Granulovacuolar degeneration (GVD) occurs in Alzheimer's disease (AD) brain due to compromised autophagy. Endoplasmic reticulum (ER) function and RNA binding protein (RBP) homeostasis regulate ...autophagy. We observed that the ER chaperones Glucose - regulated protein, 78 KDa (GRP78/BiP), Sigma receptor 1 (SigR1), and Vesicle-associated membrane protein associated protein B (VAPB) were elevated in many AD patients' subicular neurons. However, those neurons which were affected by GVD showed lower chaperone levels, and there was only minor co-localization of chaperones with GVD bodies (GVBs), suggesting that neurons lacking sufficient chaperone-mediated proteostasis enter the GVD pathway. Consistent with this notion, granular, incipient pTau aggregates in human AD and pR5 tau transgenic mouse neurons were regularly co-localized with increased chaperone immunoreactivity, whereas neurons with mature neurofibrillary tangles lacked both the chaperone buildup and significant GVD. On the other hand, APP/PS1 (APPswe/PSEN1dE9) transgenic mouse hippocampal neurons that are devoid of pTau accumulation displayed only few GVBs-like vesicles, which were still accompanied by prominent chaperone buildup. Identifying a potential trigger for GVD, we found cytoplasmic accumulations of RBPs including Matrin 3 and FUS as well as stress granules in GVBs of AD patient and pR5 mouse neurons. Interestingly, we observed that GVBs containing aggregated pTau and pTDP-43 were consistently co-localized with the exosomal marker Flotillin 1 in both AD and pR5 mice. In contrast, intraneuronal 82E1-immunoreactive amyloid-β in human AD and APP/PS1 mice only rarely co-localized with Flotillin 1-positive exosomal vesicles. We conclude that altered chaperone-mediated ER protein homeostasis and impaired autophagy manifesting in GVD are linked to both pTau and RBP accumulation and that some GVBs might be targeted to exocytosis.
Despite higher rates of suicide in men, there is a dearth of research examining the perspectives and experiences of males at risk of suicide, particularly in terms of understanding how interventions ...can be tailored to men's specific needs. The current study aimed to examine factors assisting, complicating or inhibiting interventions for men at risk, as well as outlining the roles of family, friends and others in male suicide prevention. Thirty-five male suicide survivors completed one-to-one interviews, and forty-seven family and friends of male suicide survivors participated in eight focus groups. Thematic analysis revealed five major themes: (1) development of suicidal behaviours tends to follow a common path associated with specific types of risk factors (disrupted mood, unhelpful stoic beliefs and values, avoidant coping strategies, stressors), (2) men at risk of suicide tend to systematically misinterpret changes in their behaviour and thinking, (3) understanding mood and behavioural changes in men enables identification of opportunities to interrupt suicide progression, (4) distraction, provision of practical and emotional supports, along with professional intervention may effectively interrupt acute risk of harm, and (5) suicidal ideation may be reduced through provision of practical help to manage crises, and helping men to focus on obligations and their role within families. Findings suggest that interventions for men at risk of suicidal behaviours need to be tailored to specific risk indicators, developmental factors, care needs and individuals' preferences. To our knowledge this is the first qualitative study to explore the experiences of both suicidal men and their family/friends after a suicide attempt, with the view to improve understanding of the processes which are effective in interrupting suicide and better inform interventions for men at risk.
The Parental Bonding Instrument (PBI) measures the perception of being parented to the age of 16 years. Low scores on the care dimension and high scores on the overprotection dimension are considered ...to be risk factors of depression. While the PBI has been shown to be a reliable and valid instrument, the stability of the PBI over extended periods (taking into account individual characteristics and life experience) needs to be demonstrated.
The PBI was measured in a non-clinical cohort on four waves between 1978 and 1998, along with a series of self-report measures including state depression and neuroticism. Differences in PBI change over time were examined by gender, lifetime major depression diagnosis, and life event variables, as well as by scores on neuroticism and state depression.
Acceptable retest coefficients on PBI scores over the 20-year study were found for the cohort. No differences were found in PBI scores over time on the variables examined, including sex and depression measures.
The results indicate long-term stability of the PBI over time. The influences of mood state and life experience appear to have little effect on the stability of the perception of parenting as measured by the PBI. The present study increases confidence in the PBI as a valid measure of perceived parenting over extended time periods.
The aim of this study was to identify whether the addition of cognitive impairment, depression, or both, to the assessment of physical frailty provides better outcome prediction in patients with ...advanced heart failure referred for heart transplantation (HT).
Beginning in March 2013, all patients with advanced heart failure referred to our Transplant Unit have undergone a physical frailty assessment using the Fried frailty phenotype. Cognition was assessed with the Montreal Cognitive Assessment and depression with the Depression in Medical Illness questionnaire. We assessed the value of 4 composite frailty measures: physical frailty (PF ≥ 3 of 5 = frailty), "cognitive frailty" (CogF ≥ 3 of 6 = frail), "depressive frailty" (DepF ≥ 3 of 6 = frail), and "cognitive-depressive frailty" (ComF ≥ 3 of 7 = frail) in predicting outcomes.
Frailty was assessed in 156 patients (109 men, 47 women), aged 53 ± 13 years, and with a left ventricular ejection fraction of 27% ± 14%. Inclusion of cognitive impairment or depression in the definition of frailty increased the proportion classified as frail from 33% using PF to 42% using ComF. During follow-up, 28 patients died before ventricular assist device implantation or HT. Frailty was associated with significantly lower ventricular assist device- and HT-free survival, with CogF best capturing early mortality: 12-month survival for non-frail and frail cohorts was 81% ± 5% vs 58% ± 10% (p < 0.02) using PF and 85% ± 5% vs 56% ± 9% (p < 0.002) using CogF. Combining the Depression in Medical Illness score with PF or CogF did not strengthen the relationship between frailty and mortality.
The addition of cognitive impairment to the assessment of PF strengthened its capacity to identify advanced heart failure patients referred for HT who are at high risk of early death.
Background
Olfactory deficits have a diverse etiology and can be detected with simple olfactory tests. Key olfactory pathways are located within the frontal and temporal lobes where they are ...vulnerable to damage due to head trauma. Orbitofrontal cortex (OFC) integrity is important for olfaction and aspects of behavioral regulation. We measured olfactory identification ability in a sample of impulsive violent offenders to determine its associations with history of traumatic brain injury (TBI) and a range of neuropsychiatric indices, including proxies for cognitive ability, impulsivity and social connectedness.
Methods
Male participants were drawn from the ReINVEST study, a randomized controlled trial of sertraline to reduce recidivism in violent impulsive offenders. Criteria for participation in the study included a minimum age of 18 years, a documented history of two or more violent offenses, and a score of 70 or above on the Barratt Impulsiveness Scale (BIS-11). The 16-item “Sniffin sticks” (SS) odor identification test (OI) was administered as were standardized questionnaires regarding previous TBI, additional measures to screen cognition word reading test of the Wechsler Individuals Achievement Test (WIAT), social connectedness (the Duke Social Support Scale), and a range of other neuropsychiatric conditions or symptoms. The sample SS scores were compared against published age-specific norms. Univariate and multivariate analyses were performed with SS score (linear regression, within those without hyposmia) or hyposmia (logistic regression) as the outcome.
Results
The mean OI scores were lower than population norms and 16% of participants were classified as hyposmic. Univariate analyses showed associations of SS score with age, WIAT score, impulsivity, TBI and TBI severity, social connectedness, childhood sexual abuse, suicidality and current use of heroin. In multivariate analyses, age, TBI severity and WIAT remained as significant independent predictors of SS score (within the normosmic range) or hyposmia (logistic regression).
Conclusion
Olfactory performance was associated with multiple behavioral phenomena in a pattern that would be consistent with this serving as a proxy for orbitofrontal functioning. As such, OI testing may have utility in further studies of offenders. In future, we will examine whether olfactory score predicts recidivism or response to the administration of sertraline, in terms of reducing recidivism.
Clinicians need to be able to assess the quality of the available information to aid clinical decision-making. The internet has become an important source of health information for consumers and ...their families.
This study aimed to rate the quality of websites with psychosis-related information (to provide clinicians with a basis for recommending material to guide clinical decision-making with consumers and their families), using a validated instrument as well as a purpose-developed checklist, and consider improvement in quality over a 4-year period.
Two measures of website quality were used: the DISCERN scale and the Psychosis Website Quality Checklist (PWQC). Terms related to psychosis, including "psychotic," "psychosis," "schizophrenia," "delusion," and "hallucination," were entered into Google, and the first 25 results were analyzed. In total, 6 raters with varying health professional backgrounds were used to evaluate the websites across two time points: January-March 2014 and January-March 2018.
Of the 25 websites rated, only the 6 highest ranked websites achieved a DISCERN score, indicating that they were of "good" quality (51-62 out of a possible 75), while the mean score of the websites (mean 43.96, SD 12.08) indicated an overall "fair" quality. The PWQC revealed that websites scored highly on "availability and usability" (mean 16.82, SD 3.96) but poorly on "credibility" (mean 20.99, SD 6.68), "currency" (mean 5.16, SD 2.62), and "breadth and accuracy" (mean 77.87, SD 23.20). Most sites lacked information about early intervention, recreational drug use and suicide risk, with little change in content over time. Stating an editorial or review process on the website (found in 56% of websites) was significantly associated with a higher quality score on both scales (the DISCERN scale, P=.002; the PWQC, P=.006).
The information on the internet available for clinicians to recommend to people affected by psychosis tended to be of "fair" quality. While higher-quality websites exist, it is generally not easy way to assess this on face value. Evidence of an editorial or review process was one indicator of website quality. While sites generally provided basic clinical information, most lacked material addressing weighing up risks and benefits of medication and alternatives, the role of coercive treatment and other more contentious issues. Insufficient emphasis is placed on detailed information on early intervention and importance of lifestyle modifications or how families and friends can contribute. These are likely to be the very answers that consumers and carers are seeking and this gap contributes to unmet needs among this group. We suggest that clinicians should be aware of what is available and where there are gaps.
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