Mechanobiology of the nucleus during the G2-M transition.

Cellular behavior is continuously influenced by mechanical forces. These forces span the cytoskeleton and reach the nucleus, where they trigger mechanotransduction pathways that regulate downstream biochemical events. Therefore, the nucleus has emerged as a regulator of cellular response to mechanical stimuli. Cell cycle progression is regulated by cyclin-CDK complexes. Recent studies demonstrated these biochemical pathways are influenced by mechanical signals, highlighting the interdependence of cellular mechanics and cell cycle regulation. In particular, the transition from G2 to mitosis (G2-M) shows significant changes in nuclear structure and organization, ranging from nuclear pore complex (NPC) and nuclear lamina disassembly to chromosome condensation. The remodeling of these mechanically active nuclear components indicates that mitotic entry is particularly sensitive to forces. Here, we address how mechanical forces crosstalk with the nucleus to determine the timing and efficiency of the G2-M transition. Finally, we discuss how the deregulation of nuclear mechanics has consequences for mitosis.

Remitting Seronegative Symmetrical Synovitis With Pitting Edema in an Adolescent.

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare clinical entity characterized by symmetrical tenosynovitis of both hands and ankles with pitting edema, negative rheumatoid factor (RF), absence of radiographic erosions, and excellent response to low-dose steroids. It is classically associated with elderly patients but may occur in younger patients, with only one case reported in the pediatric age. We report a case of RS3PE diagnosed in a pediatric patient.

Including microbiome information in a multi-trait genomic evaluation: a case study on longitudinal growth performance in beef cattle.

BACKGROUND: Growth rate is an important component of feed conversion efficiency in cattle and varies across the different stages of the finishing period. The metabolic effect of the rumen microbiome is essential for cattle growth, and investigating the genomic and microbial factors that underlie this temporal variation can help maximize feed conversion efficiency at each growth stage. RESULTS: By analysing longitudinal body weights during the finishing period and genomic and metagenomic data from 359 beef cattle, our study demonstrates that the influence of the host genome on the functional rumen microbiome contributes to the temporal variation in average daily gain (ADG) in different months (ADG1, ADG2, ADG3, ADG4). Five hundred and thirty-three additive log-ratio transformed microbial genes (alr-MG) had non-zero genomic correlations (rg) with at least one ADG-trait (ranging from |0.21| to |0.42|). Only a few alr-MG correlated with more than one ADG-trait, which suggests that a differential host-microbiome determinism underlies ADG at different stages. These alr-MG were involved in ribosomal biosynthesis, energy processes, sulphur and aminoacid metabolism and transport, or lipopolysaccharide signalling, among others. We selected two alternative subsets of 32 alr-MG that had a non-uniform or a uniform rg sign with all the ADG-traits, regardless of the rg magnitude, and used them to develop a microbiome-driven breeding strategy based on alr-MG only, or combined with ADG-traits, which was aimed at shaping the rumen microbiome towards increased ADG at all finishing stages. Combining alr-MG information with ADG records increased prediction accuracy of genomic estimated breeding values (GEBV) by 11 to 22% relative to the direct breeding strategy (using ADG-traits only), whereas using microbiome information, only, achieved lower accuracies (from 7 to 41%). Predicted selection responses varied consistently with accuracies. Restricting alr-MG based on their rg sign (uniform subset) did not yield a gain in the predicted response compared to the non-uniform subset, which is explained by the absence of alr-MG showing non-zero rg at least with more than one of the ADG-traits. CONCLUSIONS: Our work sheds light on the role of the microbial metabolism in the growth trajectory of beef cattle at the genomic level and provides insights into the potential benefits of using microbiome information in future genomic breeding programs to accurately estimate GEBV and increase ADG at each finishing stage in beef cattle.

The LINC complex ensures accurate centrosome positioning during prophase.

Accurate centrosome separation and positioning during early mitosis relies on force-generating mechanisms regulated by a combination of extracellular, cytoplasmic, and nuclear cues. The identity of the nuclear cues involved in this process remains largely unknown. Here, we investigate how the prophase nucleus contributes to centrosome positioning during the initial stages of mitosis, using a combination of cell micropatterning, high-resolution live-cell imaging, and quantitative 3D cellular reconstruction. We show that in untransformed RPE-1 cells, centrosome positioning is regulated by a nuclear signal, independently of external cues. This nuclear mechanism relies on the linker of nucleoskeleton and cytoskeleton complex that controls the timely loading of dynein on the nuclear envelope (NE), providing spatial cues for robust centrosome positioning on the shortest nuclear axis, before nuclear envelope permeabilization. Our results demonstrate how nuclear-cytoskeletal coupling maintains a robust centrosome positioning mechanism to ensure efficient mitotic spindle assembly.

Generation of highly pure pluripotent stem cell-derived myogenic progenitor cells and myotubes.

Driving efficient and pure skeletal muscle cell differentiation from pluripotent stem cells (PSCs) has been challenging. Here, we report an optimized protocol that generates skeletal muscle progenitor cells with high efficiency and purity in a short period of time. Human induced PSCs (hiPSCs) and murine embryonic stem cells (mESCs) were specified into the mesodermal myogenic fate using distinct and species-specific protocols. We used a specific maturation medium to promote the terminal differentiation of both human and mouse myoblast populations, and generated myotubes associated with a large pool of cell-cycle arrested PAX7+ cells. We also show that myotube maturation is modulated by dish-coating properties, cell density, and percentage of myogenic progenitor cells. Given the high efficiency in the generation of myogenic progenitors and differentiated myofibers, this protocol provides an attractive strategy for tissue engineering, modeling of muscle dystrophies, and evaluation of new therapeutic approaches in vitro.

Estimating Microbial Protein Synthesis in the Rumen-Can 'Omics' Methods Provide New Insights into a Long-Standing Question?

Rumen microbial protein synthesis (MPS) provides at least half of the amino acids for the synthesis of milk and meat protein in ruminants. As such, it is fundamental to global food protein security. Estimating microbial protein is central to diet formulation, maximising nitrogen (N)-use efficiency and reducing N losses to the environment. Whilst factors influencing MPS are well established in vitro, techniques for in vivo estimates, including older techniques with cannulated animals and the more recent technique based on urinary purine derivative (UPD) excretion, are subject to large experimental errors. Consequently, models of MPS used in protein rationing are imprecise, resulting in wasted feed protein and unnecessary N losses to the environment. Newer 'omics' techniques are used to characterise microbial communities, their genes and resultant proteins and metabolites. An analysis of microbial communities and genes has recently been used successfully to model complex rumen-related traits, including feed conversion efficiency and methane emissions. Since microbial proteins are more directly related to microbial genes, we expect a strong relationship between rumen metataxonomics/metagenomics and MPS. The main aims of this review are to gauge the understanding of factors affecting MPS, including the use of the UPD technique, and explore whether omics-focused studies could improve the predictability of MPS, with a focus on beef cattle.

Identification of intestinal and fecal microbial biomarkers using a porcine social stress model.

Understanding the relationships between social stress and the gastrointestinal microbiota, and how they influence host health and performance is expected to have many scientific and commercial implementations in different species, including identification and improvement of challenges to animal welfare and health. In particular, the study of the stress impact on the gastrointestinal microbiota of pigs may be of interest as a model for human health. A porcine stress model based on repeated regrouping and reduced space allowance during the last 4 weeks of the finishing period was developed to identify stress-induced changes in the gut microbiome composition. The application of the porcine stress model resulted in a significant increase in salivary cortisol concentration over the course of the trial and decreased growth performance and appetite. The applied social stress resulted in 32 bacteria being either enriched (13) or depleted (19) in the intestine and feces. Fecal samples showed a greater number of microbial genera influenced by stress than caecum or colon samples. Our trial revealed that the opportunistic pathogens Treponema and Clostridium were enriched in colonic and fecal samples from stressed pigs. Additionally, genera such as Streptococcus, Parabacteroides, Desulfovibrio, Terrisporobacter, Marvinbryantia, and Romboutsia were found to be enriched in response to social stress. In contrast, the genera Prevotella, Faecalibacterium, Butyricicoccus, Dialister, Alloprevotella, Megasphaera, and Mitsuokella were depleted. These depleted bacteria are of great interest because they synthesize metabolites [e.g., short-chain fatty acids (SCFA), in particular, butyrate] showing beneficial health benefits due to inhibitory effects on pathogenic bacteria in different animal species. Of particular interest are Dialister and Faecalibacterium, as their depletion was identified in a human study to be associated with inferior quality of life and depression. We also revealed that some pigs were more susceptible to pathogens as indicated by large enrichments of opportunistic pathogens of Clostridium, Treponema, Streptococcus and Campylobacter. Generally, our results provide further evidence for the microbiota-gut-brain axis as indicated by an increase in cortisol concentration due to social stress regulated by the hypothalamic-pituitary-adrenal axis, and a change in microbiota composition, particularly of bacteria known to be associated with pathogenicity and mental health diseases.

Visuospatial memory profile of patients with Parkinson's disease.

BACKGROUND: In Parkinson's Disease (PD) cognitive impairment may become evident at an early stage of the disease. Performance in the visuospatial domain has been pointed out as a possible predictor of cognitive decline for dementia. OBJECTIVES: The goal was to characterize the visuospatial memory profile, explore the predictive value of a set of visuospatial measures that better distinguish patients from controls, and investigate the relevance of the 10/36 SPART, providing cutoff scores. METHODS: A total of 43 PD patients and 45 healthy controls (HC) were recruited from the Centro Hospitalar Universitário de São João and the community, respectively. The protocol included a set of tests assessing global cognitive functioning, visuoperceptive abilities, and visuospatial memory. RESULTS: PD patients performed significantly worse than HC, showing difficulties in global cognition, visuospatial learning, and visuoconstructive and perceptive abilities. Through a discriminant analysis, the Clock Drawing Test and ACE-R's visuospatial domain were revealed as good tools to be included in the evaluation protocol. Regarding the 10/36 SPART's performance, four predictors were found (age, sex, education, and emotional distress) and cutoff scores were determined. CONCLUSIONS: The visuospatial memory profile found was congruent with that described in the literature. The results were discussed according to their relevance for clinical practice and future research.

Skin carotenoid levels in lactating dairy cows as measured using multiple spatially resolved reflection spectroscopy.

This research communication describes a pilot study measuring skin carotenoid levels of lactating dairy cows. Carotenoids are natural antioxidants, involved in cell communication and immune function, protecting against oxidative stress. They are precursors of vitamin A, important for reproduction efficiency, growth and male fertility. Therefore, easy-to-use, inexpensive methods to measure carotenoids in cattle would provide interesting data for farmers to monitor the health and nutritional status of their herds. In this study, we used a commercially available sensor based on multiple spatially resolved reflection spectroscopy (MSRRS), intended for human use, to measure the carotenoid content in bovine skin in three research herds in France, Ireland and Scotland. Carotenoid levels were measured by applying the sensor to the teat barrel, avoiding pigmented areas of skin. Mean sensor values differed significantly between herds and between diets, with pasture-based animals showing significantly higher carotenoid levels. Our results suggest that MSRRS can be used to accurately to measure skin carotenoids in cows. However, further calibration in bovines is needed to improve of the accuracy of the MSRRS sensor in cattle.

Production, characterization, and dietary supplementation effect of rumen-protected fat on ruminal function and blood parameters of sheep.

Rumen-protected fat (RPF) was produced in the 1st experimental stage through melt-emulsification technique using buriti oil (BO) as core, at concentrations of 10% (BO10), 20% (BO20), and 30% (BO30) (w/w), and carnauba wax (CW) as encapsulant material. After obtention and characterization, protected fat microspheres were tested in a 2nd experimental stage on the sheep' diet using six castrated 2-year-old male Santa Ines with initial weight 48.9 ± 5.23 kg, fistulated in rumen and distributed in a double Latin square design with 3 treatments × 3 periods, to evaluate rumen pH, temperature, protozoal count, and blood parameters. There was no difference (P > 0.05) among RPF microspheres for microencapsulation yield. However, microencapsulation efficiency increased (P < 0.05) with BO addition ranging from 36 to 61.3% for BO10 and BO30, respectively. The inclusion of BO10 in the sheep's diet did not affect the ruminal dry matter degradability (DMD) of BO over time (P > 0.05); however, BO20 and BO30 had higher (P < 0.05) DMD values than BO10. No significant differences were observed among RPF for rumen pH and temperature (P > 0.05). There was an increase (P < 0.05) in the protozoal population in the rumen environment due to the microencapsulated BO30 inclusion. There was also increase (P < 0.05) in serum albumin, cholesterol, aspartate aminotransferase (ALT), and gamma-glutamyltransferase (GGT), and a reduction (P < 0.05) in serum triglycerides of the sheep when RPF microspheres increased in the diet. Melt-emulsification proved to be a good technique for microencapsulation of buriti oil into the carnauba wax matrix. RPF from buriti oil protected into carnauba wax is recommended for sheep diet because it increases energy density, without adverse effects on the protozoal populations and blood serum metabolites from the bypass effect in the rumen.

Long COVID in Children and Adolescents: A Retrospective Study in a Pediatric Cohort.

Studies on long coronavirus disease (COVID) in children are scarce. We aimed to describe persistent symptoms and identify risk factors for its development. In our study population, 17.6% presented with long COVID, with respiratory symptoms more frequent in the first weeks and neuropsychiatric symptoms over time. Chronic conditions and obesity were risk factors, and adolescents were at a greater risk for long COVID.

Análise de diagnósticos, intervenções e atividades de enfermagem em pacientes submetidos à hemodiálise secundária à COVID-19: estudo descritivo / Analysis of nursing diagnoses, interventions, and activities in patients undergoing hemodialysis secondary to COVID-19: a descriptive study

OBJETIVO: Analisar os diagnósticos, as intervenções e atividades de enfermagem em pacientes submetidos à hemodiálise secundária à COVID-19. MÉTODO: Estudo descritivo, retrospectivo e de natureza quantitativa. A população do estudo foi representada pelos prontuários de pacientes submetidos à hemodiálise secundária à COVID-19, totalizando cerca de 64 registros. Consultaram-se os dados do instrumento de coleta de dados, bem como dados sociodemográficos, clínicos e indicadores dos diagnósticos de enfermagem. Para análise, utilizou-se da estatística descritiva e inferencial. RESULTADOS: Os principais diagnósticos de enfermagem encontrados foram: risco de infecção, risco de volume de líquidos desequilibrado, déficit no autocuidado para banho/higiene íntima e troca de gases prejudicada. As intervenções e atividades assinaladas foram correspondentes aos diagnósticos traçados. CONCLUSÃO: O estudo possibilitou identificar os principais diagnósticos, as intervenções e atividades de enfermagem em pacientes acometidos pela COVID-19 que desenvolveram lesão renal aguda.

Objective: To analyze nursing diagnoses, interventions, and activities in patients undergoing hemodialysis secondary to COVID-19. METHOD: This is a descriptive, retrospective, and quantitative study. The study population was represented by the medical records of patients undergoing hemodialysis secondary to COVID-19, totaling about 64 records. Data from the data collection instrument, sociodemographic and clinical data, and indicators of nursing diagnoses were consulted. Descriptive and inferential statistics were used for analysis. RESULTS: The main nursing diagnoses found were risk for infection, risk for imbalanced fluid volume, bathing/toileting self-care deficit, and impaired gas exchange. The registered interventions and activities corresponded to the outlined diagnoses. CONCLUSION: The study identified the main diagnoses, interventions, and nursing activities in patients affected by COVID-19 who developed acute kidney injury.

Comparative analysis of the anthelmintic efficacy of European heather extracts on Teladorsagia circumcincta and Trichostrongylus colubriformis egg hatching and larval motility.

BACKGROUND: Gastrointestinal nematode (GIN) control is traditionally achieved with the use of anthelmintic drugs, however due to regulations in organic farming and the rise in anthelmintic resistance, alternatives are sought after. A promising alternative is the use of bioactive plant feeding due to the presence of plant secondary metabolites (PSMs) such as proanthocyanidins (PAs). This study focussed on the perennial shrub heather (Ericaceae family), a plant rich in PAs, highly abundant across Europe and with previously demonstrated anthelmintic potential. METHODS: In vitro assays were used to investigate heather's anthelmintic efficacy against egg hatching and larval motility. Heather samples were collected from five European countries across two seasons, and extracts were tested against two GIN species: Teladorsagia circumcincta and Trichostrongylus colubriformis. Polyphenol group-specific ultraperformance liquid chromatography-tandem mass spectrometry analysis was performed to identify relevant polyphenol subgroups present, including the PA concentration and size and ratio of the subunits. Partial least squares analysis was performed to associate efficacy with variation in PSM composition. RESULTS: Heather extracts reduced egg hatching of both GIN species in a dose-dependent manner by up to 100%, while three extracts at the highest concentration (10 mg/ml) reduced larval motility to levels that were not significantly different from dead larvae controls. PAs, particularly the procyanidin type, and flavonol derivatives were associated with anthelmintic activity, and the particular subgroup of polyphenols associated with the efficacy was dependent on the GIN species and life stage. CONCLUSIONS: Our results provide in vitro evidence that heather, a widely available plant often managed as a weed in grazing systems, has anthelmintic properties attributed to various groups of PSMs and could contribute to sustainable GIN control in ruminant production systems across Europe.

Kyrgyzstan: Health System Review.

This analysis of the Kyrgyz health system reviews developments in its organization and governance, financing, provision of services, health reforms and health system performance. A mandatory health insurance is in place, with the Mandatory Health Insurance Fund (MHIF) under the Ministry of Health acting as single public payer for almost all hospitals and providers of primary care. The benefits package of publicly covered services is defined in the State-Guaranteed Benefits Programme (SGBP). However, many services require co-payments and in 2019 only 69% of the population was covered by mandatory health insurance. Health expenditure per capita is one of the lowest in the WHO European Region, due to the country's small GDP per capita. Private spending, almost entirely in the form of out-of-pocket expenditure and including informal payments, accounted for 46.3% of health expenditure in 2019. Financial protection is undermined by low levels of public spending for health, resulting in financial hardship for people using health services. While there is a well-developed network of health facilities, the geographical distribution of health workers is uneven and there is an overall shortage of family doctors. Access to health services remains a challenge, which has been exacerbated by the COVID-19 pandemic. While improvements have been made in recent years, communicable and noncommunicable diseases still pose a major problem and life expectancy prior to the COVID-19 pandemic was one of the lowest in the WHO European Region.

Use of WhatsApp in Dental Education: a Scoping Review.

Purpose/Objective: This study aimed to perform a critical appraisal of WhatsApp use by undergraduate students in dental education. Methods: A PRISMA-Scoping Review was carried out to explain (i) how has WhatsApp been used as a learning tool in dental education? and (ii) how has WhatsApp been evaluated as a learning tool in dental education? Inclusion criteria are specified as the population (dental students), concept (use of WhatsApp), context (institutions/universities of dental education), and types of sources of evidence (peer-reviewed publication). Results: Nine studies published between 2016 and 2020 were included in this scoping review. Mostly had a cross-sectional design. Conclusion: WhatsApp is used in dental education to facilitate communication and improve learning through discussions via the app.

TMEM8C-mediated fusion is regionalized and regulated by NOTCH signalling during foetal myogenesis.

The location and regulation of fusion events within skeletal muscles during development remain unknown. Using the fusion marker myomaker (Mymk), named TMEM8C in chicken, as a readout of fusion, we identified a co-segregation of TMEM8C-positive cells and MYOG-positive cells in single-cell RNA-sequencing datasets of limbs from chicken embryos. We found that TMEM8C transcripts, MYOG transcripts and the fusion-competent MYOG-positive cells were preferentially regionalized in central regions of foetal muscles. We also identified a similar regionalization for the gene encoding the NOTCH ligand JAG2 along with an absence of NOTCH activity in TMEM8C+ fusion-competent myocytes. NOTCH function in myoblast fusion had not been addressed so far. We analysed the consequences of NOTCH inhibition for TMEM8C expression and myoblast fusion during foetal myogenesis in chicken embryos. NOTCH inhibition increased myoblast fusion and TMEM8C expression and released the transcriptional repressor HEYL from the TMEM8C regulatory regions. These results identify a regionalization of TMEM8C-dependent fusion and a molecular mechanism underlying the fusion-inhibiting effect of NOTCH in foetal myogenesis. The modulation of NOTCH activity in the fusion zone could regulate the flux of fusion events.

Measuring the Commercial Determinants of Health and Disease: A Proposed Framework.

The commercial determinants of health (CDoH) describe the adverse health effects associated with for-profit actors and their actions. Despite efforts to advance the definition, conceptualization, and empirical analyses of CDoH, the term's practical application to mitigate these effects requires the capacity to measure the influences of specific components of CDoH and the cumulative impacts of CDoH on the health and well-being of specific populations. Building on the Global Burden of Disease Study, we begin by conceptualizing CDoH as risk factor exposures that span agency and structural influences. We identify 6 components of these influences and propose an initial set of indicators and datasets to rank exposures as high, medium, or low. These are combined into a commercial determinants of health index (CDoHi) and illustrated by 3 countries. Although now a proof of concept, comparative analysis of CDoH exposures by population, over time and space, and their associated health outcomes will become possible with further development of indicators and datasets. Expansion of the CDoHi and application to varied populations groups will enable finer targeting of interventions to reduce health harms. The measurement of improvements to health and wellness from such interventions will, in turn, inform overall efforts to address the CDoH.

The European Food Regulatory Environment Index: a tool to monitor progress in implementing food environment policies.

BACKGROUND: Evidence based health policy, such as that put forward in the European Food and Nutrition Action Plan 2015-2020 and the WHO Global Action Plan on the Prevention and Control of Noncommunicable Diseases, has a role in curbing the consumption of unhealthful foods and drink. We ask how countries are performing in the adoption of these policies and how the comprehensiveness of their food environment policies explains variations in consumption of unhealthful products across Europe. METHODS: In order to assess the state of policy adoption, we developed a composite indicator-the Food Regulatory Environment Index (FREI) for which we calculated unweighted and weighted formulations according to the strength of the evidence base. We used linear regression models to explain variations in the consumption of unhealthful products as well as variations in a composite indicator of obesogenic diets. RESULTS: Overall, wealthier countries in the Region perform better. The weighting of the constituent policies does not affect the rankings. We find negative associations between unweighted and weighted formulations of the Index and household consumption of sugary and carbonate drinks as well as with the composite indicator for obesogenic diets. CONCLUSIONS: The main strength of this study is the comprehensiveness and comparability of the policy data across the relatively large number of countries covered. There is a negative association that is statistically significant, between all formulations of the FREI and the household consumption of sugary and carbonated drinks. There is also a negative association between some FREI formulations and obesogenic diets.