Mother\u27s own milk compared with formula milk for feeding preterm or low birth weight infants: Systematic review and meta-analysis

Objectives: We assessed the effect of feeding preterm or low birth weight infants with infant formula compared with mother\u27s own milk on mortality, morbidity, growth, neurodevelopment, and disability. Methods: We searched Medline (Ovid), Embase (Ovid), and Cochrane Central Register of Controlled Studies to October 1, 2021. Results: Forty-two studies enrolling 89 638 infants fulfilled the inclusion criteria. We did not find evidence of an effect on mortality (odds ratio [OR] 1.26, 95% confidence interval [CI] 0.91-1.76), infection (OR 1.52, 95% CI 0.98-2.37), cognitive neurodevelopment (standardized mean difference -1.30, 95% CI -3.53 to 0.93), or on growth parameters. Formula milk feeding increased the risk of necrotizing enterocolitis (OR 2.99, 95% CI 1.75-5.11). The Grading of Recommendations Assessment, Development, and Evaluation certainty of evidence was low for mortality and necrotizing enterocolitis, and very low for neurodevelopment and growth outcomes. Conclusions: In preterm and low birth weight infants, low to very low-certainty evidence indicates that feeding with infant formula compared with mother\u27s own milk has little effect on all-cause mortality, infection, growth, or neurodevelopment, and a higher risk of developing necrotizing enterocolitis

Adolescent Experiences of the COVID-19 Pandemic and School Closures and Implications for Mental Health, Peer Relationships and Learning: A Qualitative Study in South-West England

The COVID-19 ‘lockdown’ and multiple school closures disrupted the daily lives and routines of the entire UK population. However, adolescents were likely particularly impacted by such measures due to this time being key for social and educational development. This qualitative study explored young people’s experiences of lockdowns and school closures. Fifteen secondary schools within south-west England were initially contacted and three schools participated in recruitment efforts. From December 2020 to March 2021, 25 students aged 14–15 participated in a combination of individual interviews (n = 5) and focus groups (n = 3). Findings revealed diverse experiences of the pandemic and highlighted the complexity of experiences according to individual student contexts. Three main themes were identified: (1) Learning environments; (2) Connection to peers; (3) Transition, adaptation and coping. These findings highlight the value young people place on face-to-face social contact with close friends, and the sense of structure provided by school, with implications for future home-based learning. Further in-depth qualitative research is needed to continue to understand the varied experiences during the course of the pandemic, particularly longer-term impacts on mental health and learning

Impact of School and Peer Connectedness on Adolescent Mental Health and Well-Being Outcomes during the COVID-19 Pandemic:A Longitudinal Panel Survey

School closures and social distancing measures during the pandemic have disrupted young people’s daily routines and social relationships. We explored patterns of change in adolescent mental health and tested the relationship between pre-pandemic levels of school and peer connectedness and changes in mental health and well-being between the first lockdown and the return to school. This is a secondary analysis of a longitudinal 3-wave panel survey. The study sample included 603 students (aged 13–14) in 17 secondary schools across south-west England. Students completed a survey pre-pandemic (October 2019), during lockdown (May 2020) and shortly after returning to school (October 2020). Multilevel models, with random effects, were conducted for anxiety, depression and well-being outcomes with school and peer connectedness as predictor variables. Symptoms of anxiety decreased from pre-pandemic to during the first UK lockdown and increased on the return to school; anxious symptoms decreased the most for students reporting feeling least connected to school pre-pandemic. Students reporting low levels of school and peer connectedness pre-pandemic experienced poorer mental health and well-being at all time points. Low school connectedness pre-pandemic was associated with a greater increase in anxious and depressive symptoms between lockdown and the return to school when compared to students with medium levels of school connectedness. No associations were found with high school connectedness or with low/high peer connectedness. For adolescents with poor school connectedness, the enforced time away from school that the pandemic caused led to reduced anxiety. Going forwards, we need to consider ways in which to promote connection with school as a way of supporting mental health and well-being

Adolescent Experiences of the COVID-19 Pandemic and School Closures and Implications for Mental Health, Peer Relationships and Learning: A Qualitative Study in South-West England

The COVID-19 ‘lockdown’ and multiple school closures disrupted the daily lives and routines of the entire UK population. However, adolescents were likely particularly impacted by such measures due to this time being key for social and educational development. This qualitative study explored young people’s experiences of lockdowns and school closures. Fifteen secondary schools within south-west England were initially contacted and three schools participated in recruitment efforts. From December 2020 to March 2021, 25 students aged 14–15 participated in a combination of individual interviews (n = 5) and focus groups (n = 3). Findings revealed diverse experiences of the pandemic and highlighted the complexity of experiences according to individual student contexts. Three main themes were identified: (1) Learning environments; (2) Connection to peers; (3) Transition, adaptation and coping. These findings highlight the value young people place on face-to-face social contact with close friends, and the sense of structure provided by school, with implications for future home-based learning. Further in-depth qualitative research is needed to continue to understand the varied experiences during the course of the pandemic, particularly longer-term impacts on mental health and learning

Impact of School and Peer Connectedness on Adolescent Mental Health and Well-Being Outcomes during the COVID-19 Pandemic: A Longitudinal Panel Survey

School closures and social distancing measures during the pandemic have disrupted young people’s daily routines and social relationships. We explored patterns of change in adolescent mental health and tested the relationship between pre-pandemic levels of school and peer connectedness and changes in mental health and well-being between the first lockdown and the return to school. This is a secondary analysis of a longitudinal 3-wave panel survey. The study sample included 603 students (aged 13–14) in 17 secondary schools across south-west England. Students completed a survey pre-pandemic (October 2019), during lockdown (May 2020) and shortly after returning to school (October 2020). Multilevel models, with random effects, were conducted for anxiety, depression and well-being outcomes with school and peer connectedness as predictor variables. Symptoms of anxiety decreased from pre-pandemic to during the first UK lockdown and increased on the return to school; anxious symptoms decreased the most for students reporting feeling least connected to school pre-pandemic. Students reporting low levels of school and peer connectedness pre-pandemic experienced poorer mental health and well-being at all time points. Low school connectedness pre-pandemic was associated with a greater increase in anxious and depressive symptoms between lockdown and the return to school when compared to students with medium levels of school connectedness. No associations were found with high school connectedness or with low/high peer connectedness. For adolescents with poor school connectedness, the enforced time away from school that the pandemic caused led to reduced anxiety. Going forwards, we need to consider ways in which to promote connection with school as a way of supporting mental health and well-being

\u3cem\u3eBorrelia burgdorferi\u3c/em\u3e cp32 BpaB Modulates Expression of the Prophage NucP Nuclease and SsbP Single-Stranded DNA-Binding Protein

The Borrelia burgdorferi BpaB proteins of the spirochete\u27s ubiquitous cp32 prophages are DNA-binding proteins, required both for maintenance of the bacteriophage episomes and for transcriptional regulation of the cp32 erp operons. Through use of DNase I footprinting, we demonstrate that BpaB binds the erp operator initially at the sequence 5′-TTATA-3′. Electrophoretic mobility shift assays indicated that BpaB also binds with high affinity to sites located in the 5′ noncoding regions of two additional cp32 genes. Characterization of the proteins encoded by those genes indicated that they are a single-stranded DNA-binding protein and a nuclease, which we named SsbP and NucP, respectively. Chromatin immunoprecipitation indicated that BpaB binds erp, ssbP, and nucP in live B. burgdorferi. A mutant bacterium that overexpressed BpaB produced significantly higher levels of ssbP and nucP transcript than did the wild-type parent

Mitotic stress is an integral part of the oncogene-induced senescence program that promotes multinucleation and cell cycle arrest

Oncogene-induced senescence (OIS) is a tumor suppression mechanism that blocks cell proliferation in response to oncogenic signaling. OIS is frequently accompanied by multinucleation; however, the origin of this is unknown. Here, we show that multinucleate OIS cells originate mostly from failed mitosis. Prior to senescence, mutant H-RasV12 activation in primary human fibroblasts compromised mitosis, concordant with abnormal expression of mitotic genes functionally linked to the observed mitotic spindle and chromatin defects. Simultaneously, H-RasV12 activation enhanced survival of cells with damaged mitoses, culminating in extended mitotic arrest and aberrant exit from mitosis via mitotic slippage. ERK-dependent transcriptional upregulation of Mcl1 was, at least in part, responsible for enhanced survival and slippage of cells with mitotic defects. Importantly, mitotic slippage and oncogene signaling cooperatively induced senescence and key senescence effectors p21 and p16. In summary, activated Ras coordinately triggers mitotic disruption and enhanced cell survival to promote formation of multinucleate senescent cells

DNMT3B Oncogenic Activity in Human Intestinal Cancer Is Not Linked to CIMP or BRAFV600E Mutation

Summary: Approximately 10% of human colorectal cancer (CRC) are associated with activated BRAFV600E mutation, typically in absence of APC mutation and often associated with a CpG island methylator (CIMP) phenotype. To protect from cancer, normal intestinal epithelial cells respond to oncogenic BRAFV600E by activation of intrinsic p53 and p16-dependent tumor suppressor mechanisms, such as cellular senescence. Conversely, CIMP is thought to contribute to bypass of these tumor suppressor mechanisms, e.g. via epigenetic silencing of tumor suppressor genes, such as p16. It has been repeatedly proposed that DNMT3B is responsible for BRAFV600E-induced CIMP in human CRC. Here we set out to test this by in silico, in vitro, and in vivo approaches. We conclude that although both BRAFV600E and DNMT3B harbor oncogenic potential in vitro and in vivo and show some evidence of cooperation in tumor promotion, they do not frequently cooperate to promote CIMP and human intestinal cancer

Expressing the human proteome for affinity proteomics: optimising expression of soluble protein domains and in vivo biotinylation

The generation of affinity reagents to large numbers of human proteins depends on the ability to express the target proteins as high-quality antigens. The Structural Genomics Consortium (SGC) focuses on the production and structure determination of human proteins. In a 7-year period, the SGC has deposited crystal structures of >800 human protein domains, and has additionally expressed and purified a similar number of protein domains that have not yet been crystallised. The targets include a diversity of protein domains, with an attempt to provide high coverage of protein families. The family approach provides an excellent basis for characterising the selectivity of affinity reagents. We present a summary of the approaches used to generate purified human proteins or protein domains, a test case demonstrating the ability to rapidly generate new proteins, and an optimisation study on the modification of >70 proteins by biotinylation in vivo. These results provide a unique synergy between large-scale structural projects and the recent efforts to produce a wide coverage of affinity reagents to the human proteome

Non-osteopenic Bone Pathology After Allo-hematopoietic Stem Cell Transplantation in Patients with Inborn Errors of Immunity

PURPOSE: There is a lack of data on post-HSCT non-osteopenic bone pathology specifically for children with inborn errors of immunity (IEI). We collected data on non-osteopenic bone pathology in children with IEI post-HSCT over two decades in a large tertiary pediatric immunology center. METHODS: Descriptive study with data analysis of bone pathology in allo-HSCT for IEI was performed between 1/1/2000 to 31/12/2018 including patients alive at follow-up to July 2022. Records were analyzed for bone pathology and risk factors. Exclusion criteria included isolated reduced bone density, fractures, and skeletal anomalies due to underlying IEI and short stature without other bone pathology. Bone pathologies were divided into 5 categories: bone tumors; skeletal dysplasia; avascular necrosis; evolving bone deformities; slipped upper femoral epiphysis. RESULTS: A total of 429 children received HSCT between 2000 and 2018; 340 are alive at last assessment. Non-osteopenic bone pathology was observed post-HSCT in 9.4% of patients (32/340, mean 7.8 years post-HSCT). Eleven patients (34%) had > 1 category of bone pathology. Seventeen patients (17/32; 53%) presented with bilateral bone pathology. The majority of patients received treosulfan-based conditioning (26/32; 81.2%). Totally, 65.6% (21/32) of patients had a history of prolonged steroid use (> 6 months). Pain was the presenting symptom in 66% of patients, and surgical intervention was required in 43.7%. The highest incidence of bone pathologies was seen in Wiskott-Aldrich syndrome (WAS) (n = 8/34; 23.5%) followed by hemophagocytic lymphohistiocytosis patients (n = 3/16; 18.8%). CONCLUSION: Non-osteopenic bone pathology in long-term survivors of allo-HSCT for IEI is not rare. Most patients did not present with complaints until at least 5 years post-HSCT highlighting the need for ongoing bone health assessment for patients with IEI. Children presenting with stunted growth and bone pathology post-HSCT should undergo skeletal survey to rule out development of post-HSCT skeletal dysplasia. Increased rates and complexity of bone pathology were seen amongst patients with Wiskott-Aldrich syndrome