Characterising the behaviours in most severe and least severe emotional outbursts in young people

Emotional outbursts are displays of intense, challenging behaviour and are prevalent in individuals with neurodevelopmental disorders. Outbursts present a danger to individuals and their carers and are cited as reasons for referral to mental health services. However, it is currently unclear how the characteristics of outbursts may determine their severity. Carers (n = 214) of individuals aged between 6 and 25 and experiencing outbursts at least once per month completed the Emotional Outburst Questionnaire. Questionnaire items were used to compare behaviours observed in most severe and least severe outbursts through quantitative and content analyses of open ended data. Signs of physiological arousal and aggression were seen significantly more in most severe outbursts compared to least severe outbursts. Least severe outbursts were seen more frequently, but most severe outbursts were reported to have a longer duration, be at a higher intensity, and have a longer recovery time. Additionally, associations were found between reduced eye contact and most severe outbursts, as well as expression of suicidal ideation and most severe outbursts. Certain behaviours, notably forms of aggression and physiological arousal, are associated with most severe outbursts. Findings of this study may allow future work examining cross-disorder differences in outbursts to inform targeted interventions aiming to reduce outburst severity and impact. Additionally, identification of such outburst characteristics could aid in measurement of outburst severity, which would allow for more reliable and valid studies on outburst interventions

Thioredoxins function as deglutathionylase enzymes in the yeast Saccharomyces cerevisiae

<p>Abstract</p> <p>Background</p> <p>Protein-SH groups are amongst the most easily oxidized residues in proteins, but irreversible oxidation can be prevented by protein glutathionylation, in which protein-SH groups form mixed disulphides with glutathione. Glutaredoxins and thioredoxins are key oxidoreductases which have been implicated in regulating glutathionylation/deglutathionylation in diverse organisms. Glutaredoxins have been proposed to be the predominant deglutathionylase enzymes in many plant and mammalian species, whereas, thioredoxins have generally been thought to be relatively inefficient in deglutathionylation.</p> <p>Results</p> <p>We show here that the levels of glutathionylated proteins in yeast are regulated in parallel with the growth cycle, and are maximal during stationary phase growth. This increase in glutathionylation is not a response to increased reactive oxygen species generated from the shift to respiratory metabolism, but appears to be a general response to starvation conditions. Our data indicate that glutathionylation levels are constitutively high in all growth phases in thioredoxin mutants and are unaffected in glutaredoxin mutants. We have confirmed that thioredoxins, but not glutaredoxins, catalyse deglutathionylation of model glutathionylated substrates using purified thioredoxin and glutaredoxin proteins. Furthermore, we show that the deglutathionylase activity of thioredoxins is required to reduce the high levels of glutathionylation in stationary phase cells, which occurs as cells exit stationary phase and resume vegetative growth.</p> <p>Conclusions</p> <p>There is increasing evidence that the thioredoxin and glutathione redox systems have overlapping functions and these present data indicate that the thioredoxin system plays a key role in regulating the modification of proteins by the glutathione system.</p

A UK survey of COVID‐19 related social support closures and their effects on older people, people with dementia, and carers

Abstract Objectives The aim of this national survey was to explore the impact of COVID‐19 public health measures on access to social support services and the effects of closures of services on the mental well‐being of older people and those affected by dementia. Methods A UK‐wide online and telephone survey was conducted with older adults, people with dementia, and carers between April and May 2020.The survey captured demographic and postcode data, social support service usage before and after COVID‐19 public health measures, current quality of life, depression, and anxiety. Multiple linear regression analysis was used to explore the relationship between social support service variations and anxiety and well‐being. Results 569 participants completed the survey (61 people with dementia, 285 unpaid carers, and 223 older adults). Paired samples t‐tests and X2‐tests showed that the mean hour of weekly social support service usage and the number of people having accessed various services was significantly reduced post COVID‐19. Multiple regression analyses showed that higher variations in social support service hours significantly predicted increased levels of anxiety in people with dementia and older adults, and lower levels of mental well‐being in unpaid carers and older adults. Conclusions Being unable to access social support services due to COVID contributed to worse quality of life and anxiety in those affected by dementia and older adults across the UK. Social support services need to be enabled to continue providing support in adapted formats, especially in light of continued public health restrictions for the foreseeable future. This article is protected by copyright. All rights reserved

Global regulation of gene expression by OxyR in an important human opportunistic pathogen

Most bacteria control oxidative stress through the H2O2-responsive transactivator OxyR, a member of the LTTR family (LysR Type Transcriptional Regulators), which activates the expression of defensive genes such as those encoding catalases, alkyl hydroperoxide reductases and superoxide dismutases. In the human opportunistic pathogen Pseudomonas aeruginosa, OxyR positively regulates expression of the oxidative stress response genes katA, katB, ahpB and ahpCF. To identify additional targets of OxyR in P. aeruginosa PAO1, we performed chromatin immunoprecipitation in combination with whole genome tiling array analyses (ChIP-chip). We detected 56 genes including all the previously identified defensive genes and a battery of novel direct targets of OxyR. Electrophoretic mobility shift assays (EMSAs) for selected newly identified targets indicated that ∼70% of those were bound by purified oxidized OxyR and their regulation was confirmed by quantitative real-time polymerase chain reaction. Furthermore, a thioredoxin system was identified to enzymatically reduce OxyR under oxidative stress. Functional classification analysis showed that OxyR controls a core regulon of oxidative stress defensive genes, and other genes involved in regulation of iron homeostasis (pvdS), quorum-sensing (rsaL), protein synthesis (rpsL) and oxidative phosphorylation (cyoA and snr1). Collectively, our results indicate that OxyR is involved in oxidative stress defense and regulates other aspects of cellular metabolism as well

Contextualising the pervasive impact of macroeconomic austerity on prison health in England: A qualitative study among international policymakers

Background: Prisons offer the state the opportunity to gain access to a population that is at particularly high risk of ill-health. Despite the supportive legal and policy structures surrounding prison rehabilitation, the oppressive nature of the austerity policy in England threatens its advanced improvement.Methods: Using grounded theory methodology, this is the first interdisciplinary qualitative study to explore the impact of macroeconomic austerity on prison health in England from the perspective of 29 international prison policymakers.Results: The far-reaching impact of austerity in England has established a regressive political system that shapes the societal attitude towards social issues, which has exacerbated the existing poor health of the prisoners. Austerity has undermined the notion of social collectivism, imposed a culture of acceptance among prison bureaucrats and the wider community, and normalised the devastating impacts of prison instability. These developments are evidenced by the increasing levels of suicide, violence, radicalisation and prison gangs among prisoners, as well as the imposition of long working hours and the high levels of absenteeism among prison staff.Conclusions: This study underscores an important and yet unarticulated phenomenon that despite being the fifth largest economy in the world, England’s poorest, marginalised and excluded population continues to bear the brunt of austerity. Reducing the prison population, using international obligations as minimum standards to protect prisoners’ right to health and providing greater resources would create a more positive and inclusive system, in line with England’s international and domestic commitments to the humane treatment of all people

Deciphering the diagenetic history of the El Abra Formation of eastern Mexico using reordered clumped isotope temperatures and U-Pb dating

Carbonates form ubiquitously throughout the history of deposition, burial, and uplift of basins. As such, they potentially record the environmental conditions at the time of formation. Carbonate clumped isotopes provide the temperature of precipitation but can be internally reordered if the host rock is exposed to elevated temperatures over geologic time scales. Here, we exploited this kinetic behavior by analyzing multiple generations of cements that capture the range of environments experienced by the El Abra Formation from eastern Mexico. From this, we developed a quantitative diagenetic history for these different phases of cementation. We observed a 70 °C range in clumped isotope temperatures from 64 °C to 134 °C for these cements, which is not compatible with their inferred precipitation environments. This suggests that bond reordering occurred during burial but did not fully reorder all cements to a common apparent temperature. We reconstructed original cement growth temperatures and the isotopic signature of the parent fluids to show that precipitation from a marine pore fluid began at 125 Ma, contemporaneous with deposition, and continued throughout burial to temperatures of at least 138 °C at 42 Ma. We show that precipitation of equant cements, which occluded 90% of the pore space, was coincident with Laramide-related burial to depths greater than 3800 m. A U-Pb age of diagenetic calcite of 77.1 ± 3.6 Ma provides independent support for our estimates of the absolute timing of precipitation of two distinct phases of the paragenesis. This is the first demonstration of the utility of integrating U-Pb age dating with reordered clumped isotope temperatures to provide quantitative constraints on the time-temperature history of cementation. Such information may ultimately lead to advances in our understanding of the formational environments and geological processes that drive diagenesis in carbonates for temperatures below the clumped isotope “blocking temperature.

COVID-19-related social support service closures and mental well-being in older adults and those affected by dementia: a UK longitudinal survey

Background: The COVID-19 pandemic has had a major impact on delivery of social support services. This might be expected to particularly affect older adults and people living with dementia (PLWD), and to reduce their well-being. Aims: To explore how social support service use by older adults, carers and PLWD, and their mental well-being changed over the first 3 months since the pandemic outbreak. Methods: Unpaid dementia carers, PLWD and older adults took part in a longitudinal online or telephone survey collected between April and May 2020, and at two subsequent timepoints 6 and 12 weeks after baseline. Participants were asked about their social support service usage in a typical week prior to the pandemic (at baseline), and in the past week at each of the three timepoints. They also completed measures of levels of depression, anxiety and mental well-being. Results: 377 participants had complete data at all three timepoints. Social support service usage dropped shortly after lockdown measures were imposed at timepoint 1 (T1), to then increase again by T3. The access to paid care was least affected by COVID-19. Cases of anxiety dropped significantly across the study period, while cases of depression rose. Well-being increased significantly for older adults and PLWD from T1 to T3. Conclusions: Access to social support services has been significantly affected by the pandemic, which is starting to recover slowly. With mental well-being differently affected across groups, support needs to be put in place to maintain better well-being across those vulnerable groups during the ongoing pandemic

Development of the PSYCHS: Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS

Aim: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). Methods: The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences. Results: Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and modest harmonization for CHR-P criteria. The semi-structured interview, named Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS. Conclusions: Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses