Perhexiline Therapy in Patients with Type 2 Diabetes: Incremental Insulin Resistance despite Potentiation of Nitric Oxide Signaling

Published: 23 September 2022Perhexiline (Px) inhibits carnitine palmitoyltransferase 1 (CPT1), which controls uptake of long chain fatty acids into mitochondria. However, occasional cases of hypoglycaemia have been reported in Px-treated patients, raising the possibility that Px may also increase sensitivity to insulin. Furthermore, Px increases anti-aggregatory responses to nitric oxide (NO), an effect which may theoretically parallel insulin sensitization. We therefore sought to examine these relationships in patients with stable Type 2 diabetes (T2D) and cardiovascular disease (n = 30). Px was initiated, and dosage was titrated, to reach the therapeutic range and thus prevent toxicity. Investigations were performed before and after 2 weeks, to examine changes in insulin sensitivity and, utilizing aggregometry in whole blood, platelet responsiveness to the anti-aggregatory effects of the NO donor sodium nitroprusside (SNP). Other parameters that affect may affect NO signalling were also evaluated. Px substantially potentiated inhibition of platelet aggregation by SNP (from 16.7 ± 3.0 to 27.3 ± 3.7%; p = 0.005). Px did not change fasting blood glucose concentrations but reduced insulin sensitivity (HOMA-IR score increased from median of 4.47 to 6.08; p = 0.028), and increased fasting plasma insulin concentrations (median 16.5 to 19.0 mU/L; p = 0.014). Increases in SNP responses tended (r = −0.30; p = 0.11) to be reciprocally related to increases in HOMA-IR, and increases in HOMA-IR were greater (p = 0.002) in patients without NO-sensitizing effects. No patient developed symptomatic hypoglycaemia, nor was there any other short-term toxicity of Px. Thus, in patients with stable T2D and cardiovascular disease, Px increases anti-aggregatory responsiveness to NO, but is not an insulin sensitizer, and does not induce hypoglycaemia. Absence of NO-sensitizing effect occurs in approximately 30% of Px-treated patients with T2D, and is associated with induction of insulin resistance in these patients.Cher-Rin Chong, Saifei Liu, Hasan Imam, Tamila Heresztyn, Benedetta C. Sallustio, Yuliy Y. Chirkov, and John D. Horowit

Patterns of psychological responses among the public during the early phase of COVID-19: A cross-regional analysis

This study aimed to compare the mediation of psychological flexibility, prosociality and coping in the impacts of illness perceptions toward COVID-19 on mental health among seven regions. Convenience sampled online survey was conducted between April and June 2020 from 9130 citizens in 21 countries. Illness perceptions toward COVID-19, psychological flexibility, prosociality, coping and mental health, socio-demographics, lockdown-related variables and COVID-19 status were assessed. Results showed that psychological flexibility was the only significant mediator in the relationship between illness perceptions toward COVID-19 and mental health across all regions (all ps = 0.001–0.021). Seeking social support was the significant mediator across subgroups (all ps range = <0.001–0.005) except from the Hong Kong sample (p = 0.06) and the North and South American sample (p = 0.53). No mediation was found for problem-solving (except from the Northern European sample, p = 0.009). Prosociality was the significant mediator in the Hong Kong sample (p =0.016) and the Eastern European sample (p = 0.008). These findings indicate that fostering psychological flexibility may help to mitigate the adverse mental impacts of COVID-19 across regions. Roles of seeking social support, problem-solving and prosociality vary across regions. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Mental health and adherence to covid-19 protective behaviors among cancer patients during the covid-19 pandemic: An international, multinational cross-sectional study

A population-based cross-sectional study was conducted during the first COVID-19 wave, to examine the impact of COVID-19 on mental health using an anonymous online survey, enrolling 9565 individuals in 78 countries. The current sub-study examined the impact of the pandemic and the associated lockdown measures on the mental health, and protective behaviors of cancer patients in comparison to non-cancer participants. Furthermore, 264 participants from 30 different countries reported being cancer patients. The median age was 51.5 years, 79.9% were female, and 28% had breast cancer. Cancer participants reported higher self-efficacy to follow recommended national guidelines regarding COVID-19 protective behaviors compared to non-cancer participants (p < 0.01). They were less stressed (p < 0.01), more psychologically flexible (p < 0.01), and had higher levels of positive affect compared to non-cancer participants. Amongst cancer participants, the majority (80.3%) reported COVID-19, not their cancer, as their priority during the first wave of the pandemic and females reported higher levels of stress compared to males. In conclusion, cancer participants appeared to have handled the unpredictable nature of the first wave of the pandemic efficiently, with a positive attitude towards an unknown and otherwise frightening situation. Larger, cancer population specific and longitudinal studies are warranted to ensure adequate medical and psychological care for cancer patients. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 &times; 10-11 to 5.0 &times; 10-21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 &times; 10-6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation

Cross Axis Wind Turbine®

A cross axis wind turbine is disclosed, which comprises of cross axis arrangement. The wind turbine consists of three vertical blades and six horizontal blades arranged in cross axis orientation. The six horizontal blades serve as the radial arms that link the three vertical blades and the hubs through connectors to form the cross axis wind turbine (CAWT). Three horizontal axis blades that make up as the upper radial arm connects the top part of the vertical blades to the hub through the top connectors. The other three horizontal axis blades that make up as the lower radial arm connects the bottom part of the vertical axis blades to the hub through the bottom connectors. To avoid air flow blockage or interference between the top radial arm and the bottom radial arm, the horizontal axis blade radial arm at the top part of the turbine is offset at an angle of 30° with respect to the bottom radial arm. In the present invention, the air stream can be channeled from the bottom of the turbine through the bottom radial arm, and the air streams that did not interact with the bottom radial arm will eventually interact with the top radial arm. The air streams channeled from the bottom of the wind turbine and moving upwards will interact with the horizontal blades and this will eventually improve the self-starting capability of the CAWT. This trademark registered in class 7

Facile Synthesis of Single Crystalline Rhenium (VI) Trioxide Nanocubes with High Catalytic Efficiency for Photodegradation of Methyl Orange

10.1016/j.jcis.2013.01.030Journal of Colloid and Interface Science39718-23JCIS

Preparation of rhenium nanoparticles via pulsed-laser decomposition and catalytic studies

10.1016/j.jcis.2011.12.015Journal of Colloid and Interface Science3691164-169JCIS

Controlling the repulsive Casimir force with the optical Kerr effect

The Casimir force between two plates can be controlled using combinations of dispersive metamaterials and nonlinear materials with the optical Kerr effect. The force can be significantly varied and switched between positive and negative values by changing the intensity of a laser pulse. The switching sensitivity increases for small separation between the plates, providing new possibilities of integrating optical devices into nanoelectromechanical systems

A comparison of comorbidities obtained from hospital administrative data and medical charts in older patients with pneumonia

10.1186/1472-6963-11-105BMC Health Services Research1110