Barriers to abortion provision: A qualitative study among medical students and gynecologists in Berlin, Germany.

OBJECTIVES: While abortion is a common medical procedure in Germany, the number of abortion-providing facilities declined by 46% between 2003 and 2022. As existing data do not paint a complete picture of the factors influencing this decline, an understanding into the perspectives of health care professionals (HCPs) is necessary. We set out to examine attitudes of HCPs in Berlin, Germany toward different aspects of abortion to identify barriers that might prevent them from providing abortions. STUDY DESIGN: We used a qualitative research design consisting of in-depth semistructured one-on-one interviews with 14 medical students and four gynecologists. We transcribed interviews verbatim and conducted qualitative content analysis. RESULTS: Many interviewees perceived abortion as a taboo and legally ambiguous intervention. They feared stigmatization when talking about or providing abortions, especially by fellow students or religious family members. Few participants objected to abortion provision on religious grounds. Some medical students underestimated the safety of abortion and overestimated the potential for side effects and complications. Medical students obtained their knowledge about abortion from various sources, such as media, religious school education, or personal experience with abortion; the topic was rarely discussed in their medical education. To decide whether to provide abortions later, many students wished for detailed abortion teaching during medical school and residency. CONCLUSIONS: Fear of stigmatization, misconceptions on abortion, and religious beliefs reduced HCPs' willingness to perform abortions. Abortion education was widely valued by medical students and could address some of the barriers to abortion provision we found in this study. IMPLICATIONS: Universities and teaching hospitals should systematically teach about abortion to counteract misinformation and help normalize abortions among HCPs. Moreover, political decision-makers should take measures in order to destigmatize abortion, like an abortion regulation outside the Criminal Code in line with international public health recommendations.

Correction: Global health research and education at medical faculties in Germany.

[This corrects the article DOI: 10.1371/journal.pone.0231302.].

Global health research and education at medical faculties in Germany.

BACKGROUND: Universities undertake the majority of publicly funded research in Germany and hence bear a responsibility to contribute to global health efforts. So far, involvement and impact of German medical faculties in global health are unknown. Our aim was to systematically asses and evaluate German medical faculties' contribution to global health related research and education, as well as their policies and practices concerning open access publishing and equitable licensing. METHODS: We assessed the involvement in global health of all 36 publicly funded medical faculties in Germany during 2010-2014 in three areas: innovation, access and education, using the following indicators: research funding and publications focused on global health or poverty-related and neglected diseases; open access publishing and policies promoting access to medical innovations worldwide; provision of global health education. Data were gathered from public databases, university websites and questionnaires sent to individual universities for validation and triangulation. RESULTS: There was a high level of variability between institutions and indicators. The proportion of research funding for poverty-related and neglected diseases research ranged between 0.0-1.1%. The top five institutions received nearly 85% of the total poverty-related and neglected diseases research funding. 20 of 36 universities had an institutional open access publishing policy, 19 had an open access publishing fund, 16 had neither. Only one university reported having used an equitable licensing policy. 22 of 36 faculties provided some global health education, but only one of them included global health in their core undergraduate medical curriculum as a compulsory course with more than just single lectures. CONCLUSION: Obtained data indicate that global health and poverty-related and neglected diseases research at German medical faculties is highly concentrated in a few institutions, open-access publishing and equitable licensing policies are mostly absent, and only little global health education exists. Universities and government should address global health strategically in both research and education at medical faculties to reflect the country's economic and political weight and human resource potential.

The effect of Rho drugs on mast cell activation and degranulation.

Mast cells are tissue-resident immune cells that produce potent proinflammatory mediators, which are stored in cytoplasmic granules. Stimulation triggers degranulation, a process that mobilizes granules to dock and fuse to the plasma membrane, releasing mediators. Mast cell degranulation has an important role in immunity but can also intensify inflammation and contribute to allergic disorders. Hence, it is important to understand signaling pathways that regulate mast cell degranulation. Here, we examined the role of Rho proteins in regulating mast cell activation leading to degranulation. RBL-2H3 cells and bone marrow-derived mast cells (BMMCs) were stimulated through aggregation of FcεRI receptors. Stimulated cells showed a large increase in the levels of activated Rac and, to a lesser extent, RhoA. Drugs were used to acutely inhibit the function of specific Rho proteins. The Rac inhibitor EHT-1864 and the RhoA inhibitor rhosin inhibited degranulation. Microscopic characterization showed that, upon stimulation, RBL-2H3 cells formed surface ridges that grew into large protrusions reminiscent of circular dorsal ruffles, which flattened into large lamellipodia. LysoTracker-labeled cells showed granules stream into peripheral protrusions. EHT-1864 reduced granule motility, whereas rhosin increased motility; both drugs affected the formation of peripheral protrusions. These results showed that, in response to stimuli, Rho proteins control discrete cytoskeletal remodeling processes that are needed for granule exocytosis. Rac is required to stimulate the remodeling of mast cells, triggering actin-mediated flattening of the cell periphery to create an active degranulation zone, whereas RhoA controls the streaming of highly motile granules into the active zone.

The course of major depression during imprisonment - A one year cohort study.

BACKGROUND: First longitudinal studies in prisoners point to improvements of depressive symptoms during imprisonment. The aim of the present study was to assess the course of major depressive disorder during imprisonment and to identify factors influencing remission. METHODS: Prisoners with major depressive disorder in a sample of consecutive admissions to the penal justice system in Santiago de Chile were reassessed after one year of imprisonment. Psychiatric diagnoses were established using the Mini-International Neuropsychiatric Interview; psychological symptoms were assessed with the Symptom-Check-List 90 Revised (SCL-90-R). Mean symptom scores were compared at baseline and follow-up using Student's t-test. Odds ratios (OR) of comorbid disorders and socio-demographic factors at baseline to predict depression at follow-up were calculated. RESULTS: N=79 out of 80 inmates (99%) with major depression at baseline were included. Thirty-five prisoners (44%) had major depression at follow-up. The mean global severity score and all mean subscale scores of the SCL-90-R improved. High suicide risk was present in 37 prisoners (47%) at admission and in 11 (14%) at follow-up. The comorbid diagnosis of PTSD (OR 6.3; p<0.001) at admission and having been previously imprisoned (OR 2.5; p=0.05) predicted major depressive disorder at follow-up. LIMITATIONS: The study could not account for temporary improvements between the assessments. CONCLUSION: In spite of important symptom improvements, only about half of the prisoners with major depression at admission remit after one year of imprisonment. New interventions should target people with major depression and comorbid PTSD at admission.

Rac1 and Rac2 control distinct events during antigen-stimulated mast cell exocytosis.

The release of preformed mediators from immune cells is through a process described as exocytosis. In mast cells, exocytosis is regulated by several coordinated intracellular signaling pathways. Here, we investigated the role of the hematopoietic-specific Rho GTPase, Rac2, and the ubiquitously expressed Rac1, in controlling mast cell exocytosis. These two isoforms showed equivalent levels of expression in mouse BMMCs. Although Rac1 and Rac2 share 92% sequence identity, they were not functionally redundant, as Rac2-/- BMMCs were defective in exocytosis, even though Rac1 levels were unaffected. Antigen-stimulated WT mast cells underwent a series of morphological transitions: initial flattening, followed by actin-mediated peripheral membrane ruffling and calcium influx, which preceded exocytosis. Whereas membrane ruffling was unaffected in Rac2-/- BMMCs, calcium influx was decreased significantly. Calcium influx was studied further by examining SOCE. In Rac2-/- BMMCs, the activation of PLCγ1 and calcium release from intracellular stores occurred normally; however, activation of plasma membrane calcium channels was defective, shown by the lack of extracellular calcium influx and a reduction of YFP-STIM1 puncta at the plasma membrane. Additionally, we used the small molecule Rac inhibitor, EHT 1864, to target Rac signaling acutely in WT BMMCs. EHT 1864 blocked exocytosis and membrane ruffling completely in conjunction with exocytosis. Our findings suggest that antigen-stimulated membrane ruffling in mast cells is a Rac1-mediated process, as this persisted in the absence of Rac2. Therefore, we define distinct modes of Rac-regulated mast cell exocytosis: Rac2-mediated calcium influx and Rac1-mediated membrane ruffling.

Functional analysis of RhoGDI inhibitory activity on vacuole membrane fusion.

RhoGDIs (Rho GDP-dissociation inhibitors) are the natural inhibitors of Rho GTPases. They interfere with Rho protein function by either blocking upstream activation or association with downstream signalling molecules. RhoGDIs can also extract membrane-bound Rho GTPases to form soluble cytosolic complexes. We have shown previously that purified yeast RhoGDI Rdi1p, can inhibit vacuole membrane fusion in vitro. In the present paper we functionally dissect Rdi1p to discover its mode of regulating membrane fusion. Overexpression of Rdi1p in vivo profoundly affected cell morphology including increased actin patches in mother cells indicative of polarity defects, delayed ALP (alkaline phosphatase) sorting and the presence of highly fragmented vacuoles indicative of membrane fusion defects. These defects were not caused by the loss of typical transport and fusion proteins, but rather were linked to the reduction of membrane localization and activation of Cdc42p and Rho1p. Subcellular fractionation showed that Rdi1p is predominantly a cytosolic monomer, free of bound Rho GTPases. Overexpression of endogenous Rdi1p, or the addition of exogenous Rdi1p, generated stable cytosolic complexes. Rdi1p structure-function analysis showed that membrane association via the C-terminal ß-sheet domain was required for the functional inhibition of membrane fusion. Furthermore, Rdi1p inhibited membrane fusion through the binding of Rho GTPases independent from its extraction activity.

Cdc42p is activated during vacuole membrane fusion in a sterol-dependent subreaction of priming.

Cdc42p is a Rho GTPase that initiates signaling cascades at spatially defined intracellular sites for many cellular functions. We have previously shown that Cdc42p is localized to the yeast vacuole where it initiates actin polymerization during membrane fusion. Here we examine the activation cycle of Cdc42p during vacuole membrane fusion. Expression of either GTP- or GDP-locked Cdc42p mutants caused several morphological defects including enlarged cells and fragmented vacuoles. Stimulation of multiple rounds of fusion enhanced vacuole fragmentation, suggesting that cycles of Cdc42p activation, involving rounds of GTP binding and hydrolysis, are required to propagate Cdc42p signaling. We developed an assay to directly examine Cdc42p activation based on affinity to a probe derived from the p21-activated kinase effector, Ste20p. Cdc42p was rapidly activated during vacuole membrane fusion, which kinetically coincided with priming subreaction. During priming, Sec18p ATPase activity dissociates SNARE complexes and releases Sec17p, however, priming inhibitors such as Sec17p and Sec18p ligands did not block Cdc42p activation. Therefore, Cdc42p activation seems to be a parallel subreaction of priming, distinct from Sec18p activity. Specific mutants in the ergosterol synthesis pathway block both Sec17p release and Cdc42p activation. Taken together, our results define a novel sterol-dependent subreaction of vacuole priming that activates cycles of Cdc42p activity to facilitate membrane fusion.