"Cold turkey" works best for smoking cessation

"Cold turkey" works best for smoking cessation. PRACTICE CHANGER: Counsel patients who want to quit smoking that abrupt smoking cessation is more effective for long-term abstinence than taking a gradual approach. STRENGTH OF RECOMMENDATION: B: Based on one well-designed, randomized controlled trial

Human parathyroid hormone for treating osteoporosis

Human parathyroid hormone should be used in patients with severe osteoporosis to decrease the rate of vertebral and nonvertebral fractures. (Strength of Recommendation [SOR]: A, based on a systematic review and randomized controlled trial [RCT].) The parathyroid hormone teriparatide (Forteo) should be reserved for patients who do not respond to bisphosphonates or who have severe bone loss. (SOR: C, based on expert opinion.

An exploratory study to assess the activity of the acarine growth inhibitor, fluazuron, against Sarcoptes scabei infestation in pigs

Background: The most common treatments for scabies in human and veterinary settings are topical 5% permethrin or systemic treatment with ivermectin. However, these treatments have very little activity against arthropod eggs, and therefore repeated treatment is frequently required. In-vitro, biochemical and molecular studies have demonstrated that human mites are becoming increasingly resistant to both acaricides. To identify alternate acaricides, we undertook a pilot study of the in vivo activity of the benzoylphenyl urea inhibitor of chitin synthesis, fluazuron, in pigs with sarcoptic mange. Findings. Pigs (n = 5) were infested with S. scabei var suis, and randomised to treatment at the start of peak infestation with fluazuron at a dose of 10 mg/kg/day per os for 7 days (n = 3) or no treatment (n = 2). Clinical scores, skin scrapings for mite counts and blood sampling for pharmacokinetic analysis were undertaken. Fluazuron was well absorbed in treated pigs with measureable blood levels up to 4 weeks post treatment. No adverse effects were observed. Modest acaricidal activity of the compound was observed, with a reduction in severity of skin lesions in treated pigs, as well as a reduction in number of scabies mite's early life stages. Conclusions: The moderate efficacy of fluazuron against scabies mites indicates a lead to the development of alternate treatments for scabies, such as combination therapies that maybe applicable for human use in the future

Molecular ecology and risk factors for third-generation cephalosporin-resistant Escherichia coli carriage by dogs living in urban and nearby rural settings

OBJECTIVES: To compare faecal third-generation cephalosporin-resistant (3GC-R) Escherichia coli isolates from dogs living in a city and in a rural area ∼30 km away; to compare isolates from dogs, cattle and humans in these regions; and to determine risk factors associated with 3GC-R E. coli carriage in these two cohorts of dogs. METHODS: Six hundred dogs were included, with faecal samples processed to recover 3GC-R E. coli using 2 mg/L cefotaxime. WGS was by Illumina and risk factor analyses were by multivariable linear regression using the results of an owner-completed survey. RESULTS: 3GC-R E. coli were excreted by 20/303 rural and 31/297 urban dogs. The dominant canine 3GC-R ST was ST963 (bla(CMY-2)), which also accounted for 25% of CMY-2-producing E. coli in humans. Phylogenetic overlap between cattle and rural dog CTX-M-14-producing E. coli ST117 was observed as well as acquisition of pMOO-32-positive E. coli ST10 by a rural dog, a plasmid common on cattle farms in the area. Feeding raw meat was associated with carrying 3GC-R E. coli in rural dogs, but not in urban dogs, where swimming in rivers was a weak risk factor. CONCLUSIONS: Given clear zoonotic potential for resistant canine E. coli, our work suggests interventions that may reduce this threat. In rural dogs, carriage of 3GC-R E. coli, particularly CTX-M producers, was phylogenetically associated with interaction with local cattle and epidemiologically associated with feeding raw meat. In urban dogs, sources of 3GC-R E. coli appear to be more varied and include environments such as rivers

Incorporating a gender lens into nutrition and health-related policies in Fiji: analysis of policies and stakeholder perspectives

Background: Gender equality, zero hunger and healthy lives and well-being for all, are three of the Sustainable Development Goals (SDGs) that underpin Fiji’s National Development Plan. Work towards each of these goals contributes to the reduction of non-communicable diseases (NCDs). There are gender differences in NCD burden in Fiji. It is, however, unclear whether a gender lens could be more effectively included in nutrition and health-related policies. Methods: This study consisted of three components: (i) a policy content analysis of gender inclusion in nutrition and health-related policies (n = 11); (ii) policy analysis using the WHO Gender Analysis tool to identify opportunities for strengthening future policy; and (iii) informant interviews (n = 18), to understand perceptions of the prospects for gender considerations in future policies. Results: Gender equality was a goal in seven policies (64%); however, most focused on women of reproductive age. One of the policies was ranked as gender responsive. Main themes from key informant interviews were: 1) a needs-based approach for the focus on specific population groups in policies; 2) gender-related roles and responsibilities around nutrition and health; 3) what is considered “equitable” when it comes to gender, nutrition, and health; 4) current considerations of gender in policies and ideas for further gender inclusion; and 5) barriers and enablers to the inclusion of gender considerations in policies. Informants acknowledged gender differences in the burden of nutrition-related NCDs, yet most did not identify a need for stronger inclusion of gender considerations within policies. Conclusions: There is considerable scope for greater inclusion of gender in nutrition and health-related policies in Fiji. This could be done by: 1) framing gender considerations in ways that are actionable and inclusive of a range of gender identities; 2) undertaking advocacy through actor networks to highlight the need for gender-responsive nutrition and health-related policies for key stakeholder groups; 3) ensuring that data collected to monitor policy implementation is disaggregated by sex and genders; and 4) promoting equitable participation in nutrition related issues in communities and governance processes. Action on these four areas are likely critical enablers to more gender equitable NCD reduction in Fiji

A Tractable Experimental Model for Study of Human and Animal Scabies

Scabies, a neglected parasitic disease caused by the microscopic mite Sarcoptes scabiei, is a major driving force behind bacterial skin infections in tropical settings. Aboriginal and Torres Strait Islander peoples are nearly twenty times more likely to die from acute rheumatic fever and rheumatic heart disease than individuals from the wider Australian community. These conditions are caused by bacterial pathogens such as Group A streptococci, which have been linked to underlying scabies infestations. Community based initiatives to reduce scabies and associated disease have expanded, but have been threatened in recent years by emerging drug resistance. Critical biological questions surrounding scabies remain unanswered due to a lack of biomedical research. This has been due in part to a lack of either a suitable animal model or an in vitro culture system for scabies mites. The pig/mite model reported here will be a much needed resource for parasite material and will facilitate in vivo studies on host immune responses to scabies, including relations to associated bacterial pathogenesis, and more detailed studies of molecular evolution and host adaptation. It represents the missing tool to extrapolate emerging molecular data into an in vivo setting and may well allow the development of clinical interventions

Challenges and Outcomes of Posterior Wall Isolation for Ablation of Atrial Fibrillation

BACKGROUND: The left atrial posterior wall (PW) often contains sites required for maintenance of atrial fibrillation (AF). Electrical isolation of the PW is an important feature of all open surgeries for AF. This study assessed the ability of current ablation techniques to achieve PW isolation (PWI) and its effect on recurrent AF. METHODS AND RESULTS: Fifty-seven consecutive patients with persistent or high-burden paroxysmal AF underwent catheter ablation, which was performed using an endocardial-only (30) or a hybrid endocardial-epicardial procedure (27). The catheter ablation lesion set included pulmonary vein antral isolation and a box lesion on the PW (roof and posterior lines). Success in creating the box lesion was assessed as electrical silence of the PW (voltage <0.1 mV) and exit block in the PW with electrical capture. Cox proportional hazards models were used for analysis of AF recurrence. PWI was achieved in 21 patients (36.8%), more often in patients undergoing hybrid ablation than endocardial ablation alone (51.9% versus 23.3%, P=0.05). Twelve patients underwent redo ablation. Five of 12 had a successful procedural PWI, but all had PW reconnection at the redo procedure. Over a median follow-up of 302 days, 56.1% of the patients were free of atrial arrhythmias. No parameter including procedural PWI was a statistically significant predictor of recurrent atrial arrhythmias. CONCLUSIONS: PWI during catheter ablation for AF is difficult to achieve, especially with endocardial ablation alone. Procedural achievement of PWI in this group of patients was not associated with a reduction in recurrent atrial arrhythmias, but reconnection of the PW was common

Modulation of Xenopus oocyte-expressed phospholemman-induced ion currents by co-expression of protein kinases

AbstractPhospholemman (PLM), the major sarcolemmal substrate for phosphorylation by cAMP-dependent kinase (PKA) protein kinase C (PKC) and NIMA kinase in muscle, induces hyperpolarization-activated anion currents in Xenopus oocytes, most probably by enhancing endogenous oocyte currents. PLM peptides from the cytoplasmic tail are phosphorylated by PKA at S68, by NIMA kinase at S63, and by PKC at both S63 and S68. We have confirmed the phosphorylation sites in the intact protein, and we have investigated the role of phosphorylation in the regulatory activity of PLM using oocyte expression experiments. We found: (1) the cytoplasmic domain is not essential for inducing currents in oocytes; (2) co-expression of PKA increased the amplitude of oocyte currents and the amount of PLM in the oocyte membrane largely, but not exclusively, through phosphorylation of S68; (3) co-expression of PKA had no effect on a PLM mutant in which all putative phosphorylation sites had been inactivated by serine to alanine mutation (SSST 62, 63, 68, 69 AAAA); (4) co-expression of PKC had no effect in this system; (5) co-expression of NIMA kinase increased current amplitude and membrane protein level, but did not require PLM phosphorylation. These findings point to a role for phosphorylation in the function of PLM

Molecular Epidemiology of Escherichia coli Producing CTX-M and pAmpC β-Lactamases from Dairy Farms Identifies a Dominant Plasmid Encoding CTX-M-32 but No Evidence for Transmission to Humans in the Same Geographical Region

Third-generation cephalosporin resistance (3GC-R) in Escherichia coli is a rising problem in human and farmed-animal populations. We conducted whole-genome sequencing analysis of 138 representative 3GC-R isolates previously collected from dairy farms in southwest England and confirmed by PCR to carry acquired 3GC-R genes. This analysis identified bla(CTX-M) (131 isolates encoding CTX-M-1, -14, -15, -and 32 and the novel variant CTX-M-214), bla(CMY-2) (6 isolates), and bla(DHA-1) (1 isolate). A highly conserved plasmid was identified in 73 isolates, representing 27 E. coli sequence types. This novel ∼220-kb IncHI2 plasmid carrying bla(CTX-M-32) was sequenced to closure and designated pMOO-32. It was found experimentally to be stable in cattle and human transconjugant E. coli even in the absence of selective pressure and was found by multiplex PCR to be present on 26 study farms representing a remarkable range of transmission over 1,500 square kilometers. However, the plasmid was not found among human urinary E. coli isolates we recently characterized from people living in the same geographical location, collected in parallel with farm sampling. There were close relatives of two bla(CTX-M) plasmids circulating among eight human and two cattle isolates, and a closely related bla(CMY-2) plasmid was found in one cattle and one human isolate. However, phylogenetic evidence of recent sharing of 3GC-R strains between farms and humans in the same region was not found. IMPORTANCE Third-generation cephalosporins (3GCs) are critically important antibacterials, and 3GC resistance (3GC-R) threatens human health, particularly in the context of opportunistic pathogens such as Escherichia coli. There is some evidence for zoonotic transmission of 3GC-R E. coli through food, but little work has been done examining possible transmission via interaction of people with the local near-farm environment. We characterized acquired 3GC-R E. coli found on dairy farms in a geographically restricted region of the United Kingdom and compared these with E. coli from people living in the same region, collected in parallel. While there is strong evidence for recent farm-to-farm transmission of 3GC-R strains and plasmids—including one epidemic plasmid that has a remarkable capacity to be transmitted—there was no evidence that 3GC-R E. coli found on study farms had a significant impact on circulating 3GC-R E. coli strains or plasmids in the local human population