Neuropathogenic Forms of Huntingtin and Androgen Receptor Inhibit Fast Axonal Transport

AbstractHuntington's and Kennedy's disease are autosomal dominant neurodegenerative diseases caused by pathogenic expansion of polyglutamine tracts. Expansion of glutamine repeats must in some way confer a gain of pathological function that disrupts an essential cellular process and leads to loss of affected neurons. Association of huntingtin with vesicular structures raised the possibility that axonal transport might be altered. Here we show that polypeptides containing expanded polyglutamine tracts, but not normal N-terminal huntingtin or androgen receptor, directly inhibit both fast axonal transport in isolated axoplasm and elongation of neuritic processes in intact cells. Effects were greater with truncated polypeptides and occurred without detectable morphological aggregates

Therapists’ perceptions and acceptability of providing internet-delivered guided self-help Acceptance and Commitment Therapy (ACT) for family carers of people with dementia (iACT4CARERS): a qualitative study

This study aimed to explore therapists' perceptions and acceptability of providing internet-delivered, therapist-guided, self-help acceptance and commitment therapy (ACT) for family carers of people with dementia (iACT4CARERS). To achieve this, a qualitative approach with semi-structured interviews was employed with eight novice therapists recruited from primary and secondary care services taking part in a feasibility study of iACT4CARERS. The interviews were audio-recorded, transcribed, and analysed using thematic analysis. Four over-arching themes were identified: (1) positive attitudes towards the intervention, (2) therapists' workload, (3) therapists' confidence to perform their role, and (4) connecting with family carers in a virtual context. Theme 1 included seeing their involvement as an opportunity for personal growth and perceiving benefits to the family carers, which contributed to greater acceptability. Theme 2 reflected that while workload and the user-friendliness of the online platform were highly acceptable among the therapists, there were also time-consuming cases that increased therapists' burden. Theme 3 revealed that practical resources provided during the training, continued supervision, and opportunities to learn from other therapists, increased therapist confidence and facilitated greater acceptability. Finally, Theme 4 highlighted that improving the connection between therapists and carers was critical in a virtual context and strategies to improve the therapist-carer relationship were recommended. The implementation of iACT4CARERS was largely acceptable for the therapists involved in the trial. Ways to strengthen the therapeutic relationship in the virtual context and practical strategies to deal with common problems may enhance therapist experience and delivery in a full-scale effectiveness trial. Key learning aims (1) To understand which factors facilitated therapists' positive perceptions and acceptability of providing internet-delivered guided self-help ACT (iACT4CARERS). (2) To understand what challenges acted as barriers to therapists' positive perceptions and acceptability of providing iACT4CARERS. (3) To learn what aspects of the training and the intervention can be refined to improve the acceptability to therapists in trials involving internet-delivered guided self-help interventions for family carers

Internet-delivered guided self-help Acceptance and Commitment Therapy for family carers of people with dementia (iACT4CARERS): A qualitative study of carer views and acceptability

Purpose: To explore carers’ views and acceptability of internet-delivered, therapist-guided, self-help Acceptance and Commitment Therapy (ACT) for family carers of people with dementia (iACT4CARERS).  Methods: A qualitative approach with semi-structured interviews was employed with family carers (N=23) taking part in a feasibility study of iACT4CARERS. The interviews were audio- recorded, transcribed and analysed using thematic analysis.  Results: Four overarching themes were identified: 1) usefulness and relevance of the content of the sessions, 2) sense of connectedness, 3) the impact of the intervention on participants and 4) acceptability of the online delivery. Positive carer experiences and intervention acceptability were facilitated by learning helpful ACT skills, perceiving the content of the session as relatable to the carers' needs, feeling connected to other carers and the therapist during the intervention, noticing the benefits of the intervention and the user-friendliness of the online platform. Recommendations for a full-scale trial were identified, such as the inclusion of some ‘face-to-face’ interactions (e.g. via video call) between carers and therapists to facilitate a bidirectional interaction and the provision of an additional aide-memoire to improve the learning experiences.  Conclusion: Overall, the intervention was acceptable to the family carers. The proposed recommendations should be considered in a full-scale trial

Internet-delivered guided self-help Acceptance and Commitment Therapy for family carers of people with dementia (iACT4CARERS): A feasibility study

Objective: The feasibility of research into internet-delivered guided self-help Acceptance and Commitment Therapy (ACT) for family carers of people with dementia is not known. This study assessed this in an uncontrolled feasibility study. Methods: Family carers of people with dementia with mild to moderate anxiety or depression were recruited from primary and secondary healthcare services in the UK. Participants were offered eight, guided, self-help online ACT sessions adapted for the needs of family carers of people with dementia with optional online peer support groups. Pre-defined primary indicators of success included recruitment of 30 eligible carers over six months and ≥70% completing at least two online sessions. Results: Thirty-three participants (110% of the target sample) were recruited over six months and 30 participants (91%) completed two or more sessions, and thus both indicators of success were met. Further, 70% of participants completed seven or all eight sessions, and 27% of participants were lost to follow-up, but none of the reasons for early withdrawal were related to the intervention. Conclusion: This study supports the feasibility, including recruitment and treatment completion. A full-scale trial to assess the clinical- and cost-effectiveness of the intervention including its long-term effects is warranted. Registration: ISRCTN trial registration 1895641

Less Common Bacterial, Fungal and Viral Infections: Review of Management in the Pregnant Patient

This review is a comprehensive summary of treatment options for pregnant patients with less common bacterial, fungal, and viral infections. It offers guidance to clinicians based on the most recently published evidence-based research and expert recommendations. A search of MEDLINE (inception to March 2021) and the CDC website was performed. Liposomal amphotericin B is the preferred therapy for cryptococcosis, histoplasmosis, oesophageal candidiasis, and coccidioidomycosis, especially during the first trimester due to teratogenic concerns with azole antifungals. For oral candidiasis, clotrimazole troches or miconazole mucoadhesive buccal tablets are recommended. A β-lactam antimicrobial is preferred over doxycycline for various manifestations of Lyme disease and the drug of choice for pneumonia is trimethoprim/sulfamethoxazole. Acyclovir is the preferred antiviral for varicella zoster virus. Fluoroquinolones, macrolides, and aminoglycosides should be avoided if possible and there are alternate agents available for an effective treatment regimen. There is a scarcity of clinical data in pregnant patients with less common bacterial, fungal and viral infections. This population lacks definitive recommendations in many clinical practice guidelines. The key to optimizing therapy is a comprehensive review of the available evidence and a careful balance of risks and benefits before final treatment decisions

A study of the cold cores population in the Serpens star-forming region

As part of the Herschel Gould Belt survey, the Serpens star-forming region was observed with the Herschel PACS and SPIRE instruments. Data analysis is ongoing and a first version of the source catalog is ready; here we show some preliminary results

A study of the cold cores population in the Perseus star-forming regions

As part of the Herschel Gould Belt survey, the Perseus star-forming cloud was observed with the Herschel PACS and SPIRE instruments. Source catalogs are preliminary, as well as the here presented core mass function

The emergence of inequality in social groups: network structure and institutions affect the distribution of earnings in cooperation games

From small communities to entire nations and society at large, inequality in wealth, social status, and power is one of the most pervasive and tenacious features of the social world. What causes inequality to emerge and persist? In this study, we investigate how the structure and rules of our interactions can increase inequality in social groups. Specifically, we look into the effects of four structural conditions—network structure, network fluidity, reputation tracking, and punishment institutions—on the distribution of earnings in network cooperation games. We analyze 33 experiments comprising 96 experimental conditions altogether. We find that there is more inequality in clustered networks compared to random networks, in fixed networks compared to randomly rewired and strategically updated networks, and in groups with punishment institutions compared to groups without. Secondary analyses suggest that the reasons inequality emerges under these conditions may have to do with the fact that fixed networks allow exploitation of the poor by the wealthy and clustered networks foster segregation between the poor and the wealthy, while the burden of costly punishment falls onto the poor, leaving them poorer. Surprisingly, we do not find evidence that inequality is affected by reputation in a systematic way but this could be because reputation needs to play out in a particular network environment in order to have an effect. Overall, our findings suggest possible strategies and interventions to decrease inequality and mitigate its negative impact, particularly in the context of mid- and large-sized organizations and online communities

Results of the COVID-19 mental health international for the general population (COMET-G) study.

INTRODUCTION: There are few published empirical data on the effects of COVID-19 on mental health, and until now, there is no large international study. MATERIAL AND METHODS: During the COVID-19 pandemic, an online questionnaire gathered data from 55,589 participants from 40 countries (64.85% females aged 35.80 ± 13.61; 34.05% males aged 34.90±13.29 and 1.10% other aged 31.64±13.15). Distress and probable depression were identified with the use of a previously developed cut-off and algorithm respectively. STATISTICAL ANALYSIS: Descriptive statistics were calculated. Chi-square tests, multiple forward stepwise linear regression analyses and Factorial Analysis of Variance (ANOVA) tested relations among variables. RESULTS: Probable depression was detected in 17.80% and distress in 16.71%. A significant percentage reported a deterioration in mental state, family dynamics and everyday lifestyle. Persons with a history of mental disorders had higher rates of current depression (31.82% vs. 13.07%). At least half of participants were accepting (at least to a moderate degree) a non-bizarre conspiracy. The highest Relative Risk (RR) to develop depression was associated with history of Bipolar disorder and self-harm/attempts (RR = 5.88). Suicidality was not increased in persons without a history of any mental disorder. Based on these results a model was developed. CONCLUSIONS: The final model revealed multiple vulnerabilities and an interplay leading from simple anxiety to probable depression and suicidality through distress. This could be of practical utility since many of these factors are modifiable. Future research and interventions should specifically focus on them