Perceived Relational Support Is Associated With Everyday Positive, But Not Negative, Affectivity in a U.S. Sample.

Research suggests that perceived social support bolsters emotional well-being. We tested whether perceived support from friends, family, and spouses/partners was associated with reduced negative and greater positive affectivity (i.e., everyday affective baseline), and whether perceived strain in these relationships had opposite effects, accounting for age and relevant covariates. Using data from the third waves of the Midlife in the United States survey and National Study of Daily Experience (n = 1,124), we found negative affectivity was not tied to relational support nor strain, but instead was associated positively with neuroticism and negatively with conscientiousness. In contrast, positive affectivity was related positively to support from friends and family, conscientiousness, and extroversion, and negatively to strain among partners and neuroticism. Exploratory analyses within second-wave Midlife in Japan data (n = 657) suggest patterns for future cross-cultural study. Some relationship dynamics may vary, but perceived support might enhance emotional well-being by bolstering positive, rather than mitigating negative, emotionality.

Using standardized patients for undergraduate clinical skills training in an introductory course to psychiatry.

BACKGROUND: The goal of this study was to assess the value and acceptance of Standardized or Simulated Patients (SPs) for training clinically inexperienced undergraduate medical students in psychiatric history taking, psychopathological assessment, and communication with psychiatric patients. METHODS: As part of a newly developed introductory course to psychiatry, pairs of 3rd year medical students conducted psychiatric assessments of SPs, including history and psychopathological state, under the supervision of a clinical lecturer. Prior to the assessment, students attended introductory lectures to communication in psychiatry and psychopathology but were clinically inexperienced. After the interview, the students' summary of their findings was discussed with other students and the lecturer. Students, lecturers, and actors were invited to a survey after the course. Questions for the students included self-reports about perceived learning success and authenticity of the interviews. RESULTS: 41 students, 6 actors and 8 lecturers completed the survey (response rates of 48%, 50%, and 100%, respectively). The survey results indicated that, despite their lack of clinical experience, students learned how to conduct a psychiatric interview, communicate in a non-judgmental and empathetic manner, take a psychiatric history and perform a psychopathological examination. SPs were perceived as authentic. The survey results suggested that this setting allowed for an enjoyable, non-distressful and motivating learning experience within a restricted time frame of just two afternoons. CONCLUSION: The results indicated that the SP approach presented is useful for teaching clinical skills in psychiatry to students with limited previous clinical experience and knowledge of psychiatry. We argue that SPs can be used to teach practical psychiatric skills already during an early phase of the curriculum. Limitations of our study include a limited sample size, a temporal gap between the course and the survey, reliance on self-reports, and lack of comparison to alternative interventions.

Molecular lesions in alleles of the Caenorhabditis elegans lin-11 gene.

The LIM homeodomain transcription factor LIN-11 is a key regulator of vulva, uterine, and neuron development in C. elegans. Multiple alleles of lin-11 are available, but none had been sequenced. We found that the reference allele, n389, is a 15900 bp deletion that also affects two other protein-coding genes, ZC247.1 and ZC247.2. The frequently used n566 allele is a 288bp deletion located in an intron and affecting the splice acceptor site.

Concurrent exercise does not prevent recognition memory deficits induced by beta-amyloid in rats.

Alzheimer's disease affects thousands of people worldwide. Alternatives aiming to prevent the disease or reduce its symptoms include different physical exercise configurations. Here we investigate the potential of concurrent exercise to prevent recognition memory deficits in an Alzheimer's disease-like model induced by the hippocampal beta-amyloid (Aß) injection in Wistar rats. We demonstrate that the concurrent exercise, which included running and strength exercises performed in the same exercise session, is ineffective in preventing recognition memory deficits in the Aß rats. Besides, higher levels of reactive oxygen species were found in the concurrent exercise group's hippocampus. The running exercise administrated alone prevented recognition memory impairments.

Protein-based condensation mechanisms drive the assembly of RNA-rich P granules.

Germ granules are protein-RNA condensates that segregate with the embryonic germline. In Caenorhabditis elegans embryos, germ (P) granule assembly requires MEG-3, an intrinsically disordered protein that forms RNA-rich condensates on the surface of PGL condensates at the core of P granules. MEG-3 is related to the GCNA family and contains an N-terminal disordered region (IDR) and a predicted ordered C-terminus featuring an HMG-like motif (HMGL). We find that MEG-3 is a modular protein that uses its IDR to bind RNA and its C-terminus to drive condensation. The HMGL motif mediates binding to PGL-3 and is required for co-assembly of MEG-3 and PGL-3 condensates in vivo. Mutations in HMGL cause MEG-3 and PGL-3 to form separate condensates that no longer co-segregate to the germline or recruit RNA. Our findings highlight the importance of protein-based condensation mechanisms and condensate-condensate interactions in the assembly of RNA-rich germ granules.

[Secondary Data Analysis of Initially Treated In-patients with Schizophrenia in a Model Project in Berlin (According to § 64b SGB V)]. / Sekundärdatenanalyse initial vollstationär behandelter Patienten mit Schizophrenie in einem Berliner Modellprojekt (nach § 64b SGB V).

AIM OF THE STUDY: Schizophrenia is one of the most severe psychiatric diseases. The German health care system still shows gaps in services for chronic psychiatric patients with intense need of treatment. The present article focused on changes in provision of health services for initially treated in-patients with schizophrenia in St. Hedwig hospitals in Berlin according to § 64b SGB V compared to patients receiving regular in-patient treatment. METHODS: By using statutory data, we analyzed target figures. We analyzed patients of 3 cohorts. Propensity Score Matching generated a control group in each cohort. RESULTS: The final analysis showed for schizophrenia patients treated in the model project that the number of hospital stays and overall length of stay decreased, but overall costs decreased only partially. Moreover, the period (in days) until next re-hospitalization was longer, while the sum of contacts to the outpatient sector increased. Conclusions The presented model project achieved the aimed shift of psychiatric health service into the outpatient sector for schizophrenia patients.

Utilization and Effectiveness of Home Treatment for People With Acute Severe Mental Illness: A Propensity-Score Matching Analysis of 19 Months of Observation.

Treatment guidelines recommend home treatment (HT) as an effective alternative to inpatient treatment for individuals with severe, acute mental illness (SAMI). Nevertheless, HT is largely unfamiliar in German-speaking countries. Here we examined the utilization and effectiveness of HT services newly implemented in a large hospital setting in Switzerland. We used a naturalistic observational study design including patients (n = 201, 18-65 years, 65.7% females) with SAMI who received HT between June 2016 and December 2017. HT patients were compared with a crude inpatient sample (n = 1078) and a matched inpatient sample (n = 201). Propensity-score matching was used to control for personal characteristics. Treatment outcomes were compared between HT patients and the matched inpatients based on routinely obtained medical data. The results showed that the HT sample consisted of more females (+21%), older (+4 years), and better educated (+10%) patients with more affective disorders (+13%) and less substance use disorders (-15%) as compared with the crude inpatient sample. The severity of symptoms was the same. After matching, there were no significant differences in the proportion of readmissions (36%), the duration until readmission and scores of the Health of the Nation Outcome Scales (HoNOS). The treatment duration of HT patients was significantly longer and, post-treatment, scores on the Global Assessment of Functioning scale (GAF) were significantly better. We conclude that HT is an effective treatment option for patients with SAMI also in Switzerland concerning the reduction of hospital days, the improvement of symptoms and functioning and readmission rates. HT cannot fully replace hospital admissions in all cases and HT may be beneficial for particular groups of patients (e.g., females and individuals with affective disorders). The study further shows the potential value of propensity-score matching in health care service research.

Spatial patterning of P granules by RNA-induced phase separation of the intrinsically-disordered protein MEG-3.

RNA granules are non-membrane bound cellular compartments that contain RNA and RNA binding proteins. The molecular mechanisms that regulate the spatial distribution of RNA granules in cells are poorly understood. During polarization of the C. elegans zygote, germline RNA granules, called P granules, assemble preferentially in the posterior cytoplasm. We present evidence that P granule asymmetry depends on RNA-induced phase separation of the granule scaffold MEG-3. MEG-3 is an intrinsically disordered protein that binds and phase separates with RNA in vitro. In vivo, MEG-3 forms a posterior-rich concentration gradient that is anti-correlated with a gradient in the RNA-binding protein MEX-5. MEX-5 is necessary and sufficient to suppress MEG-3 granule formation in vivo, and suppresses RNA-induced MEG-3 phase separation in vitro. Our findings suggest that MEX-5 interferes with MEG-3's access to RNA, thus locally suppressing MEG-3 phase separation to drive P granule asymmetry. Regulated access to RNA, combined with RNA-induced phase separation of key scaffolding proteins, may be a general mechanism for controlling the formation of RNA granules in space and time.

Cas9-assisted recombineering in C. elegans: genome editing using in vivo assembly of linear DNAs.

Recombineering, the use of endogenous homologous recombination systems to recombine DNA in vivo, is a commonly used technique for genome editing in microbes. Recombineering has not yet been developed for animals, where non-homology-based mechanisms have been thought to dominate DNA repair. Here, we demonstrate, using Caenorhabditis elegans, that linear DNAs with short homologies (∼35 bases) engage in a highly efficient gene conversion mechanism. Linear DNA repair templates with homology to only one side of a double-strand break (DSB) initiate repair efficiently, and short overlaps between templates support template switching. We demonstrate the use of single-stranded, bridging oligonucleotides (ssODNs) to target PCR fragments for repair of DSBs induced by CRISPR/Cas9 on chromosomes. Based on these findings, we develop recombineering strategies for precise genome editing that expand the utility of ssODNs and eliminate in vitro cloning steps for template construction. We apply these methods to the generation of GFP knock-in alleles and gene replacements without co-integrated markers. We conclude that, like microbes, metazoans possess robust homology-dependent repair mechanisms that can be harnessed for recombineering and genome editing.

Regulation of RNA granule dynamics by phosphorylation of serine-rich, intrinsically disordered proteins in C. elegans.

RNA granules have been likened to liquid droplets whose dynamics depend on the controlled dissolution and condensation of internal components. The molecules and reactions that drive these dynamics in vivo are not well understood. In this study, we present evidence that a group of intrinsically disordered, serine-rich proteins regulate the dynamics of P granules in C. elegans embryos. The MEG (maternal-effect germline defective) proteins are germ plasm components that are required redundantly for fertility. We demonstrate that MEG-1 and MEG-3 are substrates of the kinase MBK-2/DYRK and the phosphatase PP2A(PPTR-½). Phosphorylation of the MEGs promotes granule disassembly and dephosphorylation promotes granule assembly. Using lattice light sheet microscopy on live embryos, we show that GFP-tagged MEG-3 localizes to a dynamic domain that surrounds and penetrates each granule. We conclude that, despite their liquid-like behavior, P granules are non-homogeneous structures whose assembly in embryos is regulated by phosphorylation.

Scalable and versatile genome editing using linear DNAs with microhomology to Cas9 Sites in Caenorhabditis elegans.

Homology-directed repair (HDR) of double-strand DNA breaks is a promising method for genome editing, but is thought to be less efficient than error-prone nonhomologous end joining in most cell types. We have investigated HDR of double-strand breaks induced by CRISPR-associated protein 9 (Cas9) in Caenorhabditis elegans. We find that HDR is very robust in the C. elegans germline. Linear repair templates with short (∼30-60 bases) homology arms support the integration of base and gene-sized edits with high efficiency, bypassing the need for selection. Based on these findings, we developed a systematic method to mutate, tag, or delete any gene in the C. elegans genome without the use of co-integrated markers or long homology arms. We generated 23 unique edits at 11 genes, including premature stops, whole-gene deletions, and protein fusions to antigenic peptides and GFP. Whole-genome sequencing of five edited strains revealed the presence of passenger variants, but no mutations at predicted off-target sites. The method is scalable for multi-gene editing projects and could be applied to other animals with an accessible germline.

Shotgun metagenomics indicates novel family A DNA polymerases predominate within marine virioplankton.

Virioplankton have a significant role in marine ecosystems, yet we know little of the predominant biological characteristics of aquatic viruses that influence the flow of nutrients and energy through microbial communities. Family A DNA polymerases, critical to DNA replication and repair in prokaryotes, are found in many tailed bacteriophages. The essential role of DNA polymerase in viral replication makes it a useful target for connecting viral diversity with an important biological feature of viruses. Capturing the full diversity of this polymorphic gene by targeted approaches has been difficult; thus, full-length DNA polymerase genes were assembled out of virioplankton shotgun metagenomic sequence libraries (viromes). Within the viromes novel DNA polymerases were common and found in both double-stranded (ds) DNA and single-stranded (ss) DNA libraries. Finding DNA polymerase genes in ssDNA viral libraries was unexpected, as no such genes have been previously reported from ssDNA phage. Surprisingly, the most common virioplankton DNA polymerases were related to a siphovirus infecting an α-proteobacterial symbiont of a marine sponge and not the podoviral T7-like polymerases seen in many other studies. Amino acids predictive of catalytic efficiency and fidelity linked perfectly to the environmental clades, indicating that most DNA polymerase-carrying virioplankton utilize a lower efficiency, higher fidelity enzyme. Comparisons with previously reported, PCR-amplified DNA polymerase sequences indicated that the most common virioplankton metagenomic DNA polymerases formed a new group that included siphoviruses. These data indicate that slower-replicating, lytic or lysogenic phage populations rather than fast-replicating, highly lytic phages may predominate within the virioplankton.

Multicity outbreak of linezolid-resistant Staphylococcus epidermidis associated with clonal spread of a cfr-containing strain.

We report a multicity outbreak of cfr-containing linezolid-resistant Staphylococcus epidermidis in Ohio. Thirty-nine isolates were obtained from 2 hospitals. Two clones with different mechanisms of linezolid resistance were circulating in hospital A. One of these contained the cfr gene, and the other a ribosomal mutation. The clone containing cfr was identical in both hospitals.