Depression during pregnancy: views on antidepressant use and information sources of general practitioners and pharmacists

<p>Abstract</p> <p>Background</p> <p>The use of antidepressants during pregnancy has increased in recent years. In the Netherlands, almost 2% of all pregnant women are exposed to antidepressants. Although guidelines have been developed on considerations that should be taken into account, prescribing antidepressants during pregnancy is still a subject of debate. Physicians and pharmacists may have opposing views on using medication during pregnancy and may give contradictory advice on whether or not to take medication for depression and anxiety disorders during pregnancy. In this study, we investigated information sources used by general practitioners (GPs) and pharmacists and their common practices.</p> <p>Methods</p> <p>A questionnaire on the use of information sources and the general approach when managing depression during pregnancy was sent out to 1400 health care professionals to assess information sources on drug safety during pregnancy and also the factors that influence decision-making. The questionnaires consisted predominantly of closed multiple-choice questions.</p> <p>Results</p> <p>A total of 130 GPs (19%) and 144 pharmacists (21%) responded. The most popular source of information on the safety of drug use during pregnancy is the Dutch National Health Insurance System Formulary, while a minority of respondents contacts the Dutch national Teratology Information Service (TIS). The majority of GPs contact the pharmacy with questions concerning drug use during pregnancy. There is no clear line with regard to treatment or consensus between GPs on the best therapeutic strategy, nor do practitioners agree upon the drug of first choice. GPs have different views on stopping or continuing antidepressants during pregnancy or applying alternative treatment options. The debate appears to be ongoing as to whether or not specialised care for mother and child is indicated in cases of gestational antidepressant use.</p> <p>Conclusion</p> <p>Primary health care workers are not univocal concerning therapy for pregnant women with depression. Although more research is needed to account for all safety issues, local or national policies are indispensable in order to avoid undesirable practices, such as giving contradictory advice. GPs and pharmacists should address the subject during their regular pharmacotherapeutic consensus meetings, preferably in collaboration with the TIS or other professionals in the field.</p

The impact of perfectionism and anxiety traits on action monitoring in major depressive disorder

Perfectionism and anxiety features are involved in the clinical presentation and neurobiology of major depressive disorder (MDD). In MDD, cognitive control mechanisms such as action monitoring can adequately be investigated applying electrophysiological registrations of the error-related negativity (ERN) and error positivity (Pe). It is also known that traits of perfectionism and anxiety influence ERN amplitudes in healthy subjects. The current study explores the impact of perfectionism and anxiety traits on action monitoring in MDD. A total of 39 MDD patients performed a flankers task during an event-related potential (ERP) session and completed the multidimensional perfectionism scale (MPS) with its concern over mistakes (CM) and doubt about actions (DA) subscales and the trait form of the State Trait Anxiety Inventory. Multiple regression analyses with stepwise backward elimination revealed MPS-DA to be a significant predictor (R2:0.22) for the ERN outcomes, and overall MPS (R2:0.13) and MPS-CM scores (R2:0.18) to have significant predictive value for the Pe amplitudes. Anxiety traits did not have a predictive capacity for the ERPs. MPS-DA clearly affected the ERN, and overall MPS and MPS-CM influenced the Pe, whereas no predictive capacity was found for anxiety traits. The manifest impact of perfectionism on patients’ error-related ERPs may contribute to our understanding of the action-monitoring process and the functional significance of the Pe in MDD. The divergent findings for perfectionism and anxiety features also indicate that the wide range of various affective personality styles might exert a different effect on action monitoring in MDD, awaiting further investigation

MicroRNAs in pulmonary arterial remodeling

Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH

Sharing Data for Public Health Research by Members of an International Online Diabetes Social Network

Background: Surveillance and response to diabetes may be accelerated through engaging online diabetes social networks (SNs) in consented research. We tested the willingness of an online diabetes community to share data for public health research by providing members with a privacy-preserving social networking software application for rapid temporal-geographic surveillance of glycemic control. Methods and Findings: SN-mediated collection of cross-sectional, member-reported data from an international online diabetes SN entered into a software applicaction we made available in a “Facebook-like” environment to enable reporting, charting and optional sharing of recent hemoglobin A1c values through a geographic display. Self-enrollment by 17% (n = 1,136) of n = 6,500 active members representing 32 countries and 50 US states. Data were current with 83.1% of most recent A1c values reported obtained within the past 90 days. Sharing was high with 81.4% of users permitting data donation to the community display. 34.1% of users also displayed their A1cs on their SN profile page. Users selecting the most permissive sharing options had a lower average A1c (6.8%) than users not sharing with the community (7.1%, p = .038). 95% of users permitted re-contact. Unadjusted aggregate A1c reported by US users closely resembled aggregate 2007–2008 NHANES estimates (respectively, 6.9% and 6.9%, p = 0.85). Conclusions: Success within an early adopter community demonstrates that online SNs may comprise efficient platforms for bidirectional communication with and data acquisition from disease populations. Advancing this model for cohort and translational science and for use as a complementary surveillance approach will require understanding of inherent selection and publication (sharing) biases in the data and a technology model that supports autonomy, anonymity and privacy.Centers for Disease Control and Prevention (U.S.) (P01HK000088-01)Centers for Disease Control and Prevention (U.S.) (P01HK000016 )National Institute of Alcohol Abuse and Alcoholism (U.S.) (R21 AA016638-01A1)National Center for Research Resources (U.S.) (1U54RR025224-01)Children's Hospital (Boston, Mass.) (Program for Patient Safety and Quality

A randomized controlled trial for overweight and obesity in preschoolers: the More and Less Europe study- an intervention within the STOP project

Background Childhood overweight and obesity is a serious public health issue with an increase being observed in preschool-aged children. Treating childhood obesity is difficult and few countries use standardized treatments. Therefore, there is a need to find effective approaches that are feasible for both health care providers and families. Thus, the overall aim of this study is to assess the acceptance and effectiveness of a parent support program (the More and Less, ML) for the management of overweight and obesity followed by a mobile health (mHealth) program (the MINISTOP application) in a socially diverse population of families. Methods/design A two-arm, parallel design randomized controlled trial in 300 2-to 6-year-old children with overweight and obesity from Romania, Spain and Sweden (n = 100 from each). Following baseline assessments children are randomized into the intervention or control group in a 1:1 ratio. The intervention, the ML program, consists of 10-weekly group sessions which focus on evidence-based parenting practices, followed by the previously validated MINISTOP application for 6-months to support healthy eating and physical activity behaviors. The primary outcome is change in body mass index (BMI) z-score after 9-months and secondary outcomes include: waist circumference, eating behavior (Child Eating Behavior Questionnaire), parenting behavior (Comprehensive Feeding Practices Questionnaire), physical activity (ActiGraph wGT3x-BT), dietary patterns (based on metabolic markers from urine and 24 h dietary recalls), epigenetic and gut hormones (fasting blood samples), and the overall acceptance of the overweight and obesity management in young children (semi-structured interviews). Outcomes are measured at baseline and after: 10-weeks (only BMI z-score, waist circumference), 9-months (all outcomes), 15- and 21-months (all outcomes except physical activity, dietary patterns, epigenetics and gut hormones) post-baseline. Discussion This study will evaluate a parent support program for weight management in young children in three European countries. To boost the effect of the ML program the families will be supported by an app for 6-months. If the program is found to be effective, it has the potential to be implemented into routine care to reduce overweight and obesity in young children and the app could prove to be a viable option for sustained effects of the care provided. Trial registration ClinicalTrials.gov NCT03800823; 11 Jan 2019

The Human Minor Histocompatibility Antigen1 Is a RhoGAP

The human minor Histocompatibility Antigen HMHA-1 is a major target of immune responses after allogeneic stem cell transplantation applied for the treatment of leukemia and solid tumors. The restriction of its expression to hematopoietic cells and many solid tumors raised questions regarding its cellular functions. Sequence analysis of the HMHA-1 encoding HMHA1 protein revealed the presence of a possible C-terminal RhoGTPase Activating Protein (GAP) domain and an N-terminal BAR domain. Rho-family GTPases, including Rac1, Cdc42, and RhoA are key regulators of the actin cytoskeleton and control cell spreading and migration. RhoGTPase activity is under tight control as aberrant signaling can lead to pathology, including inflammation and cancer. Whereas Guanine nucleotide Exchange Factors (GEFs) mediate the exchange of GDP for GTP resulting in RhoGTPase activation, GAPs catalyze the low intrinsic GTPase activity of active RhoGTPases, resulting in inactivation. Here we identify the HMHA1 protein as a novel RhoGAP. We show that HMHA1 constructs, lacking the N-terminal region, negatively regulate the actin cytoskeleton as well as cell spreading. Furthermore, we show that HMHA1 regulates RhoGTPase activity in vitro and in vivo. Finally, we demonstrate that the HMHA1 N-terminal BAR domain is auto-inhibitory as HMHA1 mutants lacking this region, but not full-length HMHA1, showed GAP activity towards RhoGTPases. In conclusion, this study shows that HMHA1 acts as a RhoGAP to regulate GTPase activity, cytoskeletal remodeling and cell spreading, which are crucial functions in normal hematopoietic and cancer cells

Acceptability of the Distress Thermometer and Problem List to community-based telephone cancer helpline operators, and to cancer patients and carers

Background Cancer can be a distressing experience for cancer patients and carers, impacting on psychological, social, physical and spiritual functioning. However, health professionals often fail to detect distress in their patients due to time constraints and a lack of experience. Also, with the focus on the patient, carer needs are often overlooked. This study investigated the acceptability of brief distress screening with the Distress Thermometer (DT) and Problem List (PL) to operators of a community-based telephone helpline, as well as to cancer patients and carers calling the service. Methods Operators (n = 18) monitored usage of the DT and PL with callers (cancer patients/carers, >18 years, and English-speaking) from September-December 2006 (n = 666). The DT is a single item, 11-point scale to rate level of distress. The associated PL identifies the cause of distress. Results The DT and PL were used on 90% of eligible callers, most providing valid responses. Benefits included having an objective, structured and consistent means for distress screening and triage to supportive care services. Reported challenges included apparent inappropriateness of the tools due to the nature of the call or level of caller distress, the DT numeric scale, and the level of operator training. Conclusions We observed positive outcomes to using the DT and PL, although operators reported some challenges. Overcoming these challenges may improve distress screening particularly by less experienced clinicians, and further development of the PL items and DT scale may assist with administration. The DT and PL allow clinicians to direct/prioritise interventions or referrals, although ongoing training and support is critical in distress screening

Rapid evolution of microbe-mediated protection against pathogens in a worm host.

Microbes can defend their host against virulent infections, but direct evidence for the adaptive origin of microbe-mediated protection is lacking. Using experimental evolution of a novel, tripartite interaction, we demonstrate that mildly pathogenic bacteria (Enterococcus faecalis) living in worms (Caenorhabditis elegans) rapidly evolved to defend their animal hosts against infection by a more virulent pathogen (Staphylococcus aureus), crossing the parasitism-mutualism continuum. Host protection evolved in all six, independently selected populations in response to within-host bacterial interactions and without direct selection for host health. Microbe-mediated protection was also effective against a broad spectrum of pathogenic S. aureus isolates. Genomic analysis implied that the mechanistic basis for E. faecalis-mediated protection was through increased production of antimicrobial superoxide, which was confirmed by biochemical assays. Our results indicate that microbes living within a host may make the evolutionary transition to mutualism in response to pathogen attack, and that microbiome evolution warrants consideration as a driver of infection outcome

Restricted Genetic Diversity of HIV-1 Subtype C Envelope Glycoprotein from Perinatally Infected Zambian Infants

Background: Mother-to-child transmission of HIV-1 remains a significant problem in the resource-constrained settings where anti-retroviral therapy is still not widely available. Understanding the earliest events during HIV-1 transmission and characterizing the newly transmitted or founder virus is central to intervention efforts. In this study, we analyzed the viral env quasispecies of six mother-infant transmission pairs (MIPs) and characterized the genetic features of envelope glycoprotein that could influence HIV-1 subtype C perinatal transmission. Methodology and Findings: The V1-V5 region of env was amplified from 6 MIPs baseline samples and 334 DNA sequences in total were analyzed. A comparison of the viral population derived from the mother and infant revealed a severe genetic bottleneck occurring during perinatal transmission, which was characterized by low sequence diversity in the infant. Phylogenetic analysis indicates that most likely in all our infant subjects a single founder virus was responsible for establishing infection. Furthermore, the newly transmitted viruses from the infant had significantly fewer potential N-linked glycosylation sites in Env V1-V5 region and showed a propensity to encode shorter variable loops compared to the nontransmitted viruses. In addition, a similar intensity of selection was seen between mothers and infants with a higher rate of synonymous (dS) compared to nonsynonymous (dN) substitutions evident (dN/dS\u3c1). Conclusions: Our results indicate that a strong genetic bottleneck occurs during perinatal transmission of HIV-1 subtype C. This is evident through population diversity and phylogenetic patterns where a single viral variant appears to be responsible for infection in the infants. As a result the newly transmitted viruses are less diverse and harbored significantly less glycosylated envelope. This suggests that viruses with the restricted glycosylation in envelope glycoprotein appeared to be preferentially transmitted during HIV-1 subtype C perinatal transmission. In addition, our findings also indicated that purifying selection appears to predominate in shaping the early intrahost evolution of HIV-1 subtype C envelope sequences