Early-life stress and amyloidosis in mice share pathogenic pathways involving synaptic mitochondria and lipid metabolism.

INTRODUCTION: Early-life stress (ES) increases the risk for Alzheimer's disease (AD). We and others have shown that ES aggravates amyloid-beta (Aß) pathology and promotes cognitive dysfunction in APP/PS1 mice, but underlying mechanisms remain unclear. METHODS: We studied how ES affects the hippocampal synaptic proteome in wild-type (WT) and APP/PS1 mice at early and late pathological stages, and validated hits using electron microscopy and immunofluorescence. RESULTS: The hippocampal synaptosomes of both ES-exposed WT and early-stage APP/PS1 mice showed a relative decrease in actin dynamics-related proteins and a relative increase in mitochondrial proteins. ES had minimal effects on older WT mice, while strongly affecting the synaptic proteome of advanced stage APP/PS1 mice, particularly the expression of astrocytic and mitochondrial proteins. DISCUSSION: Our data show that ES and amyloidosis share pathogenic pathways involving synaptic mitochondrial dysfunction and lipid metabolism, which may underlie the observed impact of ES on the trajectory of AD.

Sepsis Prognostic Scores Accuracy in Predicting Adverse Outcomes in Children With Sepsis Admitted to the Pediatric Intensive Care Unit From the Emergency Department: A 10-Year Single-Center Experience.

OBJECTIVE: To compare the performance of several prognostic scores calculated in the first 24 hours of admission (day 1) in predicting mortality and morbidity among critically ill children with sepsis presenting to the pediatric emergency department (PED) and then admitted to the pediatric intensive care unit (PICU). METHODS: Single-center, retrospective cohort study in children with a diagnosis of sepsis visiting the PED and then admitted to the PICU from January 1, 2010 to December 31, 2019. Sepsis organ dysfunction scores-pediatric Sequential Organ Failure Assessment (pSOFA) (Schlapbach, Matics, Shime), quickSOFA, quickSOFA-L, Pediatric Logistic Organ Dysfunction (PELOD)-2, quickPELOD-2, and Pediatric Multiple Organ Dysfunction score-were calculated during the first 24 hours of admission (day 1) and their performance compared with systemic inflammatory response syndrome (SIRS) and severe sepsis-International Consensus Conference on Pediatric Sepsis(ICCPS)-derived criteria-using the area under the receiver operating characteristic curve. Primary outcome was PICU mortality. Secondary outcomes were: a composite of death and new disability (ie, change from baseline Pediatric Overall Performance Category score ≥1); prolonged PICU length of stay (>5 d); prolonged invasive mechanical ventilation (MV) (>3 d). RESULTS: Among 60 patients with sepsis, 4 (6.7%) died, 7 (11.7%) developed new disability, 26 (43.3%) experienced prolonged length of stay, and 21 (35%) prolonged invasive MV. The prognostic ability in mortality discrimination was significantly higher for organ dysfunction scores, with PELOD-2 showing the best performance (area under the receiver operating characteristic curve, 0.924; 95% confidence interval, 0.837-1.000), significantly better than SIRS 3 criteria (0.924 vs 0.509, P = 0.009), SIRS 4 criteria (0.924 vs 0.509, P < 0.001), and severe sepsis (0.924 vs 0.527, P < 0.001). Among secondary outcomes, PELOD-2 performed significantly better than SIRS criteria and severe sepsis to predict prolonged duration of invasive MV, whereas better than severe sepsis to predict "poor outcome" (mortality or new disability). CONCLUSIONS: Day 1 organ dysfunction scores performed better in predicting mortality and morbidity outcomes than ICCPS-derived criteria. The PELOD-2 was the organ dysfunction score with the best performance for all outcomes.

A Systematic Review and Meta-Analysis of the Management and Outcomes of Isolated Skull Fractures in Children.

STUDY OBJECTIVE: Most studies of children with isolated skull fractures have been relatively small, and rare adverse outcomes may have been missed. Our aim is to quantify the frequency of short-term adverse outcomes of children with isolated skull fractures. METHODS: PubMed, EMBASE, the Cochrane Library, Scopus, Web of Science, and gray literature were systematically searched to identify studies reporting on short-term adverse outcomes of children aged 18 years or younger with linear, nondisplaced, isolated skull fractures (ie, without traumatic intracranial injury on neuroimaging). Two investigators independently reviewed identified articles for inclusion, assessed quality, and extracted relevant data. Our primary outcome was emergency neurosurgery or death. Secondary outcomes were hospitalization and new intracranial hemorrhage on repeated neuroimaging. Meta-analyses of pooled estimate of each outcome were conducted with random-effects models, and heterogeneity across studies was assessed. RESULTS: Of the 587 studies screened, the 21 that met our inclusion criteria included 6,646 children with isolated skull fractures. One child needed emergency neurosurgery and no children died (pooled estimate 0.0%; 95% confidence interval [CI] 0.0% to 0.0%; I2=0%). Of the 6,280 children with known emergency department disposition, 4,914 (83%; 95% CI 71% to 92%; I2=99%) were hospitalized. Of the 569 children who underwent repeated neuroimaging, 6 had new evidence of intracranial hemorrhage (0.0%; 95% CI 0.0% to 9.0%; I2=77%); none required operative intervention. CONCLUSION: Children with isolated skull fractures were at extremely low risk for emergency neurosurgery or death, but were frequently hospitalized. Clinically stable children with an isolated skull fracture may be considered for outpatient management in the absence of other clinical concerns.

Why women do not ask for information on preconception health? A qualitative study.

BACKGROUND: Preconception care involves health promotion to reduce risk factors that might affect women and couples of childbearing age. The risk factors of adverse reproductive outcomes include recognized genetic diseases in the family or the individual, previous congenital diseases, miscarriage, prematurity, fetal growth restriction, infertility, chronic maternal diseases, lifestyle, and occupational or environmental factors. Effective preconception care involves a range of preventive, therapeutic and behavioural interventions. Although in Italy there are national preconception care recommendations concerning the general population, they are usually encouraged informally and only for single risk factors. At present there is increasing interest in offering a global intervention in this field. The aim of this study was to investigate attitudes and behaviours of Italian women of childbearing age and healthcare professionals regarding preconception health. METHODS: We conducted a qualitative study among women of childbearing age and healthcare professionals between February 2014 and February 2015. Five focus groups were held: 2 with non-pregnant women aged 22 to 44 years and 3 with healthcare professionals. Discussion topics included women's questions about preconception health, worries and barriers regarding preconception care interventions, attitudes and behaviours of women and healthcare professionals towards preconception health, women's information sources. In the analysis of the focus groups priority was given to what was said by the women, supplemented by information from the healthcare professionals' focus groups. RESULTS: Fourteen women of childbearing age (8 nulliparae and 6 multiparae) and 12 healthcare professionals (3 nurses, 4 midwives, 5 doctors) participated in the focus groups. The results indicate the presence of many barriers and a lack of awareness of preconception health relating to women, healthcare professionals and policies. Women's knowledge and attitudes towards primary preconception care information are described. The main reference source of information in this field for Italian women seems to be their obstetric-gynaecologist. CONCLUSIONS: The study indicates that several barriers influence preconception care in Italy. Moreover, a lack of awareness of preconception health and care among Italian women of childbearing age and healthcare professionals emerges. The findings might contribute to strategies for the implementation of preconception care guidelines.

Neonatal resuscitation in Vietnam: a national survey of a middle-income country.

AIM: Interventions that improve neonatal resuscitation are critical if we are to reduce perinatal mortality. We evaluated the consistency of resuscitation practices, and adherence to the international guidelines for neonatal resuscitation, in a large representative sample of hospitals in Vietnam. METHODS: A questionnaire was sent to 187 public central, provincial and district hospitals, representing the three levels of public hospital-based maternity services in Vietnam. RESULTS: The overall response rate was 85.7% (160/187 hospitals), and the response rate was 100%, 90.3% and 81.7% for central, provincial and district hospitals, respectively. There were 620 300 births in the surveyed hospitals during the year 2011, representing almost half of all inpatient births in Vietnam. Neonatal resuscitation was provided by obstetricians and, or, midwives at all levels. Half of the hospitals did not follow recommendations for delaying cord clamping. The majority of the hospitals did not have a wall thermometer in the delivery room (80.5%) and did not monitor neonatal temperature after birth (64.1%). A large proportion of hospitals (39.9%) used 100% oxygen to initiate resuscitation and only central hospitals avoided this practice. CONCLUSION: Our survey identified significant variations in resuscitation practices between central, provincial and district hospitals and limited adherence to international recommendations.

Postnatal acute renal failure after fetal exposure to angiotensin receptor blockers.

Maternal hypertensive treatment with angiotensin receptor blockers (ARBs) during the second and third trimester of pregnancy is associated with several fetal and neonatal complications, and potential adverse outcomes. We report a neonate presenting with transient renal acute failure during the first days of life after maternal treatment with ARBs. Women who became pregnant while taking one of these drugs must modify antihypertensive therapy with a different class drug as soon as pregnancy is recognised.