Strengthening universal HIV 'test-and-treat' approaches with social science research.

Prevention, Population and Disease management (PrePoD

The High Prevalence of Vitamin D Insufficiency across Australian Populations Is Only Partly Explained by Season and Latitude

Background Inadequate sun exposure and dietary vitamin D intake can result in vitamin D insufficiency. However, limited data are available on actual vitamin D status and predictors in healthy individuals in different regions and by season.Methods We compared vitamin D status [25-hydroxyvitamin D; 25(OH)D] in people &lt; 60 years of age using data from cross-sectional studies of three regions across Australia: southeast Queensland (27&deg;S; 167 females and 211 males), Geelong region (38&deg;S; 561 females), and Tasmania (43&deg;S; 432 females and 298 males).Results The prevalence of vitamin D insufficiency (&le; 50 nmol/L) in women in winter/spring was 40.5% in southeast Queensland, 37.4% in the Geelong region, and 67.3% in Tasmania. Season, simulated maximum daily duration of vitamin D synthesis, and vitamin D effective daily dose each explained around 14% of the variation in 25(OH)D. Although latitude explained only 3.9% of the variation, a decrease in average 25(OH)D of 1.0 (95% confidence interval, 0.7&ndash;1.3) nmol/L for every degree increase in latitude may be clinically relevant. In some months, we found a high insufficiency or even deficiency when sun exposure protection would be recommended on the basis of the simulated ultraviolet index.Conclusion Vitamin D insufficiency is common over a wide latitude range in Australia. Season appears to be more important than latitude, but both accounted for less than one-fifth of the variation in serum 25(OH)D levels, highlighting the importance of behavioral factors. Current sun exposure guidelines do not seem to fully prevent vitamin D insufficiency, and consideration should be given to their modification or to pursuing other means to achieve vitamin D adequacy.<br /

Differences in the signaling pathways of α1A- and α1B-adrenoceptors are related to different endosomal targeting

Aims: To compare the constitutive and agonist-dependent endosomal trafficking of α1A- and α1B-adrenoceptors (ARs) and to establish if the internalization pattern determines the signaling pathways of each subtype. Methods: Using CypHer5 technology and VSV-G epitope tagged α1A- and α1B-ARs stably and transiently expressed in HEK 293 cells, we analyzed by confocal microscopy the constitutive and agonist-induced internalization of each subtype, and the temporal relationship between agonist induced internalization and the increase in intracellular calcium (determined by FLUO-3 flouorescence), or the phosphorylation of ERK1/2 and p38 MAP kinases (determined by Western blot). Results and Conclusions: Constitutive as well as agonist-induced trafficking of α1A and α1B ARs maintain two different endosomal pools of receptors: one located close to the plasma membrane and the other deeper into the cytosol. Each subtype exhibited specific characteristics of internalization and distribution between these pools that determines their signaling pathways: α1A-ARs, when located in the plasma membrane, signal through calcium and ERK1/2 pathways but, when translocated to deeper endosomes, through a mechanism sensitive to β-arrestin and concanavalin A, continue signaling through ERK1/2 and also activate the p38 pathway. α1B-ARs signal through calcium and ERK1/2 only when located in the membrane and the signals disappear after endocytosis and by disruption of the membrane lipid rafts by methyl-β-cyclodextrin

Photodynamic versus white light-guided treatment of non-muscle invasive bladder cancer: a study protocol for a randomised trial of clinical and cost-effectiveness

Bladder cancer is the most frequently occurring tumour of the urinary system. Ta, T1 tumours and carcinoma in situ (CIS) are grouped as non-muscle invasive bladder cancer (NMIBC), which can be effectively treated by transurethral resection of bladder tumour (TURBT). There are limitations to the visualisation of tumours with conventional TURBT using white light illumination within the bladder. Incomplete resections occur from the failure to identify satellite lesions or the full extent of the tumour leading to recurrence and potential risk of disease progression. To improve complete resection, photodynamic diagnosis (PDD) has been proposed as a method that can enhance tumour detection and guide resection. The objective of the current research is to determine whether PDD-guided TURBT is better than conventional white light surgery and whether it is cost-effective.This article is freely available via Open Access. Click on the publisher URL to access the full-text from the publisher's site

Synthesis of an alkylmagnesium amide and interception of a ring-opened isomer of the important utility amide 2,2,6,6-tetramethylpiperidide (TMP)

Two new magnesium complexes containing the important utility amide 2,2,6,6-tetramethylpiperidide (TMP) have been synthesised. Treating the magnesium bis(alkyl) reagent (Me3SiCH2)2Mg with a molar equivalent of TMP(H) in hydrocarbon medium produces the dimeric alkylmagnesium amide complex [(Me3SiCH2)Mg(μ-TMP)]22, which was isolated in high yield. X-ray crystallography revealed that 2 was an unsymmetrical dimer as unusually the two TMP ligands adopt different conformations – one a chair, the other a twisted boat. Solution studies (multinuclear NMR and DOSY NMR spectroscopies) show that 2 undergoes a monomerisation and Schlenk equilibrium in d8-THF. When (Me3SiCH2)2Mg was reacted with two molar equivalents of TMP(H) in hydrocarbon medium [in an effort to prepare Mg(TMP)2] a crystalline sample of a surprising product, a tetranuclear triheteroanionic amide-alkoxide-amidoalkene [(TMP)Mg(μ-TMP){μ-N(H)C(Me)2CH2CH2CH2C(Me) = CH2}Mg(μ-OCH2SiMe3)]23 was obtained. Complex 3 contains two unexpected anions, namely the alkoxide produced via oxygen insertion into a Mg–C bond, and the primary amidoalkene which is produced via ring opening of the TMP anion

Why MSM in rural South African communities should be an HIV prevention research priority.

Research into HIV and men who have sex with men's (MSM) health in South Africa has been largely confined to the metropolitan centres. Only two studies were located making reference to MSM in rural contexts or same-sex behaviors among men in the same. There is growing recognition in South Africa that MSM are not only disproportionately affected by HIV and have been underserved by the country's national response, but that they contribute significantly to sustaining the high number of new infections recorded each year. We argue that to meet the objectives of the country's national strategic plan for HIV, STI and TB it is important we know how these behaviours may be contributing to the sustained rural HIV epidemic in the youngest age groups and determine what constitutes appropriate and feasible programmatic response that can be implemented in the country's public sector health services

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

The IDENTIFY study: the investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer - a multicentre observational study.

Funder: Action Bladder Cancer UKFunder: Rosetrees Trust; Id: http://dx.doi.org/10.13039/501100000833Funder: Urology Care Foundation; Id: http://dx.doi.org/10.13039/100006280OBJECTIVE: To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation. PATIENTS AND METHODS: This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries. RESULTS: Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3-34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1-30.2), UTUC (n = 128) 1.14% (95% CI 0.77-1.52), renal cancer (n = 107) 1.05% (95% CI 0.80-1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32-2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03-1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90-4.15; P < 0.001), male sex 1.30 (95% CI 1.14-1.50; P < 0.001), and smoking 2.70 (95% CI 2.30-3.18; P < 0.001). CONCLUSIONS: A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer