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Background/Objectives We aimed to investigate the effects of short-term hypocaloric diet-induced weight loss on DNA methylation profile in leukocytes from women with severe obesity. Methods Eleven women with morbid obesity (age: 36.9 [plus or minus] 10.3 years; BMI: 58.5 [plus or minus] 10.5 kg/m.sup.2) were assessed before and after 6 weeks of a hypocaloric dietary intervention. The participants were compared with women of average weight and the same age (age: 36.9 [plus or minus] 11.8 years; BMI: 22.5 [plus or minus] 1.6 kg/m.sup.2). Genome-wide DNA methylation analysis was performed in DNA extracted from peripheral blood leukocytes using the Infinium Human Methylation 450 BeadChip assay. Changes ([DELTA][beta]) in the methylation level of each CpGs were calculated. A threshold with a minimum value of 10%, p < 0.001, for the significant CpG sites based on [DELTA][beta] and a false discovery rate of Results Dietary intervention changed the methylation levels at 16,064 CpG sites. These CpGs sites were related to cancer, cell cycle-related, MAPK, Rap1, and Ras signaling pathways. However, regardless of hypocaloric intervention, a group of 878 CpGs (related to 649 genes) remained significantly altered in obese women when compared with normal-weight women. Pathway enrichment analysis identified genes related to the cadherin and Wnt pathway, angiogenesis signaling, and p53 pathways by glucose deprivation. Conclusion A short-term hypocaloric intervention in patients with severe obesity partially restored the obesity-related DNA methylation pattern. Thus, the full change of obesity-related DNA methylation patterns could be proportional to the weight-loss rate in these patients after dietary interventions., Author(s): C. F. Nicoletti [sup.1] [sup.2], C. Cortes-Oliveira [sup.1], N. Y. Noronha [sup.1], M. A. S. Pinhel [sup.1] [sup.3], W. S. Dantas [sup.2], A. Jácome [sup.4], J. S. Marchini [sup.5], [...]

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The mechanisms by which the ageing process is associated to an unhealthy lifestyle and how they play an essential role in the aetiology of systemic arterial hypertension have not yet been completely elucidated. Our objective is to investigate the influence of NOS3 polymorphisms [-786T > C and (Glu298Asp)] on systolic blood pressure (SBP) and diastolic blood pressure (DBP) response, differentially methylated regions (DMRs), and physical fitness of adult and older women after a 14-week combined training intervention. The combined training was carried out for 14 weeks, performed 3 times a week, totalling 180 minutes weekly. The genotyping experiment used Illumina Infinium Global Screening Array version 2.0 (GSA V2.0) and Illumina's EPIC Infinium Methylation BeadChip. The participants were separated into SNP rs2070744 in TT (59.7 ± 6.2 years) and TC + CC (60.0 ± 5.2 years), and SNP rs17999 in GluGlu (58.8 ± 5.7 years) and GluAsp + AspAsp (61.6 ± 4.9 years). We observed an effect of time for variables BP, physical capacities, and cholesterol. DMRs related to SBP and DBP were identified for the rs2070744 and rs17999 groups pre- and decreased numbers of DMRs post-training. When we analysed the effect of exercise training in pre- and post-comparisons, the GluGlu SNP (rs17999) showed 10 DMRs, and after enrichment, we identified several biological biases. The combined training improved the SBP and DBP values of the participants regardless of the SNPs. In addition, exercise training affected DNA methylation differently between the groups of NOS3 polymorphisms.

Background : Evidence suggests cheese has a favourable or neutral effect on cardiometabolic health, compared to butter. To date, studies have only considered the cheese matrix in its unmelted form, while the effect of melted cheese remains unknown. Objective : To test the effect of 6-week daily consumption of ∼40 g dairy fat, eaten in either as unmelted cheese, melted cheese, or in a fully deconstructed form, on markers of metabolic health in overweight adults aged ≥50 years of age. Design : A 6-week randomised parallel intervention, where 162 participants (43.3% male) received ∼40 g of dairy fat per day, in 1 of 3 treatments: (A) 120 g full-fat Irish grass-fed cheddar cheese, eaten in unmelted form ( n 58); (B) 120 g full-fat Irish grass-fed cheddar cheese eaten in melted form ( n 53); or (C) the equivalent components; butter (49 g), calcium caseinate powder (30 g), and Ca supplement (CaCO 3 ; 500 mg) ( n 51). Results : There was no difference in weight, fasting glucose, or insulin between the groups post-intervention. Melted cheese, compared to unmelted cheese, increased total cholesterol (0.23 ± 0.79 mmol L -1 vs . 0.02 ± 0.67 mmol L -1 , P = 0.008) and triglyceride concentrations (0.17 ± 0.39 mmol L -1 vs . 0.00 ± 0.42 mmol L -1 , P = 0.016). Melted cheese increased total cholesterol concentrations by 0.20 ± 0.15 mmol L -1 and triglyceride concentrations by 0.17 ± 0.08 mmol L -1 compared to unmelted cheese. No significant differences were observed between the cheese forms for change in HDL, LDL or VLDL cholesterol. Conclusion : Compared to unmelted cheese, melted cheese was found to increase total cholesterol and triglyceride concentrations in middle-aged, overweight adults with no effect on weight or glycaemic control.

Bovine dairy foods provide several essential nutrients. Fermented bovine dairy foods contain additional compounds, increasing their potential to benefit gastrointestinal health. This review explores the effects of dairy consumption on the gut microbiome and symptoms in gastrointestinal disease cohorts. Human subjects with common gastrointestinal diseases (functional gastrointestinal disorders and inflammatory bowel disease) or associated symptoms, and equivalent animal models were included. A systematic literature search was performed using PubMed, Embase and Web of Science. The search yielded 3014 studies in total, with 26 meeting inclusion criteria, including 15 human studies (1550 participants) and 11 animal studies (627 subjects). All test foods were fermented bovine dairy products, primarily fermented milk and yogurt. Six studies reported increases in gastrointestinal bacterial alpha diversity, with nine studies reporting increases in relative Lactobacillus and Bifidobacterium abundance. Six studies reported increases in beneficial short-chain fatty acids, while three reported decreases. Gastrointestinal symptoms, specifically gut comfort and defecation frequency, improved in 14 human studies. Five animal studies demonstrated reduced colonic damage and improved healing. This review shows fermented bovine dairy consumption may improve gut microbial characteristics and gastrointestinal symptoms in gastrointestinal disease cohorts. Further human intervention studies are needed, expanding test foods and capturing non-self-reported gastrointestinal measures., Competing Interests: The authors declare none., (© The Author(s) 2024.)

The hypomethylating agent 5-azacytidine (AZA) is the first-line treatment for AML patients unfit for intensive chemotherapy. The effect of AZA results in part from T-cell cytotoxic responses against MHC-I-associated peptides (MAPs) deriving from hypermethylated genomic regions such as cancer-testis antigens (CTAs), or endogenous retroelements (EREs). However, evidence supporting higher ERE MAPs presentation after AZA treatment is lacking. Therefore, using proteogenomics, we examined the impact of AZA on the repertoire of MAPs and their source transcripts. AZA-treated AML upregulated both CTA and ERE transcripts, but only CTA MAPs were presented at greater levels. Upregulated ERE transcripts triggered innate immune responses against double-stranded RNAs but were degraded by autophagy, and not processed into MAPs. Autophagy resulted from the formation of protein aggregates caused by AZA-dependent inhibition of DNMT2. Autophagy inhibition had an additive effect with AZA on AML cell proliferation and survival, increased ERE levels, increased pro-inflammatory responses, and generated immunogenic tumor-specific ERE-derived MAPs. Finally, autophagy was associated with a lower abundance of CD8 + T-cell markers in AML patients expressing high levels of EREs. This work demonstrates that AZA-induced EREs are degraded by autophagy and shows that inhibiting autophagy can improve the immune recognition of AML blasts in treated patients., (© 2024. The Author(s).)

Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) have shown increasing therapeutic potential in the last years. However, large production of EV is required for therapeutic purposes. Thereby, scaling up MSC cultivation in bioreactors is essential to allow culture parameters monitoring. In this study, we reported the establishment of a scalable bioprocess to produce MSC-EV in suspension cultures using spinner flasks and human collagen-coated microcarriers (3D culture system). We compared the EV production in this 3D culture system with the standard static culture using T-flasks (2D culture system). The EV produced in both systems were characterized and quantify by western blotting and nanoparticle tracking analysis. The presence of the typical protein markers CD9, CD63, and CD81 was confirmed by western blotting analyses for EV produced in both culture systems. The cell fold-increase was 5.7-fold for the 3D culture system and 4.6-fold for the 2D culture system, signifying a fold-change of 1.2 (calculated as the ratio of fold-increase 3D to fold-increase 2D). Furthermore, it should be noted that the total cell production in the spinner flask cultures was 4.8 times higher than that in T-flask cultures. The total cell production in the spinner flask cultures was 5.2-fold higher than that in T-flask cultures. While the EV specific production (particles/cell) in T-flask cultures (4.40 ± 1.21 × 10 8 particles/mL, p < 0.05) was higher compared to spinner flask cultures (2.10 ± 0.04 × 10 8 particles/mL, p < 0.05), the spinner flask culture system offers scalability, making it capable of producing enough MSC-EV at a large scale for clinical applications. Therefore, we concluded that 3D culture system evaluated here serves as an efficient transitional platform that enables the scaling up of MSC-EV production for therapeutic purposes by utilizing stirred tank bioreactors and maintaining xeno-free conditions., (© 2024 American Institute of Chemical Engineers.)

Background: Management of congenital hemophilia A and B is by prophylactic or on-demand replacement therapy with clotting factor concentrates. The effects of newer non-clotting factor therapies such as emicizumab, concizumab, marstacimab, and fitusiran compared with existing standards of care are yet to be systematically reviewed., Objectives: To assess the effects (clinical, economic, patient-reported, and adverse outcomes) of non-clotting factor therapies for preventing bleeding and bleeding-related complications in people with congenital hemophilia A or B compared with prophylaxis with clotting factor therapies, bypassing agents, placebo, or no prophylaxis., Search Methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, electronic databases, conference proceedings, and reference lists of relevant articles and reviews. The date of the last search was 16 August 2023., Selection Criteria: Randomized controlled trials (RCTs) evaluating people with congenital hemophilia A or B with and without inhibitors, who were treated with non-clotting factor therapies to prevent bleeds., Data Collection and Analysis: Two review authors independently reviewed studies for eligibility, assessed risk of bias, and extracted data for the primary outcomes (bleeding rates, health-related quality of life (HRQoL), adverse events) and secondary outcomes (joint health, pain scores, and economic outcomes). We assessed the mean difference (MD), risk ratio (RR), 95% confidence interval (CI) of effect estimates, and evaluated the certainty of the evidence using GRADE., Main Results: Six RCTs (including 397 males aged 12 to 75 years) were eligible for inclusion. Prophylaxis versus on-demand therapy in people with inhibitors Four trials (189 participants) compared emicizumab, fitusiran, and concizumab with on-demand therapy in people with inhibitors. Prophylaxis using emicizumab likely reduced annualized bleeding rates (ABR) for all bleeds (MD -22.80, 95% CI -37.39 to -8.21), treated bleeds (MD -20.40, 95% CI -35.19 to -5.61), and annualized spontaneous bleeds (MD -15.50, 95% CI -24.06 to -6.94), but did not significantly reduce annualized joint and target joint bleeding rates (AjBR and AtjBR) (1 trial; 53 participants; moderate-certainty evidence). Fitusiran also likely reduced ABR for all bleeds (MD -28.80, 95% CI -40.07 to -17.53), treated bleeds (MD -16.80, 95% CI -25.80 to -7.80), joint bleeds (MD -12.50, 95% CI -19.91 to -5.09), and spontaneous bleeds (MD -14.80, 95% CI -24.90 to -4.71; 1 trial; 57 participants; moderate-certainty evidence). No evidence was available on the effect of bleed prophylaxis using fitusiran versus on-demand therapy on AtjBR. Concizumab may reduce ABR for all bleeds (MD -12.31, 95% CI -19.17 to -5.45), treated bleeds (MD -10.10, 95% CI -17.74 to -2.46), joint bleeds (MD -9.55, 95% CI -13.55 to -5.55), and spontaneous bleeds (MD -11.96, 95% CI -19.89 to -4.03; 2 trials; 78 participants; very low-certainty evidence), but not target joint bleeds (MD -1.00, 95% CI -3.26 to 1.26). Emicizumab prophylaxis resulted in an 11.31-fold increase, fitusiran in a 12.5-fold increase, and concizumab in a 1.59-fold increase in the proportion of participants with no bleeds. HRQoL measured using the Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL) physical and total health scores was improved with emicizumab, fitusiran, and concizumab prophylaxis (low-certainty evidence). Non-serious adverse events were higher with non-clotting factor therapies versus on-demand therapy, with injection site reactions being the most frequently reported adverse events. Transient antidrug antibodies were reported for fitusiran and concizumab. Prophylaxis versus on-demand therapy in people without inhibitors Two trials (208 participants) compared emicizumab and fitusiran with on-demand therapy in people without inhibitors. One trial assessed two doses of emicizumab (1.5 mg/kg weekly and 3.0 mg/kg bi-weekly). Fitusiran 80 mg monthly, emicizumab 1.5 mg/kg/week, and emicizumab 3.0 mg/kg bi-weekly all likely resulted in a large reduction in ABR for all bleeds, all treated bleeds, and joint bleeds. AtjBR was not reduced with either of the emicizumab dosing regimens. The effect of fitusiran prophylaxis on target joint bleeds was not assessed. Spontaneous bleeds were likely reduced with fitusiran (MD -20.21, 95% CI -32.12 to -8.30) and emicizumab 3.0 mg/kg bi-weekly (MD -15.30, 95% CI -30.46 to -0.14), but not with emicizumab 1.5 mg/kg/week (MD -14.60, 95% CI -29.78 to 0.58). The percentage of participants with zero bleeds was higher following emicizumab 1.5 mg/kg/week (50% versus 0%), emicizumab 3.0 mg/kg bi-weekly (40% versus 0%), and fitusiran prophylaxis (40% versus 5%) compared with on-demand therapy. Emicizumab 1.5 mg/kg/week did not improve Haem-A-QoL physical and total health scores, EQ-5D-5L VAS, or utility index scores (low-certainty evidence) when compared with on-demand therapy at 25 weeks. Emicizumab 3.0 mg/kg bi-weekly may improve HRQoL measured by the Haem-A-QoL physical health score (MD -15.97, 95% CI -29.14 to -2.80) and EQ-5D-5L VAS (MD 9.15, 95% CI 2.05 to 16.25; 1 trial; 43 participants; low-certainty evidence). Fitusiran may result in improved HRQoL shown as a reduction in Haem-A-QoL total score (MD -7.06, 95% CI -11.50 to -2.62) and physical health score (MD -19.75, 95% CI -25.76 to -11.94; 1 trial; 103 participants; low-certainty evidence). The risk of serious adverse events in participants without inhibitors also likely did not differ following prophylaxis with either emicizumab or fitusiran versus on-demand therapy (moderate-certainty evidence). Transient antidrug antibodies were reported in 4% (3/80) participants to fitusiran, with no observed effect on antithrombin lowering. A comparison of the different dosing regimens of emicizumab identified no differences in bleeding, safety, or patient-reported outcomes. No case of treatment-related cancer or mortality was reported in any study group. None of the included studies assessed our secondary outcomes of joint health, clinical joint function, and economic outcomes. None of the included studies evaluated marstacimab., Authors' Conclusions: Evidence from RCTs shows that prophylaxis using non-clotting factor therapies compared with on-demand treatment may reduce bleeding events, increase the percentage of individuals with zero bleeds, increase the incidence of non-serious adverse events, and improve HRQoL. Comparative assessments with other prophylaxis regimens, assessment of long-term joint outcomes, and assessment of economic outcomes will improve evidence-based decision-making for the use of these therapies in bleed prevention., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Telemedicine includes the delivery of health-care services and sharing of health information across distances. Past research has found that telemedicine can play a role in enhancing complementary, alternative, and integrative medicine (CAIM) while allowing the maintenance of cultural values and ancestral knowledge. This scoping review synthesized evidence regarding the use of telemedicine in the context of CAIM., Methods: Following Arksey and O'Malley's scoping review framework, CINAHL, PsycINFO, MEDLINE, EMBASE and AMED databases were searched systematically. The CADTH website was also searched for grey literature. Eligible articles included a CAIM practice or therapy offered through telemedicine, with no restrictions placed on the type of telemedicine technology used. Inductive thematic analysis was conducted to synthesise common themes among the included studies., Results: Sixty-two articles were included in this synthesis. The following themes emerged: 1) the practitioner view of CAIM delivered through telemedicine, 2) the patient view of CAIM delivered through telemedicine, and 3) the technological impacts of telemedicine delivery of CAIM., Conclusions: Studies have shown that telemedicine delivery of CAIM is feasible, acceptable, and results in positive health outcomes. Some barriers remain such as the presence of chronic illness and morbidity, inability to form strong patient-provider relationships relative to face-to-face approaches, and technological difficulties. Future intervention research should focus on reducing such barriers, as well as explore which patient population would realize the greatest benefit from CAIM delivered via telemedicine, and the impact of interventions on providers and caregivers., (© 2023. The Author(s).)

Background: Sexual exploitation of children (SEC) is a widespread crime which impacts the child victim across developmental, health and well-being domains. As victims, boys have received much less clinical and research attention. While context-specific factors likely shape the SEC risk, under-recognized gender norms can deny boys' vulnerability. Professional failures to recognize and respond adequately to boys' sexual exploitation may prevent access to support., Objective: This systematic scoping review updates and broadens a previous review of literature addressing prevalence, victim/offender/facilitator characteristics, control mechanisms, as well as the health correlates and outcomes regarding sexual exploitation of boys. This review included international peer-reviewed and gray literature from 38 countries in 14 languages., Participants and Setting: Studies from the years 2000 to 2022 that included samples of boys under age 18, or sex-disaggregated data for children under 18, were included. Case studies, systematic reviews, and those reporting on retrospective experiences by adults over 18 were excluded. A total of 254,744 boys were represented across 81 studies., Methods: A systematic scoping review considered qualitative and quantitative peer-reviewed publications from eight, English-language databases. English and non-English non-peer reviewed publications ('gray literature') was identified by both ECPAT International's global network of member organizations and citation chaining., Results: Overall, 81 peer-reviewed (n = 51) and gray literature (n = 30) documents from 38 countries were included. In total, 254,744 youth participated in peer-reviewed studies (N = 217,726) and gray literature (N = 37,018). General prevalence of sexual exploitation of boys was reported at up to 5 %, with higher rates noted in specifically vulnerable sub-populations (e.g., 10 %, trans youth; 26 %, street-connected youth). The literature indicates that sexual exploitation of boys is reported as occurring primarily between 12 and 18 years old. Multi-level factors are linked to SEC, including individual (e.g., disability status), relationship (e.g., child maltreatment, dating violence), community (e.g., community violence), and societal domains (e.g., discriminatory beliefs). SEC victimization is linked with youth mental and physical health concerns, particularly sexual health. Post-traumatic stress symptomatology or disorder was rarely evaluated. Evidence-based treatments were not available, which may be related to a lack of gender-based theoretical models for understanding SEC specifically., Conclusion: The sexual exploitation of boys is a prevalent public health, child rights, and clinical issue. All young people experiencing sexual exploitation face sex- and gender-specific challenges, and this remains the case for boys with indications including family rejection, implicit community tolerance for abuse to service accessibility barriers. Actioning our duty to care for all children requires gender- and trauma-informed lenses. Ongoing surveillance of all forms of violence against children, with gender disaggregation, is essential for practice and policy advancement., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The impact of dietary factors on glycaemic control in type 2 diabetes mellitus (T2DM) is well established. However, the effectiveness of transforming portion control into a practical innovation for glycaemic control in T2DM has not yet been established for counselling in nutrition. The aim of this study was to compare the effect of general counselling in nutrition (GCN) and a portioned meal box (PMB) on fasting blood glucose, glycated haemoglobin (HbA1c) and body composition., Methods: A randomised, parallel intervention trial was conducted over 12 weeks, with GCN: carbohydrate portion control concept by using food exchange lists ( n  = 25) and PMB: portioned meal box was set by energy requirements ( n  = 25)., Results: Both GCN and PMB demonstrated reductions in HbA1c levels at the 6th and 12th weeks compared to baseline. However, no significant difference in HbA1c was observed between GCN and PMB at either the 6th or 12th week. Using PMB at least four times a week significantly decreased HbA1c during the intervention period ( p  = 0.021 and p  < 0.001 for weeks 6 and 12 when compared with baseline, respectively). Changes in body composition were observed: body weight decrease in PMB only, body fat decrease and constant muscle mass in both groups. Both methods tended to relieve hunger and increased satiety in both groups. The satisfaction evaluation showed that participants preferred to use PMB over GCN ( p  = 0.001). Additionally, participants consumed less energy, carbohydrate and fat in PMB ( p  = 0.001, p  = 0.019, and p  = 0.001, respectively) and less energy and fat in GCN ( p  = 0.006 and p  = 0.001, respectively)., Conclusion: A better diet, either through GCN or PMB, can play an important role in improving dietary intake compliance and controlling blood glucose., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer LN declared a shared parent affiliation with the authors NY, LW, CN to the handling editor at time of review., (Copyright © 2023 Maneesing, Dawangpa, Chaivanit, Songsakul, Prasertsri, Yumi Noronha, Watanabe, Nonino, Pratumvinit and Sae-Lee.)

Previous reports showed that mouse vaccination with pluripotent stem cells (PSCs) induces durable anti-tumor immune responses via T cell recognition of some elusive oncofetal epitopes. We characterize the MHC I-associated peptide (MAP) repertoire of human induced PSCs (iPSCs) using proteogenomics. Our analyses reveal a set of 46 pluripotency-associated MAPs (paMAPs) absent from the transcriptome of normal tissues and adult stem cells but expressed in PSCs and multiple adult cancers. These paMAPs derive from coding and allegedly non-coding (48%) transcripts involved in pluripotency maintenance, and their expression in The Cancer Genome Atlas samples correlates with source gene hypomethylation and genomic aberrations common across cancer types. We find that several of these paMAPs were immunogenic. However, paMAP expression in tumors coincides with activation of pathways instrumental in immune evasion (WNT, TGF-β, and CDK4/6). We propose that currently available inhibitors of these pathways could synergize with immune targeting of paMAPs for the treatment of poorly differentiated cancers., Competing Interests: Declaration of interests A.A., M.-P.H., P.T., and C.P. are named inventors on a patent application filed by Université de Montréal and covering antigens described in this article., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Pre-diabetes precedes Diabetes Mellitus (DM) disease and is a critical period for hyperglycemia treatment, especially for menopausal women, considering all metabolic alterations due to hormonal changes. Recently, the literature has demonstrated the role of physical exercise in epigenetic reprogramming to modulate the gene expression patterns of metabolic conditions, such as hyperglycemia, and prevent DM development. In the present study, we hypothesized that physical exercise training could modify the epigenetic patterns of women with poor glycemic control., Methods: 48 post-menopause women aged 60.3 ± 4.5 years were divided according to their fasting blood glucose levels into two groups: Prediabetes Group, PG (n=24), and Normal Glucose Group, NGG (n=24). All participants performed 14 weeks of physical exercise three times a week. The Infinium Methylation EPIC BeadChip measured the participants' Different Methylated Regions (DMRs)., Results: Before the intervention, the PG group had 12 DMRs compared to NGG. After the intervention, five DMRs remained different. Interestingly, when comparing the PG group before and after training, 118 DMRs were found. The enrichment analysis revealed that the genes were related to different biological functions such as energy metabolism, cell differentiation, and tumor suppression., Conclusion: Physical exercise is a relevant alternative in treating hyperglycemia and preventing DM in post-menopause women with poor glycemic control., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yumi Noronha, da Silva Rodrigues, Harumi Yonehara Noma, Fernanda Cunha Brandao, Pereira Rodrigues, Colello Bruno, Sae-Lee, Moriguchi Watanabe, Augusta de Souza Pinhel, Mello Schineider, Luciano de Almeida, Barbosa Júnior, Araújo Morais, Tavares de Sousa Júnior, Plösch, Roberto Bueno Junior and Barbosa Nonino.)

Elevated intakes of saturated fatty acids (SFA) can adversely affect serum cholesterol levels. Dairy fat contains ~60% SFA, prompting healthy eating guidelines to recommend low-fat dairy. Physiological, and environmental factors influence inter-individual variance in response to food consumption. Evidence exploring the dairy matrix has differing effects of dairy fat consumption on serum cholesterol levels when consumed in the form of cheese. The extent of this variability and determinants of response to dairy fat are currently unknown. The objective of this study was to determine factors associated with lipid metabolism response to a dairy fat intervention, with a focus on serum cholesterol. A 6-week randomized parallel intervention trial was carried out in healthy volunteers (≥50 years, BMI ≥25 kg/m 2 ). Participants ( n = 104) consumed ~40 g dairy fat daily in addition to their usual diet, in 1 of 3 forms: butter, cheese, or reduced-fat cheese and butter. For this analysis, "response" was based on the percentage (%) change in serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) from pre- to post-intervention. Participants were divided into tertiles for each lipid response. The upper and lower tertiles were used to categorize participants as "responders" and "non-responders." For TC and LDL-c, response was classified as a decrease, whereas "response" was defined as an increase for HDL-c. Clinical response was also considered, by calculating pre- and post-intervention prevalence of those meeting target levels of cholesterol recommendations. Participants demonstrating the largest % decrease (Tertile 1; "responders") in TC had significantly higher levels of TC and HDL-c, at baseline, and lower levels of triglycerides (TAGs) compared to those in tertile 3 (i.e., TC non-responders). Those with the largest % decrease in LDL-c (Tertile 1: LDL-c responders) had higher baseline levels of LDL-c and lower levels of TAGs. Multiple regression analysis revealed that the % change in TC and LDL-c was associated with baseline TC, TAG, body weight and high-sensitivity C-reactive protein (hsCRP; P < 0.05). Previous work has demonstrated the dairy food matrix affects lipid response to dairy consumption. This study suggests that phenotypic differences may also influence response to dairy fat in overweight individuals., Competing Interests: Authors EG, AO'C, and EF have previously received travel expenses and/or speaking honoraria from the National Dairy Council, UK, USA and Norway. Authors EG, AO'C, and EF have received research funding through the Food for Health Ireland project, funded by Enterprise Ireland, grant numbers TC-2013-001 and TC20180025. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 O'Connor, Feeney, Bhargava, Noronha and Gibney.)

Background: Knowledge about the risk for bleeding in patients with hemophilia (PWH) would be relevant for patients, stakeholders, and policy makers., Objectives: To perform a systematic review of the literature on risk assessment models (RAMs) and risk factors for bleeding in PWH on regular prophylaxis., Methods: We searched Medline, Embase, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews from inception through August 2019. In duplicate, reviewers screened the articles for inclusion, extracted data, and assessed the risk for bias using the Quality in Prognostic Studies (QUIPS) tool. A qualitative synthesis of the results was not performed due to high heterogeneity in risk factors, outcomes definition and measurement, and statistical analysis of the results., Results: From 1843 search results, 10 studies met the inclusion criteria. No RAM for the risk for bleeding in PWH was found. Most studies included only PWH A or both PWH A and B and were conducted in North America or Europe. Only one study had a low risk for bias in all the domains. Eight categories of risk factors were identified. The risk for bleeding was increased when factor levels were lower and in people with a significant history of bleeding or who engaged in physical activities involving contact., Conclusions: Our findings suggest that plasma factor levels, history of bleeds, and physical activity should be considered for the derivation analysis when building a RAM for bleeding in PWH, and the role of other risk factors, including antithrombotic treatment and obesity, should be explored., (© 2022 International Society on Thrombosis and Haemostasis.)

We present an uncommon challenging case of spontaneous thrombosis of the arterial duct and with alloimmune thrombocytopaenia in a full-term newborn who presented with respiratory distress, hypoglycaemia dispersed petechiae on the trunk, and significant haemorrhage of the umbilical venous catheter.

Cholesterol homeostasis has been proposed as one mechanism contributing to chemoresistance in AML and hence, inclusion of statins in therapeutic regimens as part of clinical trials in AML has shown encouraging results. Chemical screening of primary human AML specimens by our group led to the identification of lipophilic statins as potent inhibitors of AMLs from a wide range of cytogenetic groups. Genetic screening to identify modulators of the statin response uncovered the role of protein geranylgeranylation and of RAB proteins, coordinating various aspect of vesicular trafficking, in mediating the effects of statins on AML cell viability. We further show that statins can inhibit vesicle-mediated transport in primary human specimens, and that statins sensitive samples show expression signatures reminiscent of enhanced vesicular trafficking. Overall, this study sheds light into the mechanism of action of statins in AML and identifies a novel vulnerability for cytogenetically diverse AML., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Numerous wrist-wearable devices to measure physical activity are currently available, but there is a need to unify the evidence on how they compare in terms of acceptability and accuracy., Objective: The aim of this study is to perform a systematic review of the literature to assess the accuracy and acceptability (willingness to use the device for the task it is designed to support) of wrist-wearable activity trackers., Methods: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and SPORTDiscus for studies measuring physical activity in the general population using wrist-wearable activity trackers. We screened articles for inclusion and, for the included studies, reported data on the studies' setting and population, outcome measured, and risk of bias., Results: A total of 65 articles were included in our review. Accuracy was assessed for 14 different outcomes, which can be classified in the following categories: count of specific activities (including step counts), time spent being active, intensity of physical activity (including energy expenditure), heart rate, distance, and speed. Substantial clinical heterogeneity did not allow us to perform a meta-analysis of the results. The outcomes assessed most frequently were step counts, heart rate, and energy expenditure. For step counts, the Fitbit Charge (or the Fitbit Charge HR) had a mean absolute percentage error (MAPE) <25% across 20 studies. For heart rate, the Apple Watch had a MAPE <10% in 2 studies. For energy expenditure, the MAPE was >30% for all the brands, showing poor accuracy across devices. Acceptability was most frequently measured through data availability and wearing time. Data availability was ≥75% for the Fitbit Charge HR, Fitbit Flex 2, and Garmin Vivofit. The wearing time was 89% for both the GENEActiv and Nike FuelBand., Conclusions: The Fitbit Charge and Fitbit Charge HR were consistently shown to have a good accuracy for step counts and the Apple Watch for measuring heart rate. None of the tested devices proved to be accurate in measuring energy expenditure. Efforts should be made to reduce the heterogeneity among studies., (©Federico Germini, Noella Noronha, Victoria Borg Debono, Binu Abraham Philip, Drashti Pete, Tamara Navarro, Arun Keepanasseril, Sameer Parpia, Kerstin de Wit, Alfonso Iorio. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 21.01.2022.)

Relative to non-Indigenous youth, Indigenous youth have been under-represented when studying pathways to mental wellness. Yet, a broad range of adversity is acknowledged, from intergenerational and ongoing trauma arising from colonial policies. This scoping review explores resilience definitions, measures, key stressors, and what Indigenous youth identify as pathways to their wellness, based on quantitative and qualitative peer-reviewed literature in Canada and the Continental United States. Eight databases ( EBSCO , PsycINFO , Science Direct , Social Science Citation Index , Web of Science , PsycARTICLES , and EMBASE ) and hand searches of 7 relevant journals were conducted to ensure literature coverage. Two independent reviewers screened each article, with one Indigenous screener per article. The final scoping review analysis included 44 articles. In articles, no Indigenous term for resilience was found, but related concepts were identified ("walking a good path," "good mind," Grandfathers' teachings on 7 values, decision-making for 7 generations into the future, etc.). Few Indigenous-specific measures of resilience exist, with studies relying on Western measures of psychological resilience. Qualitative approaches supporting youth-led resilience definitions yielded important insights. Youth stressors included the following: substance use, family instability, and loss of cultural identity. Youth resilience strategies included the following: having a future orientation, cultural pride, learning from the natural world, and interacting with community members (e.g., relationship with Elders, being in community and on the land). Indigenous traditional knowledge and cultural continuity serve as prominent pathways to Indigenous youth resilience. More research is needed to yield a holistic, youth-centered measure of resilience that includes traditional practices., Competing Interests: Competing InterestsThe authors declare no competing interests., (© The Author(s) 2022.)