A polymorphism in IRF4 affects human pigmentation through a tyrosinase-dependent MITF/TFAP2A pathway.

Sequence polymorphisms linked to human diseases and phenotypes in genome-wide association studies often affect noncoding regions. A SNP within an intron of the gene encoding Interferon Regulatory Factor 4 (IRF4), a transcription factor with no known role in melanocyte biology, is strongly associated with sensitivity of skin to sun exposure, freckles, blue eyes, and brown hair color. Here, we demonstrate that this SNP lies within an enhancer of IRF4 transcription in melanocytes. The allele associated with this pigmentation phenotype impairs binding of the TFAP2A transcription factor that, together with the melanocyte master regulator MITF, regulates activity of the enhancer. Assays in zebrafish and mice reveal that IRF4 cooperates with MITF to activate expression of Tyrosinase (TYR), an essential enzyme in melanin synthesis. Our findings provide a clear example of a noncoding polymorphism that affects a phenotype by modulating a developmental gene regulatory network.

Open-Source Automated Insulin Delivery in Type 1 Diabetes.

BACKGROUND: Open-source automated insulin delivery (AID) systems are used by many patients with type 1 diabetes. Data are needed on the efficacy and safety of an open-source AID system. METHODS: In this multicenter, open-label, randomized, controlled trial, we assigned patients with type 1 diabetes in a 1:1 ratio to use an open-source AID system or a sensor-augmented insulin pump (control). The patients included both children (defined as 7 to 15 years of age) and adults (defined as 16 to 70 years of age). The AID system was a modified version of AndroidAPS 2.8 (with a standard OpenAPS 0.7.0 algorithm) paired with a preproduction DANA-i insulin pump and Dexcom G6 CGM, which has an Android smartphone application as the user interface. The primary outcome was the percentage of time in the target glucose range of 70 to 180 mg per deciliter (3.9 to 10.0 mmol per liter) between days 155 and 168 (the final 2 weeks of the trial). RESULTS: A total of 97 patients (48 children and 49 adults) underwent randomization (44 to open-source AID and 53 to the control group). At 24 weeks, the mean (±SD) time in the target range increased from 61.2±12.3% to 71.2±12.1% in the AID group and decreased from 57.7±14.3% to 54.5±16.0% in the control group (adjusted difference, 14 percentage points; 95% confidence interval, 9.2 to 18.8; P<0.001), with no treatment effect according to age (P = 0.56). Patients in the AID group spent 3 hours 21 minutes more in the target range per day than those in the control group. No severe hypoglycemia or diabetic ketoacidosis occurred in either group. Two patients in the AID group withdrew from the trial owing to connectivity issues. CONCLUSIONS: In children and adults with type 1 diabetes, the use of an open-source AID system resulted in a significantly higher percentage of time in the target glucose range than the use of a sensor-augmented insulin pump at 24 weeks. (Supported by the Health Research Council of New Zealand; Australian New Zealand Clinical Trials Registry number, ACTRN12620000034932.).

Adapting COVID-19 Contact Tracing Protocols to Accommodate Resource Constraints, Philadelphia, Pennsylvania, USA, 2021.

Because of constrained personnel time, the Philadelphia Department of Public Health (Philadelphia, PA, USA) adjusted its COVID-19 contact tracing protocol in summer 2021 by prioritizing recent cases and limiting staff time per case. This action reduced required staff hours to prevent each case from 21-30 to 8-11 hours, while maintaining program effectiveness.

Phase-encoded fMRI tracks down brainstorms of natural language processing with subsecond precision.

Natural language processing unfolds information overtime as spatially separated, multimodal, and interconnected neural processes. Existing noninvasive subtraction-based neuroimaging techniques cannot simultaneously achieve the spatial and temporal resolutions required to visualize ongoing information flows across the whole brain. Here we have developed rapid phase-encoded designs to fully exploit the temporal information latent in functional magnetic resonance imaging data, as well as overcoming scanner noise and head-motion challenges during overt language tasks. We captured real-time information flows as coherent hemodynamic waves traveling over the cortical surface during listening, reading aloud, reciting, and oral cross-language interpreting tasks. We were able to observe the timing, location, direction, and surge of traveling waves in all language tasks, which were visualized as "brainstorms" on brain "weather" maps. The paths of hemodynamic traveling waves provide direct evidence for dual-stream models of the visual and auditory systems as well as logistics models for crossmodal and cross-language processing. Specifically, we have tracked down the step-by-step processing of written or spoken sentences first being received and processed by the visual or auditory streams, carried across language and domain-general cognitive regions, and finally delivered as overt speeches monitored through the auditory cortex, which gives a complete picture of information flows across the brain during natural language functioning. PRACTITIONER POINTS: Phase-encoded fMRI enables simultaneous imaging of high spatial and temporal resolution, capturing continuous spatiotemporal dynamics of the entire brain during real-time overt natural language tasks. Spatiotemporal traveling wave patterns provide direct evidence for constructing comprehensive and explicit models of human information processing. This study unlocks the potential of applying rapid phase-encoded fMRI to indirectly track the underlying neural information flows of sequential sensory, motor, and high-order cognitive processes.

Identification and molecular mapping of a major gene conferring resistance to Phytophthora sansomeana in soybean 'Colfax'.

KEY MESSAGE: The first single dominant resistance gene contributing major resistance to the oomycete pathogen Phytophthora sansomeana was identified and mapped from soybean 'Colfax'. Phytophthora root rot (PRR) is one of the most important diseases in soybean (Glycine max). PRR is well known to be caused by Phytophthora sojae, but recent studies showed that P. sansomeana also causes extensive root rot of soybean. Depending upon the isolate, it might produce aggressive symptoms, especially in seeds and seedlings. Unlike P. sojae which can be effectively managed by Rps genes, no known major resistance genes have yet been reported for P. sansomeana. Our previous study screened 470 soybean germplasm lines for resistance to P. sansomeana and found that soybean 'Colfax' (PI 573008) carries major resistance to the pathogen. In this study, we crossed 'Colfax' with a susceptible parent, 'Senaki', and developed three mapping populations with a total of 234 F2:3 families. Inheritance pattern analysis indicated a 1:2:1 ratio for resistant: segregating: susceptible lines among all the three populations, indicating a single dominant gene conferring the resistance in 'Colfax' (designated as Rpsan1). Linkage analysis using extreme phenotypes anchored Rpsan1 to a 30 Mb region on chromosome 3. By selecting nine polymorphic SNP markers within the region, Rpsan1 was genetically delimited into a 21.3 cM region between Gm03_4487138_A_C and Gm03_5451606_A_C, which corresponds to a 1.06 Mb genomic region containing nine NBS-LRR genes based on Gmax2.0 assembly. The mapping results were then validated using two breeding populations derived from 'E12076T-03' × 'Colfax' and 'E16099' × 'Colfax'. Marker-assisted resistance spectrum analyses with 9 additional isolates of P. sansomeana indicated that Rpsan1 may be effective towards a broader range of P. sansomeana isolates and has strong merit in protecting soybean to this pathogen in the future.

Comparing the glycaemic outcomes between real-time continuous glucose monitoring (rt-CGM) and intermittently scanned continuous glucose monitoring (isCGM) among adults and children with type 1 diabetes: A systematic review and meta-analysis of randomized controlled trials.

AIM: To conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the effectiveness of real-time continuous glucose monitoring (rtCGM) versus intermittently scanned continuous glucose monitoring (isCGM) on key glycaemic metrics (co-primary outcomes HbA1c and time-in-range [TIR] 70-180 mg/dL, 3.9-10.0 mmol/L) among people with type 1 diabetes (T1D). METHODS: Medline, PubMed, Scopus, Web of Science and Cochrane Central Register of clinical trials were searched. Inclusion criteria were RCTs; T1D populations of any age and insulin regimen; comparing any type of rtCGM with isCGM (only the first generation had been compared to date); and reporting the glycaemic outcomes. Glycaemic outcomes were extracted post-intervention and expressed as mean differences and 95% CIs between the two comparators. Results were pooled using a random-effect meta-analysis. The risk of bias was assessed using the Cochrane RoB2 tool. The quality of evidence was assessed by the GRADE approach. RESULTS: Five RCTs met the inclusion criteria (4 parallel and 1 crossover design; 4 with CGM use <8 weeks), involving 446 participants (354 adults; 92 children and adolescents). Overall, meta-analysis showed rtCGM compared to isCGM improved absolute TIR by +7.0% (95% CI: 5.8%-8.3%, I2 = 0%, p < 0.01) accompanied by a favorable effect on time-below-range <70 mg/dL (3.9 mmol/L) - 1.7% (95%CI: -3.0% to -0.4%; p = 0.03). No differences were seen regarding HbA1c. CONCLUSIONS: This meta-analysis highlights that for people with T1D, rtCGM confers benefits over isCGM primarily related to increased TIR, with improvements in hypo- and hyperglycaemia.

Real time continuous glucose monitoring in high-risk people with insulin-requiring type 2 diabetes: A randomised controlled trial.

AIMS: To investigate the impact of real-time continuous glucose monitoring (rtCGM) on glycaemia in a predominantly indigenous (Maori) population of adults with insulin-requiring type 2 diabetes (T2D) in New Zealand. METHODS: Twelve-week, multicentre randomised controlled trial (RCT) of adults with T2D using ≥0.2 units/kg/day of insulin and elevated glycated haemoglobin (HbA1c) ≥64 mmol/mol (8.0%). Following a 2-week blinded CGM run-in phase, participants were randomised to rtCGM or control (self-monitoring blood glucose [SMBG]). The primary outcome was time in the target glucose range (3.9-10 mmol/L; TIR) during weeks 10-12, with data collected by blinded rtCGM in the control group. RESULTS: Sixty-seven participants entered the RCT phase (54% Maori, 57% female), median age 53 (range 16-70 years), HbA1c 85 (IQR 74, 94) mmol/mol (9.9 [IQR 8.9, 10.8]%), body mass index (36.7 ± 7.7 kg/m2). Mean (±SD) TIR increased from 37 (24)% to 53 (24)% [Δ 13%; 95% CI 4.2 to 22; P = 0.007] in the rtCGM group but did not change in the SMBG group [45 (21)% to 45 (25)%, Δ 2.5%, 95% CI -6.1 to 11, P = 0.84]. Baseline-adjusted between-group difference in TIR was 10.4% [95% CI -0.9 to 21.7; P = 0.070]. Mean HbA1c (±SD) decreased in both groups from 85 (18) mmol/mol (10.0 [1.7]%) to 64 (16) mmol/mol (8.0 [1.4]%) in the rtCGM arm and from 81 (12) mmol/mol (9.6 [1.1]%) to 65 (13) mmol/mol (8.1 [1.2]%) in the SMBG arm (P < 0.001 for both). There were no severe hypoglycaemic or ketoacidosis events in either group. CONCLUSIONS: Real-time CGM use in a supportive treat-to-target model of care likely improves glycaemia in a population with insulin-treated T2D and elevated HbA1c.

The incidence and prevalence of proton pump inhibitor usage among internal medicine patients after hospital admission: A retrospective cohort study.

BACKGROUND: The use of proton pump inhibitors (PPIs) has increased over the past decades. One potential gateway into new PPI use is following a hospital admission. The study aimed to examine the incidence of new PPI usage following admission to internal medicine services and the ratio of new persistent users. METHODS: A retrospective descriptive study was conducted among all adults who had been admitted to internal medicine wards at the National University Hospital of Iceland from 2010-2020. Data was obtained from the Icelandic Internal Medicine Database. The proportion of patients who started treatment with PPI within 3 months of discharge (new users) and the proportion of patients who continued to use it after 3 months (persistent users) were examined. RESULTS: Among 85.942 admissions during the study period, 7238 (15.6%) became new users, and of those 4942 (68%) were new persistent users. The incidence of new PPI use was highest for patients discharged from gastroenterology (32.2%), hematology (31.8%), and oncology (29.2%). Patients with new PPI use more commonly had a history of malignancy (19.5%) and liver disease (22.7%) and more commonly were admitted to the ICU during their hospitalization. The highest ratio of persistent usage was among patients discharged from geriatric medicine (84%). CONCLUSION: One in every six patients admitted to internal medicine wards filled out a prescription for PPI within 3 months from discharge, and a large proportion of them became persistent users. The high rate of new PPI users from oncology and hematology is noteworthy and requires further research.

Investigation of the Proton-Bound Dimer of Dihydrogen Phosphate and Formate Using Infrared Spectroscopy in Helium Droplets.

Understanding the structural and dynamic properties of proton-bound complexes is crucial for elucidating fundamental aspects of chemical reactivity and molecular interactions. In this work, the proton-bound complex between dihydrogen phosphate and formate, and its deuterated counterparts, is investigated using IR action spectroscopy in helium droplets. Contrary to the initial expectation that the stronger phosphoric acid would donate a proton to formate, both experiment and theory show that all exchangeable protons are located in the phosphate moiety. The experimental spectra show good agreement with both scaled harmonic and VPT2 anharmonic calculations, indicating that anharmonic effects are small. Some H-bending modes of the nondeuterated complex are found to be sensitive to the helium environment. In the case of the partially deuterated complexes, the experiments indicate that internal dynamics leads to isomeric interconversion upon IR excitation.

Author Correction: Environment and host as large-scale controls of ectomycorrhizal fungi.

Change history: In the HTML version of this Article, author 'Filipa Cox' had no affiliation in the author list, although she was correctly associated with affiliation 3 in the PDF. In addition, the blue circles for 'oak' were missing from Extended Data Fig. 1. These errors have been corrected online.

Environment and host as large-scale controls of ectomycorrhizal fungi.

Explaining the large-scale diversity of soil organisms that drive biogeochemical processes-and their responses to environmental change-is critical. However, identifying consistent drivers of belowground diversity and abundance for some soil organisms at large spatial scales remains problematic. Here we investigate a major guild, the ectomycorrhizal fungi, across European forests at a spatial scale and resolution that is-to our knowledge-unprecedented, to explore key biotic and abiotic predictors of ectomycorrhizal diversity and to identify dominant responses and thresholds for change across complex environmental gradients. We show the effect of 38 host, environment, climate and geographical variables on ectomycorrhizal diversity, and define thresholds of community change for key variables. We quantify host specificity and reveal plasticity in functional traits involved in soil foraging across gradients. We conclude that environmental and host factors explain most of the variation in ectomycorrhizal diversity, that the environmental thresholds used as major ecosystem assessment tools need adjustment and that the importance of belowground specificity and plasticity has previously been underappreciated.

Genome-informed trophic classification and functional characterization of virulence proteins from the maize tar spot pathogen Phyllachora maydis.

Phyllachora maydis is an ascomycete foliar fungal pathogen and the causal agent of tar spot in maize. Though P. maydis is considered an economically important foliar pathogens of maize, our general knowledge of the trophic lifestyle and functional role of effector proteins from this fungal pathogen remains limited. Here, we utilized a genome-informed approach to predict the trophic lifestyle of P. maydis and functionally characterized a subset of candidate effectors from this fungal pathogen. Leveraging the most recent P. maydis genome annotation and the CATAStrophy pipeline, we show this fungal pathogen encodes a predicted Carbohydrate-active enzymes (CAZymes) repertoire consistent with that of biotrophs. To investigate fungal pathogenicity, we selected 18 candidate effector proteins that were previously shown to be expressed during primary disease development. We assessed whether these putative effectors share predicted structural similarity with other characterized fungal effectors and determined whether any suppress plant immune responses. Using AlphaFold2 and Foldseek, we showed one candidate effector, PM02_g1115, adopts a predicted protein structure similar to that of an effector from Verticillium dahlia. Furthermore, transient expression of candidate effector-fluorescent protein fusions in Nicotiana benthamiana revealed two putative effectors, PM02_g378 and PM02_g2610, accumulated predominantly in the cytosol, and three candidate effectors, PM02_g1115, PM02_g7882, and PM02_g8240 consistently attenuated chitin-mediated reactive oxygen species production. Collectively, these results presented herein provide insights into the predicted trophic lifestyle and putative functions of effectors from P. maydis and will likely stimulate continued research to elucidate the molecular mechanisms used by P. maydis to induce tar spot.

The epidemiology and outcomes of acute kidney injury following orthopaedic procedures: A retrospective cohort study.

BACKGROUND: Acute kidney injury (AKI) is a serious complication following major surgery. This study examined the incidence and risk factors of AKI following orthopaedic surgeries in an Icelandic cohort, as well as the association between AKI and patient- and surgery-related factors. METHODS: This retrospective cohort study comprised all patients 18 years and older who underwent orthopaedic surgeries at Landspitali - The National University Hospital in the years 2006-2018 with available serum creatinine (SCr) measurements adjacent to the surgery to stage AKI. AKI was defined according to SCr portion of the KDIGO criteria. Logistic regression was used to identify patient- and surgical factors related to progression of AKI and Poisson-regression was used to explore changes in incidence. RESULTS: A total of 222 cases of AKI following 3208 surgeries (6.9%) were identified in the study period with a rise in the incidence by about 17% per year. Higher age (odds ratio (OR), 1.02, 95% confidence interval (CI), 1.01-1.04 per year) and underlying reduction in kidney function (OR 1.93 (1.30-2.81), 3.24 (2.08-4.96) and 4.08 (2.35-6.96) for estimated glomerular filtration rate (eGFR) of 30-59, 15-29 and <15 mL/min/1.73 m2 compared with eGFR >60 mL/min/1.73 m2 ) were associated with higher risk of AKI, but female sex was associated with decreased odds (OR = 0.73; 95% CI, 0.54-0.98). After correcting for age, sex, preoperative kidney function, emergency surgery and underlying comorbidities and frailty, there was an increased risk of long-term mortality in patients with AKI (HR 1.41, 95% CI 1.08-1.85), and patients who developed AKI also had accelerated progression of chronic kidney disease compared with patients who did not develop AKI. CONCLUSIONS: The incidence of AKI following orthopaedic surgeries is increasing and is associated with adverse outcomes. It is important that elderly individuals and patients who have reduced kidney function receive adequate monitoring and surveillance in the perioperative period.

Postoperative pain at Landspitali: A prospective study.

BACKGROUND: Moderate or severe postoperative pain is common despite advances in surgical technique and perioperative analgesia. This study aimed to assess the prevalence and severity of postoperative pain following procedures requiring anaesthesia and identify factors associated with increased risk of postoperative pain. METHODS: Surgical patients ≥18 years of age were prospectively questioned on level of current pain on a numerical rating scale (NRS) from 0 to 10 in the post-anaesthesia care unit (PACU) and on resting, active and worst pain experienced in the first 24 h postoperatively. Clinical data was obtained from medical records. Descriptive statistics were applied, and predictors of worst pain assessed as moderate/severe (NRS ≥ 5) on postoperative day one were assessed using multivariable logistic regression. RESULTS: Of 438 included participants, moderate/severe pain occurred in 29% on the day of surgery and 70% described their worst pain as moderate/severe on postoperative day one. Procedures with the highest incidence of moderate/severe pain on the day of surgery were gynaecology-, plastic-, abdominal-, breast-, and orthopaedic procedures. On postoperative day one, patients undergoing vascular-, orthopaedic-, and abdominal operations most commonly rated their worst pain as moderate/severe. Female sex (OR = 2.15, 95% Cl 1.21-3.88, p = .010), chronic preoperative pain (OR = 4.20, 95% Cl 2.41-7.51, p < .001), undergoing a major procedure (OR = 2.07, 95% Cl 1.15-3.80, p = .017), and any intraoperative remifentanil administration (OR = 2.16, 95% Cl 1.20-3.94, p = .01) had increased odds of rating the worst pain as moderate/severe. Increased age (OR = 0.66 per 10 years (95% Cl 0.55-0.78, p < .001)) and undergoing breast-, gynaecology-, otolaryngology-, and neurosurgery (OR = 0.15-0.34, p < .038) was associated with lower odds of moderate/severe pain on postoperative day one. DISCUSSION: In our cohort, patients rated their current pain in the PACU similarly to other studies. However, the ratio of patients rating the worst pain experienced as moderate/severe on postoperative day one was relatively high. The identified patient- and procedural-related factors associated with higher odds of postoperative pain highlight a subgroup of patients who may benefit from enhanced perioperative monitoring and pain management strategies.

Postoperative nausea and vomiting at Landspitali: A prospective study.

BACKGROUND: In the last decade, anaesthesia practice has changed at Landspitali, where the majority of patients now receive antiemetic prophylaxis, and the use of total intravenous anaesthesia is the dominant mode for maintenance of anaesthesia. The aim of this study was to assess the incidence of postoperative nausea and vomiting (PONV) in a prospective way, the use of PONV prophylaxis, and clinical risk factors associated with PONV during this era. METHODS: A prospective cohort study using a convenience sample of 438 patients ≥18 years old admitted to the postoperative care unit (PACU) after elective or emergency operations in May-July 2022 at Landspitali University Hospital in Iceland. Patients answered questionnaires in the PACU and 24 h after discharge from PACU. RESULTS: The incidence of self-reported moderate/severe nausea (5/10 or higher on NRS) in PACU was 4% and 3% on postoperative day 1. A total of 91% of delivered anaesthetics were with intravenous medications only, and 82% of patients received at least one prophylactic medication for PONV. When asked to rate the worst nausea experienced, this was described as moderate/severe by 7% in PACU and 17% on postoperative day 1. Risk factors associated with PONV were female gender (OR 1.90, 95% CI 1.04-3.53) and a history of motion sickness or PONV (2.74, 1.51-4.94), but increasing age was protective (0.83 per decade, 0.71-0.98). Despite a more liberal administration of antiemetics, patients with more risk factors per Apfel PONV risk classification had a higher incidence of PONV. CONCLUSION: The incidence of PONV is generally low in this diverse surgical population where anaesthesia is mostly maintained with total intravenous anaesthesia and PONV prophylaxis is common. PONV remains a predictable complication following anaesthesia, suggesting further improvement in its prevention is possible.

Furosemide versus placebo for fluid overload in intensive care patients-The randomised GODIF trial second version: Statistical analysis plan.

BACKGROUND: Fluid overload is associated with increased mortality in intensive care unit (ICU) patients. The GODIF trial aims to assess the benefits and harms of fluid removal with furosemide versus placebo in stable adult patients with moderate to severe fluid overload in the ICU. This article describes the detailed statistical analysis plan for the primary results of the second version of the GODIF trial. METHODS: The GODIF trial is an international, multi-centre, randomised, stratified, blinded, parallel-group, pragmatic clinical trial, allocating 1000 adult ICU patients with moderate to severe fluid overload 1:1 to furosemide versus placebo. The primary outcome is days alive and out of hospital within 90 days post-randomisation. With a power of 90% and an alpha level of 5%, we may reject or detect an improvement of 8%. The primary analyses of all outcomes will be performed in the intention-to-treat population. For the primary outcome, the Kryger Jensen and Lange method will be used to compare the two treatment groups adjusted for stratification variables supplemented with sensitivity analyses in the per-protocol population and with further adjustments for prognostic variables. Secondary outcomes will be analysed with multiple linear regressions, logistic regressions or the Kryger Jensen and Lange method as suitable with adjustment for stratification variables. CONCLUSION: The GODIF trial data will increase the certainty about the effects of fluid removal using furosemide in adult ICU patients with fluid overload. TRIAL REGISTRATIONS: EudraCT identifier: 2019-004292-40 and ClinicalTrials.org: NCT04180397.

Pharmacokinetics and Safety of Bilastine 10 mg/d in Children Aged 2 to 5 Years With Allergic Rhinoconjunctivitis or Urticaria: A Phase 3 Clinical Trial.

BACKGROUND: Bilastine is a second-generation antihistamine for the symptomatic treatment of allergic rhinoconjunctivitis (ARC) and urticaria in adults, adolescents, and children. The pharmacokinetics and safety of oral bilastine 10 mg/d in children aged 2 to 5 years were evaluated. METHODS: This was a multicenter, open-label clinical trial in children aged 2 to 5 years with seasonal or perennial ARC or urticaria treated once daily with bilastine 10 mg orodispersible tablets. The safety evaluation included treatment-emergent adverse events (TEAEs), vital signs, and physical examination. Pharmacokinetic data were pooled with data from a prior pediatric study, and pharmacokinetic modeling was performed to assess consistency. RESULTS: A total of 37 children with ARC (81.1%), urticaria (8.1%), or both (10.8%) were included in the study, with a mean (SD) age of 3.7 (1.2) years. The highest plasma concentrations of bilastine were observed 1 hour after administration (634.91 ng/mL). Eight patients (21.6%) experienced 1 TEAE each, none of which was severe. Body weight and age were not covariates of variation in either systemic clearance or the volume of distribution in children aged 2 to 5 years and did not affect the pharmacokinetic parameters of bilastine. CONCLUSIONS: The pharmacokinetics of bilastine was linear and consistent with data from a previous trial, suggesting that a 10-mg dose may be used in children (2 to <12 years). No dose adjustments are deemed necessary. Oral once-daily bilastine 10 mg presented a good safety profile in children aged 2 to 5.

Early morning sport scheduling is associated with poorer subjective sleep characteristics in British student-athletes.

This study presents the sleep characteristics of British student-athletes and examines the relationships between sport scheduling and time demands on sleep outcomes. Student-athletes (n = 157, 51% male) completed the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and the Sleep Hygiene Index (SHI). Self-reported sleep characteristics on weekdays and weekends, weekly frequencies of early morning and late evening sport sessions, and academic-related and sport-related time demands were also collected. Questionnaires revealed a high prevalence of undesired sleep characteristics including poor sleep quality (global PSQI >5 in 49.0%) and low sleep durations on weekdays (25% reporting <7 h). Paired t-tests revealed significant differences in bedtime, waketime, sleep duration, and sleep onset latency between weekdays and weekends (all p < 0.01). Hierarchical regression analyses indicated that early morning sport frequency was a significant predictor of PSQI (ß = 0.30) and SHI (ß = 0.24) global scores, weekday waketimes (ß = -0.17), and weekday sleep durations (ß = -0.25; all p < 0.05) in models adjusted for participant characteristics. Late evening sport frequency, and academic-related and sport-related time demands, were not significant predictors of any sleep outcome. Adjusting sport scheduling to avoid early start times could provide a means to improve sleep outcomes and may improve sporting performance and academic attainment.

Estimated public health impact of concurrent mask mandate and vaccinate-or-test requirement in Illinois, October to December 2021.

BACKGROUND: Facing a surge of COVID-19 cases in late August 2021, the U.S. state of Illinois re-enacted its COVID-19 mask mandate for the general public and issued a requirement for workers in certain professions to be vaccinated against COVID-19 or undergo weekly testing. The mask mandate required any individual, regardless of their vaccination status, to wear a well-fitting mask in an indoor setting. METHODS: We used Illinois Department of Public Health's COVID-19 confirmed case and vaccination data and investigated scenarios where masking and vaccination would have been reduced to mimic what would have happened had the mask mandate or vaccine requirement not been put in place. The study examined a range of potential reductions in masking and vaccination mimicking potential scenarios had the mask mandate or vaccine requirement not been enacted. We estimated COVID-19 cases and hospitalizations averted by changes in masking and vaccination during the period covering October 20 to December 20, 2021. RESULTS: We find that the announcement and implementation of a mask mandate are likely to correlate with a strong protective effect at reducing COVID-19 burden and the announcement of a vaccinate-or-test requirement among frontline professionals is likely to correlate with a more modest protective effect at reducing COVID-19 burden. In our most conservative scenario, we estimated that from the period of October 20 to December 20, 2021, the mask mandate likely prevented approximately 58,000 cases and 1,175 hospitalizations, while the vaccinate-or-test requirement may have prevented at most approximately 24,000 cases and 475 hospitalizations. CONCLUSION: Our results indicate that mask mandates and vaccine-or-test requirements are vital in mitigating the burden of COVID-19 during surges of the virus.

Behavioral interventions and behavior change techniques used to improve sleep outcomes in athlete populations: A scoping review.

BACKGROUND: Athletes display a high prevalence of undesired sleep characteristics that may affect both performance and wellbeing. OBJECTIVES: This scoping review aimed to identify and map the existing evidence of behavioral sleep interventions and their effects on sleep outcomes in athletes, and retrospectively code the behavior change techniques (BCTs) implemented using the Behavior Change Technique Taxonomy (BCTTv1). METHODS: Conducted following the JBI methodology for scoping reviews, four online databases were used to identify prospective interventions with at least one behavioral component in competitive athletes, and reporting a sleep outcome pre- and post-intervention. RESULTS: Thirty-three studies met the inclusion criteria, encompassing 892 participants with a median age of 23. Five intervention categories were identified (education, mind-body practices, direct, multi-component, and other), with each demonstrating mixed efficacy but the potential to improve sleep outcomes. The BCTs varied in type and frequency between each category, with only 18 unique BCTs identified across all studies. CONCLUSIONS: The varied efficacy of previous studies at improving sleep outcomes may be attributed to the lack of behavior change theory applied during intervention development. Designing interventions following a targeted specification of the behavioral problem, and the integration of corresponding BCTs should be considered in future research.