Pkd1 Regulates Lymphatic Vascular Morphogenesis during Development.

Lymphatic vessels arise during development through sprouting of precursor cells from veins, which is regulated by known signaling and transcriptional mechanisms. The ongoing elaboration of vessels to form a network is less well understood. This involves cell polarization, coordinated migration, adhesion, mixing, regression, and shape rearrangements. We identified a zebrafish mutant, lymphatic and cardiac defects 1 (lyc1), with reduced lymphatic vessel development. A mutation in polycystic kidney disease 1a was responsible for the phenotype. PKD1 is the most frequently mutated gene in autosomal dominant polycystic kidney disease (ADPKD). Initial lymphatic precursor sprouting is normal in lyc1 mutants, but ongoing migration fails. Loss of Pkd1 in mice has no effect on precursor sprouting but leads to failed morphogenesis of the subcutaneous lymphatic network. Individual lymphatic endothelial cells display defective polarity, elongation, and adherens junctions. This work identifies a highly selective and unexpected role for Pkd1 in lymphatic vessel morphogenesis during development

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Algebraic multigrid methods for nonconforming streamline-diffusion finite element discretization of convection-diffusion problems

The streamline-diffusion finite element method (SDFEM) for the solution of convection-diffusion problems using rotated bilinear nonconforming finite element spaces associated with a fine grid generated by multilevel refinement is considered. The existence of hierarchy of grids is exploited to generate coarse-grid spaces in an algebraic manner so that the resulting coarse-grid problems are as sparse as the original matrix. Similar finite element spaces can be also used for the iterative solution of saddle-point problems arising from the mixed discretization of elliptic problems. A new multilevel method based on algebraic generation of the coarse finite element space and respective stiffness matrices and by the matrix generated interpolation and restriction procedures is used as a preconditioner in a generalized conjugate gradient iterative method to solve the resulting highly non-symmetric systems of linear algebraic equations. The good performance of the method both in the convection-dominated and diffusion dominated limits is illustrated with numerical results on a number of two-dimensional model test problems. (orig.)Available from TIB Hannover: RR 4487(1997,30) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

HIV-associated Tuberculosis: Clinical Case

This case report presents a 35-year-old female who presented with HIV-associated multidrug-resistant tuberculosis. Resistant tuberculosis in HIV-infected patients with immunodeficiency is extremely difficult for effective treatment. Nevertheless, our clinical case showed that the cure of tuberculosis is possible in the late stages of HIV infection with the correct choice of treatment tactics, taking into account the resistance of MBT with the subsequent use of antiretroviral therapy. The progression of HIV infection, against the background of the effective antituberculous therapy, was associated with the patient's refusal to treat the underlying disease

Nutrient effects on motor neurons and the risk of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is an incurable chronic progressive neurodegenerative disease with the progressive degeneration of motor neurons in the motor cortex and lower motor neurons in the spinal cord and the brain stem. The etiology and pathogenesis of ALS are being actively studied, but there is still no single concept. The study of ALS risk factors can help to understand the mechanism of this disease development and, possibly, slow down the rate of its progression in patients and also reduce the risk of its development in people with a predisposition toward familial ALS. The interest of researchers and clinicians in the protective role of nutrients in the development of ALS has been increasing in recent years. However, the role of some of them is not well-understood or disputed. The objective of this review is to analyze studies on the role of nutrients as environmental factors affecting the risk of developing ALS and the rate of motor neuron degeneration progression. Methods: We searched the PubMed, Springer, Clinical keys, Google Scholar, and E-Library databases for publications using keywords and their combinations. We analyzed all the available studies published in 2010–2020. Discussion: We analyzed 39 studies, including randomized clinical trials, clinical cases, and metaanalyses, involving ALS patients and studies on animal models of ALS. This review demonstrated that the following vitamins are the most significant protectors of ALS development: vitamin B12, vitamin E > vitamin C > vitamin B1, vitamin B9 > vitamin D > vitamin B2, vitamin B6 > vitamin A, and vitamin B7. In addition, this review indicates that the role of foods with a high content of cholesterol, polyunsaturated fatty acids, urates, and purines plays a big part in ALS development. Conclusion: The inclusion of vitamins and a ketogenic diet in disease-modifying ALS therapy can reduce the progression rate of motor neuron degeneration and slow the rate of disease progression, but the approach to nutrient selection must be personalized. The roles of vitamins C, D, and B7 as ALS protectors need further study. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Candidate genes of regulation of skeletal muscle energy metabolism in athletes

All biological processes associated with high sports performance, including energy metabolism, are influenced by genetics. DNA sequence variations in such genes, single nucleotide variants (SNVs), could confer genetic advantages that can be exploited to achieve optimal athletic performance. Ignorance of these features can create genetic “barriers” that prevent professional athletes from pursuing a career in sports. Predictive Genomic DNA Profiling reveals single nucleotide variations (SNV) that may be associated with better suitability for endurance, strength and speed sports. (1) Background: To conduct a research on candidate genes associated with regulation of skeletal muscle energy metabolism among athletes. (2) Methods: We have searched for articles in SCOPUS, Web of Science, Google Scholar, Clinical keys, PubMed, e-LIBRARY databases for the period of 2010–2020 using keywords and keywords combinations; (4) Conclusions: Identification of genetic markers associated with the regulation of energy metabolism in skeletal muscles can help sports physicians and coaches develop personalized strategies for selecting children, teenagers and young adults for endurance, strength and speed sports (such as jogging, middle or long distance runs). However, the multifactorial aspect of sport performances, including impact of genetics, epigenetics, environment (training and etc.), is important for personalized strategies for selecting of athletes. This approach could improve sports performance and reduce the risk of sports injuries to the musculoskeletal system. © 2021 by the authors. Licensee MDPI, Basel, Switzerland