Activity

As climate change accelerates and habitats free from anthropogenic impacts diminish, populations are forced to migrate or to adapt quickly. Evolutionary rescue (ER) is a phenomenon, in which a population is able to avoid extinction through adaptation. ER is considered to be more likely at slower rates of environmental change. However, the effects of correlated characters on evolutionary rescue are seldom explored yet correlated characters could play a major role in ER. We tested how evolutionary background in different fluctuating environments and the rate of environmental change affect the probability of ER by exposing populations of the bacteria Serratia marcescens to two different rates of steady temperature increase. As suggested by theory, slower environmental change allowed populations to grow more effectively even at extreme temperatures, but at the expense of long-term survival at extreme conditions due to correlated selection. Our results indicate important gap of knowledge on the effects of correlated selection during the environmental change and on evolutionary rescue at differently changing environments.Tendon injury is a considerable problem affecting both physically active and sedentary people. The aim of this study was to examine the relationship between markers for metabolic disorders (hyperglycemia, hypercholesterolemia, and metabolic syndrome) and the risk of developing tendon injuries requiring referral to a hospital. The Copenhagen City Heart Study is a prospective study of diabetic and non-diabetic individuals from the Danish general population with different physical activity levels. The cohort was followed for 3 years via national registers with respect to tendon injuries. Data from 5856 individuals (median age 62 years) were included. The overall incidence of tendon injury in both upper and lower extremities that required an out-patient or in-house visit to a hospital was ~5.7/1000 person years. Individuals with elevated HbA1c (glycated hemoglobin) even in the prediabetic range (HbA1c>5.7%) had a ~3 times higher risk of tendon injury in the lower extremities only, as compared to individuals with normal HbA1C levels. Hypercholesterolemia (total cholesterol>5 mmol/L) increased risk of tendon injury in the upper extremities by ~1.5 times, and individuals with metabolic syndrome had ~2.5 times higher risk of tendon injury in both upper and lower extremities. In conclusion, these data demonstrate for the first time in a large cohort with different physical activity levels that the indicators for metabolic syndrome are a powerful systemic determinant of tendon injury, and two of its components, hyperglycemia and hypercholesterolemia, each independently make tendons susceptible for damage and injury.

Isavuconazole is a triazole antifungal drug, approved for the treatment of invasive aspergillosis and mucormycosis. Isavuconazole is metabolised by CYP3A4 and CYP3A5, and it has been shown that the CYP3A inducer rifampin reduces isavuconazole exposure. By extrapolation, the concomitant use of isavuconazole with moderate and strong CYP450 inducers is contraindicated, although it is known that some CYP450 inducers are less potent in comparison with rifampin.

We aim to document exposure to isavuconazole in patients concomitantly treated with a CYP450 inducer that is less potent compared to rifampin. Moreover, although it is well known that CYP3A enzymes are important for the metabolism of isavuconazole, this induction effect has never been studied in combination with the patient’s CYP3A genotype.

We report three patients treated with both isavuconazole and a CYP3A inducer that is less potent compared to rifampin (rifabutin or phenobarbital), in whom we determined isavuconazole concentrations.

These cases suggest that the CYP3A4/5 genotype is an important determinant for isavuconazole exposure and that it might also influence the CYP450 induction interaction.

CYP3A inducers that are less potent compared to rifampin, may be combined with isavuconazole in patients with loss of CYP3A5 activity (CYP3A5*3/*3). Quizartinib research buy Therapeutic drug monitoring is recommended during this combination. However, low-isavuconazole exposure was observed in the extensive metaboliser with CYP3A4*1/*1 and CYP3A5*1/*3 alleles.

CYP3A inducers that are less potent compared to rifampin, may be combined with isavuconazole in patients with loss of CYP3A5 activity (CYP3A5*3/*3). Therapeutic drug monitoring is recommended during this combination. However, low-isavuconazole exposure was observed in the extensive metaboliser with CYP3A4*1/*1 and CYP3A5*1/*3 alleles.Molecular spintronics seeks to use single or few molecules as functional building blocks for spintronic applications, directly relying on molecular properties or properties of interfaces between molecules and inorganic electrodes. Spin-crossover molecules (SCMs) are one of the most promising classes of candidates for molecular spintronics due to their bistability deriving from the existence of two spin states that can be reversibly switched by temperature, light, electric fields, etc. Building devices based on single or few molecules would entail connecting the molecule(s) with solid surfaces and understanding the fundamental behavior of the resulting assemblies. Herein, the investigations of SCMs on solid surfaces, ranging from isolated single molecules (submonolayers) to ultrathin films (mainly in the sub-10 nm range) are summarized. The achievements, challenges and prospects in this field are highlighted.One in five children in the UK are affected by domestic violence and abuse. However, primary care clinicians (GPs and nurses) struggle to effectively identify and support children and young people living in homes where it is present. The IRIS+ (Enhanced Identification and Referral to Improve Safety) training and advocacy support intervention aimed to improve how clinicians respond to children and young people affected by domestic violence and abuse. IRIS+ training was delivered as part of a feasibility study to four general practices in an urban area in England (UK). Our mixed method design included interviews and questionnaires about the IRIS+ intervention with general practice patients, including children and young people as well as with clinicians and advocacy service providers. We collected the number of identifications and referrals by clinicians of children experiencing domestic violence and abuse through a retrospective search of medical and agency records 10 months after the intervention. Forty-nine children exposed to domestic violence and abuse were recorded in medical records.