Changes in Astroglial Water Flow in the Pre-amyloid Phase of the STZ Model of AD Dementia.

Alzheimer's disease (AD) is an age-dependent neurodegenerative disease that is typically sporadic and has a high social and economic cost. We utilized the intracerebroventricular administration of streptozotocin (STZ), an established preclinical model for sporadic AD, to investigate hippocampal astroglial changes during the first 4 weeks post-STZ, a period during which amyloid deposition has yet to occur. Astroglial proteins aquaporin 4 (AQP-4) and connexin-43 (Cx-43) were evaluated, as well as claudins, which are tight junction (TJ) proteins in brain barriers, to try to identify changes in the glymphatic system and brain barrier during the pre-amyloid phase. Glial commitment, glucose hypometabolism and cognitive impairment were characterized during this phase. Astroglial involvement was confirmed by an increase in glial fibrillary acidic protein (GFAP); concurrent proteolysis was also observed, possibly mediated by calpain. Levels of AQP-4 and Cx-43 were elevated in the fourth week post-STZ, possibly accelerating the clearance of extracellular proteins, since these proteins actively participate in the glymphatic system. Moreover, although we did not see a functional disruption of the blood-brain barrier (BBB) at this time, claudin 5 (present in the TJ of the BBB) and claudin 2 (present in the TJ of the blood-cerebrospinal fluid barrier) were reduced. Taken together, data support a role for astrocytes in STZ brain damage, and suggest that astroglial dysfunction accompanies or precedes neuronal damage in AD.

Plasma ADAM10 Levels and Their Association with Alzheimer's Disease Diagnosis in Older Adults with Fewer Years of Formal Education.

INTRODUCTION: Low educational attainment is a potential risk factor for Alzheimer's disease (AD) development. Alpha-secretase ADAM10 plays a central role in AD pathology, attenuating the formation of beta-amyloid peptides and, therefore, their aggregation into senile plaques. This study seeks to investigate ADAM10 as a blood-based biomarker in mild cognitive impairment (MCI) and AD in a diverse group of community-dwelling older adults, focusing on those with limited educational attainment. METHODS: Participants were recruited from public health services. Cognition was evaluated using Mini-Mental State Examination (MMSE) and Addenbrooke's Cognitive Examination - Revised (ACE-R) batteries. Blood samples were collected to analyze plasma ADAM10 levels. A logistic regression was conducted to verify the influence of plasma ADAM10 on the AD diagnosis. RESULTS: Significant differences in age, years of education, prescribed medications, and cognitive test scores were found between the MCI and AD groups. Regarding cognitive performance, both ACE-R and MMSE scores displayed significant differences between groups, with post hoc analyses highlighting these distinctions, particularly between AD and cognitively unimpaired individuals. Elevated plasma ADAM10 levels were associated with a 4.5-fold increase in the likelihood of a diagnosis of MCI and a 5.9-fold increase in the likelihood of a diagnosis of AD. These findings suggest ADAM10 levels in plasma as a valuable biomarker for assessing cognitive status in older individuals with low education attainment. CONCLUSION: This study underscores the potential utility of plasma ADAM10 levels as a blood-based biomarker for cognitive status, especially in individuals with low educational backgrounds, shedding light on their relevance in AD development and diagnosis.

Calorie restriction protects against acute systemic LPS-induced inflammation.

Caloric restriction (CR) has been proposed as a nutritional strategy to combat chronic diseases, including neurodegenerative diseases, as well as to delay aging. However, despite the benefits of CR, questions remain about its underlying mechanisms and cellular and molecular targets.Objective: As inflammatory processes are the basis or accompany chronic diseases and aging, we investigated the protective role of CR in the event of an acute inflammatory stimulus.Methods: Peripheral inflammatory and metabolic parameters were evaluated in Wistar rats following CR and/or acute lipopolysaccharide (LPS) administration, as well as glial changes (microglia and astrocytes), in two regions of the brain (hippocampus and hypothalamus) involved in the inflammatory response. We used a protocol of 30% CR, for 4 or 8 weeks. Serum and brain parameters were analyzed by biochemical or immunological assays.Results: Benefits of CR were observed during the inflammatory challenge, where the partial reduction of serum interleukin-6, mediated by CR, attenuated the systemic response. In the central nervous system (CNS), specifically in the hippocampus, CR attenuated the response to the LPS, as evaluated by tumor necrosis factor alpha (TNFα) levels. Furthermore, in the hippocampus, CR increased the glutathione (GSH) levels, resulting in a better antioxidant response.Discussion: This study contributes to the understanding of the effects of CR, particularly in the CNS, and expands knowledge about glial cells, emphasizing their importance in neuroprotection strategies.

Resistance to cisplatin in human lung adenocarcinoma cells: effects on the glycophenotype and epithelial to mesenchymal transition markers.

The characteristics that grant the most malignancy to cancer cells are the ability to evade apoptotic mechanisms and the capacity to migrate beyond the boundaries of the original tissue. Studies by our own group and others show that changes in glycosylation are now considered hallmarks of cancer cells and are also able to impact tumor malignancy. This study aims to evaluate changes in the glycosylation profile of the A549 lung cancer cells brought about by the induction of a MDR phenotype as well as investigate the relationship between drug resistance, the cell glycophenotype and EMT. We induced resistance by employing a continuous treatment with cisplatin. Our results demonstrate overexpression of ABC transporters as well as anti-apoptotic members of the Bcl-2 family, leading to a MDR phenotype. The cells also undergo a classic EMT process, displaying the iconic cadherin switch and increased of both total and oncofetal fibronectin, coupled with increased cell motility. We also managed to show changes in the expression of both glycosyltransferases and the glycan epitopes they are responsible for building. We also suggest that perhaps not only changes in cell sialylation are common during resistance induction but are essential to it.

First report of Caryospora sp. infection in free-living green turtles (Chelonia mydas) in Northeastern Brazil.

Infection by Caryospora cheloniae has been reported to be responsible for green turtle strandings with high morbidity and mortality rates worldwide. Although studies have already shown the pathogenesis of these infections, many aspects of this protozoan are still poorly understood, including their life cycle and infection dynamics in free-living sea turtle populations. Due to the lack of information about the infection by this protozoan in sea turtles in Northeastern Brazil, our study aims to describe Caryospora sp. infection and its pathological findings in free-living Chelonia mydas found on the north coast of the Bahia state. Between 2018 and 2019, 64 specimens of green turtles were necropsied in partnership with Fundação Projeto Tamar; among these, 10 (1.56%) had oocysts morphologically compatible with Caryospora cheloniae in the evaluation of fecal samples and histopathological examination of intestinal samples. The infected animals were juvenile green turtles that were found stranded on the beaches of the north coast of Bahia. The pathological findings were restricted to the lower gastrointestinal tract, with different presentations and intensities. About 70% of the animals with coccidial infection exhibited erosive and ulcerative fibrinous enteritis. This is the first report of coccidiosis in green turtles on the north coast of Bahia.

Inherited duplications of PPP2R3B predispose to nevi and melanoma via a C21orf91-driven proliferative phenotype.

PURPOSE: Much of the heredity of melanoma remains unexplained. We sought predisposing germline copy-number variants using a rare disease approach. METHODS: Whole-genome copy-number findings in patients with melanoma predisposition syndrome congenital melanocytic nevus were extrapolated to a sporadic melanoma cohort. Functional effects of duplications in PPP2R3B were investigated using immunohistochemistry, transcriptomics, and stable inducible cellular models, themselves characterized using RNAseq, quantitative real-time polymerase chain reaction (qRT-PCR), reverse phase protein arrays, immunoblotting, RNA interference, immunocytochemistry, proliferation, and migration assays. RESULTS: We identify here a previously unreported genetic susceptibility to melanoma and melanocytic nevi, familial duplications of gene PPP2R3B. This encodes PR70, a regulatory unit of critical phosphatase PP2A. Duplications increase expression of PR70 in human nevus, and increased expression in melanoma tissue correlates with survival via a nonimmunological mechanism. PPP2R3B overexpression induces pigment cell switching toward proliferation and away from migration. Importantly, this is independent of the known microphthalmia-associated transcription factor (MITF)-controlled switch, instead driven by C21orf91. Finally, C21orf91 is demonstrated to be downstream of MITF as well as PR70. CONCLUSION: This work confirms the power of a rare disease approach, identifying a previously unreported copy-number change predisposing to melanocytic neoplasia, and discovers C21orf91 as a potentially targetable hub in the control of phenotype switching.

Prophylactic dressings in the prevention of pressure ulcer related to the use of personal protective equipment by health professionals facing the COVID-19 pandemic: A randomized clinical trial.

Device-related pressure injury (DRPI) is a serious problem that is affecting professionals working on the front lines against COVID-19 due to the prolonged use of personal protective equipment (PPE). In addition to the physical and psychological integrity of professionals, these injuries can compromise the quality of care. Therefore, using technologies to prevent this adverse effect is an urgent matter. This is a parallel two-arm randomized clinical trial without the use of a control group to compare the use of foam and extra-thin hydrocolloid in preventing DRPI associated with the use of PPE by health professionals working on the front lines against coronavirus. In total, 88 professionals were divided into two groups: foam and hydrocolloid. Data were collected using two instruments and related to demographic and professional characteristics and skin evaluation. Each volunteer received one of the dressings, both with the same dimensions and arranged over similar regions, and data were gathered at baseline and after 6 or 12 hours. Descriptive and inferential analytic statistical methods were used; the significance level adopted was 5%. No participant developed DRPI, but four areas with hyperemia were observed in the foam group (two in the forehead, one in the cheeks, and one in the nose bridge), as well as four areas with hyperemia in the hydrocolloid group (two in the nose bridge, one in the right ear, and one in the left ear). There was no difference between the groups regarding skin conditions and discomfort (P > .05). The average cost obtained was $ 5.8/person and $ 4.4/person in the foam group and the hydrocolloid group, respectively, considering the dressing measurements. The results show that foam and extra-thin hydrocolloid were effective in preventing DRPI associated with the use of PPE.

The design of anion-π interactions and hydrogen bonds for the recognition of chloride, bromide and nitrate anions.

The role of anions in several biochemical processes has given rise to enormous interest in the identification/exploration of compounds with the potential ability to recognize anions. Here, an anthracene-squaramide conjugated compound, O2C4[NH(C14H10)][(NH(C6H6)], has been modified through the substitutions (i) H → F and (ii) H → OH at the anthracene and benzene rings to improve the capabilities of these structures for recognizing chloride, bromide, and nitrate anions. Through an energy decomposition analysis method, the recognition of the anions is chiefly identified as a non-covalent process. H → F substitutions at the benzene ring and, principally, the anthracene ring favor anion recognition, since H → F substitutions create a π-acid region in the aromatic ring, as indicated based on the molecular electrostatic potential surfaces. Similarly, H → OH substitutions also improve the recognition of anions, which is related to the establishment of partly covalent chemical bonds of the form O-H(Cl-, Br- and O-), which are verified based on the quantitative analysis of the maximum and minimum values of the molecular electrostatic potential surfaces and the quantum theory of atoms in molecules method. The presence of large electron density has a key role in the recognition of Cl- anions, and the more favorable electrostatic interactions between the anthracene structure and Br- anions, relative to NO3- anions, mean that receptorBr- interactions are more attractive than receptorNO3- ones. These data can contribute to the design of structures with the relevant abilities to interact with anions.

Macrophage autophagy protects mice from cerium oxide nanoparticle-induced lung fibrosis.

BACKGROUND: Cerium (Ce) is a rare earth element, rapidly oxidizing to form CeO2, and currently used in numerous commercial applications, especially as nanoparticles (NP). The potential health effects of Ce remain uncertain, but literature indicates the development of rare earth pneumoconiosis accompanied with granuloma formation, interstitial fibrosis and inflammation. The exact underlying mechanisms are not yet completely understood, and we propose that autophagy could be an interesting target to study, particularly in macrophages. Therefore, the objective of our study was to investigate the role of macrophagic autophagy after pulmonary exposure to CeO2 NP in mice. Mice lacking the early autophagy gene Atg5 in their myeloid lineage and their wildtype counterparts were exposed to CeO2 NP by single oropharyngeal administration and sacrificed up to 1 month after. At that time, lung remodeling was thoroughly characterized (inflammatory cells infiltration, expression of fibrotic markers such as αSMA, TGFß1, total and type I and III collagen deposition), as well as macrophage infiltration (quantification and M1/M2 phenotype). RESULTS: Such pulmonary exposure to CeO2 NP induces a progressive and dose-dependent lung fibrosis in the bronchiolar and alveolar walls, together with the activation of autophagy. Blockage of macrophagic autophagy protects from alveolar but not bronchiolar fibrosis, via the modulation of macrophage polarization towards M2 phenotype. CONCLUSION: In conclusion, our findings bring novel insight on the role of macrophagic autophagy in lung fibrogenesis, and add to the current awareness of pulmonary macrophages as important players in the disease.

Sleep deprivation decreases the reproductive capacity by affecting the arrival of morulas in the uterus.

A previous animal study by our group found that sleep deprivation during preimplantation was associated with decreased pregnancy maintenance. Given its impact on human society, we aimed in the current study to assess whether sleep deprivation affects blastocyst gene expression and/or the implantation process. For this, pregnant mice (gestational day 0 [GD 0]) were assigned into paradoxical sleep deprivation (SD, 72 hr; multiple platform method) and, a control (CT) group. Animals were euthanized on GD 3.5 and blood, uterus (embryos) and fallopian tube were collected. Then, 89% of CT presented blastocysts in the uterus versus 25% from SD group. Compared to CT, SD presented lighter relative uterus weight, increased plasma concentrations of corticosterone and testosterone, decreased concentrations of progesterone and luteinizing hormone, but no statistical differences in plasma concentrations of 17ß-estradiol and follicle stimulating hormone. There were no differences in uterus and blastocyst gene expression related to embryo implantation and development, and no alteration in blastocysts global DNA methylation. Considering this, the decreased pregnancy maintenance after sleep deprivation seems not to be associated with implantation losses or developmental problems related to the blastocysts. It is likely that complications in morula development and/or its movement through the fallopian tubes affect the pregnancy rate, since only 25% of SD females presented a blastocyst on the GD 3.5. In fact, three out of four females without blastocysts in the uterus presented morula in the fallopian tubes due to a phase delay. Additionally, we suggest that the observed hormonal changes may play a role in this outcome.

Sutton Naevi as Melanoma Simulators: Can Confocal Microscopy Help in the Diagnosis?

Sutton naevi can sometimes present a challenging appearance with atypical presentation, also by dermoscopy. Reflectance confocal microscopy could help in making a diagnosis. This study prospectively collected two groups of Sutton nevi: the first one was composed by typical white halo naevi monitored for one year (13, 23%) and the second one was made up of atypical lesions excised in order to rule out melanoma, which were histologically diagnosed as Sutton naevi (21, 37%). These two groups of Sutton naevi were compared to a retrospectively collected cohort of thin melanomas with histologic regression features (23, 40%). On dermoscopy, atypical Sutton naevi and melanomas were indistinguishable. Reflectance confocal microscopy demonstrated significant differences at the dermo-epidermal junction: marked dermo-epidermal junction thickening and non-edged papilla were associated with melanoma, while the presence of nests was associated with Sutton naevi. However, reflectance confocal microscopy also detected marked intraepidermal pagetoid cells in Sutton naevi that were a combination of MelanA+ and CD1a+ cells. Sutton naevi can simulate melanoma, under both dermoscopy and reflectance confocal microscopy. Nevertheless, relevant confocal dermo-epidermal junction features and the clinical scenario can be helpful to make a final diagnosis, especially in those situations where melanoma must be ruled out.

Topical application of lectin Artin M improves wound healing in defects created in the palatal mucosa: an in vivo study in dogs.

Previous studies have shown that topical application of lectin Artin-M accelerates wound healing in the rat oral mucosa. The aim of this study was to evaluate, by means of histology and immunohistochemistry (IHC) the effects of Artin-M on wound healing in the palatal mucosa in dogs. Three full thickness wounds of 6 mm diameter were surgically created in the palatal mucosa of twenty dogs and randomly divided into three groups according to one of the treatment assigned: Group C-Control (coagulum); Group A-Artin-M gel; Group V-Vehicle (carboxymethylcellulose 3%). Each animal received all the three experimental treatments. Afterwards, four animals were killed at 2, 4, 7, 14 and 21 days post-surgery. Wounded areas were photographed and scored for macroscopic evaluation. Biopsies were harvested and used for descriptive histological analysis, proliferating cell nuclear antigen IHC and measurement of myeloperoxidase activity. The results demonstrated faster wound closure in group A in comparison to the other groups in all the periods evaluated. Histological analyses exhibited improved re-epithelialization and collagen fiber formation resulting in faster maturation of granulation tissue in group A compared to the other groups by day 14. Treatment with Artin-M gel significantly induced cell proliferation and increased volumetric density of fibroblasts at day 2 and 4 (p < 0.05). Neutrophil infiltration in group A was significantly higher than the other groups (p < 0.05) at the same time points. Collectively, our findings demonstrated that Artin-M may potentially favor wound healing on palatal mucosa lesions via recruitment of neutrophils and promotion of cell proliferation.

Erythema multiforme induced by fluconazole in an immunocompetent patient: a case report and review of the literature.

Erythema multiforme (EM) is an acute hypersensitivity reaction that affects the skin and/or mucosa. EM induced by fluconazole is extremely rare, with only 2 previously published case reports. The aims of this article are to report a rare case of severe EM induced by fluconazole in an immunocompetent patient and to review all similar published cases. A 35-year-old man presented with multiple painful superficial ulcerated lesions on the lips, superficial ulcers on the right and left ocular mucosa, and erythematous macules on the right cervical region. Moreover, multiple painful superficial ulcers covered by a serofibrinous pseudomembrane were located on the oral mucosa. The lesions appeared after the initial oral use of fluconazole (100 mg) 3 weeks previously for the treatment of onychomycosis. The clinical diagnosis was EM associated with fluconazole. The antifungal medication was discontinued, and a single dose of intramuscular Diprospan (5 mg of betamethasone dipropionate/2 mg of betamethasone disodium phosphate) was prescribed. Complete healing of all lesions at the 7-day follow-up was observed.

Diabetes Prevention Programs in Rural North America: a Systematic Scoping Review.

AIMS: The aims of this systematic scoping review were to characterize the extent to which diabetes prevention programs have focused on rural populations in North America and where possible, identify efficacious program components. METHODS: The review was guided by the PRISMA statement and five steps for scoping studies. Searches were conducted in August 2017 in Tucson, Arizona. Two teams of three independently screened full texts, excluding prior reviews, systematic reviews, and opinion pieces. Two authors abstracted data, which were reviewed by other team members. RESULTS: Of the 12,840 articles identified, 12 met all criteria. Nine studies were based in the USA and three were Canadian. Demographics reflected high enrollment of underrepresented minorities, adults, and females. Methodological rigor was low; most studies were single-arm interventions evaluated using pre-/post-measures. Weight was measured across all studies, although biological, behavioral, and psychosocial outcomes were inconsistently assessed. Eight studies reported significant changes in primary outcomes. Duration and intensity were variable; delivery was led by trained volunteers or health professionals. Seven studies reported recruitment, retention, and adherence data. CONCLUSIONS: Surprisingly, few rural diabetes prevention studies have been published. Published programs were notable for lack of youth and/or family involvement, integrated prevention and treatment programs, and heavy reliance on self-reported outcomes.

Fermentative profile and lactic acid bacterial dynamics in non-wilted and wilted alfalfa silage in tropical conditions.

This study was conducted to evaluate the fermentative profile and microbial populations of wilted and non-wilted alfalfa silages ensiled with or without inoculant and the population dynamics of lactic acid bacteria (LAB) of wilted alfalfa plant and theirs silage. A 2 × 2 × 6 factorial arrangement was used, with the absence or presence of wilting (W), with and without bacterial inoculant (I) and six fermentation periods (P) (1, 3, 7, 14, 28 and 56 days), in a completely randomized design, with three replicates. The alfalfa was slightly wilted for 6 h and increased the dry matter content from 133.9 to 233.4 g/kg. It was performed the cultivation, followed by the isolation of LAB from samples of alfalfa forage before ensiling and its silage only in non-inoculated silages, after different fermentation periods. DNA was extracted from the isolated strains of LAB; the 16S rRNA gene sequences were amplified by PCR and the sequences were compared to those available from the GenBank database. Wilting provided silages with lower pH, ammonia nitrogen and acetic acid concentrations. The wilting process did not alter the amount of LAB; however, it affected the LAB diversity of the silages. The Lactobacillus plantarum was the predominant species in non-wilted and wilted silages.

Determination of pharmaceutical compounds in hospital wastewater and their elimination by advanced oxidation processes.

This study investigates the mineralization efficiency, i.e. removal of total organic carbon (TOC) in hospital wastewater by direct ozonation, ozonation with UV radiation (O3/UV), homogeneous catalytic ozonation (O3/Fe2+) and homogeneous photocatalytic ozonation (O3/Fe2+/UV). The influence of pH and reaction time was evaluated. For the best process, toxicity and degradation efficiency of the selected pharmaceutical compounds (PhCs) were determined. The results showed that the PhCs detected in the hospital wastewater were completely degraded when the mineralization efficiency reached 54.7% for O3/UV with 120 minutes of reaction time using a rate of 1.57 g O3 h-1. This process also achieved a higher chemical oxygen demand removal efficiency (64.05%), an increased aromaticity reduction efficiency (81%) and a toxicity reduction.

Patterns of distribution of giant congenital melanocytic nevi (GCMN): The 6B rule.

BACKGROUND: Garment-related terms have been used to describe the pattern of distribution of giant congenital melanocytic nevi (GCMN). OBJECTIVE: We sought to describe patterns of distribution of GCMN and propose a classification scheme. METHODS: Photographic records of patients with GCMN from the Hospital Clinic of Barcelona were analyzed and a classification based on observed GCMN distribution patterns was created. The classification was independently applied by 8 observers to cases found in the literature. The interobserver agreement was assessed. RESULTS: Among 22 patients we observed 6 repeatable patterns of distribution of GCMN, which we termed the "6B": bolero (involving the upper aspect of the back, including the neck), back (on the back, without involvement of the buttocks or shoulders), bathing trunk (involving the genital region and buttocks), breast/belly (isolated to the chest or abdomen without involvement of bolero or bathing trunk distributions), body extremity (isolated to extremity), and body (both bolero and bathing trunk involvement). Our literature search found 113 cases of GCMN, which we were able to classify into 1 of the 6B patterns with an overall kappa of 0.89. LIMITATIONS: Some patterns occur infrequently with a dearth of images available for analysis. CONCLUSIONS: The anatomic distribution of GCMN occurs in 6 recognizable and repeatable patterns.

Respiratory and Systemic Effects of LASSBio596 Plus Surfactant in Experimental Acute Respiratory Distress Syndrome.

BACKGROUND/AIMS: Exogenous surfactant has been proposed as adjunctive therapy for acute respiratory distress syndrome (ARDS), but it is inactivated by different factors present in the alveolar space. We hypothesized that co-administration of LASSBio596, a molecule with significant anti-inflammatory properties, and exogenous surfactant could reduce lung inflammation, thus enabling the surfactant to reduce edema and improve lung function, in experimental ARDS. METHODS: ARDS was induced by cecal ligation and puncture surgery in BALB/c mice. A sham-operated group was used as control (CTRL). After surgery (6 hours), CTRL and ARDS animals were assigned to receive: (1) sterile saline solution; (2) LASSBio596; (3) exogenous surfactant or (4) LASSBio596 plus exogenous surfactant (n = 22/group). RESULTS: Regardless of exogenous surfactant administration, LASSBio596 improved survival rate and reduced collagen fiber content, total number of cells and neutrophils in PLF and blood, cell apoptosis, protein content in BALF, and urea and creatinine levels. LASSBio596 plus surfactant yielded all of the aforementioned beneficial effects, as well as increased BALF lipid content and reduced surface tension. CONCLUSION: LASSBio596 exhibited major anti-inflammatory and anti-fibrogenic effects in experimental sepsis-induced ARDS. Its association with surfactant may provide further advantages, potentially by reducing surface tension.