LRH-1 mitigates intestinal inflammatory disease by maintaining epithelial homeostasis and cell survival.

Epithelial dysfunction and crypt destruction are defining features of inflammatory bowel disease (IBD). However, current IBD therapies targeting epithelial dysfunction are lacking. The nuclear receptor LRH-1 (NR5A2) is expressed in intestinal epithelium and thought to contribute to epithelial renewal. Here we show that LRH-1 maintains intestinal epithelial health and protects against inflammatory damage. Knocking out LRH-1 in murine intestinal organoids reduces Notch signaling, increases crypt cell death, distorts the cellular composition of the epithelium, and weakens the epithelial barrier. Human LRH-1 (hLRH-1) rescues epithelial integrity and when overexpressed, mitigates inflammatory damage in murine and human intestinal organoids, including those derived from IBD patients. Finally, hLRH-1 greatly reduces disease severity in T-cell-mediated murine colitis. Together with the failure of a ligand-incompetent hLRH-1 mutant to protect against TNFα-damage, these findings provide compelling evidence that hLRH-1 mediates epithelial homeostasis and is an attractive target for intestinal disease

Atoh1 \u3csup\u3e+\u3c/sup\u3e secretory progenitors possess renewal capacity independent of Lgr5 \u3csup\u3e+\u3c/sup\u3e cells during colonic regeneration

During homeostasis, the colonic epithelium is replenished every 3–5 days by rapidly cycling Lgr5 + stem cells. However, various insults can lead to depletion of Lgr5 + stem cells, and colonic epithelium can be regenerated from Lgr5-negative cells. While studies in the small intestine have addressed the lineage identity of the Lgr5-negative regenerative cell population, in the colon this question has remained unanswered. Here, we set out to identify which cell(s) contribute to colonic regeneration by performing genetic fate-mapping studies of progenitor populations in mice. First, using keratin-19 (Krt19) to mark a heterogeneous population of cells, we found that Lgr5-negative cells can regenerate colonic crypts and give rise to Lgr5 + stem cells. Notch1 + absorptive progenitor cells did not contribute to epithelial repair after injury, whereas Atoh1 + secretory progenitors did contribute to this process. Additionally, while colonic Atoh1 + cells contributed minimally to other lineages during homeostasis, they displayed plasticity and contributed to epithelial repair during injury, independent of Lgr5 + cells. Our findings suggest that promotion of secretory progenitor plasticity could enable gut healing in colitis

Using an Ishikawa diagram as a tool to assist memory and retrieval of relevant medical cases from the medical literature

<p>Abstract</p> <p>Studying medical cases is an effective way to enhance clinical reasoning skills and reinforce clinical knowledge. An Ishikawa diagram, also known as a cause-and-effect diagram or fishbone diagram, is often used in quality management in manufacturing industries.</p> <p>In this report, an Ishikawa diagram is used to demonstrate how to relate potential causes of a major presenting problem in a clinical setting. This tool can be used by teams in problem-based learning or in self-directed learning settings.</p> <p>An Ishikawa diagram annotated with references to relevant medical cases and literature can be continually updated and can assist memory and retrieval of relevant medical cases and literature. It could also be used to cultivate a lifelong learning habit in medical professionals.</p

Exploratory investigation of impact loads during the forward handspring vault

The purpose of this study was to examine kinematic and kinetic differences in low and high intensity hand support impact loads during a forward handspring vault. A high-speed video camera (500 Hz) and two portable force platforms (500 Hz) were installed on the surface of the vault table. Two-dimensional analyses were conducted on 24 forward handspring vaults performed by 12 senior level, junior Olympic program female gymnasts (16.9 ±1.4 yr; body height 1.60 ±0.1 m; body mass 56.7 ±7.8 kg). Load intensities at impact with the vault table were classified as low (peak force 0.8 x body weight). These vaults were compared via crucial kinetic and kinematic variables using independent t-tests and Pearson correlations. Statistically significant (p < 0.001) differences were observed in peak force (t(24) = 4.75, ES = 3.37) and time to peak force (t(24) = 2.07, ES = 1.56). Statistically significant relationships between the loading rate and time to peak force were observed for high intensity loads. Peak force, time to peak force, and a shoulder angle at impact were identified as primary variables potentially involved in the determination of large repetitive loading rates on the forward handspring vault

A Study of Problem Solving Using Blocks Vehicle in a STEAM Course for Lower Elementary Levels

STEAM education is currently one of the most important parts of the elementary school curriculum. If STEAM learning can cultivate good problem-solving ability, it will also help improve judgment and thinking abilities. Several voices in the literature have argued for cooperative learning in STEAM courses. Although the effectiveness of course learning often is evaluated using course feedback forms, there is comparatively little emphasis on whether a course succeeds in realizing cooperative learning. For a course involving self-propelled toy-brick cars, there is little research on the application of low-grade pupils. Therefore, based on the integration of STEAM courses into self-propelled toy-brick car learning, this study applied two learning strategies of cooperative learning and individual learning to low-grade pupils in the second grade in elementary schools. After completing the course problem-solving ability indicators were measured and analyzed using the problem-solving ability test. The results show that the mean score of the experimental group in the problem-solving ability test was higher than that of the control group. In the problem-solving ability test, the scores of the two groups were also significantly different, which suggests that cooperative learning is more effective than individual learning strategies.acceptedVersio

Nutrition Strategies for Triathlon

Contemporary sports nutrition guidelines recommend that each athlete develop a personalised, periodised and practical approach to eating that allows him or her to train hard, recover and adapt optimally, stay free of illness and injury and compete at their best at peak races. Competitive triathletes undertake a heavy training programme to prepare for three different sports while undertaking races varying in duration from 20 min to 10 h. The everyday diet should be adequate in energy availability, provide CHO in varying amounts and timing around workouts according to the benefits of training with low or high CHO availability and spread high-quality protein over the day to maximise the adaptive response to each session. Race nutrition requires a targeted and well-practised plan that maintains fuel and hydration goals over the duration of the specific event, according to the opportunities provided by the race and other challenges, such as a hot environment. Supplements and sports foods can make a small contribution to a sports nutrition plan, when medical supplements are used under supervision to prevent/treat nutrient deficiencies (e.g. iron or vitamin D) or when sports foods provide a convenient source of nutrients when it is impractical to eat whole foods. Finally, a few evidence-based performance supplements may contribute to optimal race performance when used according to best practice protocols to suit the triathlete’s goals and individual responsiveness

Natural gaits of the non-pathological flat foot and high-arched foot

There has been a controversy as to whether or not the non-pathological flat foot and high-arched foot have an effect on human walking activities. The 3D foot scanning system was employed to obtain static footprints from subjects adopting a half-weight-bearing stance. Based upon their footprints, the subjects were divided into two groups: the flat-footed and the high-arched. The plantar pressure measurement system was used to measure and record the subjects' successive natural gaits. Two indices were proposed: distribution of vertical ground reaction force (VGRF) of plantar and the rate of the footprint areas. Using these two indices to compare the natural gaits of the two subject groups, we found that (1) in stance phase, there is a significant difference (p<0.01) in the distributions of VGRF of plantar; (2) in a stride cycle, there is also a significant difference (p<0.01) in the rates of the footprint areas. Our analysis suggests that when walking, the VGRF of the plantar brings greater muscle tension to the flat-footed while a smaller rate of the footprint areas brings greater stability to the high-arched.Comment: 8 pages, 4 figure

Bone mineral density in vocational and professional ballet dancers

Summary: According to existing literature, bone health in ballet dancers is controversial. We have verified that, compared to controls, young female and male vocational ballet dancers have lower bone mineral density (BMD) at both impact and non-impact sites, whereas female professional ballet dancers have lower BMD only at non-impact sites. Introduction: The aims of this study were to (a) assess bone mineral density (BMD) in vocational (VBD) and professional (PBD) ballet dancers and (b) investigate its association with body mass (BM), fat mass (FM), lean mass (LM), maturation and menarche. Methods: The total of 152 VBD (13 ± 2.3 years; 112 girls, 40 boys) and 96 controls (14 ± 2.1 years; 56 girls, 40 boys) and 184 PBD (28 ± 8.5 years; 129 females, 55 males) and 160 controls (27 ± 9.5 years; 110 female, 50 males) were assessed at the lumbar spine (LS), femoral neck (FN), forearm and total body by dual-energy X-ray absorptiometry. Maturation and menarche were assessed via questionnaires. Results: VBD revealed lower unadjusted BMD at all anatomical sites compared to controls (p < 0.001); following adjustments for Tanner stage and gynaecological age, female VBD showed similar BMD values at impact sites. However, no factors were found to explain the lower adjusted BMD values in VBD (female and male) at the forearm (non-impact site), nor for the lower adjusted BMD values in male VBD at the FN. Compared to controls, female PBD showed higher unadjusted and adjusted BMD for potential associated factors at the FN (impact site) (p < 0.001) and lower adjusted at the forearm (p < 0.001). Male PBD did not reveal lower BMD than controls at any site. Conclusions: both females and males VBD have lower BMD at impact and non-impact sites compared to control, whereas this is only the case at non-impact site in female PBD. Maturation seems to explain the lower BMD at impact sites in female VBD

Genetic variation in Wnt/β-catenin and ER signalling pathways in female and male elite dancers and its associations with low bone mineral density: a cross-section and longitudinal study.

The association of genetic polymorphisms with low bone mineral density in elite athletes have not been considered previously. The present study found that bone mass phenotypes in elite and pre-elite dancers are related to genetic variants at the Wnt/β-catenin and ER pathways. Some athletes (e.g. gymnasts, dancers, swimmers) are at increased risk for low bone mineral density (BMD) which, if untreated, can lead to osteoporosis. To investigate the association of genetic polymorphisms in the oestrogen receptor (ER) and the Wnt/β-catenin signalling pathways with low BMD in elite and pre-elite dancers (impact sport athletes). The study included three phases: (1) 151 elite and pre-elite dancers were screened for the presence of low BMD and traditional osteoporosis risk factors (low body weight, menstrual disturbances, low energy availability); (2) a genetic association study was conducted in 151 elite and pre-elite dancers and age- and sex- controls; (3) serum sclerostin was measured in 101 pre-elite dancers and age- and sex-matched controls within a 3-year period. Eighty dancers revealed low BMD: 56.3% had at least one traditional osteoporosis risk factor, whereas 28.6% did not display any risk factor (37.2% revealed traditional osteoporosis risk factors, but had normal BMD). Body weight, menstrual disturbances and energy availability did not fully predict bone mass acquisition. Instead, genetic polymorphisms in the ER and Wnt/β-catenin pathways were found to be risk factors for low BMD in elite dancers. Sclerostin was significantly increased in dancers compared to controls during the 3-year follow-up (p < 0.05)