Effect of a multidisciplinary stress treatment programme on the return to work rate for persons with work-related stress. A non-randomized controlled study from a stress clinic

<p>Abstract</p> <p>Background</p> <p>In recent years an increasing number of patients have been referred to the medical sector with stress symptoms. Moreover, these conditions imply increased sickness absence. This indicates a need for treatment programmes in general medical practice. The aim of this study was to test the effect of a multidisciplinary stress treatment programme on the return to work (RTW) rate in persons with work-related stress and establish predictive factors for this outcome.</p> <p>Methods</p> <p>During a two-year period 63 out of 73 referrals to the Stress Clinic (a section of a Clinic of Occupational Medicine) completed a stress treatment programme consisted of the following:</p> <p>1) Identification of relevant stressors. 2. Changing the coping strategies of the participants. 3. Evaluating/changes in participant workload and tasks. 4. Relaxation techniques. 5. Physical exercise. 6. Psychiatric evaluation when indicated by depression test score.</p> <p>On average each patient attended six one-hour sessions over the course of four months.</p> <p>A group of 34 employees referred to the Clinic of Occupational Medicine by their general practitioners served as a control group. Each participant had a one-hour consultation at baseline and after four months. A specialist in occupational medicine carried out all sessions.</p> <p>Return To Work (RTW), defined as having a job and not being on sick leave at the census, was used as outcome measure four months after baseline, and after one and two years.</p> <p>Results</p> <p>The level of sick leave in the stress treatment group dropped from 52% to 16% during the first four months of follow-up and remained stable. In the control group, the reduction in sick leave was significantly smaller, ranging from 48% at baseline to 27% after four months and 24% after one year. No statistically significant difference between the two groups was observed after one and two years. Age below 50 years and being a manager increased the odds ratio for RTW after one and two years, while gender and depression had no predictive value.</p> <p>Conclusions</p> <p>The stress treatment programme showed a significant effect on the return to work rate. The stress treatment programme seems feasible for general practitioners.</p> <p>Trial Registration</p> <p>ISRCTN04354658</p

The Seroepidemiology of Haemophilus influenzae Type B Prior to Introduction of an Immunization Programme in Kathmandu, Nepal.

Haemophilus influenzae type b (Hib) is now recognized as an important pathogen in Asia. To evaluate disease susceptibility, and as a marker of Hib transmission before routine immunization was introduced in Kathmandu, 71 participants aged 7 months-77 years were recruited and 15 cord blood samples were collected for analysis of anti-polyribosylribitol phosphate antibody levels by enzyme-linked immunosorbent assay. Only 20% of children under 5 years old had levels considered protective (>0.15 µg/ml), rising to 83% of 15-54 year-olds. Prior to introduction of Hib vaccine in Kathmandu, the majority of young children were susceptible to disease

Transcriptional characterization of human megakaryocyte polyploidization and lineage commitment

BACKGROUND: Megakaryocytes (MKs) originate from cells immuno-phenotypically indistinguishable from hematopoietic stem cells (HSCs), bypassing intermediate progenitors. They mature within the adult bone marrow and release platelets into the circulation. Until now, there have been no transcriptional studies of primary human bone marrow MKs. OBJECTIVES: To characterize MKs and HSCs from human bone marrow using single-cell RNA sequencing, to investigate MK lineage commitment, maturation steps, and thrombopoiesis. RESULTS: We show that MKs at different levels of polyploidization exhibit distinct transcriptional states. Although high levels of platelet-specific gene expression occur in the lower ploidy classes, as polyploidization increases, gene expression is redirected toward translation and posttranslational processing transcriptional programs, in preparation for thrombopoiesis. Our findings are in keeping with studies of MK ultrastructure and supersede evidence generated using in vitro cultured MKs. Additionally, by analyzing transcriptional signatures of a single HSC, we identify two MK-biased HSC subpopulations exhibiting unique differentiation kinetics. We show that human bone marrow MKs originate from these HSC subpopulations, supporting the notion that they display priming for MK differentiation. Finally, to investigate transcriptional changes in MKs associated with stress thrombopoiesis, we analyzed bone marrow MKs from individuals with recent myocardial infarction and found a specific gene expression signature. Our data support the modulation of MK differentiation in this thrombotic state. CONCLUSIONS: Here, we use single-cell sequencing for the first time to characterize the human bone marrow MK transcriptome at different levels of polyploidization and investigate their differentiation from the HSC

Safety and immunogenicity of the chlamydia vaccine candidate CTH522 adjuvanted with CAF01 liposomes or aluminium hydroxide: a first-in-human, randomised, double-blind, placebo-controlled, phase 1 trial

BACKGROUND: Chlamydia is the most common sexually transmitted bacterial infection worldwide. National screening programmes and antibiotic treatment have failed to decrease incidence, and to date no vaccines against genital chlamydia have been tested in clinical trials. We aimed to assess the safety and immunogenicity, in humans, of a novel chlamydia vaccine based on a recombinant protein subunit (CTH522) in a prime-boost immunisation schedule. METHODS: This phase 1, first-in-human, double-blind, parallel, randomised, placebo-controlled trial was done at Hammersmith Hospital in London, UK, in healthy women aged 19-45 years. Participants were randomly assigned (3:3:1) to three groups: CTH522 adjuvanted with CAF01 liposomes (CTH522:CAF01), CTH522 adjuvanted with aluminium hydroxide (CTH522:AH), or placebo (saline). Participants received three intramuscular injections of 85 μg vaccine (with adjuvant) or placebo to the deltoid region of the arm at 0, 1, and 4 months, followed by two intranasal administrations of 30 μg unadjuvanted vaccine or placebo (one in each nostril) at months 4·5 and 5·0. The primary outcome was safety and the secondary outcome was humoral immunogenicity (anti-CTH522 IgG seroconversion). This study is registered with Clinicaltrials.gov, number NCT02787109. FINDINGS: Between Aug 15, 2016, and Feb 13, 2017, 35 women were randomly assigned (15 to CTH522:CAF01, 15 to CTH522:AH, and five to placebo). 32 (91%) received all five vaccinations and all participants were included in the intention-to-treat analyses. No related serious adverse reactions were reported, and the most frequent adverse events were mild local injection-site reactions, which were reported in all (15 [100%] of 15) participants in the two vaccine groups and in three (60%) of five participants in the placebo group (p=0·0526 for both comparisons). Intranasal vaccination was not associated with a higher frequency of related local reactions (reported in seven [47%] of 15 participants in the active treatment groups vs three [60%] of five in the placebo group; p=1·000). Both CTH522:CAF01 and CTH522:AH induced anti-CTH522 IgG seroconversion in 15 (100%) of 15 participants after five immunisations, whereas no participants in the placebo group seroconverted. CTH522:CAF01 showed accelerated seroconversion, increased IgG titres, an enhanced mucosal antibody profile, and a more consistent cell-mediated immune response profile compared with CTH522:AH. INTERPRETATION: CTH522 adjuvanted with either CAF01 or aluminium hydroxide appears to be safe and well tolerated. Both vaccines were immunogenic, although CTH522:CAF01 had a better immunogenicity profile, holding promise for further clinical development. FUNDING: European Commission and The Innovation Fund Denmark

Solitary splenic metastasis from ovarian carcinosarcoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Metastatic tumors to the spleen are rare but are usually found in conjunction with metastasis to other organs. The most common sources of splenic metastasis are breast, lung and colorectal cancers as well as melanoma and ovarian carcinoma. A solitary carcinosarcoma metastasis to the spleen of any origin is very rare. To the best of our knowledge, there are fewer than 30 reported cases of ovarian primary tumors with solitary metastasis to the spleen, and only three solitary primary carcinosarcomas to the spleen have been reported, of which one is female. We present what is, to the best of our knowledge, the first case of a solitary metastatic carcinosarcoma to the spleen arising from a primary ovarian carcinsarcoma.</p> <p>Case presentation</p> <p>A 72-year-old Hispanic woman status post-total abdominal hysterectomy for ovarian carcinosarcoma presented with complaints of early satiety and abdominal pain for the past two months with a 30-lb unintentional weight loss. An initial computed tomographic scan of her abdomen and pelvis revealed a 30 cm × 27 cm splenic mass with displacement of the left kidney, stomach and liver. The patient was found to have a solitary metastatic carcinosarcoma of the spleen with biphasic epithelial (carcinomatous) and mesenchymal (sarcomatous) elements consistent with carcinosarcoma.</p> <p>Conclusion</p> <p>Carcinosarcoma of the spleen is a rare tumor. Carcinosarcomas are a biphasic neoplasm comprising malignant epithelial and mesenchymal components arising from a stem cell capable of differentiation. They can arise anywhere in the female genital tract, most commonly from the endometrium. Even though it is rare, carcinosarcomas can metastasize to the spleen. This unique case of a solitary splenic metastasis from ovarian carcinosarcoma has particular interest in medicine, especially for the specialties of surgical oncology, pathology and hematology/oncology.</p

Greater number of group identifications is associated with lower odds of being depressed: evidence from a Scottish community sample

Purpose: Group identification has been shown to be associated with reduced risk of depression, but this research has important limitations. Our aim was to establish a robust link between group identification and depression whilst overcoming previous studies’ shortcomings. Methods: 1824 participants, recruited from General Practice throughout Scotland, completed a questionnaire measuring their identification with three groups (family, community, and a group of their choice), as well as their intensity of contact with each group. They also completed a self-rated depression measure and provided demographic information. Their medical records were also accessed in order to determine if they had been prescribed antidepressants in the previous six months. Results: Number of group identifications was associated with both lower self-rated depression and lower odds of having received a prescription for antidepressants, even after controlling for number of contact-intensive groups, level of education, gender, age, and relationship status. Conclusions: Identifying with multiple groups may help to protect individuals against depression. This highlights the potential importance of social prescriptions, where health professionals encourage a depressed patient to become a member of one or more groups with which the patient believes he/she would be likely to identify

Consumption patterns of sweet drinks in a population of Australian children and adolescents (2003–2008)

<p>Abstract</p> <p>Background</p> <p>Intake of sweet drinks has previously been associated with the development of overweight and obesity among children and adolescents. The present study aimed to assess the consumption pattern of sweet drinks in a population of children and adolescents in Victoria, Australia.</p> <p>Methods</p> <p>Data on 1,604 children and adolescents (4–18 years) from the comparison groups of two quasi-experimental intervention studies from Victoria, Australia were analysed<it>.</it> Sweet drink consumption (soft drink and fruit juice/cordial) was assessed as one day’s intake and typical intake over the last week or month at two time points between 2003 and 2008 (mean time between measurement: 2.2 years).</p> <p>Results</p> <p>Assessed using dietary recalls, more than 70% of the children and adolescents consumed sweet drinks, with no difference between age groups (p = 0.28). The median intake among consumers was 500 ml and almost a third consumed more than 750 ml per day. More children and adolescents consumed fruit juice/cordial (69%) than soft drink (33%) (p < 0.0001) and in larger volumes (median intake fruit juice/cordial: 500 ml and soft drink: 375 ml). Secular changes in sweet drink consumption were observed with a lower proportion of children and adolescents consuming sweet drinks at time 2 compared to time 1 (significant for age group 8 to <10 years, p = 0.001).</p> <p>Conclusion</p> <p>The proportion of Australian children and adolescents from the state of Victoria consuming sweet drinks has been stable or decreasing, although a high proportion of this sample consumed sweet drinks, especially fruit juice/cordial at both time points.</p

Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP

Most human protein-encoding genes contain multiple exons that are spliced together, frequently in alternative arrangements, by the spliceosome. It is established that U1 snRNP is an essential component of the spliceosome, in human consisting of RNA and ten proteins, several of which are post- translationally modified and exist as multiple isoforms. Unresolved and challenging to investigate are the effects of these post translational modifications on the dynamics, interactions and stability of the particle. Using mass spectrometry we investigate the composition and dynamics of the native human U1 snRNP and compare native and recombinant complexes to isolate the effects of various subunits and isoforms on the overall stability. Our data reveal differential incorporation of four protein isoforms and dynamic interactions of subunits U1-A, U1-C and Sm-B/B’. Results also show that unstructured post- ranslationally modified C-terminal tails are responsible for the dynamics of Sm-B/B’ and U1-C and that their interactions with the Sm core are controlled by binding to different U1-70k isoforms and their phosphorylation status in vivo. These results therefore provide the important functional link between proteomics and structure as well as insight into the dynamic quaternary structure of the native U1 snRNP important for its function.This work was funded by: BBSRC (OVM), BBSRC and EPSRC (HH and NM), EU Prospects (HH), European Science Foundation (NM), the Royal Society (CVR), and fellowship from JSPS and HFSP (YM and DAPK respectively)