Barriers to accessing and receiving mental health care for paid and unpaid carers of older adults.

AIM: The aim of this qualitative study was to explore the barriers and facilitators to accessing and receiving mental health care for paid and unpaid carers of older adults. METHODS: Unpaid and paid carers for older adults in England were interviewed remotely between May and December 2022. Participants were asked about their experiences of mental health needs and support. Reflexive thematic analysis was used to analyse the data. RESULTS: Thirty-seven carers participated (npaid = 9; nunpaid = 28), with the majority caring for a parent with dementia. Thematic analysis generated four themes: lack of healthcare support, social care system failing to enable time off, personal barriers and unsupportive work culture. Healthcare professionals failed to provide any link to mental health services, including when a dementia diagnosis was received. Structural and organisational barriers were evidenced by carers being unable to take time off from their unpaid caring duties or paid caring role, due to an absence of social care support for their relative. CONCLUSIONS: This is the first study to have explored the barriers to mental health care and support for paid and unpaid carers for older adults and suggests that structural, organisational and personal barriers cause severe difficulties in accessing required support to care for older relatives, services users and residents. PUBLIC INVOLVEMENT: Two unpaid carers aided with the development of topic guides, data analysis, interpretation and dissemination. Both were supported and trained to code anonymised transcripts.

Comparison of oral cavity protein abundance among caries-free and caries-affected individuals-a systematic review and meta-analysis.

Objective: Some salivary proteins seem to be differently abundant among caries-free (CF) and caries-affected (CA) individuals, but previous results are contradictory precluding that definitive conclusion be drawn. A pooled analysis of the available evidence may provide more robust data on identifying oral cavity protein patterns among CF and CA individuals. This systematic review and meta-analysis (PROSPERO CRD42021269079) aimed to compare the oral cavity protein abundance among caries-free and caries-affected individuals. Methods: This study was conducted following PRISMA guidelines. PubMed, Embase, and Web of Science databases were systematically assessed (up to February 2023) to retrieve clinical studies written in English, German, or in Latin-based languages that compared the oral cavity protein abundance among CF and CA individuals. Data extraction and methodological quality assessment (NIH guidelines) were independently performed by two investigators. Qualitative synthesis was performed from all included studies and meta-analysis was performed using a random-effects model with inverse variance for studies that reported the concentration of proteins or enzymatic activity. Standardized mean difference (SMD) with respective 95% confidence interval (CI) were calculated for each outcome. Results: A total of 90 studies (two cohort and 88 cross-sectional designs) of more than 6,000 participants were selected for data extraction, being the quality of evidence graded as "fair" for most of them. The oral cavity of CF individuals presented lower total protein concentration [SMD = 0.37 (95% CI: 0.07-0.68; 18 studies)], lower total antioxidant capacity [SMD = 1.29 (95% CI: 0.74-1.85); 17 studies], and lower carbonic anhydrase activity [SMD = 0.83 (95% CI: 0.58-1.09); three studies], whereas CA individuals presented lower carbonic anhydrase concentration [SMD = -0.66 (95% CI: -1.00 to -0.32); three studies], urease [SMD = -0.95 (IC 95%: -1.72 to -0.17); four studies], and arginine deiminase system [SMD = -2.07 (95% CI: -3.53 to -0.62); three studies] activities. Antimicrobial peptides, secretory immunoglobulin-A concentrations and alpha-amylase activity were similar among individuals. Conclusion: Differences on oral cavity protein abundance were observed among CF and CA individuals. These data indicate some protein patterns for the oral health and dental caries conditions. Even when statistically significant, some of the results were not very consistent. Cohort studies need to be conducted to validate these results.

Unraveling tumor specific neoantigen immunogenicity prediction: a comprehensive analysis.

Introduction: Identification of tumor specific neoantigen (TSN) immunogenicity is crucial to develop peptide/mRNA based anti-tumoral vaccines and/or adoptive T-cell immunotherapies; thus, accurate in-silico classification/prioritization proves critical for cost-effective clinical applications. Several methods were proposed as TSNs immunogenicity predictors; however, comprehensive performance comparison is still lacking due to the absence of well documented and adequate TSN databases. Methods: Here, by developing a new curated database having 199 TSNs with experimentally-validated MHC-I presentation and positive/negative immune response (ITSNdb), sixteen metrics were evaluated as immunogenicity predictors. In addition, by using a dataset emulating patient derived TSNs and immunotherapy cohorts containing predicted TSNs for tumor neoantigen burden (TNB) with outcome association, the metrics were evaluated as TSNs prioritizers and as immunotherapy response biomarkers. Results: Our results show high performance variability among methods, highlighting the need for substantial improvement. Deep learning predictors were top ranked on ITSNdb but show discrepancy on validation databases. In overall, current predicted TNB did not outperform existing biomarkers. Conclusion: Recommendations for their clinical application and the ITSNdb are presented to promote development and comparison of computational TSNs immunogenicity predictors.

Novel evaluation approach for molecular signature-based deconvolution methods.

The tumoral immune microenvironment (TIME) plays a key role in prognosis, therapeutic approach and pathophysiological understanding over oncological processes. Several computational immune cell-type deconvolution methods (DM), supported by diverse molecular signatures (MS), have been developed to uncover such TIME interplay from RNA-seq tumor biopsies. MS-DM pairs were benchmarked against each other by means of different metrics, such as Pearson's correlation, R2 and RMSE, but these only evaluate the linear association of the estimated proportion related to the expected one, missing the analysis of prediction-dependent bias trends and cell identification accuracy. We present a novel protocol composed of four tests allowing appropriate evaluation of the cell type identification performance and proportion prediction accuracy of molecular signature-deconvolution method pair by means of certainty and confidence cell-type identification scores (F1-score, distance to the optimal point and error rates) as well the Bland-Altman method for error-trend analysis. Our protocol was used to benchmark six state-of-the-art DMs (CIBERSORTx, DCQ, DeconRNASeq, EPIC, MIXTURE and quanTIseq) paired to five murine tissue-specific MSs, revealing a systematic overestimation of the number of different cell types across almost all methods.

Early life oxytocin treatment improves thermo-sensory reactivity and maternal behavior in neonates lacking the autism-associated gene Magel2.

Atypical responses to sensory stimuli are considered as a core aspect and early life marker of autism spectrum disorders (ASD). Although recent findings performed in mouse ASD genetic models report sensory deficits, these were explored exclusively during juvenile or adult period. Whether sensory dysfunctions might be present at the early life stage and rescued by therapeutic strategy are fairly uninvestigated. Here we found that under cool environment neonatal mice lacking the autism-associated gene Magel2 present pup calls hypo-reactivity and are retrieved with delay by their wild-type dam. This neonatal atypical sensory reactivity to cool stimuli was not associated with autonomic thermoregulatory alteration but with a deficit of the oxytocinergic system. Indeed, we show in control neonates that pharmacogenetic inactivation of hypothalamic oxytocin neurons mimicked atypical thermosensory reactivity found in Magel2 mutants. Furthermore, pharmacological intranasal administration of oxytocin to Magel2 neonates was able to rescue both the atypical thermosensory response and the maternal pup retrieval. This preclinical study establishes for the first-time early life impairments in thermosensory integration and suggest a therapeutic potential benefit of intranasal oxytocin treatment on neonatal atypical sensory reactivity for autism.

Modulation of the thermosensory system by oxytocin.

Oxytocin (OT) is a neurohormone involved early in neurodevelopment and is implicated in multiple functions, including sensory modulation. Evidence of such modulation has been observed for different sensory modalities in both healthy and pathological conditions. This review summarizes the pleiotropic modulation that OT can exercise on an often overlooked sensory system: thermosensation. This system allows us to sense temperature variations and compensate for the variation to maintain a stable core body temperature. Oxytocin modulates autonomic and behavioral mechanisms underlying thermoregulation at both central and peripheral levels. Hyposensitivity or hypersensitivity for different sensory modalities, including thermosensitivity, is a common feature in autism spectrum disorder (ASD), recapitulated in several ASD mouse models. These sensory dysregulations occur early in post-natal development and are correlated with dysregulation of the oxytocinergic system. In this study, we discussed the potential link between thermosensory atypia and the dysregulation of the oxytocinergic system in ASD.

Exploring online identity construction for the caregivers of adults living with dementia and the value of interactions with health and social care professionals.

Becoming an informal caregiver for an adult living with dementia has been shown to have a significant impact upon the conception of identity. This study aimed to identify how identity is constructed online amongst caregivers of individuals living with dementia and how healthcare interactions can influence identity development through the analysis of online web blogs. Sixteen online blogs (172 entries) were selected through purposive and snowball sampling, and discourse analysis was used to analyse online identity construction for informal caregivers of adults living with dementia. Six areas of online identity construction were identified: changing family role; powerful expert social campaigner; being an advocate; guardian of their relative's selfhood; sustaining creative and spiritual individuality and wider community member in online and real life. Further to this, the importance of health and social care service interactions in the development of caregiver identity revealed that professionals must ensure person-centred service contacts for caregivers. This is a challenging task in the pandemic climate where interactions between health and social care professionals and caregivers are limited due to isolation measures. It is evident that the blog format can provide a forum through which the identity of the caregiver of an adult living with dementia can evolve. The six areas of identity construction reveal the multifaceted nature of identity for the caregiver and the value of belonging to an online community both in relation to identity construction and support. This finding is especially applicable in the current pandemic when accessing a face-to-face community is challenging for caregivers who may be shielding or living in isolation. The findings of this research can aid health and social care professionals in understanding the development of caregiver identity and in providing appropriate support during service interactions, on accessing virtual and face to face community support.

Pan-Cancer Molecular Patterns and Biological Implications Associated with a Tumor-Specific Molecular Signature.

Studying tissue-independent components of cancer and defining pan-cancer subtypes could be addressed using tissue-specific molecular signatures if classification errors are controlled. Since PAM50 is a well-known, United States Food and Drug Administration (FDA)-approved and commercially available breast cancer signature, we applied it with uncertainty assessment to classify tumor samples from over 33 cancer types, discarded unassigned samples, and studied the emerging tumor-agnostic molecular patterns. The percentage of unassigned samples ranged between 55.5% and 86.9% in non-breast tissues, and gene set analysis suggested that the remaining samples could be grouped into two classes (named C1 and C2) regardless of the tissue. The C2 class was more dedifferentiated, more proliferative, with higher centrosome amplification, and potentially more TP53 and RB1 mutations. We identified 28 gene sets and 95 genes mainly associated with cell-cycle progression, cell-cycle checkpoints, and DNA damage that were consistently exacerbated in the C2 class. In some cancer types, the C1/C2 classification was associated with survival and drug sensitivity, and modulated the prognostic meaning of the immune infiltrate. Our results suggest that PAM50 could be repurposed for a pan-cancer context when paired with uncertainty assessment, resulting in two classes with molecular, biological, and clinical implications.

Training interventions to improve general hospital care for older people with cognitive impairment: systematic review.

BACKGROUND: In response to increasing numbers of older people in general hospitals who have cognitive impairment such as dementia and delirium, many hospitals have developed education and training programmes to prepare staff for this area of clinical practice.AimsTo review the evidence on educational interventions on hospital care for older people with cognitive impairment. METHOD: A mixed methods systematic review and narrative synthesis was undertaken. The following electronic databases were searched: Medline, Embase, CINAHL, PsycINFO, EBM Reviews, ASSIA and Scopus, as well as Health Management Information Consortium (HMIC), ProQuest, PubMed and SCIE: Social Care Online. Initial searches were run in August 2014 (update search September 2016). Titles and abstracts of studies retrieved were screened independently. The full text of eligible studies were then independently assessed by two review team members. All included studies were assessed using a standard quality appraisal tool. RESULTS: Eight studies relating to delirium, six on dementia and two on delirium and dementia were included, each testing the use of a different educational intervention. Overall, the quality of the studies was low. In relation to delirium, all studies reported a significant increase in participants' knowledge immediately post-intervention. Two of the dementia studies reported an increase in dementia knowledge and dementia confidence immediately post-intervention. CONCLUSIONS: The variety of outcomes measured makes it difficult to summarise the findings. Although studies found increases in staff knowledge, there is insufficient evidence to conclude that educational interventions for staff lead to improved patient outcomes.Declaration of interestNone.

Early Detection of Chronic Asymptomatic Chagas Infection.

Chagas disease, also known as American trypanosomiasis, is a chronic and systemic parasitic infection which has become a serious epidemiological problem not only in endemic regions (Latin America), but also in non-endemic ones like North America, Europe, and Oceania. Subjects with the indeterminate chagasic form (ICF), a chronic asymptomatic disease stage, are the main sources of non-vectorial dissemination through blood transfusion, organ transplantation, and congenital transmission. It has been suggested that 94% of urban infections can be explained by these subjects. Under this scenario, the availability of simple and effective screening methods for ICF detection becomes crucial for both prevention of disease propagation and detection of clinical stages. Recently, a new non-invasive method has been proposed for ICF detection. It is based on surface high-resolution ECG and it could be easily adopted and included in modern ECG devices, overcoming the limitations of serological-based tests. The proposed method shows accuracy for early ICF screening, thus improving prognosis by defining the clinical stages and allowing appropriate and effective treatment.

Proactive approaches to identifying dementia and dementia risk; a qualitative study of public attitudes and preferences.

OBJECTIVES: The aim of this study was to critically explore the views of the public about the acceptability and feasibility of proactive approaches to earlier dementia diagnosis and also identification of people at high risk of dementia. DESIGN: Qualitative study using task group methodology and thematic data analysis. SETTING: Task groups were held either at the university (n=5) or at a carers' centre (n=1). PARTICIPANTS: A convenience sample of 31 of 54 participants identified by local non-statutory agencies took part in a task group. All were aged between 40 years and 80 years, 21 were women and 10men participated. RESULTS: Despite the use of task group methodology, participants expressed limited understandings of dementia and confusion between proactive approaches. Nevertheless, they highlighted a range of potential benefits and limitations of proactive approaches and the ethical issues raised. There was a preference to embed risk assessment within routine health checks, which focused on achieving a healthier lifestyle, rather than specifically on dementia. Participants emphasised the need to ensure informed consent prior to use of proactive approaches and to provide appropriate support. They also suggested alternative approaches that could potentially facilitate the early detection of dementia or reduce risk at a population level. CONCLUSIONS: As international policy on dementia shifts towards a prevention agenda there is growing interest in identifying those at risk of developing dementia. This study provides useful insights into the acceptability of the use of such proactive approaches among the public. The introduction of proactive approaches to dementia identification raises complex practical and ethical issues, particularly in the context of low public understanding of dementia. The importance of better quality information about dementia (and the likelihood of developing dementia) and provision of psychological support for those undergoing risk assessment were highlighted.