Endomyocardial fibrosis at autopsy in Cape Town

The pathology of 3 cases of endomyocardial fibrosis (EMF) encountered at autopsy in Cape Town is described. The first case of EMF in a non-White permanent resident of South Africa is documented. The macroscopic features allow distinction between EMF and the usual form of idiopathic cardiomyopathy seen in Cape Town. There is a small potential reservoir of patients in Cape Town with typical EMF, but the presence of a coexistent (valvular) lesion may lead to such hearts being ignored in studies of idiopathic cardiomyopathy.S. Afr. Med. J. 48, 1363 (1974)

Effect of Amoxicillin in combination with Imipenem-Relebactam against Mycobacterium abscessus

Infections caused by Mycobacterium abscessus are increasing in prevalence in cystic fibrosis patients. This opportunistic pathogen′s intrinsic resistance to most antibiotics has perpetuated an urgent demand for new, more effective therapeutic interventions. Here we report a prospective advance in the treatment of M. abscessus infection; increasing the susceptibility of the organism to amoxicillin, by repurposing the β-lactamase inhibitor, relebactam, in combination with the front line M. abscessus drug imipenem. We establish by multiple in vitro methods that this combination works synergistically to inhibit M. abscessus. We also show the direct competitive inhibition of the M. abscessus β-lactamase, BlaMab, using a novel assay, which is validated kinetically using the nitrocefin reporter assay and in silico binding studies. Furthermore, we reverse the susceptibility by overexpressing BlaMab in M. abscessus, demonstrating relebactam-BlaMab target engagement. Finally, we highlight the in vitro efficacy of this combination against a panel of M. abscessus clinical isolates, revealing the therapeutic potential of the amoxicillin-imipenem-relebactam combination

Genetic partitioning of interleukin-6 signalling in mice dissociates Stat3 from Smad3-mediated lung fibrosis

Idiopathic pulmonary fibrosis (IPF) is a fatal disease that is unresponsive to current therapies and characterized by excessive collagen deposition and subsequent fibrosis. While inflammatory cytokines, including interleukin (IL)-6, are elevated in IPF, the molecular mechanisms that underlie this disease are incompletely understood, although the development of fibrosis is believed to depend on canonical transforming growth factor (TGF)-β signalling. We examined bleomycin-induced inflammation and fibrosis in mice carrying a mutation in the shared IL-6 family receptor gp130. Using genetic complementation, we directly correlate the extent of IL-6-mediated, excessive Stat3 activity with inflammatory infiltrates in the lung and the severity of fibrosis in corresponding gp130757F mice. The extent of fibrosis was attenuated in B lymphocyte-deficient gp130757F;µMT−/− compound mutant mice, but fibrosis still occurred in their Smad3−/− counterparts consistent with the capacity of excessive Stat3 activity to induce collagen 1α1 gene transcription independently of canonical TGF-β/Smad3 signalling. These findings are of therapeutic relevance, since we confirmed abundant STAT3 activation in fibrotic lungs from IPF patients and showed that genetic reduction of Stat3 protected mice from bleomycin-induced lung fibrosis

The convivial and the pastoral in patient-doctor relationships : a multi-country study of patient stories of care, choice and medical authority in cancer diagnostic processes

Experiences of cancer diagnosis are changing in light of both the increasingly technological‐clinical diagnostic processes and the socio‐political context in which interpersonal relations take place. This has raised questions about how we might understand patient–doctor relationship marked by asymmetries of knowledge and social capital, but that emphasise patients’ empowered choices and individualised care. As part of an interview study of 155 participants with bowel or lung cancer across Denmark, England and Sweden, we explored participants’ stories of the decisions made during their cancer diagnostic process. By focusing on the intersections of care, choice and medical authority – a convivial pastoral dynamic – we provide a conceptual analysis of the normative ambivalences in people's stories of their cancer diagnosis. We found that participants drew from care, choice and medical authority to emphasise their relationality and interdependence with their doctors in their stories of their diagnosis. Importantly negotiations of an asymmetrical patient–doctor relationship were part of an on‐going realisation of the healthcare processes as a human endeavour. We were therefore able to draw attention to the limitations of dichotomising emancipatory‐empowerment discourses and argue for a theorisation of the patient–doctor relationship as a contextually bounded and relationally ambivalent humanity

Average luminosity distance in inhomogeneous universes

The paper studies the correction to the distance modulus induced by inhomogeneities and averaged over all directions from a given observer. The inhomogeneities are modeled as mass-compensated voids in random or regular lattices within Swiss-cheese universes. Void radii below 300 Mpc are considered, which are supported by current redshift surveys and limited by the recently observed imprint such voids leave on CMB. The averaging over all directions, performed by numerical ray tracing, is non-perturbative and includes the supernovas inside the voids. Voids aligning along a certain direction produce a cumulative gravitational lensing correction that increases with their number. Such corrections are destroyed by the averaging over all directions, even in non-randomized simple cubic void lattices. At low redshifts, the average correction is not zero but decays with the peculiar velocities and redshift. Its upper bound is provided by the maximal average correction which assumes no random cancelations between different voids. It is described well by a linear perturbation formula and, for the voids considered, is 20% of the correction corresponding to the maximal peculiar velocity. The average correction calculated in random and simple cubic void lattices is severely damped below the predicted maximal one after a single void diameter. That is traced to cancellations between the corrections from the fronts and backs of different voids. All that implies that voids cannot imitate the effect of dark energy unless they have radii and peculiar velocities much larger than the currently observed. The results obtained allow one to readily predict the redshift above which the direction-averaged fluctuation in the Hubble diagram falls below a required precision and suggest a method to extract the background Hubble constant from low redshift data without the need to correct for peculiar velocities.Comment: 34 pages, 21 figures, matches the version accepted in JCA

Feeding dihydroquercetin in wheat-based diets to laying hens: impact on egg production and quality of fresh and stored eggs

1. This study assessed the impact of dietary dihydroquercetin (DHQ) in wheat-based diets on egg production, composition and quality when fed to laying hens. A total of 80 Hy-Line Brown hens were allocated to 20 enriched layer cages, over two tiers, in groups of four birds. 2. Two wheat-based diets were used in the study. A basal diet, meeting the nutrient requirement of the hens, containing 11.56 MJ/kg AME and 172 g/kg crude protein, was mixed and split in two parts. One part was fed as prepared to the control group of birds. The second diet was made by adding 1.5 g DHQ per kg basal diet and fed to the treatment group of birds. This level was relatively high and extended the data on levels normally fed. The diets were fed in a meal form and did not contain any coccidiostat, antimicrobial growth promoters or other similar additives. Each diet was fed to hens in 10 replicate cages for four weeks, from 22 to 26 weeks of age, following randomisation. 3. Subsequently, eggs were investigated to determine the impact of dietary DHQ on the quality variables of fresh and 28-day stored eggs. 4. Overall, feeding 1.5 g/kg dietary DHQ for four weeks did not affect (P>0.05) egg production or the quality of fresh and stored eggs. Any observed egg quality changes (P<0.05) confirmed the expected effects of egg storage

Event Reconstruction in the PHENIX Central Arm Spectrometers

The central arm spectrometers for the PHENIX experiment at the Relativistic Heavy Ion Collider have been designed for the optimization of particle identification in relativistic heavy ion collisions. The spectrometers present a challenging environment for event reconstruction due to a very high track multiplicity in a complicated, focusing, magnetic field. In order to meet this challenge, nine distinct detector types are integrated for charged particle tracking, momentum reconstruction, and particle identification. The techniques which have been developed for the task of event reconstruction are described.Comment: Accepted for publication in Nucl. Instrum. A. 34 pages, 23 figure

Effect of rearing temperature on physiological measures and antioxidant status of broiler chickens fed stevia (Stevia rebaudiana B.) leaf meal and exogenous xylanase

Background The global climate is warming. Heat stress, as a result of high ambient temperatures, may negatively impact physiology and reduce growth performance of poultry. Stevia is a perennial shrub indigenous to South America where its phytochemical extracts have been used as a natural sweetener for hundreds of years. Its physiological effects, including antioxidant properties, on poultry are well known, however, the translation of these to improved growth performance is variable. Combining stevia with a commercial xylanase to enhance feed digestibility could therefore form a feeding strategy to partially mitigate the negative impact of rearing birds under high ambient temperatures. Purpose The study aimed to compare the growth performance, dietary energy and nutrient availability, oxidative status, gastrointestinal tract development, and caecal short chain fatty acid concentration; at two ambient rearing temperatures, when feeding diets containing stevia and exogenous xylanase, alone or in combination, to broiler chickens. Study design/Methods: Day-old chicks (n = 105) were reared in a single floor pen following breeder recommendations for the first 7 days, whereupon birds (n = 96) were randomly allocated to one of four experimental diets (negative control, stevia at 20 g/kg diet, xylanase at 100 FXU/kg diet, stevia at 20 g/kg diet + xylanase at 100 FXU/kg diet), in one of two environmental conditions (high ambient temperature at 32 ± 2 °C or regular rearing at breeder recommendations), in a 2 × 2 × 2 factorial design. Results Rearing birds at high ambient temperature reduced daily feed intake (p = 0.02). Birds fed stevia and reared at regular temperature had similar weight gain to birds reared in high ambient temperatures, although birds on the control diet housed at regular temperatures had the greatest weight gain (P < 0.05). Exogenous xylanase improved overall dietary metabolisable energy and improved nitrogen retention in the high ambient temperature group only (P < 0.05). Dietary stevia reduced caecal digesta butyric acid: acetic acid at regular temperature, but xylanase increased the butyric acid concentration at high ambient temperature (P < 0.05). Dietary stevia increased (P < 0.001) the hepatic carotenoid concentrations and xylanase improved (P < 0.05) hepatic vitamin E concentrations. Conclusions Rearing temperature is an important environmental factor in broiler production. Exogenous xylanase supplementation can increase feed efficiency and dietary metabolisable energy. Feeding xylanase or stevia improves hepatic antioxidant status in broilers by increasing hepatic vitamin E and carotenoids, respectively, suggesting that either may be effective in counteracting oxidative stress