Sexual function is impaired in women and men with pulmonary hypertension

Background: Sexual health related quality of life (SHRQoL) is an important pillar of health related quality of life (HRQoL). The aim of this study was to investigate sexual functioning in men and women with pulmonary hypertension (PH). Methods and results: In this cross-sectional study, a total of 78 patients were included, 49 were diagnosed with pulmonary arterial hypertension and 29 with chronic thromboembolic pulmonary hypertension (median age 53 [IQR: 46–67 years], 66.7% female). All patients completed SHRQoL questionnaires; for women: ASEX, FSFI, and FSDS and for men: ASEX and IIEF. A PH-specific SHRQoL questionnaire was created based on 4 semi-structured interviews to investigate PH-specific barriers in sexuality. More than half of the patients experienced symptoms during sexual activity, mainly dyspnea (52.6%) and palpitations (32.1%). Sexual dysfunction was present, according to the FSFI-questionnaire, in 63.0% of women. All of the men experienced at least mild dysfunction in one of the domains of the IIEF and erectile dysfunction was present in 48.0%. Sexual dysfunction occurred more often in both men and women with PH than in the general population. PAH-specific medication was not associated with sexual dysfunction, nor was subcutaneous or intravenous pump therapy (OR 1.14, 95%-CI: 0.75–1.73). Diuretics were associated with sexual dysfunction in women (OR 4.01, 95%-CI: 1.04–15.41). Of all patients committed in a relationship, 69.0% would like to discuss sexuality with their healthcare provider. Conclusion: This study showed a high prevalence of sexual dysfunction in men and women with PH. It is important for healthcare providers to discuss sexuality with patients. Graphical abstract: [Figure not available: see fulltext.].</p

The importance of the intensive care unit environment in sleep-A study with healthy participants

Sleep disruption is common among intensive care unit patients, with potentially detrimental consequences. Environmental factors are thought to play a central role in ICU sleep disruption, and so it is unclear why environmental interventions have shown limited improvements in objectively assessed sleep. In critically ill patients, it is difficult to isolate the influence of environmental factors from the varying contributions of non-environmental factors. We thus investigated the effects of the ICU environment on self-reported and objective sleep quality in 10 healthy nurses and doctors with no history of sleep pathology or current or past ICU employment participated. Their sleep at home, in an unfamiliar environment ('Control'), and in an active ICU ('ICU') was evaluated using polysomnography and the Richard-Campbell Sleep Questionnaire. Environmental sound, light and temperature exposure were measured continuously. We found that the control and ICU environment were noisier and warmer, but not darker than the home environment. Sleep on the ICU was perceived as qualitatively worse than in the home and control environment, despite relatively modest effects on polysomnography parameters compared with home sleep: mean total sleep times were reduced by 48 min, mean rapid eye movement sleep latency increased by 45 min, and the arousal index increased by 9. Arousability to an awake state by sound was similar. Our results suggest that the ICU environment plays a significant but partial role in objectively assessed ICU sleep impairment in patients, which may explain the limited improvement of objectively assessed sleep after environmental interventions

Closed-loop separation control over a sharp edge ramp using Genetic Programming

We experimentally perform open and closed-loop control of a separating turbulent boundary layer downstream from a sharp edge ramp. The turbulent boundary layer just above the separation point has a Reynolds number $Re_{\theta}\approx 3\,500$ based on momentum thickness. The goal of the control is to mitigate separation and early re-attachment. The forcing employs a spanwise array of active vortex generators. The flow state is monitored with skin-friction sensors downstream of the actuators. The feedback control law is obtained using model-free genetic programming control (GPC) (Gautier et al. 2015). The resulting flow is assessed using the momentum coefficient, pressure distribution and skin friction over the ramp and stereo PIV. The PIV yields vector field statistics, e.g. shear layer growth, the backflow area and vortex region. GPC is benchmarked against the best periodic forcing. While open-loop control achieves separation reduction by locking-on the shedding mode, GPC gives rise to similar benefits by accelerating the shear layer growth. Moreover, GPC uses less actuation energy.Comment: 24 pages, 24 figures, submitted to Experiments in Fluid

Chemical carcinogenicity revisited 1: A unified theory of carcinogenicity based on contemporary knowledge

Abstract Developments in the understanding of the etiology of cancer have profound implications for the way the carcinogenicity of chemicals is addressed. This paper proposes a unified theory of carcinogenesis that will illuminate better ways to evaluate and regulate chemicals. In the last four decades, we have come to understand that for a cell and a group of cells to begin the process of unrestrained growth that is defined as cancer, there must be changes in DNA that reprogram the cell from normal to abnormal. Cancer is the consequence of DNA coding errors that arise either directly from mutagenic events or indirectly from cell proliferation especially if sustained. Chemicals that act via direct interaction with DNA can induce cancer because they cause mutations which can be carried forward in dividing cells. Chemicals that act via non-genotoxic mechanisms must be dosed to maintain a proliferative environment so that the steps toward neoplasia have time to occur. Chemicals that induce increased cellular proliferation can be divided into two categories: those which act by a cellular receptor to induce cellular proliferation, and those which act via non-specific mechanisms such as cytotoxicity. This knowledge has implications for testing chemicals for carcinogenic potential and risk management

Chemical carcinogenicity revisited 3: Risk assessment of carcinogenic potential based on the current state of knowledge of carcinogenesis in humans

Abstract Over 50 years, we have learned a great deal about the biology that underpins cancer but our approach to testing chemicals for carcinogenic potential has not kept up. Only a small number of chemicals has been tested in animal-intensive, time consuming, and expensive long-term bioassays in rodents. We now recommend a transition from the bioassay to a decision-tree matrix that can be applied to a broader range of chemicals, with better predictivity, based on the premise that cancer is the consequence of DNA coding errors that arise either directly from mutagenic events or indirectly from sustained cell proliferation. The first step is in silico and in vitro assessment for mutagenic (DNA reactive) activity. If mutagenic, it is assumed to be carcinogenic unless evidence indicates otherwise. If the chemical does not show mutagenic potential, the next step is assessment of potential human exposure compared to the threshold for toxicological concern (TTC). If potential human exposure exceeds the TTC, then testing is done to look for effects associated with the key characteristics that are precursors to the carcinogenic process, such as increased cell proliferation, immunosuppression, or significant estrogenic activity. Protection of human health is achieved by limiting exposures to below NOEALs for these precursor effects. The decision tree matrix is animal-sparing, cost effective, and in step with our growing knowledge of the process of cancer formation

Multi-Locus Variable-Number Tandem Repeat Profiling of Salmonella enterica Serovar Typhi Isolates from Blood Cultures and Gallbladder Specimens from Makassar, South-Sulawesi, Indonesia

Multi-locus variable-number tandem repeat analysis differentiated 297 Salmonella enterica serovar Typhi blood culture isolates from Makassar in 76 genotypes and a single unique S. Typhi genotype was isolated from the cholecystectomy specimens of four patients with cholelithiasis. The high diversity in S. Typhi genotypes circulating in Makassar indicates that the number of carriers could be very large, which may complicate disease prevention and control

Incorporating New Technologies Into Toxicity Testing and Risk Assessment: Moving From 21st Century Vision to a Data-Driven Framework

Based on existing data and previous work, a series of studies is proposed as a basis toward a pragmatic early step in transforming toxicity testing. These studies were assembled into a data-driven framework that invokes successive tiers of testing with margin of exposure (MOE) as the primary metric. The first tier of the framework integrates data from high-throughput in vitro assays, in vitro-to-in vivo extrapolation (IVIVE) pharmacokinetic modeling, and exposure modeling. The in vitro assays are used to separate chemicals based on their relative selectivity in interacting with biological targets and identify the concentration at which these interactions occur. The IVIVE modeling converts in vitro concentrations into external dose for calculation of the point of departure (POD) and comparisons to human exposure estimates to yield a MOE. The second tier involves short-term in vivo studies, expanded pharmacokinetic evaluations, and refined human exposure estimates. The results from the second tier studies provide more accurate estimates of the POD and the MOE. The third tier contains the traditional animal studies currently used to assess chemical safety. In each tier, the POD for selective chemicals is based primarily on endpoints associated with a proposed mode of action, whereas the POD for nonselective chemicals is based on potential biological perturbation. Based on the MOE, a significant percentage of chemicals evaluated in the first 2 tiers could be eliminated from further testing. The framework provides a risk-based and animal-sparing approach to evaluate chemical safety, drawing broadly from previous experience but incorporating technological advances to increase efficiency