Movement behaviour typologies and their associations with adiposity indicators in children and adolescents: a latent profile analysis of 24-h compositional data.

OBJECTIVES: Growing evidence supports the important role of 24-hour movement behaviours (MB) in preventing childhood obesity. However, research to understand the heterogeneity and variability of MB among individuals and what kind of typologies of individuals are at risk of developing obesity is lacking. To bridge this gap, this study identified typologies of 24-hour MB in children and adolescents and investigated their associations with adiposity indicators. METHODS: In this cross-sectional study, 374 children and 317 adolescents from the Czech Republic wore wrist-worn accelerometers for seven consecutive days. Time spent in moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), sedentary behaviour (SB), and sleep was quantified using raw accelerometery data. Adiposity indicators included body mass index (BMI) z-score, fat mass percentage (FM%), fat mass index (FMI), and visceral adipose tissue (VAT). Bias-adjusted latent profile analysis was used on the 24-hour MB data to identify MB typologies and their associations with adiposity indicators. The models were adjusted for potential confounders. The identified typologies were labelled to reflect the behavioural profiles of bees to aid interpretability for the general public. RESULTS: Two typologies were identified in children: highly active Workers characterised by high levels of MVPA and LPA, and inactive Queens characterised by low levels of MVPA and LPA, high levels of SB and longer sleep duration compared to Workers. In adolescents, an additional typology labelled as Drones was characterised by median levels of MVPA, LPA, SB and longest sleep duration. After controlling for covariates, we found that children labelled as Queens were associated with 1.38 times higher FM%, 1.43 times higher FMI, and 1.67 times higher VAT than Workers. In adolescents, Drones had 1.14 times higher FM% and Queens had 1.36 higher VAT in comparison with Workers, respectively. CONCLUSION: Our study highlights the importance of promoting active lifestyles in children and adolescents to potentially reduce adiposity. These findings can provide insights for interventions aimed at promoting healthy MB and preventing childhood obesity.

The association between device-measured sitting time and cardiometabolic health risk factors in children.

BACKGROUND: There is limited evidence of the associations between postural-derived sitting time, waist-worn derived sedentary time and children's health and the moderation effect of physical activity (PA). This study examined associations of children's device-measured sitting time with cardiometabolic health risk factors, including moderation by physical activity. METHODS: Cross-sectional baseline data from children (mean-age 8.2 ± 0.5 years) in Melbourne, Australia (2010) participating in the TransformUs program were used. Children simultaneously wore an activPAL to assess sitting time and an ActiGraph GT3X to assess sedentary time and physical activity intensity. Cardiometabolic health risk factors included: adiposity (body mass index [BMI], waist circumference [WC]), systolic and diastolic blood pressure (SBP, DBP), high-density lipoprotein (HDL), low-density lipoprotein (LDL), cholesterol, triglycerides, fasting plasma glucose (FPG), serum insulin, and 25-hydroxyvitaminD (25[OH]D). Linear regression models (n = 71-113) assessed associations between sitting time with each health risk factor, adjusted for different PA intensities (i.e. light [LIPA], moderate-vigorous intensities [MVPA], separately on each model), age, sex, adiposity, and clustering by school. Interaction terms examined moderation. The analyses were repeated using device-measured sedentary time (i.e. ActiGraph GT3X) for comparison. RESULTS: Sitting time was positively associated with SBP (b = 0.015; 95%CI: 0.004, 0.026), DBP (b = 0.012; 95%CI:0.004, 0.020), and FPG (b = 0.001; 95%CI: 0.000, 0.000), after adjusting for higher PA intensities. The association between sitting time and insulin (b = 0.003; 95%CI: 0.000, 0.006) was attenuated after adjusting for higher PA intensities. When the models were adjusted for LIPA and MVPA, there was a negative association with LDL (b=-0.001; 95%CI: -0.002, -0.000 and b=-0.001; 95%CI: -0.003, -0.000, respectively). There was a negative association of sedentary time with WCz (b=-0.003; 95%CI: -0.005, 0.000) and BMIz (b=-0.003; 95%CI: -0.006, -0.000) when the models were adjusted by MVPA. Sedentary time was positively associated with triglycerides (b = 0.001; 95%CI: 0.000, 0.001) but attenuated after adjusting for MVPA. No evidence of moderation effects was found. CONCLUSIONS: Higher volumes of sitting and sedentary time were associated with some adverse associations on some cardiometabolic health risk factors in children. These associations were more evident when sitting time was the predictor. This suggests that reducing time spent sitting may benefit some cardiometabolic health outcomes, but future experimental research is needed to confirm causal relationships and identify the biological mechanisms that might be involved. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12609000715279.

Fluconazole-resistant Candida parapsilosis genotypes from hospitals located in five Spanish cities and one in Italy: Description of azole-resistance profiles associated with the Y132F ERG11p substitution.

BACKGROUND: Fluconazole-resistant Candida parapsilosis is a matter of concern. OBJECTIVES: To describe fluconazole-resistant C. parapsilosis genotypes circulating across hospitals in Spain and Rome and to study their azole-resistance profile associated with ERG11p substitutions. PATIENTS/METHODS: We selected fluconazole-resistant C. parapsilosis isolates (n = 528 from 2019 to 2023; MIC ≥8 mg/L according to EUCAST) from patients admitted to 13 hospitals located in five Spanish cities and Rome. Additionally, we tested voriconazole, posaconazole, isavuconazole, amphotericin B, micafungin, anidulafungin and ibrexafungerp susceptibility. RESULTS: Of the 53 genotypes found, 49 harboured the Y132F substitution, five of which were dominating city-specific genotypes involving almost half the isolates. Another genotype involved isolates harbouring the G458S substitution. Finally, we found two genotypes with the wild-type ERG11 gene sequence and one with the R398I substitution. All isolates were fully susceptible/wild-type to amphotericin B, anidulafungin, micafungin and ibrexafungerp. The azole-resistance patterns found were: voriconazole-resistant (74.1%) or voriconazole-intermediate (25.2%), posaconazole-resistant (10%) and isavuconazole non-wild-type (47.5%). Fluconazole-resistant and voriconazole non-wild-type isolates were likely to harbour substitution Y132F if posaconazole was wild type; however, if posaconazole was non-wild type, substitution G458S was indicated if isavuconazole MIC was >0.125 mg/L or substitution Y132F if isavuconazole MIC was ≤0.125 mg/L. CONCLUSIONS: We detected a recent clonal spread of fluconazole-resistant C. parapsilosis across some cities in Spain, mostly driven by dominating city-specific genotypes, which involved a large number of isolates harbouring the Y132F ERG11p substitution. Isolates harbouring substitution Y132F can be suspected because they are non-susceptible to voriconazole and rarely posaconazole-resistant.

Effectiveness of Intervention Strategies to Increase Adolescents' Physical Activity and Reduce Sedentary Time in Secondary School Settings, Including Factors Related to Implementation: A Systematic Review and Meta-Analysis.

BACKGROUND: Globally, just one in five adolescents meet physical activity guidelines and three-quarters of the school day is spent sitting. It is unclear which types of school-based interventions strategies increase physical activity and reduce sedentary time among adolescents, or how these interventions are implemented influences their effectiveness. OBJECTIVE: The three aims of our systematic review were to (a) identify intervention strategies used within secondary school settings to improve students' movement behaviours throughout school-based initiatives, delivered at or by the school; (b) determine the overall effect of the interventions (meta-analysis) on physical activity (all intensities), sedentary time, cognitive/academic, physical health and/or psychological outcomes; and (c) describe factors related to intervention implementation. METHODS: Searches were conducted in MEDLINE complete, EMBASE, CINAHL, SPORTDiscus, APA PsycINFO, and ERIC in January 2023 for studies that (a) included high school-aged adolescents; (b) involved a school-based intervention to increase physical activity and/or decrease sedentary time; and (c) were published in English. Reported effects were pooled in meta-analyses where sufficient data were obtained. RESULTS: Eighty-five articles, representing 61 interventions, met the inclusion criteria, with 23 unique intervention strategies used. Interventions that involved whole-school approaches (i.e., physical activity sessions, environmental modifications, teacher training, peer support and/or educational resources) were favourably associated with most of the outcomes. The meta-analyses showed: (a) non-significant effects for sedentary time (Standardized mean difference [SMD] = -0.02; 95%CI, -0.14, 0.11), physical activity at all intensities (light: SMD= -0.01; 95%CI, -0.08, 0.05; moderate: SMD = 0.06; 95%CI, -0.09, 0.22; vigorous: SMD = 0.08; 95%CI, -0.02, 0.18; moderate-to-vigorous: SMD = 0.05; 95%CI, -0.01, 0.12) and waist circumference (SMD = 0.09; 95%CI, -0.03, 0.21), and (b) a small statistically significant decrease in body mass index (SMD= -0.09, 95%CI -0.16, -0.0). Factors related to intervention implementation were reported in 51% of the articles. CONCLUSION: While some intervention approaches demonstrated promise, small or null effects were found in meta-analyses. Future school-based interventions should utilize a whole-school approach designed to increase adolescents' activity across the day. Consistent reporting of implementation will increase understanding of how interventions are adopted, implemented and sustained. REGISTRATION: PROSPERO (CRD42020169988).

Malaria diagnosis using a combined system of a simple and fast extraction method with a lyophilised Dual-LAMP assay in a non-endemic setting.

Malaria is a parasitic disease distributed in tropical areas but with a high number of imported cases in non-endemic countries. The most specific and sensitive malaria diagnostic methods are PCR and LAMP. However, both require specific equipment, extraction procedures and a cold chain. This study aims to solve some limitations of LAMP method with the optimization and validation of six LAMP assays, genus and species-specific, using an easy and fast extraction method, the incorporation of a reaction control assay, two ways (Dual) of result reading and reagent lyophilization. The Dual-LAMP assays were validated against the Nested-Multiplex Malaria PCR. A conventional column and saline extraction methods, and the use of lyophilized reaction tubes were also assessed. A new reaction control Dual-LAMP-RC assay was designed. Dual-LAMP-Pspp assay showed no cross-reactivity with other parasites, repeatability and reproducibility of 100%, a significant correlation between parasite concentration and time to amplification and a LoD of 1.22 parasites/µl and 5.82 parasites/µl using column and saline extraction methods, respectively. Sensitivity and specificity of the six Dual-LAMP assays reach values of 100% or close to this, being lower for the Dual-LAMP-Pm. The Dual-LAMP-RC assay worked as expected. Lyophilized Dual-LAMP results were concordant with the reference method. Dual-LAMP malaria assays with the addition of a new reaction control LAMP assay and the use of a fast and easy saline extraction method, provided low limit of detection, no cross-reactivity, and good sensitivity and specificity. Furthermore, the reagent lyophilization and the dual result reading allow their use in most settings.

Trends in antifungal resistance in Candida from a multicenter study conducted in Madrid (CANDIMAD study): fluconazole-resistant C. parapsilosis spreading has gained traction in 2022.

We previously conducted a multicenter surveillance study on Candida epidemiology and antifungal resistance in Madrid (CANDIMAD study; 2019-2021), detecting an increase in fluconazole-resistant Candida parapsilosis. We here present data on isolates collected in 2022. Furthermore, we report the epidemiology and antifungal resistance trends during the entire period, including an analysis per ward of admission. Candida spp. incident isolates from blood cultures and intra-abdominal samples from patients cared for at 16 hospitals in Madrid, Spain, were tested with the EUCAST E.Def 7.3.2 method against amphotericin B, azoles, micafungin, anidulafungin, and ibrexafungerp and were molecularly characterized. In 2022, we collected 766 Candida sp. isolates (686 patients; blood cultures, 48.8%). Candida albicans was the most common species found, and Candida auris was undetected. No resistance to amphotericin B was found. Overall, resistance to echinocandins was low (0.7%), whereas fluconazole resistance was 12.0%, being higher in blood cultures (16.0%) mainly due to fluconazole-resistant C. parapsilosis clones harboring the Y132F-R398I ERG11p substitutions. Ibrexafungerp showed in vitro activity against the isolates tested. Whereas C. albicans was the dominant species in most hospital wards, we observed increasing C. parapsilosis proportions in blood. During the entire period, echinocandin resistance rates remained steadily low, while fluconazole resistance increased in blood from 6.8% (2019) to 16% (2022), mainly due to fluconazole-resistant C. parapsilosis (2.6% in 2019 to 36.6% in 2022). Up to 7 out of 16 hospitals were affected by fluconazole-resistant C. parapsilosis. In conclusion, rampant clonal spreading of C. parapsilosis fluconazole-resistant genotypes is taking place in Madrid.

Prevalence of Chagas disease in Latin American pregnant women in Madrid, Spain: A multicentre cross-sectional study from 2011 to 2016.

OBJECTIVE: The aim of this study is to assess Trypanosoma cruzi infection prevalence among pregnant migrants living in Madrid according to the country of origin and to assess screening coverage in this at-risk population. METHODS: Retrospective multicentre cross-sectional study conducted from January 2011 to December 2016 in eight Madrid hospitals. Each hospital reviewed their microbiology data records to assess the screening coverage and serological diagnosis in all pregnant women coming from endemic areas. RESULTS: From 2011 to 2016, 149,470 deliveries were attended at the eight hospitals, and 11,048 pregnant women were screened for Chagas disease. Most cases (93.5%) were in women from Bolivia, who also showed the highest prevalence (12.4%, 95% confidence interval: 9.9-15.0). Pooled prevalence amongst the screened women was 2.9% (95% CI: 1.8-4.1). Chagas disease screening coverage varied greatly between centres, with a pooled mean coverage of 47% (95% CI: 37%-57%; 73% [95% CI: 63%-82%] for those centres with universal screening vs. 10% [95% CI: 6%-15%] for those with a selective screening approach; p < 0.001). CONCLUSION: Our study provides useful data for policy makers and epidemiologists in a non-endemic area without congenital Chagas screening programmes.

Effectiveness of geriatric assessment and management in older cancer patients: a systematic review and meta-analysis.

BACKGROUND: Frailty and multimorbidity among older cancer patients affect treatment tolerance and efficacy. Comprehensive geriatric assessment and management is recommended to optimize cancer treatment, but its effect on various outcomes remains uncertain. OBJECTIVE: Our objective was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) and cost-effectiveness studies comparing comprehensive geriatric assessment (with or without implementation of recommendations) to usual care in older cancer patients. METHODS: We searched MEDLINE, EMBASE, CINAHL, and Cochrane trials from inception to January 27, 2023, for RCTs and cost-effectiveness studies. Pooled estimates for outcomes were calculated using random-effects models. RESULTS: A total of 19 full-text articles representing 17 RCTs were included. Average participant age was 72-80 years, and 31%-62% were female. Comprehensive geriatric assessment type, mode of delivery, and evaluated outcomes varied across studies. Meta-analysis revealed no difference in risk of mortality (risk ratio [RR] = 1.08. 95% confidence interval [CI] = 0.91 to 1.29), hospitalization (RR = 0.92, 95% CI = 0.77 to 1.10), early treatment discontinuation (RR = 0.89, 95% CI = 0.67 to 1.19), initial dose reduction (RR = 0.99, 95% CI = 0.99 to 1.26), and subsequent dose reduction (RR = 0.87, 95% CI = 0.70 to 1.09). However, the risk of treatment toxicity was statistically significantly lower in the comprehensive geriatric assessment group (RR = 0.78, 95% CI = 0.70 to 0.86). No cost-effectiveness studies were identified. CONCLUSION: Compared with usual care, comprehensive geriatric assessment was not associated with a difference in risk of mortality, hospitalization, treatment discontinuation, and dose reduction but was associated with a lower risk of treatment toxicity indicating its potential to optimize cancer treatment in this population. Further research is needed to evaluate cost-effectiveness.

Antifungal resistance in Candida spp within the intra-abdominal cavity: study of resistance acquisition in patients with serial isolates.

OBJECTIVES: Antifungal susceptibility testing is mostly conducted on blood-cultured Candida spp isolates. Because the intra-abdominal cavity has been highlighted as a hidden echinocandin-resistant C. glabrata reservoir, we assessed whether testing sequential isolates from a given patient might increase the chances of detecting antifungal resistance. METHODS: Intra-abdominal initial and sequential isolates from the same species from patients included in the CANDIdaemia in MADrid study (January 2019 to June 2022) were studied. We assessed antifungal susceptibility to amphotericin B, azoles, anidulafungin, micafungin, and ibrexafungerp using European Committee on Antimicrobial Susceptibility Testing (EUCAST) methodology and molecularly characterized resistant isolates. RESULTS: We collected 308 isolates (C. albicans [n = 179/308; 58.1%], C. glabrata [n = 101/308; 32.8%], C. tropicalis [n = 17/308; 5.5%], and C. parapsilosis [n = 11/308; 3.6%]) from 112 patients distributed as incident (n = 125/308) and sequential (n = 183/308). Per patient resistance rates of fluconazole (13.4% [15/112] vs. 8% [9/112]); 5.4% proportions difference (95% CI, -2.7% to 13.5%, p 0.09) and echinocandins (8.9% [10/112] vs. 1.8% [2/112]); 7.1% proportions difference (95% CI; 1.2-12.9%; p 0.01) were higher when considering all available isolates than only incident isolates. Resistance was detected in 18 of 112 patients and would have been overlooked in 11 of 18 (61.1%) patients if only incident isolates had been studied. Of the patients who harboured fluconazole or echinocandin-resistant isolates, 14 of 15 and 8 of 10 had received or were receiving fluconazole or echinocandins, respectively. DISCUSSION: Testing sequential Candida isolates from intra-abdominal samples is required to detect antifungal resistance, particularly to echinocandins, in patients whose incident isolates turned out to be susceptible. Furthermore, patients with echinocandin-resistant infections had frequently used echinocandins and had common secondary resistance acquisition.

Enhancing screening adherence for strongyloides infection in latinx inpatients with COVID-19: a local protocol implementation study.

Strongyloides stercoralis hyperinfection syndrome has been observed in immunosuppressed coronavirus disease 2019 (COVID-19) patients. Detecting and treating asymptomatic Strongyloides infection in individuals from endemic areas can effectively prevent hyperinfection. Unfortunately, many clinicians are unaware of this neglected infection. Therefore, we aimed to evaluate whether including Strongyloides screening in COVID-19 management protocols would encourage this practice. To accomplish this, we conducted a retrospective single-center study at 'Hospital Universitario 12 de Octubre' in Madrid, Spain, comparing two consecutive cohorts. The first cohort comprised all Latinx patients over 18 years old who were admitted for COVID-19 between March 1st and April 30th, 2020. The second cohort consisted of Latinx patients admitted between July 1st and December 31st, 2020, following an amendment to the COVID-19 management protocol that recommended screening for strongyloidiasis in at-risk patients. We identified 559 and 795 patients in the first and second periods, respectively. The percentage of individuals screened increased significantly from 8.8% to 51.6% after the screening recommendation was included in the protocol (odds ratio [OR] 11.08, 95% confidence interval [CI] 8.01-15.33). In both periods, the screening rate was significantly higher among those receiving immunosuppression than those who did not receive steroids and/or tocilizumab. No other factors influenced the screening rate. In conclusion, including strongyloidiasis screening recommendations in COVID-19 management protocols led to its increased implementation. However, the overall screening rate remained low, emphasizing the need for further efforts to enhance screening practices.

Epidemiological characteristics and prevalence rates of research reproducibility across disciplines: A scoping review of articles published in 2018-2019.

Background: Reproducibility is a central tenant of research. We aimed to synthesize the literature on reproducibility and describe its epidemiological characteristics, including how reproducibility is defined and assessed. We also aimed to determine and compare estimates for reproducibility across different fields. Methods: We conducted a scoping review to identify English language replication studies published between 2018 and 2019 in economics, education, psychology, health sciences, and biomedicine. We searched Medline, Embase, PsycINFO, Cumulative Index of Nursing and Allied Health Literature - CINAHL, Education Source via EBSCOHost, ERIC, EconPapers, International Bibliography of the Social Sciences (IBSS), and EconLit. Documents retrieved were screened in duplicate against our inclusion criteria. We extracted year of publication, number of authors, country of affiliation of the corresponding author, and whether the study was funded. For the individual replication studies, we recorded whether a registered protocol for the replication study was used, whether there was contact between the reproducing team and the original authors, what study design was used, and what the primary outcome was. Finally, we recorded how reproducibilty was defined by the authors, and whether the assessed study(ies) successfully reproduced based on this definition. Extraction was done by a single reviewer and quality controlled by a second reviewer. Results: Our search identified 11,224 unique documents, of which 47 were included in this review. Most studies were related to either psychology (48.6%) or health sciences (23.7%). Among these 47 documents, 36 described a single reproducibility study while the remaining 11 reported at least two reproducibility studies in the same paper. Less than the half of the studies referred to a registered protocol. There was variability in the definitions of reproduciblity success. In total, across the 47 documents 177 studies were reported. Based on the definition used by the author of each study, 95 of 177 (53.7%) studies reproduced. Conclusions: This study gives an overview of research across five disciplines that explicitly set out to reproduce previous research. Such reproducibility studies are extremely scarce, the definition of a successfully reproduced study is ambiguous, and the reproducibility rate is overall modest. Funding: No external funding was received for this work.

The Arabidopsis DNA glycosylase MBD4L repairs the nuclear genome in vivo.

DNA glycosylases remove mispaired or modified bases from DNA initiating the base excision repair (BER) pathway. The DNA glycosylase MBD4 (methyl-CpG-binding domain protein 4) has been functionally characterized in mammals, but not yet in plants, where it is called MBD4-like (MBD4L). Mammalian MBD4 and Arabidopsis recombinant MBD4L excise U and T mispaired with G, as well as 5-fluorouracil (5-FU) and 5-bromouracil (5-BrU) in vitro. Here, we investigate the ability of Arabidopsis MBD4L to remove some of these substrates from the nuclear genome in vivo in coordination with uracil DNA glycosylase (AtUNG). We found that mbd4l mutants are hypersensitive to 5-FU and 5-BrU, as they displayed smaller size, less root growth, and higher cell death than control plants in both media. Using comet assays, we determined BER-associated DNA fragmentation in isolated nuclei and observed reduced DNA breaks in mbd4l plants under both conditions, but particularly with 5-BrU. The use of ung and ung x mbd4l mutants in these assays indicated that both MBD4L and AtUNG trigger nuclear DNA fragmentation in response to 5-FU. Consistently, we here report the nuclear localization of AtUNG based on the expression of AtUNG-GFP/RFP constructs in transgenic plants. Interestingly, MBD4L and AtUNG are transcriptionally coordinated but display not completely overlapping functions. MBD4L-deficient plants showed reduced expression of BER genes and enhanced expression of DNA damage response (DDR) gene markers. Overall, our findings indicate that Arabidopsis MBD4L is critical for maintaining nuclear genome integrity and preventing cell death under genotoxic stress conditions.

Loneliness in older adults living with cancer: A scoping review of the quantitative and qualitative evidence on behalf of the International Society of Geriatric Oncology Nursing and Allied Health Interest Group.

INTRODUCTION: Loneliness is common in older adults. Cancer and its treatments can heighten loneliness and result in poor outcomes. However, little is known about loneliness in older adults with cancer. Our objective was to provide an overview of the prevalence of loneliness, contributing factors, evolution during the cancer trajectory, impact on treatment, and interventions to reduce loneliness. MATERIALS AND METHODS: We conducted a scoping review including studies on loneliness in adults with cancer aged ≥65. Original, published studies of any designs (excluding case reports) were included. A two-step screening process was performed. RESULTS: Out of 8,720 references, 19 studies (11 quantitative, 6 qualitative, 2 mixed-methods), mostly from the United States, Netherlands, and/or Belgium, and most published from 2010, were included. Loneliness was assessed by the De Jong Gierveld Loneliness Scale, and the UCLA loneliness scale. Up to 50% of older adults felt lonely. Depression and anxiety were often correlated with loneliness. Loneliness may increase over the first 6-12 months during treatment. One study assessed the feasibility of an intervention aiming at reducing primarily depression and anxiety and secondarily, loneliness in patients with cancer aged ≥70 after five 45-min sessions with a mental health professional. No studies investigated the impact of loneliness on cancer care and health outcomes. DISCUSSION: This review documents the scarcity of literature on loneliness in older adults with cancer. The negative impacts of loneliness on health in the general population are well known; a better understanding of the magnitude and impact of loneliness in older adults with cancer is urgently warranted.

Correction: Díaz-García et al. Candida Genotyping of Blood Culture Isolates from Patients Admitted to 16 Hospitals in Madrid: Genotype Spreading during the COVID-19 Pandemic Driven by Fluconazole-Resistant C. parapsilosis. J. Fungi 2022, 8, 1228.

In the original publication [...].

The impact of height-adjustable desks and classroom prompts on classroom sitting time, social, and motivational factors among adolescents.

PURPOSE: This quasi-experimental study examined the impact of height-adjustable desks in combination with prompts to break up prolonged sitting time during class time and identified social and motivational factors associated with breaking up sitting time among adolescents. Teachers' perceptions of strategies were also examined. METHODS: Over 17 weeks, 1 classroom in a government secondary school in Melbourne, Australia, was equipped with 27 height-adjustable desks and prompts (posters and desk stickers) to break up classroom sitting time. Teachers received professional development in the use of the desks and prompts. One group of adolescents (n = 55) had 2-5 lessons/week using the height-adjustable desks in an intervention classroom, and a comparison group matched by year level and subject (n = 50) was taught in traditional "seated" classrooms. Adolescents wore an activPAL monitor at baseline (T0), 4 weeks (T1), and 17 weeks (T2) and completed a survey at T0 and T2. Six teachers participated in interviews at T2. Effect sizes were calculated (d). RESULTS: Linear mixed models found that, compared to the traditional "seated" classrooms, the adolescents in the intervention classroom had significantly lower sitting time (T1: -9.7 min/lesson, d = -0.96; T2: -6.7 min/lesson, d = -0.70) and time spent in sitting bouts >15 min (T2: -11.2 min/lesson, d = -0.62), and had significantly higher standing time (T1: 7.3 min/lesson, d = 0.84; T2: 5.8 min/lesson, d = 0.91), number of breaks from sitting (T1: 1.3 breaks/lesson, d = 0.49; T2: 1.8 breaks/lesson, d = 0.67), and stepping time (T1: 2.5 min/lesson, d = 0.66). Intervention classroom adolescents reported greater habit strength (d = 0.58), self-efficacy for breaking up sitting time (d = 0.75), and indicated that having a teacher/classmate remind them to stand as helpful (d = 0.50). CONCLUSION: This intervention shows promise for targeting sitting behaviors in the classroom and indicates that incorporating social and motivational strategies may further enhance outcomes.

A phase 2 study of nivolumab combined with ibrutinib in patients with diffuse large B-cell Richter transformation of CLL.

Richter transformation (RT) is a rare complication of chronic lymphocytic leukemia (CLL) that has dismal outcomes. Upregulation of PD-1/PD-L1 drives immunological evasion in patients with RT. We hypothesized that combining nivolumab, a PD-1 blocking antibody, with the BTK inhibitor (BTKi) ibrutinib could potentiate tumor-cell killing. We conducted an investigator-initiated phase 2 clinical trial to assess the efficacy of combined nivolumab and ibrutinib in patients with diffuse large B-cell lymphoma (DLBCL) RT and CLL. Patients included were ≥18 years of age with adequate hepatic and renal function. Patients received nivolumab every 2 weeks of a 4-week cycle for a maximum of 24 cycles. A standard dose ibrutinib was initiated from cycle 2 onward and continued daily until progression. For patients who were already on ibrutinib at the time of study entry, the same was continued while nivolumab was initiated. A total of 24 patients with RT with a median age of 64.5 years (range, 47-88) were enrolled. Ten patients (42%) had received prior treatment for RT and 13 patients (54%) had received a prior BTKi. A total of 10 patients (42%) responded with a median duration of response of 15 months. The median overall survival was 13 months. Four of 24 (17%) patients had checkpoint inhibition-related immunological toxicities. In the CLL cohort, 10 patients were enrolled, of whom 3 patients converted from partial to complete remission; 1 patient had a grade 2 immunological toxicity. Combined nivolumab and ibrutinib is an active regimen for patients with DLBCL RT with an overall response rate of 42%. Given the limited treatment options for patients with RT, checkpoint inhibition provides a potential therapeutic option. This trial is registered at www.clinicaltrials.gov as #NCT02420912.

Global Emergence of Resistance to Fluconazole and Voriconazole in Candida parapsilosis in Tertiary Hospitals in Spain During the COVID-19 Pandemic.

Background: Candida parapsilosis is a frequent cause of candidemia worldwide. Its incidence is associated with the use of medical implants, such as central venous catheters or parenteral nutrition. This species has reduced susceptibility to echinocandins, and it is susceptible to polyenes and azoles. Multiple outbreaks caused by fluconazole-nonsusceptible strains have been reported recently. A similar trend has been observed among the C. parapsilosis isolates received in the last 2 years at the Spanish Mycology Reference Laboratory. Methods: Yeast were identified by molecular biology, and antifungal susceptibility testing was performed using the European Committee on Antimicrobial Susceptibility Testing protocol. The ERG11 gene was sequenced to identify resistance mechanisms, and strain typing was carried out by microsatellite analysis. Results: We examined the susceptibility profile of 1315 C. parapsilosis isolates available at our reference laboratory between 2000 and 2021, noticing an increase in the number of isolates with acquired resistance to fluconazole, and voriconazole has increased in at least 8 different Spanish hospitals in 2020-2021. From 121 recorded clones, 3 were identified as the most prevalent in Spain (clone 10 in Catalonia and clone 96 in Castilla-Leon and Madrid, whereas clone 67 was found in 2 geographically unrelated regions, Cantabria and the Balearic Islands). Conclusions: Our data suggest that concurrently with the coronavirus disease 2019 pandemic, a selection of fluconazole-resistant C. parapsilosis isolates has occurred in Spain, and the expansion of specific clones has been noted across centers. Further research is needed to determine the factors that underlie the successful expansion of these clones and their potential genetic relatedness.

Candida Genotyping of Blood Culture Isolates from Patients Admitted to 16 Hospitals in Madrid: Genotype Spreading during the COVID-19 Pandemic Driven by Fluconazole-Resistant C. parapsilosis.

BACKGROUND: Candidaemia and invasive candidiasis are typically hospital-acquired. Genotyping isolates from patients admitted to different hospitals may be helpful in tracking clones spreading across hospitals, especially those showing antifungal resistance. METHODS: We characterized Candida clusters by studying Candida isolates (C. albicans, n = 1041; C. parapsilosis, n = 354, and C. tropicalis, n = 125) from blood cultures (53.8%) and intra-abdominal samples (46.2%) collected as part of the CANDIMAD (Candida in Madrid) study in Madrid (2019-2021). Species-specific microsatellite markers were used to define the genotypes of Candida spp. found in a single patient (singleton) or several patients (cluster) from a single hospital (intra-hospital cluster) or different hospitals (widespread cluster). RESULTS: We found 83 clusters, of which 20 were intra-hospital, 49 were widespread, and 14 were intra-hospital and widespread. Some intra-hospital clusters were first detected before the onset of the COVID-19 pandemic, but the number of clusters increased during the pandemic, especially for C. parapsilosis. The proportion of widespread clusters was significantly higher for genotypes found in both compartments than those exclusively found in either the blood cultures or intra-abdominal samples. Most C. albicans- and C. tropicalis-resistant genotypes were singleton and presented exclusively in either blood cultures or intra-abdominal samples. Fluconazole-resistant C. parapsilosis isolates belonged to intra-hospital clusters harboring either the Y132F or G458S ERG11p substitutions; the dominant genotype was also widespread. CONCLUSIONS: the number of clusters-and patients involved-increased during the COVID-19 pandemic mainly due to the emergence of fluconazole-resistant C. parapsilosis genotypes.

Blood-based biomarkers of cancer-related cognitive impairment in non-central nervous system cancer: A scoping review.

This scoping review was designed to synthesize the extant literature on associations between subjective and/or objective measures of cancer-related cognitive impairment (CRCI) and blood-based biomarkers in adults with non-central nervous system cancers. The literature search was done for studies published from the start of each database searched (i.e., MEDLINE, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, grey literature) through to October 20, 2021. A total of 95 studies are included in this review. Of note, a wide variety of biomarkers were evaluated. Most studies evaluated patients with breast cancer. A variety of cognitive assessment measures were used. The most consistent significant findings were with various subjective and objective measures of CRCI and levels of interleukin-6 and tumor necrosis factor. Overall, biomarker research is in an exploratory phase. However, this review synthesizes findings and proposes directions for future research.