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The aim of the study is to assess the psychometric properties of the Portuguese version of the 18-items Dysfunctional Attitudes Scale (Form B) in a Portuguese sample of people aged 60 and over. Background: The 18-item Dysfunctional Attitudes Scale (Form B) is an instrument for assessing dysfunctional attitudes and can be useful as a predictor of depression for both initial episodes and relapses Methods: This was a one-stage cross-sectional survey of Portuguese-speaking people aged 60 years and over, able to read and write, functionally autonomous, and living in the community in their usual residences. The instrument was evaluated for its psychometric properties. Convergent validity with the Beck Depression Inventory-II was assessed. Results: The Portuguese version of the 18-item Dysfunctional Attitudes Scale (Form B) was structured into three factors, which explained a total of 58.95% of the total variance of the instrument. The exploratory factor analysis resulted in a modified model in which three factors were obtained with an eigenvalue greater than one (Kaiser’s criterion). Three factors were obtained instead of two as in the original study. It showed an internal consistency (Cronbach’s alpha = 0.770) and an interclass correlation coefficient ranging from 0.166 to 0.449, and the overall convergent validity with the Beck Depression Inventory-II was considered good; Conclusions: The Portuguese version of the Dysfunctional Attitudes Scale (DAS-18B) of people aged 60 and over demonstrated good psychometric properties.

Abstract Efficient detection of the magnetic state is a critical step towards useful antiferromagnet-based spintronic devices. Recently, finite tunneling magnetoresistance (TMR) has been demonstrated in tunnel junctions with antiferromagnetic electrodes, however, these studies have been mostly limited to junctions with two identical antiferromagnet (AFM) electrodes, where the matching of the spin-split Fermi surfaces played critical role. It remains unclear if AFMs can provide a finite net spin polarization, and hence be used as a spin polarizer or detector. In this work, we experimentally fabricate single-sided antiferromagnetic tunnel junctions consisting of one AFM electrode (Mn3Sn) and one ferromagnet (FM) electrode (CoFeB), where the spin polarized tunneling transport from AFM is detected by the FM layer. We observe a high TMR at cryogenic temperature (>100% at 10 K) in these asymmetric AFM tunnel junctions, suggesting a large effective spin polarization from Mn3Sn despite its nearly vanishing magnetization. The large TMR is consistent with recent theoretical studies where the broken symmetry in non-collinear AFMs is predicted to lift the spin degeneracy in the band structure. Our work provides strong evidence that spin polarized electrical transport can be achieved from AFMs.

Abstract Identifying components of modularized psychological interventions that contribute to symptom reduction is essential to improving depression treatment. In a secondary analysis of a randomized controlled trial (RCT), session-specific effects of Metacognitive Training-Silver, a group intervention for older adults with depression, were investigated. Thirty-eight older adults with major depressive disorder or dysthymia participated in up to eight sessions of MCT-Silver. A clinical assessment of depressive symptoms (Hamilton Depression Rating Scale) as well as additional interviews and questionnaires administered as part of the RCT were completed at pre- and post-intervention. Depressive symptoms, negative (meta)cognitive beliefs, emotion regulation strategies and attitudes toward aging were assessed pre- and post-session. The rate of change in each variable per module, elevation following the module in which the variable was addressed, and the rate of change post module were examined via linear mixed models. Clinician-rated depressive symptoms were significantly reduced from pre- to post-intervention (Cohens d = 1.31). Self-reported depression and negative mental filter measured within sessions improved significantly over treatment, whereas black-and-white thinking improved after module #3 (Should Statements, All or Nothing Thinking and Acceptance). Module-specific within-session effects were found for overgeneralization (module #1: Mental Filter) and rumination (module #6: Rumination and Social Withdrawal). Improvement in mental filter in module #1 was significantly associated with depression reduction. This study provides initial evidence that MCT-Silver partially meets its aims of reducing depression and specific cognitive variables within and across sessions. Improvement of the instrument used to measure change may improve detection of module-specific effects. Trial registration: NCT03691402.

Abstract Background Fecal microbiota transplantation (FMT) is a therapeutic intervention used to treat diseases associated with the gut microbiome. In the human gut microbiome, phages have been implicated in influencing human health, with successful engraftment of donor phages correlated with FMT treatment efficacy. The impact that gastrointestinal phages exert on human health has primarily been connected to their ability to modulate the bacterial communities in the gut. Nonetheless, how FMT affects recipients’ phage populations, and in turn, how this influences the gut environment, is not yet fully understood. In this study, we investigated the effects of FMT on the phageome composition of participants within the Gut Bugs Trial (GBT), a double-blind, randomized, placebo-controlled trial that investigated the efficacy of FMT in treating obesity and comorbidities in adolescents. Stool samples collected from donors at the time of treatment and recipients at four time points (i.e., baseline and 6 weeks, 12 weeks, and 26 weeks post-intervention), underwent shotgun metagenomic sequencing. Phage sequences were identified and characterized in silico to examine evidence of phage engraftment and to assess the extent of FMT-induced alterations in the recipients’ phageome composition. Results Donor phages engrafted stably in recipients following FMT, composing a significant proportion of their phageome for the entire course of the study (33.8 ± 1.2% in females and 33.9 ± 3.7% in males). Phage engraftment varied between donors and donor engraftment efficacy was positively correlated with their phageome alpha diversity. FMT caused a shift in recipients’ phageome toward the donors’ composition and increased phageome alpha diversity and variability over time. Conclusions FMT significantly altered recipients' phage and, overall, microbial populations. The increase in microbial diversity and variability is consistent with a shift in microbial population dynamics. This proposes that phages play a critical role in modulating the gut environment and suggests novel approaches to understanding the efficacy of FMT in altering the recipient’s microbiome. Trial registration The Gut Bugs Trial was registered with the Australian New Zealand Clinical Trials Registry (ACTR N12615001351505). Trial protocol: the trial protocol is available at https://bmjopen.bmj.com/content/9/4/e026174 . Video Abstract

IntroductionGut microbiome transfer (GMT or faecal microbiome transfer) is gaining increasing attention as a potential treatment for a range of medical conditions. However, public awareness and acceptance are not well understood.MethodsTo better understand the public perception of microbiome transfer in New Zealand, we undertook a nationwide online survey. The anonymous survey was designed and distributed between 2022-2023. Inclusion criteria included being aged 16 years or older and a resident of New Zealand. Distribution channels included social media advertising, posters in public areas, e-mail newsletters, and a survey facilitation company.ResultsA total of 2441 completed surveys were analyzed. Most respondents (71%) had tertiary education, 59% were female, with 62% identifying as NZ European, 12% as Māori, and 3% as Pacific peoples. The findings identified a high level of awareness and acceptability, with 76% of respondents having heard of GMT, and 96% indicating they would consider it if proven efficacious for a health condition they had. High levels of acceptance were observed across all ethnicities. Encapsulated oral FMT treatment was the preferred transfer method.DiscussionPrimary concerns related to GMT included the diet, health, and screening of stool donors, as well as the demonstration of safety and efficacy. These findings will help inform health professionals and researchers about the public’s needs and preferences regarding GMT.

Depression is a prevalent illness among the elderly, so psychotherapeutic interventions are needed to promote health and quality of life. This literature review aims to identify trials of any psychotherapeutic interventions aimed at reducing depressive symptoms in older adults. A systematic literature review with a meta-analysis will be carried out. The following databases will be searched: CINAHL Plus with Full Text, MedicLatina, MEDLINE with Full Text, and Psychology and Behavioral Sciences Collection. To minimize bias, four reviewers will independently assess the inclusion of studies. The fifth reviewer will be responsible for disaggregating inclusion and exclusion between two authors. The results of the analysis will be grouped in a table with the characteristics of the included studies, including author, year, sample, objectives, methods, assessment instruments, psychotherapeutic interventions, results, follow-up and a data compilation scheme. This scientific article is a systematic review protocol for which the data has already been extracted and is being analyzed. Examples of possible strategies to include cognitive restructuring and mental health programs for older adults in community settings. With this clear and direct identification of psychotherapeutic interventions, it will be clearer for mental health professionals to be able to intervene effectively to promote the mental health and well-being of older adults.PROSPERO registration numberCRD42023449190

Abstract Background Horizontal gene transfer (HGT) describes the transmission of DNA outside of direct ancestral lineages. The process is best characterised within the bacterial kingdom and can enable the acquisition of genetic traits that support bacterial adaptation to novel niches. The adaptation of bacteria to novel niches has particular relevance for faecal microbiota transplantation (FMT), a therapeutic procedure which aims to resolve gut-related health conditions of individuals, through transplanted gut microbiota from healthy donors. Results Three hundred eighty-one stool metagenomic samples from a placebo-controlled FMT trial for obese adolescents (the Gut Bugs Trial) were analysed for HGT, using two complementary methodologies. First, all putative HGT events, including historical HGT signatures, were quantified using the bioinformatics application WAAFLE. Second, metagenomic assembly and gene clustering were used to assess and quantify donor-specific genes transferred to recipients following the intervention. Both methodologies found no difference between the level of putative HGT events in the gut microbiomes of FMT and placebo recipients, post-intervention. HGT events facilitated by engrafted donor species in the FMT recipient gut at 6 weeks post-intervention were identified and characterised. Bacterial strains contributing to this subset of HGT events predominantly belonged to the phylum Bacteroidetes. Engraftment-dependent horizontally transferred genes were retained within recipient microbiomes at 12 and 26 weeks post-intervention. Conclusion Our study suggests that novel microorganisms introduced into the recipient gut following FMT have no impact on the basal rate of HGT within the human gut microbiome. Analyses of further FMT studies are required to assess the generalisability of this conclusion across different FMT study designs and for the treatment of different gut-related conditions. Video Abstract

Introduction Epilepsy is a common neurological disorder characterised by recurrent seizures. Almost half of patients who have an unprovoked first seizure (UFS) have additional seizures and develop epilepsy. No current predictive models exist to determine who has a higher risk of recurrence to guide treatment. Emerging evidence suggests alterations in cognition, mood and brain connectivity exist in the population with UFS. Baseline evaluations of these factors following a UFS will enable the development of the first multimodal biomarker-based predictive model of seizure recurrence in adults with UFS.Methods and analysis 200 patients and 75 matched healthy controls (aged 18–65) from the Kingston and Halifax First Seizure Clinics will undergo neuropsychological assessments, structural and functional MRI, and electroencephalography. Seizure recurrence will be assessed prospectively. Regular follow-ups will occur at 3, 6, 9 and 12 months to monitor recurrence. Comparisons will be made between patients with UFS and healthy control groups, as well as between patients with and without seizure recurrence at follow-up. A multimodal machine-learning model will be trained to predict seizure recurrence at 12 months.Ethics and dissemination This study was approved by the Health Sciences and Affiliated Teaching Hospitals Research Ethics Board at Queen’s University (DMED-2681-22) and the Nova Scotia Research Ethics Board (1028519). It is supported by the Canadian Institutes of Health Research (PJT-183906). Findings will be presented at national and international conferences, published in peer-reviewed journals and presented to the public via patient support organisation newsletters and talks.Trial registration number NCT05724719.

Abstract T’Ho virus is a poorly characterized orthoflavivirus most closely related to Rocio virus and Ilheus virus, two orthoflaviviruses associated with human disease, suggesting that T’Ho virus could also be a human pathogen. The genome of T’Ho virus has been sequenced but an isolate has never been recovered, impeding its phenotypic characterization. In an attempt to generate recombinant T’Ho virus, the entire viral genome was synthesized as three overlapping DNA fragments, joined by Gibson assembly, and transfected into mosquito cells. Several cell culture passages were performed, but virus was not recovered. Subsequent experiments focused on the development of a chimeric orthoflavivirus that contains the premembrane and envelope protein genes of T’Ho virus in the genetic background of Zika virus. The chimeric virus replicated in mosquito (C6/36) and vertebrate (Vero) cells, demonstrating that the major structural glycoproteins of T’Ho virus permit entry into both cell types. The chimeric virus produced plaques in Vero cells that were significantly smaller than those produced by Zika virus. The chimeric virus can potentially be used as a surrogate diagnostic reagent in place of T’Ho virus in plaque reduction neutralization tests, allowing T’Ho virus to be considered in the differential diagnosis.

Introduction Autism (formally autism spectrum disorder) encompasses a group of complex neurodevelopmental conditions, characterised by differences in communication and social interactions. Co-occurring chronic gastrointestinal symptoms are common among autistic individuals and can adversely affect their quality of life. This study aims to evaluate the efficacy of oral encapsulated faecal microbiome transfer (FMT) in improving gastrointestinal symptoms and well-being among autistic adolescents and adults.Methods and analysis This double-blind, randomised, placebo-controlled trial will recruit 100 autistic adolescents and adults aged 16–45 years, who have mild to severe gastrointestinal symptoms (Gastrointestinal Symptoms Rating Scale (GSRS) score ≥2.0). We will also recruit eight healthy donors aged 18–32 years, who will undergo extensive clinical screening. Recipients will be randomised 1:1 to receive FMT or placebo, stratified by biological sex. Capsules will be administered over two consecutive days following an overnight bowel cleanse with follow-up assessments at 6, 12 and 26 weeks post-treatment. The primary outcome is GSRS score at 6 weeks. Other assessments include anthropometry, body composition, hair cortisol concentration, gut microbiome profile, urine/plasma gut-derived metabolites, plasma markers of gut inflammation/permeability and questionnaires on general well-being, sleep quality, physical activity, food diversity and treatment tolerability. Adverse events will be recorded and reviewed by an independent data monitoring committee.Ethics and dissemination Ethics approval for the study was granted by the Central Health and Disability Ethics Committee on 24 August 2021 (reference number: 21/CEN/211). Results will be published in peer-reviewed journals and presented to both scientific and consumer group audiences.Trial registration number ACTRN12622000015741.

IntroductionSchizophrenia-Spectrum-Disorders are associated with poor long-term outcome as well as disability and often severely affect the lives of patients and their families often from symptom onset. Up to 70% of first episode psychosis (FEP) patients suffer from comorbid substance use disorders (SUD). We aimed at studying the course of illness in FEP patients within evidence-based care, with and without comorbid SUD, to examine how decreased, remitted or persistent substance use impacted rates of a combined symptomatic and functional long-term recovery compared with patients without SUD.MethodsACCESS III is an integrated care model for FEP or patients in the early phase of non-affective and affective psychotic disorders. Treatment trajectories of patients, who had been in ACCESS care for 1 year, with and without SUD were compared with regard to the course of illness and quality of life using Mixed Model Repeated Measures (MMRM) and recovery rates were compared using binary logistic regression. Change in substance use was coded as either persistent, decreased/remitted or no use.ResultsACCESS III was a prospective 1-year study (N = 120) in patients aged 12–29 years. Of these, 74 (61.6%) had a comorbid SUD at admission. There were no group differences regarding the course of illness between patients with or without comorbid SUD or between patients with a substance abuse or substance dependence. The only outcome parameter that was affected by SUD was quality of life, with larger improvement found in the group without substance use (p = 0.05) compared to persistent and remitted users. Using LOCF, 44 patients (48.9%) fulfilled recovery criteria at the endpoint; recovery did not differ based on substance use status.DiscussionSUD and especially substance dependence are common in psychotic disorders even in FEP patients. Evidence-based integrated care led to long-term improvement in patients with comorbid SUD and rate of recovery did not differ for patients with substance use.

Identifying factors that influence the stability of DNA methylation measurements across biological replicates is of critical importance in basic and clinical research. Using a within-person between-group experimental design (n = 31, number of observations = 192), we report the stability of biological replicates over a variety of unique temporal scenarios, both in the absence and presence of acute psychosocial stress, and between individuals who have experienced early life adversity (ELA) and non-exposed individuals. We found that varying time intervals, acute stress, and ELA exposure influenced the stability of repeated DNA methylation measurements. In the absence of acute stress, probes were less stable as time passed; however, stress exerted a stabilizing influence on probes over longer time intervals. Compared to non-exposed individuals, ELA-exposed individuals had significantly lower probe stability immediately following acute stress. Additionally, we found that across all scenarios, probes used in most epigenetic-based algorithms for estimating epigenetic age or immune cell proportions had average or below-average stability, except for the Principal Component and DunedinPACE epigenetic ageing clocks, which were enriched for more stable probes. Finally, using highly stable probes in the absence of stress, we identified multiple probes that were hypomethylated in the presence of acute stress, regardless of ELA status. Two hypomethylated probes are located near the transcription start site of the glutathione-disulfide reductase gene (GSR), which has previously been shown to be an integral part of the stress response to environmental toxins. We discuss implications for future studies concerning the reliability and reproducibility of DNA methylation measurements. Abbreviations: DNAm – DNA methylation, CpG − 5’-cytosine-phosphate-guanine-3,’ ICC – Interclass correlation coefficient, ELA – Early-life adversity, PBMCs – Peripheral blood mononuclear cells, mQTL – Methylation quantitative trait loci, TSS – Transcription start site, GSR – Glutathione-disulfide reductase gene, TSST – Trier social stress test, PC – Principal component.

IntroductionDepression is one of the most common psychological disorders in later life. Although psychological interventions are recommended by treatment guidelines, most older adults with depression remain untreated. The aim of this study is to evaluate the efficacy of the Portuguese version of Metacognitive Training for Depression in later life (MCT-Silver).MethodsThis is a study protocol of an observer-blind, parallel-group, randomized controlled trial to compare the efficacy of MCT-Silver with a treatment as usual (TAU) control group among older adults (age 65 years and older) with depressive symptoms according to the Montgomery-Asberg Depression Scale. Participants will be tested at three assessment time points (baseline, immediately following the intervention [8 weeks], and 3 months after the intervention). The primary outcome is change in self-rated depression symptoms assessed by the Beck Depression Inventory (BDI-II). Secondary outcomes include clinician-rated depression, self-esteem, dysfunctional beliefs, metacognitive beliefs, ruminations, attitudes toward aging and quality of life. A self-designed subjective appraisal rating scale consisting of 21-items will be used to assess participant acceptance of MCT-Silver.DiscussionMCT-Silver is an innovative intervention, which aims to reduce dysfunctional thoughts as well as depression-related behaviors and coping strategies through the metacognitive perspective. Until now, the training has only been tested in Germany. It is expected that after 8 weeks of treatment and 3 months later, the experimental group will demonstrate significant reductions in depressive symptoms, metacognitive beliefs, dysfunctional attitudes and ruminative responses compared to the TAU group. Moreover, quality of life, self-esteem, and attitudes towards aging will be significantly improved in MCT-Silver compared to the TAU group.Clinical trial registrationClinicalTrials.gov, NCT05640492.

The COVID-19 pandemic was associated with declines in mental health and increased interest in pet ownership. We aimed to extend past theories and research linking pet ownership and mental health by investigating whether pet ownership was associated with mental health during the initial phases of the COVID-19 pandemic in a sample of American adults. We also tested whether the association of pet ownership and mental health was moderated by relationship status. Participants were 2,906 American adults who were recruited for an online survey study between May 2020 and May 2021. Pet ownership was assessed via dichotomous self-report (yes/no) and mental health was assessed using a 13-item questionnaire. The sample was 69.2% female with an average age of 46.0 years. 36.1% of the sample owned a pet and 68.5% of the sample was currently partnered. There was no overall association of pet ownership and mental health during the COVID-19 pandemic (estimated mean difference (EMD) = 0.35, 95CI = −0.10, 0.80, p = 0.12). However, we found evidence for an association that was moderated by relationship status. Pet ownership was associated with better mental health among partnered individuals (EMD = 0.76, 95CI = 0.21, 1.30, p = 0.006). There was no association of pet ownership and mental health among unpartnered individuals (EMD = −0.41, 95CI = −1.20, 0.37, p = 0.30). Our findings suggest that relationship status may represent a critical moderator of the link between pet ownership and mental health. Future studies are needed to identify specific mechanisms of pet ownership that could explain its varied impact on the mental health of partnered and unpartnered individuals.

Abstract Novel treatments for muscle wasting are of significant value to patients with disease states that result in muscle weakness, injury recovery after immobilization and bed rest, and for astronauts participating in long-duration spaceflight. We utilized an anti-myostatin peptibody to evaluate how myostatin signaling contributes to muscle loss in hindlimb suspension. Male C57BL/6 mice were left non-suspended (NS) or were hindlimb suspended (HS) for 14 days and treated with a placebo vehicle (P) or anti-myostatin peptibody (D). Hindlimb suspension (HS-P) resulted in rapid and significantly decreased body mass (−5.6% by day 13) with hindlimb skeletal muscle mass losses between −11.2% and −22.5% and treatment with myostatin inhibitor (HS-D) partially attenuated these losses. Myostatin inhibition increased hindlimb strength with no effect on soleus tetanic strength. Soleus mass and fiber CSA were reduced with suspension and did not increase with myostatin inhibition. In contrast, the gastrocnemius showed histological evidence of wasting with suspension that was partially mitigated with myostatin inhibition. While expression of genes related to protein degradation (Atrogin-1 and Murf-1) in the tibialis anterior increased with suspension, these atrogenes were not significantly reduced by myostatin inhibition despite a modest activation of the Akt/mTOR pathway. Taken together, these findings suggest that myostatin is important in hindlimb suspension but also motivates the study of other factors that contribute to disuse muscle wasting. Myostatin inhibition benefitted skeletal muscle size and function, which suggests therapeutic potential for both spaceflight and terrestrial applications.

Introduction Individuals with anorexia nervosa (AN) harbour distinct gut microbiomes compared with healthy individuals, which are sufficient to induce weight loss and anxiety-like behaviours when transplanted into germ-free mice. We hypothesise that faecal microbiome transfer (FMT) from healthy donors would help restore the gut microbiome of individuals with AN, which in turn, may aid patient recovery.Methods We aim to conduct an open-label pilot study in 20 females aged 16–32 years in Auckland, New Zealand who meet the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) criteria for AN and have a body mass index 13–19 kg/m2. We will recruit four healthy, lean, female donors, aged 18–32 years, who will undergo extensive clinical screening prior to stool donation. Faecal microbiota will be harvested from donors and double encapsulated in delayed release, acid-resistant capsules. All participants will receive a single course of 20 FMT capsules (five from each donor) which they can choose to take over two or four consecutive days. Stool and blood samples will be collected from participants over a period of 3 months to assess their gut microbiome profile, metabolome, levels of intestinal inflammation and nutritional status. Our primary outcome is a shift in the gut microbiome composition at 3 weeks post-FMT (Bray-Curtis dissimilarity). We will also monitor participants’ body composition (whole-body dual-energy X-ray absorptiometry scans), eating disorder psychopathology, mental health and assess their views on, and tolerability of, treatment. All adverse events will be recorded and reviewed by an independent data monitoring committee.Ethics and dissemination Ethics approval was provided by the Central Health and Disability Ethics Committee (Ministry of Health, New Zealand, 21/CEN/212). Results will be published in peer-reviewed journals and presented to both scientific and consumer group audiences.Trial registration number ACTRN12621001504808.

Attachment theory proposes that close relationships help us to regulate our emotions in stressful and positive situations. However, no previous studies have examined preferences for a partner’s emotional response to one’s own stressful and positive situations or tested whether these preferences differ based on attachment orientation. This study examines the association of attachment orientation and preferences for partners’ emotional responses relative to one’s own emotional responses in stressful and positive contexts among 425 United States adults who were currently in a committed relationship of ≥6 months. Data were collected in 2020. Overall, participants preferred their partners to feel and express less distress, less worry, more calm, and more hope than themselves during stressful situations and for their partners to feel and express more excitement, pride, and hope than themselves during positive situations. Higher attachment anxiety predicted preferences for partners to feel and express more distress/worry in stressful situations, whereas higher attachment avoidance predicted preferences for partners to feel and express less hope in stressful situations. Statistical interactions of attachment anxiety × attachment avoidance indicated that the combination of low attachment anxiety and high attachment avoidance (dismissing avoidance) was associated with preferences for partners to feel and express less positive emotions in positive situations, whereas the combination of high attachment anxiety and high attachment avoidance (fearful avoidance) was associated with preferences for partners to feel and express more negative emotions in stressful situations and less positive emotions in positive situations. This investigation provides novel evidence for links between attachment orientation and preferences for partners’ emotional responses in two theoretically important contexts, which has implications for the nature and function of emotion regulation in close relationships. Future research is needed to determine the generalizability of these findings to more collectivist cultural contexts.

Stimulants are effective in treating attention-deficit/hyperactivity disorder (ADHD). Psychiatrist Charles Bradley first made this discovery in 1937 when he found that children treated with amphetamines showed improvements in school performance and behavior. Between 1995 and 2008, stimulants to treat ADHD increased six-fold among American adults and adolescents at an annual rate of 6.5%. Stimulants without a prescription, known as nonmedical use or misuse, have also increased. The highest rates of nonmedical prescription drug misuse in the United States are seen most notably in young adults between 18 and 25 years, based on data from the Substance Abuse and Mental Health Services Administration in 2021. Aside from undergraduate students, nonmedical prescription stimulant use is prevalent among medical students worldwide. A recent literature review reported the utilization of stimulants without a prescription in 970 out of 11,029 medical students. The percentages of medical students across the country misusing stimulants varied from 5.2% to 47.4%. Academic enhancement, reported in 50% to 89% of college students with stimulant misuse, is the most common reason for nonmedical stimulant use. With the increasing use of stimulants among adolescents and adults, it is unclear what long-term outcomes will be since little data are available that describe differences in how side effects are experienced for prescribed and non-prescribed users. The present narrative review focuses on these adverse effects in this population and the reasonings behind misuse and nonmedical use.

California Leafy Green Products Handler Marketing Agreement (LGMA) established food safety metrics with guidance recommendations of 366 m (1,200 feet) and 1,609 m (1 mile) distances between production fields of leafy greens and a concentrated animal feeding operation (CAFO) containing >1,000 and >80,000 head of cattle, respectively. This study evaluated the effect of these distance metrics and environmental factors on the occurrence of airborne Escherichia coli in proximity to seven commercial beef cattle feedlots located in Imperial Valley, California. A total of 168 air samples were collected from seven beef cattle feedlots during March and April 2020, which were the months implicated in the 2018 Yuma Arizona lettuce outbreak of E. coli O157:H7. The distance between air sampling sites and the edge of the feedlot ranged from ∼0 to ∼2,200 m (∼1.3 mile), with each sample comprised of 1,000 L of processed air taken at a 1.2 m elevation over a 10-minute duration. E. coli colonies were enumerated on CHROMagar ECC selective agar and confirmed with conventional PCR. Meteorological data (air temperature, wind speed, wind direction, relative humidity) were collected in situ. The prevalence and mean concentration of E. coli were 6.55% (11/168) and 0.09 CFU per 1,000 L of air, with positive samples limited to within 37 m (120 ft) of the feedlot. Based on logistic regression, the odds of airborne E. coli detection were associated with little to no wind and close proximity to a feedlot. This pilot study found limited dispersal of airborne E. coli in proximity to commercial feedlots in Imperial Valley, with light-to-no wind and proximity within 37 m of a feedlot significant factor-associated airborne E. coli in this produce-growing region of California.

Early life adversity (ELA) is a risk factor for early onset morbidities and mortality, a relationship that may be driven in part by immune system dysregulation. One mechanism of dysregulation that has yet to be fully examined in the context of ELA is alterations to immune cell dynamics in response to acute stress. Using a within-person between-group experimental design, we investigated stress-induced changes in immune cell populations, and how these changes may be altered in individuals with a history of ELA. Participants were young adults (N = 34, aged 18–25 years, 53% female, 47% with a history of ELA). Complete immune cell counts were measured at four time-points over a 5-hour window across two sessions (Trier Social Stress Test [TSST] vs. no-stress) separated by a week. Across all participants, total white blood cells increased over time (F(3,84)=38.97, p

BackgroundMetacognitive Training for Depression in older adults (MCT-Silver; www.uke.de/mct-silver) is a cognitive-behavioral based group intervention that aims at reducing depression by targeting (meta)cognitive beliefs and rumination. In the present study, it was examined whether negative cognitive beliefs, positive metacognitive beliefs and/or rumination may be implicated as mediators of MCT-Silver’s effects on depression.Materials and methodsWe conducted a secondary analysis of a randomized controlled trial comparing MCT-Silver to an active control intervention (cognitive remediation) including 66 older adults (60 years and older) with complete baseline data. Clinician-rated (Hamilton Depression Rating Scale) and self-reported (Beck Depression Inventory-II) depression, negative cognitive beliefs (Dysfunctional Attitudes Scale-18B), positive metacognitive beliefs (positive beliefs subscale; Metacognition Questionnaire-30) and rumination (10-item Ruminative Response Scale) were assessed before (pre) and after 8 weeks of treatment (post), as well as 3 months later (follow-up). It was examined whether change in depression (pre- to follow-up) was mediated by change in negative cognitive beliefs, positive metacognitive beliefs and/or rumination (pre- to post-assessment).ResultsMediation results differed for self-reported vs. clinician-rated depression. The effect of MCT-Silver on reduction in clinician-rated depression was mediated by a reduction in self-reported rumination, whereas reduction in self-reported depression was mediated by a reduction in negative cognitive beliefs. Positive metacognitive beliefs were not a significant mediator for either outcome.ConclusionThe current study provides initial evidence for the roles of negative cognitive beliefs and rumination in the treatment of depression in later life with MCT-Silver. Given the divergence of findings and lack of causal precedence, mechanisms of change for MCT-Silver cannot yet be equivocally identified.

IntroductionHealthy individuals with poor cardiovascular control, but who do not experience syncope (fainting), adopt an innate strategy of increased leg movement in the form of postural sway that is thought to counter orthostatic (gravitational) stress on the cardiovascular system. However, the direct effect of sway on cardiovascular hemodynamics and cerebral perfusion is unknown. If sway produces meaningful cardiovascular responses, it could be exploited clinically to prevent an imminent faint.MethodsTwenty healthy adults were instrumented with cardiovascular (finger plethysmography, echocardiography, electrocardiogram) and cerebrovascular (transcranial Doppler) monitoring. Following supine rest, participants performed a baseline stand (BL) on a force platform, followed by three trials of exaggerated sway (anterior-posterior, AP; mediolateral, ML; square, SQ) in a randomized order.ResultsAll exaggerated postural sway conditions improved systolic arterial pressure (SAP, p = 0.001) responses, while blunting orthostatic reductions in stroke volume (SV, p < 0.01) and cerebral blood flow (CBFv, p < 0.05) compared to BL. Markers of sympathetic activation (power of low-frequency oscillations in SAP, p < 0.001) and maximum transvalvular flow velocity (p < 0.001) were reduced during exaggerated sway conditions. Responses were dose-dependent, with improvements in SAP (p < 0.001), SV (p < 0.001) and CBFv (p = 0.009) all positively correlated with total sway path length. Coherence between postural movements and SAP (p < 0.001), SV (p < 0.001) and CBFv (p = 0.003) also improved during exaggerated sway.DiscussionExaggerated sway improves cardiovascular and cerebrovascular control and may supplement cardiovascular reflex responses to orthostatic stress. This movement provides a simple means to boost orthostatic cardiovascular control for individuals with syncope, or those with occupations that require prolonged motionless standing.

Evaluation of the effects of feeding NutraGen supplement (NutraGen, NTG; Phibro Animal Health, Teaneck, NJ, USA) on growth performance, energetic efficiency, carcass characteristcs, and characteristics of digestion in calf-fed Holstein steers fed a conventional growing-finishing diet. Trial 1 evaluated growth performance, dietary energetics and carcass characteristics. Two hundred Holstein steer calves (134 ± 5 kg) were blocked by initial body weight (BW) and randomly assigned to 40 pens (5 steers/pen). Dietary treatments consisted of a steam-flaked corn-based growing-finishing diet supplemented with 0, 0.2, 0.4, or 0.6% NTG (DM basis). In trial 2, four Holstein steers (170 ±6 kg) with cannulas in the rumen and proximal duodenum were used in a 4 × 4 Latin square experiment to evaluate digestibility and ruminal characteristics using the treatments from trial 1. Compared to non-supplemented cattle, NTG increased BW (2.0%, P = 0.02) and tended to increase ADG (3.6%, P = 0.07) during the initial 56 d period. However, there were no treatment effects on overall growth performance and efficiency of dietary energy utilization after the first 56 days (P > 0.10). Supplementation of NTG increased (linear effect; P ≤ 0.03) longissimus muscle area and kidney, pelvic, and heart fat. There was no effect (P ≥ 0.05) of NTG supplementation on other carcass characteristics, liver abscess incidence, or liver abscess scars. Supplementation decreased the molar proportion of ruminal propionate (P = 0.05) and tended to increase acetate:propionate molar ratio (P = 0.09). However, there was no effect of NTG supplementation on ruminal and total tract diet digestion. NTG increased performance of Holstein steers during the first 56 d on feed in the feedlot. In addition, the steers had an increase in KPH fat and LM area, indicating that the additive induced change in metabolism of the steers.

The mitochondrion is intimately linked to energy and overall metabolism and therefore the morphology of mitochondrion can be very informative for inferring the metabolic state of cells. In this study we report an approach for automatic classification of mitochondrial morphologies using supervised machine learning to efficiently classify them from a large number of cells at a time. Fluorescence microscopy images of the chronic encysted form of parasite Toxoplasma gondii were used for this development. Manually classifying these morphologies from the hundreds of parasites within typical tissue cysts is tedious and error prone. In addition, because of inherent biological heterogeneity in morphologies, there can be variability and lack of reproducibility in manual classification. We used image segmentation to detect mitochondrial shapes and used features extracted from them in a multivariate logistic regression model to classify the detected shapes into five morphological classes: Blobs, Tadpoles, Lasso/Donuts, Arcs, and Other. The detected shapes from a subset of images were first used to obtain consensus classification among expert users to obtain a labeled set. The model was trained using the labeled set from five cysts and its performance was tested on the mitochondrial morphologies from ten other cysts that were not used in training. Results showed that the model had an average overall accuracy of 87%. There was high degree of confidence in the classification of Blobs and Arcs (average F scores 0.91 and 0.73) which constituted the majority of morphologies (85%). Although the current development used microscopy images from tissue cysts of Toxoplasma gondii, the approach is adaptable with minor adjustments and can be used to automatically classify morphologies of organelles from a variety of cells.

Bans on the use of ionophores in several regions of the world has led to a need to identify alternative feed additivies to be added in cattle diets. Essential oil blends have been identified as a potential alternative to ionophores in feedlot diets. The objective of this study was to evaluate the effects of a supplemental a blend of essential oils and 25-hydroxyvitamin D3 on growth performance, energetic efficiency, and carcass characteristics in calf-fed Holstein steers. Ninety Holstein steer calves (123 ± 7 kg; 4 months old) were randomly assigned to 18 pens (5 steers/pen; 6 pens/treatment). Dietary treatments consisted of a steam-flaked corn-based diet supplemented with (DM basis): (1) no additives (CON); (2) 30 mg/kg DM of monensin (MON); (3) 200 mg/kg DM of a mixture of essential oils plus 25-hydroxyvitamin D3 (EO+HYD). There were no treatment effects (P > 0.05) on initial, intermediate and final cattle live weight; moreover, cattle had similar (P > 0.05) average daily gain (ADG) and dry matter intake (DMI) among dietary treatments. However, during the first 112 days of feed, calf-fed Holstein steers supplemented with EO+HYD had a greater (P ≤ 0.05) gain to feed ratio (G/F) than cattle fed the control diet but similar (P > 0.05) G/F to cattle supplemented with MON. However, there was no effect (P > 0.05) of dietary treatments on 112 to 286 d and the overall G/F ratio of calf-fed Holstein steers. Calf-fed Holstein steers supplemented with EO+HYD had greater (P ≤ 0.05) estimated net energy for maintenance (NEm) and net energy for gain (NEg) based on cattle growth performance than cattle fed the CON diet. Cattle supplemented with MON had an intermediate and similar (P > 0.05) NEm and NEg compared to the other two dietary treatments. However, when observed vs. expected NEm and NEg were calculated, cattle supplemented with MON and EO+HYD had greater efficiency of dietary energy utilization than cattle fed the CON diet. Calf-fed Holstein steers supplemented with MON had greater (P < 0.05) fat thickness than EO+HYD supplemented steers, and both were intermediate (P ≥ 0.05) to that of cattle fed the CON diet. There were no other effects (P > 0.05) on kidney, pelvic and heart fat, longissimus area, marbling score, and retail yield. The health status of cattle and liver abscesses or liver scars at slaughter were similar (P > 0.05). We conclude that supplementing calf-fed Holstein steers with MON or EO+HYD for over 285 days increased dietary net energy utilization for maintenance and gain of the diet by 3 and 4%, respectively, compared to non-supplemented steers.

Introduction Depression is a common mental disorder and is a major cause of years lived with disability. The COVID-19 pandemic has caused an increase in the prevalence of depression worldwide. Our aim is to identify and synthesise the determinants of depression, the diagnostic assessment tools used to evaluate depression, and the interventions carried out since the beginning of the COVID-19 pandemic in the population aged 60 and older.Methods and analysis A systematic review of the literature will be conducted. The following databases will be searched: CINAHL Plus with Full Text, MedicLatina, MEDLINE with Full Text, and Psychology and Behavioural Sciences Collection. The search strategy will include the following Medical Subject Headings or similar terms: “Depression”, “Depressive Disorder”, “Depressive Symptoms”, “Older Adults”, “Aging”, “Elderly”, Pandemic” and “COVID-19”. Two independent reviewers will ascertain whether the resulting articles meet inclusion and exclusion criteria, and perform the analysis of data quality. Disagreements will be resolved by a third reviewer. All studies reported between December 2019 and March 2022 meeting the following criteria will be included: studies in adults aged 60 and over, and articles written in English, Portuguese, Spanish or German. Information on determinants of depression, assessment instruments used to assess depressive symptoms and/or interventions to decrease depression are reported. Studies will not be excluded based on geographical area study context (eg, community, culture or specific environment). All studies related to diagnostic assessment, care planning and/or intervention strategies specifically for older adults with depression will be included.Ethics and dissemination As only secondary data will be analysed, no ethical approval is required for this study. This scientific article is a systematic review protocol for which data have not yet been extracted or analysed. The results will be disseminated through peer-reviewed publications.PROSPERO registration number CRD42022299775.

Animals must learn through experience which foods are nutritious and should be consumed, and which are toxic and should be avoided. Enteroendocrine cells (EECs) are the principal chemosensors in the GI tract, but investigation of their role in behavior has been limited by the difficulty of selectively targeting these cells in vivo. Here, we describe an intersectional genetic approach for manipulating EEC subtypes in behaving mice. We show that multiple EEC subtypes inhibit food intake but have different effects on learning. Conditioned flavor preference is driven by release of cholecystokinin whereas conditioned taste aversion is mediated by serotonin and substance P. These positive and negative valence signals are transmitted by vagal and spinal afferents, respectively. These findings establish a cellular basis for how chemosensing in the gut drives learning about food.

Abstract Background Donor selection is an important factor influencing the engraftment and efficacy of fecal microbiota transplantation (FMT) for complex conditions associated with microbial dysbiosis. However, the degree, variation, and stability of strain engraftment have not yet been assessed in the context of multiple donors. Methods We conducted a double-blinded randomized control trial of FMT in 87 adolescents with obesity. Participants were randomized to receive multi-donor FMT (capsules containing the fecal microbiota of four sex-matched lean donors) or placebo (saline capsules). Following a bowel cleanse, participants ingested a total of 28 capsules over two consecutive days. Capsules from individual donors and participant stool samples collected at baseline, 6, 12, and 26 weeks post-treatment were analyzed by shotgun metagenomic sequencing allowing us to track bacterial strain engraftment and its functional implications on recipients’ gut microbiomes. Results Multi-donor FMT sustainably altered the structure and the function of the gut microbiome. In what was effectively a microbiome competition experiment, we discovered that two donor microbiomes (one female, one male) dominated strain engraftment and were characterized by high microbial diversity and a high Prevotella to Bacteroides (P/B) ratio. Engrafted strains led to enterotype-level shifts in community composition and provided genes that altered the metabolic potential of the community. Despite our attempts to standardize FMT dose and origin, FMT recipients varied widely in their engraftment of donor strains. Conclusion Our study provides evidence for the existence of FMT super-donors whose microbiomes are highly effective at engrafting in the recipient gut. Dominant engrafting male and female donor microbiomes harbored diverse microbial species and genes and were characterized by a high P/B ratio. Yet, the high variability of strain engraftment among FMT recipients suggests the host environment also plays a critical role in mediating FMT receptivity. Trial registration The Gut Bugs trial was registered with the Australian New Zealand Clinical Trials Registry ( ACTRN12615001351505 ). Trial protocol The trial protocol is available at https://bmjopen.bmj.com/content/9/4/e026174 . Video Abstract

Abstract Background Vaginal seeding is the administration of maternal vaginal bacteria to babies following birth by caesarean section (CS), intended to mimic the microbial exposure that occurs during vaginal birth. Appropriate development of the infant gut microbiome assists early immune development and might help reduce the risk of certain health conditions later in life, such as obesity and asthma. We aimed to explore the views of pregnant women on this practice. Methods We conducted a sequential mixed-methods study on the views of pregnant women in New Zealand (NZ) on vaginal seeding. Phase one: brief semi-structured interviews with pregnant women participating in a clinical trial of vaginal seeding (n = 15); and phase two: online questionnaire of pregnant women throughout NZ (not in the trial) (n = 264). Reflexive thematic analysis was applied to interview and open-ended questionnaire data. Closed-ended questionnaire responses were analysed using descriptive statistics. Results Six themes were produced through analysis of the open-ended data: “seeding replicates a natural process”, “microbiome is in the media”, “seeding may have potential benefits”, “seeking validation by a maternity caregiver”, “seeding could help reduce CS guilt”, and “the unknowns of seeding”. The idea that vaginal seeding replicates a natural process was suggested by some as an explanation to help overcome any initial negative perceptions of it. Many considered vaginal seeding to have potential benefit for the gut microbiome, while comparatively fewer considered it to be potentially beneficial for specific conditions such as obesity. Just under 30% of questionnaire respondents (n = 78; 29.5%) had prior knowledge of vaginal seeding, while most (n = 133; 82.6%) had an initially positive or neutral reaction to it. Few respondents changed their initial views on the practice after reading provided evidence-based information (n = 60; 22.7%), but of those who did, most became more positive (n = 51; 86.4%). Conclusions Given its apparent acceptability, and if shown to be safe and effective for the prevention of early childhood obesity, vaginal seeding could be a non-stigmatising approach to prevention of this condition among children born by CS. Our findings also highlight the importance of lead maternity carers in NZ remaining current in their knowledge of vaginal seeding research.

The genetic identity of taste-responsive neurons has not been determined. The authors describe neurons in the gustatory region of the parabrachial nucleus that express the transcription factor Satb2, project to taste-associated regions, and modulate taste preferences.

During threat exposure, survival depends on defensive reactions. Prior works linked large glutamatergic populations in the midbrain periaqueductal gray (PAG) to defensive freezing and flight, and established that the overarching functional organization axis of the PAG is along anatomically-defined columns. Accordingly, broad activation of the dorsolateral column induces flight, while activation of the lateral or ventrolateral (l and vl) columns induces freezing. However, the PAG contains diverse cell types that vary in neurochemistry. How these cell types contribute to defense remains unknown, indicating that targeting sparse, genetically-defined populations may reveal how the PAG generates diverse behaviors. Though prior works showed that broad excitation of the lPAG or vlPAG causes freezing, we found in mice that activation of lateral and ventrolateral PAG (l/vlPAG) cholecystokinin-expressing (CCK) cells selectively caused flight to safer regions within an environment. Furthermore, inhibition of l/vlPAG-CCK cells reduced predator avoidance without altering other defensive behaviors like freezing. Lastly, l/vlPAG-CCK activity decreased when approaching threat and increased during movement to safer locations. These results suggest CCK cells drive threat avoidance states, which are epochs during which mice increase distance from threat and perform evasive escape. Conversely, l/vlPAG pan-neuronal activation promoted freezing, and these cells were activated near threat. Thus, CCK l/vlPAG cells have opposing function and neural activation motifs compared to the broader local ensemble defined solely by columnar boundaries. In addition to the anatomical columnar architecture of the PAG, the molecular identity of PAG cells may confer an additional axis of functional organization, revealing unexplored functional heterogeneity.

Abstract Marine Protected Areas (MPAs) are a widely‐used tool for conserving biodiversity. Features that support marine mammal foraging have been suggested as important components to include in MPAs, but research is needed to understand the relationship between these features and diversity. For example, the Northeast Canyons and Seamounts Marine National Monument represents an area known to support marine mammal foraging and was designated to protect an area of high marine mammal diversity. However, no comparisons have been made between marine mammal diversity in the Monument and other areas. We used 3,174,167 km of survey effort and 189,175 sightings to assess alpha and beta diversity in the Monument and 500 randomly selected sites along the east coast of the United States. We used linear models to relate diversity to variables that represent marine mammal foraging areas. Our analyses showed a gradient of higher to lower diversity from north to south and that the shelf‐edge, canyons, and areas of likely upwelling support high diversity. We also found that the Monument protects a diverse and unique marine mammal community. Our analyses contribute to efforts to designate MPAs to conserve habitat that is important for protecting species by identifying drivers of biodiversity and potential sites for protecting 30% of the planet by 2030.

ZBTB11 mutations have been identified in patients with intellectual disability and morphological brain and neuromuscular defects, although the etiology was unknown. Here, the authors demonstrate that ZBTB11 regulates mitochondrial function by facilitating NRF-2-mediated activation of complex I and mitoribosome genes.

PurposeSyncope (transient loss of consciousness and postural tone) and presyncope are common manifestations of autonomic dysfunction that are usually triggered by orthostasis. The global impact of syncope on quality of life (QoL) is unclear. In this systematic review, we report evidence on the impact of syncope and presyncope on QoL and QoL domains, identify key factors influencing QoL in patients with syncopal disorders, and combine available data to compare QoL between syncopal disorders and to population normative data.MethodsA comprehensive literature search of academic databases (MEDLINE (PubMed), Web of Science, CINAHL, PsycINFO, and Embase) was conducted (February 2021) to identify peer-reviewed publications that evaluated the impact of vasovagal syncope (VVS), postural orthostatic tachycardia syndrome (POTS), or orthostatic hypotension (OH) on QoL. Two team members independently screened records for inclusion and extracted data relevant to the study objectives.ResultsFrom 12,258 unique records identified by the search, 36 studies met the inclusion criteria (VVS: n = 20; POTS: n = 13; VVS and POTS: n = 1; OH: n = 2); 12 distinct QoL instruments were used. Comparisons of QoL scores between patients with syncope/presyncope and a control group were performed in 16 studies; significant QoL impairments in patients with syncope/presyncope were observed in all studies. Increased syncopal event frequency, increased autonomic symptom severity, and the presence of mental health disorders and/or comorbidities were associated with lower QoL scores.ConclusionThis review synthesizes the negative impact of syncope/presyncope on QoL and identifies research priorities to reduce the burden of these debilitating disorders and improve patient QoL.

BackgroundIn animal models, prenatal zinc deficiency induced epigenetic changes in the fetus, but data in humans are lacking. We aimed to examine associations between maternal zinc levels during pregnancy and DNA methylation in LINE-1 and Alu repetitive sequences in young adult offspring, as well as anthropometry and cardiometabolic parameters.MethodsParticipants were 74 pregnant women from the Chiang Mai Low Birth Weight cohort, and their offspring followed up at 20 years of age. Maternal plasma zinc concentrations were measured at approximately 36 weeks of gestation. DNA methylation levels in LINE-1 and Alu repetitive sequences were measured in the offspring, as well as anthropometry and cardiometabolic parameters (lipid profile, blood pressure, and glucose metabolism).ResultsOver half of mothers (39/74; 53%) were zinc deficient (ConclusionsLower maternal zinc concentrations late in gestation were associated with changes in DNA methylation in later life. Thus, zinc deficiency during pregnancy may induce alterations in total LINE-1 methylation and LINE-1 hypermethylation loci. These results suggest a possible epigenetic link between zinc deficiency during pregnancy and long-term outcomes in the offspring.

Escape from threats has paramount importance for survival. However, it is unknown if a single circuit controls escape vigor from innate and conditioned threats. Cholecystokinin (cck)-expressing cells in the hypothalamic dorsal premammillary nucleus (PMd) are necessary for initiating escape from innate threats via a projection to the dorsolateral periaqueductal gray (dlPAG). We now show that in mice PMd-cck cells are activated during escape, but not other defensive behaviors. PMd-cck ensemble activity can also predict future escape. Furthermore, PMd inhibition decreases escape speed from both innate and conditioned threats. Inhibition of the PMd-cck projection to the dlPAG also decreased escape speed. Intriguingly, PMd-cck and dlPAG activity in mice showed higher mutual information during exposure to innate and conditioned threats. In parallel, human functional magnetic resonance imaging data show that a posterior hypothalamic-to-dlPAG pathway increased activity during exposure to aversive images, indicating that a similar pathway may possibly have a related role in humans. Our data identify the PMd-dlPAG circuit as a central node, controlling escape vigor elicited by both innate and conditioned threats.

Background: Birth by caesarean section (CS) is associated with aberrant gut microbiome development and greater disease susceptibility later in life. We investigated whether oral administration of maternal vaginal microbiota to infants born by CS could restore their gut microbiome development in a pilot single-blinded, randomised placebo-controlled trial (Australian New Zealand Clinical Trials Registry, ACTRN12618000339257). Methods: Pregnant women scheduled for a CS underwent comprehensive antenatal pathogen screening. At birth, healthy neonates were randomised to receive a 3 ml solution of either maternal vaginal microbes (CS-seeded, n = 12) or sterile water (CS-placebo, n = 13). Vaginally-born neonates were used as the reference control (VB, n = 22). Clinical assessments occurred within the first 2 h of birth, and at 1 month and 3 months of age. Infant stool samples and maternal vaginal extracts from CS women underwent shotgun metagenomic sequencing. The primary outcome was gut microbiome composition at 1 month of age. Secondary outcomes included maternal strain engraftment, functional potential of the gut microbiome, anthropometry, body composition, and adverse events. Findings: Despite the presence of viable microbial cells within transplant solutions, there were no observed differences in gut microbiome composition or functional potential between CS-seeded and CS-placebo infants at 1 month or 3 months of age. Both CS groups displayed the characteristic signature of low Bacteroides abundance, which contributed to a number of biosynthesis pathways being underrepresented when compared with VB microbiomes. Maternal vaginal strain engraftment was rare. Vaginal seeding had no observed effects on anthropometry or body composition. There were no serious adverse events associated with treatment. Interpretation: Our pilot findings question the value of vaginal seeding given that oral administration of maternal vaginal microbiota did not alter early gut microbiome development in CS-born infants. The limited colonisation of maternal vaginal strains suggest that other maternal sources, such as the perianal area, may play a larger role in seeding the neonatal gut microbiome. Funding: Health Research Council of New Zealand, A Better Start – National Science Challenge.

One of today’s greatest conservation challenges is balancing policies, laws, and management strategies established to achieve economic goals that depend on extracting ocean resources with those established to conserve marine biodiversity. We use the Northeast Canyons and Seamounts Marine National Monument (NCSM) as a case study to explore the consequences of changing from a policy that prevents fishing to a fisheries management policy. We found that opening the NCSM to commercial fishing reduces species protections. Fishing with pelagic and bottom tending fixed gear exposes species inhabiting the sea surface and midwater regions to entanglement and bycatch risk. Fishing with bottom tending fixed gear also exposes deep-sea coral habitat to gear known to have detrimental impacts. The NCSM was designated as a marine national monument due to the area’s unique ecological resources that are a subject of scientific interest. Our case study demonstrates that a fisheries management policy is insufficient to protect these ecological resources.

Animals must balance needs to approach threats for risk assessment and to avoid danger. The dorsal periaqueductal gray (dPAG) controls defensive behaviors, but it is unknown how it represents states associated with threat approach and avoidance. We identified a dPAG threatavoidance ensemble in mice that showed higher activity farther from threats such as the open arms of the elevated plus maze and a predator. These cells were also more active during threat avoidance behaviors such as escape and freezing, even though these behaviors have antagonistic motor output. Conversely, the threat approach ensemble was more active during risk assessment behaviors and near threats. Furthermore, unsupervised methods showed that avoidance/approach states were encoded with shared activity patterns across threats. Lastly, the relative number of cells in each ensemble predicted threat avoidance across mice. Thus, dPAG ensembles dynamically encode threat approach and avoidance states, providing a flexible mechanism to balance risk assessment and danger avoidance.

Understanding genetic diversity and structure in a rare species is critical for prioritizing both in situ and ex situ conservation efforts. One such rare species is Physaria filiformis (Brassicaceae), a threatened, winter annual plant species. The species has a naturally fragmented distribution, occupying three different soil types spread across four disjunct geographical locations in Missouri and Arkansas. The goals of this study were to understand: (1) whether factors associated with fragmentation and small population size (i.e., inbreeding, genetic drift or genetic bottlenecks) have reduced levels of genetic diversity, (2) how genetic variation is structured and which factors have influenced genetic structure, and (3) how much extant genetic variation of P. filiformis is currently publicly protected and the implications for the development of conservation strategies to protect its genetic diversity. Using 16 microsatellite markers, we genotyped individuals from 20 populations of P. filiformis from across its geographical range and one population of Physaria gracilis for comparison and analyzed genetic diversity and structure. Populations of P. filiformis showed comparable levels of genetic diversity to its congener, except a single population in northwest Arkansas showed evidence of a genetic bottleneck and two populations in the Ouachita Mountains of Arkansas showed lower genetic variation, consistent with genetic drift. Populations showed isolation by distance, indicating that migration is geographically limited, and analyses of genetic structure grouped individuals into seven geographically structured genetic clusters, with geographic location/spatial separation showing a strong influence on genetic structure. At least one population is protected for all genetic clusters except one in north-central Arkansas, which should therefore be prioritized for protection. Populations in the Ouachita Mountains were genetically divergent from the rest of P. filiformis; future morphological analyses are needed to identify whether it merits recognition as a new, extremely rare species.

Anxiety is a widely studied phenomenon in behavioral neuroscience, but the recent literature lacks an overview of the major conceptual framework underlying anxiety research to introduce young researchers to the field. In this mini-review article, which is aimed toward new undergraduate and graduate students, we discuss how researchers exploit the approach-avoidance conflict, an internal conflict rodents face between exploration of novel environments and avoidance of danger, to inform rodent assays that allow for the measurement of anxiety-related behavior in the laboratory. We review five widely-used rodent anxiety assays, consider the pharmacological validity of these assays, and discuss neural circuits that have recently been shown to modulate anxiety using the assays described. Finally, we offer related lines of inquiry and comment on potential future directions.

The Northeast Canyons and Seamounts Marine National Monument (NECSMNM) was designated by President Barack Obama in 2016, using his authority under the Antiquities Act of 1906. The Act allows a President to proclaim as national monuments “historic landmarks, historic and prehistoric structures, and other objects of historic or scientific interest” that are “upon the lands owned or controlled” by the United States but to reserve each designation to “the smallest area compatible with the proper care and management of the objects to be protected.” Protection in general excludes commercial scale extraction and is in perpetuity. Here we present analyses of physiographic and ecological datasets that facilitated assessment of the conservation benefits of protections for a new monument. We also review and synthesize the ecological literature to describe processes that operate in continental margin and deep-sea settings, in order to demonstrate the monument area is bounded for proper management and is an object of scientific interest. Results indicate that the current monument designation is an area of high diversity and ecological connectivity across depths and along the continental margin. The monument boundaries contain hot spots (areas of high abundance and species richness) for seafloor communities (inclusive of benthic invertebrate and demersal fish) as well as marine mammals in the epipelagic. Many species are sensitive to disturbance and vulnerable to human activities (e.g., deep-sea corals and sponges) with very long recovery times and extremely low resilience. The monument contains at least nine exemplars of offshore northwest Atlantic marine wildlife communities and habitats (e.g., deep shelf invertebrates, shelf fish, deep sea corals and sponges in canyons and on seamounts, deep sea fish, chemosynthetic communities, deep sea soft sediment, shelf edge cetaceans, and seabirds). The region is relatively undisturbed and can serve as a reference site to focus future research on ecological processes in an increasingly industrialized ocean and one subject to the synergies of regional climate effects. These results suggest that there is great potential for discovery and novel research in this first Atlantic Ocean Marine National Monument.

Orthostatic fluid shifts reduce the effective circulating volume and thus contribute to syncope susceptibility. Recurrent syncope has a devastating impact on quality of life and is challenging to manage effectively. To blunt orthostatic fluid shifts, static calf compression garments are often prescribed to patients with syncope, but have questionable efficacy. Intermittent calf compression, which mimics the skeletal muscle pump to minimize pooling and filtration, holds promise for the management of syncope. We aimed to evaluate the effectiveness of intermittent calf compression for increasing orthostatic tolerance (OT; time to presyncope). We conducted a randomized single-blind crossover study, in which participants (n = 21) underwent three graded 60° head-up-tilt tests to presyncope with combined lower body negative pressure on separate days. Low frequency intermittent calf compression (ICLF; 4 s on and 11 s off) at 0–30 and 0–60 mmHg was applied during two tests and compared to a placebo condition where the garment was fitted, but no compression applied. We measured continuous leg circumference changes (strain gauge plethysmography), cardiovascular responses (finger plethysmography; Finometer Pro), end tidal gases (nasal cannula), and cerebral blood flow velocity (CBFv, transcranial Doppler). The 0–60 mmHg ICLF increased OT (33 ± 2.2 min) compared to both placebo (26 ± 2.4 min; p < 0.001) and 0–30 mmHg ICLF (25 ± 2.7 min; p < 0.001). Throughout testing 0–60 mmHg ICLF reduced orthostatic fluid shifts compared to both placebo and 0–30 mmHg ICLF (p < 0.001), with an associated improvement in stroke volume (p < 0.001), allowing blood pressure to be maintained at a reduced heart rate (p < 0.001). In addition, CBFv was higher with 0–60 mmHg ICLF than 0–30 mmHg ICLF and placebo (p < 0.001). Intermittent calf compression is a promising novel intervention for the management of orthostatic intolerance, which may provide affected individuals renewed independence and improved quality of life.

Background: Psychological online interventions (POIs) reduce depression but we know little about factors influencing their effectiveness. We evaluated a new, brief POI for depression and conducted exploratory moderator analyses. Methods: In this online trial (German Clinical Trials Register; DRKS00011045), we allocated participants to treatment as usual (TAU; n = 67) or POI (n = 65). At first, we randomized participants; later we allocated participants based on depression severity in order to counter baseline differences. The unguided POI addressed behavioral activation and depressive thinking in a single module with 25 webpages (including a smartphone application). We did one assessment at baseline and a post-assessment four weeks later. Results: At post-assessment, depression (p = .586), behavioral activation (p = .332), and dysfunctional attitudes (p = .499) did not differ between groups. When concurrent treatments (medication/psychotherapy) remained constant/decreased, the POI outperformed TAU (p = .031). POI-participants with lower willingness to change (p = .030) or higher education (p = .017) were less likely to worsen (i.e., experience increased depressive symptoms) compared to TAU. Discussion: The targeted sample size was not reached, measurements were self-reported, and randomization failed. The POI's content may have been too limited. Concurrent treatments, which were more often sought out by TAU participants, diminished group differences and should be considered in future studies. Brief POIs may protect against worsening of depressive symptoms among highly educated participants or those with low willingness to change. Keywords: Psychological online intervention, Depression, Moderator analysis, Behavioral activation, Cognitive restructuring

Puberty is initiated by hormonal changes in the adolescent body that trigger physical and behavioral changes to reach adult maturation. As these changes occur, some adolescents experience concerning pubertal symptoms that are associated with dysfunction of the autonomic nervous system (ANS). Vasovagal syncope (VVS) and Postural Orthostatic Tachycardia Syndrome (POTS) are common disorders of the ANS associated with puberty that are related to orthostatic intolerance and share similar symptoms. Compared to young males, young females have decreased orthostatic tolerance and a higher incidence of VVS and POTS. As puberty is linked to changes in specific sex and non-sex hormones, and hormonal therapy sometimes improves orthostatic symptoms in female VVS patients, it is possible that pubertal hormones play a role in the increased susceptibility of young females to autonomic dysfunction. The purpose of this paper is to review the key hormonal changes associated with female puberty, their effects on the ANS, and their potential role in predisposing some adolescent females to cardiovascular autonomic dysfunctions such as VVS and POTS. Increases in pubertal hormones such as estrogen, thyroid hormones, growth hormone, insulin, and insulin-like growth factor-1 promote vasodilatation and decrease blood volume. This may be exacerbated by higher levels of progesterone, which suppresses catecholamine secretion and sympathetic outflow. Abnormal heart rate increases in POTS patients may be exacerbated by pubertal increases in leptin, insulin, and thyroid hormones acting to increase sympathetic nervous system activity and/or catecholamine levels. Given the coincidental timing of female pubertal hormone surges and adolescent onset of VVS and POTS in young women, coupled with the known roles of these hormones in modulating cardiovascular homeostasis, it is likely that female pubertal hormones play a role in predisposing females to VVS and POTS during puberty. Further research is necessary to confirm the effects of female pubertal hormones on autonomic function, and their role in pubertal autonomic disorders such as VVS and POTS, in order to inform the treatment and management of these debilitating disorders.

Merkel cell carcinoma has historically had dismal prognosis with limited cytotoxic chemotherapy options that provide durable control of metastatic disease. The advent of anti-programmed death protein (anti-PD1)/anti-programmed death-ligand 1 (anti-PD-L1) directed immunotherapy has shown initial promise in Merkel cell carcinoma and radiation might augment immune responses. We present a case report of a 70-year-old male who underwent resection of Merkel cell carcinoma of the right thigh with a close margin and positive right inguinal involvement. Due to high-risk features, the patient was treated with adjuvant radiation to the right groin and with systemic carboplatin/etoposide, but developed local failure requiring salvage surgical resection. The patient then developed metastatic disease with biopsy proven retroperitoneal involvement refractory to doxorubicin/cyclophosphamide chemotherapy. The patient was then transitioned to single-agent pembrolizumab with a partial response for 10 months until developing progressive disease involving the left inguinal and left external iliac nodal regions. The progressive left inguinal/pelvic disease was treated with conventionally fractionated intensity modulated radiation therapy to a dose of 45 Gy delivered in 25 fractions. Following radiation therapy, the patient had complete response of all sites of disease throughout the body on imaging by RECIST criteria including retroperitoneal and mediastinal disease outside the radiation field. At 20 months post-radiation, the patient remains on pembrolizumab without evidence of disease on imaging. Herein, we present a case of durable response of metastatic Merkel cell carcinoma treated with concurrent radiation and pembrolizumab, providing evidence that radiation might improve systemic responses to anti-PD1/PD-L1 directed immune therapy. Ongoing prospective trials evaluating the utility of radiation in conjunction with immunotherapy for Merkel cell carcinoma are anticipated to provide clarity on the frequency and durability of abscopal responses when radiation is combined with immune checkpoint inhibitors.