Development of a non-human primate BCG infection model for the evaluation of candidate tuberculosis vaccines.

The lack of validated immunological correlates of protection makes tuberculosis vaccine development difficult and expensive. Using intradermal bacille Calmette-Guréin (BCG) as a surrogate for aerosol Mycobacterium tuberculosis (M.tb) in a controlled human infection model could facilitate vaccine development, but such a model requires preclinical validation. Non-human primates (NHPs) may provide the best model in which to do this. Cynomolgus and rhesus macaques were infected with BCG by intradermal injection. BCG was quantified from a skin biopsy of the infection site and from draining axillary lymph nodes, by culture on solid agar and quantitative polymerase chain reaction. BCG was detected up to 28 days post-infection, with higher amounts of BCG detected in lymph nodes after high dose compared to standard dose infection. Quantifying BCG from lymph nodes of cynomolgus macaques 14 days post-high dose infection showed a significant reduction in the amount of BCG detected in the BCG-vaccinated compared to BCG-naïve animals. Demonstrating a detectable vaccine effect in the lymph nodes of cynomolgus macaques, which is similar in magnitude to that seen in an aerosol M.tb infection model, provides support for proof-of-concept of an intradermal BCG infection model and evidence to support the further evaluation of a human BCG infection model

Phosphorylation of Mouse Immunity-Related GTPase (IRG) Resistance Proteins Is an Evasion Strategy for Virulent Toxoplasma gondii

GTPases of the mouse IRG protein family, mediators of resistance against Toxoplasma gondii in the mouse, are inactivated by a polymorphic kinase of the parasite, resulting in enhanced parasite virulence

The Seventh Data Release of the Sloan Digital Sky Survey

This paper describes the Seventh Data Release of the Sloan Digital Sky Survey (SDSS), marking the completion of the original goals of the SDSS and the end of the phase known as SDSS-II. It includes 11663 deg^2 of imaging data, with most of the roughly 2000 deg^2 increment over the previous data release lying in regions of low Galactic latitude. The catalog contains five-band photometry for 357 million distinct objects. The survey also includes repeat photometry over 250 deg^2 along the Celestial Equator in the Southern Galactic Cap. A coaddition of these data goes roughly two magnitudes fainter than the main survey. The spectroscopy is now complete over a contiguous area of 7500 deg^2 in the Northern Galactic Cap, closing the gap that was present in previous data releases. There are over 1.6 million spectra in total, including 930,000 galaxies, 120,000 quasars, and 460,000 stars. The data release includes improved stellar photometry at low Galactic latitude. The astrometry has all been recalibrated with the second version of the USNO CCD Astrograph Catalog (UCAC-2), reducing the rms statistical errors at the bright end to 45 milli-arcseconds per coordinate. A systematic error in bright galaxy photometr is less severe than previously reported for the majority of galaxies. Finally, we describe a series of improvements to the spectroscopic reductions, including better flat-fielding and improved wavelength calibration at the blue end, better processing of objects with extremely strong narrow emission lines, and an improved determination of stellar metallicities. (Abridged)Comment: 20 pages, 10 embedded figures. Accepted to ApJS after minor correction

Consumers’ experiences of back pain in rural Western Australia: Access to information and services, and self-management behaviours.

Background: Coordinated, interdisciplinary services, supported by self-management underpin effective management for chronic low back pain (CLBP). However, a combination of system, provider and consumer-based barriers exist which limit the implementation of such models into practice, particularly in rural areas where unique access issues exist. In order to improve health service delivery for consumers with CLBP, policymakers and service providers require a more in depth understanding of these issues. The objective of this qualitative study was to explore barriers experienced by consumers in rural settings in Western Australia (WA) to accessing information and services and implementing effective self-management behaviours for CLBP. Methods: Fourteen consumers with a history of CLBP from three rural sites in WA participated. Maximum variation sampling was employed to ensure a range of experiences were captured. An interviewer, blinded to quantitative pain history data, conducted semi-structured telephone interviews using a standardised schedule to explore individuals’ access to information and services for CLBP, and self-management behaviours. Interviews were digitally recorded and transcribed verbatim. Inductive analysis techniques were used to derive and refine key themes. Results: Five key themes were identified that affected individuals’ experiences of managing CLBP in a rural setting, including: 1) poor access to information and services in rural settings; 2) inadequate knowledge and skills among local practitioners; 3) feelings of isolation and frustration; 4) psychological burden associated with CLBP; and 5) competing lifestyle demands hindering effective self-management for CLBP.Conclusions: Consumers in rural WA experienced difficulties in knowing where to access relevant information for CLBP and expressed frustration with the lack of service delivery options to access interdisciplinary and specialist services for CLBP. Competing lifestyle demands such as work and family commitments were cited as key barriers to adopting regular self-management practices. Consumer expectations for improved health service coordination and a workforce skilled in pain management are relevant to future service planning, particularly in the contexts of workforce capacity, community health services, and enablers to effective service delivery in primary care

Magnesium prophylaxis of new-onset atrial fibrillation: A systematic review and meta-analysis.

PurposeAtrial fibrillation (AF) is the most common cardiac arrhythmia in intensive care units (ICU) and is associated with increased morbidity and mortality. Magnesium prophylaxis has been shown to reduce incidence of AF in cardiac surgery patients, however, evidence outside this population is limited. The objective of this study is to summarize studies examining magnesium versus placebo in the prevention of NOAF outside the setting of cardiac surgery.SourceWe performed a comprehensive search of MEDLINE, EMBASE, and Cochrane Library (CENTRAL) from inception until January 3rd, 2023. We included all interventional research studies that compared magnesium to placebo and excluded case reports and post cardiac surgery patients. We conducted meta-analysis using the inverse variance method with random effects modelling.Principal findingsOf the 1493 studies imported for screening, 87 full texts were assessed for eligibility and six citations, representing five randomized controlled trials (n = 4713), were included in the review, with four studies (n = 4654) included in the pooled analysis. Administration of magnesium did not significantly reduce the incidence of NOAF compared to placebo (OR 0.72, [95% CI 0.48 to 1.09]).ConclusionUse of magnesium did not reduce the incidence of NOAF, however these studies represent diverse groups and are hindered by significant bias. Further studies are necessary to determine if there is benefit to magnesium prophylaxis for NOAF in non-cardiac surgery patients

Cellular accumulation of 14Cmethylaminoisobutyric acid by system A is lower in placentas of growth restricted compared to normally grown fetuses

No abstract available