Our study revealed impaired HRQOL in semi-precious stone miners evaluated using both questionnaire tools of SGRQ and WHOQOL-BREF, of which SGRQ had superior performance. Respiratory symptoms, functional impairment, and pack-years of cigarette smoking were the most important determinants of the workers’ general HRQOL.

Our study revealed impaired HRQOL in semi-precious stone miners evaluated using both questionnaire tools of SGRQ and WHOQOL-BREF, of which SGRQ had superior performance. Respiratory symptoms, functional impairment, and pack-years of cigarette smoking were the most important determinants of the workers’ general HRQOL.

To evaluate the efficacy and safety of cabozantinib in Japanese patients with advanced hepatocellular carcinoma (HCC) who had progressed following one or two lines of systemic therapy including sorafenib. An exploratory evaluation in sorafenib-naïve patients was performed.

In this open-label, single-arm, phase 2 trial, patients received oral cabozantinib 60mg once daily. The primary endpoint was progression-free survival (PFS) rate at Week 24. Secondary endpoints included PFS, overall survival (OS), objective response rate (ORR, best response of complete/partial response), disease control rate (DCR, objective response or stable disease) and safety.

Thirty-four patients received cabozantinib across 17 centers (prior sorafenib cohort, n = 20; sorafenib-naïve cohort, n = 14). PFS rate at 24weeks was 59.8% [90% confidence interval (CI) 36.1-77.2%] in the prior sorafenib cohort, 16.7% (90% CI 4.0-36.8%) in the sorafenib-naïve cohort and 40.1% (90% CI 24.8-55.0%) overall. Median PFS was 7.4months for the prior sorafenib cohort, 3.6months for the sorafenib-naïve cohort, and 5.6months overall. OS rate at 6months was 100.0%, 78.6% and 91.1%, respectively; DCR was 85.0%, 64.3% and 76.5%, respectively. The ORR was 0.0% for both cohorts. All patients required dose modifications due to adverse events, the most common of these were palmar-plantar erythrodysesthesia syndrome and diarrhea. Three patients (8.8%) discontinued due to adverse events other than disease progression.

Cabozantinib 60mg/day has a favorable benefit/risk profile for Japanese patients with advanced HCC who have previously received one or two lines of systemic anticancer therapy including sorafenib. (Clinical trial registration NCT03586973).

Cabozantinib 60 mg/day has a favorable benefit/risk profile for Japanese patients with advanced HCC who have previously received one or two lines of systemic anticancer therapy including sorafenib. (Clinical trial registration NCT03586973).The metabolically engineered plant pathogen Ustilago maydis MB215 Δcyp3 Petefria1 has been cultivated to produce more than 80 g/L itaconate in 16 L scale pH and temperature controlled fermentation, in fed-batch mode with two successive feedings. The effect of pH as well as successive rounds of feeding has been quantified via elemental balances. Volumetric itaconic acid productivity gradually decreased with successive glucose feedings with increasing itaconic titers, with nearly constant product yield. Extracellular pH was decreased from 6 down to 3.5 and the fermentation was characterized in specific uptake, production, and growth rates. Notable is that the biomass composition changes significantly from growth phase to itaconic acid production phase, carbon content increases from 42% to around 62%. Despite the gradual decrease in itaconic acid levels with decreasing pH (nearly 50% decrease in itaconic acid at pH 3.5, compared to pH 6), significant itaconate production is still observed at pH 4 (around 63 g/L). Biomass yield remained nearly constant until pH 4. Taken together, these results strongly illustrate the potential of engineered Ustilago maydis in itaconate production at commercial levels.Co-cultures consisting of three thermophilic and lignocellulolytic bacteria, namely Clostridium thermocellum, C. stercorarium, and Thermoanaerobacter thermohydrosulfuricus, degrade lignocellulosic material in a synergistic manner. When cultured in a defined minimal medium two of the members appeared to be auxotrophic and unable to grow, but the growth of all species was observed in all co-culture combinations, indicating cross-feeding of unidentified growth factors between the members. Growth factors also appeared to be present in water-soluble extractives obtained from wheat straw, allowing for the growth of the auxotrophic monocultures in the defined minimal medium. PIK-III Cell enumeration during growth on wheat straw in this medium revealed different growth profiles of the members that varied between the co-cultures. End-product profiles also varied substantially between the cultures, with significantly higher ethanol production in all co-cultures compared to the mono-cultures. Understanding interactions between co-culture members, and the additional nutrients provided by lignocellulosic substrates, will aid us in consolidated bioprocessing design.This review integrates from the single muscle fibre to exercising human the current understanding of the role of skeletal muscle for whole-body potassium (K+) regulation, and specifically the regulation of skeletal muscle [K+]. We describe the K+ transport proteins in skeletal muscle and how they contribute to, or modulate, K+ disturbances during exercise. Muscle and plasma K+ balance are markedly altered during and after high-intensity dynamic exercise (including sports), static contractions and ischaemia, which have implications for skeletal and cardiac muscle contractile performance. Moderate elevations of plasma and interstitial [K+] during exercise have beneficial effects on multiple physiological systems. Severe reductions of the trans-sarcolemmal K+ gradient likely contributes to muscle and whole-body fatigue, i.e. impaired exercise performance. Chronic or acute changes of arterial plasma [K+] (hyperkalaemia or hypokalaemia) have dangerous health implications for cardiac function. The current mechanisms to explain how raised extracellular [K+] impairs cardiac and skeletal muscle function are discussed, along with the latest cell physiology research explaining how calcium, β-adrenergic agonists, insulin or glucose act as clinical treatments for hyperkalaemia to protect the heart and skeletal muscle in vivo. Finally, whether these agents can also modulate K+-induced muscle fatigue are evaluated.