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.

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.

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.

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.

Evidence of Fluconazole-Resistant Candida parapsilosis Genotypes Spreading across Hospitals Located in Madrid, Spain and Harboring the Y132F ERG11p Substitution.

We have been monitoring the antifungal resistance in Candida parapsilosis isolates collected from inpatients at Madrid metropolitan area hospitals for the last 3 years. The study aimed to elucidate the presence of fluconazole-resistant C. parapsilosis genotypes in Madrid. From January 2019 to December 2021, a total of 354 C. parapsilosis isolates (n = 346 patients) from blood (76.6%) or intraabdominal samples were collected and genotyped using species-specific microsatellite markers. Antifungal susceptibilities to amphotericin B, the triazoles, micafungin, anidulafungin, and ibrexafungerp were performed according to EUCAST E.Def 7.3.2; the ERG11 gene was sequenced in fluconazole-resistant isolates. A total of 13.6% (n = 48/354) isolates (one per patient) were found to be resistant to fluconazole and non-wild-type to voriconazole but fully susceptible to ibrexafungerp. Resistant isolates were mostly sourced from blood (n = 45/48, 93.8%) and were detected in five hospitals. Two hospitals accounted for a high proportion of resistant isolates (n = 41/48). Resistant isolates harbored either the Y132F ERG11p amino acid substitution (n = 43) or the G458S substitution (n = 5). Isolates harboring the Y132F substitution clustered into a clonal complex involving three genotypes (one genotype accounted for n = 39/43 isolates) that were found in four hospitals. Isolates harboring the G458S substitution clustered into another genotype found in a fifth hospital. C. parapsilosis genotypes demonstrating resistance to fluconazole have been spreading across hospitals in Madrid, Spain. Over the last 3 years, the frequency of isolation of such isolates and the number of hospitals affected is on the rise.

Ibrutinib and Venetoclax for First-Line Treatment of CLL.

BACKGROUND: Ibrutinib, an inhibitor of Bruton's tyrosine kinase, and venetoclax, an inhibitor of B-cell lymphoma 2 protein, have been approved for patients with chronic lymphocytic leukemia (CLL). Preclinical investigations have indicated potential synergistic interaction of their combination. METHODS: We conducted an investigator-initiated phase 2 study of combined ibrutinib and venetoclax involving previously untreated high-risk and older patients with CLL. All patients had at least one of the following features: chromosome 17p deletion, mutated TP53, chromosome 11q deletion, unmutated IGHV, or an age of 65 years or older. Patients received ibrutinib monotherapy (420 mg once daily) for 3 cycles, followed by the addition of venetoclax (weekly dose escalation to 400 mg once daily). Combined therapy was administered for 24 cycles. Response assessments were performed according to International Workshop on Chronic Lymphocytic Leukemia 2008 criteria. Minimal residual disease was assessed by means of multicolor flow cytometry in bone marrow (sensitivity, 10-4). RESULTS: A total of 80 patients were treated. The median age was 65 years (range, 26 to 83). A total of 30% of the patients were 70 years of age or older. Overall, 92% of the patients had unmutated IGHV, TP53 aberration, or chromosome 11q deletion. With combined treatment, the proportions of patients who had complete remission (with or without normal blood count recovery) and remission with undetectable minimal residual disease increased over time. After 12 cycles of combined treatment, 88% of the patients had complete remission or complete remission with incomplete count recovery, and 61% had remission with undetectable minimal residual disease. Responses were noted in older adults and across all high-risk subgroups. Three patients had laboratory evidence of tumor lysis syndrome. The adverse-event profile was similar to what has been reported with ibrutinib and venetoclax. CONCLUSIONS: In this study, combined venetoclax and ibrutinib was an effective oral regimen for high-risk and older patients with CLL. (Funded by AbbVie and others; ClinicalTrials.gov number, NCT02756897.).

Blood and intra-abdominal Candida spp. from a multicentre study conducted in Madrid using EUCAST: emergence of fluconazole resistance in Candida parapsilosis, low echinocandin resistance and absence of Candida auris.

OBJECTIVES: We prospectively monitored the epidemiology and antifungal susceptibility of Candida spp. from blood cultures and intra-abdominal samples in patients admitted to hospitals in the Madrid area. METHODS: Between 2019 and 2021, we prospectively collected incident isolates [one per species, patient and compartment (blood cultures versus intra-abdominal samples)] from patients admitted to any of 16 hospitals located in Madrid. We studied the antifungal susceptibilities to amphotericin B, triazoles, micafungin, anidulafungin and ibrexafungerp following the EUCAST E.Def 7.3.2 procedure. RESULTS: A total of 2107 Candida spp. isolates (1895 patients) from blood cultures (51.7%) and intra-abdominal samples were collected. Candida albicans, the Candida glabrata complex, the Candida parapsilosis complex, Candida tropicalis and Candida krusei accounted for 96.9% of the isolates; in contrast, Candida auris was undetected. Fluconazole resistance in Candida spp. was higher in blood cultures than in intra-abdominal samples (9.1% versus 8.2%; P > 0.05), especially for the C. parapsilosis complex (16.6% versus 3.6%, P < 0.05), whereas echinocandin resistance tended to be lower in blood cultures (0.5% versus 1.0%; P > 0.05). Resistance rates have risen, particularly for fluconazole in blood culture isolates, which increased sharply in 2021. Ibrexafungerp showed in vitro activity against most isolates. Species distributions and resistance rates varied among hospitals. CONCLUSIONS: Whereas no C. auris isolates were detected, fluconazole-resistant C. parapsilosis isolates have been spreading across the region and this has pulled up the rate of fluconazole resistance. In contrast, the rate of echinocandin resistance continues to be low.

Understanding Australian adolescent girls' use of digital technologies for healthy lifestyle purposes: a mixed-methods study.

BACKGROUND: Little is known about girls' use of a broad range of digital technologies to support a healthy lifestyle, particularly during the later adolescent years when they are expected to take greater responsibility for individually managing their health and wellbeing. The present study was designed to gain an in-depth understanding of adolescent girls', 15 to 17 years of age, use of a broad range of digital technologies to support multiple healthy lifestyle purposes. METHODS: This study used a mixed-methods sequential research design (i.e. quantitative and qualitative data in two consecutive phases). A quantitative online survey was conducted to determine the use of digital technologies for healthy lifestyle purposes. Qualitative semi-structured interviews were conducted with a subset of survey respondents to explore factors influencing their technology use and preferences. RESULTS: Descriptive analysis of survey data (online survey, n = 336) demonstrated the popularity of social media and online video sharing platforms, with evidence that the use of digital technologies does not occur in isolation and girls draw on several resources simultaneously to achieve their desired healthy lifestyle outcomes. Thematic analysis of interview data (semi-structured interviews, n = 29) revealed seven interrelated themes around factors influencing girls' use of, and satisfaction with, different digital technologies: accessibility, social connectivity, credibility, relatability, inspiration, safety, and customisability. CONCLUSIONS: The findings reiterate that one size doesn't fit all girls, and often one size might not even fit one girl, and thus highlight the challenge of catering to such varied use cases. Overall, it appears that current digital technology offerings meet the needs and preferences of adolescent girls for healthy lifestyle purposes, however there may be benefit in allowing greater customisation of use, and consumer driven tailoring of content, according to personal preferences and changing circumstances.

"Everything kind of revolves around technology": a qualitative exploration of families' screen use experiences, and intervention suggestions.

BACKGROUND: Managing children's screen time is challenging for most families. Interventions have had limited success in reducing screen time, potentially due to a lack of understanding of the experiences, needs and recommendations of families. This study aimed to 1) understand the screen time experiences of families, particularly during COVID-19 lockdowns; and 2) explore parent and child suggestions for the design, components, and content of a screen time management program. METHODS: Parents and children from 30 families living in Victoria, Australia completed a semi-structured interview (63 interviews) via Zoom in October-November 2021. Parents were maged 40.8 (± 8.9) years and predominantly female (90%). Children were maged 11.4 (± 2.4) years and 47% female. The interviews were audio recorded, transcribed verbatim and analysed using inductive thematic analysis combined with a summative content analysis approach. RESULTS: Three themes under Aim 1 emerged. Theme 1) 'Screen time management experiences and practices', including rules and strategies, challenges, and the impact of COVID-19 lockdowns. Theme 2) 'Impact of screens on family interaction and communication' including conflicts within the family, reduced face-to-face interactions, and negative impact on child's behaviour and wellbeing. Theme 3) 'Benefits of increased screen time due to COVID-19 lockdowns' including continuation of social interactions, extracurricular activities, improved technology skills and using screens as a 'babysitter'. Findings from Aim 2 suggest that families want a screen time management program delivered online to parents and children, which includes static and interactive content that incorporates health information, alternative activities, cyber-safety information, tips for goal setting and rewards, screen monitoring tools, links to reputable information, and parent social connections. Reminders via text message or through the online platform would help maintain engagement in the program. CONCLUSIONS: Families are experiencing challenges in managing the complex balance between the increased need for screens and the impact it has on the family. These findings provide valuable parent and child insights to assist in developing screen time management programs that are created with an understanding of the needs and challenges of families.

KASP: a genotyping method to rapid identification of resistance in Plasmodium falciparum.

BACKGROUND: The emergence and spread of anti-malarial resistance continues to hinder malaria control. Plasmodium falciparum, the species that causes most human malaria cases and most deaths, has shown resistance to almost all known anti-malarials. This anti-malarial resistance arises from the development and subsequent expansion of Single Nucleotide Polymorphisms (SNPs) in specific parasite genes. A quick and cheap tool for the detection of drug resistance can be crucial and very useful for use in hospitals and in malaria control programmes. It has been demonstrated in different contexts that genotyping by Kompetitive Allele Specific PCR (KASP), is a simple, fast and economical method that allows a high-precision biallelic characterization of SNPs, hence its possible utility in the study of resistance in P. falciparum. METHODS: Three SNPs involved in most cases of resistance to the most widespread anti-malarial treatments have been analysed by PCR plus sequencing and by KASP (C580Y of the Kelch13 gene, Y86N of the Pfmdr1 gene and M133I of the Pfcytb gene). A total of 113 P. falciparum positive samples and 24 negative samples, previously analysed by PCR and sequencing, were selected for this assay. Likewise, the samples were genotyped for the MSP-1 and MSP-2 genes, and the Multiplicity of Infection (MOI) and parasitaemia were measured to observe their possible influence on the KASP method. RESULTS: The KASP results showed the same expected mutations and wild type genotypes as the reference method, with few exceptions that correlated with very low parasitaemia samples. In addition, two cases of heterozygotes that had not been detected by sequencing were found. No correlation was found between the MOI or parasitaemia and the KASP values of the sample. The reproducibility of the technique shows no oscillations between repetitions in any of the three SNPs analysed. CONCLUSIONS: The KASP assays developed in this study were efficient and versatile for the determination of the Plasmodium genotypes related to resistance. The method is simple, fast, reproducible with low cost in personnel, material and equipment and scalable, being able to core KASP arrays, including numerous SNPs, to complete the main pattern of mutations associated to P. falciparum resistance.

Invasive aspergillosis in solid organ transplantation: Diagnostic challenges and differences in outcome in a Spanish national cohort (Diaspersot study).

BACKGROUND: The diagnosis of invasive aspergillosis (IA) can be problematic in solid organ transplantation (SOT). The prognosis greatly varies according to the type of transplant, and the impact of prophylaxis is not well defined. PATIENTS AND METHODS: The Diaspersot cohort analyses the impact of IA in SOT in Spain during the last 10 years. Proven and probable/putative IA was included. RESULTS: We analysed 126 cases of IA. The incidences of IA were as follows: 6.5%, 2.9%, 1.8% and 0.6% for lung, heart, liver and kidney transplantation, respectively. EORTC/MSG criteria confirmed only 49.7% of episodes. Tree-in-bud sign or ground-glass infiltrates were present in 56.3% of patients, while serum galactomannan (optical density index >0.5) was positive in 50.6%. A total of 41.3% received combined antifungal therapy. Overall mortality at 3 months was significantly lower (p < 0.001) in lung transplant recipients (14.8%) than in all other transplants [globally: 48.6%; kidney 52.0%, liver 58.3%, heart 31.2%, and combined 42.9%]. Fifty-four percent of episodes occurred despite the receipt of antifungal prophylaxis, and in 10%, IA occurred during prophylaxis (breakthrough infection), with both nebulised amphotericin (in lung transplant recipients) and candins (in the rest). CONCLUSIONS: Invasive aspergillosis diagnostic criteria, applied to SOT patients, may differ from those established for haematological patients. IA in lung transplants has a higher incidence, but is associated with a better prognosis than other transplants. Combination therapy is frequently used for IA in SOT. Prophylactic measures require optimisation of its use within this population.

Newborn infants who received skin-to-skin contact with fathers after Caesarean sections showed stable physiological patterns.

AIM: Separating infants and their parents after a Caesarean section is still the routine care worldwide. This study investigated three caregiving models on the wakefulness and physiological parameters of full-term infants after an elective Caesarean section. METHODS: Newborn infants born in a Chilean public hospital in 2009-12 were randomised to three groups: cot, fathers' arms or skin-to-skin contact with their father. They were assessed at 15-minute intervals, from 45 to 120 minutes after the Caesarean section. Their physiological parameters were measured, and their wakefulness was assessed using the Neonatal Behavioural Assessment Scale. RESULTS: We studied 95 infant (53% girls) born at a mean gestational age of 38.9 ± 0.9 weeks. Heart rates were significantly higher in the skin-to-skin than cot or fathers' arms groups and showed greater stability over time. Wakefulness was initially higher in the skin-to-skin group, but there were no significant differences by the end of the observation. There were no differences between the groups in peripheral oxygen saturation. Skin-to-skin contact had no negative impact on the infants. CONCLUSION: The skin-to-skin group showed some advantages over the cot and fathers' arms groups when it came to establishing stable physiological parameters and wakefulness. This approach should be supported during mother-infant separation.

PRISMA-S: an extension to the PRISMA statement for reporting literature searches in systematic reviews.

BACKGROUND: Literature searches underlie the foundations of systematic reviews and related review types. Yet, the literature searching component of systematic reviews and related review types is often poorly reported. Guidance for literature search reporting has been diverse and, in many cases, does not offer enough detail to authors who need more specific information about reporting search methods and information sources in a clear, reproducible way. This document presents the PRISMA-S (Preferred Reporting Items for Systematic reviews and Meta-Analyses literature search extension) checklist, and explanation and elaboration. METHODS: The checklist was developed using a three-stage Delphi survey process, followed by a consensus conference and public review process. RESULTS: The final checklist includes sixteen reporting items, each of which is detailed with exemplar reporting and rationale. CONCLUSIONS: The intent of PRISMA-S is to complement the PRISMA Statement and its extensions by providing a checklist that could be used by interdisciplinary authors, editors, and peer reviewers to verify that each component of a search is completely reported and, therefore, reproducible.

Guidelines for Reporting Trial Protocols and Completed Trials Modified Due to the COVID-19 Pandemic and Other Extenuating Circumstances: The CONSERVE 2021 Statement.

Importance: Extenuating circumstances can trigger unplanned changes to randomized trials and introduce methodological, ethical, feasibility, and analytical challenges that can potentially compromise the validity of findings. Numerous randomized trials have required changes in response to the COVID-19 pandemic, but guidance for reporting such modifications is incomplete. Objective: As a joint extension for the CONSORT and SPIRIT reporting guidelines, CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstances) aims to improve reporting of trial protocols and completed trials that undergo important modifications in response to extenuating circumstances. Evidence: A panel of 37 international trial investigators, patient representatives, methodologists and statisticians, ethicists, funders, regulators, and journal editors convened to develop the guideline. The panel developed CONSERVE following an accelerated, iterative process between June 2020 and February 2021 involving (1) a rapid literature review of multiple databases (OVID Medline, OVID EMBASE, and EBSCO CINAHL) and gray literature sources from 2003 to March 2021; (2) consensus-based panelist meetings using a modified Delphi process and surveys; and (3) a global survey of trial stakeholders. Findings: The rapid review yielded 41 673 citations, of which 38 titles were relevant, including emerging guidance from regulatory and funding agencies for managing the effects of the COVID-19 pandemic on trials. However, no generalizable guidance for all circumstances in which trials and trial protocols might face unanticipated modifications were identified. The CONSERVE panel used these findings to develop a consensus reporting guidelines following 4 rounds of meetings and surveys. Responses were received from 198 professionals from 34 countries, of whom 90% (n = 178) indicated that they understood the concept definitions and 85.4% (n = 169) indicated that they understood and could use the implementation tool. Feedback from survey respondents was used to finalize the guideline and confirm that the guideline's core concepts were applicable and had utility for the trial community. CONSERVE incorporates an implementation tool and checklists tailored to trial reports and trial protocols for which extenuating circumstances have resulted in important modifications to the intended study procedures. The checklists include 4 sections capturing extenuating circumstances, important modifications, responsible parties, and interim data analyses. Conclusions and Relevance: CONSERVE offers an extension to CONSORT and SPIRIT that could improve the transparency, quality, and completeness of reporting important modifications to trials in extenuating circumstances such as COVID-19.

Stress testing journals: a quasi-experimental study of rejection rates of a previously published paper.

BACKGROUND: When a journal receives a duplicate publication, the ability to identify the submitted work as previously published, and reject it, is an assay to publication ethics best practices. The aim of this study was to evaluate how three different types of journals, namely open access (OA) journals, subscription-based journals, and presumed predatory journals, responded to receiving a previously published manuscript for review. METHODS: We performed a quasi-experimental study in which we submitted a previously published article to a random sample of 602 biomedical journals, roughly 200 journals from each journal type sampled: OA journals, subscription-based journals, and presumed predatory journals. Three hundred and three journals received a Word version in manuscript format, while 299 journals received the formatted publisher's PDF version of the published article. We then recorded responses to the submission received after approximately 1 month. Responses were reviewed, extracted, and coded in duplicate. Our primary outcome was the rate of rejection of the two types of submitted articles (PDF vs Word) within our three journal types. RESULTS: We received correspondence back from 308 (51.1%) journals within our study timeline (32 days); (N = 46 predatory journals, N = 127 OA journals, N = 135 subscription-based journals). Of the journals that responded, 153 received the Word version of the paper, while 155 received the PDF version. Four journals (1.3%) accepted our paper, 291 (94.5%) journals rejected the paper, and 13 (4.2%) requested a revision. A chi-square test looking at journal type, and submission type, was significant (χ2 (4) = 23.50, p < 0.001). All four responses to accept our article came from presumed predatory journals, 3 of which received the Word format and 1 that received the PDF format. Less than half of journals that rejected our submissions did so because they identified ethical issues such as plagiarism with the manuscript (133 (45.7%)). CONCLUSION: Few journals accepted our submitted paper. However, our findings suggest that all three types of journals may not have adequate safeguards in place to recognize and act on plagiarism or duplicate submissions.

Prevalence of submicroscopic malaria infection in immigrants living in Spain.

BACKGROUND: The importance of submicroscopic malaria infections in high-transmission areas could contribute to maintain the parasite cycle. Regarding non-endemic areas, its importance remains barely understood because parasitaemia in these afebrile patients is usually below the detection limits for microscopy, hence molecular techniques are often needed for its diagnosis. In addition to this, the lack of standardized protocols for the screening of submicroscopic malaria in immigrants from endemic areas may underestimate the infection with Plasmodium spp. The aim of this study was to assess the prevalence of submicroscopic malaria in afebrile immigrants living in a non-endemic area. METHODS: A prospective, observational, multicentre study was conducted. Afebrile immigrants were included, microscopic observation of Giemsa-stained thin and thick blood smears, and two different molecular techniques detecting Plasmodium spp. were performed. Patients with submicroscopic malaria were defined as patients with negative blood smears and detection of DNA of Plasmodium spp. with one or both molecular techniques. Demographic, clinical, analytical and microbiological features were recorded and univariate analysis by subgroups was carried out with STATA v15. RESULTS: A total of 244 afebrile immigrants were included in the study. Of them, 14 had a submicroscopic malaria infection, yielding a prevalence of 5.7% (95% confidence interval 3.45-9.40). In 71.4% of the positive PCR/negative microscopy cases, Plasmodium falciparum alone was the main detected species (10 out of the 14 patients) and in 4 cases (28.6%) Plasmodium vivax or Plasmodium ovale were detected. One patient had a mixed infection including three different species. CONCLUSIONS: The prevalence of submicroscopic malaria in afebrile immigrants was similar to that previously described in Spain. Plasmodium vivax and P. ovale were detected in almost a third of the submicroscopic infections. Screening protocols for afebrile immigrants with molecular techniques could be useful for a proper management of these patients.

Adoption, implementation and sustainability of school-based physical activity and sedentary behaviour interventions in real-world settings: a systematic review.

BACKGROUND: Globally, many children fail to meet the World Health Organization's physical activity and sedentary behaviour guidelines. Schools are an ideal setting to intervene, yet despite many interventions in this setting, success when delivered under real-world conditions or at scale is limited. This systematic review aims to i) identify which implementation models are used in school-based physical activity effectiveness, dissemination, and/or implementation trials, and ii) identify factors associated with the adoption, implementation and sustainability of school-based physical activity interventions in real-world settings. METHODS: The review followed PRISMA guidelines and included a systematic search of seven databases from January 1st, 2000 to July 31st, 2018: MEDLINE, EMBASE, CINAHL, SPORTDiscus, PsycINFO, CENTRAL, and ERIC. A forward citation search of included studies using Google Scholar was performed on the 21st of January 2019 including articles published until the end of 2018. Study inclusion criteria: (i) a primary outcome to increase physical activity and/or decrease sedentary behaviour among school-aged children and/or adolescents; (ii) intervention delivery within school settings, (iii) use of implementation models to plan or interpret study results; and (iv) interventions delivered under real-world conditions. EXCLUSION CRITERIA: (i) efficacy trials; (ii) studies applying or testing school-based physical activity policies, and; (iii) studies targeting special schools or pre-school and/or kindergarten aged children. RESULTS: 27 papers comprising 17 unique interventions were included. Fourteen implementation models (e.g., RE-AIM, Rogers' Diffusion of Innovations, Precede Proceed model), were applied across 27 papers. Implementation models were mostly used to interpret results (n = 9), for planning evaluation and interpreting results (n = 8), for planning evaluation (n = 6), for intervention design (n = 4), or for a combination of designing the intervention and interpreting results (n = 3). We identified 269 factors related to barriers (n = 93) and facilitators (n = 176) for the adoption (n = 7 studies), implementation (n = 14 studies) and sustainability (n = 7 studies) of interventions. CONCLUSIONS: Implementation model use was predominately centered on the interpretation of results and analyses, with few examples of use across all study phases as a planning tool and to understand results. This lack of implementation models applied may explain the limited success of interventions when delivered under real-world conditions or at scale. TRIAL REGISTRATION: PROSPERO (CRD42018099836).

Exploring when and how adolescents sit: cross-sectional analysis of activPAL-measured patterns of daily sitting time, bouts and breaks.

BACKGROUND: This study describes patterns of adolescents' objectively-measured sitting volume, sitting bouts, and breaks in sitting during different days and periods of the day, and explored differences by sex and weekdays versus weekend days. METHODS: ActivPAL™ data were collected in August 2014-December 2015 from adolescents attending secondary government schools in Melbourne Australia. Eight periods (early morning, mid-morning, morning break, late morning, lunch, early afternoon, late-afternoon and evening) were extracted for each day. School time, class time and out-of-school time were also extracted for weekdays. The percentage of time sitting, percentage of each hour in prolonged sitting (sitting bout ≥10 min), and number of sitting breaks/hour were calculated for each period. Differences by sex, and week and weekend days were determined using t-tests. RESULTS: Participants (n = 297, 15.4 ± 1.6 years) spent 68% of their day sitting; ~ 30% of each hour in prolonged sitting and 3.1 sitting breaks/hour. Sitting time was greater during class time (75%) and school (70%) compared to out-of-school time (65%). Sitting patterns differed between week and weekend days for all periods except the evening period. Girls had higher proportion of sitting during class than boys (76% vs 72% respectively) and school hours (72% vs 67%), more prolonged sitting during school hours (27% vs 23%), and more sitting breaks per hour during out-of-school time (2.6 vs 2.4), but fewer during class (2.5 vs 3.3) and school hours (2.7 vs 3.3). Sitting patterns did not differ by sex on weekend days. CONCLUSIONS: Adolescents spent two-thirds of their waking hours sitting, with distinct patterns on weekdays and weekend days. Even though boys and girls were exposed to the same school day routine, girls spent more time sitting and had fewer sitting breaks. Class times, school breaks and the evening period were identified as key intervention periods. Further research is needed to understand the behavioural differences, and guide future intervention design.