Die godsdiensgegewe in twee romans van Berta Smit

Die verskyningsdatum van haar debuutwerk, Die vrou en die bees gee aan Berta Smit ’n plek tussen die Sestigers. In werklikheid het haar werke egter raakpunte met die sogenaamde Ouer prosa sowel as met die Nuwer prosa. Soos die meeste prosawerke voor Sestig gaan haar romans uit van ’n vaste norm, naamlik die Christelike

No Higher Risk of CRPS After External Fixation of Distal Radial Fractures – Subgroup Analysis Under Randomised Vitamin C Prophylaxis§

Operative and conservative treatment of wrist fractures might lead to complex regional pain syndrome (CRPS) type I

“Facing Our Fears”: Using facilitated film viewings to engage communities in HIV research involving MSM in Kenya

Kenya is a generally homophobic country where homosexuality is criminalised and people who engage in same sex sexuality face stigma and discrimination. In 2013, we developed a 16 min documentary entitled "Facing Our Fears" that aimed at sharing information on how and why men who have sex with men (MSM) are involved in on-going KEMRI HIV prevention research, and associated community engagement. To consider the film's usefulness as a communication tool, and its perceived security risks in case the film was publicly released, we conducted nine facilitated viewings with 122 individuals representing seven different stakeholder groups. The documentary was seen as a strong visual communication tool with potential to reduce stigma related to homosexuality, and facilitated film viewings were identified as platforms with potential to support open dialogue about HIV research involving MSM. Despite the potential, there were concerns over possible risks to LGBT communities and those working with them following public release. We opted-giving emphasis to the "do no harm" principle-to use the film only in facilitated settings where audience knowledge and attitudes can be carefully considered and discussed. The results highlight the importance of carefully assessing the range of possible impacts when using visuals in community engagement.</p

Pharmacological Modulation of Dopamine Receptor D2-Mediated Transmission Alters the Metabolic Phenotype of Diet Induced Obese and Diet Resistant C57Bl6 Mice

High fat feeding induces a variety of obese and lean phenotypes in inbred rodents. Compared to Diet Resistant (DR) rodents, Diet Induced Obese (DIO) rodents are insulin resistant and have a reduced dopamine receptor D2 (DRD2) mediated tone. We hypothesized that this differing dopaminergic tone contributes to the distinct metabolic profiles of these animals. C57Bl6 mice were classified as DIO or DR based on their weight gain during 10 weeks of high fat feeding. Subsequently DIO mice were treated with the DRD2 agonist bromocriptine and DR mice with the DRD2 antagonist haloperidol for 2 weeks. Compared to DR mice, the bodyweight of DIO mice was higher and their insulin sensitivity decreased. Haloperidol treatment reduced the voluntary activity and energy expenditure of DR mice and induced insulin resistance in these mice. Conversely, bromocriptine treatment tended to reduce bodyweight and voluntary activity, and reinforce insulin action in DIO mice. These results show that DRD2 activation partly redirects high fat diet induced metabolic anomalies in obesity-prone mice. Conversely, blocking DRD2 induces an adverse metabolic profile in mice that are inherently resistant to the deleterious effects of high fat food. This suggests that dopaminergic neurotransmission is involved in the control of metabolic phenotype

Solid-phase synthesis of macrocyclic peptides via side-chain anchoring of the ornithine delta-amine

Cyclic peptides represent a popular class of macrocyclic drug candidates and therefore their solid phase synthesis has attracted much attention. In this contribution we present an efficient method of side-chain anchoring for ornithine and lysine residues to be used in the standard Fmoc-based synthesis of cyclic peptides via on-resin cyclization. We demonstrate that the side chain of ornithine and lysine protected with N-Bocgroup can efficiently be converted to the isocyanate which is then immobilized on Wang-type resin in almost quantitative yield. We further show the synthesis of four biologically active cyclic peptides employing the side chain ornithine anchoring. Our method is at least on a par with the previously reported methodologies in terms of yield and the purity of the final products and is arguably operationally more straightforward.NWOGravitation program 2013Bio-organic Synthesi

Transcriptional signatures of somatic neoblasts and germline cells in <i>Macrostomum lignano</i>

The regeneration-capable flatworm <i>Macrostomum lignano</i> is a powerful model organism to study the biology of stem cells in vivo. As a flatworm amenable to transgenesis, it complements the historically used planarian flatworm models, such as <i>Schmidtea mediterranea</i>. However, information on the transcriptome and markers of stem cells in <i>M. lignano</i> is limited. We generated a de novo transcriptome assembly and performed the first comprehensive characterization of gene expression in the proliferating cells of <i>M. lignano</i>, represented by somatic stem cells, called neoblasts, and germline cells. Knockdown of a selected set of neoblast genes, including <i>Mlig-ddx39</i>, <i>Mlig-rrm1</i>, <i>Mlig-rpa3</i>, <i>Mlig-cdk1</i>, and <i>Mlig-h2a</i>, confirmed their crucial role for the functionality of somatic neoblasts during homeostasis and regeneration. The generated <i>M. lignano</i> transcriptome assembly and gene expression signatures of somatic neoblasts and germline cells will be a valuable resource for future molecular studies in <i>M. lignano</i>

Understanding Adherence to Daily and Intermittent Regimens of Oral HIV Pre-exposure Prophylaxis Among Men Who Have Sex with Men in Kenya

A qualitative assessment of Kenyan men who have sex with men taking daily and intermittent oral HIV preexposure prophylaxis (PrEP) found stigma, sex work, mobility, and alcohol impacted adherence. We analyzed quantitative data from the same cohort to explore different definitions of intermittent adherence. Volunteers were randomized to daily emtricitabine/tenofovir or placebo, or intermittent (prescription: Mondays/Fridays/after sex, maximum1 dose/day)emtricitabine/tenofovir or placebo (2:1:2:1), and followed for 4 months. By electronic monitoring, median adherence for daily dosing was 80 %. Median adherence for intermittent dosing was 71 % per a ‘‘relaxed’’ definition (accounting for off-prescription dosing) and 40 % per a ‘‘strict’’ definition (limited to the prescription). Factors associated with lower adherence included travel, transactional sex, and longer follow-up; higher adherence was associated with daily dosing and an income. The definition of intermittent dosing strongly affects interpretation of adherence. These findings suggest interventions should address challenges of mobility, sex work, and long-term PrEP

Effect of an opt-out point-of-care HIV-1 nucleic acid testing intervention to detect acute and prevalent HIV infection in symptomatic adult outpatients and reduce HIV transmission in Kenya: a randomized controlled trial

Background: In sub-Saharan Africa, adult outpatients with symptoms of acute infectious illness are not routinely tested for prevalent or acute HIV infection (AHI) when seeking healthcare. Methods: Adult symptomatic outpatients aged 18–39 years were evaluated by a consensus AHI risk score. Patients with a risk score ≥ 2 and no previous HIV diagnosis were enrolled in a stepped-wedge trial of opt-out delivery of point-of-care (POC) HIV-1 nucleic acid testing (NAAT), compared with standard provider-initiated HIV testing using rapid tests in the observation period. The primary outcome was the number of new diagnoses in each study period. Generalized estimating equations with a log-binomial link and robust variance estimates were used to account for clustering by health facility. The trial is registered with ClinicalTrials.gov NCT03508908. Results: Between 2017 and 2020, 13 (0.9%) out of 1374 participants in the observation period and 37 (2.5%) out of 1500 participants in the intervention period were diagnosed with HIV infection. Of the 37 newly diagnosed cases in the intervention period, two (5.4%) had AHI. Participants in the opt-out intervention had a two-fold greater odds of being diagnosed with HIV (odds ratio = 2.2, 95% confidence interval: 1.39–3.51) after adjustment for factors imbalanced across study periods. Conclusions: Among symptomatic adults aged 18–39 years targeted by our POC NAAT intervention, we identified one chronic HIV infection for every 40 patients and one AHI patient for every 750 patients tested. Although AHI yield was low in this population, routinely offered opt-out testing could diagnose twice as many patients as an approach relying on provider discretion

A Pharmaceutical Care Program to Improve Adherence to Statin Therapy:A Randomized Controlled Trial

BACKGROUND: Despite the well-known beneficial effects of statins, many patients do not adhere to chronic medication regimens. OBJECTIVE: To implement and assess the effectiveness of a community pharmacy based pharmaceutical care program developed to improve patients' adherence to statin therapy. METHODS: An open-label, prospective, randomized controlled trial was conducted at 26 community pharmacies in the Netherlands. New users of statins who were aged 18 years or older were randomly assigned to receive either usual care or a pharmacist intervention. The intervention consisted of 5 individual counseling sessions by a pharmacist during a 1-year period. During these sessions, patients received structured education about the importance of medication adherence, lipid levels were measured, and the association between adherence and lipid levels was discussed. Adherence to statin therapy was assessed as discontinuation rates 6 and 12 months after statin initiation, and as the medication possession ratio (MPR), and compared between the pharmaceutical care and usual care groups. RESULTS: A total of 899 subjects (439 in the pharmaceutical care group and 460 in the usual care group) were evaluable for effectiveness analysis. The pharmaceutical care program resulted in a significantly lower rate of discontinuation within 6 months after initiating therapy versus usual care (HR 0.66, 95% Cl 0.46 to 0.96). No significant difference between groups was found in discontinuation at 12 months (HR 0.84, 95% Cl 0.65 to 1.10). Median MPR was very high (>99%) in both groups and did not differ between groups. CONCLUSIONS: These results demonstrate the feasibility and effectiveness of a community pharmacy based pharmaceutical care program to improve medication adherence in new users of statins. Frequent counseling sessions (every 3 months) are necessary to maintain the positive effects on discontinuation. Although improvements are modest, the program can be applied easily to a larger population and have a large impact, as the interventions are relatively inexpensive and easy to, implement in clinical practice