Ultrastructure of neurovascular changes in human diabetic retinopathy

The previous concept regarding diabetic retinopathy assigned a primary role to hyperglycemia-induced microvascular alterations, while neuronal and glial abnormalities were considered to be secondary to either ischemia or exudation. The aim of this study was to reveal the potential role of neuronal and glial cells in initial and advanced alterations of the retinopathy in human type 2 diabetes. Electron microscopy and histochemical studies were performed on 38 surgically removed human eyes (28 obtained from diabetic patients and 10 from non-diabetic patients). Morphometric analysis of basement membrane material and lipids was performed. An accumulation of metabolic by-products was found in the capillary wall with aging: this aspect was significantly more pronounced in diabetics. Müller glial cells were found to contribute to alterations of the capillary wall and to occlusion, as well as to the development of proliferative retinopathy and cystoid degeneration of the retina. Our results showed morphological evidence regarding the role of neuronal and glial cells in the pathology of diabetic retinopathy, prior and in addition to microangiopathy. These morphological findings support a neurovascular pathogenesis at the origin of diabetic retinopathy, thus the current treatment approach should be completed by neuroprotective measures

Unimolecular Variant of the Fluorescence Turn-On Oxidative Coupling of Catecholamines with Resorcinols

Reported herein is a unimolecular variant of the fluorescence turn-on oxidative coupling of catecholamines with resorcinols ("FluoResCat") based on the easily accessible conjugate 4-(2-((2,4-dihydroxybenzyl)amino)ethyl)benzene-1,2-diol (1). The process involves an alkali-activatable sequence of autoxidation and intramolecular cyclization steps with loss of carbon, leading to a fluorescent methanobenzofuroazocinone product identical to that obtained from the oxidative coupling of dopamine with resorcinol. A mechanistic route for this unexpected reaction, mimicking the synthesis of the natural fluorophore matlaline, would involve highly constrained polycyclic spiro intermediates (liquid chromatography–mass spectrometry analysis of intermediates, model reactions, and density functional theory calculations). Emission turn-on from 1 in response to oxygen, superoxide-generating systems, or gaseous ammonia/volatile amines may be of interest for sensing applications, for example, in smart packaging

Age and diabetes related changes of the retinal capillaries: an ultrastructural and immunohistochemical study

Normal human aging and diabetes are associated with a gradual decrease of cerebral flow in the brain with changes in vascular architecture. Thickening of the capillary basement membrane and microvascular fibrosis are evident in the central nervous system of elderly and diabetic patients. Current findings assign a primary role to endothelial dysfunction as a cause of basement membrane (BM) thickening, while retinal alterations are considered to be a secondary cause of either ischemia or exudation. The aim of this study was to reveal any initial retinal alterations and variations in the BM of retinal capillaries during diabetes and aging as compared to healthy controls. Moreover, we investigated the potential role of vascular endothelial growth factor (VEGF) and pro-inflammatory cytokines in diabetic retina.Transmission electron microscopy (TEM) was performed on 46 enucleated human eyes with particular attention to alterations of the retinal capillary wall and Müller glial cells. Inflammatory cytokines expression in the retina was investigated by immunohistochemistry.Our electron microscopy findings demonstrated that thickening of the BM begins primarily at the level of the glial side of the retina during aging and diabetes. The Müller cells showed numerous cytoplasmic endosomes and highly electron-dense lysosomes which surrounded the retinal capillaries. Our study is the first to present morphological evidence that Müller cells start to deposit excessive BM material in retinal capillaries during aging and diabetes. Our results confirm the induction of pro-inflammatory cytokines TNF-α and IL-1β within the retina as a result of diabetes.These observations strongly suggest that inflammatory cytokines and changes in the metabolism of Müller glial cells rather than changes in of endothelial cells may play a primary role in the alteration of retinal capillaries BM during aging and diabetes

"Volentes pro meliori ... providere ... super ludo": provvedimenti sul gioco per i territori veneziani (secoli XIII-XVI). Ricognizioni preliminari.

Ricognizione e analisi della normativa sul gioco prodotta, fra medioevo ed età moderna, da Venezia per i territori soggetti come premessa per una politica ludica sovracittadina

Pattern and characteristics of advanced cancer patients admitted to hospices in Italy

Abstract The aim of this multicenter study was to assess the pattern and the characteristics of advanced cancer patients admitted to hospices. A consecutive sample of patients admitted in a period of 6 months was taken into consideration. Two hundred thirty-six patients admitted to hospices were consecutively assessed. Ninety-six percent of patients were admitted in acute hospital in the previous 3 months, with a mean time spent in hospital of 34.5 days, and 47 % of patients had received chemotherapy the month before hospice admission. Thirty-four percent of patients for whom data were available had significant persistent pain, and 44 % of them presented episodes of breakthrough pain. Sixty-one percent of patients were receiving opioid drugs at admission, and 70 % the day before death, with parenteral morphine and transdermal fentanyl being the opioids most frequently administered. The mean admission time in hospice was 18.4 days. Eighty-six percent died in hospice. Palliative sedation was performed in 25 % of patients who died in hospice. The short survival and the number of patients dying in hospice were the principal finding, as it appears that hospice admission is only one way for end of life treatments. Patients receive specialized palliative care only for 2-3 weeks before death, implying an inacceptable timing for patients with several problems presumed to be present early during the course of disease. Data from hospice activities in Italy strongly suggest to spread palliative care in other settings, other than home care and hospice, to intercept oncologic patients in their disease trajectory early

Eumelanin broadband absorption develops from aggregation-modulated chromophore interactions under structural and redox control

Eumelanins, the chief photoprotective pigments in man and mammals, owe their black color to an unusual broadband absorption spectrum whose origin is still a conundrum. Excitonic effects from the interplay of geometric order and disorder in 5,6-dihydroxyindole (DHI)-based oligomeric/polymeric structures play a central role, however the contributions of structural (scaffold-controlled) and redox ( €-electron-controlled) disorder have remained uncharted. Herein, we report an integrated experimental-theoretical entry to eumelanin chromophore dynamics based on poly(vinyl alcohol)-controlled polymerization of a large set of 5,6-dihydroxyindoles and related dimers. The results a) uncover the impact of the structural scaffold on eumelanin optical properties, disproving the widespread assumption of a universal monotonic chromophore; b) delineate eumelanin chromophore buildup as a three-step dynamic process involving the rapid generation of oxidized oligomers, termed melanochromes (phase I), followed by a slow oxidant-independent band broadening (phase II) leading eventually to scattering (phase III); c) point to a slow reorganization-stabilization of melanochromes via intermolecular redox interactions as the main determinant of visible broadband absorption

ACESSIBILIDADE, EDUCAÇÃO SUPERIOR E ENSINO REMOTO: EFETIVAÇÃO CAMUFLADA

 A pandemia do Covid 19 trouxe a necessidade de mudanças emergências em vários âmbitos da sociedade, inclusive no âmbito educacional. Entretanto, a urgência das medidas pode não ter contemplado todas as necessidades para a garantia da acessibilidade em suas diversas dimensões, visando a promoção do ensino na modalidade remota. Com base nessa discussão, este estudo teve por objetivo analisar a acessibilidade no ensino remoto para a educação superior em uma universidade federal, em tempos de pandemia Covid 19, a partir da política educacional. Foi realizada a busca por documentos publicados pelo Ministério da Educação e resoluções publicadas pela Pró-Reitoria de Graduação -ProGrad e Pró-Reitoria de Assuntos Comunitários e Estudantis-ProACE de uma universidade federal do interior do estado de São Paulo, no período de março de 2020 a dezembro de 2020. A análise dos dados se deu a partir dos apontamentos de Dermeval Saviani em suas produções referente ao contexto pandêmico. Os resultados da pesquisa indicam que não houve a implementação de uma política educacional que se atentasse para a garantia da acessibilidade, em sua amplitude, na educação superior, no ano de 2020, com a adoção do ensino remoto

Properties of fast submillimeter time structures during a large solar flare

We report properties of fast varying submillimeter emission during one of the strongest solar radio flares of solar cycle 23. Emission was obtained by the Solar Submillimeter-Wave Telescope at 212 and 405 GHz and compared with hard X-ray and γ-ray counts up to few tens of MeV photon energy ranges. We employ different methods to detect and characterize flux density variations and find that during the impulsive phase of the event, the closer in time to the peak flare, the higher the occurrence of the fastest and brightest time structures. The good comparison with hard X-ray and γ-ray count rates indicates that fast submillimeter pulses are the signatures of primary energetic injections. The characteristics of the fast spikes at 212 and 405 GHz, such as their flux density and localization, compared to those of the underlying slower impulsive component, also suggest that their nature is different.Fil: Raulin, Jean Pierre. Universidade Presbiteriana Mackenzie; BrasilFil: Kaufmann, Pierre. Universidade Estadual de Campinas; Brasil. Universidade Presbiteriana Mackenzie; BrasilFil: de Castro, Carlos G. Giménez. Universidade Presbiteriana Mackenzie; BrasilFil: Pacini, Alessandra A.. Universidade Presbiteriana Mackenzie; BrasilFil: Makhmutov, Vladimir S.. Russian Academy Of Sciences; RusiaFil: Levato, Orlando Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Complejo Astronómico "El Leoncito". Universidad Nacional de Córdoba. Complejo Astronómico "El Leoncito". Universidad Nacional de la Plata. Complejo Astronómico "El Leoncito". Universidad Nacional de San Juan. Complejo Astronómico "El Leoncito"; ArgentinaFil: Rovira, Marta Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; Argentin