Long-term supplementation with anthocyanin-rich or -poor Rubus idaeus berries does not influence microvascular architecture nor cognitive outcome in the APP/PS-1 mouse model of Alzheimer’s disease

Disruption of microvascular architecture is a common pathogenic mechanism in the progression of Alzheimer's disease (AD). Given the anti-angiogenic activity of berry (poly)phenols, we investigated whether long-term feeding of Rubus idaeus (raspberries) could ameliorate cerebral microvascular pathology and improve cognition in the APP/PS-1 mouse model of AD. Male C57Bl/6J mice (50 wild type, 50 APP/PS-1) aged 4-months were fed for 24-weeks, with a normal diet enriched with either 100 mg/day glucose (control diet) or supplemented with glucose and freeze-dried anthocyanin-rich (red) or -poor (yellow) raspberries (100 mg/day) and assessed/sampled post intervention. Cerebral microvascular architecture of wild-type mice was characterised by regularly spaced capillaries with uniform diameters, unlike APP/PS-1 transgenic mice which showed dysregulated microvascular architecture. Long-term feeding of raspberries demonstrated limited modulation of microbiota and no substantive effect on microvascular architecture or cognition in either mice model although changes were evident in endogenous cerebral and plasmatic metabolite

Long-term supplementation with anthocyanin-rich or -poor Rubus idaeus berries does not influence microvascular architecture nor cognitive outcome in the APP/PS-1 mouse model of Alzheimer's disease

Disruption of microvascular architecture is a common pathogenic mechanism in the progression of Alzheimer's disease (AD). Given the anti-angiogenic activity of berry (poly)phenols, we investigated whether long-term feeding of Rubus idaeus (raspberries) could ameliorate cerebral microvascular pathology and improve cognition in the APP/PS-1 mouse model of AD. Male C57Bl/6J mice (50 wild type, 50 APP/PS-1) aged 4-months were fed for 24-weeks, with a normal diet enriched with either 100 mg/day glucose (control diet) or supplemented with glucose and freeze-dried anthocyanin-rich (red) or -poor (yellow) raspberries (100 mg/day) and assessed/sampled post intervention. Cerebral microvascular architecture of wild-type mice was characterised by regularly spaced capillaries with uniform diameters, unlike APP/PS-1 transgenic mice which showed dysregulated microvascular architecture. Long-term feeding of raspberries demonstrated limited modulation of microbiota and no substantive effect on microvascular architecture or cognition in either mice model although changes were evident in endogenous cerebral and plasmatic metabolite

Classification of early tuberculosis states to guide research for improved care and prevention: an international Delphi consensus exercise

The current active–latent paradigm of tuberculosis largely neglects the documented spectrum of disease. Inconsistency with regard to definitions, terminology, and diagnostic criteria for different tuberculosis states has limited the progress in research and product development that are needed to achieve tuberculosis elimination. We aimed to develop a new framework of classification for tuberculosis that accommodates key disease states but is sufficiently simple to support pragmatic research and implementation. Through an international Delphi exercise that involved 71 participants representing a wide range of disciplines, sectors, income settings, and geographies, consensus was reached on a set of conceptual states, related terminology, and research gaps. The International Consensus for Early TB (ICE-TB) framework distinguishes disease from infection by the presence of macroscopic pathology and defines two subclinical and two clinical tuberculosis states on the basis of reported symptoms or signs of tuberculosis, further differentiated by likely infectiousness. The presence of viable Mycobacterium tuberculosis and an associated host response are prerequisites for all states of infection and disease. Our framework provides a clear direction for tuberculosis research, which will, in time, improve tuberculosis clinical care and elimination policies

The utility of high-flow nasal oxygen for severe COVID-19 pneumonia in a resource-constrained setting: A multi-centre prospective observational study.

BACKGROUND: The utility of heated and humidified high-flow nasal oxygen (HFNO) for severe COVID-19-related hypoxaemic respiratory failure (HRF), particularly in settings with limited access to intensive care unit (ICU) resources, remains unclear, and predictors of outcome have been poorly studied. METHODS: We included consecutive patients with COVID-19-related HRF treated with HFNO at two tertiary hospitals in Cape Town, South Africa. The primary outcome was the proportion of patients who were successfully weaned from HFNO, whilst failure comprised intubation or death on HFNO. FINDINGS: The median (IQR) arterial oxygen partial pressure to fraction inspired oxygen ratio (PaO2/FiO2) was 68 (54-92) in 293 enroled patients. Of these, 137/293 (47%) of patients [PaO2/FiO2 76 (63-93)] were successfully weaned from HFNO. The median duration of HFNO was 6 (3-9) in those successfully treated versus 2 (1-5) days in those who failed (p<0.001). A higher ratio of oxygen saturation/FiO2 to respiratory rate within 6 h (ROX-6 score) after HFNO commencement was associated with HFNO success (ROX-6; AHR 0.43, 0.31-0.60), as was use of steroids (AHR 0.35, 95%CI 0.19-0.64). A ROX-6 score of ≥3.7 was 80% predictive of successful weaning whilst ROX-6 ≤ 2.2 was 74% predictive of failure. In total, 139 patents (52%) survived to hospital discharge, whilst mortality amongst HFNO failures with outcomes was 129/140 (92%). INTERPRETATION: In a resource-constrained setting, HFNO for severe COVID-19 HRF is feasible and more almost half of those who receive it can be successfully weaned without the need for mechanical ventilation

Clinical features and outcomes of COVID-19 admissions in a population with a high prevalence of HIV and tuberculosis: a multicentre cohort study

Background There is still a paucity of evidence on the outcomes of coronavirus disease 2019 (COVID-19) among people living with human immunodeficiency virus (PWH) and those co-infected with tuberculosis (TB), particularly in areas where these conditions are common. We describe the clinical features, laboratory findings and outcome of hospitalised PWH and human immunodeficiency virus (HIV)-uninfected COVID-19 patients as well as those co-infected with tuberculosis (TB). Methods We conducted a multicentre cohort study across three hospitals in Cape Town, South Africa. All adults requiring hospitalisation with confirmed COVID-19 pneumonia from March to July 2020 were analysed. Results PWH comprised 270 (19%) of 1434 admissions. There were 47 patients with active tuberculosis (3.3%), of whom 29 (62%) were PWH. Three-hundred and seventy-three patients (26%) died. The mortality in PWH (n = 71, 26%) and HIV-uninfected patients (n = 296, 25%) was comparable. In patients with TB, PWH had a higher mortality than HIV-uninfected patients (n = 11, 38% vs n = 3, 20%; p = 0.001). In multivariable survival analysis a higher risk of death was associated with older age (Adjusted Hazard Ratio (AHR) 1.03 95%CI 1.02–1.03, p < 0.001), male sex (AHR1.38 (95%CI 1.12–1.72, p = 0.003) and being “overweight or obese” (AHR 1.30 95%CI 1.03–1.61 p = 0.024). HIV (AHR 1.28 95%CI 0.95–1.72, p 0.11) and active TB (AHR 1.50 95%CI 0.84–2.67, p = 0.17) were not independently associated with increased risk of COVID-19 death. Risk factors for inpatient mortality in PWH included CD4 cell count < 200 cells/mm3, higher admission oxygen requirements, absolute white cell counts, neutrophil/lymphocyte ratios, C-reactive protein, and creatinine levels. Conclusion In a population with high prevalence of HIV and TB, being overweight/obese was associated with increased risk of mortality in COVID-19 hospital admissions, emphasising the need for public health interventions in this patient population

Trace elements at the intersection of marine biological and geochemical evolution

Life requires a wide variety of bioessential trace elements to act as structural components and reactive centers in metalloenzymes. These requirements differ between organisms and have evolved over geological time, likely guided in some part by environmental conditions. Until recently, most of what was understood regarding trace element concentrations in the Precambrian oceans was inferred by extrapolation, geochemical modeling, and/or genomic studies. However, in the past decade, the increasing availability of trace element and isotopic data for sedimentary rocks of all ages has yielded new, and potentially more direct, insights into secular changes in seawater composition – and ultimately the evolution of the marine biosphere. Compiled records of many bioessential trace elements (including Ni, Mo, P, Zn, Co, Cr, Se, and I) provide new insight into how trace element abundance in Earth's ancient oceans may have been linked to biological evolution. Several of these trace elements display redox-sensitive behavior, while others are redox-sensitive but not bioessential (e.g., Cr, U). Their temporal trends in sedimentary archives provide useful constraints on changes in atmosphere-ocean redox conditions that are linked to biological evolution, for example, the activity of oxygen-producing, photosynthetic cyanobacteria. In this review, we summarize available Precambrian trace element proxy data, and discuss how temporal trends in the seawater concentrations of specific trace elements may be linked to the evolution of both simple and complex life. We also examine several biologically relevant and/or redox-sensitive trace elements that have yet to be fully examined in the sedimentary rock record (e.g., Cu, Cd, W) and suggest several directions for future studies

Risk factors for Coronavirus disease 2019 (Covid-19) death in a population cohort study from the Western Cape province, South Africa

Risk factors for coronavirus disease 2019 (COVID-19) death in sub-Saharan Africa and the effects of human immunodeficiency virus (HIV) and tuberculosis on COVID-19 outcomes are unknown. We conducted a population cohort study using linked data from adults attending public-sector health facilities in the Western Cape, South Africa. We used Cox proportional hazards models, adjusted for age, sex, location, and comorbidities, to examine the associations between HIV, tuberculosis, and COVID-19 death from 1 March to 9 June 2020 among (1) public-sector “active patients” (≥1 visit in the 3 years before March 2020); (2) laboratory-diagnosed COVID-19 cases; and (3) hospitalized COVID-19 cases. We calculated the standardized mortality ratio (SMR) for COVID-19, comparing adults living with and without HIV using modeled population estimates.Among 3 460 932 patients (16% living with HIV), 22 308 were diagnosed with COVID-19, of whom 625 died. COVID19 death was associated with male sex, increasing age, diabetes, hypertension, and chronic kidney disease. HIV was associated with COVID-19 mortality (adjusted hazard ratio [aHR], 2.14; 95% confidence interval [CI], 1.70–2.70), with similar risks across strata of viral loads and immunosuppression. Current and previous diagnoses of tuberculosis were associated with COVID-19 death (aHR, 2.70 [95% CI, 1.81–4.04] and 1.51 [95% CI, 1.18–1.93], respectively). The SMR for COVID-19 death associated with HIV was 2.39 (95% CI, 1.96–2.86); population attributable fraction 8.5% (95% CI, 6.1–11.1)

The current aetiology of malignant pleural effusion in the Western Cape Province, South Africa

CITATION: Koegelenberg, C. F. N. et al. 2018. The current aetiology of malignant pleural effusion in the Western Cape Province, South Africa. South African Medical Journal, 108(4):275-277, doi:10.7196/SAMJ.2018.v108i4.12914.The original publication is available at http://www.samj.org.zaBackground: Malignant pleural effusion (MPE) represents a very common cause of pleural exudates, and is one of the most challenging pleural disorders to manage. This could be attributed to the paucity of high-quality experimental evidence, and inconsistent practice worldwide. South Africa (SA) currently has no data regarding the aetiology of MPE. Objectives: To identify the most common malignancies causing MPE in a population served by a large tertiary hospital in SA, and specifically the relative contribution of mesothelioma. A secondary objective was to evaluate the efficacy of chemical pleurodesis in a subset of patients. Methods: We retrospectively included all known cases of MPE evaluated at our institution over a 3-year period with a tissue diagnosis of MPE. Results: The most common causes of MPE in a total of 274 patients were lung cancer (n=174, 63.5%), breast cancer (n=32, 11.7%), unknown primary (n=22, 11.7%) and mesothelioma (n=27, 9.9%). Talc pleurodesis was performed in 81 of 194 patients (41.8%) referred to our division, and was radiologically successful in 22 of 25 (88.0%) followed up to 3 months. Conclusions: The main cause of MPE in our setting was lung cancer, followed by breast cancer, unknown primary and mesothelioma. Chemical pleurodesis was a viable palliative measure for MPE in this population.http://www.samj.org.za/index.php/samj/article/view/12262Publisher's versio

Pathogenesis, clinical features, and phenotypes of pulmonary hypertension associated with interstitial lung disease: A consensus statement from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative ‐ Group 3 Pulmonary Hypertension

Abstract Pulmonary hypertension (PH) is a frequent complication of interstitial lung disease (ILD). Although PH has mostly been described in idiopathic pulmonary fibrosis, it can manifest in association with many other forms of ILD. Associated pathogenetic mechanisms are complex and incompletely understood but there is evidence of disruption of molecular and genetic pathways, with panvascular histopathologic changes, multiple pathophysiologic sequelae, and profound clinical ramifications. While there are some recognized clinical phenotypes such as combined pulmonary fibrosis and emphysema and some possible phenotypes such as connective tissue disease associated with ILD and PH, the identification of further phenotypes of PH in ILD has thus far proven elusive. This statement reviews the current evidence on the pathogenesis, recognized patterns, and useful diagnostic tools to detect phenotypes of PH in ILD. Distinct phenotypes warrant recognition if they are characterized through either a distinct presentation, clinical course, or treatment response. Furthermore, we propose a set of recommendations for future studies that might enable the recognition of new phenotypes