This study examined the efficacy of a probiotic in reducing depressive symptom severity in people with subthreshold depression. In a double-blind, randomised, placebo-controlled trial, a probiotic (1 × 10^9 live cells per strain: Limosilactobacillus fermentum LF16 (DSM26956), Lacticaseibacillus rhamnosus LR06 (DSM21981), Lactiplantibacillus plantarum LP01 (LMG P-21021) and Bifidobacterium longum 04 (DSM23233)) or placebo was taken daily for 12 weeks. Data were collected at baseline, 6 and 12 weeks including psychological symptom severity (Beck Depression Inventory, BDI; Patient Health Questionnaire, PHQ; Hospital Anxiety Depression Scale, HADS; and Depression Anxiety and Stress Scale, DASS). Biomarkers of glycaemia, inflammation (high-sensitivity C-reactive protein, hs-CRP), antioxidant status (total glutathione (GSH)) and stress (cortisol awakening response, CAR) were also measured. Thirty-nine participants (nineteen probiotic; twenty placebo) were enrolled. There were no significant between-group differences in the examined psychological symptom severity scores, despite certain significant within-group changes observed in both groups from baseline to 6 and/or 12 weeks of follow-up. Regarding biomarkers, the probiotic group showed reduced hs-CRP (–1520; 95 % CI –273·7, −2766·2 ng/dl) and CAR (–0·28; 95 % CI −0·05, −0·51 μg/dl) at 12 weeks, but increased total GSH (3·9; 95 % CI 0·1, 7·5 ng/dl) at 6 weeks, compared with the placebo. The current study reported favourable decreases in depressive symptoms in both groups. Although the within-group changes observed in the probiotic group were supported by favourable inflammatory, antioxidant status and stress biomarker changes compared with the placebo, further research is required to shed more light on the role of gut microbiota modulation on emotional regulation.

In our article, we share the lessons we have learned after creating and running a successful legal laboratory over the past seven years at Yale Law School. Our legal laboratory, which focuses on the intersection of law and severe brain injury, represents a unique pedagogical model for legal academia, and is closely influenced by the biomedical laboratory.

Maternal trauma has intergenerational implications, including worse birth outcomes, altered brain morphology, and poorer mental health. Research investigating intergenerational effects of maternal trauma on infant stress reactivity and regulation is limited. Maternal mental health during pregnancy may be a contributor: psychopathology is a sequela of trauma exposure and predictor of altered self-regulatory capacity in offspring of affected mothers. We assessed associations among maternal lifetime trauma and infant stress responsivity, mediated by psychological symptoms in pregnancy. Mothers reported lifetime trauma history and anxiety, depressive, and posttraumatic stress symptoms during pregnancy. At infant age 6 months, stress reactivity and regulation were assessed via maternal behavior ratings (Infant Behavior Questionnaire-Revised, IBQ-R) and behavioral (negative mood) and physiological (respiratory sinus arrhythmia, RSA) markers during a laboratory stressor (Still-Face Paradigm). Maternal trauma was directly associated with lower infant physiological regulation and indirectly associated with lower levels of both infant behavioral and physiological regulation via higher maternal anxiety during pregnancy. Maternal trauma was also indirectly associated with higher infant reactivity via higher maternal anxiety during pregnancy. Post hoc analyses indicated differential contributions of maternal prenatal versus postnatal anxiety to infant outcomes. Findings highlight potential contributory mechanisms toward maladaptive child stress response, which has been associated with poor behavioral, cognitive, and academic outcomes.

Background: Admission laboratory screening for asymptomatic COVID-19 has been utilized to mitigate healthcare-associated SARS-CoV-2 transmission. A better understanding of the impact of such testing across a variety of patient populations is needed. Methods: Beginning April 2020, every patient admitted within an academic healthcare system underwent SARS-CoV-2 PCR testing upon admission. Between April 20, 2020 through June 14, 2021, results were analyzed in asymptomatic patients across 4 inpatient facilities: a tertiary-care adult hospital, a free-standing pediatric hospital, a community-based hospital, and a behavioral health hospital. Positivity rates and the number needed to test (NNT) to identify 1 asymptomatic infected patient were calculated overall, by hospital type, by patient vaccination status, and by CDC-defined levels of community transmission. Weekly community incidence rates of COVID-19 for the system’s metropolitan service area (8 central Tennessee counties) were obtained from Tennessee Department of Health records. Weekly COVID-19 incidence rates per 100,000 people were calculated using US Census Bureau data. Using a national survey of hospital epidemiologists, a clinically meaningful NNT was identified (ie, 1 positive patient per 100 patients tested). A crude admission testing cost (covering testing supplies, reagents, and lab personnel costs) was obtained from operational data ($50 per test) to assess testing utility. Results: In total, 51,187 tests were collected during the study period with a positivity rate of 1.8%. No periods of low transmission were observed (Table 1). During high transmission periods, the NNT met the clinically relevant threshold in all populations. In addition, the NNT approached or met the 1:100 threshold for most locations during periods of less transmission, suggesting continued benefit even as infection rates decline. In all transmission periods, the NNT for non–fully vaccinated patients met the clinically meaningful threshold, in contrast to testing of fully vaccinated patients (Table 2). Discussion: Implementing an asymptomatic patient admission testing program can provide clinically relevant value based on the NNT, even during lower periods of transmission and in different patient populations. Limiting admission testing to non–fully vaccinated patients during periods of lower transmission may be a strategy to address cost and resource concerns around this practice. Further investigations into the impact of booster vaccination and newer SARS-CoV-2 variants on admission testing programs are also necessary. Although the impact of such testing on healthcare-associated COVID-19 among patients and healthcare workers could not be clearly determined, these data provide important information as facilities weigh the costs and benefits of such testing.

Funding: None

Disclosures: None

Variation in human cognitive ability is of consequence to a large number of health and social outcomes and is substantially heritable. Genetic linkage, genome-wide association, and copy number variant studies have investigated the contribution of genetic variation to individual differences in normal cognitive ability, but little research has considered the role of rare genetic variants. Exome sequencing studies have already met with success in discovering novel trait-gene associations for other complex traits. Here, we use exome sequencing to investigate the effects of rare variants on general cognitive ability. Unrelated Scottish individuals were selected for high scores on a general component of intelligence (g). The frequency of rare genetic variants (in n = 146) was compared with those from Scottish controls (total n = 486) who scored in the lower to middle range of the g distribution or on a proxy measure of g. Biological pathway analysis highlighted enrichment of the mitochondrial inner membrane component and apical part of cell gene ontology terms. Global burden analysis showed a greater total number of rare variants carried by high g cases versus controls, which is inconsistent with a mutation load hypothesis whereby mutations negatively affect g. The general finding of greater non-synonymous (vs. synonymous) variant effects is in line with evolutionary hypotheses for g. Given that this first sequencing study of high g was small, promising results were found, suggesting that the study of rare variants in larger samples would be worthwhile.

Amphiphilic diacetylenes (DAs) can self-assemble into photopolymerizable liposomes that can be used to construct effective pathogen sensors. Here, modified commercial inkjet printers are used to disperse DAs into water, facilitating self-assembly. The liposomes are of similar size, but are significantly less polydisperse than liposomes formed using conventional sonication methods. The process is efficient, readily scalable and tolerant of structural modification. The derivitization of approximately 5% of the DA head groups and the incorporation of fluorophores into the hydrophobic bilayer allows for the preparation of novel multifluorophore PDA sensing systems that can provide enhanced bacterial discrimination in a single experiment by way of a fluorescent fingerprint.

Amultidisciplinary collaborative study examining cognition in a large sample of twins is outlined. A common experimental protocol and design is used in The Netherlands, Australia and Japan to measure cognitive ability using traditional IQ measures (i.e., psychometric IQ), processing speed (e.g., reaction time [RT] and inspection time [IT]), and working memory (e.g., spatial span, delayed response [DR] performance). The main aim is to investigate the genetic covariation among these cognitive phenotypes in order to use the correlated biological markers in future linkage and association analyses to detect quantitativetrait loci (QTLs). We outline the study and methodology, and report results from our preliminary analyses that examines the heritability of processing speed and working memory indices, and their phenotypic correlation with IQ. Heritability of Full Scale IQ was 87% in the Netherlands, 83% in Australia, and 71% in Japan. Heritability estimates for processing speed and working memory indices ranged from 33–64%. Associations of IQ with RT and IT (−0.28 to −0.36) replicated previous findings with those of higher cognitive ability showing faster speed of processing. Similarly, significant correlations were indicated between IQ and the spatial span working memory task (storage [0.31], executive processing [0.37]) and the DR working memory task (0.25), with those of higher cognitive ability showing better memory performance. These analyses establish the heritability of the processing speed and working memory measures to be used in our collaborative twin study of cognition, and support the findings that individual differences in processing speed and working memory may underlie individual differences in psychometric IQ.

Focus groups are a means of gathering qualitative data from a group of participants who discuss a given topic. This method has been used in health care research for the past 30 years, but has seen limited use in radiation therapy research. Focus group discussions are a useful tool for investigating a variety of educational, training and clinical issues from the perspective of practitioners, students and patients. This paper reviews the issues associated with using focus groups as a means of data collection. In particular, it addresses some of the decisions which have to be made about group composition and conduct of the discussions. The literature review is contextualised using a recent example of how the authors used focus groups to investigate fitness to practise in radiation therapy. Other challenges such as familiarity between participants and researchers, power relationships and anonymity are addressed. The paper concludes with a consideration of data analysis.

Folic acid (pteroylmonoglutamic acid) has historically been used as the reference folate in human intervention studies assessing the relative bioavailability of dietary folate. Recent studies using labelled folates indicated different plasma response kinetics to folic acid than to natural (food) folates, thus obviously precluding its use in single-dose experiments. Since differences in tissue distribution and site of biotransformation were hypothesised, the question is whether folic acid remains suitable as a reference folate for longer-term intervention studies, where the relative bioavailability of natural (food) folate is assessed based on changes in folate status. Healthy adults aged 18–65 years (n 163) completed a 16-week placebo-controlled intervention study in which the relative bioavailability of increased folate intake (453 nmol/d) from folate-rich foods was assessed by comparing changes in plasma and erythrocyte folate concentration with changes induced by an equal reference dose of supplemental (6S)-5-methyltetrahydrofolic acid or folic acid. The relative increase in plasma folate concentration in the food group was 31 % when compared with that induced by folic acid, but 39 % when compared with (6S)-5-methyltetrahydrofolic acid. The relative increase in erythrocyte folate concentration in the food group when compared with that induced by folic acid was 43 %, and 40 % when compared with (6S)-5-methyltetrahydrofolic acid. When recent published observations were additionally taken into account it was concluded that, in principle, folic acid should not be used as the reference folate when attempting to estimate relative natural (food) folate bioavailability in longer-term human intervention studies. Using (6S)-5-methyltetrahydrofolic acid as the reference folate would avoid future results' validity being questioned.

The purpose of the present paper is to review our current understanding of the chemistry and biochemistry of folic acid and related folates, and to discuss their impact on public health beyond that already established in relation to neural-tube defects. Our understanding of the fascinating world of folates and C1 metabolism, and their role in health and disease, has come a long way since the discovery of the B-vitamin folic acid by Wills (1931), and its first isolation by Mitchell et al. (1941). However, there is still much to do in perfecting methods for the measurement of folate bioavailability, and status, with a high extent of precision and accuracy. Currently, examination of the relationships between common gene polymorphisms involved in C1 metabolism and folate bioavailability and folate status, morbidity, mortality and longevity is evaluated as a series of individual associations. However, in the future, examination of the concurrent effects of such common gene polymorphisms may be more beneficial.