Does the use of higher versus lower oxygen concentration improve neurodevelopmental outcomes at 18-24 months in very low birthweight infants?

BACKGROUND: Immediately after birth, the oxygen saturation is between 30 and 50%, which then increases to 85-95% within the first 10 min. Over the last 10 years, recommendations regarding the ideal level of the initial fraction of inspired oxygen (FiO2) for resuscitation in preterm infants have changed from 1.0, to room air to low levels of oxygen (< 0.3), up to moderate concentrations (0.3-0.65). This leaves clinicians in a challenging position, and a large multi-center international trial of sufficient sample size that is powered to look at safety outcomes such as mortality and adverse neurodevelopmental outcomes is required to provide the necessary evidence to guide clinical practice with confidence. METHODS: An international cluster, cross-over randomized trial of initial FiO2 of 0.3 or 0.6 during neonatal resuscitation in preterm infants at birth to increase survival free of major neurodevelopmental outcomes at 18 and 24 months corrected age will be conducted. Preterm infants born between 230/7 and 286/7 weeks' gestation will be eligible. Each participating hospital will be randomized to either an initial FiO2 concentration of either 0.3 or 0.6 to recruit for up to 12 months' and then crossed over to the other concentration for up to 12 months. The intervention will be initial FiO2 of 0.6, and the comparator will be initial FiO2 of 0.3 during respiratory support in the delivery room. The sample size will be 1200 preterm infants. This will yield 80% power, assuming a type 1 error of 5% to detect a 25% reduction in relative risk of the primary outcome from 35 to 26.5%. The primary outcome will be a composite of all-cause mortality or the presence of a major neurodevelopmental outcome between 18 and 24 months corrected age. Secondary outcomes will include the components of the primary outcome (death, cerebral palsy, major developmental delay involving cognition, speech, visual, or hearing impairment) in addition to neonatal morbidities (severe brain injury, bronchopulmonary dysplasia; and severe retinopathy of prematurity). DISCUSSION: The use of supplementary oxygen may be crucial but also potentially detrimental to preterm infants at birth. The HiLo trial is powered for the primary outcome and will address gaps in the evidence due to its pragmatic and inclusive design, targeting all extremely preterm infants. Should 60% initial oxygen concertation increase survival free of major neurodevelopmental outcomes at 18-24 months corrected age, without severe adverse effects, this readily available intervention could be introduced immediately into clinical practice. TRIAL REGISTRATION: The trial was registered on January 31, 2019, at ClinicalTrials.gov with the Identifier: NCT03825835.

Is Maternal Body Weight or Composition Associated with Onset of Lactogenesis II, Human Milk Production, or Infant Consumption of Mother's Own Milk? A Systematic Review and Meta-Analysis.

Maternal adiposity impacts lactation performance, but the pathways are unclear. We conducted a systematic review to understand whether maternal adiposity (body mass index [BMI] or percentage fat mass) is associated with onset of lactogenesis II (copious milk; hours), human milk production (expressed volume/24 h), and infant consumption of mother's own milk (volume/24 h). We used random-effects standard meta-analyses to compare the relative risk (RR) of delayed lactogenesis II (>72 h) between mothers classified as underweight (BMI <18.5 kg/m2), healthy weight (BMI, 18.5-24.9 kg/m2), and overweight/obese (BMI ≥25 kg/m2) and random-effects meta-regressions to examine associations with hours to lactogenesis II and infant milk consumption. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. We included 122 articles. Mothers with underweight (RR: 0.64; 95% CI: 0.49, 0.83; I2 = 39.48%; 8 articles/data points) or healthy weight status (RR: 0.67; 95% CI: 0.57, 0.79; I2 = 70.91%; 15 articles/data points) were less likely to experience delayed lactogenesis II than mothers with overweight/obesity. We found no association between maternal BMI and time to onset of lactogenesis II (ß: 1.45 h; 95% CI: -3.19, 6.09 h; P = 0.52, I2 = 0.00%; 8 articles, 17 data points). Due to limited data, we narratively reviewed articles examining BMI or percentage fat mass and milk production (n = 6); half reported an inverse association and half no association. We found no association between maternal BMI (ß: 6.23 mL; 95% CI: -11.26, 23.72 mL; P = 0.48, I2 = 47.23%; 58 articles, 75 data points) or percentage fat mass (ß: 7.82 mL; 95% CI: -1.66, 17.29 mL; P = 0.10, I2 = 28.55%; 30 articles, 41 data points) and infant milk consumption. The certainty of evidence for all outcomes was very low. In conclusion, mothers with overweight/obesity may be at risk of delayed lactogenesis II. The available data do not support an association with infant milk consumption, but the included studies do not adequately represent mothers with obesity. This study was registered in PROSPERO as 285344.

Local manufacturing processes contribute to variability in human mesenchymal stromal cell expansion while growth media supplements contribute to variability in gene expression and cell function: a Biomedical Excellence for Safer Transfusion (BEST) collaborative study.

BACKGROUND AIMS: Culture-derived mesenchymal stromal cells (MSCs) exhibit variable characteristics when manufactured using different methods, source material and culture media. The purpose of this multicenter study was to assess the impact on MSC expansion, gene expression and other characteristics when different laboratories expanded MSCs from cultures initiated with bone marrow-MSC aliquots derived from the same donor source material yet with different growth media. METHODS: Eight centers expanded MSCs using four human platelet lysate (HPL) and one fetal bovine serum (FBS) products as media supplements. The expanded cells were taken through two passages then assessed for cell count, viability, doubling time, immunophenotype, cell function, immunosuppression and gene expression. Results were analyzed by growth media and by center. RESULTS: Center methodologies varied by their local seeding density, feeding regimen, inoculation density, base media and other growth media features (antibiotics, glutamine, serum). Doubling times were more dependent on center than on media supplements. Two centers had appropriate immunophenotyping showing all MSC cultures were positive for CD105, CD73, CD90 and negative for CD34, CD45, CD14, HLA-DR. MSCs cultured in media supplemented with FBS compared with HPL featured greater T-cell inhibition potential. Gene expression analysis showed greater impact of the type of media supplement (HPL versus FBS) than the manufacturing center. Specifically, nine genes were decreased in expression and six increased when combining the four HPL-grown MSCs versus FBS (false discovery rate [FDR] <0.01), however, without significant difference between different sources of HPL (FDR <0.01). CONCLUSIONS: Local manufacturing process plays a critical role in MSC expansion while growth media may influence function and gene expression. All HPL and FBS products supported cell growth.

Extracellular vesicle small RNA cargo discriminates non-cancer donors from pediatric B-lymphoblastic leukemia patients.

Pediatric B-acute lymphoblastic leukemia (B-ALL) is a disease of abnormally growing B lymphoblasts. Here we hypothesized that extracellular vesicles (EVs), which are nanosized particles released by all cells (including cancer cells), could be used to monitor B-ALL severity and progression by sampling plasma instead of bone marrow. EVs are especially attractive as they are present throughout the circulation regardless of the location of the originating cell. First, we used nanoparticle tracking analysis to compare EVs between non-cancer donor (NCD) and B-ALL blood plasma; we found that B-ALL plasma contains more EVs than NCD plasma. We then isolated EVs from NCD and pediatric B-ALL peripheral blood plasma using a synthetic peptide-based isolation technique (Vn96), which is clinically amenable and isolates a broad spectrum of EVs. RNA-seq analysis of small RNAs contained within the isolated EVs revealed a signature of differentially packaged and exclusively packaged RNAs that distinguish NCD from B-ALL. The plasma EVs contain a heterogenous mixture of miRNAs and fragments of long non-coding RNA (lncRNA) and messenger RNA (mRNA). Transcripts packaged in B-ALL EVs include those involved in negative cell cycle regulation, potentially suggesting that B-ALL cells may use EVs to discard gene sequences that control growth. In contrast, NCD EVs carry sequences representative of multiple organs, including brain, muscle, and epithelial cells. This signature could potentially be used to monitor B-ALL disease burden in pediatric B-ALL patients via blood draws instead of invasive bone marrow aspirates.

The SickKids Caribbean Initiative to improve care for children with cancer and blood disorders.

To improve pediatric hematology and oncology outcomes, there is a recognized potential for partnerships between low- and high-resource institutions within health care systems. The SickKids Caribbean Initiative is a partnership between health care professionals at the Hospital for Sick Children in Toronto, Canada, and seven Caribbean institutions across six countries (Bahamas, Barbados, Jamaica, Saint Lucia, Saint Vincent and the Grenadines, and Trinidad and Tobago). The primary aim of the SickKids Caribbean Initiative has been to improve the outcomes and the quality of life of children in the Caribbean aged <18 years who have cancer and blood disorders. This article describes five key activities undertaken within the SickKids Caribbean Initiative, including providing education and training, assisting with case consultations and diagnostic services, developing local oncology databases, engaging in advocacy and ensuring stakeholder engagement, and coordinating administration and project management.

Las colaboraciones de instituciones de recursos bajos y altos dentro de los sistemas de atención de salud tienen un potencial reconocido para mejorar las respuestas a los tratamientos hematológicos y oncológicos pediátricos. La iniciativa SickKids para el Caribe es una asociación entre profesionales de la salud del Hospital for Sick Children de Toronto (Canadá) y siete instituciones de seis países del Caribe (Bahamas, Barbados, Jamaica, Santa Lucía, San Vicente y las Granadinas y Trinidad y Tabago). El objetivo principal de la iniciativa SickKids para el Caribe ha sido mejorar la respuesta a los tratamientos y la calidad de vida de los menores de 18 años del Caribe con cáncer o trastornos hematológicos. En este artículo se describen cinco actividades clave emprendidas en el marco de la iniciativa SickKids para el Caribe, consistentes en impartir formación y capacitación, prestar asistencia en materia de consultas de pacientes y servicios de diagnóstico, crear bases de datos locales en el área de la oncología, participar en actividades de promoción y garantizar la participación de las partes interesadas, y coordinar la administración y gestión de proyectos.

Há um potencial reconhecido para parcerias entre instituições com poucos e muitos recursos dentro dos sistemas de saúde para melhorar os resultados de hematologia e oncologia pediátricas. A iniciativa SickKids no Caribe é uma parceria entre profissionais de saúde do Hospital for Sick Children em Toronto, Canadá, e sete instituições em seis países do Caribe (Bahamas, Barbados, Jamaica, Santa Lúcia, São Vicente e Granadinas e Trinidad e Tobago). O objetivo principal da iniciativa SickKids no Caribe tem sido melhorar os desfechos e a qualidade de vida das crianças caribenhas com menos de 18 anos que têm câncer e doenças hematológicas. Este artigo descreve cinco atividades principais realizadas no âmbito da iniciativa SickKids no Caribe: oferecimento de educação e capacitação; assistência em consultas de casos e serviços diagnósticos; desenvolvimento de bancos de dados locais em oncologia; promoção da causa, assegurando o envolvimento das partes interessadas; e coordenação da administração e da gestão de projetos.

Developing a partnership to improve health care delivery to children <18 years with cancer and blood disorders in the English-speaking Caribbean: lessons from the SickKids-Caribbean Initiative (SCI).

In 2013, the SickKids-Caribbean Initiative (SCI) was formalised among The Hospital for Sick Children in Toronto, Canada, the University of the West Indies, and Ministries of Health in six Caribbean countries (Barbados, The Bahamas, Jamaica, St. Lucia, St. Vincent and the Grenadines, and Trinidad and Tobago). The aim was to improve the outcomes and quality of life of children (<18 years) with cancer and blood disorders in the partner countries. Core activities included filling a human resource gap by training paediatric haematologists/oncologists and specialised registered nurses; improving capacity to diagnose and treat diverse haematology/oncology cases; developing and maintaining paediatric oncology databases; creating ongoing advocacy activities with international agencies, decision makers, and civil society; and establishing an integrated administration, management, and funding structure. We describe core program components, successes, and challenges to inform others seeking to improve health service delivery in a multidisciplinary and complex partnership.

The SickKids Caribbean Initiative to improve care for children with pediatric cancer and blood disorders / La iniciativa SickKids para el Caribe para mejorar la atención a pacientes pediátricos con cáncer o trastornos hematológicos / Iniciativa SickKids no Caribe: melhorar o atendimento a crianças com câncer e doenças hematológicas

[ABSTRACT]. To improve pediatric hematology and oncology outcomes, there is a recognized potential for partnerships between low and high-resource institutions within health care systems. The SickKids Caribbean Initiative is a partnership between health care professionals at the Hospital for Sick Children in Toronto, Canada, and seven Caribbean institutions across six countries (Bahamas, Barbados, Jamaica, Saint Lucia, Saint Vincent and the Grenadines, and Trinidad and Tobago). The primary aim of the SickKids Caribbean Initiative has been to improve the outcomes and the quality of life of children in the Caribbean aged <18 years who have cancer and blood disorders. This article describes five key activities undertaken within the SickKids Caribbean Initiative, including providing education and training, assisting with case consultations and diagnostic services, developing local oncology databases, engaging in advocacy and ensuring stakeholder engagement, and coordinating administration and project management.

[RESUMEN]. Las colaboraciones de instituciones de recursos bajos y altos dentro de los sistemas de atención de salud tienen un potencial reconocido para mejorar las respuestas a los tratamientos hematológicos y oncológicos pediátricos. La iniciativa SickKids para el Caribe es una asociación entre profesionales de la salud del Hospital for Sick Children de Toronto (Canadá) y siete instituciones de seis países del Caribe (Bahamas, Barbados, Jamaica, Santa Lucía, San Vicente y las Granadinas y Trinidad y Tabago). El objetivo principal de la iniciativa SickKids para el Caribe ha sido mejorar la respuesta a los tratamientos y la calidad de vida de los menores de 18 años del Caribe con cáncer o trastornos hematológicos. En este artículo se describen cinco actividades clave emprendidas en el marco de la iniciativa SickKids para el Caribe, consistentes en impartir formación y capacitación, prestar asistencia en materia de consultas de pacientes y servicios de diagnóstico, crear bases de datos locales en el área de la oncología, participar en actividades de promoción y garantizar la participación de las partes interesadas, y coordinar la administración y gestión de proyectos.

[RESUMO]. Há um potencial reconhecido para parcerias entre instituições com poucos e muitos recursos dentro dos sistemas de saúde para melhorar os resultados de hematologia e oncologia pediátricas. A iniciativa SickKids no Caribe é uma parceria entre profissionais de saúde do Hospital for Sick Children em Toronto, Canadá, e sete instituições em seis países do Caribe (Bahamas, Barbados, Jamaica, Santa Lúcia, São Vicente e Granadinas e Trinidad e Tobago). O objetivo principal da iniciativa SickKids no Caribe tem sido melhorar os desfechos e a qualidade de vida das crianças caribenhas com menos de 18 anos que têm câncer e doenças hematológicas. Este artigo descreve cinco atividades principais realizadas no âmbito da iniciativa SickKids no Caribe: oferecimento de educação e capacitação; assistência em consultas de casos e serviços diagnósticos; desenvolvimento de bancos de dados locais em oncologia; promoção da causa, assegurando o envolvimento das partes interessadas; e coordenação da administração e da gestão de projetos.

Drivers of malnutrition among late adolescent and young women in rural Pakistan: a cross-sectional assessment of the MaPPS trial.

OBJECTIVE: This study aimed to characterise the burden of malnutrition and assess how underlying determinants at the structural and intermediary levels contributed to malnutrition among late adolescent and young women in rural Pakistan. DESIGN: Cross-sectional enrolment data assessment. SETTING AND PARTICIPANTS: This study was conducted using data from adolescent and young women (n=25 447) enrolled in the Matiari emPowerment and Preconception Supplementation Trial, collected from June 2017 to July 2018 in Matiari District, Pakistan. The WHO-based cut-offs were applied to anthropometric measures to estimate body mass index (BMI) categories (underweight, overweight, obese) and stunting. Hierarchical models were generated to evaluate the association between the determinants with BMI categories and stunting among late adolescent girls and young women, respectively. PRIMARY AND SECONDARY OUTCOME MEASURES: The main outcomes of interest were BMI categories and stunting. Explanatory variables included measures of socioeconomic status, education, occupation, health, well-being, food security, empowerment and food practices. RESULTS: Regardless of age group, the prevalence of underweight was high (36.9%; 95% CI 36.3% to 37.5%). More late adolescent girls were underweight, while more young women were overweight/obese (p<0.001). Stunting affected 9.2% (95% CI 8.9% to 9.6%) of participants, of which 35.7% were additionally underweight and 7.3% overweight/obese. Compared with those in the normal weight category, those underweight were more likely to be impoverished and less empowered. Those overweight/obese were more likely to be from a higher wealth quintile and food secure. Increased education level and food security were associated with reductions stunting risk. CONCLUSIONS: This study informs the data gap and need for comprehensive research on adolescent nutritional status. Findings suggest factors related to poverty played an important, underlying role in undernutrition among participants. Commitment to improving the nutritional status of all adolescent and young women in Pakistan will be critical given the observed burden of malnutrition. TRIAL REGISTRATION NUMBER: NCT03287882.

Evaluation and management of intimate partner violence in the emergency department.

Intimate partner violence (IPV) and emergency medicine intersect when individuals experiencing IPV present to emergency departments for medical care, either on their own or when brought in by law enforcement authorities for medical evaluation and social services. Coordination of care is required, with particular attention paid to the sensitive nature of the patient's presentation and with an emphasis on trauma-informed care. Emergent medical needs must be balanced with concerns for the patient's emotional well-being and the need for advocacy and social services. This supplement reviews best practices and evidence-based recommendations for the evaluation and management of patients who have experienced IPV, with a focus on the considerations for traumatic injuries in these patients.

Extru-seq: a method for predicting genome-wide Cas9 off-target sites with advantages of both cell-based and in vitro approaches.

We present a novel genome-wide off-target prediction method named Extru-seq and compare it with cell-based (GUIDE-seq), in vitro (Digenome-seq), and in silico methods using promiscuous guide RNAs with large numbers of valid off-target sites. Extru-seq demonstrates a high validation rate and retention of information about the intracellular environment, both beneficial characteristics of cell-based methods. Extru-seq also shows a low miss rate and could easily be performed in clinically relevant cell types with little optimization, which are major positive features of the in vitro methods. In summary, Extru-seq shows beneficial features of cell-based and in vitro methods.

Effectiveness of Switching to Long-acting Injectable Aripiprazole in Patients with Recent-onset and Chronic Schizophrenia.

Objective: This study investigated the effectiveness of switching to once-monthly long-acting injectable (LAI) aripiprazole from other second-generation antipsychotics including LAI paliperidone palmitate in both recent-onset and chronic schizophrenia patients. Methods: This was a 24-week prospective, open-label, flexible dose-switching study in patients with schizophrenia. Scores on the Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance (PSP) scale, Clinical Global Impression (CGI), Subjective Well-being Under Neuroleptics-Short Form (SWN-K), and a computerized emotional recognition test (ERT) were evaluated. Subjects were divided into two groups (recent onset and chronic) based on 5 years' duration of the illness. Results: Among the 82 patients participating, 67 (81.7%) completed the 24-week study. The discontinuation rate after switching to LAI aripiprazole did not differ according to clinical characteristics including type of previous antipsychotics. Scores on the PANSS, PSP, SWN-K, CGI, and ERT were significantly improved after a switch to LAI aripiprazole without exacerbation of metabolic parameters and bodyweight. The improvements in the PANSS, PSP, and CGI scores were significantly greater in patients with recent-onset than in those with chronic schizophrenia; the improvement in metabolic parameters was significantly greater in the latter group. Conclusion: High rates of successful switching to LAI aripiprazole from other antipsychotics suggest its good tolerability and effectiveness. Improvements in psychopathology and social functioning were more evident in patients with recent- onset schizophrenia, and improvements in metabolic abnormalities were more prominent in patients with chronic schizophrenia.

Effects of Dietary Habits on General and Abdominal Obesity in Community-dwelling Patients with Schizophrenia.

Objective: To investigate the effects of dietary habits on general and abdominal obesity in community-dwelling patients with schizophrenia spectrum disorder according to sex. Methods: A total of 270 patients with schizophrenia spectrum disorder registered at mental health welfare centers and rehabilitation facilities were recruited. General obesity was defined as a body mass index ≥ 30 kg/m2, and abdominal obesity was defined as a waist circumstance ≥ 90 cm in men and ≥ 85 cm in women. Dietary habits were evaluated using dietary guidelines published by the Korean Ministry of Health and Welfare. Demographic and clinical characteristics along with dietary habits and information related to obesity were collected. Factors related to obesity were evaluated separately by sex. Results: Dietary habits differed according to sex, in that scores for healthy eating habits were lower in men than in women. In men, the prevalences of general and abdominal obesity were 17.0% and 37.3%, respectively. In women, the prevalences of general and abdominal obesity were 23.1% and 38.5%, respectively. Regression analysis showed that the scores of regular eating habits were negatively associated with general and abdominal obesity in men, and the scores of healthy eating habits were negatively associated with general and abdominal obesity in women. Conclusion: Among patients with schizophrenia, regular eating habits might reduce the risk of obesity in men, and healthy eating habits might reduce the risk of obesity in women. Nutrition education should be provided to community- dwelling patients with schizophrenia to prevent obesity in this population.

Anti-dementia medication use in Aotearoa New Zealand: An exploratory study using health data from the Integrated Data Infrastructure (IDI).

OBJECTIVE: Anti-dementia medications such as acetylcholinesterase inhibitors are an important part of the management pathway for dementia. However, there are limited data in New Zealand that have examined the rates and patterns of use of funded anti-dementia medication and how use differs with ethnicity, age and sex. METHODS: This was a retrospective population-based descriptive study. Using the Integrated Data Infrastructure, we identified individuals of all ages coded for a diagnosis of dementia and estimated the proportion dispensed funded anti-dementia medication - donepezil tablets and rivastigmine patches - between 1 July 2016 and 30 June 2020. Rates of medication use in five main ethnic groups (Maori, Pacific peoples, Asian, European, and Middle Eastern, Latin American and African) in the <65, 65-79 and 80 and over (80+) age groups were compared and also between males and females in all sub-groups. Log-binomial models were used to calculate relative risks to determine any differences in anti-dementia medication use in the five ethnic groups and the three age groups and between males and females in each of the four study years. RESULTS: Overall, one-third of the dementia population received a funded anti-dementia medication in the total population (all ages) between 2016 and 2020. Donepezil tablets were dispensed in 31.6-34.0% and rivastigmine patches in 1.4-2.1% across the four study years. Compared to people of European ethnicity, Maori, Pacific peoples, and Middle Eastern, Latin American and African groups were less likely to be dispensed an anti-dementia medication (Maori: relative risk = 0.79-0.81, p < 0.0001; Pacific peoples: relative risk = 0.72-0.74, p < 0.0001; Middle Eastern, Latin American and African: relative risk = 0.73-0.78, p < 0.05). Compared to the age 80+ group, the 65-79 age group was more likely (relative risk = 1.50-1.54, p < 0.0001), while the age <65 group was less likely (relative risk = 0.67-0.71, p < 0.0001) to be dispensed an anti-dementia medication. There were no statistically significant differences in anti-dementia medication use between males and females. CONCLUSION: This study provides important information about funded anti-dementia medication use in New Zealand and how this differs by ethnicity, age and sex. Despite higher dementia prevalence in Maori and Pacific peoples, these groups were less likely to receive funded anti-dementia medication.

The SickKids Caribbean Initiative to improve care for children with cancer and blood disorders / La iniciativa SickKids para el Caribe para mejorar la atención a pacientes pediátricos con cáncer o trastornos hematológicos / Iniciativa SickKids no Caribe: melhorar o atendimento a crianças com câncer e doenças hematológicas

ABSTRACT To improve pediatric hematology and oncology outcomes, there is a recognized potential for partnerships between low- and high-resource institutions within health care systems. The SickKids Caribbean Initiative is a partnership between health care professionals at the Hospital for Sick Children in Toronto, Canada, and seven Caribbean institutions across six countries (Bahamas, Barbados, Jamaica, Saint Lucia, Saint Vincent and the Grenadines, and Trinidad and Tobago). The primary aim of the SickKids Caribbean Initiative has been to improve the outcomes and the quality of life of children in the Caribbean aged <18 years who have cancer and blood disorders. This article describes five key activities undertaken within the SickKids Caribbean Initiative, including providing education and training, assisting with case consultations and diagnostic services, developing local oncology databases, engaging in advocacy and ensuring stakeholder engagement, and coordinating administration and project management.

RESUMEN Las colaboraciones de instituciones de recursos bajos y altos dentro de los sistemas de atención de salud tienen un potencial reconocido para mejorar las respuestas a los tratamientos hematológicos y oncológicos pediátricos. La iniciativa SickKids para el Caribe es una asociación entre profesionales de la salud del Hospital for Sick Children de Toronto (Canadá) y siete instituciones de seis países del Caribe (Bahamas, Barbados, Jamaica, Santa Lucía, San Vicente y las Granadinas y Trinidad y Tabago). El objetivo principal de la iniciativa SickKids para el Caribe ha sido mejorar la respuesta a los tratamientos y la calidad de vida de los menores de 18 años del Caribe con cáncer o trastornos hematológicos. En este artículo se describen cinco actividades clave emprendidas en el marco de la iniciativa SickKids para el Caribe, consistentes en impartir formación y capacitación, prestar asistencia en materia de consultas de pacientes y servicios de diagnóstico, crear bases de datos locales en el área de la oncología, participar en actividades de promoción y garantizar la participación de las partes interesadas, y coordinar la administración y gestión de proyectos.

RESUMO Há um potencial reconhecido para parcerias entre instituições com poucos e muitos recursos dentro dos sistemas de saúde para melhorar os resultados de hematologia e oncologia pediátricas. A iniciativa SickKids no Caribe é uma parceria entre profissionais de saúde do Hospital for Sick Children em Toronto, Canadá, e sete instituições em seis países do Caribe (Bahamas, Barbados, Jamaica, Santa Lúcia, São Vicente e Granadinas e Trinidad e Tobago). O objetivo principal da iniciativa SickKids no Caribe tem sido melhorar os desfechos e a qualidade de vida das crianças caribenhas com menos de 18 anos que têm câncer e doenças hematológicas. Este artigo descreve cinco atividades principais realizadas no âmbito da iniciativa SickKids no Caribe: oferecimento de educação e capacitação; assistência em consultas de casos e serviços diagnósticos; desenvolvimento de bancos de dados locais em oncologia; promoção da causa, assegurando o envolvimento das partes interessadas; e coordenação da administração e da gestão de projetos.

TAPE-seq is a cell-based method for predicting genome-wide off-target effects of prime editor.

Prime editors (PEs) are powerful tools that widen the possibilities for sequence modifications during genome editing. Although methods based on the analysis of Cas9 nuclease or nickase activity have been used to predict genome-wide off-target activities of PEs, no tool that directly uses PEs for this purpose has been reported yet. In this study, we present a cell-based assay, named TAgmentation of Prime Editor sequencing (TAPE-seq), that provides genome-wide off-target candidates for PEs. TAPE-seq analyses are successfully performed using many different versions of PEs. The TAPE-seq predictions are compared with results from two other off-site prediction methods, Cas9 nuclease-based GUIDE-seq and Cas9 nickase-based Digenome-seq (nDigenome-seq). TAPE-seq shows a lower miss rate, and a higher area under the receiver operating characteristic curve compared to the other methods. TAPE-seq also identified valid off-target sites that were missed by the other methods.

Cell-Free Amniotic Fluid and Regenerative Medicine: Current Applications and Future Opportunities.

Amniotic fluid (AF) provides critical biological and physical support for the developing fetus. While AF is an excellent source of progenitor cells with regenerative properties, recent investigations indicate that cell-free AF (cfAF), which consists of its soluble components and extracellular vesicles, can also stimulate regenerative and reparative activities. This review summarizes published fundamental, translational, and clinical investigations into the biological activity and potential use of cfAF as a therapeutic agent. Recurring themes emerge from these studies, which indicate that cfAF can confer immunomodulatory, anti-inflammatory, and pro-growth characteristics to the target cells/tissue with which they come into contact. Another common observation is that cfAF seems to promote a return of cells/tissue to a homeostatic resting state when applied to a model of cell stress or disease. The precise mechanisms through which these effects are mediated have not been entirely defined, but it is clear that cfAF can safely and effectively treat cutaneous wounds and perhaps orthopedic degenerative conditions. Additional applications are currently being investigated, but require further study to dissect the fundamental mechanisms through which its regenerative effects are mediated. By doing so, rational design can be used to fully unlock its potential in the biotechnology lab and in the clinic.

Mental health interventions in adolescence.

Adolescent mental health (MH) disorders with striking prominence include anxiety, self-harm and depression. The current review aims to highlight high-quality reviews of novel interventions, mainly Cochrane reviews, and/or quality meta-analyses published between 2019 and 2022 on three adolescent mental health challenges. Recent evidence about the effectiveness of psychosocial interventions is encouraging. However, the shift to virtual treatment methods during the pandemic was supported by a relatively thin body of research. Future research and policy in child and youth MH must address the consequences of the pandemic or comparable disruptions on adolescent MH, as well as mitigation strategies. An emphasis on integrated digital, community and school platforms for mental health within child and adolescent health services would benefit from a greater focus on early recognition and prevention.

Characterizing Retail Food Environments in Peri-Urban Pakistan during the COVID-19 Pandemic.

(1) Background: To date, there are limited data in low- and middle-income countries (LMICs) that collect, monitor, and evaluate food environments in standardized ways. The development of a pilot survey tool, tailored to LMICs and focused on retail food environments, is necessary for improving public health nutrition. (2) Methods: A novel survey tool was developed and piloted in a sample of village retail food environments (n = 224) in Matiari, Pakistan between October 2020 to April 2021. Villages were randomly selected, and food outlets were surveyed within a 500-m radius from each village center. Descriptive statistics (counts and percentages) were used to describe the characteristics of food outlets and the availability of food. To test whether there was a difference in characteristics or in the mean of number of healthy, unhealthy, and total food items available by village size, a χ2 test or one-way ANOVA was conducted, respectively. (3) Results: In total, 1484 food outlets were surveyed for food accessibility, availability, and promotion across small (n = 54), medium (n = 112), and large villages (n = 58). In small and medium-sized villages, mobile food vendors were the predominant food outlet type (47.8% and 45.1%, respectively), whereas in large villages, corner stores (36%) were more prominent. The mean number of total food items (p < 0.006) and unhealthy food items (p < 0.001) available in food outlets differed by village size. The proportion of food outlets with available fruits, meat and poultry, water, and sugar-sweetened beverages also differed by village size (p < 0.001). (4) Conclusions: This study informs the global evidence gap in the current understanding of food environments in various ethnically diverse and dynamic LMICs, and the developed methodology will be useful to other LMICs for measuring and monitoring the food environment, especially among vulnerable population groups. This work complements current national and provincial survey efforts in Pakistan.

Practices and predictors of menstrual hygiene management material use among adolescent and young women in rural Pakistan: A cross-sectional assessment.

Background: In low- and middle-income countries (LMICs), women often use inappropriate materials to manage menstruation, which can threaten their health. Improper practices can also have critical downstream consequences beyond physiologic health, including restricting adolescent girls' access to academic pursuits. Methods: We used cross-sectional data collected through a structured questionnaire from the menstruating adolescents and young women 15-23 years of age living in rural Pakistan (n = 25 305). We aimed to describe menstrual hygiene management (MHM) practices and generate a predictive model of the socioeconomic and demographic factors related to the use of MHM materials. Beliefs and barriers around MHM were also summarized. The outcome variable included: those who practiced appropriate and inappropriate MHM practices. Logistic regression was used to generate the predictive model, with results presented as odds ratios (OR) and 95% confidence interval (CI). Results: Inappropriate MHM practices were reported by 75% (n = 19 006) of participants. The majority 61.9% (n = 15 667) reported using old cloths, 12.6% (n = 3191) used nothing, and 0.5% (n = 136) used old cloth with a sanitary pad. One-fourth of participants reported appropriate MHM material use, including 16.2% (n = 4087) sanitary pads, 8.6% (n = 2167) new cloth, and a few reported using sanitary pads with new cloth 0.2% (n = 45). Inappropriate MHM practices were more common in lowest wealth quintile (OR = 4.41; 95% CI = 2.77-7.01, P < 0.0001), followed by those with no education (OR = 3.9; 95% CI = 3.36-4.52, P < 0.0001). Conclusions: The study indicates the need for multi-sectoral efforts to introduce MHM-specific and MHM-sensitive interventions to improve MHM practices, ranging from the availability of low-cost MHM materials to the inclusion of MHM education in school curriculums and within the community platforms.

Purpura fulminans due to Enterococcus cecorum in an asplenic patient.

Enterococcus cecorum was initially isolated from the intestine of poultry and is an uncommon cause of human infection. We report here what we believe to be the first case of overwhelming post-splenectomy infection (OPSI) with purpura fulminans due to Enterococcus cecorum in a 51-year-old man. As opposed to other enterococci, Enterococcus cecorum remains susceptible to third-generation cephalosporin which is the first line empirical antibiotic therapy for both patients with purpura fulminans and asplenic patients with sepsis. Despite adequate antibiotic therapy, evolution in the intensive care unit (ICU) was overwhelming with death occurring 10 h after ICU admission.