Acute Alcohol Consumption and Arrhythmias in Young Adults: The MunichBREW II Study.

BACKGROUND: and aims: Acute excessive alcohol intake may cause the holiday heart syndrome, characterized by cardiac arrhythmias including atrial fibrillation. Since underlying data are scarce, the study aimed to prospectively investigate the temporal course of occurring cardiac arrhythmias following binge drinking in young adults. METHODS: A total of 202 volunteers planning acute alcohol consumption with expected peak breath alcohol concentrations (BAC) of ≥1.2 g/kg were enrolled. The study comprised 48-hour electrocardiogram (ECG) monitoring covering baseline (hour 0), 'drinking period' (hours 1-5), 'recovery period' (hours 6-19), and two control periods corresponding to 24 hours after the 'drinking' and 'recovery periods', respectively. Acute alcohol intake was monitored by BAC measurements during the 'drinking period'. ECGs were analyzed for mean heart rate, atrial tachycardia, premature atrial complexes (PAC), premature ventricular complexes (PVC), and heart rate variability (HRV) measures. RESULTS: Data revealed an increase in heart rate and an excess of atrial tachycardias with increasing alcohol intake. HRV analysis indicated an autonomic modulation with sympathetic activation during alcohol consumption and the subsequent 'recovery period', followed by parasympathetic predominance thereafter. PACs occurred significantly more frequently in the 'control periods', whereas PVCs were more frequent in the 'drinking period'. Ten participants experienced notable arrhythmic episodes, including atrial fibrillation and ventricular tachycardias, primarily during the 'recovery period'. CONCLUSIONS: The study demonstrates the impact of binge drinking on heart rate alterations and increased atrial tachycardias during 'drinking period', and the occurrence of clinically relevant arrythmias during the 'recovery period', emphasizing the holiday heart syndrome as a health concern.

Alda-1 attenuation of binge alcohol-caused atrial arrhythmias through a novel mechanism of suppressed c-Jun N-terminal Kinase-2 activity.

Holiday Heart Syndrome (HHS) is caused by excessive binge alcohol consumption, and atrial fibrillation (AF) is the most common arrhythmia among HHS patients. AF is associated with substantial morbidity and mortality, making its prevention and treatment of high clinical interest. This study defines the anti-AF action of Alda-1 (an established cardioprotective agent) and the underlying mechanisms of the action in our well-characterized HHS and cellular models. We found that Alda-1 effectively eliminated binge alcohol-evoked Ca2+ triggered activities (Ca2+ waves, prolonged Ca2+ transient diastolic decay) and arrhythmia inducibility in intact mouse atria. We then demonstrated that alcohol impaired human RyR2 channels (isolated from organ donors' hearts). The functional role of alcohol-caused RyR2 channel dysfunction in Ca2+ triggered arrhythmic activities was evidenced in a unique transgenic mouse model with a loss-of-function mutation (RyR2E4872Q+/-). Alda-1 is known to activate aldehyde dehydrogenase 2 (ALDH2), a key enzyme in alcohol detoxification. However, we found an increased level of ALDH2 and a preserved normal balance of pro- vs anti-apoptotic signaling in binge alcohol exposed hearts and H9c2 differentiated myocytes, which suggests that the link of alcohol-ALDH2-apoptosis is unlikely to be a key factor leading to binge alcohol-evoked arrhythmogenicity. We have previously reported that binge alcohol-activated stress response kinase JNK2 causatively drives Ca2+-triggered atrial arrhythmogenicity. Here, we found that JNK2-specific inhibition in either isolated human RyR2 channels or intact mouse atria abolished alcohol-evoked RyR2 channel dysfunction and Ca2+ triggered arrhythmic activities, suggesting a strong alcohol-JNK2-RyR2 interaction in atrial arrhythmogenicity. Furthermore, we revealed, for the first time, that Alda-1 suppresses JNK2 (but not JNK1) enzyme activity independently of ALDH2, which in turn alleviates binge alcohol-evoked Ca2+ triggered atrial arrhythmogenesis. Our findings provide novel mechanistic insights into the anti-arrhythmic action of Alda-1 and suggest that Alda-1 represents a potential preventative agent for AF management for HHS patients.

The effect of birth timing manipulation around carnival on birth indicators in Brazil.

This paper studies the patterns and consequences of birth timing manipulation around the carnival holiday in Brazil. We document how births are displaced around carnival and estimate the effect of displacement on birth indicators. We show that there is extensive birth timing manipulation in the form of both anticipation and postponement that results in a net increase in gestational length and reductions in neonatal and early neonatal mortality, driven by postponed births that would otherwise happen through scheduled c-sections. We also find a reduction in birthweight for high-risk births at the bottom of the weight distribution, driven by anticipation. Therefore, restrictions on usual delivery procedures due to the carnival holiday can be both beneficial and detrimental, raising a double-sided issue to be addressed by policymakers.

A synthetic approach to the Holiday Climate Index for the Mediterranean Coast of Türkiye.

Climate change affects the comfort level of tourists visiting coastal areas. Researching these impacts is important for a more comprehensive understanding of climate change and for developing effective adaptation solutions. Considering this fact, the study derived the Holiday Climate Index (HCI: Coast, HCI: Urban, and HCI: Combined) in the Mediterranean coastal provinces of Türkiye from 1976 to 2020. Utilizing the derived indices, the effects of climate-related holiday comfort on the number of tourist arrivals as well as on overnight stays between 1976 and 2020 were examined by panel data analysis. The study examined how comfort patterns could change during the period 2026-2050 under the pessimistic RCP8.5 scenario. It was detected that the comfort level significantly and positively affects the number of arrivals and overnight stays of tourists. Besides, comfort levels were found to deteriorate in the period 2026-2050 compared to the reference period, 1976-2020. As the comfort conditions get worse, the number of tourist arrivals and overnight stays is expected to decline in the future. It is envisaged that the results of the study can be useful for tourists, tourism professionals, operators, other stakeholders, and policymakers.

Quantifying climatic suitability for tourism in Southwest Indian Ocean Tropical Islands: Applying the Holiday Climate Index to Réunion Island.

Climate is a key resource for tourists and tourism providers. Varied approaches to quantifying climate resources for tourism have been developed in the last 40 years, computing indices from a range of meteorological variables to measure the comparative climatic suitability of different destinations through time. This study provides the first application of a tourism climate index in the tropical southwest Indian Ocean, applying the recently developed Holiday Climate Index (HCI) for Réunion Island. The suitability of this index is evaluated for the case of this French department, with a particular focus on air conditioning availability in tourism accommodation establishments as this index excludes night-time thermal comfort. Both iterations of the HCI (HCIBeach and HCIUrban) are computed with meteorological data from Roland Garros Airport for the period 1991-2020, exploring monthly, annual, and seasonal climatic suitability. Mean monthly HCI scores reveal considerable seasonality in climatic suitability for tourism on the island with scores ranging from 89.3 ('excellent') to 36.9 ('marginal') for the HCIBeach and 85.0 ('excellent') to 27.5 ('unacceptable') for the HCIUrban, with more favourable scores calculated for July and August, displaying a clear austral winter peak seasonal classification. Over the 30-year period, there is no statically significant change in mean annual climatic suitability, and at a monthly scale, only one month of the year for each index displays statistically significant trends. These results are important in informing tourism strategies for the island to maximise visitor satisfaction through targeting advertising more deliberately for peak touristic climate suitability during the winter months.

Assessing the impact of dust events on the Holiday Climate Index in the Taklimakan Desert region.

As a significant sector within the tourism industry, desert tourism has developed rapidly in recent years, contributing significantly to local economic development. On the other hand, desert tourism is constantly influenced by the desert climate, characterized by high temperatures, aridity, and dust events. This study examines and analyzes the impact of dust events on the Holiday Climate Index (HCI) using an improved methodology. It incorporates comprehensive meteorological data including temperature, relative humidity, cloud cover, precipitation, wind speed and dust events of Tazhong, located in the heart of the Taklimakan Desert. The results indicate that the maximum mean monthly HCI dips from an ideal level (91) to a very good level (73), the minimum dips from good level (66) to a marginal level (47), and the annual comfortable days (HCI ≥ 80) decrease from 180.5 to 95.3 after considering the impacts of dust events. The corrective HCI indicates that autumn, especially October, offers relatively comfortable climatic conditions for tourism, with the mean monthly comfortable days reach 20.1. These findings can better guide desert tourism activities and also demonstrate that the impact of dust weather on tourism activities cannot be ignored.

Weekend / holiday effect on stroke mortality in regional Australia: A ten-year retrospective study.

BACKGROUND: There is a deficiency in the evidence from rural and regional centres in Australia on the weekend effect following presentation with acute stroke. OBJECTIVE: To estimate the association between admission over a weekend/holiday and all-cause mortality 3-day, 7-day, 14-day, 1-month, 3-month, 6-month, and 12-month following acute stroke. METHODS: The records of stroke patients admitted to a main regional hospital in Australia from 2010 to 2020 were linked with the National Death Index. Time to death following ischaemic, haemorrhagic, and total stroke at different time points was modelled using Weibull, Exponential, or Gompertz regression based on best model fit determined by Akaike's information criterion. RESULTS: Of 1669 patients, 1273 (76.3%) were admitted on a weekday, and 396 (23.7%) on a weekend/ or holiday. After adjusting for age, sex, and Charlson Comorbidity Index, stroke type and country of birth, admissions over a weekend/holiday following total stroke were significantly associated with an increased risk of dying within three days from admission [hazard ratio (HR): 1.59, 95% confidence interval: 1.01-2.50]. In haemorrhagic stroke, increased risk of death was significantly higher at three days (HR: 2.19, 95% confidence interval: 1.17-4.08), 14 days (HR: 1.73, 95% confidence interval: 1.02-2.93), and 1 month (HR: 1.82, 95% confidence interval: 1.09-3.03) following admission on the weekend/ or holiday compared to those admitted during the weekdays. CONCLUSIONS: This study reports a short-term adverse weekend/holiday effect following admission for haemorrhagic stroke or total stroke. No significant weekend/holiday effect was found in ischaemic stroke.

A nationwide survey for the provision of acute stroke rehabilitation in Japan: initial dose and weekend/holiday rehabilitation.

OBJECTIVES: The early initiation of acute stroke rehabilitation with a sufficient dose, including at weekends/holidays, is important to improve functional outcome. We investigated the status of acute stroke rehabilitation in Japan by using a nationwide survey. MATERIALS AND METHODS: Facility features, rehabilitation dose provided in the first week in each stroke subtype, and weekend/holiday rehabilitation were investigated by using the results of a web-based survey among primary stroke centers. The relationships between facility features and weekend/holiday rehabilitation were also analyzed. RESULTS: A total of 639 stroke centers (66.6%) completed the questionnaire. The overall median dose was 2.0 (interquartile range, 1.7-3.0) U/day (1U = 20 min). After 7 days, the overall median dose increased to 4.0 (2.0-5.4) U/day. Almost 50% of facilities replied that they could not provide a sufficient dose of rehabilitation; the main reason was a lack of therapists (31%). For rehabilitation on long weekends, no rehabilitation was provided on 3-day weekends in 19% of facilities, and in 5% of facilities on ≥4-day weekends. The mean number of therapists was almost 50% less in the facilities that provided no rehabilitation on 3-day weekends compared to those that provided daily rehabilitation (19.4 vs. 36.2 therapists, respectively, p < 0.001). CONCLUSIONS: In this survey, the provision of acute stroke rehabilitation, including non-working days, was clarified. According to the results, prospective interventional or observational studies are needed to design more effective rehabilitation programs to improve outcome. In particular, it is important to determine the optimal dose and intensity of acute stroke rehabilitation.

Assessment of prolonged safety and tolerability of erenumab in migraine patients in a long-term open-label study (APOLLON).

BACKGROUND: Efficacy and safety of human monoclonal antibody erenumab used for migraine prophylaxis have been shown in clinical studies. APOLLON is an open-label, multi-center, single arm study, which permits dose adjustments of erenumab and includes an option for a drug holiday. The findings contribute to the accumulating long-term evidence regarding erenumab's tolerability and safety profile in individuals experiencing episodic and chronic migraines. METHODS: The study population consisted of adult patients with episodic or chronic migraine, who had successfully completed the HER-MES study (NCT03828539). Patients were treated with erenumab for 128 weeks at a flexible dose of either 70 mg or 140 mg. Treatment discontinuation attempts were allowed as voluntary single treatment interruption ('drug holiday') of up to 24 weeks. RESULTS: 701 patients were enrolled in APOLLON. The exposure associated incidence rate (EAIR) of adverse events (AEs) (N = 601) per 100 subject years was 101.71 (95% CI [92.28; 111.14]) meaning a patient could expect having about one adverse event per each year of treatment. EAIR was higher in females (n = 524, EAIR: 104.40, 95% CI [93.93; 114.86]) than in males (n = 77, EAIR: 86.55, 95% CI [65.39; 107.71]) and increased with initial monthly migraine days (MMD) and prior prophylactic treatment failures. A total of 155 patients discontinued erenumab treatment during open-label treatment phase. Of these, 29 were due to AEs (4.1% of total cohort) and out of these 65.5% (N = 19) were considered treatment-related. Safety parameters were in line with HER-MES data and did not reveal new safety signals. Drug holidays were realized by 108 patients (15.4%), of which 64.8% (N = 70) returned to treatment. The mean number of monthly headache days (MHDs), MMDs, and days with acute headache medication significantly increased during drug holiday. After resumption of erenumab treatment, a rapid reduction of the migraine parameters was observed. CONCLUSIONS: APOLLON provides long-term safety and tolerability data confirming the beneficial safety profile of erenumab over a period of 128 weeks. In addition, reversibility of migraine deterioration during drug holiday was shown and most patients returned to their treatment with similar response rates compared to initial treatment. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04084314 ( https://clinicaltrials.gov/study/NCT04084314 ), First submitted: 2019-09-06.

Multifaceted regulation of the sumoylation of the Sgs1 DNA helicase.

Homologous recombination repairs DNA breaks and sequence gaps via the production of joint DNA intermediates such as Holliday junctions. Dissolving Holliday junctions into linear DNA repair products requires the activity of the Sgs1 helicase in yeast and of its homologs in other organisms. Recent studies suggest that the functions of these conserved helicases are regulated by sumoylation; however, the mechanisms that promote their sumoylation are not well understood. Here, we employed in vitro sumoylation systems and cellular assays to determine the roles of DNA and the scaffold protein Esc2 in Sgs1 sumoylation. We show that DNA binding enhances Sgs1 sumoylation in vitro. In addition, we demonstrate the Esc2's midregion (MR) with DNA-binding activity is required for Sgs1 sumoylation. Unexpectedly, we found that the sumoylation-promoting effect of Esc2-MR is DNA independent, suggesting a second function for this domain. In agreement with our biochemical data, we found the Esc2-MR domain, like its SUMO E2-binding C-terminal domain characterized in previous studies, is required for proficient sumoylation of Sgs1 and its cofactors, Top3 and Rmi1, in cells. Taken together, these findings provide evidence that while DNA binding enhances Sgs1 sumoylation, Esc2-based stimulation of this modification is mediated by two distinct domains.

How do 24-h movement behaviours change during and after vacation? A cohort study.

BACKGROUND: For adults, vacations represent a break from daily responsibilities of work - offering the opportunity to re-distribute time between sleep, sedentary behaviour, light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) across the 24-h day. To date, there has been minimal research into how activity behaviour patterns change on vacation, and whether any changes linger after the vacation. This study examined how daily movement behaviours change from before, to during and after vacations, and whether these varied based on the type of vacation and vacation duration. METHODS: Data collected during the Annual Rhythms In Adults' lifestyle and health (ARIA) study were used. 308 adults (mean age 40.4 years, SD 5.6) wore Fitbit Charge 3 fitness trackers 24 h a day for 13 months. Minute-by-minute movement behaviour data were aggregated into daily totals. Multi-level mixed-effects linear regressions were used to compare movement behaviours during and post-vacation (4 weeks) to pre-vacation levels (14 days), and to examine the associations with vacation type and duration. RESULTS: Participants took an average of 2.6 (SD = 1.7) vacations of 12 (SD = 14) days' (N = 9778 days) duration. The most common vacation type was outdoor recreation (35%) followed by family/social events (31%), rest (17%) and non-leisure (17%). Daily sleep, LPA and MVPA all increased (+ 21 min [95% CI = 19,24] p < 0.001, + 3 min [95% CI = 0.4,5] p < 0.02, and + 5 min [95% CI = 3,6] p < 0.001 respectively) and sedentary behaviour decreased (-29 min [95% CI = -32,-25] p < 0.001) during vacation. Post-vacation, sleep remained elevated for two weeks; MVPA returned to pre-vacation levels; and LPA and sedentary behaviour over-corrected, with LPA significantly lower for 4 weeks, and sedentary behaviour significantly higher for one week. The largest changes were seen for "rest" and "outdoor" vacations. The magnitude of changes was smallest for short vacations (< 3 days). CONCLUSIONS: Vacations are associated with favourable changes in daily movement behaviours. These data provide preliminary evidence of the health benefits of vacations. TRIAL REGISTRATION: The study was prospectively registered on the Australian New Zealand Clinical Trial Registry (Trial ID: ACTRN12619001430123).

Bone Mineral Density Response to Long-Term Bisphosphonate Treatment and Discontinuation in a Real-World Clinical Service.

OBJECTIVE: Bisphosphonate treatment does not increase bone mineral density (BMD) in all subjects particularly at the femoral neck (FN). Our aim was to evaluate the relationship between response to oral bisphosphonate (oBP) at the FN and change in BMD following discontinuation. METHODS: Data were collected retrospectively from postmenopausal women on oBP for ≥3 years, attending a real-world metabolic clinic at initiation of oBP, discontinuation, and 1 to 2 years post discontinuation. Improvement in BMD ≥4% in the FN and ≥5% for the lumbar spine (LS) were deemed clinically meaningful and used as least significant change (LSC) values. We divided subjects based on FN BMD response and compared outcomes between responders and non-responders after oBP discontinuation. RESULTS: Of the 213 subjects, 32.1% showed an increase ≥LSC at the FN compared to 57.1% at the LS on treatment (P < .0001). FN responders had lower BMD levels at pretreatment baseline than non-responders both at the FN (0.58 vs 0.62 g/cm2; P = .003) and LS (0.76 vs 0.79 g/cm2; P = .044). Off-treatment, more subjects lost BMD ≥LSC at FN in the responder group than in the non-responder group (37.5% vs 14.2%; P < .001). BMD remained above pre-treatment levels in responders after a median follow-up of 1.52 years. CONCLUSION: BMD response at FN is suboptimal in patients on oBP and is much less common than LS response. FN responders tend to lose the accumulated bone quickly off-treatment, though BMD remains above pretreatment levels. These observations suggest that new approaches may be needed to optimize osteoporosis management in real-world patients.

Fracture Risk Assessment and Drug Holiday in a Real-Life Setting.

PURPOSE: Describe fracture risk assessment practices among physicians treating osteoporosis in a real-life setting. METHODS: This is a retrospective cohort study in a tertiary academic center. Inclusion criteria involved adults (aged ≥18 years) who received minimum adequate therapy (bisphosphates, raloxifene, or denosumab ≥ 3 years or teriparatide ≥ 18 months). Of 1,814 charts randomly selected and reviewed, 274 patients met the inclusion criteria. Risk stratification tools included fragility fractures, Dual-energy X-ray Absorptiometry (DXA), and fracture risk assessment using the FRAX tool. Fracture risk assessment was performed before therapy initiation (N= 274) and at the time of institution of the drug holiday (N=119). High-risk patients were defined as the presence of a fragility fracture, T-score ≤-2.5, or a high-risk score by FRAX calculation. FRAX scores were independently calculated by the research team for comparison and assessment purposes. RESULTS: Before initiation of therapy (N=274) versus upon starting a drug holiday (DH; N=119), 29.9% versus 3.4% had a history of fragility fractures (P<0.001), 58.8% versus 67.2% had a DXA scan performed (P>0.05), 10.5% versus 10.9% of physicians calculated a FRAX score (P>0.05), and 71.5% versus 66.4% were considered at high risk and eligible for therapy. A DXA scan was performed after DH in 40.2% of these patients and at least once in 95.3% of the entire cohort. CONCLUSION: The reporting of FRAX score in DXA scan reports may significantly increase its utilization in fracture risk assessment. We recommend comprehensive fracture risk assessment utilizing history of prevalent osteoporosis fractures, DXA assessment, and FRAX scoring.

Exploring the feasibility of using evidence-based feeding practices to promote children's healthy eating in holiday clubs.

OBJECTIVE: Encouraging healthy eating is a public health priority in the United Kingdom (UK), given the high prevalence of poor diet and overweight/obesity among school-aged children. Holiday clubs are organisations providing childcare and activities during the school holidays and frequently provide food to children at risk of food insecurity, primarily through government-funded programmes like the Holiday Activities and Food programme. However, the research suggests that holiday clubs could do more to maximise opportunities to promote children's healthy eating by using evidence-based feeding practices. DESIGN: During August-September 2020, video-based interviews were conducted exploring staff perceptions of the feasibility of using four evidence-based feeding practices to promote children's healthy eating: modelling; involvement in food choice; involvement in food preparation and cooking and involvement in meal planning. Feasibility was assessed using four dimensions of a feasibility framework (acceptability, demand, practicality and implementation). SETTING: UK holiday clubs. PARTICIPANTS: Twenty-five staff actively involved in delivering UK holiday clubs (project leaders, coordinators, cooks and coaches/youth workers). RESULTS: Staff generally reported good acceptability (dimension 1) and demand (dimension 2) for the feeding practices. However, the practicality (dimension 3) of using the practices was dependent on various factors (logistics, resources, staff readiness, children, peers and parents). Promisingly, in the fourth feasibility dimension (implementation), staff provided numerous practical solutions to overcome these barriers. CONCLUSIONS: Evidence-based feeding practices can be implemented in numerous ways and are therefore generally feasible in holiday clubs. Holiday clubs should be empowered to use evidence-based feeding practices through training resources, sharing networks and provision of sustainable funding.

Short- and long-term impacts of the COVID-19 epidemic on urban PM2.5 variations: Evidence from a megacity, Chengdu.

As the new coronavirus pandemic enters its third year, its long-term impact on the urban environment cannot be ignored, especially in megacities with more than millions of people. Here, we analyzed the changes in the concentration levels, emission sources, temporal variations and holiday effects of ambient fine particulate matter (PM2.5) and its chemical components in the pre- and post-epidemic eras based on high-resolution, long time-series datasets of PM2.5 and its chemical components in Chengdu. In the post-epidemic era, the PM2.5 concentration in Chengdu decreased by 7.4%, with the components of PM2.5 decreasing to varying degrees. The positive matrix factorization (PMF) results indicated that the emissions from soil dust and industrial production were significantly lower during the COVID-19 lockdown period and post-epidemic era than those in the pre-epidemic era. In contrast, the contribution of secondary aerosols to PM2.5 during these two periods increased by 2.7% and 6.6%, respectively. Notably, we found that PM2.5 and its components substantially decreased on workdays and holidays in the post-epidemic era due to the reduced traffic volume and outdoor activities. This provides direct evidence that changes in the habitual behavior patterns of urban residents in the post-epidemic era could exert an evident positive impact on the urban environment. However, the higher PM2.5 concentration was observed due to the increased consumption of regular (As4S4, Xionghuang in Chinese) and "sulfur incense" during the Dragon Boat Festival holiday in the post-epidemic era. Finally, we examined the potential effects of sporadic COVID-19 outbreaks on the PM2.5 concentration in Chengdu, and there was no decrease in PM2.5 during two local COVID-19 outbreak events due to the strong influence of secondary pollution processes.

Changes in fitness and fatness in Australian schoolchildren during the summer holidays: fitness lost, fatness regained? A cohort study.

BACKGROUND: Emerging evidence suggests that children's fatness increases and fitness declines at a greater rate during the summer holiday period, compared with the school year. The aim of this study was to compare rates of change in fitness and fatness over the in-term and summer holiday periods among Australian schoolchildren. A secondary aim was to explore whether rates of change differed according to the child's sex, socio-economic status (SES), pubertal status and weight status. METHODS: Children (n = 381) initially in Grade 4 (age 9) were recruited for this 2-year longitudinal study. Fatness (% body fat, BMI z-score, waist-to-height ratio) and fitness (20-m shuttle run and standing broad jump) were measured at the start and end of two consecutive years. Rates of change were calculated for the two in-school periods (Grades 4 and 5) and for the summer holiday period. Rates of change in fatness and fitness between in-school and holiday periods were compared, and differences in rates of change according to sex, socio-economic status, and weight status were explored. RESULTS: During the holidays, percentage body fat increased at a greater rate (annualised rate of change [RoC]: +3.9 vs. Grade 4 and + 4.7 vs. Grade 5), and aerobic fitness declined at a greater rate (RoC - 4.7 vs. Grade 4 and - 4.4 vs. Grade 5), than during the in-school periods. There were no differences in rates of change for BMI z-score, waist-to-height ratio or standing broad jump. Body fatness increased faster in the holidays (relative to the in-school period) in children who are overweight and from low-SES families. Aerobic fitness declined more rapidly in the holidays in children who are overweight. CONCLUSION: This study highlights that during the summer holiday period, children experience greater increases in fatness and declines in fitness, with children who live with low-SES families and are overweight being more affected. The findings suggest the need for targeted interventions during this period to address these negative health trends. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry, identifier ACTRN12618002008202. Retrospectively registered on 14 December 2018.

Effect of national holidays on health outcomes of patients receiving peritoneal dialysis in a single center over a ten-year period.

BACKGROUND: National holidays are associated with high mortality in some diseases, but little is known about patients undergoing peritoneal dialysis (PD). The research aimed to investigate the impact of national holidays on the health outcomes of PD patients. METHODS: Over ten years, all episodes of unplanned hospitalization, death, and peritonitis in PD patients were collected in our center. Seven national holidays in China were chosen, and non-holiday days were selected as the control period. The effect of national holidays was observed by comparing the hospitalization, death, and peritonitis rates between holiday and non-holiday groups. RESULTS: There were 297 events in all holiday periods and 1247 in non-holiday periods. There is no significant difference in hospitalization rate between holiday and non-holiday groups (32.4% ± 6.4% vs. 29.2% ± 3.4%, p = 0.175). So is the death rate [6.3% (4.8-12.3%) vs.5.0% (4.2-8.9%), p = 0.324] and peritonitis rate [0.19 (0.13-0.53) vs. 0.22 (0.18-0.27), p = 0.445] between the two groups. Significant differences were observed in the distribution of peritonitis causes between the two groups (p = 0.017). The rate of secondary to other infections in the holiday group was significantly higher than in the non-holiday group (25.0 vs. 10.3%, p = 0.015). CONCLUSION: Our study suggested no national holiday effect on health outcomes of PD patients based on ten-year data in our center.

Trametinib-Resistant Melanoma Cells Displaying MITFhigh/NGFRlow/IL-8low Phenotype Are Highly Responsive to Alternating Periods of Drug Withdrawal and Drug Rechallenge.

Despite significant advances in targeted therapies against the hyperactivated BRAFV600/MEK pathway for patients with unresectable metastatic melanoma, acquired resistance remains an unsolved clinical problem. In this study, we focused on melanoma cells resistant to trametinib, an agent broadly used in combination therapies. Molecular and cellular changes were assessed during alternating periods of trametinib withdrawal and rechallenge in trametinib-resistant cell lines displaying either a differentiation phenotype (MITFhigh/NGFRlow) or neural crest stem-like dedifferentiation phenotype (NGFRhigh/MITFlow). Neither drug withdrawal nor drug rechallenge induced cell death, and instead of loss of fitness, trametinib-resistant melanoma cells adapted to altered conditions by phenotype switching. In resistant cells displaying a differentiation phenotype, trametinib withdrawal markedly decreased MITF level and activity, which was associated with reduced cell proliferation capacity, and induced stemness assessed as NGFR-positive cells and senescence features, including IL-8 expression and secretion. All these changes could be reversed by trametinib re-exposure, which emphasizes melanoma cell plasticity. Trametinib-resistant cells displaying a dedifferentiation phenotype were less responsive presumably due to the already low level of MITF, a master regulator of the melanoma phenotype. Considering new directions of the development of anti-melanoma treatment, our study suggests that the phenotype of melanomas resistant to targeted therapy might be a crucial determinant of the selection of second-line therapy for melanoma patients.

Pandemic mobility, second homes and housing market change in a rural amenity area during COVID-19 - The Brecon Beacons National Park, Wales.

The Covid-19 pandemic has been presented as a critical change driver for rural amenity areas, precipitating urban flight and a decentralisation of housing choice and investment. House prices in both near-urban and more distant rural markets saw considerable growth in 2020 and 2021, linked to a mix of second home investment, expanded demand for holiday letting, migration to exploit flexible-working opportunities, and homebuying for early retirement. These demand-side pressures, apparently accentuated by the pandemic, combine with supply-side constraints on development in rural areas (which can accommodate a limited amount of additional housing) to produce significant housing stress. However, processes affecting some areas, in different parts of the world, have arguably been generalised to all areas, and localised processes remain under-investigated. This monograph explores the experience of the Brecon Beacons National Park in Wales, UK - an amenity area with good connectivity to a number of major urban centres and therefore sources of extra-local housing demand. Focusing on second home buying, as a leading element of extra-local pressure in amenity areas, the monograph considers the particular circumstances of this area. It shows that a combination of amplified demand-side factors, linked to the pandemic, and heightened supply-side constraints, due to a phosphate crisis affecting the National Park's major river catchments, requires a programme of actions that extends beyond the housing domain in order to resolve escalating housing market challenges and associated community and economic risks.

Dynamics of the Cardioelectric Field on the Body Surface during Atrial Depolarization in Rats with Experimental Holiday Heart Syndrome.

In model experiments reproducing the holiday heart syndrome in rats, a discrepancy between the depolarization of the right and left atria has been revealed, which manifested by an atypical arrangement of positive and negative cardiopotentials in the cardioelectric field on the body surface during the P wave and the absence of inversion of the areas of cardioelectric potentials before the onset of P waves in lead II ECG from the limbs.