The internal thoracic artery in human foetuses

The aim of this study was to examine the internal thoracic artery (ITA) in human foetuses. The research material consisted of 32 human foetuses (18 female, 14 male) from the 21st to 24th week of intrauterine life. After intravascular injection with white latex LBS 3060, the foetuses were fixed in 10% neutral formalin solution. The whole course of the ITA was prepared. Photographic documentation was performed with a Nikon Coolpix 4500 digital camera, and source pictures of arteries were rendered in a Digital Computer System Analysis. The ITA was evaluated with regard to its origin, length, distance from the edge of the sternum to two intercostal spaces (2nd, 5th) and division into terminal branches. The right ITA (RITA) arose from the ascending (68.7%), arcuate (21.9%) and descending (3.2%) parts of the subclavian artery. In other cases (6.2%) it was a branch of the thyrocervical trunk. The left ITA (LITA) was a branch of the ascending (78.1%) and arcuate (21.9%) parts of the subclavian artery. The ITA was longer in male foetuses. Regardless of sex, the LITA was longer than the RITA. Coefficient correlation between the RITA and LITA was 0.92 (p < 0.001). The distance of the ITA from the edge of sternum in the 2nd and 5th intercostal spaces on both sides was greater in females. It appeared most frequently in the 6th space (43.7% right-sided and 56.3% left-sided). Typical bifurcation of the ITA into the superior epigastric artery and the musculophrenic artery was observed in 78.1% of cases on the right side and in 81.25% of cases on the left side

Ryczałt od dochodów spółek – stan obecny i postulaty de lege ferenda

The subject of the article is to&nbsp;identify the deficiencies in&nbsp;the functioning of the corporate income tax and develop de lege ferenda postulates. In their deliberations, the authors will address both the classical system of income taxation and the flat-rate tax on corporate income. The flat-rate tax on corporate income represents an alternative taxation mechanism, linked to&nbsp;the moment of profit distribution. The article will diagnose deficiencies in&nbsp;selected areas of corporate taxation (the current state of affairs) and provide recommendations for changes.Przedmiotem artykułu jest zidentyfikowanie deficytów funkcjonowania podatku dochodowego od osób prawnych i wypracowanie postulatów de lege ferenda. W swoich rozważaniach autorzy odniosą się zarówno do klasycznego systemu opodatkowania dochodów, jak i do ryczałtu od dochodów spółek. Ryczałt od dochodów spółek stanowi alternatywny mechanizm opodatkowania, powiązany z momentem wypłaty zysków. W artykule autorzy diagnozują deficyty w wybranych obszarach opodatkowania spółek (obecny stan rzeczy) oraz przedstawiają rekomendacje zmian

Prognozowanie rozwoju technologii drogowych na podstawie metody delfickiej – wybrane zagadnienia

An objective of this research project is an analysis of development directions of new materials, technologies and pavement structures used in road industry, taking into account special environmental conditions and sustainable development rules. Results of&nbsp;the first round of conducted study based on the foresight method are described in this paper. Such results are helpful to provide support for making a long term strategy decisions by the government. Selected results and analysis in the scope of identification of the main research areas and hypothesis connected with developments of road technology are shown in this paper with a special focus on the construction of the durable pavements. It was found that the most important task is related to developments of the asphalt and cement pavements technology providing at least 30 years durability period. The construction of such pavements is possible only when high quality of work is provided and there is further road technology development as a result of the science and industry cooperation. &nbsp;Celem realizowanego projektu badawczego jest analiza kierunków rozwoju nowych materiałów, technologii i konstrukcji nawierzchni stosowanych w&nbsp;budownictwie drogowym z uwzględnieniem szczególnych uwarunkowań środowiskowych i zasad zrównoważonego rozwoju. W artykule przedstawiono wyniki pierwszej rundy badania eksperckiego w którym wykorzystano metodę foresightu. Badania studialne przydatne są w informowaniu decydentów politycznych oraz środowisk opiniotwórczych o&nbsp;pożądanych kierunkach długoterminowego rozwoju i zmian. W niniejszym artykule przedstawiono wybrane wyniki badań i analiz w zakresie identyfikacji głównych obszarów i tez badawczych związanych z prognozowanymi kierunkami rozwoju budownictwa drogowego. Omówiono zidentyfikowany obszar badawczy dotyczący technologii budowy trwałych nawierzchni drogowych w Polsce. Wykazano, że najważniejszym obecnie zadaniem w zakresie budowy nawierzchni drogowych jest prowadzenie prac nad rozwojem technologii asfaltowych i z betonu cementowego, które zapewnią co najmniej 30-letnią trwałość nowo budowanym nawierzchniom. Stwierdzono, że budowa trwałych nawierzchni drogowych jest możliwa tylko w przypadku zapewnienia wysokiej jakości wykonawstwa robót oraz rozwoju badań w&nbsp;ramach współpracy jednostek naukowych z&nbsp;szeroko pojętą gospodarką

Clinically relevant depressive symptoms in young stroke patients - results of the sifap1 study

BACKGROUND Although post-stroke depression is widely recognized, less is known about depressive symptoms in the acute stage of stroke and especially in young stroke patients. We thus investigated depressive symptoms and their determinants in such a cohort. METHODS The Stroke in Young Fabry Patients study (sifap1) prospectively recruited a large multinational European cohort (n = 5,023) of patients with a cerebrovascular event aged 18-55. For assessing clinically relevant depressive symptoms (CRDS, defined by a BDI-score ≥18) the self-reporting Beck Depression Inventory (BDI) was obtained on inclusion in the study. Associations with baseline parameters, stroke severity (National Institutes of Health Stroke Scale, NIHSS), and brain MRI findings were analyzed. RESULTS From the 2007 patients with BDI documentation, 202 (10.1%) had CRDS. CRDS were observed more frequently in women (12.6 vs. 8.2% in men, p < 0.001). Patients with CRDS more often had arterial hypertension, diabetes mellitus, and hyperlipidemia than patients without CRDS (hypertension: 58.0 vs. 47.1%, p = 0.017; diabetes mellitus: 17.9 vs. 8.9%, p < 0.001; hyperlipidemia: 40.5 vs. 32.3%, p = 0.012). In the subgroup of patients with ischemic stroke or TIA (n = 1,832) no significant associations between CRDS and cerebral MRI findings such as the presence of acute infarcts (68.1 vs. 65.8%, p = 0.666), old infarctions (63.4 vs. 62.1%, p = 0.725) or white matter hyper-intensities (51.6 vs. 53.7%, p = 0.520) were found. CONCLUSION Depressive symptoms were present in 10.1% of young stroke patients in the acute phase, and were related to risk factors but not to imaging findings

Identification of Novel and Rare Variants Associated with Handgrip Strength Using Whole Genome Sequence Data from the NHLBI Trans-Omics in Precision Medicine (TOPMed) Program

Handgrip strength is a widely used measure of muscle strength and a predictor of a range of morbidities including cardiovascular diseases and all-cause mortality. Previous genome-wide association studies of handgrip strength have focused on common variants primarily in persons of European descent. We aimed to identify rare and ancestry-specific genetic variants associated with handgrip strength by conducting whole-genome sequence association analyses using 13,552 participants from six studies representing diverse population groups from the Trans-Omics in Precision Medicine (TOPMed) Program. By leveraging multiple handgrip strength measures performed in study participants over time, we increased our effective sample size by 7-12%. Single-variant analyses identified ten handgrip strength loci among African-Americans: four rare variants, five low-frequency variants, and one common variant. One significant and four suggestive genes were identified associated with handgrip strength when aggregating rare and functional variants; all associations were ancestry-specific. We additionally leveraged the different ancestries available in the UK Biobank to further explore the ancestry-specific association signals from the single-variant association analyses. In conclusion, our study identified 11 new loci associated with handgrip strength with rare and/or ancestry-specific genetic variations, highlighting the added value of whole-genome sequencing in diverse samples. Several of the associations identified using single-variant or aggregate analyses lie in genes with a function relevant to the brain or muscle or were reported to be associated with muscle or age-related traits. Further studies in samples with sequence data and diverse ancestries are needed to confirm these findings

Lessons from everyday stroke care for clinical research and vice versa: comparison of a comprehensive and a research population of young stroke patients

Peer reviewe

Clonal Hematopoiesis is Associated With Protection From Alzheimer\u27s Disease

Clonal hematopoiesis of indeterminate potential (CHIP) is a premalignant expansion of mutated hematopoietic stem cells. As CHIP-associated mutations are known to alter the development and function of myeloid cells, we hypothesized that CHIP may also be associated with the risk of Alzheimer\u27s disease (AD), a disease in which brain-resident myeloid cells are thought to have a major role. To perform association tests between CHIP and AD dementia, we analyzed blood DNA sequencing data from 1,362 individuals with AD and 4,368 individuals without AD. Individuals with CHIP had a lower risk of AD dementia (meta-analysis odds ratio (OR) = 0.64, P = 3.8 × 1

Cerebral small vessel disease genomics and its implications across the lifespan

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.Peer reviewe

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care