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Brain-derived neurotrophic factor (BDNF), which facilitates neuroplasticity and synaptogenesis, may be decreased in bipolar disorder, but has not been systematically investigated in people with newly diagnosed bipolar disorder and unaffected first-degree relatives.
To compare BDNF levels in patients with newly diagnosed bipolar disorder, their unaffected first-degree relatives and healthy controls.
The study investigated plasma BDNF levels in patients (n = 371) with newly diagnosed bipolar disorder, their unaffected first-degree relatives (n = 98) and healthy controls (n = 200) using enzyme-linked immunosorbent assay. We further investigated associations between BDNF levels and illness-related variables and medication status.
BDNF levels were found to be 22.0% (95% CI 1.107–1.343) higher in patients with bipolar disorder compared with healthy controls (P < 0.001) and 15.6% higher in unaffected first-degree relatives compared with healthy controls (95% CI 1.007–1.327, P = 0.04), when adjusting for age and gender. Further, BDNF levels were positively associated with duration of illness at a trend level (P = 0.05), age (P = 0.001) and use of anti-epileptic medication (P = 0.05).
These findings suggest that BDNF levels are not decreased in the early stages of bipolar disorder and in unaffected first-degree relatives contrasting with prior findings during later stages of the illness.
Changes in inflammatory and metabolic markers are implicated in the pathogenesis in both the development and progression of bipolar disorder (BD). Notwithstanding, these markers have not been investigated in newly diagnosed BD.
We compared high-sensitive C-reactive protein (hs-CRP) and homocysteine (Hcy) levels in 372 patients with newly diagnosed BD, 106 unaffected first-degree relatives (URs), and 201 healthy control persons (HCs). Within the patient group, we also investigated possible associations between hs-CRP and Hcy, respectively, with illness-related characteristics and psychotropic medication.
No statistically significant differences in Hcy and hs-CRP levels were found when comparing BD and URs with HCs. Similarly, there were no differences when comparing only patients in remission or patients with affective symptoms, respectively, with HCs. Hcy levels were found to be 11.9% (95% CI: 1.030–1.219) higher in patients with BD when compared with their URs (p = 0.008), when adjusting for folate and cobalamin status, age, sex, and self-reported activity levels. Hcy levels were significantly associated with folate, cobalamin, gender, and age in all models (p < 0.05).
Our results do not support hs-CRP or Hcy as markers in newly diagnosed BD.
Rey’s Auditory Verbal Learning Test (AVLT) is a widely used word list memory test. We update normative data to include adjustment for verbal memory performance differences between men and women and illustrate the effect of this sex adjustment and the importance of excluding participants with mild cognitive impairment (MCI) from normative samples.
This study advances the Mayo’s Older Americans Normative Studies (MOANS) by using a new population-based sample through the Mayo Clinic Study of Aging, which randomly samples residents of Olmsted County, Minnesota, from age- and sex-stratified groups. Regression-based normative T-score formulas were derived from 4428 cognitively unimpaired adults aged 30–91 years. Fully adjusted T-scores correct for age, sex, and education. We also derived T-scores that correct for (1) age or (2) age and sex. Test-retest reliability data are provided.
From raw score analyses, sex explained a significant amount of variance in performance above and beyond age (8–10%). Applying original age-adjusted MOANS norms to the current sample resulted in significantly fewer-than-expected participants with low delayed recall performance, particularly in women. After application of new T-scores adjusted only for age, even in normative data derived from this sample, these age-adjusted T-scores showed scores <40 T occurred more frequently among men and less frequently among women relative to T-scores that also adjusted for sex.
Our findings highlight the importance of using normative data that adjust for sex with measures of verbal memory and provide new normative data that allow for this adjustment for the AVLT.
Fruit intake is associated with lower risk of cardiometabolic diseases. However, effects of dried fruits on cardiometabolic health are not well researched. We investigated the effect of daily dried fruit consumption compared with a carbohydrate-rich snack on cardiometabolic disease risk factors in adults with increased cardiometabolic risk. A two-period randomised crossover trial was conducted in adults (n 55) with elevated BMI and at least one additional risk factor for cardiometabolic disease to compare the effects of consuming 3/4 cup/d mixed dried fruits (plums, figs, dates and raisins) or an energy- and carbohydrate-matched control snack for 4 weeks. The primary outcome was LDL-cholesterol; secondary outcomes included other lipids and lipoproteins, glucose and insulin, C-reactive protein, blood pressure and vascular stiffness. Linear mixed models were used for data analysis. Lipid and lipoprotein concentrations did not differ between conditions; however, dried fruit increased LDL-cholesterol (0·10 mmol/l, 95 % CI 0·01, 0·20) compared with baseline. Compared with the control, dried fruit increased mean fasting glucose (0·08 mmol/l, 95 % CI 0·005, 0·16; P = 0·038). Vascular outcomes, fasting insulin and C-reactive protein did not differ between conditions. Mean weight changes did not differ (P = 0·55) but tended to increase after both conditions (dried fruit 0·3 kg, 95 % CI –0·09, 0·65; control 0·4 kg, 95 % CI 0·01, 0·75). Thus, short-term daily consumption of a large portion of mixed dried plums, figs, dates and raisins, without structured dietary guidance, did not improve cardiometabolic risk factors, compared with carbohydrate-rich snacks, in adults with increased baseline cardiometabolic risk.
This paper presents a novel solution for precision draping of prepreg composite fabrics onto double curved molds. Our contributions relate to system design, including hardware and software components, and to system integration. On the hardware side, design and implementation of a drape tool with up to 120 suction cups positioned individually by linear actuators are described. On the software side, design and implementation of the software architecture are presented, along with necessary algorithms within sensor technologies and mathematical modeling. The essential system’s components were verified individually, and the entire integrated system was successfully validated in the Proof-of-Concept experiments, performed on an experimental physical model of the system.
Cardiovascular risk prediction tools are important for cardiovascular disease (CVD) prevention, however, which algorithms are appropriate for people with severe mental illness (SMI) is unclear.
To determine the cost-effectiveness using the net monetary benefit (NMB) approach of two bespoke SMI-specific risk algorithms compared to standard risk algorithms for primary CVD prevention in those with SMI, from an NHS perspective.
A microsimulation model was populated with 1000 individuals with SMI from The Health Improvement Network Database, aged 30–74 years without CVD. Four cardiovascular risk algorithms were assessed; (1) general population lipid, (2) general population BMI, (3) SMI-specific lipid and (4) SMI-specific BMI, compared against no algorithm. At baseline, each cardiovascular risk algorithm was applied and those high-risk (> 10%) were assumed to be prescribed statin therapy, others received usual care. Individuals entered the model in a ‘healthy’ free of CVD health state and with each year could retain their current health state, have cardiovascular events (non-fatal/fatal) or die from other causes according to transition probabilities.
The SMI-specific BMI and general population lipid algorithms had the highest NMB of the four algorithms resulting in 12 additional QALYs and a cost saving of approximately £37,000 (US$ 58,000) per 1000 patients with SMI over 10 years.
The general population lipid and SMI-specific BMI algorithms performed equally well. The ease and acceptability of use of a SMI-specific BMI algorithm (blood tests not required) makes it an attractive algorithm to implement in clinical settings.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Cognitive impairment has emerged as a key treatment priority in neuropsychiatric disorders. However, there is a lack of treatments with solid and lasting efficacy on cognition. A neurocircuitry-based biomarker model of pro-cognitive effects is critically needed to select among new candidate treatments. In a recent review of functional magnetic resonance imaging (fMRI) studies in mood disorders, we found that cognitive impairments are consistently accompanied by aberrant (hypo- and hyper-) activity in the dorsal prefrontal cortex (PFC) and the default mode network (DMN), and that activity change in these regions commonly occurs with cognitive improvements. Here, we (i) review the putative model from our recent review article, which explains the discrepant findings regarding the direction of aberrant dorsal PFC activity and treatment-related activity change in mood disorders. Inspired by the Research Domain Criteria project, we do this in order to (ii) examine whether a similar pattern of activity change occurs across distinct neuropsychiatric disorders and thereby provides a common biomarker for pro-cognitive effects. Lastly, we (iii) discuss whether dorsal PFC and DMN target engagement is a putative transdiagnostic neurocircuitry-based biomarker model for pro-cognitive effects, and (iv) outline the necessary next steps to address this question.
Epidemiological studies suggest that consumption of potatoes is associated with increased risk of cardiometabolic diseases. However, few clinical trials have empirically tested this. The aim of this single-blind, randomised, crossover study was to evaluate the effect of daily potato consumption, compared with refined grains, on risk factors for cardiometabolic diseases. It was hypothesised that no difference in cardiometabolic endpoints would be detected between conditions, but diet quality would improve with potato consumption. Healthy participants on self-selected diets received one potato-based side dish or one refined grain-based side dish daily, for 4 weeks, separated by a minimum 2-week break. Dishes were isoenergetic, carbohydrate-matched and prepared without excess saturated fat or Na. Participants were instructed to consume the side dish with a meal in place of carbohydrates habitually consumed. Lipids/lipoproteins, markers of glycaemic control, blood pressure, weight and pulse wave velocity were measured at baseline and condition endpoints. Diet quality was calculated, based on 24-h recalls, using the Healthy Eating Index (HEI)-2015. Fifty adults (female n 34; age 40 (sd 13) years; BMI 24·5 (sd 3·6) kg/m2) completed the present study. No between-condition differences were detected for fasting plasma glucose (–0·05 mmol/l, 95 % CI –0·14, 0·04; P = 0·15), the primary outcome or any other outcomes. Compared with refined grains, the HEI-2015 score (3·5, 95 % CI 0·6, 6·4; P = 0·01), K (547 mg, 95 % CI 331, 764, P < 0·001) and fibre (2·4 g, 95 % CI 0·6, 4·2, P = 0·01) were higher following the potato condition. Consuming non-fried potatoes resulted in higher diet quality, K and fibre intake, without adversely affecting cardiometabolic risk.
Against the backdrop of mounting calls for the global scaling-up of mental health services – including quality care and prevention services – there is very little guidance internationally on strategies for scaling-up such services. Drawing on lessons from scale-up attempts in six low- and middle-income countries (LMICs), and using exemplars from the front-lines in South Africa; we illustrate how health reforms towards people-centred chronic disease management provide enabling policy window opportunities for embedding mental health scale-up strategies into these reforms. Rather than going down the oft-trodden road of vertical funding for scale-up of mental health services, we suggest using the policy window that stresses global policy shifts towards strengthening of comprehensive integrated primary health care systems that are responsive to multimorbid chronic conditions. This is indeed a substantial opportunity to firmly locate mental health within these horizontal health systems strengthening funding agendas. While this approach will promote systems more enabling of scaling up of mental health services, implications for donor funders and researchers alike is the need for increased time commitments, resources and investment in local control.
Against the backdrop of mounting calls for the global scaling-up of mental health services – including quality care and prevention services – there is very little guidance internationally on strategies for scaling-up such services. Drawing on lessons from scale-up attempts in six low- and middle-income countries, and using exemplars from the front-lines in South Africa, we illustrate how health reforms towards people-centred chronic disease management provide enabling policy window opportunities for embedding mental health scale-up strategies into these reforms. Rather than going down the oft-trodden road of vertical funding for scale-up of mental health services, we suggest using the policy window that stresses global policy shifts towards strengthening of comprehensive integrated primary health care systems that are responsive to multimorbid chronic conditions. This is indeed a substantial opportunity to firmly locate mental health within these horizontal health systems strengthening funding agendas. Although this approach will promote systems more enabling of scaling-up of mental health services, implications for donor funders and researchers alike is the need for increased time commitments, resources and investment in local control.
The ice-cored Galena Creek Rock Glacier, Wyoming, USA, has been the subject of a number of studies that sought to determine the origin of its ice. We present new observations of the rock glacier's internal structure from ground-penetrating radar to constrain ice and debris distribution and accumulation. We imaged dipping reflectors in the center of the glacier that are weak and discontinuous, in contrast to strong reflectors toward the edge of the cirque beneath large debris-avalanche chutes. These reflectors form a network of concave-up, up-glacier dipping layers. We interpret these as englacial debris bands formed by large debris falls buried by subsequent ice and snow accumulation. They are discontinuous where ice outpaces debris accumulation, but with sufficient debris accumulation an interleaved pattern of ice and debris layers can form. We propose a model in which the ice in these interleaved layers is snowfall preserved by debris-facilitated accumulation. Large debris falls that occur in early spring bury sections of the snowpack, which are then preserved through summer and incorporated into the rock glacier body over time. This study highlights the importance of sequential accumulation of ice and debris for understanding the dynamics of rock glaciers and debris-covered glaciers.
Documentation of code status and advance directives for end-of-life (EOL) care improves care and quality of life, decreases cost of care, and increases the likelihood of an experience desired by the patient and his/her family. However, the use of advance directives and code status remains low and only a few organizations maintain code status in electronic form. Members of the American Medical Informatics Association’s Ethics Committee identified a need for a patient’s EOL care wishes to be documented correctly and communicated easily through the electronic health record (EHR) using a minimum data set for the storage and exchange of code status information. After conducting an environmental scan that produced multiple resources, Ethics Committee members used multiple conference calls and a shared document to arrive at consensus on the proposed minimum data set. Ethics Committee members developed a minimum required data set with links to the HL7 C_CDA Advance Directives Module. Data categories include information on the organization obtaining the code status information, the patient, any supporting documentation, and finally the desired code status information including mandatory, optional, and conditional elements. The “minimum set of attributes” to exchange advance directive / code status data described in this manuscript enables communication of patient wishes across multiple providers and health care settings. The data elements described serve as a starting point for a dialog among informatics professionals, physicians experienced in EOL care, and EHR vendors, with the goal of developing standards for incorporating this functionality into the EHR systems.
Atmospheric emissions of nitrogen (N) from New Zealand dairy farms are significant but have the potential to be affected by manure management prior to land application. The current work examined whether reducing cattle manure dry matter (DM) from 0.16 high DM (HDM) to 0.06 low DM (LDM), to enhance infiltration and reduce ammonia (NH3) emissions when applied to grassland, would affect nitrous oxide (N2O) emissions. Pasture was cut, simulating grazing, and either amended with HDM (173 kg N/ha) or LDM manure (48 kg N/ha) or left unamended. Ammonia emissions from HDM manure were higher than from LDM manure, as a flux or as a percentage of total ammoniacal nitrogen (TAN, i.e. NH3 + NH4+) applied, due to more TAN being retained near the soil surface and the higher soil surface pH under HDM manure treatment. Cumulative N2O emissions over 37 days from HDM plots were higher than from the control but not from the LDM plots. After 5 days, the daily N2O emission rate was larger from HDM plots than from LDM and control plots. The N2O fluxes from LDM and HDM treatments did not differ, either as a proportion of TAN applied or as a proportion of total-N applied. Increasing DM contributed to reductions in both oxygen (O2) availability and relative gas diffusivity, and thus potentially N2O production. Under the conditions of the current study, lower manure DM content reduced NH3 emissions but did not increase cumulative losses of N2O.
Neuropsychiatric illnesses including mood disorders are accompanied by cognitive impairment, which impairs work capacity and quality of life. However, there is a lack of treatment options that would lead to solid and lasting improvement of cognition. This is partially due to the absence of valid and reliable neurocircuitry-based biomarkers for pro-cognitive effects. This systematic review therefore examined the most consistent neural underpinnings of cognitive impairment and cognitive improvement in unipolar and bipolar disorders. We identified 100 studies of the neuronal underpinnings of working memory and executive skills, learning and memory, attention, and implicit learning and 9 studies of the neuronal basis for cognitive improvements. Impairments across several cognitive domains were consistently accompanied by abnormal activity in dorsal prefrontal (PFC) cognitive control regions—with the direction of this activity depending on patients’ performance levels—and failure to suppress default mode network (DMN) activity. Candidate cognition treatments seemed to enhance task-related dorsal PFC and temporo-parietal activity when performance increases were observed, and to reduce their activity when performance levels were unchanged. These treatments also attenuated DMN hyper-activity. In contrast, nonspecific cognitive improvement following symptom reduction was typically accompanied by decreased limbic reactivity and reversal of pre-treatment fronto-parietal hyper-activity. Together, the findings highlight some common neural correlates of cognitive impairments and cognitive improvements. Based on this evidence, studies are warranted to examine the reliability and predictive validity of target engagement in the identified neurocircuitries as a biomarker model of pro-cognitive effects.
Available information about seabird breeding population trends on Stinker Point (Elephant Island, Maritime Antarctic Peninsula) is outdated by decades. This study reports current numbers of breeding species, and evaluates population trends over 28 years. We counted breeding pairs of seabirds along all ice-free areas on Stinker Point during two distinct periods (summers of 1985/86–1991/92 and 2009/10–2013/14). Thirteen species currently breed in the area: four Sphenisciformes, four Procellariiformes, one Suliforme and four Charadriiformes. Chinstrap penguin Pygoscelis antarcticus has the highest number of breeding pairs (4971±590), followed by gentoo penguin Pygoscelis papua (1242±339). Comparisons between the two intervals showed declining trends for almost all breeding populations, although southern giant petrels Macronectes giganteus are experiencing a subtle population growth. Population decreases in locations with low human disturbance, such as Stinker Point, may indicate sensibility to climate and environmental change and need further investigation.
Returning genomic research results to family members raises complex questions. Genomic research on life-limiting conditions such as cancer, and research involving storage and reanalysis of data and specimens long into the future, makes these questions pressing. This author group, funded by an NIH grant, published consensus recommendations presenting a framework. This follow-up paper offers concrete guidance and tools for implementation. The group collected and analyzed relevant documents and guidance, including tools from the Clinical Sequencing Exploratory Research (CSER) Consortium. The authors then negotiated a consensus toolkit of processes and documents. That toolkit offers sample consent and notification documents plus decision flow-charts to address return of results to family of living and deceased participants, in adult and pediatric research. Core concerns are eliciting participant preferences on sharing results with family and on choice of a representative to make decisions about sharing after participant death.
Little is known about the association of cortical Aβ with depression and anxiety among cognitively normal (CN) elderly persons.
We conducted a cross-sectional study derived from the population-based Mayo Clinic Study of Aging in Olmsted County, Minnesota; involving CN persons aged ≥ 60 years that underwent PiB-PET scans and completed Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI). Cognitive diagnosis was made by an expert consensus panel. Participants were classified as having abnormal (≥1.4; PiB+) or normal PiB-PET (<1.4; PiB−) using a global cortical to cerebellar ratio. Multi-variable logistic regression analyses were performed to calculate odds ratios (OR) and 95% confidence intervals (95% CI) after adjusting for age and sex.
Of 1,038 CN participants (53.1% males), 379 were PiB+. Each one point symptom increase in the BDI (OR = 1.03; 1.00–1.06) and BAI (OR = 1.04; 1.01–1.08) was associated with increased odds of PiB-PET+. The number of participants with BDI > 13 (clinical depression) was greater in the PiB-PET+ than PiB-PET- group but the difference was not significant (OR = 1.42; 0.83–2.43). Similarly, the number of participants with BAI > 10 (clinical anxiety) was greater in the PiB-PET+ than PiB-PET− group but the difference was not significant (OR = 1.77; 0.97–3.22).
As expected, depression and anxiety levels were low in this community-dwelling sample, which likely reduced our statistical power. However, we observed an informative albeit weak association between increased BDI and BAI scores and elevated cortical amyloid deposition. This observation needs to be tested in a longitudinal cohort study.
The aim of this study was to identify the risk correlates for coexisting common mental disorders (CMDs) in the chronic care population in South Africa, with the view to identifying particularly vulnerable patient populations.
The sample comprised 2549 chronic care patients enrolled in the baseline and endline rounds of a facility detection survey conducted by the Programme for Improving Mental Health Care in three large facilities in the Dr Kenneth Kaunda district in the North West province of South Africa. Participants were screened for depression using the Patient Health Questionnaire (PHQ9) and for alcohol misuse using the Alcohol Use Disorders Identification Test (AUDIT). Data were analysed according to the number of morbidities, disorder type (physical or mental) and demographic variables. Multimorbidity was defined as the presence of two or more disorders (physical and/or mental).
Just over one-third of the sample reported two or more physical conditions. Women were more at risk of being depressed than were men, with men more at risk of alcohol misuse. Those who were employed were at lower risk of having coexisting CMDs, while being younger, HIV positive, and food deprived were all found to be associated with higher risk for having coexisting CMDs.
In the face of the large treatment gap for CMDs in South Africa, and the role that coexisting CMDs can play in exacerbating the burden of chronic physical diseases, mental health screening and treatment interventions should target HIV-positive, younger patients living in circumstances where there is household food insecurity.