Notes

Breast cancer in young women-a multicenter 10-year experience.
These results are important for understanding and targeting of neuromodulatory therapies in the ALIC and may help explain why differences in therapeutic effect are observed for different areas of the ALIC.
These results are important for understanding and targeting of neuromodulatory therapies in the ALIC and may help explain why differences in therapeutic effect are observed for different areas of the ALIC.Children with epilepsy have more sleep disorders compared to healthy children. The bidirectional interaction between epilepsy and sleep is not completely understood. However, disruption of sleep architecture during childhood may have consequences for cognitive development. As children with drug-refractory epilepsy often have intellectual disability, sleep disruption could be an important contributing factor in severity of their cognitive impairment. To better understand these interactions, sleep architecture in children with drug-refractory epilepsy and epileptic encephalopathies should be investigated. In this review, we conducted a systematic literature search on this topic. Articles that investigated sleep macro- and/or microstructure by means of electroencephalogram/polysomnography were included, as well as articles that used validated questionnaires. Sixteen articles were reviewed, eight of which used polysomnography. Only 2 articles examined sleep in children with epileptic encephalopathies. Consistent findings on measures of sleep architecture were a reduction in REM percentage and an increase in sleep fragmentation when comparing drug-refractory patients with non-refractory and healthy subjects. The findings on slow wave sleep were less clear. Studies with questionnaires unambiguously confirmed subjectively more sleep problems in children with drug-refractory epilepsy. This is the first review of literature in this patient population. More good quality sleep studies in children with drug-refractory epilepsy are warranted. The use of wearables in the home setting together with automatic sleep staging could provide more insights.Skeletal muscle stem cells (MuSCs), also called satellite cells, are instrumental for postnatal muscle growth and skeletal muscle regeneration. Numerous signaling cascades regulate the fate of MuSCs during muscle regeneration but the molecular mechanism by which MuSCs sense mechanical stimuli remain unclear. Here, we describe that Piezo1, a mechanosensitive ion channel, keeps MuSCs in a quiescent state and prevents senescence. Absence of Piezo1 induces precocious activation of MuSCs, attenuates proliferation, and impairs differentiation, essentially abolishing efficient skeletal muscle regeneration and replenishment of the MuSC pool. Furthermore, we discovered that inactivation of Piezo1 results in compensatory up-regulation of T-type voltage-gated Ca2+ channels, leading to increased Ca2+ influx, which strongly induces NOX4 expression via cPKC. Elevated NOX4 expression in Piezo1-deficient MuSCs increases ROS levels and DNA damage, causing P53-dependent cellular senescence and cell death. The importance of the P53/P21-axis for mediating Piezo1-dependent cellular defects was confirmed by pharmacological inhibition of P53 in Piezo1-deficient mice, which abrogates increased senescence of muscle cells and normalizes muscle regeneration. Our findings uncover an essential role of Piezo1-mediated mechano-signaling in MuSCs for maintaining quiescence and preventing senescence. Reduced mechano-signaling due to decreased physical activity during aging may contribute to the increase of senescent cells and the decline of MuSC numbers in geriatric mice and humans.Spermatogonial stem cells (SSCs) originate from gonocytes that differentiate from primordial germ cells (PGCs). In the developing mouse testis, expression of the gene LIM homeobox 1 (Lhx1) marks the most undifferentiated SSCs, which has not yet been reported for spermatogonia-like cells generated in vitro. Previously, it was shown that a chemical intervention in male mouse embryonic stem (ES) cells in serum culture, including Sirtuin 1 (SIRT1) inhibitor Ex-527, DNA methyltransferase (DNMT) inhibitor RG-108 and electrophilic redox cycling compound tert-butylhydroquinone (tBHQ), was associated with molecular markers of PGC to gonocyte differentiation. Here, we report the in vitro differentiation of male mouse ES cells, cultured under dual chemical inhibition of GSK3β and MEK (2i) with leukemia inhibitory factor (LIF) (2iL) and serum, into cells with spermatogonia-like morphology (CSMs) and population-averaged expression of spermatogonia-specific genes by removal of 2iL and a specific schedule of twice daily partial medium replacement. Combination of this new protocol with the previously reported chemical intervention increased population-averaged gene expression of Lhx1 in the resulting CSMs. Furthermore, we detected single CSMs with strong nuclear LHX1/5 protein signal only in the chemical intervention group. We propose that further investigation of CSMs may provide new insights into male germline development.Research in the field of hepatology is limited by the incomplete recapitulation of all major aspects of human hepatic metabolism in most established models. This restricts our ability to study the molecular mechanisms underlying hepatic diseases, and it leads to inadequate assessment of toxicology during drug development, resulting in tremendous unnecessary costs for the pharma industry. Animal models differ in their metabolism compared to the human system, while primary human cells dedifferentiate rapidly and are not suitable for long-term culture and studies. To overcome these obstacles, several protocols for in vitro differentiation of pluripotent stem cells into hepatocyte like cells (HLCs) have been established. These cells are currently used for modeling inherited and acquired diseases, and to test for drug efficacy and toxicity. Unfortunately, HLCs lack maturity and resemble rather fetal than adult hepatocytes. Novel 3D-based models may overcome these drawbacks in the future. In this review, we critically analyse the most common differentiation protocols and their evolution. In addition, we introduce recently developed techniques for 3D differentiation. Finally, we discuss drawbacks, challenges, and advantages of the distinct systems for routine toxicity tests, disease modeling and future cell replacement therapies.Glomerulopathy with fibronectin deposits (GFND) is an autosomal dominant kidney disease exhibiting microscopic hematuria, proteinuria, and hypertension that may lead to end-stage renal failure. In this study, using non-integrative episomal vectors an induced pluripotent stem cell (iPSC) line, FHUSTCi001-A, was derived from peripheral blood mononuclear cells of an 11-year-old boy with GFND carrying a heterozygous c.5602G > A (p.V1868M) mutation in the FN1 gene. The generated iPSC line has a normal karyotype, expresses pluripotency markers, and has the capacity to form all three germ layers in vivo. This iPSC line offers a useful cellular model to study the pathogenesis of GFND disease.
Nike ZoomX Vaporfly (NVF) improves running economy and performance. The biomechanical mechanisms of these shoes are not fully understood, although thicker midsoles and carbon fiber plates are considered to play an important role in the spring-like leg characteristics during running. Leg stiffness (k
) in the spring-mass model has been commonly used to investigate spring-like running mechanics during running.

Does k
during running differ between NVF and traditional (TRAD) shoes?

Eighteen male habitual forefoot and/or midfoot strike runners ran on a treadmill at 20km/h with NVF and TRAD shoes, respectively. k
, vertical oscillation of the center of mass (∆CoM), spatiotemporal parameters, and mechanical loading were determined.

k
was 4.8% lower in the NVF shoe condition than in the TRAD condition, although no significant difference was observed. ∆CoM was not significantly different between shoe conditions. Spatiotemporal parameters and mechanical loading were also not significantly different between shoe conditions.

The NVF shoe is well known as improving the running economy and running performance for the cause by characteristics of better spring function. Contrary to expectation, k
and other parameters were not significantly different during running in the NVF compared to TRAD shoe at 20km/h. These findings indicate that well-trained runners' spring-like running mechanics would not alter even if wearing the NVF shoes.
The NVF shoe is well known as improving the running economy and running performance for the cause by characteristics of better spring function. Contrary to expectation, kleg and other parameters were not significantly different during running in the NVF compared to TRAD shoe at 20 km/h. These findings indicate that well-trained runners' spring-like running mechanics would not alter even if wearing the NVF shoes.
Altered walking gait is a typical impairment following ankle sprains which may increase susceptibility to recurring injuries and development of posttraumatic osteoarthritis at the ankle. There is a lack of targeted gait training interventions focusing on specific modifications in individuals with chronic ankle instability (CAI). Additionally, there is a need to focus on cartilage health changes following gait training to mitigate osteoarthritis progression.

To determine the immediate and retention effects of gait training using auditory biofeedback (AudFB) in patients with chronic ankle instability (CAI) on biomechanics and talar cartilage characteristics.

Eighteen participants with CAI were randomly assigned into Control (n = 7) or AudFB (n = 11) groups. Each group completed 8-sessions of 30-minute treadmill walking. The AudFB group received biofeedback through a pressure sensor fashioned to the lateral foot and instructions to walk while avoiding noise from the sensor. The Control group did not receive instructions during sessions. An in-shoe insole system measured peak pressure, maximum force, and center of the pressure gait line (COP) during walking. Ultrasonography captured talar cartilage thickness and echo intensity before and after walking. Biomechanics and ultrasound were measured at baseline, immediately, and 1-week after the intervention. Repeated measures mixed-methods analysis of variance assessed changes within groups across time.

The AudFB group significantly reduced pressure and force in the lateral foot and medially shifted their COP at Immediate and 1-week Post. There were no observed changes in the Control group. In addition, neither group demonstrated changes in ultrasound measures at follow-up.

Implementation of auditory biofeedback during gait training can be a valuable tool for clinicians treating patients with CAI.
Implementation of auditory biofeedback during gait training can be a valuable tool for clinicians treating patients with CAI.Toxoplasmosis is an important zoonosis caused by the intracellular protozoan Toxoplasma gondii. This parasite is known to infect almost all warm blooded animals, and meat containing tissue cysts is one of the main sources of infection for omnivorous an carnivorous animals. Over recent years, increasing numbers of omnivorous and carnivorous animals have been drawn to urban or suburban areas by easy access to food or safe shelter, and the presence of wild animals has became more natural to urban residents. However, infected animals can act as intermediate hosts to T. gondii and contribute to the transmission of disease to humans and domestic animals, as well as other wild animal species. This extensive spread of the parasite in the natural environment can be attributed to geographic location, landform or local climate. The present paper summarizes the data available on the prevalence of T. gondii infection among wildlife from Poland, Germany, Slovakia, Czechia, Austria and Hungary. The findings highlight the importance of conducting studies on the presence of the parasite in wildlife, where the data is limited or outdated.
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