Wilkersoncamp1129

This study aimed to conduct a systematic review and meta-analysis to compare differences in health utilities (HUs) assessed by self and proxy respondents in children, as well as to evaluate the effects of health conditions, valuation methods, and proxy types on the differences.

Eligible studies published in PubMed, Embase, Web of Science, and Cochrane Library up to December 2019 were identified according to PRISMA guidelines. Meta-analyses were performed to calculate the weighted mean differences (WMDs) in HUs between proxy- versus self-reports. Mixed-effects meta-regressions were applied to explore differences in WMDs among each health condition, valuation method and proxy type.

A total of 30 studies were finally included, comprising 211 pairs of HUs assessed by 15,294 children and 16,103 proxies. This study identified 34 health conditions, 10 valuation methods, and 3 proxy types. In general, proxy-reported HUs were significantly different from those assessed by children themselves, while the direction and magnitude of these differences were inconsistent regarding health conditions, valuation methods, and proxy types. Meta-regression demonstrated that WMDs were significantly different in patients with ear diseases relative to the general population; in those measured by EQ-5D, Health utility index 2 (HUI2), and Pediatric asthma health outcome measure relative to Visual analogue scale method; while were not significantly different in individuals adopting clinician-proxy and caregiver-proxy relative to parent-proxy.

Divergence existed in HUs between self and proxy-reports. Our findings highlight the importance of selecting appropriate self and/or proxy-reported HUs in health-related quality of life measurement and economic evaluations.

Divergence existed in HUs between self and proxy-reports. Our findings highlight the importance of selecting appropriate self and/or proxy-reported HUs in health-related quality of life measurement and economic evaluations.

The mechanism of synaptic loss in Alzheimer's disease is poorly understood and may be associated with tau pathology. In this combined positron emission tomography (PET) and magnetoencephalography (MEG) study, we aimed to investigate spatial associations between regional tau pathology ([

F]flortaucipir PET), synaptic density (synaptic vesicle 2A [

C]UCB-J PET) and synaptic function (MEG) in Alzheimer's disease.

Seven amyloid-positive Alzheimer's disease subjects from the Amsterdam Dementia Cohort underwent dynamic 130-min [

F]flortaucipir PET, dynamic 60-min [

C]UCB-J PET with arterial sampling and 2 × 5-min resting-state MEG measurement. [

F]flortaucipir- and [

C]UCB-J-specific binding (binding potential, BP

) and MEG spectral measures (relative delta, theta and alpha power; broadband power; and peak frequency) were assessed in cortical brain regions of interest. Associations between regional [

F]flortaucipirBP

, [

C]UCB-J BP

and MEG spectral measures were assessed using Spearman correlations and generalized estimating equation models.

Across subjects, higher regional [

F]flortaucipir uptake was associated with lower [

C]UCB-J uptake. Within subjects, the association between [

C]UCB-J and [

F]flortaucipir depended on within-subject neocortical tau load; negative associations were observed when neocortical tau load was high, gradually changing into opposite patterns with decreasing neocortical tau burden. Both higher [

F]flortaucipir and lower [

C]UCB-J uptake were associated with altered synaptic function, indicative of slowing of oscillatory activity, most pronounced in the occipital lobe.

These results indicate that in Alzheimer's disease, tau pathology is closely associated with reduced synaptic density and synaptic dysfunction.

These results indicate that in Alzheimer's disease, tau pathology is closely associated with reduced synaptic density and synaptic dysfunction.

Kabuki syndrome is a genetic disorder that affects several body systems and presents with variations in symptoms and severity. The syndrome is named for a common phenotype of faces resembling stage makeup used in a Japanese traditional theatrical art named kabuki. Natural Product Library The most frequent cause of this syndrome is mutations in the H3K4 family of histone methyltransferases while a smaller percentage results from genetic alterations affecting the histone demethylase, KDM6A. Because of the rare presentation of the latter form of the disease, little is known about how missense changes in the KDM6A protein sequence impact protein function.

In this study, we use molecular mechanic and molecular dynamic simulations to enhance the annotation and mechanistic interpretation of the potential impact of eleven KDM6A missense variants found in Kabuki syndrome patients. These variants (N910S, D980V, S1025G, C1153R, C1153Y, P1195L, L1200F, Q1212R, Q1248R, R1255W, and R1351Q) are predicted to be pathogenic, likely pathogenic or sfunction. This type of comprehensive structure- and MD-based analyses should help develop improved impact scoring systems to interpret the damaging effects of variants in this protein and other related proteins as well as provide detailed mechanistic insight that is not currently predictable from sequence alone.

Our study demonstrates that the KDM6A Kabuki syndrome variants may impair histone demethylase function through various mechanisms that include altered protein integrity, local environment, molecular interactions and protein dynamics. Molecular dynamics simulations of the wild type and the variants are critical to gain a better understanding of molecular dysfunction. This type of comprehensive structure- and MD-based analyses should help develop improved impact scoring systems to interpret the damaging effects of variants in this protein and other related proteins as well as provide detailed mechanistic insight that is not currently predictable from sequence alone.

Birth asphyxia is one of the leading causes of intrapartum stillbirth and neonatal mortality worldwide. We sought to explore the experiences of health care workers in managing foetal distress and birth asphyxia to gain an understanding of the challenges in a low-income setting.

We conducted in-depth interviews with 12 midwives and 4 doctors working in maternity units from different health facilities in Northern Uganda in 2018. We used a semi-structured interview guide which included questions related to; health care workers' experiences of maternity care, care for foetal distress and birth asphyxia, views on possible preventive actions and perspectives of the community. Audio recorded interviews were transcribed verbatim and analysed using inductive content analysis.

Four categories emerged (i) Understanding of and actions for foetal distress and birth asphyxia including knowledge, misconception and interventions; (ii) Challenges of managing foetal distress and birth asphyxia such as complexities of the referral system, refusal of referral, lack of equipment, and human resource problems, (iii) Expectations and blame from the community, and finally (iv) Health care worker' insights into prevention of foetal distress and birth asphyxia.