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Background: The delivery of quality primary healthcare (PHC) services is vital for enhancing the health status of rural communities, yet persistent barriers exist in resource-constrained rural settings. Aim: The study explored perspectives on the barriers to and facilitators of implementing the Ideal Clinic Realisation and Maintenance (ICRM) programme as a quality assurance initiative in a rural KwaZulu-Natal subdistrict. Setting: Professional nurses and healthcare managers from seven PHC clinics in a rural subdistrict of KwaZulu-Natal and supervising managers from a district hospital participated in this study. Methods: Telephonic semi-structured interviews were conducted using a qualitative case study approach with the purposively selected sample. Data were inductively and thematically analysed. Results: Themes included ICRM programme organisation, barriers and facilitators for implementing the ICRM programme. Barriers in rural PHC settings included overburdened clinics, suboptimal infrastructure, staff burnout, poor communication and non-adherence to clinical guidelines. Despite obstacles, programme implementation was facilitated through stakeholder support and teamwork. Participants emphasised the need for infrastructure upgrades, more human and physical resources, and maintenance of stakeholder support. Conclusion: If challenges are mitigated and supportive factors are leveraged, the potential for successful programme implementation and improved healthcare delivery can benefit both healthcare providers and recipients. Contribution: Through providing insight into the perspectives of both implementers and supervisors, the study informs stakeholders and policymakers about difficulties encountered and potential improvements to be made in the implementation of the ICRM programme in rural PHC.

Introduction: The majority of emergency paediatric death in African countries occur within the first 24 h of admission. A coloured triage system is widely implemented in high-income countries and the emergency triage and assessment treatment (ETAT) is recommended by the World Health Organization, but not put into practice in Mozambique. We implemented a three-colour triage system in a rural district hospital with lay-staff workers conducting the first triage. Methods: A retrospective, before and after, mortality analysis was performed using routine patient files from the district hospital between 2014 and 2017. The triage system was implemented in August 2016. Inclusion criteria were children under 15 years of age that entered the emergency centre. Primary outcome was child mortality rate. Secondary outcomes included the percentage agreement between the clinical and non-clinical staff and the duration from triage to first treatment. We used a negative binomial model in STATA 15 to compare mortality rates, and Kappa statistics to estimate the agreement between clinical and non-clinical staff. Results: 4176 admissions were included. The mortality rate ratio (MMR) was 45% lower after the start of the intervention (2016; MRR = 0.55; 0.38, 0.81; p = 0.002), compared to before. To estimate the agreement between non-clinical and clinical staff, 548 (of the 671) patient files were included. The agreement was estimated at 88.7% (Kappa = 0.644; p

PURPOSE:Chronic disease is often associated with a reduced energy level, which limits the capacity to work full-time. This study aims to investigate whether the construct work endurance is part of disability assessment in European countries and what assessment procedures are used. We defined work endurance as the ability to sustain working activities for a number of hours per day and per week. MATERIALS AND METHODS:We conducted a survey using two self-constructed questionnaires. We addressed 35 experts from 19 countries through the European Union of Medicine in Assurance and Social Security (EUMASS). We gathered descriptive data on various aspects of (the assessment of) work endurance. RESULTS:Experts from 16 countries responded. In most countries work endurance is assessed. We found few professional guidelines specific for the assessment of work endurance. Both somatic and mental diseases may cause limited work endurance. Methods to assess work endurance vary, objective methods rating as most suitable. Almost half of the countries report controversies on the assessment of work endurance. CONCLUSIONS:Work endurance is recognised and assessed as an aspect of work disability assessment in Europe. However, controversies exist and evidence based guidelines, including reliable and valid methods to assess work endurance, are lacking.

Whereas progress in HIV testing and treatment has been made globally, the UNAIDS goal of "90 90 90" is still out of sight in rural northern Mozambique. New strategies that promote testing in hard to reach groups will aid Mozambique's response to the HIV epidemic. HIV self-testing (HIVST) is recommended by the WHO as an additional approach to augment the HIV testing services available to adolescents. This study evaluates acceptability and performance of a directly assisted oral HIVST intervention for adolescents in rural Mozambique.Adolescents aged 16-20 years were included at schools and invited to attend the local hospital's youth friendly service for directly assisted oral HIVST. Baseline and post-test questionnaires were obtained. OraQuick Rapid HIV-1/2 Anti body test® was used. Results were read by the participant and by a nurse. Results were confirmed by finger prick HIV test (Determine® HIV 1/2 Alere and Unigold™ HIV Trinity Biotech) according to the Mozambican national standard.Between September and November 2016, 496 adolescents were included, of which 299 performed an oral HIV self-test. 70% were first time testers. The positivity rate was 1.7%. The inter-rater agreement between adolescent and nurse was 99.6% (kappa 0.93); there were no false negative or false positive results of the oral HIV self-test. Five tests were invalid. 7.1% found the test difficult to use. Over 80% preferred directly assisted HIVST compared to the standard finger prick testing. While 20% thought it would be good to do HIVST at home, 76% preferred to do HIVST at the health centre, for reasons including increased security, privacy, and the presence of a counsellor.Directly assisted oral HIVST is a feasible intervention for adolescents in rural Mozambique and showed encouraging results for first time HIV testers.

Chronic renal transplant dysfunction is characterized by loss of renal function and tissue remodeling, including chronic inflammation and lymph vessel formation. Proteoglycans are known for their chemokine presenting capacity. We hypothesize that interruption of the lymphatic chemokine-proteoglycan interaction interferes with the lymphatic outflow of leukocytes from the renal graft and might decrease the anti-graft allo-immune response.In a rat renal chronic transplant dysfunction model (female Dark-Agouti to male Wistar Furth), chemokines were profiled by qRT-PCR in microdissected tubulo-interstitial tissue. Disruption of lymphatic chemokine-proteoglycan interaction was studied by (non-anticoagulant) heparin-derived polysaccharides in vitro and in renal allografts. The renal allograft function was assessed by rise in plasma creatinine and urea.Within newly-formed lymph vessels of transplanted kidneys, numerous CD45+ leukocytes were found, mainly MHCII+, ED-1-, IDO-, HIS14-, CD103- antigen presenting cells, most likely representing a subset of dendritic cells. Treatment of transplanted rats with regular heparin and two different (non-)anticoagulant heparin derivatives revealed worsening of kidney function only in the glycol-split heparin treated group despite a two-fold reduction of tubulo-interstitial leukocytes (p

Some diseases associated with a temporary deterioration in kidney function and/or development of proteinuria show an apparently complete functional remission once the initiating trigger is removed. While it was earlier thought that a transient impairment of kidney function is harmless, accumulating evidence now suggests that these patients are more prone to developing renal failure later in life. We therefore sought to investigate to what extent renal functional changes, inflammation and collagen deposition are reversible after cessation of disease induction, potentially explaining residual sensitivity to damage. Using a rat model of Angiotensin II (Ang II)-induced hypertensive renal disease we show the development of severe hypertension (212 ± 10.43 vs. 146 ± 1.4 mmHg, p

One of the most potent pro-fibrotic cytokines is transforming growth factor (TGFβ). TGFβ is involved in the activation of fibroblasts into myofibroblasts, resulting in the hallmark of fibrosis: the pathological accumulation of collagen. Interleukin-1β (IL1β) can influence the severity of fibrosis, however much less is known about the direct effects on fibroblasts. Using lung and dermal fibroblasts, we have investigated the effects of IL1β, TGFβ1, and IL1β in combination with TGFβ1 on myofibroblast formation, collagen synthesis and collagen modification (including prolyl hydroxylase, lysyl hydroxylase and lysyl oxidase), and matrix metalloproteinases (MMPs). We found that IL1β alone has no obvious pro-fibrotic effect on fibroblasts. However, IL1β is able to inhibit the TGFβ1-induced myofibroblast formation as well as collagen synthesis. Glioma-associated oncogene homolog 1 (GLI1), the Hedgehog transcription factor that is involved in the transformation of fibroblasts into myofibroblasts is upregulated by TGFβ1. The addition of IL1β reduced the expression of GLI1 and thereby also indirectly inhibits myofibroblast formation. Other potentially anti-fibrotic effects of IL1β that were observed are the increased levels of MMP1, -2, -9 and -14 produced by fibroblasts exposed to TGFβ1/IL1β in comparison with fibroblasts exposed to TGFβ1 alone. In addition, IL1β decreased the TGFβ1-induced upregulation of lysyl oxidase, an enzyme involved in collagen cross-linking. Furthermore, we found that lung and dermal fibroblasts do not always behave identically towards IL1β. Suppression of COL1A1 by IL1β in the presence of TGFβ1 is more pronounced in lung fibroblasts compared to dermal fibroblasts, whereas a higher upregulation of MMP1 is seen in dermal fibroblasts. The role of IL1β in fibrosis should be reconsidered, and the differences in phenotypical properties of fibroblasts derived from different organs should be taken into account in future anti-fibrotic treatment regimes.

The role of fibroblast growth factor-2 (FGF-2) in maintaining undifferentiated human embryonic stem cells (hESC) was investigated using a targeted phosphoproteomics approach to specifically profile tyrosine phosphorylation events following FGF-2 stimulation. A cumulative total number of 735 unique tyrosine phosphorylation sites on 430 proteins were identified, by far the largest inventory to date for hESC. Early signaling events in FGF-2 stimulated hESC were quantitatively monitored using stable isotope dimethyl labeling, resulting in temporal tyrosine phosphorylation profiles of 316 unique phosphotyrosine peptides originating from 188 proteins. Apart from the rapid activation of all four FGF receptors, trans-activation of several other receptor tyrosine kinases (RTKs) was observed as well as induced tyrosine phosphorylation of downstream proteins such as PI3-K, MAPK and several Src family members. Both PI3-K and MAPK have been linked to hESC maintenance through FGF-2 mediated signaling. The observed activation of the Src kinase family members by FGF-2 and loss of pluripotent marker expression post Src kinase inhibition may point to the regulation of cytoskeletal and actin depending processes to maintain undifferentiated hESC.

Unraveling the functional dynamics of phosphorylation networks is a crucial step in understanding the way in which biological networks form a living cell. Recently there has been an enormous increase in the number of measured phosphorylation events. Nevertheless, comparative and integrative analysis of phosphoproteomes is confounded by incomplete coverage and biases introduced by different experimental workflows. As a result, we cannot differentiate whether phosphosites indentified in only one or two samples are the result of condition or species specific phosphorylation, or reflect missing data. Here, we evaluate the impact of incomplete phosphoproteomics datasets on comparative analysis, and we present bioinformatics strategies to quantify the impact of different experimental workflows on measured phosphoproteomes. We show that plotting the saturation in observed phosphosites in replicates provides a reproducible picture of the extent of a particular phosphoproteome. Still, we are still far away from a complete picture of the total human phosphoproteome. The impact of different experimental techniques on the similarity between phosphoproteomes can be estimated by comparing datasets from different experimental pipelines to a common reference. Our results show that comparative analysis is most powerful when datasets have been generated using the same experimental workflow. We show this experimentally by measuring the tyrosine phosphoproteome from Caenorhabditis elegans and comparing it to the tyrosine phosphoproteome of HeLa cells, resulting in an overlap of about 4%. This overlap between very different organisms represents a three-fold increase when compared to dataset of older studies, wherein different workflows were used. The strategies we suggest enable an estimation of the impact of differences in experimental workflows on the overlap between datasets. This will allow us to perform comparative analyses not only on datasets specifically generated for this purpose, but also to extract insights through comparative analysis of the ever-increasing wealth of publically available phosphorylation data.