Interstitial lung diseases (ILDs), which can arise from a broad spectrum of distinct aetiologies, can manifest as a pulmonary complication of an underlying autoimmune and connective tissue disease ...(CTD-ILD), such as rheumatoid arthritis-ILD and systemic sclerosis (SSc-ILD). Patients with clinically distinct ILDs, whether CTD-related or not, can exhibit a pattern of common clinical disease behaviour (declining lung function, worsening respiratory symptoms and higher mortality), attributable to progressive fibrosis in the lungs. In recent years, the tyrosine kinase inhibitor nintedanib has demonstrated efficacy and safety in idiopathic pulmonary fibrosis (IPF), SSc-ILD and a broad range of other fibrosing ILDs with a progressive phenotype, including those associated with CTDs. Data from phase II studies also suggest that pirfenidone, which has a different-yet largely unknown-mechanism of action, may also have activity in other fibrosing ILDs with a progressive phenotype, in addition to its known efficacy in IPF. Collectively, these studies add weight to the hypothesis that, irrespective of the original clinical diagnosis of ILD, a progressive fibrosing phenotype may arise from common, underlying pathophysiological mechanisms of fibrosis involving pathways associated with the targets of nintedanib and, potentially, pirfenidone. However, despite the early proof of concept provided by these clinical studies, very little is known about the mechanistic commonalities and differences between ILDs with a progressive phenotype. In this review, we explore the biological and genetic mechanisms that drive fibrosis, and identify the missing evidence needed to provide the rationale for further studies that use the progressive phenotype as a target population.
Aerosols of biological origin play a vital role in the Earth system, particularly in the interactions between atmosphere, biosphere, climate, and public health. Airborne bacteria, fungal spores, ...pollen, and other bioparticles are essential for the reproduction and spread of organisms across various ecosystems, and they can cause or enhance human, animal, and plant diseases. Moreover, they can serve as nuclei for cloud droplets, ice crystals, and precipitation, thus influencing the hydrological cycle and climate. The sources, abundance, composition, and effects of biological aerosols and the atmospheric microbiome are, however, not yet well characterized and constitute a large gap in the scientific understanding of the interaction and co-evolution of life and climate in the Earth system. This review presents an overview of the state of bioaerosol research, highlights recent advances, and outlines future perspectives in terms of bioaerosol identification, characterization, transport, and transformation processes, as well as their interactions with climate, health, and ecosystems, focusing on the role bioaerosols play in the Earth system.
•Aerosols of biological origin play a vital role in the Earth system.•Bioaerosols are essential for biological reproduction and can cause diseases.•Bioparticles can serve as nuclei for cloud droplets, ice crystals, and precipitation.•Interaction and co-evolution of life and climate in the Earth system•Overview of the state of bioaerosol research and recent advances
Summary Hepatitis B virus (HBV) is the leading cause of chronic liver disease and liver-related death worldwide, with the majority of these cases occurring in areas of Africa and Asia where HBV ...prevalence is high. Many of the countries that are affected by hepatitis B are also affected by a high HIV burden, leading to frequent HIV/HBV co-infection. The consequences of co-infection, including increased liver-related morbidity and mortality, increased hepatitis B viral replication, immune reconstitution to HBV in the setting of antiretroviral therapy, and hepatotoxicity from antiretroviral drugs, are especially important in regions with expanding antiretroviral programmes. Little data, however, are available on HIV/HBV co-infection from regions with high chronic hepatitis B prevalence. This Review discusses the epidemiology, natural history, pathogenesis, and management of HIV/HBV co-infection from these areas. Topics for future research relevant to HIV/HBV co-infection in Africa and Asia are also highlighted.
The authors examines issues related to the molecular identification of organic compounds in the atmosphere. Topics discussed include optically active compounds and nucleating compounds.
Few estimates exist of the life expectancy of HIV-positive adults receiving antiretroviral treatment (ART) in low- and middle-income countries. We aimed to estimate the life expectancy of patients ...starting ART in South Africa and compare it with that of HIV-negative adults.
Data were collected from six South African ART cohorts. Analysis was restricted to 37,740 HIV-positive adults starting ART for the first time. Estimates of mortality were obtained by linking patient records to the national population register. Relative survival models were used to estimate the excess mortality attributable to HIV by age, for different baseline CD4 categories and different durations. Non-HIV mortality was estimated using a South African demographic model. The average life expectancy of men starting ART varied between 27.6 y (95% CI: 25.2-30.2) at age 20 y and 10.1 y (95% CI: 9.3-10.8) at age 60 y, while estimates for women at the same ages were substantially higher, at 36.8 y (95% CI: 34.0-39.7) and 14.4 y (95% CI: 13.3-15.3), respectively. The life expectancy of a 20-y-old woman was 43.1 y (95% CI: 40.1-46.0) if her baseline CD4 count was ≥ 200 cells/µl, compared to 29.5 y (95% CI: 26.2-33.0) if her baseline CD4 count was <50 cells/µl. Life expectancies of patients with baseline CD4 counts ≥ 200 cells/µl were between 70% and 86% of those in HIV-negative adults of the same age and sex, and life expectancies were increased by 15%-20% in patients who had survived 2 y after starting ART. However, the analysis was limited by a lack of mortality data at longer durations.
South African HIV-positive adults can have a near-normal life expectancy, provided that they start ART before their CD4 count drops below 200 cells/µl. These findings demonstrate that the near-normal life expectancies of HIV-positive individuals receiving ART in high-income countries can apply to low- and middle-income countries as well. Please see later in the article for the Editors' Summary.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We sought to assess mental health at the time of antiretroviral therapy (ART) initiation and subsequent retention in care over a six-month follow-up period. A total of 136 people living with HIV in ...South Africa were administered surveys measuring demographic information and mental health indicators at the time of ART initiation. Follow-up was completed via chart abstraction to assess for six-month outcomes of retention in care and viral suppression. At enrollment, 45/136 (33%), 67/136 (49%), and 45/136 (33%) participants screened positive for depression, anxiety, and alcohol use disorder, respectively. After six months of follow-up, 96/136 (71%) participants remained in care; 35/87 (40.2%) participants who remained in care had a level <50 copies/mL. Those with depression (49% vs. 77% retained; p < 0.01) and those with alcohol use disorder (52% vs. 76% retained; p < 0.01) were less likely to be retained in care. In multivariable logistic regression, depression OR 3.46 (95% CI: 1.33, 7.97; p < 0.01) and alcohol abuse OR 3.89 (95% CI: 1.70, 8.97; p < 0.01) were independently associated with loss from care. These results emphasize the importance of mental health on early ART outcomes and the HIV care continuum.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tenofovir (TDF) is part of the WHO recommended first-line antiretroviral therapy (ART); however, there are limited data comparing TDF to other nucleoside reverse transcriptase inhibitors in ...resource-limited-settings. Using a routine workplace and community-based ART cohort in South Africa, we assessed single drug substitution, HIV RNA suppression, CD4 count increase, loss-from-care, and mortality between TDF, stavudine (d4T) 30 mg dose, and zidovudine (AZT).
In a prospective cohort study we included ART naïve patients aged ≥17 years-old who initiated ART containing TDF, d4T, or AZT between 2007 and 2009. For analysis of single drug substitutions we used a competing-risks time-to-event analysis; for loss-from-care, mixed-effect Poisson modeling; for HIV RNA suppression, competing-risks logistic regression; for CD4 count slope, mixed-effects linear regression; and for mortality, proportional hazards modeling.
Of 6,196 patients, the initial drug was TDF for 665 (11%), d4T for 4,179 (68%), and AZT for 1,352 (22%). During the first 6 months of ART, the adjusted hazard ratio for a single drug substitution was 2.3 for d4T (95% confidence interval CI: 0.27, 19) and 5.2 for AZT (95% CI: 1.1, 23), compared to TDF; whereas, after 6 months, it was 10 (95% CI: 5.8, 18) and 4.4 (95% CI: 2.5, 7.8) for d4T and AZT, respectively. Virologic suppression was similar by agent; however, CD4 count rise was lowest for AZT. The adjusted hazard ratio for loss-from-care, when compared to TDF, was 1.5 (95% CI: 1.1, 1.9) for d4T and 1.2 (95% CI: 1.1, 1.4) for AZT. The adjusted hazard ratio for mortality, when compared to TDF, was 2.7 (95% CI: 2.0, 3.5) and 1.4 (95% CI: 1.3, 1.5) and for d4T and AZT, respectively.
In routine care, TDF appeared to perform better than either d4T or AZT, most notably with less drug substitution and mortality than for either other agent.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Climate change vulnerability assessment of species Foden, Wendy B.; Young, Bruce E.; Akçakaya, H. Resit ...
Wiley interdisciplinary reviews. Climate change,
January/February 2019, Letnik:
10, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Assessing species' vulnerability to climate change is a prerequisite for developing effective strategies to conserve them. The last three decades have seen exponential growth in the number of studies ...evaluating how, how much, why, when, and where species will be impacted by climate change. We provide an overview of the rapidly developing field of climate change vulnerability assessment (CCVA) and describe key concepts, terms, steps and considerations. We stress the importance of identifying the full range of pressures, impacts and their associated mechanisms that species face and using this as a basis for selecting the appropriate assessment approaches for quantifying vulnerability. We outline four CCVA assessment approaches, namely trait‐based, correlative, mechanistic and combined approaches and discuss their use. Since any assessment can deliver unreliable or even misleading results when incorrect data and parameters are applied, we discuss finding, selecting, and applying input data and provide examples of open‐access resources. Because rare, small‐range, and declining‐range species are often of particular conservation concern while also posing significant challenges for CCVA, we describe alternative ways to assess them. We also describe how CCVAs can be used to inform IUCN Red List assessments of extinction risk. Finally, we suggest future directions in this field and propose areas where research efforts may be particularly valuable.
This article is categorized under:
Climate, Ecology, and Conservation > Extinction Risk
Assessing species' vulnerability to climate change is becoming a prerequisite for conservation planning, but choosing approaches, methods and data can be challenging. Key to informing such choices is consideration of the full range of climate change pressures and their likely mechanisms of impact on individuals, subpopulations and species. Navigate a sound path through do's and don'ts, and explore resources and future perspectives in this exciting field.
Mutations in the acid β-glucocerebrosidase (GBA1) gene, responsible for the lysosomal storage disorder Gaucher's disease (GD), are the strongest genetic risk factor for Parkinson's disease (PD) known ...to date. Here we generate induced pluripotent stem cells from subjects with GD and PD harbouring GBA1 mutations, and differentiate them into midbrain dopaminergic neurons followed by enrichment using fluorescence-activated cell sorting. Neurons show a reduction in glucocerebrosidase activity and protein levels, increase in glucosylceramide and α-synuclein levels as well as autophagic and lysosomal defects. Quantitative proteomic profiling reveals an increase of the neuronal calcium-binding protein 2 (NECAB2) in diseased neurons. Mutant neurons show a dysregulation of calcium homeostasis and increased vulnerability to stress responses involving elevation of cytosolic calcium. Importantly, correction of the mutations rescues such pathological phenotypes. These findings provide evidence for a link between GBA1 mutations and complex changes in the autophagic/lysosomal system and intracellular calcium homeostasis, which underlie vulnerability to neurodegeneration.
The reorganization of patterns of species diversity driven by anthropogenic climate change, and the consequences for humans, are not yet fully understood or appreciated. Nevertheless, changes in ...climate conditions are useful for predicting shifts in species distributions at global and local scales. Here we use the velocity of climate change to derive spatial trajectories for climatic niches from 1960 to 2009 (ref. 7) and from 2006 to 2100, and use the properties of these trajectories to infer changes in species distributions. Coastlines act as barriers and locally cooler areas act as attractors for trajectories, creating source and sink areas for local climatic conditions. Climate source areas indicate where locally novel conditions are not connected to areas where similar climates previously occurred, and are thereby inaccessible to climate migrants tracking isotherms: 16% of global surface area for 1960 to 2009, and 34% of ocean for the 'business as usual' climate scenario (representative concentration pathway (RCP) 8.5) representing continued use of fossil fuels without mitigation. Climate sink areas are where climate conditions locally disappear, potentially blocking the movement of climate migrants. Sink areas comprise 1.0% of ocean area and 3.6% of land and are prevalent on coasts and high ground. Using this approach to infer shifts in species distributions gives global and regional maps of the expected direction and rate of shifts of climate migrants, and suggests areas of potential loss of species richness.
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Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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