Triple Therapy for Cystic Fibrosis (Elexacaftor, Tezacaftor, and Ivacaftor): Desensitization After Skin Rash.

Cystic fibrosis (CF) is an autosomal recessive disorder of the CF transmembrane conductance regulator (CFTR) gene. CFTR modulators are novel approved therapies, and triple therapy with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is the current gold standard for patients with at least one F508del mutation. CFTR modulators are usually well-tolerated, but some adverse effects may occur, including skin rash. We report a case of a female patient who developed a severe skin rash after initiating treatment with ELX/TEZ/IVA. Modulator therapy and contraception were discontinued, and consequently, there was a drop in lung function and reappearance of respiratory symptoms. After rash resolution, a gradual reintroduction of ELX/TEZ/IVA was started, and this is the protocol the authors have summarized. Triple therapy with CFTR modulators has a significant impact on lung function and the quality of life of CF patients who have at least one F508del mutation, justifying its reintroduction and desensitization even after a severe adverse effect.

Radon signature of CO2 flux constrains the depth of degassing: Furnas volcano (Azores, Portugal) versus Syabru-Bensi (Nepal Himalayas).

Substantial terrestrial gas emissions, such as carbon dioxide (CO2), are associated with active volcanoes and hydrothermal systems. However, while fundamental for the prediction of future activity, it remains difficult so far to determine the depth of the gas sources. Here we show how the combined measurement of CO2 and radon-222 fluxes at the surface constrains the depth of degassing at two hydrothermal systems in geodynamically active contexts: Furnas Lake Fumarolic Field (FLFF, Azores, Portugal) with mantellic and volcano-magmatic CO2, and Syabru-Bensi Hydrothermal System (SBHS, Central Nepal) with metamorphic CO2. At both sites, radon fluxes reach exceptionally high values (> 10 Bq m-2 s-1) systematically associated with large CO2 fluxes (> 10 kg m-2 day-1). The significant radon‒CO2 fluxes correlation is well reproduced by an advective-diffusive model of radon transport, constrained by a thorough characterisation of radon sources. Estimates of degassing depth, 2580 ± 180 m at FLFF and 380 ± 20 m at SBHS, are compatible with known structures of both systems. Our approach demonstrates that radon‒CO2 coupling is a powerful tool to ascertain gas sources and monitor active sites. The exceptionally high radon discharge from FLFF during quiescence (≈ 9 GBq day-1) suggests significant radon output from volcanoes worldwide, potentially affecting atmosphere ionisation and climate.

Ecological features of a rocky intertidal community exposed to sewage effluent.

Sewage is among the largest components of coastal pollution, showing a variable scale and size when causing an impact. In this study, temporal and spatial sewage-related gradients were identified using univariate and multivariate methods. Phosphates and nitrogen-based nutrients, except nitrate, were associated to sewage. Abundance and species richness decrease with distance from the sewage outfall while evenness increased. Filter-feeder bivalves and grazer crustaceans showed preference for the sewage discharge site. Gastropods were more abundant at an intermediate distance, likely reflecting primary production enhancement by sewage. Beta diversity was lower at the location and time with highest sewage loadings. The turnover component of beta diversity expressed as an absolute or proportional value was also useful to detect temporal and spatial sewage-related gradients. Highly energetic hydrodynamics contributes to ameliorate sewage impacts, yet not enough to veil the effect of pollution in this study.

Neural gliding and neural tensioning differently impact flexibility, heat and pressure pain thresholds in asymptomatic subjects: A randomized, parallel and double-blind study.

OBJECTIVE: To compare the effect of neural gliding and tensioning on hamstring flexibility, nerve function (heat and cold thresholds) and pain sensitivity (pain intensity and pressure pain threshold) of the mobilized and non-mobilized lower limbs at post-intervention and 24 h follow up. DESIGN: Randomized, parallel and double blinded trial. SETTING/PARTICIPANTS: Forty-eight asymptomatic participants. INTERVENTION(S): Participants received neural gliding (n = 23) or tensioning (n = 25). Main Outcome Measures - Straight leg raising (SLR; in degrees), heat and cold threshold (ºC), pressure pain threshold (PPT; in Kgf) and pain intensity (visual analogue scale), taken at baseline, post-intervention and at 24 h follow up. RESULTS: There was a significant interaction between time, intervention and limb for SLR (F2,45 = 3.83; p = 0.029). A significant interaction between time and intervention for PPT (F2,45 = 3.59; p = 0.036) and heat threshold (F2,45 = 5.10; p = 0.01). A significant effect of time (F2,45 = 9.42; p < 0.001) and of limb (F1,46 = 4.78; p = 0.035) for pain intensity during SLR, and a significant effect of time (F2,45 = 3.65; p = 0.034) for pain intensity during PPT. CONCLUSION: Gliding and tensioning had similar and positive effects for flexibility in the mobilized limb, but tensioning was superior for the non-mobilized limb. Gliding was superior to tensioning for pressure pain and heat thresholds.

Forward head posture is associated with pressure pain threshold and neck pain duration in university students with subclinical neck pain.

OBJECTIVE: The aims of this study are to investigate the association between: (i) forward head posture (FHP) and pressure pain thresholds (PPTs); (ii) FHP and maladaptive cognitive processes; and (iii) FHP and neck pain characteristics in university students with subclinical neck pain. MATERIALS/METHODS: A total of 140 university students, 90 asymptomatic and 50 with subclinical neck pain, entered the study. Demographic data, anthropometric data, FHP, and PPTs were collected for both groups. In addition, pain characteristics, pain catastrophizing, and fear of movement were assessed for participants with neck pain. FHP was characterized by the angle between C7, the tragus of the ear, and the horizontal line. Correlation analysis and multivariate regression analysis were conducted. RESULTS: Participants with subclinical neck pain showed significantly lower PPTs than participants without neck pain (p < .05), but similar FHP (p > .05). No significant association was found between FHP and PPTs in the asymptomatic group. In the group of participants with subclinical neck pain, PPTs at the right trapezius and neck pain duration explained 19% of the variance of FHP (R2 = 0.23; adjusted R2 = 0.19; p < .05). CONCLUSION: This study suggests that FHP is not associated with PPTs in asymptomatic university students. In university students with subclinical neck pain, increased FHP was associated with right trapezius hypoalgesia and with neck pain of shorter duration. These findings are in contrast with current assumptions on the association between neck pain and FHP.