Dietary fat induced chylomicron-mediated LPS translocation in a bicameral Caco-2cell model.

BACKGROUND: There is increasing evidence that dietary fat, especially saturated fat, promotes the translocation of lipopolysaccharide (LPS) via chylomicron production in the gut. Chylomicrons can subsequently transport LPS to other parts of the body, where they can induce low-grade chronic inflammation that is linked to various metabolic and gut-related diseases. To identify promising (food) compounds that can prevent or ameliorate LPS-related low-grade inflammation, we developed and optimized a bicameral in vitro model for dietary fat-induced LPS translocation that closely mimics the in vivo situation and facilitates high-throughput screening. METHODS: Caco-2 cells were cultured in monolayers and differentiated to a small intestinal phenotype in 21 days. Thereafter, optimal conditions for fat-induced chylomicron production were determined by apical exposure of Caco-2 cells to a dilution range of in vitro digested palm oil and sunflower oil, optionally preceded by a 1-week apical FBS deprivation (cultured without apical fetal bovine serum). Chylomicron production was assessed by measuring basolateral levels of the chylomicron-related marker apolipoprotein B. Next, LPS was coincubated at various concentrations with the digested oils, and fat-induced LPS translocation to the basolateral side was assessed. RESULTS: We found that dietary fat-induced LPS translocation in Caco-2 cells was optimal after apical exposure to digested oils at a 1:50 dilution in combination with 750 ng/mL LPS, preceded by 1 week of apical FBS deprivation. Coincubation with the chylomicron blocker Pluronic L81 confirmed that fat-induced LPS translocation is mediated via chylomicron production in this Caco-2 cell model. CONCLUSION: We developed a robust Caco-2 cell model for dietary fat-induced LPS translocation that can be used for high-throughput screening of (food) compounds that can reduce LPS-related low-grade inflammation.

Assessing the dynamic changes in vitiligo: reliability and validity of the Vitiligo Disease Activity Score (VDAS) and Vitiligo Disease Improvement Score (VDIS).

BACKGROUND: The assessment of the individual evolution of vitiligo is important for therapeutic decision making in daily practice. A fast, simple and validated physician-reported score to assess clinical changes in depigmentation over time in separate parts (activity and improvement) is currently missing. OBJECTIVE: The main objective of the study was to develop and validate the Vitiligo Disease Activity Score (VDAS) and Vitiligo Disease Improvement Score (VDIS). METHODS: The Vitiligo Disease Activity Score (VDAS) and Vitiligo Disease Improvement Score (VDIS) were evaluated based on a photo set of 66 patients with two different time points. In the first (short) version, only the number of changing body regions was counted based on 15 predefined areas (VDAS15 and VDIS15 ), while in the second (extensive) version the degree of worsening or improvement from +4 to -4 for each body area was added for a more detailed assessment (VDAS60 and VDIS60 ). Content and construct validity were tested. In addition inter-, intrarater reliability and feasibility were evaluated by 7 (test) and 5 (retest) physicians. RESULTS: Evidence for content and construct validity was provided. Overall, VDAS15 , VDIS15 , VDAS60 and VDIS60 demonstrated good to excellent inter-rater reliability [intraclass correlation (ICC): VDAS: range = 0.797-0.900; VDIS: range = 0.726-0.798]. The intrarater reliability ICCs were 0.865 and 0.781 for the VDAS15 and VDIS15 , respectively. Similar results were obtained for the VDAS60 and VDIS60 (ICC = 0.913 and 0.800, respectively). Completion time was short (median: 122 s/patient (first round); 95 s/patient (second round)]. LIMITATIONS: Single tertiary centre mainly of skin phototype 2 to 3. CONCLUSION: The VDAS and VDIS appear to be valid, reliable and feasible instruments to score the evolution of vitiligo lesions. This accommodates the current urgent need for a simple, standardized and practical assessment of vitiligo activity and improvement over time.

Characteristics of chest pain in COVID-19 patients in the emergency department.

INTRODUCTION: Patients with coronavirus disease 2019 (COVID-19) can present with chest pain. However, the characteristics of this chest pain are unknown. We performed a single-centre observational study to review and summarise chest pain characteristics in COVID-19 patients at first presentation to the emergency department (ED). METHODS: We collected data on characteristics of 'chest pain' reported by COVID-19 patients who attended the ED of Bernhoven Hospital, the Netherlands from 4 through 30 March 2020. RESULTS: We included 497 COVID-19 patients, of whom 83 (17%) reported chest pain upon presentation to the ED. Chest pain characteristics were: present since disease onset (88%), retrosternal location (43%), experienced as compressing/pressure pain (61%), no radiation (61%) and linked to heavy coughing (39%). Patients who reported chest pain were younger than those without chest pain (61 vs 73 years; p < 0.001). Patients with syncope were older (75 vs 72 years; p = 0.017), had a shorter duration of symptoms (5 vs 7 days; p < 0.001) and reported fewer respiratory complaints (68% vs 90%; p < 0.001) than those without syncope. Patients with new-onset atrial arrhythmias presented with a shorter duration of symptoms (5 vs 7 days; p = 0.013), experienced fewer respiratory complaints (72% vs 89%; p = 0.012) and more frequently had a history of cardiovascular disease (79% vs 50%; p = 0.003) than patients who presented without arrythmias. CONCLUSION: Chest pain and other cardiac symptoms were frequently observed in COVID-19 patients. Treating physicians should be aware that chest pain, arrhythmias and syncope can be presenting symptoms of COVID-19.

Decision making in treatment of symptomatic severe aortic stenosis: a survey study in Dutch heart centres.

AIM: To provide insight into the basic characteristics of decision making in the treatment of symptomatic severe aortic stenosis (SSAS) in Dutch heart centres with specific emphasis on the evaluation of frailty, cognition, nutritional status and physical functioning/functionality in (instrumental) activities of daily living [(I)ADL]. METHODS: A questionnaire was used that is based on the European and American guidelines for SSAS treatment. The survey was administered to physicians and non-physicians in Dutch heart centres involved in the decision-making pathway for SSAS treatment. RESULTS: All 16 Dutch heart centres participated. Before a patient case is discussed by the heart team, heart centres rarely request data from the referring hospital regarding patients' functionality (n = 5), frailty scores (n = 0) and geriatric consultation (n = 1) as a standard procedure. Most heart centres 'often to always' do their own screening for frailty (n = 10), cognition/mood (n = 9), nutritional status (n = 10) and physical functioning/functionality in (I)ADL (n = 10). During heart team meetings data are 'sometimes to regularly' available regarding frailty (n = 5), cognition/mood (n = 11), nutritional status (n = 8) and physical functioning/functionality in (I)ADL (n = 10). After assessment in the outpatient clinic patient cases are re-discussed 'sometimes to regularly' in heart team meetings (n = 10). CONCLUSIONS: Dutch heart centres make an effort to evaluate frailty, cognition, nutritional status and physical functioning/functionality in (I)ADL for decision making regarding SSAS treatment. However, these patient data are not routinely requested from the referring hospital and are not always available for heart team meetings. Incorporation of these important data in a structured manner early in the decision-making process may provide additional useful information for decision making in the heart team meeting.

Expanding the time interval between ovulation triggering and oocyte injection: does it affect the embryological and clinical outcome?

STUDY QUESTION: Is the time interval between ovulation triggering and oocyte denudation/injection associated with embryological and clinical outcome after ICSI? SUMMARY ANSWER: Expanding the time interval between ovulation triggering and oocyte denudation/injection is not associated with any clinically relevant impact on embryological or clinical outcome. WHAT IS KNOWN ALREADY: The optimal time interval between ovulation triggering and insemination/injection appears to be 38-39 h and most authors agree that an interval of >41 h has a negative influence on embryological and clinical pregnancy outcomes. However, in ART centres with a heavy workload, respecting these exact time intervals is frequently challenging. Therefore, we questioned to what extent a wider time interval between ovulation triggering and oocyte injection would affect embryological and clinical outcome in ICSI cycles. STUDY DESIGN, SIZE, DURATION: A single-centre retrospective cohort analysis was performed including 8811 ICSI cycles from 2010 until 2015. Regarding the time interval between ovulation triggering and oocyte injection, seven categories were considered: <36 h, 36 h, 37 h, 38 h, 39 h, 40 h and ≥41 h. In all cases, denudation was performed immediately prior to injection. The main outcome measures were oocyte maturation, fertilization and embryo utilization rate (embryos adequate for transfer or cryopreservation) per fertilized oocyte. Clinical pregnancy rate (CPR) and live birth rate (LBR) were considered as secondary outcomes. Utilization rate, CPR and LBR were subdivided into two groups according to the day of embryo transfer: Day 3 or Day 5. PARTICIPANTS/MATERIALS, SETTING, METHODS: During the study period, oocyte retrieval was routinely performed 36 h post-triggering except in the <36 h group. The interval of <36 h occurred only if OR was carried out before the planned 36 h trigger interval and was followed by immediate injection. Only cycles with fresh autologous gametes were included. The exclusion criteria were: injection with testicular/epididymal sperm, managed natural cycles, conventional IVF, combined conventional IVF/ICSI, preimplantation genetic testing and IVM cycles. Female age, number of oocytes, pre-preparation sperm concentration, post-preparation sperm concentration and motility, day of transfer, number of embryos transferred and quality of the best embryo transferred were identified as potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Among the seven interval groups, adjusted mean maturation rates ranged from 76.4% to 83.2% and differed significantly (P < 0.001). Similarly, there was a significant difference in adjusted mean fertilization rates (range 69.2-79.3%; P < 0.001). The adjusted maturation and fertilization rates were significantly higher when denudation/injection was performed >41 h post-triggering compared to 38 h post-triggering (reference group). Oocyte denudation/injection at <36 h post-triggering had no significant effect on maturation, fertilization or embryo utilization rates compared to injection at 38 h. No effect of the time interval was observed on CPRs and LBRs, after adjusting for potential confounders. When oocyte injection was performed before 36 h the adjusted analysis showed that compared to 38 h after ovulation triggering the chance of having a live birth tends to be lower although the difference was not statistically significant (odds ratio 0.533, 95% CI: 0.252-1.126; P = 0.099). Injection ≥41 h post-triggering did not affect LBR compared to injection at 38 h post-ovulation. LIMITATIONS, REASONS FOR CAUTION: As this is a large retrospective study, the influence of uncontrolled variables cannot be excluded. These results should not be extrapolated to other ART procedures such as IVM, conventional IVF or injection with testicular/epididymal sperm. WIDER IMPLICATIONS OF THE FINDINGS: Our results indicate that the optimal injection time window may be less stringent than previously thought as both embryological and clinical outcome parameters were not significantly affected in our analysis. This is reassuring for busy ART centres that might not always be able to follow strict time intervals. STUDY FUNDING/COMPETING INTEREST(S): No funding. The authors declare no conflict of interest related to the present study. TRIAL REGISTRATION NUMBER: N/A.

Parameters of poor prognosis in preimplantation genetic testing for monogenic disorders.

STUDY QUESTION: What is the likelihood of success of a single cycle of preimplantation genetic testing for monogenic disorders (PGT-M), measured as the cumulative live birth rate (CLBR) and based on various patient demographics? SUMMARY ANSWER: For all women aged ≤40 years, the CLBR was at least 10% when the number of oocytes was ≥7 (range 10-30%) or was at least 5% when the number of oocytes was ≥3 (range 5-17%). WHAT IS KNOWN ALREADY: The number of oocytes is significantly associated with the number of embryos for genetic testing and the clinical outcome in PGT-M. Embryos diagnosed as affected or embryos that remain without diagnosis cannot be used for embryo transfer. The size of the group of embryos non-suitable for transfer varies between 25% and 81%, depending on the indication. Thus, PGT-M is more likely to be more severely impacted by suboptimal ovarian response, poor fertilization and suboptimal embryo development than conventional IVF/ICSI schemes without PGT. STUDY DESIGN, SIZE, DURATION: This was a single-centre retrospective comparative cohort study, of cycles between January 2011 and December 2015. A total number of 2265 PGT-M cycles were compared to 2833 conventional ICSI cycles. The principal aim of our study was the identification of the parameters of poor CLBR in couples undergoing PGT-M using multiplex short tandem repeat (STR) markers on blastomere biopsy DNA. The secondary aim was to compare the parameters of poor CLBR of the PGT-M population to those of couples undergoing ICSI without PGT. PARTICIPANTS/MATERIALS, SETTING, METHODS: The baseline characteristics of the PGT-M group were compared to the conventional ICSI group. A multiple regression analysis was applied to account for the following potential confounding factors: female age, number of previous ART cycles, number of oocytes/suitable embryos for transfer and dosage of gonadotrophins used for ovarian stimulation. MAIN RESULTS AND THE ROLE OF CHANCE: The PGT-M group was younger (female age 32.0 vs 34.5 years), had a higher number of previous ART cycles (1.1 vs 0.9 cycles) and used more gonadotrophins (2367 vs 1984 IU). Per cycle, the PGT-M group had more retrieved oocytes (11.8 vs 8.3 oocytes), fewer suitable embryos for transfer (1.7 vs 2.8 embryos) and a lower CLBR (29.4% vs 35.0%). Multiple regression analysis showed that the CLBR in the PGT-M group was significantly influenced by female age, the number of previous ART cycles, the number of oocytes and the dose of ovarian stimulation. In both groups, the predicted CLBR increased with increasing numbers of oocytes and suitable embryos. At least two retrieved oocytes or one embryo per single PGT-M cycle could confer an estimated CLBR above 10%. By assessing female age and the number of retrieved oocytes together, it was shown that for all women aged ≤40 years, the predicted CLBR per single PGT-M cycle was ≥10% when the number of oocytes was ≥7 or was ≥5% when the number of oocytes was ≥3. LIMITATIONS, REASONS FOR CAUTION: Despite the large sample size, the findings are confined by limited confounder adjustment and the lack of specific PGT-M comparators. WIDER IMPLICATIONS OF THE FINDINGS: This study aimed to describe the likelihood of success of PGT-M treatment, measured as CLBR, based on various patient demographics. In a PGT-M program, couples need to be informed of the prognosis more specifically when it is futile. The table of predicted CLBRs presented in this study is a useful tool in counselling PGT-M couples for making reproductive choices. STUDY FUNDING/COMPETING INTEREST(S): No funding was required and there are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Measuring Activated Clotting Time during Cardiac Catheterization and PCI: The Effect of the Sampling Site.

RESULTS: In 100 patients (mean age 67.1, 65% male), no significant differences were observed in ACT values obtained from the guiding catheter and arterial sheath (mean difference (MD) -18.3 s; standard deviation (SD) 96 s; P=0.067). Contrarily, ACT values obtained from the intravenous line were significantly lower as compared to values obtained from the guiding catheter (MD 25.7 s; SD 75.5; P=0.003) and arterial sheath (MD 39 s; SD 102.8; P < 0.001). Furthermore, ACT measurements from the arterial sheath showed a statistically significant proportional bias when compared to the other sampling sites (sheath vs. catheter, r = 0.761, P=0.001; sheath vs. IVL, r = 1.013, P < 0.001). CONCLUSIONS: The present study shows statistical significance and possibly clinically relevant variations between ACT measurements from different sample sites. Bias in ACT measurements may be minimized by using uniform protocols for ACT measurement during cardiac catheterization.

2020 ESC Guidelines on acute coronary syndrome without ST-segment elevation : Recommendations and critical appraisal from the Dutch ACS and Interventional Cardiology working groups.

Recently, the European Society of Cardiology (ESC) has updated its guidelines for the management of patients with acute coronary syndrome (ACS) without ST-segment elevation. The current consensus document of the Dutch ACS working group and the Working Group of Interventional Cardiology of the Netherlands Society of Cardiology aims to put the 2020 ESC Guidelines into the Dutch perspective and to provide practical recommendations for Dutch cardiologists, focusing on antiplatelet therapy, risk assessment and criteria for invasive strategy.

Cardiovascular disease risk and its determinants in people living with HIV across different settings in South Africa.

OBJECTIVES: Socio-economic factors and lifestyle are known to differ across geographies and populations, which may result in distinct risk profiles for cardiovascular disease (CVD). This study assessed carotid intima-media thickness (CIMT), a proxy for CVD, and its determinants in two groups of people living with HIV (PLHIV) in two different settings in South Africa. METHODS: A cross-sectional analysis was conducted comparing data from the Ndlovu Cohort Study in the Limpopo Province (group 1) and from three clinical trials in Johannesburg (group 2). The association between demographics, conventional CVD risk factors, HIV-related factors and CIMT in groups 1 and 2 was analysed with two separate multivariable linear regression models. RESULTS: Group 1 consisted of 826 participants (mean age 42.2 years) and mean (± standard deviation) CIMT was 0.626 ± 0.128 mm. In this group, sex, age, body mass index (BMI), cholesterol, glucose and antiretroviral therapy (ART) duration (ß = 0.011 mm per 5 years; P = 0.02) were associated with higher CIMT. There were positive interactions between age and ART duration and age and cholesterol. Group 2 consisted of 382 participants (mean age 39.5 years) and mean (± standard deviation) CIMT was 0.560 ± 0.092 mm. In this group, only sex, education level, BMI and cholesterol were associated with higher CIMT, albeit with weaker associations than in group 1. CONCLUSIONS: Conventional CVD risk factors were the main drivers of CIMT. The impact of some of these risk factors appeared to increase with age. Differences in sample size, age and viral suppression might explain why an effect of ART was observed in group 1 but not in group 2.

Preimplantation genetic testing with HLA matching: from counseling to birth and beyond.

Preimplantation genetic testing-human leukocyte antigen '(PGT-HLA) only' refers to the HLA typing of single or few cells biopsied from in vitro fertilized preimplantation embryos. The aim of the procedure is to establish a pregnancy, in which the fetus is HLA compatible with an affected sibling in need of a hematopoietic stem cell transplantation (HSCT). During PGT-M-HLA, the identification of a HLA-compatible embryo is combined with the detection of mutation(s) underlying immunodeficiencies and hemoglobinopathies. We report a combined retrospective and prospective cohort analysis of PGT-(M-)HLA procedures carried out from 1998 until 2017, with follow-up of transplantations to 2019. During the study period, 234 couples from 22 countries were invited for a multidisciplinary consultation. Two couples were rejected and 70 couples declined (various reasons), leaving 162 couples for which 414 clinical cycles were carried out. Cleavage stage biopsy followed by single-cell multiplex PCR for short tandem repeat-based haplotyping was applied in most cases (98.7%). The diagnostic efficiency was high (94.8%) but only 16.5% of the embryos was genetically suitable for transfer. Fresh and frozen-thawed embryo transfer resulted in 67 clinical pregnancies, 63 deliveries, and 74 live births, of which 60 children were HLA compatible. This yielded a live birth delivery rate of 30.3% per transfer. Information on neonatal characteristics of the matching PGT-(M-)HLA children showed reassuring outcomes. So far, HSCT was carried out successfully for 25 out of 26 cases. In conclusion, our data show that PGT-(M-)HLA is a valuable procedure: the high complexity and limited delivery rate are balanced by the successful HSCT outcome and the positive impact on families.

Mucin expression in gastric- and gastro-oesophageal signet-ring cell cancer: results from a comprehensive literature review and a large cohort study of Caucasian and Asian gastric cancer.

BACKGROUND: The literature on the prognostic relevance of signet-ring cell (SRC) histology in gastric cancer (GC) is controversial which is most likely related to inconsistent SRC classification based on haematoxylin-eosin staining. We hypothesised that mucin stains can consistently identify SRC-GC and predict GC patient outcome. METHODS: We performed a comprehensive literature review on mucin stains in SRC-GC and characterised the mucin expression in 851 Caucasian GC and 410 Asian GC using Alcian Blue (AB)-Periodic Acid-Schiff (PAS), MUC2 (intestinal-type mucin), and MUC5AC (gastric-type mucin). The relationship between mucin expression and histological phenotype [poorly cohesive (PC) including proportion of SRCs, non-poorly cohesive (non-PC), or mucinous (MC)], clinicopathological variables, and patient outcome was analysed. RESULTS: Depending on mucin expression and cut-offs, the positivity rates of SRC-GC reported in the literature varied from 6 to 100%. Patients with MUC2 positive SRC-GC or SRC-GC with (gastro)intestinal phenotype had poorest outcome. In our cohort study, PC with ≥ 10% SRCs expressed more frequently MUC2, MUC5AC, and ABPAS (p < 0.001, p = 0.004 and p < 0.001, respectively). Caucasians with AB positive GC or combined ABPAS-MUC2 positive and MUC5AC negative had poorest outcome (all p = 0.002). This association was not seen in Asian patients. CONCLUSIONS: This is the first study to suggest that mucin stains do not help to differentiate between SRC-GC and non-SRC-GC. However, mucin stains appear to be able to identify GC patients with different outcome. To our surprise, the relationship between outcome and mucin expression seems to differ between Caucasian and Asian GC patients which warrants further investigations.

Factors influencing the clinical outcome of preimplantation genetic testing for polycystic kidney disease.

STUDY QUESTION: What are the factors influencing the success rate for couples undergoing preimplantation genetic testing (PGT) for polycystic kidney disease (PKD)? SUMMARY ANSWER: In our study cohort, the live birth delivery rate is significantly associated with female age while the male infertility accompanying autosomal dominant PKD (ADPKD) does not substantially affect the clinical outcome. WHAT IS KNOWN ALREADY: While women with ADPKD have no specific fertility problems, male ADPKD patients may present with reproductive system abnormalities and infertility. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study involves 91 PGT cycles for PKD for 43 couples (33 couples for PKD1, 2 couples for PKD2 and 8 couples for autosomal recessive PKD (ARPKD)) from January 2005 until December 2016 with follow-up of transfers until end of 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sixteen single-cell clinical tests for PKD based on multiplex PCR of short tandem repeat markers, with or without a specific mutation were developed and applied for diagnosis of 584 Day 3 cleavage stage embryos. In 18 couples, the male partner was affected with ADPKD (=Group A) and 12 of them had a documented infertility status. Group A underwent 52 cycles to oocyte retrieval. For 18 other couples, the female partner was affected with ADPKD (=Group B) and four male partners from this group had a documented history of infertility. This group underwent 31 cycles to OR. MAIN RESULTS AND THE ROLE OF CHANCE: Genetic analysis resulted in 545 embryos (93.3%) with a diagnosis, of which 215 (36.8%) were genetically transferable. Transfer of 74 embryos in 53 fresh cycles and of 34 cryopreserved embryos in 33 frozen-warmed embryo transfer cycles resulted in a live birth delivery rate of 38.4% per transfer with 31 singleton live births, two twin live births and one ongoing pregnancy. The observed cumulative delivery rate was 57.8% per couple after five treatment cycles. Thirty cryopreserved embryos still remain available for transfer. The clinical pregnancy rate per transfer (fresh + frozen; 45.9% in group A versus 60.0% in group B, P < 0.05) and the live birth delivery rate per transfer (fresh + frozen; 27.0% in group A versus 42.9% in group B, P < 0.05) was significantly lower for couples with the male partner affected with ADPKD compared with couples with the female partner affected with ADPKD. However, a multivariate logistic regression analysis showed that only female age was associated with live birth delivery rate (odds ratio = 0.87; 95% CI: 0.77-0.99; P = 0.032). LIMITATIONS, REASONS FOR CAUTION: This study is based on retrospective data from a single centre with Day 3 one-cell and two-cell biopsy. Further analysis of a larger cohort of PKD patients undergoing PGT is required to determine the impact of male infertility associated with ADPKD on the cumulative results. WIDER IMPLICATIONS OF THE FINDINGS: Knowledge about factors affecting the clinical outcome after PGT can be a valuable tool for physicians to counsel PKD patients about their reproductive options. Males affected with ADPKD who suffer from infertility should be advised to seek treatment in time to improve their chances of conceiving a child. STUDY FUNDING/COMPETING INTEREST(S): No funding was obtained. There are no competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Correction to: Cardiovascular causes of sudden unexpected death in children and adolescents (0-17 years) : A nationwide autopsy study in the Netherlands.

Correction to:Neth Heart J 2018 https://doi.org/10.1007/s12471-018-1152-y In the version of the article originally published online, there was an error in the 'Methods and results' section of the Abstract. It is stated that 'In the 10-14 year group, hypertrophic cardiomyopathy (n = 1) and ruptured ….

[Geriatric rehabilitation care: Doing the right things right]. / Geriatrische Revalidatiezorg: De juiste dingen goed doen.

BACKGROUND: Geriatric rehabilitation concerns short-term integrated multidisciplinary care aimed at functional recovery and social participation for relatively frail elderly. Given the geriatric clients' complex care issues, nurses should possess sufficient and appropriate competencies in order to identify and assess the relevant symptoms and intervene effectively. Yet, nurses experience a certain apprehensiveness to perform their tasks and express difficulties in multidisciplinary communication and collaboration in a constructive manner. In addition to the client's and informal care giver's perception of their input in the geriatric rehabilitation process, this study provides an in-depth understanding of the way nurses perceive their role in geriatric rehabilitation. METHODS/DESIGN: This descriptive study entails a quantitative and a qualitative component. The quantitative component concerns questionnaires for clients, informal care givers, nurses, and team leaders. The qualitative component aims to obtain in-depth information (i. e. opinions, meanings, and reflections) with regard to the decision making process and the performance of the rehabilitation care by means of open-ended questions (in the questionnaire) and semi-structured interviews. RESULTS: Clients and informal care givers rate specific themes in geriatric rehabilitation in a more negative light than nurses and team leaders do. These themes concern the provision of information in the hospital (prior to admission in the rehabilitation facility), involvement in the draw-up of the treatment plan and rehabilitation goals, geriatric rehabilitation as a 24/7 activity, and taking into account the client's other life events. The latter three findings in particular, are caused by nurses' apprehensiveness to perform their tasks adequately. DISCUSSION: Nurses working in geriatric rehabilitation, experience apprehensiveness to perform their tasks adequately. Uncertainty about the client's reaction or fear of damaging the relationship of trust, results in nurses not involving the clients and informal care givers in the draw-up of the rehabilitation goals. Apprehensiveness also submerges as the lack of experience or specific competences in considering the client's other life events. The recommendations address these aspects in particular.

Cardiovascular causes of sudden unexpected death in children and adolescents (0-17 years) : A nationwide autopsy study in the Netherlands.

BACKGROUND: Little is known about the causes of unexpected death in minors (0-17 years). In young adults an important cause is cardiovascular disease, with primary arrhythmogenic disorders, atherosclerotic events, cardiomyopathies and myocarditis as main contributors. The aim of this autopsy study was to determine the contribution of cardiovascular disease to unexpected death in minors. METHODS AND RESULTS: In the Netherlands, systematic investigation of all cases of unexplained death in minors was compulsory in a nationwide governmental project during a 15-month period. Autopsies were performed according to a standardised protocol (autopsy rate 85%). A cardiovascular cause of death was found in 13/56 cases (23%). In the group <1 year, the main cardiovascular causes were various congenital defects (n = 3) and myocarditis (n = 2). In the 1-9 year group, no cardiovascular causes were found. In the 10-14 year group, coronary anomalies (n = 2) and arrhythmogenic cardiomyopathy (n = 1) were observed. In the 15­17 year group, hypertrophic cardiomyopathy (n = 1) and ruptured ascending aortic aneurysm (n = 1) were among the observed cardiovascular causes [corrected]. In 14/56 (25%) cases autopsy revealed no structural abnormalities that could explain the sudden death, mostly in the group <1 year. CONCLUSION: This national cohort with a high autopsy rate reveals a high incidence (23%) of cardiovascular diseases as the pathological substrate of sudden unexpected death in children. Another high percentage of minors (25%) showed no structural abnormalities, with the possibility of a genetic arrhythmia. These findings underline the importance of systematic autopsy in sudden death in minors, with implications for cardiogenetic screening of relatives.

General, but not myeloid or type II lung epithelial cell, myeloid differentiation factor 88 deficiency abrogates house dust mite induced allergic lung inflammation.

Asthma is a highly prevalent chronic allergic inflammatory disease of the airways affecting people worldwide. House dust mite (HDM) is the most common allergen implicated in human allergic asthma. HDM-induced allergic responses are thought to depend upon activation of pathways involving Toll-like receptors and their adaptor protein myeloid differentiation factor 88 (MyD88). We sought here to determine the role of MyD88 in myeloid and type II lung epithelial cells in the development of asthma-like allergic disease using a mouse model. Repeated exposure to HDM caused allergic responses in control mice characterized by influx of eosinophils into the bronchoalveolar space and lung tissue, lung pathology and mucus production and protein leak into bronchoalveolar lavage fluid. All these responses were abrogated in mice with a general deficiency of MyD88 but unaltered in mice with MyD88 deficiency, specifically in myeloid or type II lung epithelial cells. We conclude that cells other than myeloid or type II lung epithelial cells are responsible for MyD88-dependent HDM-induced allergic airway inflammation.

Effectiveness of Africa's tropical protected areas for maintaining forest cover.

The effectiveness of parks for forest conservation is widely debated in Africa, where increasing human pressure, insufficient funding, and lack of management capacity frequently place significant demands on forests. Tropical forests house a substantial portion of the world's remaining biodiversity and are heavily affected by anthropogenic activity. We analyzed park effectiveness at the individual (224 parks) and national (23 countries) level across Africa by comparing the extent of forest loss (as a proxy for deforestation) inside parks to matched unprotected control sites. Although significant geographical variation existed among parks, the majority of African parks had significantly less forest loss within their boundaries (e.g., Mahale Park had 34 times less forest loss within its boundary) than control sites. Accessibility was a significant driver of forest loss. Relatively inaccessible areas had a higher probability (odds ratio >1, p < 0.001) of forest loss but only in ineffective parks, and relatively accessible areas had a higher probability of forest loss but only in effective parks. Smaller parks less effectively prevented forest loss inside park boundaries than larger parks (T = -2.32, p < 0.05), and older parks less effectively prevented forest loss inside park boundaries than younger parks (F2,154 = -4.11, p < 0.001). Our analyses, the first individual and national assessment of park effectiveness across Africa, demonstrated the complexity of factors (such as geographical variation, accessibility, and park size and age) influencing the ability of a park to curb forest loss within its boundaries.

Process evaluation of the implementation of scorecard-based antenatal risk assessment, care pathways and interdisciplinary consultation: the Healthy Pregnancy 4 All study.

OBJECTIVE: To evaluate the implementation of a complex intervention in the antenatal healthcare field in 14 Dutch municipalities. The intervention consisted of the implementation of a systematic scorecard-based risk assessment in pregnancy, subsequent patient-tailored care pathways, and consultations of professionals from different medical and social disciplines. METHODS: Saunders's seven-step method was used for the development of a programme implementation monitoring plan, with specific attention to the setting and context of the programme. Data were triangulated from multiple sources, and prespecified criteria were applied to examine the evidence for implementation. RESULTS: Six out of 11 municipalities (54%) met the implementation criteria for the entire risk assessment programme, whereas three municipalities (27%) met the criteria if the three components of implementation were analysed separately. CONCLUSIONS: A process evaluation of implementation of a complex intervention is possible. The results can be used to improve understanding of the associations between specific programme elements and programme outcomes on effectiveness of the intervention. Additionally, the results are important for formative purposes to assess how future implementation of antenatal risk assessment can be improved in comparable contexts.

A novel approach to detect test-seeking behaviour in the blood donor population: making the invisible visible.

BACKGROUND AND OBJECTIVES: Individuals may donate blood in order to determine their infection status after exposure to an increased infection risk. Such test-seeking behaviour decreases transfusion safety. Instances of test seeking are difficult to substantiate as donors are unlikely to admit to such behaviour. However, manifestation in a population of repeat donors may be determined using statistical inference. MATERIALS AND METHODS: Test-seeking donors would be highly motivated to donate following infection risk, influencing the timing of their donation. Donation intervals within 2005-2014 of all Dutch blood donors who acquired syphilis (N = 50), HIV (N = 13), HTLV (N = 4) or HCV (N = 2) were compared to donation intervals of uninfected blood donors (N = 7 327 836) using the Anderson-Darling test. We adjusted for length bias as well as for age, gender and donation type of the infected. Additionally, the power of the proposed method was investigated by simulation. RESULTS: Among the Dutch donors who acquired infection, we found only a non-significant overrepresentation of short donation intervals (P = 0·54). However, we show by simulation that both relatively short and long donation intervals among infected donors can reveal test seeking. The power of the method is >90% if among 69 infected donors >35 (51%) are test seeking, or if among 320 infected donors >90 (30%) are test seeking. CONCLUSION: We show how statistical analysis may be used to reveal the extent of test seeking in repeat blood donor populations. In the Dutch setting, indications for test-seeking behaviour were not statistically significant. This may, however, be due to the low number of infected individuals.

A review of biophysical and socio-economic effects of unconventional oil and gas extraction - Implications for South Africa.

The impacts associated with unconventional oil and gas (UOG) extraction will be cumulative in nature and will most likely occur on a regional scale, highlighting the importance of using strategic decision-making and management tools. Managing possible impacts responsibly is extremely important in a water scarce country such as South Africa, versus countries where more water may be available for UOG extraction activities. This review article explains the possible biophysical and socio-economic impacts associated with UOG extraction within the South African context and how these complex impacts interlink. Relevant policy and governance frameworks to manage these impacts are also highlighted.