Vaccinations among medical and nursing students: Coverage and opportunities

Healthcare students are a specific subgroup of healthcare workers as they are often not identified by the occupational medicine systems in healthcare facilities, because of their shared time between hospital wards and universities. Nevertheless, they should comply with the same vaccination recommendations as employed healthcare workers because they are in close and repeated contact with patients. Occupational immunization recommendations may vary between countries, but always include vaccine-preventable diseases that might lead to nosocomial outbeaks and/or fatal outcomes for healthcare workers or patients. Studies conclude that vaccine coverage is too low in healthcare students, and that they are often not aware of their possibility to be vectors of infections to frail patients. Efforts should be made to educate medical and nursing students on vaccines, to convince them of the utility of immunization and to offer them an increased access to occupational vaccinations in hospitals and universities.     

Pregnancy outcomes following pulsatile GnRH treatment: results of a large multicenter retrospective study

Objectives

The aim of the present study was to evaluate the efficacy of pulsatile GnRH treatment in a large French cohort of patients with hypogonadotropic hypogonadism.

Methods

A retrospective study involving all women treated with pulsatile GnRH, over a 3-year period, in 24 French centers. Pregnancy rate and pregnancy outcome were the criteria for evaluation.

Results

The study included 248 women who received a total of 829 treatment cycles. The treatment routes of administration were subcutaneous (56.1% of the patients), intravenous (31.1%), or both (12.7%). The pregnancy rate per treatment cycle was 25%, while the mean number of cycles needed to obtain a pregnancy was 2.8 ± 1.7. The miscarriage rate was 8.2% and the multiple pregnancy rates 8.8%. The mean delivery term was 38.4 ± 2.4 weeks and the mean birth weight was 3009 ± 561 g. No severe ovarian hyperstimulation was recorded. Ovarian cysts occurred in 2.3% of the treatment cycles, local allergies in 1.7%.

Conclusion

Our study has shown that pulsatile GnRH treatment was well tolerated, without severe hyperstimulation. It induced a good pregnancy rate with favorable pregnancy outcomes.     

Interleukin-1-Mediated phospholipid breakdown and arachidonic acid release in human synovial cells

Objective. Interleukin-1 (IL-1), an important mediator contributing to joint destruction in rheumatoid arthritis, is known to stimulate the release of arachidonic acid (AA) and prostaglandin E₂ (PGE₂) from adherent synoviocytes. To study the intracellular pathways involved in these functions, we stimulated cultures of human synovial cells with recombinant IL-1β. Methods. AA liberation was measured after labeling synovial cells with ³H-AA, and PGE₂ levels were determined by high performance liquid chromatography or radioimmunoassay. Identification of ³H-AA-labeled phospholipids was performed by thin layer chromatography. Cell-associated phospholipase A₂ (PLA₂) enzymatic activity was determined by an assay with cell-free systems and exogenous substrates. Results. Stimulation of synovial cells with recombinant IL-1β induced a decrease in phosphatidylcholine (PC), phosphatidylinositol (PI), and phosphatidylethanolamine (PE), and a marked increase in cell-associated PLA₂ activity as compared with controls. In the presence of either quinacrine, an inhibitor of PLA₂ pathway activation, or neomycin, which binds to PI mono- and biphosphate thus blocking their degradation by phospholipases, AA and PGE₂ secretion were reduced in a dose-dependent manner. Kinetic studies revealed that quinacrine had little blocking activity on the IL-1-mediated AA release after 1 hour of stimulation but completely abolished it after 5 or 8 hours. In contrast, neomycin exerted a partial but significant inhibitory effect from the first hour of stimulation onward. Addition of quinacrine was also demonstrated to abolish the IL-1-induced hydrolysis of PC and PE but not PI, indicating that PC and PE are the preferred substrates for PLA₂ enzymatic activity in human synovial cells. Conclusion. Our findings strongly suggest that AA and PGE₂ production by IL-1-triggered synoviocytes are largely dependent upon PLA₂-mediated hydrolysis of PC and PE and to a lesser extent upon the earlier degradation of PI.     

Establishment of tissue-specific tolerance is driven by regulatory T cells selected by thymic epithelium

Grafts of thymic epithelium (TE) rudiments restore T cell development and function in allogeneic athymic mice. These TE chimeras are specifically tolerant to grafts of peripheral tissues (e.g. skin and heart) from the TE donor strain, although they harbor peripheral immunocompetent T cells capable of rejecting those grafts. Initial analysis has shown that TE chimeras also harbor TE-selected CD4 T lymphocytes that inhibit graft rejection by tissue-reactive T cells in immunocompetent recipients. Peripheral tolerance in TE chimeras is thus maintained by dominant mechanisms dependent on regulatory CD4 T lymphocytes. Here we show that TE-selected regulatory T cells recruit nontolerant tissue-reactive CD4 and CD8 T cells to express similar regulatory functions. Only recent thymic emigrants, but not peripheral resident mature T cells are susceptible to this process of functional education, which also requires exposure to specific antigens and occurs entirely in the periphery. We propose that these mechanisms play a major role in establishing and maintaining natural self tolerance to tissue-specific antigens.     

Autonomic failure in Parkinson’s disease is associated with striatal dopamine deficiencies

Journal of Neurology - Autonomic dysfunction is a common non-motor symptom in Parkinson’s disease (PD). Dopamine and serotonin are known to play a role in autonomic regulation, and,...     

Prevalence,severity and correlates of fatigue in newly diagnosed patients with myelodysplastic syndromes

The primary objective of this study was to investigate factors associated with fatigue severity in newly diagnosed patients with higher‐risk myelodysplastic syndromes (MDS). The secondary objectives were to assess symptom prevalence and to examine the relationships between fatigue, quality of life (QoL) and overall symptom burden in these patients. The analyses were conducted in 280 higher‐risk MDS patients. Pre‐treatment patient‐reported fatigue was evaluated with the Functional Assessment of Chronic Illness Therapy (FACIT)‐Fatigue scale and QoL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire‐Core 30 (EORTC QLQ‐C30). Female gender (P = 0·018), poor performance status (i.e., ECOG of 2–4) (P < 0·001) and lower levels of haemoglobin (Hb) (P = 0·026) were independently associated with higher fatigue severity. The three most prevalent symptoms were as follows: fatigue (92%), dyspnoea (63%) and pain (55%). Patients with higher levels of fatigue also had greater overall symptom burdens. The mean global QoL scores of patients with the highest versus those with the lowest levels of fatigue were 29·2 [standard deviation (SD), 18·3] and 69·0 (SD, 18·8), respectively and this difference was four times the magnitude of a clinically meaningful difference. Patient‐reported fatigue severity revealed the effects of disease burden on overall QoL more accurately than did degree of anaemia. Special attention should be given to the female patients in the management of fatigue.     

CDK13-related disorder: Report of a series of 18 previously unpublished individuals and description of an epigenetic signature

PurposeRare genetic variants in CDK13 are responsible for CDK13-related disorder (CDK13-RD), with main clinical features being developmental delay or intellectual disability, facial features, behavioral problems, congenital heart defect, and seizures. In this paper, we report 18 novel individuals with CDK13-RD and provide characterization of genome-wide DNA methylation.MethodsWe obtained clinical phenotype and neuropsychological data for 18 and 10 individuals, respectively, and compared this series with the literature. We also compared peripheral blood DNA methylation profiles in individuals with CDK13-RD, controls, and other neurodevelopmental disorders episignatures. Finally, we developed a support vector machine–based classifier distinguishing CDK13-RD and non–CDK13-RD samples.ResultsWe reported health and developmental parameters, clinical data, and neuropsychological profile of individuals with CDK13-RD. Genome-wide differential methylation analysis revealed a global hypomethylated profile in individuals with CDK13-RD in a highly sensitive and specific model that could aid in reclassifying variants of uncertain significance.ConclusionWe describe the novel features such as anxiety disorder, cryptorchidism, and disrupted sleep in CDK13-RD. We define a CDK13-RD DNA methylation episignature as a diagnostic tool and a defining functional feature of the evolving clinical presentation of this disorder. We also show overlap of the CDK13 DNA methylation profile in an individual with a functionally and clinically related CCNK-related disorder.