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The aims of this study were to evaluate changes in inflammatory and oxidative stress levels following treatment with N-acetylcysteine (NAC) or mitochondrial-enhancing agents (CT), and to assess the how these changes may predict and/or moderate clinical outcomes primarily the Montgomery-Åsberg Depression Rating Scale (MADRS).
This study involved secondary analysis of a placebo-controlled randomised trial (n = 163). Serum samples were collected at baseline and week 16 of the clinical trial to determine changes in Interleukin-6 (IL-6) and total antioxidant capacity (TAC) following adjunctive CT and/or NAC treatment, and to explore the predictability of the outcome or moderator effects of these markers.
In the NAC-treated group, no difference was observed in serum IL-6 and TAC levels after 16 weeks of treatment with NAC or CT. However, results from a moderator analysis showed that in the CT group, lower IL-6 levels at baseline was a significant moderator of MADRS χ2 (df) = 4.90, p = 0.027) and Clinical Global Impression-Improvement (CGI-I, χ2 (df) = 6.28 p = 0.012). In addition, IL-6 was a non-specific but significant predictor of functioning (based on the Social and Occupational Functioning Assessment Scale (SOFAS)), indicating that individuals with higher IL-6 levels at baseline had a greater improvement on SOFAS regardless of their treatment (p = 0.023).
Participants with lower IL-6 levels at baseline had a better response to the adjunctive treatment with the mitochondrial-enhancing agents in terms of improvements in MADRS and CGI-I outcomes.
Catechol-O-methyltransferase (COMT) has a central role in brain dopamine, noradrenalin and adrenalin signaling, and has been suggested to be involved in the pathogenesis and pharmacological treatment of affective disorders. The functional single nucleotide polymorphism (SNP) in exon 4 (Val158Met, rs4680) influences the COMT enzyme activity. The Val158Met polymorphism is a commonly studied variant in psychiatric genetics, and initial studies in schizophrenia and bipolar disorder presented evidence for association with the Met allele. In unipolar depression, while some of the investigations point at an association between the Met/Met genotype and others have found a link between the Val/Val genotype and depression, most of the studies cannot detect any difference in Val158Met allele frequency between depressed individuals and controls.
In the present study, we further elucidated the impact of COMT polymorphisms including the Val158Met in MDD. We investigated 1,250 subjects with DSM-IV and/or ICD-10 diagnosis of major depression (MDD), and 1,589 control subjects from UK. A total of 24 SNPs spanning the COMT gene were successfully genotyped using the Illumina HumaHap610-Quad Beadchip (22 SNPs), SNPlex™ genotyping system (1 SNP), and Sequenom MassARRAY® iPLEX Gold (1 SNP). Statistical analyses were implemented using PASW Statistics18, FINETTI (http://ihg.gsf.de/cgi-bin/hw/hwa1.pl), UNPHASED version 3.0.10 program and Haploview 4.0 program.
Neither single-marker nor haplotypic association was found with the functional Val158Met polymorphism or with any of the other SNPs genotyped. Our findings do not provide evidence that COMT plays a role in MDD or that this gene explains part of the genetic overlap with bipolar disorder.
Gene × environment (G × E) interactions in eating pathology have been increasingly investigated, however studies have been limited by sample size due to the difficulty of obtaining genetic data.
To synthesize existing G × E research in the eating disorders (ED) field and provide a clear picture of the current state of knowledge with analyses of larger samples.
Complete data from seven studies investigating community (n = 1750, 64.5% female) and clinical (n = 426, 100% female) populations, identified via systematic review, were included. Data were combined to perform five analyses: 5-HTTLPR × Traumatic Life Events (0–17 events) to predict ED status (n = 909), 5-HTTLPR × Sexual and Physical Abuse (n = 1097) to predict bulimic symptoms, 5-HTLPR × Depression to predict bulimic symptoms (n = 1256), and 5-HTTLPR × Impulsivity to predict disordered eating (n = 1149).
The low function (s) allele of 5-HTTLPR interacted with number of traumatic life events (P < .01) and sexual and physical abuse (P < .05) to predict increased likelihood of an ED in females but not males (Fig. 1). No other G × E interactions were significant, possibly due to the medium to low compatibility between datasets (Fig. 1).
Early promising results suggest that increased knowledge of G × E interactions could be achieved if studies increased uniformity of measuring ED and environmental variables, allowing for continued collaboration to overcome the restrictions of obtaining genetic samples.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.
Background: Challenges in predicting risk of recurrence for individual patients with meningioma limits appropriate selection of patients who may benefit from adjuvant radiation therapy to delay recurrence. Here, we aimed to develop and validate a combined clinicomolecular predictor of early recurrence for individual patients with meningiomas. Methods: A methylation-based predictor of 5-year recurrence-free-survival (RFS) was developed using DNA-methylation profiles from a training cohort of 228 patients. Model performance was compared to a standard-of-care histological-based model using three independent cohorts (N=54 ;N=140; N=64 patients). Subsequently, a nomogram that integrated the methylome-based predictor with prognostic clinical factors was developed and validated. Results: The methylome-based predictor of 5-year RFS performed favorably compared to a grade-based predictor when tested using the three validation cohorts (ΔAUC=0.10, 95%CI 0.03 – 0.018) and was independently associated with RFS on multivariable Cox regression analysis (HR=3.6, 95%CI 1.8–7.2, P<0.001). A nomogram combining the methylome-predictor with clinical factors demonstrated greater discrimination for recurrence than a nomogram using clinical factors alone (ΔAUC=0.25, 95%CI 0.22–0.27) and resulted in two risk groups with distinct recurrence patterns (HR=7.7, 95%CI 5.3–11.1, P<0.001) and clinical implications. Conclusions: Our validated models provide important novel prognostic information that could be used to individualize decisions regarding post-operative therapeutic interventions in meningioma.
Global inequity in access to and availability of essential mental health services is well recognized. The mental health treatment gap is approximately 50% in all countries, with up to 90% of people in the lowest-income countries lacking access to required mental health services. Increased investment in global mental health (GMH) has increased innovation in mental health service delivery in LMICs. Situational analyses in areas where mental health services and systems are poorly developed and resourced are essential when planning for research and implementation, however, little guidance is available to inform methodological approaches to conducting these types of studies. This scoping review provides an analysis of methodological approaches to situational analysis in GMH, including an assessment of the extent to which situational analyses include equity in study designs. It is intended as a resource that identifies current gaps and areas for future development in GMH. Formative research, including situational analysis, is an essential first step in conducting robust implementation research, an essential area of study in GMH that will help to promote improved availability of, access to and reach of mental health services for people living with mental illness in low- and middle-income countries (LMICs). While strong leadership in this field exists, there remain significant opportunities for enhanced research representing different LMICs and regions.
Background: A previously healthy 26 year-old male presented with confusion and recurrent hypoglycemia (blood glucose lows of 2.5 mmol/L) while on vacation in Las Vegas. He denied substance or heavy alcohol use and the toxicology screen was negative. He was transferred home to Winnipeg for further care and was found to have only patchy memories of his trip and the days leading up to the trip, consistent with mixed anterograde and retrograde amnesia. MoCA score at presentation was 16/30 with points lost on orientation, delayed recall and visuospatial-executive tasks. MRI revealed T2 hyperintensities and diffusion abnormalities in bilateral hippocampi and globus pallidi. Electroencephalography showed triphasic waves. The patient was found to have a pancreatic insulinoma, which was surgically resected. In follow-up nine weeks later he was near his cognitive baseline, though he had ongoing difficulties with delayed recall. Repeat MRI showed improvement but not resolution of hippocampal and pallidal signal change, with mild hippocampal atrophy.
Neuropathological and animal studies have shown that structures most sensitive to hypoglycemic neural injury include the hippocampus, basal ganglia, and neocortex. The clinical and radiographic findings in this case illustrate an unusual presentation of insulinoma and the effects of hypoglycemia on the brain. Methods: N/A Results: N/A Conclusions: N/A
Little is known about the combined use of benzodiazepines and antidepressants in older psychiatric patients. This study examined the prescription pattern of concurrent benzodiazepines in older adults treated with antidepressants in Asia, and explored its demographic and clinical correlates.
The data of 955 older adults with any type of psychiatric disorders were extracted from the database of the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) project. Demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. Both univariate and multiple logistic regression analyses were performed.
The proportion of benzodiazepine and antidepressant combination in this cohort was 44.3%. Multiple logistic regression analysis revealed that higher doses of antidepressants, younger age (<65 years), inpatients, public hospital, major comorbid medical conditions, antidepressant types, and country/territory were significantly associated with more frequent co-prescription of benzodiazepines and antidepressants.
Nearly, half of the older adults treated with antidepressants in Asia are prescribed concurrent benzodiazepines. Given the potentially adverse effects of benzodiazepines, the rationale of benzodiazepines and antidepressants co-prescription needs to be revisited.
The Binary Population and Spectral Synthesis suite of binary stellar evolution models and synthetic stellar populations provides a framework for the physically motivated analysis of both the integrated light from distant stellar populations and the detailed properties of those nearby. We present a new version 2.1 data release of these models, detailing the methodology by which Binary Population and Spectral Synthesis incorporates binary mass transfer and its effect on stellar evolution pathways, as well as the construction of simple stellar populations. We demonstrate key tests of the latest Binary Population and Spectral Synthesis model suite demonstrating its ability to reproduce the colours and derived properties of resolved stellar populations, including well-constrained eclipsing binaries. We consider observational constraints on the ratio of massive star types and the distribution of stellar remnant masses. We describe the identification of supernova progenitors in our models, and demonstrate a good agreement to the properties of observed progenitors. We also test our models against photometric and spectroscopic observations of unresolved stellar populations, both in the local and distant Universe, finding that binary models provide a self-consistent explanation for observed galaxy properties across a broad redshift range. Finally, we carefully describe the limitations of our models, and areas where we expect to see significant improvement in future versions.
Suicide-related behaviours are common in schizophrenia and are significantly associated with premature death. The objective of this meta-analysis study was to estimate the pooled prevalence of suicide-related behaviours in schizophrenia patients in China.
The relevant literature was searched systematically via the relevant electronic databases (PubMed, Embase, PsycINFO, Chinese National Knowledge Infrastructure, Wanfang Databases and Chinese Biological Medical Literature Database) from their inception until 14 September 2016. Only original studies that reported the prevalence of suicide-related behaviours including suicidal ideation (SI), suicide plan, suicide attempt (SA) and completed suicide were selected.
Nineteen articles met the inclusion criteria and were analysed. The pooled lifetime prevalence of SI and SA were 25.8% (95% CI 14.7–41.1%) and 14.6% (95% CI 9.1–22.8%), respectively. The 1-month prevalence of SI was 22.0% (95% CI 18.2–26.4%). Subgroup analyses of lifetime SI and SA showed that gender, sample size, survey year, study location and source of patients have no significant mediating effects on the results.
Suicide-related behaviours are common in Chinese schizophrenia patients. Due to the high mortality risk, regular screening and effective suicide prevention programmes are warranted.
To characterize contacts in general wards, a prospective survey of healthcare workers (HCWs), patients and visitors was conducted using self-reported diary, direct observation and telephone interviews. Nurses, doctors and assorted HCWs reported a median of 14, 18 and 15 contact persons over one work shift, respectively. Within 1 h, we observed 3·5 episodes with 25·6 min of cumulative contact time for nurses, 2·9 episodes and 22·1 min for doctors and 5·0 episodes with 44·3 min for assorted-HCWs. In interactions with patients, nurses had multiple brief episodes of contact; doctors had fewer episodes and less cumulative contact time; assorted-HCWs had fewer contact episodes of longer durations (than for nurses and doctors). Assortative mixing occurred amongst HCWs: those of the same HCW type were the next most frequent class of contact after patients. Over 24-h, patients contacted 14 persons with 23 episodes and 314·5 min of contact time. Patient-to-patient contact episodes were rare, but a maximum of five were documented from one patient participant. 22·9% of visitors reported contact with patients other than the one they visited. Our study revealed differences in the characteristics of contacts among different HCW types and potential transmission routes from patients to others within the ward environment.
To evaluate the clinicopathological and mycological manifestations of fungal rhinosinusitis occurring in the Tengku Ampuan Rahimah Hospital, in Klang, Malaysia, which has a tropical climate.
Records of patients treated from 2009 to 2016 were analysed retrospectively. Data from the records were indexed based on age, gender, clinical presentations, symptom duration, clinical signs and mycological growth.
Of 80 samples, 27 (33.75 per cent) had fungal growth. Sixteen patients were classified as having non-invasive fungal rhinosinusitis and 11 as having invasive fungal rhinosinusitis. The commonest clinical presentation was nasal polyposis in non-invasive fungal rhinosinusitis patients (p < 0.05) and ocular symptoms in invasive fungal rhinosinusitis patients (p < 0.05). The commonest organism was aspergillus sp. (p < 0.05) in non-invasive fungal rhinosinusitis and mucorales in invasive fungal rhinosinusitis.
There is an almost equal distribution of both invasive and non-invasive fungal rhinosinusitis, as seen in some Asian countries. Invasive fungal rhinosinusitis, while slightly uncommon when compared to non-invasive fungal rhinosinusitis, is potentially life threatening, and may require early and extensive surgical debridement. The clinical presentation of nasal polyposis was often associated with non-invasive fungal rhinosinusitis, whereas ocular symptoms were more likely to be associated with invasive fungal rhinosinusitis.
Microdeletion syndrome is an important topic in intellectual disability, associated with various psychiatric symptoms, such as autism, attention deficit, hyperactivity, obsession and compulsion, and psychosis. In this article, we provide a clinical update on the following syndromes and their associated psychiatric disorders: Prader–Willi syndrome, Angelman syndrome, Williams syndrome, Wolf–Hirschhorn syndrome, cri du chat syndrome, DiGeorge syndrome and Rubinstein–Taybi syndrome.
• Gain an up-to-date understanding of the microdeletion syndromes commonly seen in daily practice
• Appreciate the association between underlying chromosomal abnormalities and the resultant intellectual disabilities in microdeletion syndromes
• Gain up-to-date knowledge about the treatment options for the various microdeletion syndromes commonly seen in daily practice
Traumatic events are common globally; however, comprehensive population-based cross-national data on the epidemiology of posttraumatic stress disorder (PTSD), the paradigmatic trauma-related mental disorder, are lacking.
Data were analyzed from 26 population surveys in the World Health Organization World Mental Health Surveys. A total of 71 083 respondents ages 18+ participated. The Composite International Diagnostic Interview assessed exposure to traumatic events as well as 30-day, 12-month, and lifetime PTSD. Respondents were also assessed for treatment in the 12 months preceding the survey. Age of onset distributions were examined by country income level. Associations of PTSD were examined with country income, world region, and respondent demographics.
The cross-national lifetime prevalence of PTSD was 3.9% in the total sample and 5.6% among the trauma exposed. Half of respondents with PTSD reported persistent symptoms. Treatment seeking in high-income countries (53.5%) was roughly double that in low-lower middle income (22.8%) and upper-middle income (28.7%) countries. Social disadvantage, including younger age, female sex, being unmarried, being less educated, having lower household income, and being unemployed, was associated with increased risk of lifetime PTSD among the trauma exposed.
PTSD is prevalent cross-nationally, with half of all global cases being persistent. Only half of those with severe PTSD report receiving any treatment and only a minority receive specialty mental health care. Striking disparities in PTSD treatment exist by country income level. Increasing access to effective treatment, especially in low- and middle-income countries, remains critical for reducing the population burden of PTSD.
Supernova (SN) 1987A has provided a unique opportunity to study how SN ejecta evolve in 30 years time scale. We report our ALMA spectral observations of SN 1987A, taken in 2014, 2015 and 2016, with detections of CO, 28SiO, HCO+ and SO, with weaker lines of 29SiO.
We find a dip in the SiO line profiles, suggesting that the ejecta morphology is likely elongated. The difference of the CO and SiO line profiles is consistent with hydrodynamic simulations, which show that Rayleigh-Taylor instabilities causes mixing of gas, with heavier elements much more disturbed, making more elongated structure.
Using 28SiO and its isotopologues, Si isotope ratios were estimated for the first time in SN 1987A. The estimated ratios appear to be consistent with theoretical predictions of inefficient formation of neutron rich atoms at lower metallicity, such as observed in the Large Magellanic Cloud (about half a solar metallicity).
The deduced large HCO+ mass and small SiS mass, which are inconsistent to the predictions of chemical model, might be explained by some mixing of elements immediately after the explosion. The mixing might have made some hydrogen from the envelope to sink into carbon and oxygen-rich zone during early days after the explosion, enabling the formation of a substantial mass of HCO+. Oxygen atoms may penetrate into silicon and sulphur zone, suppressing formation of SiS.
Our ALMA observations open up a new window to investigate chemistry, dynamics and explosive-nucleosynthesis in supernovae.
We have recently released version 2.0 of the Binary Population and Spectral Synthesis (BPASS) population synthesis code. This is designed to construct the spectra and related properties of stellar populations built from ~200,000 detailed, individual stellar models of known age and metallicity. The output products enable a broad range of theoretical predictions for individual stars, binaries, resolved and unresolved stellar populations, supernovae and their progenitors, and compact remnant mergers. Here we summarise key applications that demonstrate that binary populations typically reproduce observations better than single star models.
We describe the performance of the Boolardy Engineering Test Array, the prototype for the Australian Square Kilometre Array Pathfinder telescope. Boolardy Engineering Test Array is the first aperture synthesis radio telescope to use phased array feed technology, giving it the ability to electronically form up to nine dual-polarisation beams. We report the methods developed for forming and measuring the beams, and the adaptations that have been made to the traditional calibration and imaging procedures in order to allow BETA to function as a multi-beam aperture synthesis telescope. We describe the commissioning of the instrument and present details of Boolardy Engineering Test Array’s performance: sensitivity, beam characteristics, polarimetric properties, and image quality. We summarise the astronomical science that it has produced and draw lessons from operating Boolardy Engineering Test Array that will be relevant to the commissioning and operation of the final Australian Square Kilometre Array Path telescope.
Suicide is a leading cause of death for young people. Children living in sub-Saharan Africa, where HIV rates are disproportionately high, may be at increased risk.
To identify predictors, including HIV status, of suicidal ideation and behaviour in Rwandan children aged 10–17.
Matched case–control study of 683 HIV-positive, HIV-affected (seronegative children with an HIV-positive caregiver), and unaffected children and their caregivers.
Over 20% of HIV-positive and affected children engaged in suicidal behaviour in the previous 6 months, compared with 13% of unaffected children. Children were at increased risk if they met criteria for depression, were at high-risk for conduct disorder, reported poor parenting or had caregivers with mental health problems.
Policies and programmes that address mental health concerns and support positive parenting may prevent suicidal ideation and behaviour in children at increased risk related to HIV.
Vitamin D plays an important role in skeletal health throughout life. Some studies have hypothesised that vitamin D may reduce the risk of other diseases. Our study aimed to estimate age-specific and sex-specific serum 25-hydroxyvitamin D (25(OH)D) status and to identify the determinants of serum 25(OH)D status in Hong Kong, a subtropical city in southern China. In 2009–2010, households in Hong Kong were followed up to identify acute respiratory illnesses, and sera from 2694 subjects were collected in three to four different study phases to permit measurement of 25(OH)D levels at different times of the year. A questionnaire survey on diet and lifestyle was conducted among children, with simultaneous serum collection in April and May 2010. The mean of serum 25(OH)D levels in age groups ranged from 39 to 63 nmol/l throughout the year with the mean values in all age groups in spring below 50 nmol/l. Children aged 6–17 years, and girls and women had significantly lower serum 25(OH)D levels than adults, and boys and men, respectively (all P< 0·001). We estimated that serum 25(OH)D levels in Hong Kong followed a lagged pattern relative to climatic season by 5 weeks with lowest observed levels in early spring (March). For children aged 6–17 years, reporting a suntan, having at least 1 servings of fish/week and having at least 1 serving of eggs/week were independently associated with higher serum 25(OH)D levels. Adequate sunlight exposure and increased intake of dietary vitamin D could improve vitamin D status, especially for children and females in the winter and spring.
It is unclear if the impact of psychoeducational family intervention for patients with schizophrenia can be sustained over 10 years. In this study, we explored the 14-year effect of psychoeducational family intervention for patients with schizophrenia in a Chinese rural area.
The data from a cluster randomized control trial (CRCT) study of psychoeducational family intervention in a 14-year follow-up was analyzed. All patients with schizophrenia (n = 326) who participated in the CRCT drawn from six townships in Xinjin County of Chengdu in 1994, of whom 238 (73.0%) who were still alive, and their informants were followed up in 2008. The Patients Follow-up Scale, the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning were used in the follow-up study.
There were no significant differences of marital status, mean scores of PANSS positive symptoms, negative symptoms, general mental health, and total scores among the psychoeducational family intervention, medication, and control groups in 2008. The psychoeducational family intervention group had a significantly higher rate of antipsychotic medication and a higher level of work ability than other two groups. The control group had a significantly higher rate of never-treated (26.0%) than psychoeducational family intervention group (6.5%).
Psychoeducational family intervention might be still effective in the 14-year follow-up, especially in patients’ treatment adherence/compliance and social functioning. Psychoeducational family intervention might be more effective in places where family members frequently participated in patients’ care and had a lower level of knowledge on mental illness. Family intervention should be considered when making mental health policy and planning mental health services.