Platelet-derived transforming growth factor-β1 promotes keratinocyte proliferation in cutaneous wound healing.

Platelets are a recognised potent source of transforming growth factor-β1 (TGFβ1), a cytokine known to promote wound healing and regeneration by stimulating dermal fibroblast proliferation and extracellular matrix deposition. Platelet lysate has been advocated as a novel personalised therapeutic to treat persistent wounds, although the precise platelet-derived growth factors responsible for these beneficial effects have not been fully elucidated. The aim of this study was to investigate the specific role of platelet-derived TGFβ1 in cutaneous wound healing. Using a transgenic mouse with a targeted deletion of TGFβ1 in megakaryocytes and platelets (TGFβ1fl/fl .PF4-Cre), we show for the first time that platelet-derived TGFβ1 contributes to epidermal and dermal thickening and cellular turnover after excisional skin wounding. In vitro studies demonstrate that human dermal fibroblasts stimulated with platelet lysate containing high levels of platelet-derived TGFβ1 did not exhibit enhanced collagen deposition or proliferation, suggesting that platelet-derived TGFβ1 is not a key promoter of these wound healing processes. Interestingly, human keratinocytes displayed enhanced TGFβ1-driven proliferation in response to platelet lysate, reminiscent of our in vivo findings. In summary, our novel findings define and emphasise an important role of platelet-derived TGFβ1 in epidermal remodelling and regeneration processes during cutaneous wound healing

Nutrient enrichment mediates the effect of biodegradable and conventional microplastics on macroinvertebrate communities

There is growing concern regarding the lack of evidence on the effects bioplastics may have on natural ecosystems, whilst their production continues to increase as they are considered as a greener alternative to conventional plastics. Most research is limited to investigations of the response of individual taxa under laboratory conditions, with few experiments undertaken at the community or ecosystem scale, either investigating microplastics independently or in combination with other pollutants, such as nutrient enrichment. The aim of this study is to experimentally compare the effects of oil-based (high density polyethylene – HDPE) with those of bio-based biodegradable (polylactic acid – PLA) microplastics and their interaction with nutrient enrichment on freshwater macroinvertebrate communities under seminatural conditions. There were no significant differences in total abundance, alpha and beta diversities, or community composition attributable to the type of microplastics, their concentration, or nutrient enrichment compared with the control. However, there was a significant difference in macroinvertebrate alpha diversity between high concentrations of both microplastic types under ambient nutrient conditions, with lower diversity in communities exposed to HDPE compared with PLA. Nutrient enrichment mediated the effect of microplastic type, such that the diversity of macroinvertebrate communities exposed to HDPE were similar to those communities exposed to PLA. These findings suggest that the effects of microplastic pollution on macroinvertebrate communities are very weak at large-scale settings under seminatural conditions and that these effects might be mediated by the nutrient status of freshwater ecosystems. More research under large-scale, long-term, seminatural settings are needed in order to elucidate the impact of both conventional plastics and bioplastics on natural environments and their interactive effect with other occurring stressors and pollutants

Vibrational Relaxation and Redistribution Dynamics in Ruthenium(II) Polypyridyl-Based Charge-Transfer Excited States: A Combined Ultrafast Electronic and Infrared Absorption Study

Ultrafast time-resolved electronic and infrared absorption measurements have been carried out on a series of Ru­(II) polypyridyl complexes in an effort to delineate the dynamics of vibrational relaxation in this class of charge transfer chromophores. Time-dependent density functional theory calculations performed on compounds of the form [Ru­(CN-Me-bpy)x(bpy)3‑x]2+ (x = 1–3 for compounds 1–3, respectively, where CN-Me-bpy is 4,4′-dicyano-5,5′-dimethyl-2,2′-bipyridine and bpy is 2,2′-bipyridine) reveal features in their charge-transfer absorption envelopes that allow for selective excitation of the Ru­(II)–(CN-Me-bpy) moiety, the lowest-energy MLCT state(s) in each compound of the series. Changes in band shape and amplitude of the time-resolved differential electronic absorption data are ascribed to vibrational cooling in the CN-Me-bpy-localized 3MLCT state with a time constant of 8 ± 3 ps in all three compounds. This conclusion was corroborated by picosecond time-resolved infrared absorption measurements; sharpening of the CN stretch in the 3MLCT excited state was observed with a time constant of 3.0 ± 1.5 ps in all three members of the series. Electronic absorption data acquired at higher temporal resolution revealed spectral modulation over the first 2 ps occurring with a time constant of τ = 170 ± 50 fs, in compound 1; corresponding effects are significantly attenuated in compound 2 and virtually absent in compound 3. We assign this feature to intramolecular vibrational redistribution (IVR) within the 3MLCT state and represents a rare example of this process being identified from time-resolved electronic absorption data for this important class of chromophores

Heat and fluid flow in a scraped-surface heat exchanger containing a fluid with temperature-dependent viscosity

Scraped-surface heat exchangers (SSHEs) are extensively used in a wide variety of industrial settings where the continuous processing of fluids and fluid-like materials is involved. The steady non-isothermal flow of a Newtonian fluid with temperature-dependent viscosity in a narrow-gap SSHE when a constant temperature difference is imposed across the gap between the rotor and the stator is investigated. The mathematical model is formulated and the exact analytical solutions for the heat and fluid flow of a fluid with a general dependence of viscosity on temperature for a general blade shape are obtained. These solutions are then presented for the specific case of an exponential dependence of viscosity on temperature. Asymptotic methods are employed to investigate the behaviour of the solutions in several special limiting geometries and in the limits of weak and strong thermoviscosity. In particular, in the limit of strong thermoviscosity (i.e., strong heating or cooling and/or strong dependence of viscosity on temperature) the transverse and axial velocities become uniform in the bulk of the flow with boundary layers forming either just below the blade and just below the stationary upper wall or just above the blade and just above the moving lower wall. Results are presented for the most realistic case of a linear blade which illustrate the effect of varying the thermoviscosity of the fluid and the geometry of the SSHE on the flow

Competition Drives Clumpy Species Coexistence in Estuarine Phytoplankton

Understanding the mechanisms that maintain biodiversity is a fundamental problem in ecology. Competition is thought to reduce diversity, but hundreds of microbial aquatic primary producers species coexist and compete for a few essential resources (e.g., nutrients and light). Here, we show that resource competition is a plausible mechanism for explaining clumpy distribution on individual species volume (a proxy for the niche) of estuarine phytoplankton communities ranging from North America to South America and Europe, supporting the Emergent Neutrality hypothesis. Furthermore, such a clumpy distribution was also observed throughout the Holocene in diatoms from a sediment core. A Lotka-Volterra competition model predicted position in the niche axis and functional affiliation of dominant species within and among clumps. Results support the coexistence of functionally equivalent species in ecosystems and indicate that resource competition may be a key process to shape the size structure of estuarine phytoplankton, which in turn drives ecosystem functioning

Timeliness of Clinic Attendance is a good predictor of Virological Response and Resistance to Antiretroviral drugs in HIV-infected patients

Ensuring long-term adherence to therapy is essential for the success of HIV treatment. As access to viral load monitoring and genotyping is poor in resource-limited settings, a simple tool to monitor adherence is needed. We assessed the relationship between an indicator based on timeliness of clinic attendance and virological response and HIV drug resistance

Prevalence and Incidence of Parkinson\u27s Disease in Latin America: A Meta-Analysis

\ua9 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. Background: Parkinson\u27s disease (PD) is a rapidly growing neurodegenerative disorder, but up-to-date epidemiological data are lacking in Latin America. We sought to estimate the prevalence and incidence of PD and parkinsonism in Latin America. Methods: We searched Medline, Embase, Scopus, Web of Science, Scientific Electronic Library Online, and Literatura Latino-Americana e do Caribe em Ci\ueancias da Sa\ufade or the Latin American and Caribbean Health Science Literature databases for epidemiological studies reporting the prevalence or incidence of PD or parkinsonism in Latin America from their inception to 2022. Quality of studies was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist. Data were pooled via random-effects meta-analysis and analyzed by data source (cohort studies or administrative databases), sex, and age group. Significant differences between groups were determined by meta-regression. Results: Eighteen studies from 13 Latin American countries were included in the review. Meta-analyses of 17 studies (nearly 4 million participants) found a prevalence of 472 (95% CI, 271–820) per 100,000 and three studies an incidence of 31 (95% CI, 23–40) per 100,000 person-years for PD; and seven studies found a prevalence of 4300 (95% CI, 1863–9613) per 100,000 for parkinsonism. The prevalence of PD differed by data source (cohort studies, 733 [95% CI, 427–1255] vs. administrative databases. 114 [95% CI, 63–209] per 100,000, P < 0.01), age group (P < 0.01), but not sex (P = 0.73). PD prevalence in ≥60 years also differed significantly by data source (cohort studies. 1229 [95% CI, 741–2032] vs. administrative databases, 593 [95% CI, 480–733] per 100,000, P < 0.01). Similar patterns were observed for parkinsonism. Conclusions: The overall prevalence and incidence of PD in Latin America were estimated. PD prevalence differed significantly by the data source and age, but not sex. \ua9 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Inter-sectoral and multilevel coordination alone do not reduce deforestation and advance environmental justice:Why bold contestation works when collaboration fails

Policy makers, academics, and conservationists often posit that poor coordination between different land use sectors, and between levels of governance, as an underlying challenge for reducing deforestation and forest degradation. This paper analyzes this argument using data from interviews with over 500 respondents from government, nongovernmental organizations, private companies, local and indigenous communities, activists, and individuals involved in 35 diverse land use initiatives in three countries: Peru, Indonesia, and Mexico. We find that while there is strong evidence of widespread coordination failures between sectors and levels, more fundamental political issues preclude effective coordination. We argue that political coalitions act to oppose environmental objectives and to impede their opponents from participating in land use governance. Moreover, we find that where coordination between actors does occur, it does not necessarily produce environmentally sustainable and socially just land use outcomes. Where we do find successful initiatives to reduce deforestation and benefit local people, effective coordination between well-informed actors is often present, but it does not occur spontaneously, and is instead driven by political organizing over time by activists, local people, nongovernmental organizations, and international donors. We suggest that the global environmental community must recognize explicitly these political dimensions of land use governance in order to successfully collaborate with local people to reduce deforestation

Functional and Molecular Analysis of Human Osteoarthritic Chondrocytes Treated with Bone Marrow-Derived MSC-EVs

\ua9 2024 by the authors.Osteoarthritis (OA) is a degenerative joint disease, causing impaired mobility. There are currently no effective therapies other than palliative treatment. Mesenchymal stromal cells (MSCs) and their secreted extracellular vesicles (MSC-EVs) have shown promise in attenuating OA progression, promoting chondral regeneration, and modulating joint inflammation. However, the precise molecular mechanism of action driving their beneficial effects has not been fully elucidated. In this study, we analyzed MSC-EV-treated human OA chondrocytes (OACs) to assess viability, proliferation, migration, cytokine and catabolic protein expression, and microRNA and mRNA profiles. We observed that MSC-EV-treated OACs displayed increased metabolic activity, proliferation, and migration compared to the controls. They produced decreased proinflammatory (Il-8 and IFN-γ) and increased anti-inflammatory (IL-13) cytokines, and lower levels of MMP13 protein coupled with reduced expression of MMP13 mRNA, as well as negative microRNA regulators of chondrogenesis (miR-145-5p and miR-21-5p). In 3D models, MSC-EV-treated OACs exhibited enhanced chondrogenesis-promoting features (elevated sGAG, ACAN, and aggrecan). MSC-EV treatment also reversed the pathological impact of IL-1β on chondrogenic gene expression and extracellular matrix component (ECM) production. Finally, MSC-EV-treated OACs demonstrated the enhanced expression of genes associated with cartilage function, collagen biosynthesis, and ECM organization and exhibited a signature of 24 differentially expressed microRNAs, associated with chondrogenesis-associated pathways and ECM interactions. In conclusion, our data provide new insights on the potential mechanism of action of MSC-EVs as a treatment option for early-stage OA, including transcriptomic analysis of MSC-EV-treated OA, which may pave the way for more targeted novel therapeutics

Burden of Parkinsonism and Parkinson\u27s Disease on Health Service Use and Outcomes in Latin America

\ua9 2023 - The authors. Published by IOS Press.Background: Little is known about the burden of parkinsonism and Parkinson\u27s disease (PD) in Latin America. Better understanding of health service use and clinical outcomes in PD is needed to improve its prognosis. Objective: The aim of the study was to estimate the burden of parkinsonism and PD in six Latin American countries. Methods: 12,865 participants aged 65 years and older from the 10/66 population-based cohort study were analysed. Baseline assessments were conducted in 2003-2007 and followed-up 4 years later. Parkinsonism and PD were defined using current clinical criteria or self-reported diagnosis. Logistic regression models assessed the association between parkinsonism/PD with baseline health service use (community-based care or hospitalisation in the last 3 months) and Cox proportional hazards regression models with incident dependency (subjective assessment by interviewer based on informant interview) and mortality. Separate analyses for each country were combined via fixed effect meta-analysis. Results: At baseline, the prevalence of parkinsonism and PD was 7.9% (n = 934) and 2.6% (n = 317), respectively. Only parkinsonism was associated with hospital admission at baseline (OR 1.89, 95% CI 1.30-2.74). Among 7,296 participants without dependency at baseline, parkinsonism (HR 2.34, 95% CI 1.81-3.03) and PD (2.10, 1.37-3.24) were associated with incident dependency. Among 10,315 participants with vital status, parkinsonism (1.73, 1.50-1.99) and PD (1.38, 1.07-1.78) were associated with mortality. The Higgins I2 tests showed low to moderate levels of heterogeneity across countries. Conclusions: Our findings show that older people with parkinsonism or PD living in Latin America have higher risks of developing dependency and mortality but may have limited access to health services