Propylene glycol inactivates respiratory viruses and prevents airborne transmission

Viruses are vulnerable as they transmit between hosts, and we aimed to exploit this critical window. We found that the ubiquitous, safe, inexpensive and biodegradable small molecule propylene glycol (PG) has robust virucidal activity. Propylene glycol rapidly inactivates a broad range of viruses including influenza A, SARS-CoV-2 and rotavirus and reduces disease burden in mice when administered intranasally at concentrations commonly found in nasal sprays. Most critically, vaporised PG efficiently abolishes influenza A virus and SARS-CoV-2 infectivity within airborne droplets, potently preventing infection at levels well below those tolerated by mammals. We present PG vapour as a first-in-class non-toxic airborne virucide that can prevent transmission of existing and emergent viral pathogens, with clear and immediate implications for public health

Selective androgen receptor modulation for muscle weakness in chronic obstructive pulmonary disease: a randomised control trial

Background Selective androgen receptor modulators (SARMs) increase muscle mass via the androgen receptor. This phase 2A trial investigated the effects of a SARM, GSK2881078, in conjunction with exercise, on leg strength in patients with chronic obstructive pulmonary disease (COPD) and impaired physical function. Methods 47 postmenopausal women and 50 men with COPD (forced expiratory volume in 1 s 30%–65% predicted; short physical performance battery score: 3–11) were enrolled into a randomised double-blind, placebo control trial. Patients were randomised 1:1 to once daily placebo or oral GSK2881078 (females: 1.0 mg; males: 2.0 mg) for 13 weeks with a concurrent home-exercise programme, involving strength training and physical activity. Primary endpoints were change from baseline in leg strength at 90 days (one-repetition maximum; absolute (kg) and relative (% change)) and multiple safety outcomes. Secondary endpoints included lean body mass, physical function and patient-reported outcomes. Results GSK2881078 increased leg strength in men. The difference in adjusted mean change from baseline and adjusted mean percentage change from baseline between treatment and placebo were: for women, 8.0 kg (90% CI −2.5 to 18.4) and 5.2% (90% CI −4.7 to 15.0), respectively; for men, 11.8 kg (90% CI −0.5 to 24.0) and 7.0% (90% CI 0.5 to 13.6), respectively. Lean body mass increased, but no changes in patient-reported outcomes were observed. Reversible reductions in high-density lipoprotein-cholesterol and transient elevations in hepatic transaminases were the main treatment-related safety findings. Conclusions GSK2881078 was well tolerated and short-term treatment increased leg strength, when expressed as per cent predicted, in men with COPD more than physical training alone

Anti-nociceptive and desensitizing effects of olvanil on capsaicin-induced thermal hyperalgesia in the rat

Background: Olvanil (NE 19550) is a non-pungent synthetic analogue of capsaicin, the natural pungent ingredient of capsicum which activates the transient receptor potential vanilloid type-1 (TRPV1) channel and was developed as a potential analgesic compound. Olvanil has potent anti-hyperalgesic effects in several experimental models of chronic pain. Here we report the inhibitory effects of olvanil on nociceptive processing using cultured dorsal root ganglion (DRG) neurons and compare the effects of capsaicin and olvanil on thermal nociceptive processing in vivo; potential contributions of the cannabinoid CB1 receptor to olvanil’s anti-hyperalgesic effects were also investigated. Methods: A hot plate analgesia meter was used to evaluate the anti-nociceptive effects of olvanil on capsaicin-induced thermal hyperalgesia and the role played by CB1 receptors in mediating these effects. Single cell calcium imaging studies of DRG neurons were employed to determine the desensitizing effects of olvanil on capsaicin-evoked calcium responses. Statistical analysis used Student’s t test or one way ANOVA followed by Dunnett’s post-hoctest as appropriate. Results: Both olvanil (100 nM) and capsaicin (100 nM) produced significant increases in intracellular calcium concentrations [Ca2+]I in cultured DRG neurons. Olvanil was able to des ensitise TRPV1 responses to further capsaicin exposure more effectively than capsaicin. Intra plantar injection of capsaicin (0.1, 0.3 and 1μg) produced a robust TRPV1-dependant thermal hyperalgesia in rats, whilst olvanil (0.1, 0.3 and 1μg) produced no hyperalgesia, emphasizing its lack of pungency. The highest dose of olvanil significantly reduced the hyperalgesic effects of capsaicin in vivo. Intraplantar injection of the selective cannabinoid CB1 receptor antagonist rimonabant (1μg) altered neither capsaicin-induced thermal hyperalgesia nor the desensitizing properties of olvanil, indicating a lack of involvement of CB1receptors. Conclusions: Olvanil is effective in reducing capsaicin-induced thermal hyperalgesia, probably via directly desensitizingTRPV1 channels in a CB 1 receptor-independent fashion. The results presented clearly support the potential for olvanil in the development of new topical analgesic preparations for treating chronic pain conditions while avoiding the unwanted side effects of capsaicin treatments

Post-stroke infection: A systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p><b>s</b>troke is the main cause of disability in high-income countries, and ranks second as a cause of death worldwide. Patients with acute stroke are at risk for infections, but reported post-stroke infection rates vary considerably. We performed a systematic review and meta-analysis to estimate the pooled post-stroke infection rate and its effect on outcome.</p> <p>Methods</p> <p>MEDLINE and EMBASE were searched for studies on post-stroke infection. Cohort studies and randomized clinical trials were included when post-stroke infection rate was reported. Rates of infection were pooled after assessment of heterogeneity. Associations between population- and study characteristics and infection rates were quantified. Finally, we reviewed the association between infection and outcome.</p> <p>Results</p> <p>87 studies were included involving 137817 patients. 8 studies were restricted to patients admitted on the intensive care unit (ICU). There was significant heterogeneity between studies (P < 0.001, I²= 97%). The overall pooled infection rate was 30% (24-36%); rates of pneumonia and urinary tract infection were 10% (95% confidence interval [CI] 9-10%) and 10% (95%CI 9-12%). For ICU studies, these rates were substantially higher with 45% (95% CI 38-52%), 28% (95%CI 18-38%) and 20% (95%CI 0-40%). Rates of pneumonia were higher in studies that specifically evaluated infections and in consecutive studies. Studies including older patients or more females reported higher rates of urinary tract infection. Pneumonia was significantly associated with death (odds ratio 3.62 (95%CI 2.80-4.68).</p> <p>Conclusions</p> <p>Infection complicated acute stroke in 30% of patients. Rates of pneumonia and urinary tract infection after stroke were 10%. Pneumonia was associated with death. Our study stresses the need to prevent infections in patients with stroke.</p

Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom prospective diabetes study (UKPDS: 23)

Objective: To evaluate baseline risk factors for coronary artery disease in patients with type 2 diabetes mellitus. Design: A stepwise selection procedure, adjusting for age and sex, was used in 2693 subjects with complete data to determine which risk factors for coronary artery disease should be included in a Cox proportional hazards model. Subjects: 3055 white patients (mean age 52) with recently diagnosed type 2 diabetes mellitus and without evidence of disease related to atheroma. Median duration of follow up was 7.9 years. 335 patients developed coronary artery disease within 10 years. Outcome measures: Angina with confirmatory abnormal electrocardiogram; non-fatal and fatal myocardial infarction. Results: Coronary artery disease was significantly associated with increased concentrations of low density lipoprotein cholesterol, decreased concentrations of high density lipoprotein cholesterol, and increased triglyceride concentration, haemoglobin A(1c), systolic blood pressure, fasting plasma glucose concentration, and a history of smoking. The estimated hazard ratios for the upper third relative to the lower third were 2.26 (95% confidence interval 1.70 to 3.00) for low density lipoprotein cholesterol, 0.55 (0.41 to 0.73) for high density lipoprotein cholesterol, 1.52 (1.15 to 2.01) for haemoglobin A(1c), and 1.82 (1.34 to 2.47) for systolic blood pressure. The estimated hazard ratio for smokers was 1.41(1.06 to 1.88). Conclusion: A quintet of potentially modifiable risk factors for coronary artery disease exists in patients with type 2 diabetes mellitus. These risk factors are increased concentrations of low density lipoprotein cholesterol, decreased concentrations of high density lipoprotein cholesterol, raised blood pressure, hyperglycaemia, and smoking

Risk factors for stroke in type 2 diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS) 29.

OBJECTIVE: To investigate modifiable and nonmodifiable risk factors for stroke in type 2 diabetes mellitus. PATIENTS AND METHODS: A total of 3776 patients aged 25 to 65 years newly diagnosed as having type 2 diabetes mellitus without known cardiovascular or other serious disease were studied for a median of 7.9 years. An initial stepwise evaluation of risk factors was done in 2704 patients with all risk factors measured, with the final Cox model analysis being of 3776 patients who had complete data on the selected variables. RESULTS: Of 3776 patients, 99 (2.6%) had a stroke. Significant risk factors for stroke in a multivariate model were age (estimated hazard ratio [95% confidence interval], 4.78 [2.56-8.92] for &gt; or =60 vs &lt;50 years), male sex (1.63 [1.08-2.47)] vs female), hypertension (2.47 [1.64-3.74)] vs normotension), and in 3728 patients who had electrocardiography at study entry, atrial fibrillation (8.05 [3.52-18.44] vs sinus rhythm). Obesity, lack of exercise, smoking, poor glycemic control, hyperinsulinemia, dyslipidemia, and microalbuminuria were not significantly associated with stroke in the model. CONCLUSION: In patients with type 2 diabetes, aggressive antihypertensive therapy and routine anticoagulation therapy for atrial fibrillation may reduce the risk of stroke

Crowning glory: public law, power and the monarchy

‘New public law’ has a keen interest in the deployment of power and the shifting nature of the public and private. In this article, we argue that the historical legacy of the Crown has hindered the ability of public lawyers to respond to changes in modes of governance in the UK. The constitutional law textbook tradition has played a key role in limiting critiques of the Crown because of the obfuscation that surrounds the legal and political status of the Monarch. However, instead of discounting the significance of the monarchy, we use it as a resource for exploring governing power, the blurring of boundaries and constitutional renewal. Our starting point is the life, death and, most importantly, the funeral of Diana, Princess of Wales. The latter event exposed the political relevance of the ‘personal’ in a most dramatic way, generating claims about the ‘feminisation of the government’ and ‘emotions augmenting democracy’. We follow through on these claims in order to focus on the effects of adopting private, intimate-sphere norms in the public sphere, in particular public-sphere decision making. While aware of the risks associated with this ‘transformation’ of democracy, we conclude that the increasing centrality of the intimate merits onsideration in new public law’s search for progressive tools of modern governance