561 research outputs found

    Poor blood pressure control in general practice: In search of explanations

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    SummaryBackgroundArterial hypertension is managed mainly by general practitioners. The blood pressure level of most patients treated in a general practice setting is greater than or equal to 140/90mmHg.AimsTo understand why a blood pressure level greater than or equal to 140/90mmHg does not lead to a change of treatment.MethodsOver a 2-week period, 479 hypertensive patients were included in a cross-sectional study by 27 general practitioners. Consultation data were collected, as were reasons why patients with a blood pressure level greater than or equal to 140/90mmHg did not have their treatment changed.ResultsBlood pressure level was greater than or equal to 140/90mmHg in 58% of patients; treatment was changed in 15% of these individuals. The lack of change in treatment was justified by the physicians as follows: the blood pressure measurements were not considered to be representative (about 30% of cases); the therapeutic result was considered to be satisfactory in the circumstances (about 30% of cases); change was not appropriate given the patient's specific context (the remaining third of cases). The proportion of uncontrolled hypertensive patients whose treatment remained the same was significantly higher among patients with a disease that affected their lifestyle or threatened their life expectancy.ConclusionThe disappointing therapeutic results observed in the management of arterial hypertension do not arise only from poor application of guidelines by general practitioners. Reluctance to rely on blood pressure measurements, a perception that guidelines are revised frequently and are not always clear, and consideration of the general practitioner's activity in the patient's specific context are the main factors involved

    The Public Health Dimension of Disasters—Health Outcome Assessment of Disasters

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    A broad range of health problems are related to disasters. Insight into these health problems is needed for targeted disaster management. Disaster health outcome assessment can provide insight into the health effects of disasters. During the 15th World Congress on Disaster and Emergency Medicine in Amsterdam (2007), experts in the field of disaster epidemiology discussed important aspects of disaster health outcome assessment, such as: (1) what is meant by disaster health outcome assessment?; (2) why should one conduct a disaster health outcome assessment, and what are the objectives?, and (3) who benefits from the information obtained by a disaster health outcome assessment? A disaster health outcome assessment can be defined as a systematic assessment of the current and potential health problems in a population affected by a disaster. Different methods can be used to examine these health problems such as: (1) rapid assessment of health needs; (2) (longitudinal) epidemiological studies using questionnaires; (3) continuous surveillance of health problems using existing registration systems; (4) assessment of the use and distribution of health services; and (5) research into the etiology of the health effects of disasters. The public health impact of a disaster may not be immediately evident. Disaster health outcome assessment provides insight into the health related consequences of disasters. The information that is obtained by performing a disaster health outcome assessment can be used to initiate and adapt the provision of health care. Besides information for policy-makers, disaster health outcome assessments can contribute to the knowledge and evidence base of disaster health outcomes (scientific objective). Finally, disaster health outcome assessment might serve as a signal of recognition of the problems of the survivors. Several stakeholders may benefit from the information obtained from a disaster health outcome assessment. Disaster decision-makers and the public health community benefit from performing a disaster health outcome assessment, since it provides information that is useful for the different aspects of disaster management. Also, by providing information about the nature, prevalence, and course of health problems, (mental) health care workers can anticipate the health needs and requirements in the affected population. It is important to realize that the disaster is not over when the acute care has been provided. Instead, disasters will cause many other health problems and concerns such as infectious diseases and mental health problems. Disaster health outcome assessments provide insight into the public health impact of disaster

    The sonic hedgehog signaling pathway is reactivated in human renal cell carcinoma and plays orchestral role in tumor growth

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    <p>Abstract</p> <p>Background</p> <p>Human clear cell renal cell carcinoma (CRCC) remains resistant to therapies. Recent advances in Hypoxia Inducible Factors (HIF) molecular network led to targeted therapies, but unfortunately with only limited clinical significance. Elucidating the molecular processes involved in kidney tumorigenesis and resistance is central to the development of improved therapies, not only for kidney cancer but for many, if not all, cancer types. The oncogenic PI3K/Akt, NF-kB and MAPK pathways are critical for tumorigenesis. The sonic hedgehog (SHH) signaling pathway is crucial to normal development.</p> <p>Results</p> <p>By quantitative RT-PCR and immunoblot, we report that the SHH signaling pathway is constitutively reactivated in tumors independently of the von Hippel-Lindau (VHL) tumor suppressor gene expression which is inactivated in the majority of CRCC. The inhibition of the SHH signaling pathway by the specific inhibitor cyclopamine abolished CRCC cell growth as assessed by cell counting, BrdU incorporation studies, fluorescence-activated cell sorting and β-galactosidase staining. Importantly, inhibition of the SHH pathway induced tumor regression in nude mice through inhibition of cell proliferation and neo-vascularization, and induction of apoptosis but not senescence assessed by in vivo studies, immunoblot and immunohistochemistry. Gli1, cyclin D1, Pax2, Lim1, VEGF, and TGF-β were exclusively expressed in tumors and were shown to be regulated by SHH, as evidenced by immunoblot after SHH inhibition. Using specific inhibitors and immunoblot, the activation of the oncogenic PI3K/Akt, NF-kB and MAPK pathways was decreased by SHH inhibition.</p> <p>Conclusions</p> <p>These findings support targeting SHH for the treatment of CRCC and pave the way for innovative and additional investigations in a broad range of cancers.</p

    Realization of a density-dependent Peierls phase in a synthetic, spin-orbit coupled Rydberg system

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    We experimentally realize a Peierls phase in the hopping amplitude of excitations carried by Rydberg atoms, and observe the resulting characteristic chiral motion in a minimal setup of three sites. Our demonstration relies on the intrinsic spin-orbit coupling of the dipolar exchange interaction combined with time-reversal symmetry breaking by a homogeneous external magnetic field. Remarkably, the phase of the hopping amplitude between two sites strongly depends on the occupancy of the third site, thus leading to a correlated hopping associated to a density-dependent Peierls phase. We experimentally observe this density-dependent hopping and show that the excitations behave as anyonic particles with a non-trivial phase under exchange. Finally, we confirm the dependence of the Peierls phase on the geometrical arrangement of the Rydberg atoms.Comment: 10 pages, 7 figure

    PAK1 modulates a PPARγ/NF-κB cascade in intestinal inflammation

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    P21-activated kinases (PAKs) are multifunctional effectors of Rho GTPases with both kinase and scaffolding activity. Here, we investigated the effects of inflammation on PAK1 signaling and its role in colitis-driven carcinogenesis. PAK1 and p-PAK1 (Thr423) were assessed by immunohistochemistry, immunofluorescence, and Western blot. C57BL6/J wildtype mice were treated with a single intraperitoneal TNFα injection. Small intestinal organoids from these mice and from PAK1-KO mice were cultured with TNFα. NF-κB and PPARγ were analyzed upon PAK1 overexpression and silencing for transcriptional/translational regulation. PAK1 expression and activation was increased on the luminal intestinal epithelial surface in inflammatory bowel disease and colitis-associated cancer. PAK1 was phosphorylated upon treatment with IFNγ, IL-1β, and TNFα. In vivo, mice administered with TNFα showed increased p-PAK1 in intestinal villi, which was associated with nuclear p65 and NF-κB activation. p65 nuclear translocation downstream of TNFα was strongly inhibited in PAK1-KO small intestinal organoids. PAK1 overexpression induced a PAK1–p65 interaction as visualized by co-immunoprecipitation, nuclear translocation, and increased NF-κB transactivation, all of which were impeded by kinase-dead PAK1. Moreover, PAK1 overexpression downregulated PPARγ and mesalamine recovered PPARγ through PAK1 inhibition. On the other hand PAK1 silencing inhibited NF-κB, which was recovered using BADGE, a PPARγ antagonist. Altogether these data demonstrate that PAK1 overexpression and activation in inflammation and colitis-associated cancer promote NF-κB activity via suppression of PPARγ in intestinal epithelial cells

    Incidence and main factors associated with early unplanned hospital readmission among French medical inpatients aged 75 and over admitted through emergency units

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    Background: among elderly patients, readmission in the month following hospital discharge is a frequent occurrence which involves a risk of functional decline, particularly among frail subjects. While previous studies have identified risk factors of early readmission, geriatric syndromes, as markers of frailty have not been assessed as potential predictors. Objective: to evaluate the risk of early unplanned readmission, and to identify predictors in inpatients aged 75 and over, admitted to medical wards through emergency departments. Design: prospective multi-centre study. Setting: nine French hospitals. Subjects: one thousand three hundred and six medical inpatients, aged 75 and older admitted through emergency departments (SAFES cohort). Methods: using logistic regressions, factors associated with early unplanned re-hospitalisation (defined as first unplanned readmission in the thirty days after discharge) were identified using data from the first week of hospital index stay obtained by comprehensive geriatric assessment. Results: data from a thousand out of 1,306 inpatients were analysed. Early unplanned readmission occurred in 14.2% of inpatients and was not related with sociodemographic characteristics, comorbidity burden or cognitive impairment. Pressure sores (OR=2.05, 95% CI = 1.0-3.9), poor overall condition (OR = 2.01, 95% CI = 1.3-3.0), recent loss of ability for self-feeding (OR = 1.9, 95% CI = 1.2-2.9), prior hospitalisation during the last 3 months (OR = 1.6, 95% CI = 1.1-2.5) were found to be risk factors, while sight disorders appeared as negatively associated (OR = 0.5, 95% CI = 0.3--0.8). Conclusions: markers of frailty (poor overall condition, pressure sores, prior hospitalisation) or severe disability (for self-feeding) were the most important predictors of early readmission among elderly medical inpatients. Early identification could facilitate preventive strategies in risk grou
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