The context of embryonic development and its ethical relevance

Research on human stem cells and embryos creates ethical issues. Here I discuss ten frequently used arguments against research and point out their weaknesses. These arguments include the possessed potentiality of the embryo per se and, in contrast to other cell systems, the "slippery slope" argument, the right of disposal of parents, totipotency versus pluripotency, the burden of proof for research, natural versus artificial, and three arguments based on the precaution principle (the open biological questions, uncertainty regarding clinically applicable therapies, and the problem solving rule). I finally suggest a different answer to the ethical questions concerning research on human embryos and embryonic stem cells, which takes into consideration their biological context.     

A novel in vitro co-culture model to examine contact formation between astrocytic processes and cerebral vessels

Here, we developed a novel in vitro co-culture model, in which process-bearing astrocytes and isolated cerebral microvessels from mice were co-cultured. Astrocytes formed contacts with microvessels from both adult and neonatal mice. However, concentrated localization of the immunofluorescence signal for aquaporin-4 (AQP4) at contact sites between perivascular endfoot processes and blood vessels was only detected with neonatal mouse microvessels. Contact between astrocytic processes and microvessels was retained, whereas concentrated localization of AQP4 signal at contact sites was lost, by knockdown of dystroglycan or α-syntrophin, reflecting polarized localization of AQP4 at perivascular regions in the brain. Further, using our in vitro co-culture model, we found that astrocytes predominantly extend processes to pericytes located at the abluminal surface of microvessels, providing additional evidence that this model is representative of the in vivo situation. Altogether, we have developed a novel in vitro co-culture model that can reproduce aspects of the in vivo situation and is useful for assessing contact formation between astrocytes and blood vessels.     

Highly heterogeneous residual malaria risk in western Thailand

Over the past decades, the malaria burden in Thailand has substantially declined. Most infections now originate from the national border regions. In these areas, the prevalence of asymptomatic infections is still substantial and poses a challenge for the national malaria elimination program. To determine epidemiological parameters as well as risk factors for malaria infection in western Thailand, we carried out a cohort study in Kanchanaburi and Ratchaburi provinces on the Thailand-Myanmar border. Blood samples from 999 local participants were examined for malaria infection every 4 weeks between May 2013 and Jun 2014. Prevalence of Plasmodium falciparum and Plasmodium vivax was determined by quantitative PCR (qPCR) and showed a seasonal variation with values fluctuating from 1.7% to 4.2% for P. vivax and 0% to 1.3% for P. falciparum. Ninety percent of infections were asymptomatic. The annual molecular force of blood-stage infection (_molFOB) was estimated by microsatellite genotyping to be 0.24 new infections per person-year for P. vivax and 0.02 new infections per person-year for P. falciparum. The distribution of infections was heterogenous, that is, the vast majority of infections (>80%) were found in a small number of individuals (<8% of the study population) who tested positive at multiple timepoints. Significant risk factors were detected for P. vivax infections, including previous clinical malaria, occupation in agriculture and travel to Myanmar. In contrast, indoor residual spraying was associated with a protection from infection. These findings provide a recent landscape of malaria epidemiology and emphasize the importance of novel strategies to target asymptomatic and imported infections.     

A comparison of two global positioning system devices for team-sport running protocols

The comparability and reliability of global positioning system (GPS) devices during running protocols associated with team-sports was investigated. Fourteen moderately-trained males completed 690 m of straight-line movements, a 570 m change of direction (COD) course and a 642.5 m team-sport simulated circuit (TSSC); on two occasions. Participants wore a FieldWiz GPS device and a Catapult MinimaxX S4 10-Hz GPS device. Typical error of measurement (TE) and coefficient of variation (CV%) were calculated between GPS devices, for the variables of total distance and peak speed. Reliability comparisons were made within FieldWiz GPS devices, between sessions. Small TE were observed between FieldWiz and Catapult GPS devices for total distance and peak speed during straight-line (16.9 m [2%], 1.2 km·h⁻¹ [4%]), COD (31.8 m [6%], 0.4 km·h⁻¹ [2%]) and TSSC protocols (12.9 m [2%], 0.5 km·h⁻¹ [2%]), respectively, with no significant mean bias (p > 0.05). Small TE were also observed for the FieldWiz GPS device between sessions (p > 0.05) for straight-line (9.6 m [1%], 0.2 km·h⁻¹ [1%]), COD (12.8 m [2%], 0.2 km·h⁻¹ [1%]) and TSSC protocols (6.9 m [1%], 0.6 km·h⁻¹ [2%]), respectively. Data from the FieldWiz GPS device appears comparable to established devices and reliable across a range of movement patterns associated with team-sports.     

Preliminary investigation of teaching older adults the tuck-and-roll strategy: Can older adults learn to fall with reduced impact severity

Falls are common and potentially disastrous for older adults. A novel approach that could augment current fall prevention procedures is to teach older adults movement strategies to reduce the risk of injury. The purpose of the study was to determine whether older adults can learn a movement strategy (“tuck-and-roll”) that reduces fall impact severity. Learning was quantified with short-term acquisition, bilateral transfer and 1-week-retention. 14 healthy older individuals participated (63.9 ± 5.6 years) in the investigation. Participants were randomly assigned into either training group (n = 7) or active control group (n = 7). All participants performed standardized sideway falls at baseline, immediately post intervention and 1-week-retention tests. During the falling assessments, kinetic and kinematic impact severity parameters were measured. The results for short-term learning revealed that the training group showed greater reduction in hip impact force (33% reduction) than the control group (16% reduction). Furthermore, there was partial bilateral transfer effect and 1-week retention observed in the training group. The observations provide preliminary evidence that teaching tuck-and-roll strategy to older adults has potential effect. The observations provide preliminary evidence that older adults might reduce impact severity utilizing tuck-and-roll strategy during unpredictably-timed sideway falls.     

Diez recomendaciones para mejorar la enseñanza de la Geriatría en el pregrado

IntroductionPopulation ageing and scientific progress have made specific training in Geriatrics essential for any medical students. There are different international recommendations on the teaching of Geriatric Medicine at undergraduate level, but they are still far from being offered systematically. The aim of this work was to develop a National list of recommendations in order to improve training in Geriatric Medicine at the undergraduate level.Material and methodsA list of 10 recommendations was produced by reflecting on the Geriatric training situation in Spain in 2016/2017 and international recommendations. Consensus was reached among the members of the Spanish Society of Geriatrics and Gerontology (SEGG) working group on «Geriatric training at undergraduate level» through 2 meetings and online discussions.ResultsA list of 10 of recommendations on Geriatric training in Spanish Medical Schools is proposed, including areas such as, the status of the discipline in the curriculum, length, contents, practical training, lecturers, teaching methods, and innovation.ConclusionsThese recommendations are intended to improve Geriatrics training. They can be used by different Medical Schools either to adapt their programs or to start training in Geriatric Medicine.     

Potential roles and targeted therapy of the CXCLs/CXCR2 axis in cancer and inflammatory diseases

The chemokine receptor CXCR2 and its ligands are implicated in the progression of tumours and various inflammatory diseases. Activation of the CXCLs/CXCR2 axis activates multiple signalling pathways, including the PI3K, p38/ERK, and JAK pathways, and regulates cell survival and migration. The CXCLs/CXCR2 axis plays a vital role in the tumour microenvironment and in recruiting neutrophils to inflammatory sites. Extensive infiltration of neutrophils during chronic inflammation is one of the most important pathogenic factors in various inflammatory diseases. Chronic inflammation is considered to be closely correlated with initiation of cancer. In addition, immunosuppressive effects of myeloid-derived suppressor cells (MDSCs) against T cells attenuate the anti-tumour effects of T cells and promote tumour invasion and metastasis. Over the last several decades, many therapeutic strategies targeting CXCR2 have shown promising results and entered clinical trials. In this review, we focus on the features and functions of the CXCLs/CXCR2 axis and highlight its role in cancer and inflammatory diseases. We also discuss its potential use in targeted therapies.     

Circulating small non-coding RNAs provide new insights into vitamin K nutrition and reproductive physiology in teleost fish

Background

Vitamin K (VK) is a fat-soluble vitamin known for its essential role in blood coagulation, but also on other biological processes (e.g. reproduction, brain and bone development) have been recently suggested. Nevertheless, the molecular mechanisms behind its particular function on reproduction are not yet fully understood.

Diabetic gut microbiota dysbiosis as an inflammaging and immunosenescence condition that fosters progression of retinopathy and nephropathy

The increased prevalence of type 2 diabetes mellitus (T2DM) and life expectancy of diabetic patients fosters the worldwide prevalence of retinopathy and nephropathy, two major microvascular complications that have been difficult to treat with contemporary glucose-lowering medications. The gut microbiota (GM) has become a lively field research in the last years; there is a growing recognition that altered intestinal microbiota composition and function can directly impact the phenomenon of ageing and age-related disorders. In fact, human GM, envisaged as a potential source of novel therapeutics, strongly modulates host immunity and metabolism. It is now clear that gut dysbiosis and their products (e.g. p-cresyl sulfate, trimethylamine?N?oxide) dictate a secretory associated senescence phenotype and chronic low-grade inflammation, features shared in the physiological process of ageing (“inflammaging”) as well as in T2DM (“metaflammation”) and in its microvascular complications. This review provides an in-depth look on the crosstalk between GM, host immunity and metabolism. Further, it characterizes human GM signatures of elderly and T2DM patients. Finally, a comprehensive scrutiny of recent molecular findings (e.g. epigenetic changes) underlying causal relationships between GM dysbiosis and diabetic retinopathy/nephropathy complications is pinpointed, with the ultimate goal to unravel potential pathophysiological mechanisms that may be explored, in a near future, as personalized disease-modifying therapeutic approaches.     

Knockout of Nr2e3 prevents rod photoreceptor differentiation and leads to selective L-/M-cone photoreceptor degeneration in zebrafish

Mutations in the photoreceptor cell-specific nuclear receptor gene Nr2e3 increased the number of S-cone photoreceptors in human and murine retinas and led to retinal degeneration that involved photoreceptor and non-photoreceptor cells. The mechanisms underlying these complex phenotypes remain unclear. In the hope of understanding the precise role of Nr2e3 in photoreceptor cell fate determination and differentiation, we generated a line of Nr2e3 knockout zebrafish using CRISPR technology. In these Nr2e3-null animals, rod precursors undergo terminal mitoses but fail to differentiate as rods. Rod-specific genes are not expressed and the outer segment (OS) fails to form. Formation and differentiation of cone photoreceptors is normal. Specifically, there is no increase in the number of UV-cone or S-cone photoreceptors. Laminated retinal structure is maintained. After normal development, L-/M-cones selectively degenerate, with progressive shortening of OS that starts at age 1 month. The amount of cone phototransduction proteins is concomitantly reduced, whereas UV- and S-cones have normal OS lengths even at age 10 months. In vitro studies show Nr2e3 synergizes with Crx and Nrl to enhance rhodopsin gene expression. Nr2e3 does not affect cone opsin expression. Our results extend the knowledge of Nr2e3's roles and have specific implications for the interpretation of the phenotypes observed in human and murine retinas. Furthermore, our model may offer new opportunities in finding treatments for enhanced S-cone syndrome (ESCS) and other retinal degenerative diseases.