of heterogeneity between studies and regions.Due to climate change sorghum might gain widespread in the Western countries, as the grain is adapted to hot climate. Additionally sorghum contains a notable amount of health-promoting nutrients. However, Western countries do not have a long history of sorghum consumption, and thus little experience in processing it. Milling systems in these areas were mostly developed for wheat or rye milling. In the present work, the effectiveness of sorghum milling when using a stone and a roller milling system (pilot scale) was investigated as well as its impact on the chemical and physical properties of the obtained flour fractions and whole-grain flours. Pemigatinib Results showed that both milling systems could be successfully adapted to producing chemically and physically distinct flour and bran fractions from the small sorghum kernels. Fractions with increased bran material that contained higher amounts of ash, protein, fat, total dietary fiber, and total phenolic content but less starch, showed enhanced water absorption indices and water solubility indices. Interestingly, no significant difference was found in the ash and fat content of the different fractions obtained from stone milling. Overall, the study provided information on the production and composition of distinct flour fractions, which offer a wider range of future food applications.The mixing process plays a pivotal role in the quality of pharmaceuticals and food/dietary supplements, as it can impact the homogeneity of the substances in their dosage form and affect characteristics such as dissolution and stability. Thus, the choice of the right mixing device is paramount for compounding pharmacies. In this paper, we evaluated the mixing efficacy of a new 3-axis mixer device and determined its optimal working conditions. Three different formulations were compounded with the device and a total of 540 individual assays were performed by HPLC or ICP-MS to validate its use, in addition to a direct comparison among it and two alternative mixing methods. The 3-axis mixer device was able to provide homogeneous mixtures and finished capsules with adequate content uniformity with a broad range of conditions of use (mixing times from 2 to 8 min, and speed of rotation from 10 to 100 rpm). In addition, the device was superior to classical mixing methods (such as the use of manually shaken plastic bags) and at least equivalent to well-established ones (Y-shaped mixer). Finally, we proposed a cleaning procedure that was also adequate to prevent cross-contamination among products compounded with the same device.Human atherosclerotic plaque contains smooth muscle cells (SMCs) negative for the contractile phenotype (α-smooth muscle actin) but positive for proprotein convertase subtilisin/kexin type 9 (PCSK9). Thus, we generated rat SMCs which overexpressed human PCSK9 (SMCsPCSK9) with the aim of investigating the role of PCSK9 in the phenotype of SMCs. PCSK9 overexpression in SMCsPCSK9 led to a significant downregulation of the low-density lipoprotein receptor (Ldlr) as well as transgelin (Sm22α), a marker of the contractile phenotype. The cell proliferation rate of SMCsPCSK9 was significantly faster than that of the control SMCs (SMCspuro). Interestingly, overexpression of PCSK9 did not impact the migratory capacity of SMCs in response to 10% FCS, as determined by Boyden's chamber assay. Expression and activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr) was significantly increased in the presence of PCSK9, both in SMCPCSK9 and after treatment with recombinant PCSK9. The transcriptional activity of sterol regulatory element-binding protein (SREBP) was also increased in the presence of PSCK9, suggesting a direct role of PCSK9 in the control of SRE-responsive genes, like HMGCR. We also observed that cholesterol biosynthesis is elevated in SMCPCSK9, potentially explaining the increased proliferation observed in these cells. Finally, concentration-dependent experiments with simvastatin demonstrated that SMCsPCSK9 were partially resistant to the antiproliferative and antimigratory effect of this drug. Taken together, these data further support a direct role of PCSK9 in proliferation, migration, and phenotypic changes in SMCs-pivotal features of atherosclerotic plaque development. We also provide new evidence on the role of PCSK9 in the pharmacological response to statins-gold standard lipid-lowering drugs with pleiotropic action.
Tibial nonunion is a common bone union disorder leading to abnormal gait, and thus reducing quality of life in the social dimension.
The aim of our work was to comprehensively assess gait parameters of patients who had undergone Ilizarov treatment for tibial nonunion compared to a control group of healthy individuals.
This study evaluated patients treated for aseptic tibial nonunion with the Ilizarov method. 24 patients with a mean age of 55.0 years were included in the study. The control group consisted of 32 healthy volunteers with no significant medical history who were selected to match the gender and age of patients in the study group so that the groups were homogeneous. A Zebris Medical GmbH pedobarographic platform was used to assess the gait parameters.
For all gait parameters examined, force forefoot max, force backfoot max, step length, stance phase, swing phase and step time, we observed statistically significant differences between the group that had undergone treatment and the control group.
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