Pulmonary oedema after hexoprenaline administration in preterm labour A report of 4 cases

Despite the widespread use of ,a-sympathomimetic agents for preterm labour there appears to be a limited appreciation of the need for cardiovascular monitoring in the mother. Four patients in whom pulmonary oedema developed during tocolysis with hexoprenaline are described and the aetiological factors and pathogenesis of this potentially lethal complication discussed. Guidelines for the safe use of hexoprenaline in preterm labour are suggested

Retinal Expression of Wnt-Pathway Mediated Genes in Low-Density Lipoprotein Receptor-Related Protein 5 (Lrp5) Knockout Mice

Mutations in low-density lipoprotein receptor-related protein 5 (Lrp5) impair retinal angiogenesis in patients with familial exudative vitreoretinopathy (FEVR), a rare type of blinding vascular eye disease. The defective retinal vasculature phenotype in human FEVR patients is recapitulated in Lrp5 knockout $(Lrp5^{-/-})$ mouse with delayed and incomplete development of retinal vessels. In this study we examined gene expression changes in the developing $Lrp5^{−/−}$ mouse retina to gain insight into the molecular mechanisms that underlie the pathology of FEVR in humans. Gene expression levels were assessed with an Illumina microarray on total RNA from $Lrp5^{−/−}$ and WT retinas isolated on postnatal day (P) 8. Regulated genes were confirmed using RT-qPCR analysis. Consistent with a role in vascular development, we identified expression changes in genes involved in cell-cell adhesion, blood vessel morphogenesis and membrane transport in $Lrp5^{−/−}$ retina compared to WT retina. In particular, tight junction protein claudin5 and amino acid transporter slc38a5 are both highly down-regulated in $Lrp5^{−/−}$ retina. Similarly, several Wnt ligands including Wnt7b show decreased expression levels. Plasmalemma vesicle associated protein (plvap), an endothelial permeability marker, in contrast, is up-regulated consistent with increased permeability in $Lrp5^{−/−}$ retinas. Together these data suggest that Lrp5 regulates multiple groups of genes that influence retinal angiogenesis and may contribute to the pathogenesis of FEVR

A study of family mediation during divorce in the Pakistani Muslim community in Bradford. Some observations on the implications for the theory and practice of conflict resolution.

Conflict resolution theory and practice have been increasingly criticised for ignoring the centrality of culture in their attempts to find theories and models that are applicable universally, not only across cultures but also across levels of society. Mediation is one form of conflict resolution, which has come to occupy a central position in the resolution of disputes both at international and local levels. At the level of family disputes, family mediation has failed to engage users from different ethnic groups in England and Wales. This thesis explores the hypothesis that culture and, in particular, culturally defined concepts of gender are the important factors determining the success or failure of mediation in divorce disputes.J. A. Clark Charitable Trus

Omega-3 polyunsaturated fatty acids preserve retinal function in type 2 diabetic mice

Objective: Diabetic retinopathy (DR) is associated with hyperglycemia-driven microvascular pathology and neuronal compromise in the retina. However, DR is also linked to dyslipidemia. As omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) are protective in proliferative retinopathy, we investigated the capacity of ω-3PUFAs to preserve retinal function in a mouse model of type 2 diabetes mellitus (T2DM). Design: Male leptin-receptor-deficient (db/db) mice were maintained for 22 weeks (4 weeks–26 weeks of life) on calorically and compositionally matched diets, except for 2% enrichment in either ω-3 or ω-6PUFAs. Visual function was assessed at 9, 14 and 26 weeks by electroretinography. Retinal capillary and neuronal integrity, as well as glucose challenge responses, were assessed on each diet. Results: The ω-3PUFA diet significantly preserved retinal function in the mouse model of T2DM to levels similar to those observed in nondiabetic control mice on normal chow. Conversely, retinal function gradually deteriorated in db/db mice on a ω-6PUFA-rich diet. There was also an enhanced ability of ω-3PUFA-fed mice to respond to glucose challenge. The protection of visual function appeared to be independent of cytoprotective or anti-inflammatory effects of ω-3PUFAs. Conclusion: This study identifies beneficial effects of dietary ω-3PUFAs on visual function in T2DM. The data are consistent with dyslipidemia negatively impacting retinal function. As ω-3PUFA lipid dietary interventions are readily available, safe and inexpensive, increasing ω-3PUFA intake in diabetic patients may slow the progression of vision loss in T2DM

The role of irritability in the relation between job stressors, emotional reactivity, and counterproductive work behaviour

Researchers have stressed the importance of assessing individual differences in personality as an approach to understanding aggressive and deviant conduct across different contexts. This study investigated the moderation role of irritability, a specific aggression-related disposition, in the process of work stressors that are conducive to counterproductive work behaviour (CWB) within the stressor–emotion model. From a total sample of 1147 Italian workers (53.5% women), high- and low-irritability groups were identified. Then, using a multigroup structural equations model, we simultaneously examined all the relations in both high- and low-irritability groups, and investigated whether these relations were different between them. Results showed that job stressors elicited negative emotions that, in turn, lead to CWB. Moreover, some job stressors influenced CWB directly only in the high-irritability group. Overall, irritability moderated the relation among job stressors and CWB but not the relation among job stressors and negative emotions, with the sole exception of role conflict. As well, irritability did not moderate the relation between emotion and CWB. Thus, high-irritability employees may be more prone to react aggressively to job stressors via multiple functioning paths. The principal differences between low- and high-irritability individuals could be how they manage the impact of perceived stressors on emotions and behaviour

Patient-Reported Outcomes (PROs) in NRG Oncology RTOG 1010: Phase III Trial Evaluating the Addition of Trastuzumab to Trimodality Treatment of HER2 Overexpressing (HER2+) Esophageal Adenocarcinoma (EAC)

Purpose/Objective(s): NRG/RTOG 1010 evaluated the benefit of trastuzumab for patients (pts) with HER2+ localized EAC receiving trimodality therapy. Adding trastuzumab did not improve disease-free (primary endpoint) or overall survival, nor treatment toxicity (Lancet Oncology 2022). The primary PRO objective was improvement (impr) in the FACT-Esophageal Cancer Subscale (ECS) score with trastuzumab at restaging prior to surgery. A secondary objective was to assess if impr in ECS score is associated with pathologic complete response (pCR). Materials/Methods: Pts with HER2+ EAC (T1N1-2; T2-3N0-2) were stratified by presence of adenopathy & randomized 1:1 to weekly paclitaxel, carboplatin with 50.4 Gy radiation (CRT) followed by surgery ± trastuzumab (CRT+T), 4mg/kg week 1, 2mg/kg/weekly x 5 during CRT, 6 mg/kg x1 prior to surgery, and then 6mg/kg every 3 weeks (wks) x 13. The ECS, v4, was done at baseline, 6-8 wks post-CRT and at 1 & 2 years. Impr in ECS and its Swallowing Index (SI) & Eating Index (EI) were defined as increases of 5, 2 & 2 points, respectively, from baseline. PRO sample size provided ≥ 80% power with 1-sided 0.05 alpha & a chi-squared test to determine if the proportion of pts categorized as improved at 6-8 wks is ≥ 25% higher for the CRT+T arm. Correlation between pCR & impr in ECS score was evaluated via chi-squared test. Results: From 2010-2015, 203 HER2+ pts were randomized; 194 eligible. Of 171 PRO consenting pts, the ECS was completed by 162 (95%) at baseline, 108 (64%) 6-8 wks, 82 (49%) 1 year & 55 (33%) at 2 years. The main reason for FACT-E noncompliance was pt death. Patient & tumor characteristics were similar between arms. Median age was 63 years; 86% male; 96% white; 65% Zubrod 0, 80% cT3 & 71% cN1-2 (AJCC 7th ed). For ECS scores at 6-8 wks, the mean change (Δ) was higher (better) from baseline at 4.6 (95% CI: 1.3, 7.8) for the CRT+T arm vs 0.9 (95% CI: -2.7, 4.6) for the CRT arm; the proportion of pts with an impr in 6-8 wks ECS was higher on the CRT+T arm (46% vs 38% on the CRT arm) although not significantly different (p=0.39). Table 1 shows ECS, SI & EI scores for all timepoints. At 6-8 wks, 30% with a pCR had an impr in ECS vs 45% of nonpCR pts (p=0.18). There were no significant correlations between pCR and ECS, SI & EI impr at any time points. Conclusion: The addition of trastuzumab to trimodality therapy for localized HER2+ EAC did not significantly improve survival or PROs. ECS score improvement following therapy was not associated with a pCR. The higher proportion of pts with improved ECS at 6-8 weeks and 2 years in the CRT+T arm is interesting and suggests that HER2 may still be an important target to explore

The purple line as a measure of labour progress: a longitudinal study

Background: Vaginal examination (VE) and assessment of the cervix is currently considered to be the gold standard for assessment of labour progress. It is however inherently imprecise with studies indicating an overall accuracy for determining the diameter of the cervix at between 48-56%. Furthermore, VEs can be unpleasant, intrusive and embarrassing for women, and are associated with the risk of introducing infection. In light of increasing concern world wide about the use of routine interventions in labour it may be time to consider alternative, less intrusive means of assessing progress in labour. The presence of a purple line during labour, seen to rise from the anal margin and extend between the buttocks as labour progresses has been reported. The study described in this paper aimed to assess in what percentage of women in labour a purple line was present, clear and measurable and to determine if any relationship existed between the length of the purple line and cervical dilatation and/or station of the fetal head. Methods: This longitudinal study observed 144 women either in spontaneous labour (n=112) or for induction of labour (n=32) from admission through to final VE. Women were examined in the lateral position and midwives recorded the presence or absence of the line throughout labour immediately before each VE. Where present, the length of the line was measured using a disposable tape measure. Within subjects correlation, chi-squared test for independence, and independent samples t-test were used to analyse the data. Results: The purple line was seen at some point in labour for 109 women (76%). There was a medium positive correlation between length of the purple line and cervical dilatation (r=+0.36, n=66, P=0.0001) and station of the fetal head (r=+0.42, n=56, P<0.0001). Conclusions: The purple line does exist and there is a medium positive correlation between its length and both cervical dilatation and station of the fetal head. Where the line is present, it may provide a useful guide for clinicians of labour progress along side other measures. Further research is required to assess whether measurement of the line is acceptable to women in labour and also clinicians

Fibrillization of Human Tau Is Accelerated by Exposure to Lead via Interaction with His-330 and His-362

and its mutants at physiological pH. interaction with His-330 and His-362, with sub-micromolar affinity. in the pathogenesis of Alzheimer disease and provide critical insights into the mechanism of lead toxicity