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Background: Neuroinflammation and Alzheimer's disease (AD) co-pathology may contribute to disease progression and severity in dementia with Lewy bodies (DLB). This study aims to clarify whether a different pattern of neuroinflammation, such as alteration in microglial and astroglial morphology and distribution, is present in DLB cases with and without AD co-pathology. Methods: The morphology and load (% area of immunopositivity) of total (Iba1) and reactive microglia (CD68 and HLA-DR), reactive astrocytes (GFAP) and proteinopathies of alpha-synuclein (KM51/pser129), amyloid-beta (6 F/3D) and p-tau (AT8) were assessed in a cohort of mixed DLB + AD (n = 35), pure DLB (n = 15), pure AD (n = 16) and control (n = 11) donors in limbic and neocortical brain regions using immunostaining, quantitative image analysis and confocal microscopy. Regional and group differences were estimated using a linear mixed model analysis. Results: Morphologically, reactive and amoeboid microglia were common in mixed DLB + AD, while homeostatic microglia with a small soma and thin processes were observed in pure DLB cases. A higher density of swollen astrocytes was observed in pure AD cases, but not in mixed DLB + AD or pure DLB cases. Mixed DLB + AD had higher CD68-loads in the amygdala and parahippocampal gyrus than pure DLB cases, but did not differ in astrocytic loads. Pure AD showed higher Iba1-loads in the CA1 and CA2, higher CD68-loads in the CA2 and subiculum, and a higher astrocytic load in the CA1-4 and subiculum than mixed DLB + AD cases. In mixed DLB + AD cases, microglial load associated strongly with amyloid-beta (Iba1, CD68 and HLA-DR), and p-tau (CD68 and HLA-DR), and minimally with alpha-synuclein load (CD68). In addition, the highest microglial activity was found in the amygdala and CA2, and astroglial load in the CA4. Confocal microscopy demonstrated co-localization of large amoeboid microglia with neuritic and classic-cored plaques of amyloid-beta and p-tau in mixed DLB + AD cases. Conclusions: In conclusion, microglial activation in DLB was largely associated with AD co-pathology, while astrocytic response in DLB was not. In addition, microglial activity was high in limbic regions, with prevalent AD pathology. Our study provides novel insights into the molecular neuropathology of DLB, highlighting the importance of microglial activation in mixed DLB + AD. [ABSTRACT FROM AUTHOR]

Objective: To study whether intrauterine application of auto-crosslinked polymers of hyaluronic acid (ACP) gel after dilation and curettage (D&C) improves reproductive outcomes.Design: Follow-up of a prospective randomized trial.Setting: University and university-affiliated teaching hospitals.Patient(s): Women with a miscarriage at <14 weeks' gestation with at least one previous D&C were randomized to D&C plus ACP gel (intervention) or D&C alone (control). A hysteroscopy was performed after 8-12 weeks, and if intrauterine adhesion (IUAs) were encountered, adhesiolysis was executed.Intervention(s): Participants received a questionnaire 30 months after treatment.Main Outcome Measure(s): Ongoing pregnancy and outcome of subsequent pregnancies.Result(s): Ongoing pregnancies were recorded in 74.6% (50/67) of the intervention group versus 67.2% (43/64) of the control group, and in, respectively, 94.3% (50/53) versus 71.7% (43/60) in the women wishing to conceive. The median times to conception leading to a live birth were, respectively, 21.9 versus 36.1 months. Reduced menstrual blood loss was reported in 7.5% (5/67) versus 20.3% (13/64) and dysmenorrhea in 14.9% (10/67) versus 34.4% (22/64), respectively.Conclusion(s): Application of ACP gel following D&C performed after miscarriage seems to have a favorable effect on subsequent reproductive outcomes in women with at least one previous D&C. Given the fact that the study was not powered for reproductive outcomes, the data should be interpreted with caution. The effect may be underestimated due to routine removal of IUAs.Dutch Clinical Trial Registry Number: NTR 3120. [ABSTRACT FROM AUTHOR]

Objective: To answer the questions: Are perinatal reproductive hormone profiles different in case of a twin compared with a singleton pregnancy? Are reproductive endocrine profiles of twin girls influenced by their male co-twin and vice versa?Design: Prospective cohort study from January 2004 to October 2009.Setting: Not applicable.Patient(s): A total of 204 mothers of twins and 248 singleton control subjects, aged >18 years, pregnant with a twin or singleton and no endocrine disease or malignancy.Intervention(s): Blood samples were collected at mid-gestation from the mother and at delivery from the mothers and the umbilical cords. Estrogens, androgens, sex hormone-binding globulin, progesterone, and gonadotropins were measured.Main Outcome Measure(s): Hormonal profiles were compared between singletons and twins, different types of twins, and opposite-sex and same-sex twins.Result(s): Estrogen and progesterone concentrations were higher in mothers of twins compared with singletons, but twin babies had lower estrogen and progesterone concentrations at birth. Opposite-sex twin girls did not have higher androgens in cord blood compared with same-sex twin girls. Boys of an opposite-sex twin had lower luteinizing hormone concentrations compared with dizygotic twin boys with a brother as a co-twin.Conclusion(s): Children from a twin are not overexposed to sex steroids at the time of birth, despite higher concentrations in their mothers, and girls from opposite sex twins do not show androgenic influences from their male co-twin. The female co-twin may influence the hypothalamic-pituitary-testicular axis of her brother via central inhibition. [ABSTRACT FROM AUTHOR]

Background: Self-rated health (SRH) has been found to predict sickness absence (SA). The present study investigated the effect of replacing single-item SRH by a multi-item health measure on SA predictions. Methods: Longitudinal study of 2059 Norwegian nurses with assessments in three waves each separated by 1 year. Health was measured by single-item SRH and multi-item SF-12 in waves 1 and 2. SA was self-reported in all three waves and high SA was defined as more than or equal to 31 SA days within the last 12 months. Predictions of high SA by a model including age, prior SA and single-item SRH were compared with predictions by a model including age, prior SA and multi-item SF-12. Both models were bootstrapped to correct for over-optimism and prospectively validated for their predictions in a new time frame. Results: 1253 nurses (61%) had complete data for analysis. The SF-12 model predicted the risk of high SA more accurately (X2= 4.294; df = 8) and was more stable over time than the SRH model (model X2= 14.495; df = 8). Both prediction models correctly discriminated between high-risk and low-risk individuals in 73% of the cases at wave 2 and in 71% of the cases at wave 3. Conclusions: The accuracy of predictions increased when single-item SRH was replaced by multi-item SF-12, but the discriminative ability did not improve. Single-item SRH suffices to identify employees at increased risk of high SA. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to investigate the association between 11 patient safety culture dimensions and the implementation of 7 organizational patient safety defences. [ABSTRACT FROM PUBLISHER]

Grey matter (GM) atrophy is a prominent aspect of multiple sclerosis pathology and an important outcome in studies. GM atrophy measurement requires accurate GM segmentation. Several methods are used in vivo for measuring GM volumes in MS, but assessing their validity in vivo remains challenging. In this postmortem study, we evaluated the correlation between postmortem MRI cortical volume or thickness and the cortical thickness measured on histological sections. Sixteen MS brains were scanned in situ using 3DT1-weighted MRI and these images were used to measure regional cortical volume using FSL-SIENAX, FreeSurfer, and SPM, and regional cortical thickness using FreeSurfer. Subsequently, cortical thickness was measured histologically in 5 systematically sampled cortical areas. Linear regression analyses were used to evaluate the relation between MRI regional cortical volume or thickness and histological cortical thickness to determine which postprocessing technique was most valid. After correction for multiple comparisons, we observed a significant correlation with the histological cortical thickness for FSL-SIENAX cortical volume with manual editing (std. β = 0.345, adjusted R2 = 0.105, P = 0.005), and FreeSurfer cortical volume with manual editing (std. β = 0.379, adjusted R2 = 0.129, P = 0.003). In addition, there was a significant correlation between FreeSurfer cortical thickness with manual editing and histological cortical thickness (std. β = 0.381, adjusted R2 = 0.130, P = 0.003). The results support the use of FSL-SIENAX and FreeSurfer in cases of severe MS pathology. Interestingly none of the methods were significant in automated mode, which supports the use of manual editing to improve the automated segmentation. Hum Brain Mapp 37:2223-2233, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objectives To describe the patient safety culture of Dutch emergency departments (EDs), to examine associations between safety culture dimensions and patient safety grades as reported by ED staff and to compare these associations between nurses and physicians. Design Cross-sectional survey conducted in 2007. Setting Thirty-three non-academic EDs in the Netherlands. Participants Four hundred and eighty nurses, 159 physicians and 91 other professionals. Main Outcome Measure Self-reported level of patient safety. Results In unadjusted analyses, all dimensions of safety culture were positively associated with the reported level of patient safety and six of these associations with patient safety were statistically significant after adjustment (‘teamwork across units’, ‘frequency of event reporting’, communication openness', ‘feedback about and learning from errors’, ‘hospital management support for patient safety’). Differences between nurses and physicians were found on two dimensions (‘frequency of event reporting’ and ‘ hospital management support for patient safety’). Physicians tended to grade patient safety higher than nurses whilst having equal judgements on these two dimensions. Conclusions Staff identified several dimensions of safety culture that are associated with staff-reported safety in the ED. Physicians and nurses identified distinct dimensions of safety culture as associated with reported level of patient safety. [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: Cardiac function may differ after valvular (VS) and coronary artery (CAS) surgery and this may affect assessment of fluid responsiveness. The aim of the study was to compare VS and CAS in the value of cardiac filling pressures and volumes herein. Methods: There were eight consecutive patients after VS and eight after CAS, with femoral and pulmonary artery catheters in place. In each patient, five sequential fluid loading steps of 250ml of colloid each were done. We measured central venous pressure (CVP), pulmonary artery occlusion pressure (PAOP) and, by transpulmonary thermodilution, cardiac index (CI) and global end-diastolic (GEDVI) and intrathoracic blood volume (ITBVI) indices. Fluid responsiveness was defined by a CI increase >5% or >10% per step. Results: Global ejection fraction was lower and PAOP was higher after VS than CAS. In responding steps after VS (n =9–14) PAOP and volumes increased, while CVP and volumes increased in responding steps (n =12–19) after CAS. Baseline PAOP was lower in responding steps after VS only. Hence, baseline PAOP as well as changes in PAOP and volumes were of predictive value after VS and changes in CVP and volumes after CAS, in receiver operating characteristic curves. After VS, PAOP and volume changes equally correlated to CI changes. After CAS, only changes in CVP and volumes correlated to those in CI. Conclusions: While volumes are equally useful in monitoring fluid responsiveness, the predictive and monitoring value of PAOP is greater after VS than after CAS. In contrast, the CVP is of similar value as volume measurements in monitoring fluid responsiveness after CAS. The different value of pressures rather than of volumes between surgery types is likely caused by systolic left ventricular dysfunction in VS. The study suggests an effect of systolic cardiac function on optimal parameters of fluid responsiveness and superiority of the pulmonary artery catheter over transpulmonary dilution, for haemodynamic monitoring of VS patients. [Copyright &y& Elsevier]

Objectives: We examined the relation between angiographic, electrocardiographic, and gadolinium-enhanced cardiovascular magnetic resonance (CMR) characteristics of microvascular obstruction (MVO), and their predictive value on functional recovery after acute myocardial infarction (AMI). Background: Microvascular obstruction on CMR has been shown to predict left ventricular (LV) remodeling, but it is not well known how it compares with commonly used criteria of microvascular injury, and earlier reports have produced conflicting results on the significance and extent of MVO. Methods: Thrombolysis In Myocardial Infarction (TIMI) flow grade, myocardial blush grade (MBG), and ST-segment resolution were assessed in 60 patients with AMI treated with primary stenting. Cardiovascular magnetic resonance was performed between 2 and 9 days after revascularization to determine early MVO on first-pass perfusion imaging, late MVO on late gadolinium-enhanced imaging, and infarct size and transmural extent. Cine imaging was used to determine LV volumes and global and regional function at baseline and 4-month follow-up. Results: Early and late MVO were both related to incomplete ST-segment resolution (p = 0.002 and p = 0.01, respectively), but not to TIMI flow grade and MBG. Of all angiographic, electrocardiographic, and CMR variables, late MVO was the strongest parameter to predict changes in end-diastolic volume (β = 0.53; p = 0.001), end-systolic volume (β = 8.67; p = 0.001), and ejection fraction (β = 3.94; p = 0.006) at follow-up. Regional analysis showed that late MVO had incremental diagnostic value to transmural extent of infarction (odds ratio: 0.18; p < 0.0001). Conclusions: In patients after revascularized AMI, late MVO proved a more powerful predictor of global and regional functional recovery than all of the other characteristics, including transmural extent of infarction. [Copyright &y& Elsevier]

Simple Summary: We studied children with cancer who receive vincristine chemotherapy as a one-hour infusion and compared them to children who received vincristine as a push injection. We investigated if there was a difference in the development of vincristine induced peripheral neuropathy, the most common side effect of vincristine. We found that in general there were no differences between the two groups (one-hour group versus push group). However, in children using both vincristine and azole antifungals, we noticed that children who received vincristine as a one-hour infusion experienced less severe vincristine induced peripheral neuropathy compared to children who received vincristine as a push injection. Therefore, in children who require both azole antifungal medication as well as vincristine it might be beneficial to administer the vincristine as a one-hour infusion instead of a push injection. However, this finding needs to be confirmed in other studies as well. Vincristine (VCR) is a frequently used chemotherapeutic agent. However, it can lead to VCR-induced peripheral neuropathy (VIPN). In this study we investigated if one-hour infusions of VCR instead of push-injections reduces VIPN in pediatric oncology patients. We conducted a multicenter randomized controlled trial in which participants received all VCR administrations through push injections or one-hour infusions. VIPN was measured at baseline and 1–5 times during treatment using Common Terminology Criteria of Adverse Events (CTCAE) and pediatric-modified Total Neuropathy Score. Moreover, data on co-medication, such as azole antifungals, were collected. Overall, results showed no effect of administration duration on total CTCAE score or ped-mTNS score. However, total CTCAE score was significantly lower in patients receiving one-hour infusions concurrently treated with azole antifungal therapy (β = -1.58; p = 0.04). In conclusion, generally VCR administration through one-hour infusions does not lead to less VIPN compared to VCR push injections in pediatric oncology patients. However, one-hour infusions lead to less severe VIPN compared to push-injections when azole therapy is administered concurrently with VCR. These results indicate that in children treated with VCR and requiring concurrent azole therapy, one-hour infusions might be beneficial over push injections, although larger trials are needed to confirm this association. [ABSTRACT FROM AUTHOR]