Adeno-associated virus 2 infection in children with non-A-E hepatitis.

An outbreak of acute hepatitis of unknown aetiology in children was reported in Scotland1 in April 2022 and has now been identified in 35 countries2. Several recent studies have suggested an association with human adenovirus with this outbreak, a virus not commonly associated with hepatitis. Here we report a detailed case-control investigation and find an association between adeno-associated virus 2 (AAV2) infection and host genetics in disease susceptibility. Using next-generation sequencing, PCR with reverse transcription, serology and in situ hybridization, we detected recent infection with AAV2 in plasma and liver samples in 26 out of 32 (81%) cases of hepatitis compared with 5 out of 74 (7%) of samples from unaffected individuals. Furthermore, AAV2 was detected within ballooned hepatocytes alongside a prominent T cell infiltrate in liver biopsy samples. In keeping with a CD4+ T-cell-mediated immune pathology, the human leukocyte antigen (HLA) class II HLA-DRB1*04:01 allele was identified in 25 out of 27 cases (93%) compared with a background frequency of 10 out of 64 (16%; P = 5.49 × 10-12). In summary, we report an outbreak of acute paediatric hepatitis associated with AAV2 infection (most likely acquired as a co-infection with human adenovirus that is usually required as a 'helper virus' to support AAV2 replication) and disease susceptibility related to HLA class II status.

The association between discordant umbilical arterial resistance in growth-restricted fetuses and adverse outcomes.

BACKGROUND: Assessing the umbilical artery pulsatility index via Doppler measurements plays a crucial role in evaluating fetal growth impairment. OBJECTIVE: This study aimed to investigate perinatal outcomes associated with discordant pulsatility indices of umbilical arteries in fetuses with growth restriction. STUDY DESIGN: In this retrospective cohort study, all singleton pregnancies were included if their estimated fetal weight and/or abdominal circumference fell below the 10th percentile for gestational age (2017-2022). Eligible cases included singleton pregnancies with concurrent sampling of both umbilical arteries within 14 days of birth at the ultrasound evaluation closest to delivery. The exclusion criteria included births before 22 weeks of gestation, evidence of absent or reverse end-diastolic flow in either umbilical artery, and known fetal genetic or structural anomalies. The study compared cases with discordant umbilical artery pulsatility index values (defined as 1 umbilical artery pulsatility index at ≤95th percentile and the other umbilical artery pulsatility index at >95th percentile for gestational age) to pregnancies where both umbilical artery pulsatility indices had normal pulsatility index values and those with both umbilical arteries displaying abnormal pulsatility index values. The primary outcome assessed was the occurrence of composite adverse neonatal outcomes. Multivariable logistic regressions were performed, adjusting for relevant covariates. RESULTS: The study encompassed 1014 patients, including 194 patients (19.1%) with discordant umbilical artery pulsatility index values among those who had both umbilical arteries sampled close to delivery, 671 patients (66.2%) with both umbilical arteries having normal pulsatility index values, and 149 patients (14.7%) with both umbilical arteries exhibiting abnormal values. Pregnancies with discordant umbilical artery pulsatility index values displayed compromised sonographic parameters compared with those with both umbilical arteries showing normal pulsatility index values. Similarly, the number of abnormal umbilical artery pulsatility index values was associated with adverse perinatal outcomes in a dose-response manner. Cases with 1 abnormal (discordant) umbilical artery pulsatility index value showed favorable sonographic parameters and perinatal outcomes compared with cases with both abnormal umbilical artery pulsatility index values, and cases with both abnormal umbilical artery pulsatility index values showed worse sonographic parameters and perinatal outcomes compared with cases with discordant UA PI values. Multivariate analysis revealed that discordant umbilical artery pulsatility indices were significantly and independently associated with composite adverse perinatal outcomes, with an adjusted odds ratio of 1.75 (95% confidence interval, 1.24-2.47; P = .002). CONCLUSION: Evaluating the resistance indices of both umbilical arteries may provide useful data and assist in assessing adverse perinatal outcomes among fetuses with growth restriction.

Determinants of durable humoral and T cell immunity in myeloma patients following COVID-19 vaccination.

OBJECTIVE: To describe determinants of persisting humoral and cellular immune response to the second COVID-19 vaccination among patients with myeloma. METHODS: This is a prospective, observational study utilising the RUDYstudy.org platform. Participants reported their second and third COVID-19 vaccination dates. Myeloma patients had an Anti-S antibody level sample taken at least 21 days after their second vaccination and a repeat sample before their third vaccination. RESULTS: 60 patients provided samples at least 3 weeks (median 57.5 days) after their second vaccination and before their third vaccination (median 176.0 days after second vaccine dose). Low Anti-S antibody levels (<50 IU/mL) doubled during this interval (p = .023) and, in the 47 participants with T-spot data, there was a 25% increase negative T-spot tests (p = .008). Low anti-S antibody levels prior to the third vaccination were predicted by lower Anti-S antibody level and negative T-spot status after the second vaccine. Independent determinants of a negative T-spot included increasing age, previous COVID infection, high CD4 count and lower percentage change in Anti-S antibody levels. CONCLUSIONS: Negative T-spot results predict low Anti-S antibody levels (<50 IU/mL) following a second COVID-19 vaccination and a number of biomarkers predict T cell responses in myeloma patients.

Characterising illness stages and recovery trajectories of eating disorders in young people via remote measurement technology (STORY): a multi-centre prospective cohort study protocol.

BACKGROUND: Eating disorders (EDs) are serious, often chronic, conditions associated with pronounced morbidity, mortality, and dysfunction increasingly affecting young people worldwide. Illness progression, stages and recovery trajectories of EDs are still poorly characterised. The STORY study dynamically and longitudinally assesses young people with different EDs (restricting; bingeing/bulimic presentations) and illness durations (earlier; later stages) compared to healthy controls. Remote measurement technology (RMT) with active and passive sensing is used to advance understanding of the heterogeneity of earlier and more progressed clinical presentations and predictors of recovery or relapse. METHODS: STORY follows 720 young people aged 16-25 with EDs and 120 healthy controls for 12 months. Online self-report questionnaires regularly assess ED symptoms, psychiatric comorbidities, quality of life, and socioeconomic environment. Additional ongoing monitoring using multi-parametric RMT via smartphones and wearable smart rings ('Oura ring') unobtrusively measures individuals' daily behaviour and physiology (e.g., Bluetooth connections, sleep, autonomic arousal). A subgroup of participants completes additional in-person cognitive and neuroimaging assessments at study-baseline and after 12 months. DISCUSSION: By leveraging these large-scale longitudinal data from participants across ED diagnoses and illness durations, the STORY study seeks to elucidate potential biopsychosocial predictors of outcome, their interplay with developmental and socioemotional changes, and barriers and facilitators of recovery. STORY holds the promise of providing actionable findings that can be translated into clinical practice by informing the development of both early intervention and personalised treatment that is tailored to illness stage and individual circumstances, ultimately disrupting the long-term burden of EDs on individuals and their families.

Internet videoconferencing delivered cognitive behaviour therapy for generalized anxiety disorder: A randomized controlled trial.

OBJECTIVE: Generalized anxiety disorder (GAD) is a chronic mental health condition that results in significant individual and societal burden. Cognitive-behaviour therapy (CBT) therapy is an effective treatment for GAD, however, many individuals experience logistical barriers when accessing evidence-based care. Remote treatments may help to reduce these barriers, however, currently, there are few studies examining the efficacy of high-intensity remote methods for GAD treatment. The current study aims to examine the efficacy of CBT delivered via videoconferencing (VCBT) for GAD using a randomized controlled trial design comparing an immediate treatment group to a waitlist control. METHOD: Seventy-eight adults (Mage = 36.92; SD = 12.92; 84.4% female) with GAD were enrolled in the study. RESULTS: Those in the treatment group demonstrated a statistically significant reduction in GAD symptoms from pre-treatment to post-treatment (d = 1.03) and pre-treatment to 3-month follow-up (d = 1.50). Large between-group effect sizes were also observed at post-treatment (d = .80). Twenty-five participants (64.10%) in the VCBT group no longer met diagnostic criteria for GAD at post-treatment, and 26/39 (66.67%) no longer met criteria at 3-month follow-up. Ninety-six per cent of participants were satisfied with the treatment. CONCLUSION: The results contribute towards advancing our knowledge on the efficacy and acceptability of VCBT for patients with GAD.

Long-Term Outcomes of Multiple versus a Single Course of Antenatal Steroids: A Systematic Review.

Multiple courses versus a single course of antenatal corticosteroids (ACS) have been associated with mild respiratory benefits but also adverse outcomes like smaller head circumference and birth weight. Long-term effects warrant study. We systematically reviewed long-term outcomes (≥1 year) in both preterm and term birth after exposure to preterm multiple courses (including a rescue dose or course) versus a single course. We searched seven databases from January 2000 to October 2021. We included follow-up studies of randomized controlled trials (RCTs) and cohort studies with births occurring in/after the year 2000, given advances in perinatal care. Two reviewers assessed titles/abstracts, articles, quality, and outcomes including psychological disorders, neurodevelopment, and anthropometry. Six follow-up studies of three RCTs and two cohort studies (over 2,860 children total) met inclusion criteria. Among children born preterm, randomization to multiple courses versus a single course of ACS was not associated with adjusted beneficial or adverse neurodevelopmental/psychological or other outcomes, but data are scant after a rescue dose (120 and 139 children, respectively, low certainty) and nonexistent after a rescue course. For children born at term (i.e., 27% of the multiple courses of ACS 5-year follow-up study of 1,728 preterm/term born children), preterm randomization to multiple courses (at least one additional course) versus a single course was significantly associated with elevated odds of neurosensory impairment (adjusted odds ratio = 3.70, 95% confidence interval: 1.57-8.75; 212 and 247 children, respectively, moderate certainty). In this systematic review of long-term outcomes after multiple courses versus a single course of ACS, there were no significant benefits or risks regarding neurodevelopment in children born preterm but little data after one rescue dose and none after a rescue course. However, multiple courses (i.e., at least one additional course) should be considered cautiously: after term birth, there are no long-term benefits but neurosensory harms. KEY POINTS: · We systematically reviewed the long-term impact of multiple versus a single course of ACS.. · Long-term follow-up data were scant after a rescue dose and absent after one rescue course of ACS.. · In children born preterm, multiple courses of ACS were not associated with long-term benefits/harms.. · In children born at term, multiple courses of ACS were associated with neurosensory impairment.. · Preterm administration of multiple courses of ACS should be considered cautiously..

Efficacy and acceptability of a self-guided internet-delivered cognitive-behavioral educational program for obsessive-compulsive symptoms with international recruitment.

Cognitive-behavioural therapy is an effective treatment for obsessive-compulsive disorder (OCD). However, there are many barriers in accessing this treatment, with stigma being a particularly prominent barrier for many patients. Self-guided internet-delivered cognitive-behavioural therapy (ICBT), which does not require any contact with a therapist, has the potential to overcome this barrier. However, there is limited research on the efficacy of self-guided ICBT for OCD. The aim of the current study was to examine the efficacy of self-guided ICBT for OCD in a large international sample. Two hundred and sixteen participants were included in the study (Mage = 34.00; SD = 12.57; 72.7% female). On the primary outcome measure, the Yale-Brown Obsessive-Compulsive Scale (YBOCS), a medium within-group effect size was found from pre-treatment to post-treatment (g = 0.63), and a large within-group effect size was found from pre-treatment to 3-month follow-up (g = 0.98). Approximately one-quarter to one-third of participants met criteria for clinically significant improvement at post-treatment and 3-month follow-up (11% and 17% met criteria for remission at post-treatment and 3-month follow-up, respectively). These results demonstrate that self-guided ICBT may be an efficacious treatment for individuals with OCD who cannot or do not wish to engage with a mental health professional, resulting in medium to large effect sizes.

Correlates of depression in individuals with obsessive compulsive disorder.

The existing literature examining the correlates of depression in individuals with obsessive compulsive disorder (OCD) is characterized by inconsistent results. The aim of the current study was to replicate and extend the literature by exploring whether various clinical and demographic factors are related to the occurrence of depression in a large sample (N = 243) of individuals with OCD (M age = 33.00; SD = 12.47; 74% female). Individuals with OCD who had elevated comorbid depressive symptoms [Patient Health Questionnaire-9 item (PHQ-9) ≥10] scored significantly higher on all OCD symptom subtypes (p range < .001-.048), had greater obsessive and compulsive severity (ps < .001), scored higher on perfectionism (p < .001), and had higher disgust sensitivity and propensity scores (ps < .001) compared with individuals who did not have comorbid depressive symptoms (PHQ-9 < 10). Of these variables, obsession severity (ß = 0.22, p = .004), OCD contamination subtype (ß = 0.16, p = .032) and perfectionism (ß = 0.25, p < .001) were found to be associated with depressive symptoms on the PHQ-9. The findings of this study contribute to the understanding of factors which are associated with depression comorbidity in individuals with OCD.

Predictors of outcome in self-guided internet-delivered cognitive-behavior therapy for obsessive-compulsive disorder: A preliminary investigation.

Internet-delivered cognitive-behavioral therapy (ICBT) is an effective treatment for obsessive-compulsive disorder (OCD). ICBT can be delivered in a self-guided or clinician-guided format. While a literature is emerging on the predictors of response to clinician-guided ICBT, there is a lack of research examining the predictors of response to self-guided ICBT. The aim of the present study was to examine predictors of outcome in a large sample of participants with OCD who commenced a self-guided ICBT intervention. One hundred and fifty-seven participants (Mage = 34.82; SD = 10.49; 78% female) were included in the study. Regression analyses were conducted to determine clinical and demographic predictors of (1) posttreatment symptom severity and (2) a clinically meaningful treatment response for both the intention-to-treat (ITT) and completer samples. The regression models significantly predicted posttreatment outcome for both the ITT (F(8, 148) = 15.844, p < .001) and completer sample (F(8, 101) = 5.929, p < .001), explaining 46% and 34% of the variance respectively. Higher baseline OCD severity, younger age, experiencing higher contamination or symmetry symptoms, and a history of past treatment were all found to be significantly associated with higher posttreatment severity in the ITT sample. In the completer sample only higher baseline OCD severity and severity of harm-related obsessions and checking compulsions was significantly associated with higher posttreatment severity. When predicting treatment response the regression models for both the ITT and completer sample were nonsignificant.

Health Care Utilization in the First 7 Years in Children with Fetal Growth Abnormalities: A Retrospective Cohort Study.

OBJECTIVE: To investigate the relationship between birth weight for gestational age and health care utilization of term offspring from birth to 7 years. STUDY DESIGN: We used a population-based retrospective cohort study of infants (≥37 weeks' gestational age) born between 2003 and 2007 in the Canadian province of Nova Scotia (n = 42 050). Perinatal records were linked to provincial administrative health data from birth to age 7 years. The primary outcome was health care utilization (physician visits and hospital admissions) and costs. Birth weight was categorized as small for gestational age (SGA, <10th percentile), appropriate for gestational age (AGA), or large for gestational age (LGA, >90th percentile). Regression models adjusted for potential confounders were used to investigate the associations. RESULTS: Children born SGA had a higher number of specialist visits and hospital admissions, a longer length of stay for the birth admission, and, as a result, higher physician and hospital costs amounting to a cost differential of Can $1222 during the first 7 years of life compared with children born AGA. By contrast, health care use and costs did not differ between children born LGA and AGA. CONCLUSION: Former SGA term infants have a moderate increase in health care use and costs in early childhood compared with former AGA infants, and LGA birth at term is not associated with higher health care utilization.

Making informed choices about cannabis use during pregnancy and lactation: A qualitative study of information use.

BACKGROUND: Cannabis use during pregnancy and lactation continues to increase as some perceive cannabis to be helpful for symptom management and coping. As such, pregnant and lactating people are faced with challenging decisions, weighing benefits against the potential risks of cannabis use. To help clinicians facilitate informed choices, we explored the self-identified information needs of pregnant and lactating people who are deciding whether or not to use cannabis. We aimed to describe the modes and sources of their information-seeking and their satisfaction with the information they found. METHODS: We interviewed 52 people in Canada who made the decision to start, stop, or continue using cannabis during pregnancy and lactation. Participants were recruited from advertisements in prenatal clinics and on social media. We utilized an inductive approach to analysis focused on information used in decision-making about cannabis use, including the process of seeking and evaluating that information. RESULTS: Participants were deliberate in their search for information, most commonly seeking information on risks of use. Information sources were mainly online material or people in their social networks. Clinicians were not commonly described as a knowledgeable or supportive source of information. Overwhelmingly, participants described the information they found as insufficient and emphasized the need for more comprehensive and trustworthy sources of information. CONCLUSIONS: Participants identified distinct and unmet information needs associated with their decision to use cannabis. They described a desire for clear evidence about the impact of cannabis use, including information about how to balance the benefits they perceived from cannabis use with the risks of harm.

Exploring patients' perspectives of gestational diabetes mellitus screening and counselling in Ontario: A grounded theory study.

INTRODUCTION: Gestational diabetes mellitus (GDM) is associated with adverse perinatal outcomes. Approaches to screening for GDM continue to evolve, introducing potential variability of care. This study explored the impact of these variations on GDM counselling and screening from the perspectives of pregnant individuals. METHODS: Following a Corbin and Strauss approach to qualitative, grounded theory we recruited 28 individuals from three cities in Ontario, Canada who had a singleton pregnancy under the care of either a midwife, family physician or obstetrician. Convenience and purposive sampling techniques were used. Semi-structured telephone interviews were conducted and transcribed verbatim between March and December 2020. Transcripts were analysed inductively resulting in codes, categories and themes. RESULTS: Three themes were derived from the data about GDM screening and counselling: 'informing oneself', 'deciding' and 'screening'. All participants, regardless of geographical region, or antenatal care provider, moved through these three steps during the GDM counselling and screening process. Differences in counselling approaches between pregnancy care providers were noted throughout the 'informing' and 'deciding' stages of care. Factors influencing these differences included communication, healthcare autonomy and patient motivation to engage with health services. No differences were noted within care provider groups across the three geographic regions. Participant experiences of GDM screening were influenced by logistical challenges and personal preferences towards testing. CONCLUSION: Informing oneself about GDM may be a crucial step for facilitating decision-making and screening uptake, with an emphasis on information provision to facilitate patient autonomy and motivation. PATIENT OR PUBLIC CONTRIBUTION: Participants of our study included patients and service users. Participants were actively involved in the study design due to the qualitative, patient-centred nature of the research methods employed. Analysis of results was structured according to the emergent themes of the data which were grounded in patient perspectives and experiences.

Do Psychological and Behavioural Factors Change Over Pregnancy?

OBJECTIVES: To investigate how psychological and behavioural factors change from the first to the last half of pregnancy. METHODS: In this prospective cohort study, we assessed the changes in psychological and behavioural factors across 10 domains among 445 women (mean age = 30.9 years) in Ontario, Canada. We collected data using 2 standardized questionnaires administered at <21 and 32-36 weeks of gestation. We computed intraclass correlation coefficients, percentages of no change, decrease, and increase, and mean differences between the 2 surveys. RESULTS: Most psychological and behavioural factors had intraclass correlation coefficients < 0.50 between the first and the second half of pregnancy, suggesting remarkable changes over the course of pregnancy. We observed significant decreases in self-efficacy, compensatory health beliefs, guilt regarding binge eating, emotional eating, dietary restriction, pregnancy-related nausea and food cravings, sleep duration, and physical activity. We also found increases in anxious and depressive symptoms and the tendency to accept friends' and family's beliefs regarding pregnancy. CONCLUSIONS: In the first prospective analysis, we found that many psychological and behavioural factors changed significantly over pregnancy.

The Impact of Infant Sex on Multiple Courses versus a Single Course of Antenatal Corticosteroids: A Secondary Analysis of a Randomized Controlled Trial.

OBJECTIVE: Animal literature has suggested that the impact of antenatal corticosteroids (ACS) may vary by infant sex. Our objective was to assess the impact of infant sex on the use of multiple courses versus a single course of ACS and perinatal outcomes. STUDY DESIGN: We conducted a secondary analysis of the Multiple Courses of Antenatal Corticosteroids for Preterm Birth trial, which randomly allocated pregnant people to multiple courses versus a single course of ACS. Our primary outcome was a composite of perinatal mortality or clinically significant neonatal morbidity (including neonatal death, stillbirth, severe respiratory distress syndrome, intraventricular hemorrhage [grade III or IV], cystic periventricular leukomalacia, and necrotizing enterocolitis [stage II or III]). Secondary outcomes included individual components of the primary outcome as well as anthropometric measures. Baseline characteristics were compared between participants who received multiple courses versus a single course of ACS. An interaction between exposure to ACS and infant sex was assessed for significance and multivariable regression analyses were conducted with adjustment for predefined covariates, when feasible. RESULTS: Data on 2,300 infants were analyzed. The interaction term between treatment status (multiple courses vs. a single course of ACS) and infant sex was not significant for the primary outcome (p = 0.86), nor for any of the secondary outcomes (p > 0.05). CONCLUSION: Infant sex did not modify the association between exposure to ACS and perinatal outcomes including perinatal mortality or neonatal morbidity or anthropometric outcomes. However, animal literature indicates that sex-specific differences after exposure to ACS may emerge over time and thus investigating long-term sex-specific outcomes warrants further attention. KEY POINTS: · We explored the impact of infant sex on perinatal outcomes after multiple versus a single course of ACS.. · Infant sex was not a significant effect modifier of ACS exposure and perinatal outcomes.. · Animal literature indicates that sex-specific differences after ACS exposure may emerge over time.. · Further investigation of long-term sex-specific outcomes is warranted..

Parent Survey Identifies Low-Cost Emotional and Educational Supports in NICU and Beyond.

BACKGROUND: Families face significant mental health challenges after preterm birth. However, there are few low-cost and sustainable services to help with mental health challenges. PURPOSE: To understand suggestions for low-cost and sustainable mental health supports to help families. METHODS: This was an internet-based survey made available to preterm families through the Canadian Premature Babies Foundation social media (Facebook private parents' group). RESULTS: Families reported that peer support, such as connecting with other parents and families who experience preterm birth, was most beneficial. Parents also reported ways to allow families to access the existing mental health services, such as providing child care options and improving advertisement of available resources. IMPLICATIONS: Our results can help implement beneficial low-cost and sustainable mental health supports across many contexts (eg, hospitals and community organization) both in-person and online.

Guided versus self-guided internet delivered cognitive behavioural therapy for diagnosed anxiety and related disorders: a preliminary meta-analysis.

Guided and self-guided internet-delivered cognitive-behavioural therapy (ICBT) has been demonstrated to be efficacious in the treatment of anxiety and related disorders (ARDs). The aim of the current study was to examine the efficacy of guided and self-guided ICBT for adults diagnosed with ARDs using a meta-analytic synthesis of randomised controlled trials directly comparing the two treatment approaches. Eleven studies (n = 1414) were included. There was a small, but significantly pooled between-group effect size at post-treatment (g = 0.16; 95% CI: 0.03-0.28) favouring guided ICBT. At follow-up, the between-group effect size was small and non-significant (g = 0.13; 95% CI: -0.04-0.30). Gender distribution moderated outcome at post-treatment (higher proportions of females resulted in a smaller between-group effect size). Type of support provided in the guided-treatment arm moderated treatment outcome at follow-up (those receiving synchronous support had a larger between-group effect size). Amount of guidance in the guided-treatment arm moderated effect sizes at post-treatment and follow-up (more guidance leading to larger between-group effect sizes). Automated reminders, disorder type, and treatment length did not moderate outcomes. The results suggest that guided and self-guided ICBT interventions result in similar outcomes, however guided interventions may be marginally more effective in the short term.

Defective Mitochondrial Dynamics and Protein Degradation Pathways Underlie Cadmium-Induced Neurotoxicity and Cell Death in Huntington's Disease Striatal Cells.

Exposure to heavy metals, including cadmium (Cd), can induce neurotoxicity and cell death. Cd is abundant in the environment and accumulates in the striatum, the primary brain region selectively affected by Huntington's disease (HD). We have previously reported that mutant huntingtin protein (mHTT) combined with chronic Cd exposure induces oxidative stress and promotes metal dyshomeostasis, resulting in cell death in a striatal cell model of HD. To understand the effect of acute Cd exposure on mitochondrial health and protein degradation pathways, we hypothesized that expression of mHTT coupled with acute Cd exposure would cooperatively alter mitochondrial bioenergetics and protein degradation mechanisms in striatal STHdh cells to reveal novel pathways that augment Cd cytotoxicity and HD pathogenicity. We report that mHTT cells are significantly more susceptible to acute Cd-induced cell death as early as 6 h after 40 µM CdCl2 exposure compared with wild-type (WT). Confocal microscopy, biochemical assays, and immunoblotting analysis revealed that mHTT and acute Cd exposure synergistically impair mitochondrial bioenergetics by reducing mitochondrial potential and cellular ATP levels and down-regulating the essential pro-fusion proteins MFN1 and MFN2. These pathogenic effects triggered cell death. Furthermore, Cd exposure increases the expression of autophagic markers, such as p62, LC3, and ATG5, and reduces the activity of the ubiquitin-proteasome system to promote neurodegeneration in HD striatal cells. Overall, these results reveal a novel mechanism to further establish Cd as a pathogenic neuromodulator in striatal HD cells via Cd-triggered neurotoxicity and cell death mediated by an impairment in mitochondrial bioenergetics and autophagy with subsequent alteration in protein degradation pathways.

Grazing management for soil carbon in Australia: A review.

The livestock industry accounts for a considerable proportion of agricultural greenhouse gas emissions, and in response, the Australian red meat industry has committed to an aspirational target of net-zero emissions by 2030. Increasing soil carbon storage in grazing lands has been identified as one method to help achieve this, while also potentially improving production and provision of other ecosystem services. This review examined the effects of grazing management on soil carbon and factors that drive soil carbon sequestration in Australia. A systematic literature search and meta-analysis was used to compare effects of stocking intensity (stocking rate or utilisation) and stocking method (i.e, continuous, rotational or seasonal grazing systems) on soil organic carbon, pasture herbage mass, plant growth and ground cover. Impacts on below ground biomass, soil nitrogen and soil structure are also discussed. Overall, no significant impact of stocking intensity or method on soil carbon sequestration in Australia was found, although lower stocking intensity and incorporating periods of rest into grazing systems (rotational grazing) had positive effects on herbage mass and ground cover compared with higher stocking intensity or continuous grazing. Minimal impact of grazing management on pasture growth rate and below-ground biomass has been reported in Australia. However, these factors improved with grazing intensity or rotational grazing in some circumstances. While there is a lack of evidence in Australia that grazing management directly increases soil carbon, this meta-analysis indicated that grazing management practices have potential to benefit the drivers of soil carbon sequestration by increasing above and below-ground plant production, maintaining a higher residual biomass, and promoting productive perennial pasture species. Specific recommendations for future research and management are provided in the paper.

Predictors of response to cognitive behavioural therapy (CBT) for individuals with obsessive-compulsive disorder (OCD): a systematic review.

BACKGROUND: Cognitive behavioural therapy (CBT) is considered the first-line treatment for obsessive-compulsive disorder (OCD). However, some individuals with OCD remain symptomatic following CBT, and therefore understanding predictors of outcome is important for informing treatment recommendations. AIMS: The current study aimed to provide the first synthesis of predictors of outcome following CBT for OCD in adults with a primary diagnosis of OCD, as classified by DSM-5. METHOD: Eight studies (n=359; mean age range=29.2-37.7 years; 55.4% female) were included in the systematic review. RESULTS: Congruent with past reviews, there was great heterogeneity of predictors measured across the included studies. Therefore, a narrative synthesis of findings was conducted. Findings from this systematic review indicated that some OCD-related pre-treatment variables (i.e. pre-treatment severity, past CBT treatment, and levels of avoidance) and during treatment variables (i.e. poor working alliance and low treatment adherence) may be important to consider when making treatment recommendations. However, the results also indicate that demographic variables and psychological co-morbidities may not be specific predictors of treatment response. CONCLUSIONS: These findings add to the growing body of literature on predictors of CBT treatment outcomes for individuals with OCD.

Immune response to COVID-19 vaccination is attenuated by poor disease control and antimyeloma therapy with vaccine driven divergent T-cell response.

Myeloma patients frequently respond poorly to bacterial and viral vaccination. A few studies have reported poor humoral immune responses in myeloma patients to COVID-19 vaccination. Using a prospective study of myeloma patients in the UK Rudy study cohort, we assessed humoral and interferon gamma release assay (IGRA) cellular immune responses to COVID-19 vaccination post second COVID-19 vaccine administration. We report data from 214 adults with myeloma (n = 204) or smouldering myeloma (n = 10) who provided blood samples at least three weeks after second vaccine dose. Positive Anti-spike antibody levels (> 50 iu/ml) were detected in 189/203 (92.7%), positive IGRA responses were seen in 97/158 (61.4%) myeloma patients. Only 10/158 (6.3%) patients were identified to have both a negative IGRA and negative anti-spike protein antibody response. In all, 95/158 (60.1%) patients produced positive results for both anti-spike protein serology and IGRA. After adjusting for disease severity and myeloma therapy, poor humoral immune response was predicted by male gender. Predictors of poor IGRA included anti-CD38/anti-BCMA (B-cell maturation antigen) therapy and Pfizer-BioNTech vaccination. Further work is required to understand the clinical significance of divergent cellular response to vaccination.