Background: To study choroidal thickness (CT) in type 2 diabetes mellitus (DM2) patients with moderate diabetic retinopathy (DR) and to correlate with changes in retinal thickness (RT) with ...swept-source OCT (SS-OCT) compared to healthy subjects. Methods: Fifty-four DM2 patients with moderate DR without diabetic macular edema (DME) and 73 age-matched healthy subjects were evaluated using SS-OCT to measure changes in total RT and CT in the nine areas of the Early Treatment Diabetic Retinopathy Study (ETDRS) macular grid. Results: The mean age was 64.06 ± 11.98 years and 60.79 ± 8.62 years in the diabetic and control groups, respectively. Total RT showed statistically significant differences in the temporal inner area, with higher values in the DM2 group (p = 0.010). CT did not show differences between the groups. There was a significant negative correlation between RT and age in all of the outer ETDRS areas and a positive significant correlation in the central area for the DM2 group. There was also a negative significant correlation between CT and age in all of the ETDRS areas except for the inferior inner area. In the DM2 group, a negative correlation was observed between RT and CT in the central area (p = 0.039) and in both horizontal parafoveal areas (temporal inner, p = 0.028; nasal inner, p= 0.003). Conclusion: DM2 patients with moderate DR have no changes with regard to CT. Both CT and RT decreased with age in DM2, showing a negative correlation between these factors in the central and horizontal parafoveal areas of the ETDRS grid.
Circumscribed choroidal hemangioma (CCH) is a rare congenital ocular tumor type that is usually benign and asymptomatic. CCH has only been reported once previously in the literature in association ...with a visceral neoplasm. Here, we present a newly described association between CCH and hepatic hemangioma (HH). We report the case of a 57-year-old woman diagnosed with asymptomatic HHs who presented with a 2- to 3-month history of central scotoma and blurred vision in her left eye. Assessment identified an orange-red elevated lesion with a central serous retinal detachment and subretinal edema. Complementary tests suggested a CCH. To our knowledge, CCH has only been reported once previously in association with a visceral neoplasm, making this newly described association between CCH and HH of clinical relevance. Ophthalmologists should be aware of the possible association between CCH and other visceral tumors as this association offers an opportunity for the early detection of this pathology.
This study evaluated whether processing non-timber forest products (NTFPs) and establishing trade partnerships between forest communities and companies enhance the outcomes of NTFP commercialization. ...In particular, we evaluated whether product processing, partnerships, or their combination was associated with a number of outcomes related to the well-being of forest inhabitants and forest conservation. We based our analyses on ethnographic and quantitative data (i.e., survey and systematic observations) gathered at seven communities from five societies of the Brazilian and Bolivian Amazon. Our results indicated that product processing and partnerships do not represent a silver bullet able to improve the results of NTFP commercialization in terms of well-being and conservation indicators. Compared with cases without interventions, households adopting partnerships but not product processing were most often associated with improved economic proxies of well-being (total income, NTFP income, food consumption and gender equality in income). In comparison, the combination of product processing and partnerships was associated with similar outcomes. Unexpectedly, product processing alone was associated with negative outcomes in the economic indicators of well-being. All of the investigated strategies were associated with less time spent in social and cultural activities. With respect to forest conservation, the strategies that included a partnership with or without processing produced similar results: while household deforestation tended to decrease, the hunting impact increased. Processing alone was also associated with higher levels of hunting, though it did not reduce deforestation. Our results indicate that establishing partnerships may enhance the outcomes of NTFP trade in terms of the financial outcomes of local communities, but practitioners need to use caution when adopting the processing strategy and they need to evaluate potential negative results for indicators of social and cultural activities. With respect to conservation, the three strategies are promising for reducing deforestation, but more pervasive impacts, such as hunting, might increase.
The aim of this study is to determine the perceptions of university students toward teaching–learning processes during the COVID-19 pandemic. This research gathers inquiries made worldwide on the ...perceptions of students in higher education during a state of alarm. The proposed objectives were (a) to analyse the perception of students toward teaching–learning processes in university; (b) to determine the assessment given by students about the changes that took place in university teaching as a result of COVID-19; and (c) to explore resources (hardware and software), professional collaboration, digital pedagogy and student empowerment (motivation) regarding digital education and recent changes in university teaching due to the pandemic. This study used a non-experimental, descriptive design based on opinion polls or surveys. The results show a positive correlation between digital pedagogy, student motivation and digital environments. As a conclusion, we encourage the scientific community to continue delving into the motivation, collaboration and reflective exchange of experiences, self-learning and promotion of initiatives that foster the development of competencies in future teachers. It is also important to continue the research on integrated designs in training processes in university, tutoring and continuous evaluation, as they are key for digital transformation in universities.
Mucopolysaccharidosis type II is a lysosomal storage disorder caused by a deficiency of iduronate-2-sulfatase (IDS) and characterized by the accumulation of the primary storage substrate, ...glycosaminoglycans (GAGs). Understanding central nervous system (CNS) pathophysiology in neuronopathic MPS II (nMPS II) has been hindered by the lack of CNS biomarkers. Characterization of fluid biomarkers has been largely focused on evaluating GAGs in cerebrospinal fluid (CSF) and the periphery; however, GAG levels alone do not accurately reflect the broad cellular dysfunction in the brains of MPS II patients. We utilized a preclinical mouse model of MPS II, treated with a brain penetrant form of IDS (ETV:IDS) to establish the relationship between markers of primary storage and downstream pathway biomarkers in the brain and CSF. We extended the characterization of pathway and neurodegeneration biomarkers to nMPS II patient samples. In addition to the accumulation of CSF GAGs, nMPS II patients show elevated levels of lysosomal lipids, neurofilament light chain, and other biomarkers of neuronal damage and degeneration. Furthermore, we find that these biomarkers of downstream pathology are tightly correlated with heparan sulfate. Exploration of the responsiveness of not only CSF GAGs but also pathway and disease-relevant biomarkers during drug development will be crucial for monitoring disease progression, and the development of effective therapies for nMPS II.
Cells treated with hsp90 inhibitors exhibit pleiotropic changes, including an expansion of the mitochondrial compartment, accompanied by mitochondrial fragmentation and condensed mitochondrial ...morphology, with ultimate compromise of mitochondrial integrity and apoptosis.
We identified several mitochondrial oxidative phosphorylation complex subunits, including several encoded by mtDNA, that are upregulated by hsp90 inhibitors, without corresponding changes in mRNA abundance. Post-transcriptional accumulation of mitochondrial proteins observed with hsp90 inhibitors is also seen in cells treated with proteasome inhibitors. Detailed studies of the OSCP subunit of mitochondrial F1F0-ATPase revealed the presence of mono- and polyubiquitinated OSCP in mitochondrial fractions. We demonstrate that processed OSCP undergoes retrotranslocation to a trypsin-sensitive form associated with the outer mitochondrial membrane. Inhibition of proteasome or hsp90 function results in accumulation of both correctly targeted and retrotranslocated mitochondrial OSCP.
Cytosolic turnover of mitochondrial proteins demonstrates a novel connection between mitochondrial and cytosolic compartments through the ubiquitin-proteasome system. Analogous to defective protein folding in the endoplasmic reticulum, a mitochondrial unfolded protein response may play a role in the apoptotic effects of hsp90 and proteasome inhibitors.
The increase in diabetic retinopathy (DR) prevalence demonstrates the need for the determination of biomarkers for assessing disease development to obtain an early diagnosis and stop its progression. ...We aimed to analyse total retinal (RT) and inner retinal layer (IRL) thicknesses in type 2 diabetes mellitus (DM2) patients and correlate these results with retinal sensitivity using swept-source OCT (SS-OCT) and microperimetry. For this purpose, a total of 54 DM2 subjects with moderate diabetic retinopathy (DR) with no signs of diabetic macular oedema (DME) and 73 age-matched healthy individuals were assessed using SS-OCT to quantify retinal thickness in the nine macular areas of the ETDRS grid. Retinal sensitivity was measured via microperimetry with a Macular Integrity Assessment Device (MAIA). The mean ages were 64.06 ± 11.98 years for the DM2 group and 60.79 ± 8.62 years for the control group. DM2 patients presented lower visual acuity (p < 0.001) and a thicker RT (260.70 ± 19.22 μm in the control group vs. 271.90 ± 37.61 μm in the DM2 group, p = 0.01). The retinal nerve fibre layer (RNFL) was significantly lower in the outer nasal area (50.38 ± 8.20 μm vs. 45.17 ± 11.25 μm, p = 0.005) in ganglion cells and inner plexiform layers (GCL+) in DM2. A positive correlation between the LDL-C and RNFL and a negative correlation between HDL-C levels and the inner temporal and central RNFL thickness were detected. The central (p = 0.021) and inner nasal (p = 0.01) areas were negatively correlated between the RNFL and MAIA, while GCL++ was positively correlated with the outer inferior (p = 0.015) and outer nasal areas (p = 0.024). Retinal sensitivity and macular RNFL thickness decrease in DM2 patients with moderate DR with no DME, and this study enables an accurate approach to this disease with personalised assessment based on the DR course or stage. Thus, GCL+ and GCL++ thinning may support ganglion cell loss before the RNFL is affected.
NMR-based metabolomics investigations of human biofluids offer great potential to uncover new biomarkers. In contrast to protocols for sample collection and biobanking, procedures for sample ...preparation prior to NMR measurements are still heterogeneous, thus compromising the comparability of the resulting data. Herein, we present results of an investigation of the handling of cerebrospinal fluid (CSF) samples for NMR metabolomics research. Origins of commonly observed problems when conducting NMR experiments on this type of sample are addressed, and suitable experimental conditions in terms of sample preparation and pH control are discussed. Sample stability was assessed by monitoring the degradation of CSF samples by NMR, hereby identifying metabolite candidates, which are potentially affected by sample storage. A protocol was devised yielding consistent spectroscopic data as well as achieving overall sample stability for robust analysis. We present easy to adopt standard operating procedures with the aim to establish a shared sample handling strategy that facilitates and promotes inter-laboratory comparison, and the analysis of sample degradation provides new insights into sample stability.
The current pressure on the built historical heritage requires a global evaluation to develop strategies for its preservation. A combined vision of the state of conservation of architectural heritage ...is essential to highlight the vulnerabilities of the structure from which harmonized measures can be proposed for its mitigation.
This study proposes a multi-criteria analysis methodology that considers a qualitative and quantitative approach to organize the global conservation state of heritage buildings hierarchically. A global index can be determined on the basis of the generation of an interoperable data matrix by defining a set of indicators to assess different components of a building. This index describes the risk with respect to the stability, safety, and habitability of the building.
This methodology aims to achieve the state of the building in an integral way by obtaining a simple and objective index that enables efficient comparison among different buildings. The application of this methodology to a historic area allows creating a hierarchical map of risk to stablish priorities for intervention and enable a sustainable and critical management and planning over the actions of maintenance, conservation, and restoration. In this way, a holistic vision of the complex reality of built heritage and the urban landscape is obtained to identify critical areas of priority intervention.
While drug toxicity (especially hepatotoxicity) is the most frequent reason cited for withdrawal of an approved drug, no simple solution exists to adequately predict such adverse events. Simple ...cytotoxicity assays in HepG2 cells are relatively insensitive to human hepatotoxic drugs in a retrospective analysis of marketed pharmaceuticals. In comparison, a panel of pre-lethal mechanistic cellular assays hold the promise to deliver a more sensitive approach to detect endpoint-specific drug toxicities. The panel of assays covered by this review includes steatosis, cholestasis, phospholipidosis, reactive intermediates, mitochondria membrane function, oxidative stress, and drug interactions. In addition, the use of metabolically competent cells or the introduction of major human hepatocytes in these in vitro studies allow a more complete picture of potential drug side effect. Since inter-individual therapeutic index (TI) may differ from patient to patient, the rational use of one or more of these cellular assay and targeted in vivo exposure data may allow pharmaceutical scientists to select drug candidates with a higher TI potential in the drug discovery phase.
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