Some reviews suggest benefits of nonpharmacological interventions for informal caregivers of people with dementia and mild cognitive impairment. These benefits may transfer to the care-recipients ...(CRs) through increased caregiving capability, reduced burden and depression among caregivers, and decreased negative mood contagion. However, large-scale review on these effects on the CRs is lacking. We searched PsycINFO, CINAHL with Full Text, MEDLINE, and PubMed from inception to end of 2020 and found 142 articles that reported randomized controlled trials (RCTs) of caregiver interventions using CR outcomes. Interventions were found to reduce neuropsychiatric symptoms (NPS) in general and behavioral and mood disturbance specifically, enhance cognition and quality of life, and delay institutionalization and mortality, with care coordination/case management, educational intervention with psychotherapeutic components (psychoeducation-b), and direct training of the CR (with caregiver involvement) being the more potent interventions. The kinds of benefit depend on the types of intervention. NPS was reduced by psychoeducation-b, care coordination/case management, and CR training. Cognition and quality of life were enhanced by CR training and care coordination/case management, respectively. Institutionalization was delayed by multicomponent interventions and respite (based on one study). However, the effects were generally small to very small. Together with existing findings on caregiver outcomes, a tripartite scaffolding model of caregiver support is proposed. The model is composed of three components: (a) care coordination/case management (i.e., enhanced usual care), (b) psychoeducation-b, and (c) CR training. Future directions in terms of developing consensual guidelines, a registry of intervention manuals, and family-centered programs with flexibility in delivery are discussed.
Public Significance Statement
Beyond the benefits for the caregivers themselves, psychosocial interventions targeting mainly caregivers also improve the conditions of the persons with dementia, though to a lesser degree. Such findings provide further support for the value of caregiver interventions as societies confront a rising dementia population. Long-term enhanced care alongside education with psychotherapeutic content and individualized training for the families may be an optimal approach.
Autoreactivity to histones is a pervasive feature of several human autoimmune disorders, including systemic lupus erythematosus (SLE). Specific post-translational modifications (PTMs) of histones ...within neutrophil extracellular traps (NETs) may potentially drive the process by which tolerance to these chromatin-associated proteins is broken. We hypothesized that NETs and their unique histone PTMs might be capable of inducing autoantibodies that target histones.
We developed a novel and efficient method for the in vitro production, visualization, and broad profiling of histone-PTMs of human and murine NETs. We also immunized Balb/c mice with murine NETs and profiled their sera on autoantigen and histone peptide microarrays for evidence of autoantibody production to their immunogen.
We confirmed specificity toward acetyl-modified histone H2B as well as to other histone PTMs in sera from patients with SLE known to have autoreactivity against histones. We observed enrichment for distinctive histone marks of transcriptionally silent DNA during NETosis triggered by diverse stimuli. However, NETs derived from human and murine sources did not harbor many of the PTMs toward which autoreactivity was observed in patients with SLE or in MRL/lpr mice. Further, while murine NETs were weak autoantigens in vivo, there was only partial overlap in the immunoglobulin G (IgG) and IgM autoantibody profiles induced by vaccination of mice with NETs and those seen in patients with SLE.
Isolated in vivo exposure to NETs is insufficient to break tolerance and may involve additional factors that have yet to be identified.
Background
Health literacy, the ability to access, understand, evaluate and apply health information, was found to contribute to positive health outcomes, possibly via promoting healthy behaviours. ...However, the specific pathways linking different health literacy skills to health and well‐being have remained unclear.
Methods
A cross‐sectional survey with structural questionnaires was administered among 2236 adults in Hong Kong (mean age = 46.10 ± 19.05). Health literacy was measured by HLS‐Asian‐47. Participants' physical conditions and subjective well‐being were predicted by health literacy and health behaviours with structural modelling path analysis.
Results
Health literacy in finding and understanding information showed a direct effect on enhancing physical health, while applying information capacity had an indirect positive effect via promoting health behaviours, which was moderated by sex. Only among women, this indirect effect predicting fewer physical symptoms and better well‐being was significant.
Conclusions
Different health literacy dimensions showed distinct direct and indirect pathways in influencing health for men and women. Based on the findings, skill trainings should be developed to enhance both gender's abilities of finding and understanding health information, while the ability of applying health information should also be improved for modifying lifestyle and promoting health, particularly for women.
Patient or Public Contribution
Two thousand and two hundred thirty‐six adults from different districts of Hong Kong participated in the study, and responded to questions on health literacy, behaviours and health status.
Abstract
Emerging evidence of an altered gut microbiome in autism spectrum disorder (ASD) suggests a pathomechanism through the gut–brain axis despite the inconsistent microbiome profile reported ...across studies. One of the knowledge gaps in the existing ASD microbiota studies is the lack of systematic exploration of the role of comorbid functional gastrointestinal disorder (FGID) in the association of ASD and altered gut microbiome. Consequently, 92 ASD and 112 age-matched typically developing (TD) boys were profiled on general psychopathology, FGID status by Rome IV classification, and gut microbiota using 16S ribosomal RNA amplicon sequencing at the V4 hypervariable region. Compared to TD, a significant decrease in the within-sample abundance of taxa was observed in ASD, regardless of FGID status. The microbiota of ASD FGID+ and ASD FGID− clustered apart from the TD groups. The microbiota of ASD FGID+ also showed qualitative differences from that of ASD FGID− and had the highest-level
Firmicutes: Bacteroidetes
ratio, which was paralleled by elevated levels of anxiety and overall psychopathology. The altered gastrointestinal microbiota composition in ASD appeared to be independent of comorbid FGID. Further studies should address how FGID may mediate neuropsychiatric symptoms in ASD through inflammation along the microbiota–gut–brain axis.
Noise correlations in neuronal responses can have a strong influence on the information available in large populations. In addition, the structure of noise correlations may have a great impact on the ...utility of different algorithms to extract this information that may depend on the specific algorithm, and hence may affect our understanding of population codes in the brain. Thus, a better understanding of the structure of noise correlations and their interplay with different readout algorithms is required. Here we use eigendecomposition to investigate the structure of noise correlations in populations of about 50-100 simultaneously recorded neurons in the primary visual cortex of anesthetized monkeys, and we relate this structure to the performance of two common decoders: the population vector and the optimal linear estimator. Our analysis reveals a non-trivial correlation structure, in which the eigenvalue spectrum is composed of several distinct large eigenvalues that represent different shared modes of fluctuation extending over most of the population, and a semi-continuous tail. The largest eigenvalue represents a uniform collective mode of fluctuation. The second and third eigenvalues typically show either a clear functional (i.e., dependent on the preferred orientation of the neurons) or spatial structure (i.e., dependent on the physical position of the neurons). We find that the number of shared modes increases with the population size, being roughly 10% of that size. Furthermore, we find that the noise in each of these collective modes grows linearly with the population. This linear growth of correlated noise power can have limiting effects on the utility of averaging neuronal responses across large populations, depending on the readout. Specifically, the collective modes of fluctuation limit the accuracy of the population vector but not of the optimal linear estimator.
Aims and objectives
To investigate room temperature and relative humidity affecting nurses’ comfort and protection in wearing N95 respirators during clinical bedside procedures.
Background
N95 ...respirators are most commonly used to protect healthcare workers against airborne diseases. The elastic head straps required for tight‐fit may cause headache, facial pain and/or ear lobe discomfort. Although some past fit test results showed that these respirators are likely to fit comfortably, in reality, any discomfort from use may influence negatively their appeal and acceptability and thus lower their effectiveness to protect the wearers.
Design
This study used a comparative study design to compare nurses’ comfort and protection in wearing N95 respirator during clinical nursing procedures.
Method
The participants (84) were first‐year undergraduate nursing students from a university in Hong Kong. They were divided randomly into four groups (A, B, C and D), with 21 in each group. In this study, they performed the Personal Respirator Sampling Test (PRST), a self‐developed portable, real‐time fit test method based on the conventional fit test set‐up. After this, they were asked to complete a usability questionnaire, which was used to record their evaluations of the six perceptions of comfort of wearing N95 respirators.
Results
The participants expressed being comfortable with the respirators at warm temperatures of 20 to 24°C. For those participants in Group A who had performed fit tests and fit checks, they did not feel hot nor had difficulties with breathing. However, they did feel tightness in the respirators and experienced discomfort on their ear lobes.
Conclusion
Room temperature is the significant factor affecting the comfort in wearing N95 respirators. It is noteworthy that any discomforts from wearing respirators will negatively influence their appeal and proper use. Without doubt, comfortable fit makes healthcare workers more likely use respirators, hence complying with occupational health and safety regulations.
Relevance to clinical practice
N95 respirator wearer's comfort is affected by room temperature. Wearer's comfort can affect his/her morale in performing bedside procedures in clinical practice.
The effects of Danshen and its active components (tanshinone I, tanshinone IIA, dihydrotanshinone and cryptotanshinone) on tolbutamide 4-hydroxylation was investigated in the rat. Danshen (0.125–2
...mg/ml) decreased 4-hydroxy-tolbutamide formation
in vitro and
in vivo. Enzyme kinetics studies showed that inhibition of tolbutamide 4-hydroxylase activity was competitive and concentration-dependent. The K
i values of the tanshinones were: dihydrotanshinone (8.92
μM), cryptotanshinone (24.5
μM), tanshinone I (80.3
μM) and tanshinone IIA (242.9
μM). In freshly prepared primary rat hepatocytes, tanshinones inhibited tolbutamide 4-hydroxylation in a concentration-dependent manner, with EC
40 values in the order: cryptotanshinone (15.8
μM), tanshinone IIA (16.2
μM), dihydrotanshinone (20.1
μM) and tanshinone I (48.2
μM). In whole animal studies, single dose Danshen treatment (50 or 200
mg/kg, i.p.) increased tolbutamide clearance (17–26.9%), decreased AUC (14.4–20.9%) and increased the Vd (7.26%). Three-day Danshen treatment (200
mg/kg/day, i.p.) decreased the C
initial, increased T
1/2 and Vd but did not affect tolbutamide clearance and AUC. Tolbutamide-4-hydroxylation
in vivo was decreased by Danshen after acute and after 3-day treatment, with decreases in the AUC of 4-hydroxy-tolbutamide (15–28%) over the time period studied. Despite competitive inhibition of rat CYP2C11
in vitro and
in vivo, as shown by the decrease in tolbutamide 4-hydroxylation, only minor changes in tolbutamide pharmacokinetics was observed. This study illustrated that the herb-drug interaction potential should be monitored by both
in vitro and
in vivo biotransformation/ pharmacokinetic parameters.
Background Gloves are a necessary contact precaution to prevent transmission of infectious pathogens that spread by direct or indirect contact with an infected person or a contaminated environment. ...This article reports a study investigating hand and environmental contamination levels when health care workers (HCWs) followed two different methods of removing gloves at two distances from the rubbish bin. Methods Fifty HCWs performed a personal or causal glove removal method (pretest) and a Centers for Disease Control (CDC)-recommended glove removal method (posttest) at distances of 2 feet and 3 feet from the rubbish bin after the application of fluorescent solution (the simulated contaminant) onto their gloved hands. Results The incidence of the small patch of fluorescent stain (<1 cm2 ) on the front of the doffed gloves was significantly lower in the posttest than in the pretest. The incidence of small and large patches (>1 cm2 ) on the front of the doffed gloves and on the cover of the rubbish bin was significantly lower at 3 feet than at 2 feet. Health care assistants had significantly higher levels of contamination than other HCWs in the pretest but not in the posttest. There was no significant difference in hand contamination rate between pretest and posttest based on distance from the rubbish bin and type of HCW. Conclusion The impact of the glove removal procedure and the distance to the bin in which used gloves are discarded should be taken into consideration on a daily basis, along with the supervision of infection control measures by minor staff.
The RAG1 and RAG2 proteins catalyze V(D)J recombination and are essential for generation of the diverse repertoire of antigen
receptor genes and effective immune responses. RAG2 is composed of a ...âcoreâ domain that is required for the recombination
reaction and a C-terminal nonessential or ânon-coreâ region. Recent evidence has emerged arguing that the non-core region
plays a critical regulatory role in the recombination reaction, and mutations in this region have been identified in patients
with immunodeficiencies. Here we present the first structural data for the RAG2 protein, using NMR spectroscopy to demonstrate
that the C terminus of RAG2 contains a noncanonical PHD finger. All of the non-core mutations of RAG2 that are implicated
in the development of immunodeficiencies are located within the PHD finger, at either zinc-coordinating residues or residues
adjacent to an α-helix on the surface of the domain that participates in binding to the signaling molecules, phosphoinositides.
Functional analysis of disease and phosphoinositide-binding mutations reveals novel intramolecular interactions within the
non-core region and suggests that the PHD finger adopts two distinct states. We propose a model in which the equilibrium between
these states modulates recombination activity. Together, these data identify the PHD finger as a novel and functionally important
domain of RAG2.
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