Rac1 links integrin-mediated adhesion to the control of lactational differentiation in mammary epithelia

The expression of tissue-specific genes during mammary gland differentiation relies on the coincidence of two distinct signaling events: the continued engagement of β1 integrins with the extracellular matrix (ECM) and a hormonal stimulus from prolactin (Prl). How the integrin and Prl receptor (PrlR) systems integrate to regulate milk protein gene synthesis is unknown. In this study, we identify Rac1 as a key link. Dominant-negative Rac1 prevents Prl-induced synthesis of the milk protein β-casein in primary mammary epithelial cells cultured as three-dimensional acini on basement membrane. Conversely, activated Rac1 rescues the defective β-casein synthesis that occurs under conditions not normally permissive for mammary differentiation, either in β1 integrin–null cells or in wild-type cells cultured on collagen. Rac1 is required downstream of integrins for activation of the PrlR/Stat5 signaling cascade. Cdc42 is also necessary for milk protein synthesis but functions via a distinct mechanism to Rac1. This study identifies the integration of signals provided by ECM and hormones as a novel role for Rho family guanosine triphosphatases

The Impact of Locoregional Therapy in Nonmetastatic Inflammatory Breast Cancer: A Population-Based Study

Background. Inflammatory breast cancer (IBC) is a rare but most aggressive breast cancer subtype. The impact of locoregional therapy on survival in IBC is controversial. Methods. Patients with nonmetastatic IBC between 1988 and 2013 were identified in the Surveillance, Epidemiology, and End Results (SEER) registry. Results. We identified 7,304 female patients with nonmetastatic inflammatory breast cancer (IBC) who underwent primary tumor surgery. Most patients underwent total mastectomy with only 409 (5.6%) undergoing a partial mastectomy. In addition, 4,559 (62.4%) were also treated with radiation therapy. The patients who underwent mastectomy had better survival compared to partial mastectomy (49% versus 43%, p = 0.003). The addition of radiation therapy was also associated with improved 5-year survival (55% versus 40%, p < 0.001). Multivariate analysis showed that black race HR (1.22, 95% CI 1.18-1.35), ER negative status (HR 1.22, 95% CI 1.16-1.28), and higher grade (HR 1.14, 95% CI 1.07-1.20) were associated with poor outcome. Cox proportional hazards model showed that total mastectomy (HR 0.75, 95% CI 0.65-0.85) and radiation (HR 0.64, 95% CI 0.61-0.69) were associated with improved survival. Conclusions. Optimal locoregional therapy for women with nonmetastatic IBC continues to be mastectomy and radiation therapy. These data reinforce the prevailing treatment algorithm for nonmetastatic IBC

Enhancing arsenic mitigation in Bangladesh: Findings from institutional, psychological, and technical investigations

As part of a trans-disciplinary research project, a series of surveys and interventions were conducted in different arsenic-affected regions of rural Bangladesh. Surveys of institutional stakeholders identified deep tubewells and piped water systems as the most preferred options, and the same preferences were found in household surveys of populations at risk. Psychological surveys revealed that these two technologies were well-supported by potential users, with self-efficacy and social norms being the principal factors driving behavior change. The principal drawbacks of deep tubewells are that installation costs are too high for most families to own private wells, and that for various socio-cultural-religious reasons, people are not willing to walk long distances to access communal tubewells. In addition, water sector planners have reservations about greater exploitation of the deep aquifer, out of concern for current or future geogenic contamination. Groundwater models and field studies have shown that in the great majority of the affected areas, the risk of arsenic contamination of deep groundwater is small; salinity, iron, and manganese are more likely to pose problems. These constituents can in some cases be avoided by exploiting an intermediate depth aquifer of good chemical quality, which is hydraulically and geochemically separate from the arsenic-contaminated shallow aquifer. Deep tubewells represent a technically sound option throughout much of the arsenic-affected regions, and future mitigation programs should build on and accelerate construction of deep tubewells. Utilization of deep tubewells, however, could be improved by increasing the tubewell density (which requires stronger financial support) to reduce travel times, by considering water quality in a holistic way, and by accompanying tubewell installation with motivational interventions based on psychological factors. By combining findings from technical and social sciences, the efficiency and success of arsenic mitigation in general - and installation of deep tubewells in particular - can be significantly enhanced

Improving the quality of care of children in community clinics: an intervention and evaluation in Bangladesh.

Community health care providers (CHCPs) in 40 rural community clinics of Comilla district, Bangladesh, were trained using a newly developed case-management job aid based on the World Health Organization Integrated Management of Childhood Illness and a communication guide.To assess 1) the change in knowledge of the CHCPs after training; 2) the absolute quality of care provided by the CHCPs (determined as the proportion of children aged <5 years [under-fives] correctly diagnosed, treated and referred); and 3) the consultation behaviour of the CHCPs.Change in knowledge was assessed by tests pre-and post-training. The quality of care was determined by reassessments at the clinic exit by a medical officer, without a baseline comparison. Consultation behaviour was assessed through direct observation. The study was performed during 2014-2015.The mean standard knowledge score of the CH-CPs increased from 19 to 25 (P < 0.001). Of 1490 under-fives examined, 91% were correctly diagnosed, 86% were correctly treated and 99.5% received a correct referral decision. The CHCPs performed well on most of the measures of good communication, although one third did not explain the diagnosis and treatment to patients.The training was effective in changing knowledge. The CHCPs applied the knowledge gained and provided good quality care. Following these results, the Bangladesh Ministry of Health and Family Welfare has scaled up the training nationwide. The lessons learnt should be useful for other countries

Concentrations of lead, mercury, arsenic, cadmium, manganese, and aluminum in the blood of Pakistani children with and without autism spectrum disorder and their associated factors

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with early onset in utero or childhood. Environmental exposure to six metals (Pb, Hg, As, Cd, Mn, Al) is believed to be associated with ASD directly or interactively with genes. Objective: To assess the association of ASD among Pakistani children with the six metals and genotype frequencies of three GST genes (GSTP1, GSTM1, GSTT1).Methods: We enrolled 30 ASD cases, age 2-12 years old, and 30 age- and sex-matched typically developing (TD) controls in Karachi, Pakistan. We assessed associations of ASD status with various factors using Conditional Logistic Regression models. We also used General Linear Models to assess possible interaction of blood Mn and Pb concentrations with the three GST genes in relation to ASD status.Results: The unadjusted difference between ASD and TD groups in terms of geometric mean blood Pb concentrations was marginally significant (p = 0.05), but for Al concentrations, the adjusted difference was marginally significant (p = 0.06).Conclusions: This is the first study reporting six blood metal concentrations of Pakistani children with ASD. Estimates provided for possible interactions of GST genes with Mn and Pb in relation to ASD status are valuable for designing future similar studies

Perturbative expansion for master equation and it applications

We construct generally applicable small-loss rate expansions for the density operator of an open system. Successive terms of those expansions yield characteristic loss rates for dissipation processes. Three applications are presented in order to give further insight into the context of those expansions. The first application, of a two-level atom coupling to a bosonic environment, shows the procedure and the advantage of the expansion, whereas the second application that consists of a single mode field in a cavity with linewidth $\kappa$ due to partial transmission through one mirror illustrates a practical use of those expansions in quantum measurements, and the third one, for an atom coupled to modes of a lossy cavity shows the another use of the perturbative expansion.Comment: 10 pages, 1 figur

Patient Feedback Systems at the Primary Level of Health Care Centres in Bangladesh: A Mixed Methods Study

This paper documents, and reflects on key strengths and weaknesses of, existing patient feedback management systems at primary health care in Bangladesh and proposes key implications for future policy and practice. A mixed-method study was conducted in two Upazila (sub-district) Health Complexes (UHC) within one district in Bangladesh. It reports qualitative data from thematic analysis of in-depth interviews (n = 15) with key stakeholders; non-participant observations of feedback environment at UHCs; document review; and a stakeholder workshop. Patient feedback data from publicly available web portals were also analyzed. Multiple parallel patient feedback systems exist at health facilities. Key strengths across all systems included common goals of ensuring accountability and patient voice and high-level commitment. Common weaknesses included lack of documented processes, limited awareness of available channels among patients and a lack of documented actions following feedback. The findings helped to provide a few implications for future policy and practice on patient feedback management

Competing biosecurity and risk rationalities in the Chittagong poultry commodity chain, Bangladesh

This paper anthropologically explores how key actors in the Chittagong live bird trading network perceive biosecurity and risk in relation to avian influenza between production sites, market maker scenes and outlets. They pay attention to the past and the present, rather than the future, downplaying the need for strict risk management, as outbreaks have not been reported frequently for a number of years. This is analysed as ‘temporalities of risk perception regarding biosecurity’, through Black Swan theory, the idea that unexpected events with major effects are often inappropriately rationalized (Taleb in The Black Swan. The impact of the highly improbable, Random House, New York, 2007). This incorporates a sociocultural perspective on risk, emphasizing the contexts in which risk is understood, lived, embodied and experienced. Their risk calculation is explained in terms of social consent, practical intelligibility and convergence of constraints and motivation. The pragmatic and practical orientation towards risk stands in contrast to how risk is calculated in the avian influenza preparedness paradigm. It is argued that disease risk on the ground has become a normalized part of everyday business, as implied in Black Swan theory. Risk which is calculated retrospectively is unlikely to encourage investment in biosecurity and, thereby, points to the danger of unpredictable outlier events

Rac1 Controls Both the Secretory Function of the Mammary Gland and Its Remodeling for Successive Gestations.

An important feature of the mammary gland is its ability to undergo repeated morphological changes during each reproductive cycle with profound tissue expansion in pregnancy and regression in involution. However, the mechanisms that determine the tissue's cyclic regenerative capacity remain elusive. We have now discovered that Cre-Lox ablation of Rac1 in mammary epithelia causes gross enlargement of the epithelial tree and defective alveolar regeneration in a second pregnancy. Architectural defects arise because loss of Rac1 disrupts clearance in involution following the first lactation. We show that Rac1 is crucial for mammary alveolar epithelia to switch from secretion to a phagocytic mode and rapidly remove dying neighbors. Moreover, Rac1 restricts the extrusion of dying cells into the lumen, thus promoting their eradication by live phagocytic neighbors while within the epithelium. Without Rac1, residual milk and cell corpses flood the ductal network, causing gross dilation, chronic inflammation, and defective future regeneration