An umbrella review of systematic reviews on interventions of physical activity before pregnancy, during pregnancy, and postpartum to control and/or reduce weight gain.

BACKGROUND: The increasing prevalence of overweight and obesity worldwide represents a (chronic) complex public health problem. This is also seen among women of childbearing age despite increased efforts to promote physical activity (PA) interventions. Excessive gestational weight gain (GWG) is associated with negative health outcomes for both mothers and offspring. OBJECTIVES: To summarize current systematic reviews (SRs) on PA interventions during pregnancy and postpartum to prevent excessive GWG and identify the most effective approaches. SEARCH STRATEGY: A literature search was conducted on major electronic databases (MEDLINE/Pubmed, Cochrane, Web of Science, Epistemonikos) from inception to March 2023. SELECTION CRITERIA: This study included SRs and meta-analyses of studies involving women aged 18 years or older from diverse ethnic backgrounds, who were either in the preconception period, pregnant, or within 1 year postpartum and who had no contraindications for exercise. Women with chronic diseases, such as pre-existing diabetes (type 1 or type 2) were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data from selected studies assessing the impact of PA in preconception, pregnancy, and postpartum. Methodologic quality was assessed with the AMSTAR-2 tool. A narrative summary of results addresses relationships between PA and weight before, during, and after pregnancy, informing future research priorities for preventing excessive weight gain. This study is registered on PROSPERO (CRD420233946666). MAIN RESULTS: Out of 892 identified articles, 25 studies were included after removing duplicates, unrelated titles, and screening titles and abstracts for eligibility. The results demonstrate that PA can help prevent excessive GWG and postpartum weight retention. Structured and supervised moderate-intensity exercise, at least twice a week, and each session lasting a minimum of 35 min seems to provide the greatest benefits. CONCLUSIONS: Women who comply with the PA program and recommendations are more likely to achieve adequate GWG and return to their pre-pregnancy body mass index after delivery. Further research is warranted to explore how preconception PA influences pregnancy and postpartum outcomes given the absence of identified preconception-focused interventions.

CHAMPP4KIDS: Mixed methods study protocol to evaluate acceptability and feasibility of Parenting for Lifelong Health materials in a Canadian context.

BACKGROUND: Parents and caregivers play a key role in children's healthy development and well-being. Traditional parenting interventions promote positive parenting practices and are key to preventing child maltreatment. However, numerous barriers can limit access to programs, barriers which were further exacerbated by the COVID-19 pandemic. The Parenting for Lifelong Health group developed mass media and public health communication materials to promote positive caregiving behaviours on a population level. The Champions of Positive Parenting 4 Kids (CHAMPP4KIDS) study will examine the acceptability and feasibility of these materials for service providers and caregivers of children aged 2-6 years in Ontario, Canada. METHODS: This study will use a convergent mixed-methods design. Consenting service providers (n = 200) and caregivers (n = 100) will complete a quantitative survey to rate, rank and give feedback on Parenting for Lifelong Health tip sheets and social media ads. Caregivers will also complete self-report scales measuring depression and anxiety. We will hold focus group discussions with a sub-sample of surveyed providers (n = 40) and caregivers (n = 25). An adapted Trials of Improved Practices methodology will explore caregiver perspectives after implementing the tip sheets. Primary quantitative outcomes will be descriptive statistics of rankings, Likert Scale scores and descriptive analysis of caregiver depression and anxiety. Qualitative data will be analyzed using Rapid Qualitative Inquiry and triangulated through a convergent coding matrix. DISCUSSION: The Parenting for Lifelong Health COVID-19 parenting materials offer succinct, engaging parenting information in a mass media format that addresses some challenges associated with accessing in-person programming. The CHAMPP4KIDS study will provide mixed methods insights on the materials' acceptability and feasibility from different groups in a Canadian context, with a focus on marginalized families. The use of Trials of Improved Practices methodology could prove a useful tool for participant-led adaptation of existing parenting, early childhood development and other health intervention materials.

Validation of the inventory: lockdown and its impact on the university Community.

BACKGROUND: Significant consequences of COVID-19 within academic/professional life are, at the psychological level, related to worry, tension, stress; coping strategies and lifestyle changes. This study describes the process of design and validation of an inventory (QPIC), which aims to assess the psychological impact that a situation of confinement can produce among university students and teachers. METHODS: Design of the instrument and psychometric tests. A sample of 862 students and 229 professors affiliated to Spanish and Colombian universities was used. Data were collected in April 2020 with the request of the favourable Bioethics Committee IR/2020. RESULTS: Six experts carried out the content validation. A confirmatory factor analysis of the theoretical dimensions proposed for the scales was performed and the internal consistency of each of the three initial scales was confirmed (0.866, 0.813 and 0.834). CONCLUSION: A rigorous and reliable instrument is achieved, consisting of two final scales: (a) Worry, tension and stress scale (b) Coping scale, which helps to measure individual psychological effects in housebound situations. It is an instrument designed, constructed ad hoc to assess the impact of confinement and subjected to validation. The factor structure and reliability of the instrument are examined and good psychometric properties are obtained. The application of this inventory will make it possible to assess the impact on people's mental health during a period of confinement.

Field-based molecular detection of Batrachochytrium dendrobatidis in critically endangered Atelopus toads and aquatic habitats in Ecuador.

Batrachochytrium dendrobatidis (Bd) is a lethal fungal species that parasitizes vertebrates and is associated with the worldwide decline of amphibian populations. The development of sensitive, rapid detection methods, particularly DNA-based techniques, is critical for effective management strategies. This study evaluates the efficacy of DNA extraction and a portable PCR device in a mountable field laboratory setup for detecting Bd near the habitats of three critically endangered Atelopus toad species in Ecuador. We collected skin swabs from Atelopus balios, A. nanay, and A. bomolochos, and environmental DNA (eDNA) samples from streams in Andean and coastal regions of Ecuador. For eDNA, a comparison was made with duplicates of the samples that were processed in the field and in a standard university laboratory. Our findings revealed Bd detection in eDNA and swabs from 6 of 12 water samples and 10 of 12 amphibian swab samples. The eDNA results obtained in the field laboratory were concordant with those obtained under campus laboratory conditions. These findings highlight the potential of field DNA-based monitoring techniques for detecting Bd in amphibian populations and their aquatic habitats, particularly in remote areas. Furthermore, this research aligns with the National Action Plan for the Conservation of Ecuadorian Amphibians and contributes to the global effort to control this invasive and deadly fungus.

Physical activity and unexpected weight change in Ontario children and youth during the COVID-19 pandemic: A cross-sectional analysis of the Ontario Parent Survey 2.

The objective of this study was to investigate the association between children's parent-reported physical activity levels and weight changes during the COVID-19 pandemic among children and youth in Ontario Canada. A cross-sectional online survey was conducted in parents of children 5-17 years living in Ontario from May to July 2021. Parents recalled their child's physical activity and weight change during the year prior to their completion of the survey. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multinomial logistic regression for the association between physical activity and weight gain or loss, adjusted for child age and gender, parent ethnicity, current housing type, method of school delivery, and financial stability. Overall, 86.8% of children did not obtain 60 minutes of moderate-to-vigorous physical activity per day and 75.4% of parents were somewhat or very concerned about their child's physical activity levels. For all physical activity exposures (outdoor play, light physical activity, and moderate-to-vigorous physical activity), lower physical activity was consistently associated with increased odds of weight gain or loss. For example, the adjusted OR for the association between 0-1 days of moderate-to-vigorous physical activity versus 6-7 days and child weight gain was 5.81 (95% CI 4.47, 7.56). Parent concern about their child's physical activity was also strongly associated with child weight gain (OR 7.29; 95% CI 5.94, 8.94). No differences were observed between boys and girls. This study concludes that a high proportion of children in Ontario had low physical activity levels during the COVID-19 pandemic and that low physical activity was strongly associated with parent reports of both weight gain and loss among children.

A longitudinal study examining the associations between prenatal and postnatal maternal distress and toddler socioemotional developmental during the COVID-19 pandemic.

Elevated psychological distress, experienced by pregnant women and parents, has been well-documented during the COVID-19 pandemic. Most research focuses on the first 6-months postpartum, with single or limited repeated measures of perinatal distress. The present longitudinal study examined how perinatal distress, experienced over nearly 2 years of the COVID-19 pandemic, impacted toddler socioemotional development. A sample of 304 participants participated during pregnancy, 6-weeks, 6-months, and 15-months postpartum. Mothers reported their depressive, anxiety, and stress symptoms, at each timepoint. Mother-reported toddler socioemotional functioning (using the Brief Infant-Toddler Social and Emotional Assessment) was measured at 15-months. Results of structural equation mediation models indicated that (1) higher prenatal distress was associated with elevated postpartum distress, from 6-weeks to 15-months postpartum; (2) associations between prenatal distress and toddler socioemotional problems became nonsignificant after accounting for postpartum distress; and (3) higher prenatal distress was indirectly associated with greater socioemotional problems, and specifically elevated externalizing problems, through higher maternal distress at 6 weeks and 15 months postpartum. Findings suggest that the continued experience of distress during the postpartum period plays an important role in child socioemotional development during the COVID-19 pandemic.

Routine screening for adverse childhood experiences (ACEs) still doesn't make sense.

When a serious health or social problem is identified as both prevalent and in need of attention, a common response is to propose that various systems implement routine identification, such as universal screening. However, these well-intentioned responses often fail to consider the key requirements necessary to determine whether benefits outweigh harms. Unfortunately, this continues to be the case for calls to implement routine screening for Adverse Childhood Experiences (ACEs). Persistent evidence gaps for this type of screening include the lack of any randomized controlled trials demonstrating that ACEs screening programs lead to any benefits. Rather than being informed by established screening principles, the calls to proceed with ACEs screening appear to rely on the assumption that simply identifying risk factors can lead to beneficial outcomes that outweigh any risk of harms. This may reflect a gap in understanding that patterns identified at the population level (e.g., that more ACEs are associated with more health and social problems) cannot be directly translated to practices at the level of the individual. This commentary does not question the importance of ACEs; rather it identifies that directing limited resources to screening approaches for which there is no evidence that benefits outweigh harms is problematic. Instead, we advocate for the investment in high-quality trials of prevention interventions to determine where best to direct limited resources to reduce the occurrence of ACEs, and for the prioritization of evidence-based treatment services for those with existing health and social conditions, whether or not they are attributed to ACEs.

ncRNAs Orchestrate Chemosensitivity Induction by Neddylation Blockades.

We performed an integrative transcriptomic in silico analysis using lung adenocarcinoma A549 cells treated with the neddylation inhibitor MLN4924 and the gefitinib-resistant PC9 cell line (PC9GR). We focused on the transcriptional effects of the top differentially expressed ncRNA biotypes and their correlating stemness factors. Interestingly, MLN4924-treated cells showed a significant upregulation of mRNAs involved in carcinogenesis, cell attachment, and differentiation pathways, as well as a parallel downregulation of stemness maintenance and survival signaling pathways, an effect that was inversely observed in PC9GR cells. Moreover, we found that stemness factor expression could be contrasted by selected up-regulated ncRNAs upon MLN4924 treatment in a dose and time-independent manner. Furthermore, upregulated miRNAs and lncRNA-targeted mRNAs showed an evident enrichment of proliferation, differentiation, and apoptosis pathways, while downregulated ncRNA-targeted mRNAs were implicated in stem cell maintenance. Finally, our results proved that stemness (KLF4 and FGFR2) and epithelial-mesenchymal transition (ZEB2, TWIST2, SNAI2, CDH2, and VIM) factors, which are highly expressed in PC9GR cells compared to gefitinib-sensitive PC9 cells, could be abrogated with the neddylation inhibitor MLN4924 mainly through activation of epithelial differentiation pathways, thus exerting a protective role in lung cancer cells and chemosensitivity against lung tumorigenic transformation.

Peroxisomal Localization of a Truncated HMG-CoA Reductase under Low Cholesterol Conditions.

3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase, HMGCR) is one of the rate-limiting enzymes in the mevalonate pathway required for cholesterol biosynthesis. It is an integral membrane protein of the endoplasmic reticulum (ER) but has occasionally been described in peroxisomes. By co-immunofluorescence microscopy using different HMGCR antibodies, we present evidence for a dual localization of HMGCR in the ER and peroxisomes in differentiated human monocytic THP-1 cells, primary human monocyte-derived macrophages and human primary skin fibroblasts under conditions of low cholesterol and statin treatment. Using density gradient centrifugation and Western blot analysis, we observed a truncated HMGCR variant of 76 kDa in the peroxisomal fractions, while a full-length HMGCR of 96 kDa was contained in fractions of the ER. In contrast to primary human control fibroblasts, peroxisomal HMGCR was not found in fibroblasts from patients suffering from type-1 rhizomelic chondrodysplasia punctata, who lack functional PEX7 and, thus, cannot import peroxisomal matrix proteins harboring a type-2 peroxisomal targeting signal (PTS2). Moreover, in the N-terminal region of the soluble 76 kDa C-terminal catalytic domain, we identified a PTS2-like motif, which was functional in a reporter context. We propose that under sterol-depleted conditions, part of the soluble HMGCR domain, which is released from the ER by proteolytic processing for further turnover, remains sufficiently long in the cytosol for peroxisomal import via a PTS2/PEX7-dependent mechanism. Altogether, our findings describe a dual localization of HMGCR under combined lipid depletion and statin treatment, adding another puzzle piece to the complex regulation of HMGCR.

Next-Generation Sequencing Trends among Adult Patients with Select Advanced Tumor Types: A Real-World Evidence Evaluation.

There are limited data on the prevalence of next-generation sequencing (NGS) in the United States, especially in light of the increasing importance of identifying actionable oncogenic variants due to molecular biomarker-based therapy approvals. This retrospective study of adult patients with select metastatic solid tumors and central nervous system tumors from the Optum Clinformatics Data Mart US health care claims database (January 1, 2014, to June 30, 2021; N = 63,209) examined NGS use trends over time. A modest increase in NGS was observed across tumor types from 2015 (0.0% to 1.5%) to 2021 (2.1% to 17.4%). A similar increase in NGS rates was also observed across key periods; however, rates in the final key period remained <10% for patients with breast, colorectal, head and neck, soft tissue sarcoma, and thyroid cancers, as well as central nervous system tumors. The median time to NGS from diagnosis was shortest among patients with non-small-cell lung cancer and longest for patients with breast cancer. Predictors of NGS varied by tumor type; test rates for minorities in select tumor types appeared comparable to the White population. Despite improving payer policies to expand coverage of NGS and molecular biomarker-based therapy approvals, NGS rates remained low across tumor types. Given the potential for improved patient outcomes with molecular biomarker-based therapy, further efforts to improve NGS rates are warranted.

Outcomes for clinical trials involving adults with chronic kidney disease: a multinational Delphi survey involving patients, caregivers, and health professionals.

BACKGROUND: Many outcomes of high priority to patients and clinicians are infrequently and inconsistently reported across trials in CKD, which generates research waste and limits evidence-informed decision making. We aimed to generate consensus among patients/caregivers and health professionals on critically important outcomes for trials in CKD prior to kidney failure and the need for kidney replacement therapy, and to describe the reasons for their choices. METHODS: Online two-round international Delphi survey. Adult patients with CKD (all stages and diagnoses), caregivers and health professionals, who could read English, Spanish, or French were eligible. Participants rated the importance of outcomes using a Likert scale (7-9 indicating critical importance) and a best-worst scale. The scores for the two groups were assessed to determine absolute and relative importance. Comments were analysed thematically. RESULTS: In total, 1 399 participants from 73 countries completed Round 1 of the Delphi survey including 628 (45%) patients/caregivers and 771 (55%) health professionals. In Round 2, 790 participants (56% response rate) from 63 countries completed the survey including 383 (48%) patients/caregivers and 407 (52%) health professionals. The overall top five outcomes were: kidney function, need for dialysis/transplant, life participation, cardiovascular disease, and death. In the final round, patients/caregivers indicated higher scores for most outcomes (17/22 outcomes), and health professionals gave higher priority to mortality, hospitalization, and cardiovascular disease (mean difference > 0.3). Consensus was based upon the two groups yielding median scores of ≥ 7 and mean scores > 7, and the proportions of both groups rating the outcome as 'critically important' being greater than 50%. Four themes reflected the reasons for their priorities: imminent threat of a health catastrophe, signifying diminishing capacities, ability to self-manage and cope, and tangible and direct consequences. CONCLUSION: Across trials in CKD, the outcomes of highest priority to patients, caregivers, and health professionals were kidney function, need for dialysis/transplant, life participation, cardiovascular disease, and death.

Real-world treatment outcomes of immune checkpoint inhibitors used off-label in oncology: A comprehensive cancer institution experience.

Off-label use (OLU) is quite common in oncology due to the complexity of cancer and the time-consuming regulatory process. However, outcomes of OLU in cancer treatment remain unclear. This study aimed to evaluate the overall survival (OS), event-free survival (EFS), duration of treatment (DOT), and reason for treatment discontinuation in patients receiving immune checkpoint inhibitors (ICI) as OLU for solid tumors from 2011 to 2020. The study collected data on 356 episodes (353 patients), with a median age of 64.4 years, 36.2% women, and 14.6% ECOG ≥ 2. Median OS was 15.7 (11.9-18.7) months, and median EFS was 5.4 (3.8-6.6) months. Men, patients with metastatic disease or ECOG-PS higher than 1, had worse survival outcomes. The findings derived from this study provide valuable information regarding the real-world use of ICI-OLU and contributes to enhancing the decision-making process for individuals with cancer. Further research on immunotherapy outcomes of OLU in cancer is needed.

Social support buffers the impact of pregnancy stress on perceptions of parent-infant closeness during the COVID-19 pandemic.

Pregnant individuals and parents have experienced elevated mental health problems and stress during COVID-19. Stress during pregnancy can be harmful to the fetus and detrimental to the parent-child relationship. However, social support is known to act as a protective factor, buffering against the adverse effects of stress. The present study examined whether (1) prenatal stress during COVID-19 was associated with parent-infant closeness at 6 months postpartum, and (2) social support moderated the effect of prenatal stress on the parent-infant relationship. In total, 181 participants completed questionnaires during pregnancy and at 6 months postpartum. A hierarchical linear regression analysis was conducted to assess whether social support moderated the effect of stress during pregnancy on parent-infant closeness at 6 months postpartum. Results indicated a significant interaction between prenatal stress and social support on parents' perceptions of closeness with their infants at 6 months postpartum (ß = .805, p = .029); parents who experienced high prenatal stress with high social support reported greater parent-infant closeness, compared to those who reported high levels of stress and low social support. Findings underscore the importance of social support in protecting the parent-infant relationship, particularly in times of high stress, such as during the COVID-19 pandemic.

Individuos y progenitores en estado de embarazo experimentan elevados problemas de salud mental y estrés durante el COVID-19. El estrés durante el embarazo puede ser dañino para el feto y perjudicial para la relación progenitor-niño. Sin embargo, es sabido que el apoyo social actúa como un factor de protección, sirviendo como agente amortiguador contra los adversos efectos del estrés. El presente estudio longitudinal examinó si 1) el estrés prenatal durante el COVID-19 se asociaba con la cercanía madre-infante a los seis meses después del parto, y 2) el apoyo social moderaba el efecto del estrés prenatal en la relación madre-infante. Un total de 181 participantes completaron cuestionarios durante el embarazo y a los seis meses después del parto. Un análisis de regresión lineal jerárquico se llevó a cabo para evaluar si el apoyo social moderaba el efecto del estrés durante el embarazo en cuanto a la cercanía progenitor-infante a los seis meses después del parto. Los resultados indicaron una interacción significativa entre el estrés prenatal y el apoyo social sobre las percepciones que los progenitores tenían de la cercanía con sus infantes a los seis meses después del parto (ß = .805, p = .029); los progenitores que experimentaron un alto estrés prenatal con un alto apoyo social reportaron una mayor cercanía progenitor-infante, comparados con aquellos que reportaron altos niveles de estrés y bajo apoyo social. Los resultados subrayan la importancia del apoyo social para proteger la relación progenitor-infante, particularmente en épocas de alto estés, tal como durante la pandemia del COVID-19.

Les personnes enceintes et les parents font l'expérience de plus grands problèmes de santé mentale et de plus de stress durant la crise du COVID-19. Le stress durant la grossesse peut être néfaste pour le foetus et vient au détriment de la relation parent-enfant. Cependant l'on sait que le soutien social est un facteur de protection, faisant tampon face aux effets adverses du stress. Cette étude longitudinale a examiné si 1) le stress prénatal durant le COVID-19 était lié à la proximité mère-nourrisson à six mois postpartum, et 2) le soutien social a modéré l'effet du stress prénatale sur la relation mère-nourrisson. En tout 181 participants ont rempli des questionnaires durant la grossesse et à sic mois postpartum. Une analyse de régression linéaire hiérarchique a été faite pour évaluer si le soutien social a modéré l'effet du stress durant la grossesse sur la proximité parent-nourrisson à six mois postpartum. Les résultats ont indiqué une interaction importante entre le stress prénatal et le soutien social sur les perceptions des parents de la proximité avec leurs nourrissons à six mois postpartum (ß = ,805, p = ,029); les parents qui ont fait l'expérience d'un stress prénatal élevé avec un soutien social élevé ont signalé une plus grande proximité parent-nourrisson, comparé à ceux ayant signalé des niveaux de stress élevés et un faible soutien social. Les résultats soulignent l'importance du soutien social dans la protection de la relation parent-nourrisson, particulièrement en temps de stress élevé, comme durant la pandémie de COVID-19.

Relation and effect of resilience on burnout in nurses: A literature review and meta-analysis.

AIM: To study the relation between burnout and resilience and to identify the profile of nurses presenting this quality. BACKGROUND AND INTRODUCTION: Healthcare professionals are subject to high rates of burnout. Resilience could be an important factor in preventing or alleviating this condition. METHODS: The PubMed, ProQuest, Scopus and ScienceDirect databases were consulted in February 2022 using the equation 'burnout AND resilience AND nurs*'. The inclusion criteria applied were that the texts should describe quantitative studies, be published in English or Spanish, in any year, and be directly related to the question considered. The meta-analysis was performed using StatsDirect statistical software. RESULTS: Analysis of the 29 studies shows that among the dimensions of burnout, nurses are especially prone to emotional exhaustion, and are less affected by depersonalisation and low personal accomplishment. Those who score highly for resilience tend to have longer service experience, acceptable salaries and less work overload. Meta-analysis reveals an inverse correlation between resilience and burnout (r = -0.41; n = 2750), exhaustion (r = -0.27; n = 6966) and depersonalisation (r = -0.23; n = 6115). CONCLUSION: Many nurses present low levels of resilience and suffer from burnout syndrome. The application of programmes to enhance their resilience would help prevent burnout and optimise the potential to provide quality health care. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Resilience is inversely correlated with burnout, depersonalisation and emotional exhaustion. Accordingly, healthcare organisations should develop and implement evidence-based programmes to foster nurses' resilience and thus reduce their susceptibility to burnout.

Efficacy of HDAC Inhibitors in Driving Peroxisomal ß-Oxidation and Immune Responses in Human Macrophages: Implications for Neuroinflammatory Disorders.

Elevated levels of saturated very long-chain fatty acids (VLCFAs) in cell membranes and secreted lipoparticles have been associated with neurotoxicity and, therefore, require tight regulation. Excessive VLCFAs are imported into peroxisomes for degradation by ß-oxidation. Impaired VLCFA catabolism due to primary or secondary peroxisomal alterations is featured in neurodegenerative and neuroinflammatory disorders such as X-linked adrenoleukodystrophy and multiple sclerosis (MS). Here, we identified that healthy human macrophages upregulate the peroxisomal genes involved in ß-oxidation during myelin phagocytosis and pro-inflammatory activation, and that this response is impaired in peripheral macrophages and phagocytes in brain white matter lesions in MS patients. The pharmacological targeting of VLCFA metabolism and peroxisomes in innate immune cells could be favorable in the context of neuroinflammation and neurodegeneration. We previously identified the epigenetic histone deacetylase (HDAC) inhibitors entinostat and vorinostat to enhance VLCFA degradation and pro-regenerative macrophage polarization. However, adverse side effects currently limit their use in chronic neuroinflammation. Here, we focused on tefinostat, a monocyte/macrophage-selective HDAC inhibitor that has shown reduced toxicity in clinical trials. By using a gene expression analysis, peroxisomal ß-oxidation assay, and live imaging of primary human macrophages, we assessed the efficacy of tefinostat in modulating VLCFA metabolism, phagocytosis, chemotaxis, and immune function. Our results revealed the significant stimulation of VLCFA degradation with the upregulation of genes involved in peroxisomal ß-oxidation and interference with immune cell recruitment; however, tefinostat was less potent than the class I HDAC-selective inhibitor entinostat in promoting a regenerative macrophage phenotype. Further research is needed to fully explore the potential of class I HDAC inhibition and downstream targets in the context of neuroinflammation.

Exploring the effect of prenatal maternal stress on the microbiomes of mothers and infants: A systematic review.

Prenatal maternal stress (PNMS)-characterized by exposure to stress, anxiety, depression, or intimate partner violence-has been linked to biological alterations in infants, including disruptions to their intestinal microbiota, which have long-term implications for children's developmental outcomes. Significant research has been done examining the effects of PNMS on the microbiome in animals, but less is known about these effects in human research. The current systematic review aimed to synthesize current findings on the association between PNMS and mother and infant microbiomes. Medline, Embase, PsycInfo, Web of Science, and Eric databases were searched through to February 2022. A total of eight studies (n = 2219 infants, 2202 mothers) were included in the qualitative synthesis. Findings provided promising evidence of the role that PNMS plays in altering the microbial composition, diversity, and gut immunity in mothers and infants. Notably, majority of included studies found that higher PNMS was linked to increases in genera from the phylum Proteobacteria. The factors influencing these effects are explored including nutrition, birth mode, and parenting behaviors. Potential interventions to mitigate the adverse effects of PNMS are discussed, along with recommendations for future studies with longitudinal designs to better understand the appropriate type and timing of interventions needed to promote "healthy" maternal and infant microbial functioning.

A film-based intervention to reduce child maltreatment among migrant and displaced families from Myanmar: Protocol of a pragmatic cluster randomized controlled trial.

BACKGROUND: Child maltreatment is a global public health crisis with negative consequences for physical and mental health. Children in low- and middle-income countries (LMIC)-particularly those affected by poverty, armed conflict, and forced migration-may be at increased risk of maltreatment due to heightened parental distress and disruptions to social support networks. Parenting interventions have been shown to reduce the risk of child maltreatment as well as improve a range of caregiver and child outcomes, yet large-scale implementation remains limited in low-resource displacement settings. This study will examine the impact of an entertainment-education narrative film intervention on reducing physical and emotional abuse and increasing positive parenting among migrant and displaced families from Myanmar living in Thailand. METHOD: The study is a pragmatic, superiority cluster randomized controlled trial with approximately 40 communities randomized to the intervention or treatment as usual arms in a 1:1 ratio. Participating families in the intervention arm will be invited to attend a community screening of the film intervention and a post-screening discussion, as well as receive a poster depicting key messages from the film. Primary outcomes are changes in physical abuse, emotional abuse, and positive parenting behaviour. Secondary outcomes include caregiver knowledge of positive parenting, caregiver attitudes towards harsh punishment, caregiver psychological distress, and family functioning. Outcomes will be assessed at 3 time points: baseline, 4 weeks post-intervention, and 4-month follow up. A mixed methods process evaluation will be embedded within the trial to assess intervention delivery, acceptability, perceived impacts, and potential mechanisms of change. DISCUSSION: To our knowledge, this study will be the first randomized controlled trial evaluation of a film-based intervention to reduce child maltreatment among migrant and displaced families in a LMIC. An integrated knowledge translation approach will inform uptake of study findings and application to potential scale up pending evaluation results. TRIAL REGISTRATION: The study was prospectively registered with the Thai Clinical Trials Registry on 22 February 2023 (TCTR20230222005).

Automated Breast Density Assessment in MRI Using Deep Learning and Radiomics: Strategies for Reducing Inter-Observer Variability.

BACKGROUND: Accurate breast density evaluation allows for more precise risk estimation but suffers from high inter-observer variability. PURPOSE: To evaluate the feasibility of reducing inter-observer variability of breast density assessment through artificial intelligence (AI) assisted interpretation. STUDY TYPE: Retrospective. POPULATION: Six hundred and twenty-one patients without breast prosthesis or reconstructions were randomly divided into training (N = 377), validation (N = 98), and independent test (N = 146) datasets. FIELD STRENGTH/SEQUENCE: 1.5 T and 3.0 T; T1-weighted spectral attenuated inversion recovery. ASSESSMENT: Five radiologists independently assessed each scan in the independent test set to establish the inter-observer variability baseline and to reach a reference standard. Deep learning and three radiomics models were developed for three classification tasks: (i) four Breast Imaging-Reporting and Data System (BI-RADS) breast composition categories (A-D), (ii) dense (categories C, D) vs. non-dense (categories A, B), and (iii) extremely dense (category D) vs. moderately dense (categories A-C). The models were tested against the reference standard on the independent test set. AI-assisted interpretation was performed by majority voting between the models and each radiologist's assessment. STATISTICAL TESTS: Inter-observer variability was assessed using linear-weighted kappa (κ) statistics. Kappa statistics, accuracy, and area under the receiver operating characteristic curve (AUC) were used to assess models against reference standard. RESULTS: In the independent test set, five readers showed an overall substantial agreement on tasks (i) and (ii), but moderate agreement for task (iii). The best-performing model showed substantial agreement with reference standard for tasks (i) and (ii), but moderate agreement for task (iii). With the assistance of the AI models, almost perfect inter-observer variability was obtained for tasks (i) (mean κ = 0.86), (ii) (mean κ = 0.94), and (iii) (mean κ = 0.94). DATA CONCLUSION: Deep learning and radiomics models have the potential to help reduce inter-observer variability of breast density assessment. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 1.

Toward Prevention and Reduction of Alzheimer's Disease.

Different investigations lead to the urgent need to generate validated clinical protocols as a tool for medical doctors to orientate patients under risk for a preventive approach to control Alzheimer's disease. Moreover, there is consensus that the combined effects of risk factors for the disease can be modified according to lifestyle, thus controlling at least 40% of cases. The other fraction of cases are derived from candidate genes and epigenetic components as a relevant factor in AD pathogenesis. At this point, it appears to be of critical relevance the search for molecular biomarkers that may provide information on probable pathological events and alert about early detectable risks to prevent symptomatic events of the disease. These precocious detection markers will then allow early interventions of non-symptomatic subjects at risk. Here, we summarize the status and potential avenues of prevention and highlight the usefulness of biological and reliable markers for AD.

Frecuencia de eventos cardiovasculares en pacientes con lupus eritematoso sistémico / Frequency of cardiovascular events in patients with systemic lupus erythematosus

Resumen Introducción: el progreso en los tratamientos para el lupus eritematoso sistémico (LES) resultó en una disminución de la mortalidad; sin embargo, la enfermedad cardiovascular y las complicaciones infecciosas aún son las principales causas de muerte. La evidencia apoya la participación del sistema inmunológico en la generación de la placa aterosclerótica, así como su conexión con las enfermedades autoinmunes. Objetivos: describir la frecuencia de eventos cardiovasculares (ECV) en el Registro de Lupus Eritematoso Sistémico de la Sociedad Argentina de Reumatología (RELESSAR) transversal, así como sus principales factores de riesgo asociados. Materiales y métodos: estudio descriptivo y transversal para el cual se tomaron los pacientes ingresados en el registro RELESSAR transversal. Se describieron las variables sociodemográficas y clínicas, las comorbilidades, score de actividad y daño. ECV se definió como la presencia de al menos una de las siguientes patologías: enfermedad arterial periférica, cardiopatía isquémica o accidente cerebrovascular. El evento clasificado para el análisis fue aquel posterior al diagnóstico del LES. Se conformaron dos grupos macheados por edad y sexo 1:2. Resultados: 1515 pacientes mayores de 18 años participaron del registro. Se describieron 80 pacientes con ECV (5,3%). En este análisis se incluyeron 240 pacientes conformando dos grupos. La edad media fue de 47,8 (14,4) y 47,6 (14,2) en el grupo con y sin ECV respectivamente. Los pacientes con ECV tuvieron mayor duración del LES en meses, mayor índice de Charlson, mayor SLICC (Systemic Lupus International Collaborating Clinics/American College of Rheumatology), mayor frecuencia de manifestaciones neurológicas, síndrome antifosfolípido, hospitalizaciones y uso de ciclofosfamida. Las únicas variables asociadas en el análisis multivariado fueron el índice de Charlson (p=0,004) y el SLICC (p<0,001). Conclusiones: los ECV influyen significativamente en nuestros pacientes, y se asocian a mayor posibilidad de daño irreversible y comorbilidades.

Abstract Introduction: progress in treatments for systemic lupus erythematosus (SLE) has resulted in a decrease in mortality; however, cardiovascular and infectious diseases remain the leading causes of death. Evidence supports the involvement of the immune system in the generation of atherosclerotic plaque, as well as its connection to autoimmune diseases. Objectives: to describe the frequency of cardiovascular disease (CVD) in the cross-sectional RELESSAR registry, as well as its associated variables. Materials and methods: a descriptive and cross-sectional study was performed using patients admitted to the cross-sectional RELESSAR registry. Sociodemographic variables, clinical variables, comorbidities, activity and damage scores were described. CVD was defined as at least one of the following: peripheral arterial disease, ischemic heart disease, or cerebrovascular accident. All patients with at least one CVD were included in our analysis (heart attack, central nervous system vascular disease, and peripheral arteries atherosclerotic disease). The event classified for the analysis was that after the diagnosis of SLE. SLE diagnosis was previous to CVD. Two groups matched by age and sex, 1:2 were formed. Results: a total of 1515 patients older than 18 years participated in the registry. Eighty patients with CVD (5.3%) were described in the registry. Two-hundred and forty patients were included, according to two groups. The mean age was 47.8 (SD 14.4) and 47.6 (SD 14.2) in patients with and without CVD, respectively. Patients with CVD had a longer duration of SLE in months, a higher Charlson index, a higher SLICC, increased frequency of neurological manifestations, antiphospholipid syndrome, hospitalizations, and use of cyclophosphamide. The associated variables in the multivariate were the Charlson Index (p=0.004) and the SLICC (p<0.001). Conclusions: CVDs have a significant influence on our patients, being associated with a greater possibility of damage and comorbidities.