Search

The treatment of large segmental defects of long bones resulting from trauma, infection, or bone tumor resections is a major challenge for orthopedic surgeons. The reconstruction of bone defects with acellular allografts can be used as an osteoconductive approach. However, devitalized allografts are associated with high rates of clinical failure as a result of poor intrinsic osteoinduction properties and a lack of further remodeling. Nevertheless, evidence suggests that due to its anabolic properties, teriparatide (PTH1-34) could be effective as an adjuvant therapy for massive allograft healing. Therefore, our goal was to investigate in a murine critical-sized defect model whether the intermittent administration of PTH1-34 improves the incorporation and revitalization of acellular structural bone allografts. Thus, a 2.5-mm critical-sized defect was established in the right femur of C57BL/6 mice, followed by the reconstruction with a devitalized cortical structural allograft. A titanium micro locking plate was applied to the anterior femoral surface and secured in place with self-tapping locking screws. Subsequently, daily doses of PTH1–34 (30, and 40 µg/kg) or saline were administered to the mice for 14 days after surgery. The mice were maintained without PTH1–34 therapy for an additional 7 days before being euthanized at 3 weeks post-surgery. Bone graft consolidation was assessed on radiographic images and by histomorphometric analysis. Additionally, to determine the frequency of osteoprogenitor cells in the bone marrow and their in vitro osteogenic capacity, stromal cells were isolated from the bone marrow of animals treated with 30 or 40 µg/kg/day of PTH1-34 following the same protocol used for the experimental animals. Our results suggest that intermittent PTH1-34 treatment at 30 µg/kg/day after femoral allograft reconstruction surgery accelerated the healing process as evidenced by new bone formation induced on endosteal and periosteal surfaces, enhanced revitalization of allogeneic graft, and increased frequency and osteogenic capacity of bone marrow stromal cells (BMSC). These findings should encourage further studies aimed at investigating the potential therapeutic use of intermittent PTH1-34, specifically with regards to the optimal dosing regimen in clinically challenging orthopedic scenarios.

The red palm weevil Rhynchophorus ferrugineus (Coleoptera: Curculionidae) is an economically-important invasive species that attacks multiple species of palm trees around the world. A better understanding of gene content and function in R. ferrugineus has the potential to inform pest control strategies and thereby mitigate economic and biodiversity losses caused by this species. Using 10x Genomics linked-read sequencing, we produced a haplotype-resolved diploid genome assembly for R. ferrugineus from a single heterozygous individual with modest sequencing coverage ($$\sim$$ ∼ 62x). Benchmarking against conserved single-copy Arthropod orthologs suggests both pseudo-haplotypes in our R. ferrugineus genome assembly are highly complete with respect to gene content, and do not suffer from haplotype-induced duplication artifacts present in a recently published hybrid assembly for this species. Annotation of the larger pseudo-haplotype in our assembly provides evidence for 23,413 protein-coding loci in R. ferrugineus, including over 13,000 predicted proteins annotated with Gene Ontology terms and over 6000 loci independently supported by high-quality Iso-Seq transcriptomic data. Our assembly also includes 95% of R. ferrugineus chemosensory, detoxification and neuropeptide-related transcripts identified previously using RNA-seq transcriptomic data, and provides a platform for the molecular analysis of these and other functionally-relevant genes that can help guide management of this widespread insect pest.

Menopausal transition is a physiological process encompassing hormonal and body changes that impact women's health and life quality. This period may be characterized by the Stages of Reproductive Aging Workshop (STRAW + 10) criteria using menstrual patterns. Use of the STRAW + 10 is uncertain in HIV infection. We aimed to characterize menopausal transition in women with HIV (WWH) using the STRAW + 10 criteria, hormonal measures and menopause symptoms.We performed a cross-sectional study, nested to the HIV-Infected Women's Cohort, in Rio de Janeiro, Brazil. Eligible women included those aged 30 years or older, without clinical or surgical menopause, hormonal contraception, replacement therapy and ovarian disorders. We conducted face-to-face interviews and collected blood samples for follicle stimulating hormone (FSH) and estradiol measures.We enrolled 328 WWH (28.3% of women in the cohort). The distribution of age, hormonal levels and reported symptoms per each STRAW + 10 stage was consistent with the expected distribution in the menopausal transition. Age and FSH significantly increased and estradiol decreased from stage -2 (7 + days of menstrual delay) to stage +2 (8 + years of amenorrhea).The present results support use of the STRAW + 10 to characterize the menopausal transition of WWH with good clinical and immunological control.

Objectives: This study examined the impacts of COVID-19 lockdown on health and lifestyle factors for older adults in Sydney, Australia. The study examined demographic differences, social engagement, loneliness, physical activity, emotion regulation, technology use, and grandparenting experiences and their contribution to emotional health and quality of life during lockdown.Methods: Participants were 201 community-dwelling older adults (60-87 years, M = 70.55, SD = 6.50; 67.8% female) who completed self-report scales measuring physical and emotional health outcomes, quality of life, health service utilization, changes in diet and physical activity, impacts on grandparenting roles, and uptake of new technology.Results: One-third of older adults experienced depression, and 1 in 5 experienced elevated anxiety and/or psychological distress during lockdown. Specific emotion regulation strategies, better social and family engagement, and new technology use were associated with better emotional health and quality of life; 63% of older adults used new technologies to connect with others.Conclusions: Older adults were adaptable and resilient during lockdown, demonstrating high uptake of new technologies to remain connected to others, while negative emotional health outcomes were linked to loneliness and unhelpful emotion regulation.Clinical Implications: Further diversifying use of video technologies may facilitate improved physical and emotional health outcomes.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that currently has no cure. Identifying biochemical changes associated with neurodegeneration prior to symptom onset, will provide insight into the biological mechanisms associated with neurodegenerative processes, that may also aid in identifying potential drug targets. The current study therefore investigated associations between plasma neurofilament light chain (NF-L), a marker of neurodegeneration, with plasma metabolites that are products of various cellular processes. Plasma NF-L, measured by ultrasensitive Single molecule array (Simoa) technology (Quanterix) and plasma metabolites, measured by mass-spectrometry (AbsoluteIDQ® p400HR kit, BIOCRATES), were assessed in the Kerr Anglican Retirement Village Initiative in Ageing Health (KARVIAH) cohort comprising 100 cognitively normal older adults. Metabolites belonging to biogenic amine (creatinine, symmetric dimethylarginine, asymmetric dimethylarginine; ADMA, kynurenine, trans-4-hydroxyproline), amino acid (citrulline, proline, arginine, asparagine, phenylalanine, threonine) and acylcarnitine classes were observed to have positive correlations with plasma NF-L, suggesting a link between neurodegeneration and biological pathways associated with neurotransmitter regulation, nitric oxide homoeostasis, inflammation and mitochondrial function. Additionally, after stratifying participants based on low/high brain amyloid-β load (Aβ ±) assessed by positron emission tomography, while creatinine, SDMA and citrulline correlated with NF-L in both Aβ- and Aβ+ groups, ADMA, proline, arginine, asparagine, phenylalanine and acylcarnitine species correlated with NF-L only in the Aβ+ group after adjusting for confounding variables, suggesting that the association of these metabolites with neurodegeneration may be relevant to AD-related neuropathology. Metabolites identified to be associated with plasma NF-L may have the potential to serve as prognostic markers for neurodegenerative diseases, however, further studies are required to validate the current findings in an independent cohort, both cross-sectionally and longitudinally.

The purpose of this study was to determine the prevalence of bladder lesions diagnosed during transurethral resection of the prostate (TURP), to identify the associated risk factors, and to correlate the macroscopic descriptions with the pathological findings. This was a single-center retrospective case series conducted at a hospital in the city of Sao Paulo, Brazil. We reviewed the medical and surgical records of patients who underwent TURP between January 2012 and December 2017. The final sample comprised 513 patients, with a mean age of 70.8 years. Bladder lesions were identified during TURP in 109 (21.2%) of the patients, and 90 of those lesions were submitted for pathological examination. The most common macroscopic finding was bullous edema, which was seen in 57 (63.3%) of the 90 lesions examined. The pathological analysis revealed chronic cystitis in 61 lesions (67.8%) and malignant lesions in 16 (17.8%). Of the 57 lesions described as bullous edema, 5 (8.8%) were found to be malignant. Alterations in the bladder mucosa appear to be more common among elderly patients who use an indwelling urinary catheter for a prolonged period and among patients with recurrent urinary tract infections. In addition, the risk of a bladder lesion being malignant is apparently higher in current and former smokers than in never smokers. Our findings suggest that at-risk patients should undergo biopsy or resection of incidental bladder lesions even if those lesions seem to be benign, due to the low level of agreement between the visual analysis and the pathological examination.

Background/Objective: Hepcidin, an iron-regulating hormone, suppresses the release of iron by binding to the iron exporter protein, ferroportin, resulting in intracellular iron accumulation. Given that iron dyshomeostasis has been observed in Alzheimer’s disease (AD) together with elevated serum hepcidin levels, the current study examined whether elevated serum hepcidin levels are an early event in AD pathogenesis by measuring the hormone in cognitively normal older adults at risk of AD, based on high neocortical amyloid-β load (NAL). Methods: Serum hepcidin levels in cognitively normal participants (n = 100) aged between 65–90 years were measured using ELISA. To evaluate NAL, all participants underwent 18F-florbetaben positron emission tomography. A standard uptake value ratio (SUVR)

OBJECTIVE Parkinson's Disease (PD) is a progressive neurodegenerative disorder, manifesting with subtle early signs, which often hinder timely and early diagnosis and treatment. The development of accessible, technology-based methods for longitudinal PD symptoms tracking in daily living offers the potential for transforming the disease assessment and accelerating PD diagnosis. METHODS A privacy-aware method for classifying PD patients and healthy controls (HC), on the grounds of speech impairment present in PD, is proposed here. Voice features from running speech signals were extracted from recordings passively captured over voice phone calls. Features are fed in a language-aware training of multiple- and single-instance learning classifiers, along with demographic variables, exploiting a multilingual cohort of 498 subjects (392/106 self-reported HC/PD patients) to classify PD. RESULTS By means of leave-one-subject-out cross-validation, the best-performing models yielded 0.69/0.68/0.63/0.83 area under the Receiver Operating Characteristic curve (AUC) for the binary classification of PD patient vs. HC in sub-cohorts of English/Greek/German/Portuguese-speaking subjects, respectively. Out-of-sample testing of the best performing models was conducted in an additional dataset, generated by 63 clinically-assessed subjects (24/39 HC/early PD patients). Testing has resulted in 0.84/0.93/0.83 AUC for the English/Greek/German-speaking sub-cohorts, respectively. Comparative analysis with other approaches for language-aware PD detection justified the efficiency of the proposed one, considering the ecological validity of the acquired voice data. CONCLUSIONS The present work demonstrates increased robustness in PD detection using voice data captured in-the-wild. SIGNIFICANCE A high-frequency, privacy-aware and unobtrusive PD screening tool is introduced for the first time, based on analysis of voice samples captured during routine phone calls.

Synchrotron scanning X-ray microscopy has been established as a mature technique, bridging the gap between conventional optical microscopy and high-resolution electron microscopy and, notably, adding advantages like large penetration in bulky samples, dose reduction and spectroscopy. The CARNAUBA beamline at the 4th generation synchrotron source Sirius-LNLS provides an X-ray nanoprobe for simultaneous multi-analytical and coherent X-ray imaging techniques, with spectroscopic capabilities in the 2.05 to 15 keV energy range. The sample is raster-scanned through the nanoprobe to provide two-dimensional maps, which can then be combined with a rotation for computed tomography. In this contribution, some relevant scientific cases for the Day-1 experiments will be presented, along with original instrument solutions for in situ, in operando, cryogenic and in vivo sample environments.

Conhecida antigamente como Lepra, a Hanseniase e uma doenca cronica infectocontagiosa, de alto poder incapacitante, sendo este o principal responsavel de pessoas acometidas pela patologia serem estigmatizadas e discriminadas por muitos individuos na sociedade. Este trabalho teve como objetivo descrever a vivencia de academicos do curso de enfermagem, durante estagio extracurricular voluntario realizado em uma estrategia de saude da familia no municipio de Baiao-PA, Brasil. Trata-se de um estudo descritivo de natureza relato de experiencia, sobre a atuacao da equipe de enfermagem no tratamento, diagnostico e prevencao da hanseniase. A vivencia dessa construcao permitiu evidenciar o papel do profissional da enfermagem dentro da atencao basica, em especial na execucao do programa de vigilância a Hanseniase, norteando a importância desse profissional para dar suporte a saude e proporcionar um vinculo com o usuario. Alem de propiciar aos discentes conhecer o cotidiano da enfermagem dentro da unidade e aproximar os mesmos do mercado de trabalho, construindo conhecimento tecnico e cientifico para o cuidar cada vez mais pautado em evidencias.

Epidemiological and interventional studies have linked saturated fatty acids (SFA) with elevated levels of low-density lipoprotein cholesterol (LDL-C) and increased CVD risk. However, the effects of the SFA chain length on postprandial lipemia in humans are not well elucidated. The aim of this study was to investigate the impact of short, medium and long-chain SFA on postprandial blood lipids in healthy volunteers. Sixteen healthy volunteers consumed test biscuits containing 40 g of either butter (BB), coconut oil (CB) or lard (LB) in a single-blinded, randomized crossover design. Blood samples were collected fasting and 2, 3, 4, and 6 hours postprandially and assessed for blood lipids (total cholesterol, TC; high-density lipoprotein cholesterol, HDL-C; LDL-C and triglyceride, TG). The postprandial TG response following CB was 59.8% lower than following BB (p 0.01) and 58.8% lower than LB (p 0.01), although no difference was observed between the BB and the LB responses. The net area under the LDL-C concentration curve was significantly larger after consumption of the CB compared to the BB, despite no significant differences in postprandial net area under the TC and HDL-C concentration curves. Consumption of medium-chain SFA as CB resulted in lower postprandial TG excursions compared to short-chain SFA as BB and long-chain SFA as LB, despite their identical fat and caloric content. These results suggest that SFA differ in their potential to elevate postprandial lipid levels, and that coconut oil, a rich source of medium-chain SFA may not be as hyperlipidemic as animal fats rich in long chain SFA. ANZCTR IDENTIFIER: 12617000903381. CLINICAL TRIAL REGISTRY NUMBER: The study was registered with the Australia New Zealand Trial registry as ACTRN12617000903381.

Chromobacterium violaceum is a rare opportunistic pathogen that causes highly fatal infections in domestic animals and humans. This report describes a fatal case suggestive of septicemia in a four-day-old female calf with chromobacteriosis. The calf had suppurative omphalophlebitis, suppurative fibrinous polyarthritis, anterior uveitis with bilateral fibrin deposition, fibrinous peritonitis, lymph node abscess and multifocal lymphocytic and neutrophilic encephalitis with multifocal hemorrhages. C. violaceum was isolated from the spleen and peri-renal lymph node and its identity was confirmed by PCR and sequencing. The pathogen was sensitive to azithromycin, gentamicin, enrofloxacin, norfloxacin, marbofloxacin, ciprofloxacin, erythromycin, sulphazotrim, fluorfenicol, tetracycline and doxycycline as well as resistant to penicillin, ampicillin, vancomycin, amoxicillin, amoxicillin + clavulanic acid, cephalothin, cephalexin, oxacillin, B polymyxin, neomycin and bacitracin. This is the first report of chromobacteriosis in a calf from Brazil.

In the beginning of 2020, the coronavirus (Covid-19) pandemic has raised significant challenges for the Higher Education Institutions (HEIs) worldwide. Due to Covid-19 outbreak, HEIs were forced to close due to social lockdown, placing online teaching-learning environments/modalities to the foreground of the educational settings. In an effort to examine how this ‘new normal’ has affected users’ Quality of Interaction (QoI) within the Learning Management System (LMS) Moodle, a modeling approach based on fuzzy logic (FuzzyQoI), was used here and applied to LMS Moodle data, drawn from an undergraduate discipline, offered by a public Greek HEI during the Covid-19 period. The results have shown the ability of the FuzzyQoI model to express the time-depended dynamics of the users’ QoI and associate it with the societal effects of Covid-19. Clearly, these findings shed light upon the way users interact with a LMS online learning when societal disruptors, such as Covid-19, come in to play, informing HEIs’ policy makers for monitoring and re-examining online (teaching-learning) practices.

The associated natural gas produced on crude oil offshore platforms is often flared. The potential of two small-scale Gas-to-Liquids processes to monetise this gas whilst reducing carbon dioxide emissions is investigated in this work. Compact NETmix microreactors are considered for the reactor stages, and the process energy expenditure is reduced through heat integration of endothermic reforming stages, where syngas (a mixture of hydrogen and carbon monoxide) is produced, with exothermic Fischer-Tropsch stages, which convert syngas into liquid fuels. The base concept of the two Gas-to-Liquids processes considered differs mainly on the reforming stage: Steam Methane Reforming or Dry Methane Reforming. The two Gas-to-Liquids routes proposed are compared in terms of capital expenditure, operational expenditure and their emissions reduction potential compared to flaring.

Background The highly encouraging findings from the Finnish Geriatric Intervention Study (known as FINGER) led to the global initiative for dementia risk reduction known as world-wide FINGERS (WW FINGERS). As part of the collaboration, our Australian AU-ARROW trial will follow the general protocol of the FINGER trial, and will also be aligned with the U.S. arm of the study, US-POINTER, though will have minor cultural and dietary modifications to determine the validity of the intervention in an Australian setting. Method AU-ARROW is a randomised, single-blind 2-year clinical trial that will recruit 600 participants aged 60-79 satisfying specific inclusion/exclusion criteria, including normal cognition and one or more cardiovascular risk factors that place them at greater risk of cognitive decline. Participants will be distributed across two sites (a) Macquarie University Health Clinics, Sydney, NSW and (b) Sarich Neuroscience Research Institute, Edith Cowan University, Perth, WA, and will be randomised equally into either the innovative multi-modal intervention group or the study control group, who will receive general lifestyle advice and annual health check-ups, without treatment. Multi-modal intervention consists of aerobic exercise, resistance training and stretching; dietary advice with monitoring to encourage adherence to the MIND diet; cognitive training sessions via the Brain HQ computerised online training system; and medical monitoring and regular health education sessions. Heart rate trackers, diet and exercise log books, and the monitoring of Brain HQ sessions will all help with adherence. Primary outcome measure is improvement in global cognitive score, measured using neurocognitive tests identical to those in the US-POINTER protocol. Additional neurocognitive tests, physical function improvements, detailed diet monitoring and sleep monitoring will provide added data. The unique extra value of AU-ARROW trial consists of the testing for Alzheimer’s disease (AD) blood biomarkers in all participants; as well as the AD Aβ amyloid-specific ligand-PET imaging, brain MRI and retinal biomarker tests that half of the participants will undergo. These tests will provide comprehensive data which have the ultimate purpose of increasing knowledge of the preclinical stages of AD, and help not only to develop preclinical AD diagnostic tests but also efficacy of AU-ARROW’s intervention.

Coronavirus (Covid-19) pandemic has imposed a complete shut-down of face-to-face teaching to universities and schools, forcing a crash course for online learning plans and technology for students and faculty. In the midst of this unprecedented crisis, video conferencing platforms (e.g., Zoom, WebEx, MS Teams) and learning management systems (LMSs), like Moodle, Blackboard and Google Classroom, are being adopted and heavily used as online learning environments (OLEs). However, as such media solely provide the platform for e-interaction, effective methods that can be used to predict the learner’s behavior in the OLEs, which should be available as supportive tools to educators and metacognitive triggers to learners. Here we show, for the first time, that Deep Learning techniques can be used to handle LMS users’ interaction data and form a novel predictive model, namely DeepLMS, that can forecast the quality of interaction (QoI) with LMS. Using Long Short-Term Memory (LSTM) networks, DeepLMS results in average testing Root Mean Square Error (RMSE) $$ < 0.009 , and average correlation coefficient between ground truth and predicted QoI values $$r\ge 0.97$$ r ≥ 0.97 $$(p ( p < 0.05 ) , when tested on QoI data from one database pre- and two ones during-Covid-19 pandemic. DeepLMS personalized QoI forecasting scaffolds user’s online learning engagement and provides educators with an evaluation path, additionally to the content-related assessment, enriching the overall view on the learners’ motivation and participation in the learning process.

The primary manifestations of Parkinson Disease (PD) concern abnormalities of movement associated with the constant deterioration of motor skills. Such motor impairment affects patients’ movement accuracy and coordination, disrupting their daily life. Taking into account recent studies stating that computer-based physical therapy games can be used as a PD rehabilitation option, we propose a novel Exergame, the iPrognosis Warming up Game (http://www.i-prognosis.eu/), as a user-friendly tool that could both serve as a computer-based physical therapy game, as well as a means of accurately and automatically identifying the severity of PD motor symptoms. To this regard, we propose a novel deep learning methodology for motor impairment stage prediction that relies solely on human body motion data extracted from the recorded game sessions. Experimental results using a dataset of both early and advanced PD patients reveal a good classification performance of the proposed methodology, predicting the motor impairment stage of PD patients and paving the way for additional research in the field.

The red palm weevil Rhynchophorus ferrugineus (Coleoptera: Curculionidae) is an economically-important invasive species that attacks multiple species of palm trees around the world. A better understanding of gene content and function in R. ferrugineus has the potential to inform pest control strategies and thereby mitigate economic and biodiversity losses caused by this species. Using 10x Genomics linked-read sequencing, we produced a haplotype-resolved diploid genome assembly for R. ferrugineus from a single heterozygous individual with modest sequencing coverage (~62x). Benchmarking against conserved single-copy Arthropod orthologs suggests both pseudo-haplotypes in our R. ferrugineus genome assembly are highly complete with respect to gene content, and do not suffer from haplotype-induced duplication artifacts present in a recently published hybrid assembly for this species. Annotation of the larger pseudo-haplotype in our assembly provides evidence for 23,413 protein-coding loci in R. ferrugineus, including over 13,000 predicted proteins annotated with Gene Ontology terms and over 6,000 loci independently supported by high-quality Iso-Seq transcriptomic data. Our assembly also includes 95% of R. ferrugineus chemosensory, detoxification and neuropeptide-related transcripts identified previously using RNA-seq transcriptomic data, and provides a platform for the molecular analysis of these and other functionally-relevant genes that can help guide management of this widespread insect pest.

IntroductionIgA nephropathy (IgAN) is the most common primary glomerulopathy worldwide. According to the Oxford Classification, changes in the kidney vascular compartment are not related with worse outcomes. This paper aims to assess the impact of thrombotic microangiopathy (TMA) in the outcomes of Brazilian patients with IgAN.Materials and MethodsAnalysis of clinical data and kidney biopsy findings from patients with IgAN to assess the impact of TMA on renal outcomes.ResultsThe majority of the 118 patients included were females (54.3%); mean age of 33 years (25;43); hypertension and hematuria were observed in 67.8% and 89.8%, respectively. Median creatinine: 1.45mg/dL; eGFR: 48.8ml/min/1.73m2; 24-hour proteinuria: 2.01g; low serum C3: 12.5%. Regarding to Oxford Classification: M1: 76.3%; E1: 35.6%; S1: 70.3%; T1/T2: 38.3%; C1/C2: 28.8%. Average follow-up: 65 months. Histologic evidence of TMA were detected in 21 (17.8%) patients and those ones presented more frequently hypertension (100% vs. 61%, p vs 87.6%, p=0.0001), worse creatinine levels (3.8 vs. 1.38 mg/dL, p=0.0001), eGFR (18 vs. 60 ml/min/1.73m2), p =0.0001), low serum C3 (28.5% vs. 10.4%, p =0.003), lower hemoglobin levels (10.6 vs. 12.7g/dL, p<0.001) and platelet counts (207,000 vs. 267,000, p=0.001). Biopsy findings of individuals with TMA revealed only greater proportions of E1 (68% vs. 32%, p = 0.002). Individuals with TMA were followed for less time (7 vs. 65 months, pvs. 21,6%, pConclusionsIn this study patients with TMA had worse clinical manifestations and outcomes. In terms of histologic evidence, E1 distinguished patients with TMA from other patients. These findings indicate that vascular compartment may also be a prognostic marker in IgAN patients.

Hypertensive individuals are at greater risk for developing chronic kidney disease (CKD). Reducing proteinuria has been suggested as a possible therapeutic approach to treat CKD. However, the mechanisms underlying the development of proteinuria in hypertensive conditions are incompletely understood. Cardiac and vascular dysfunction is associated with changes in the O-GlcNAcylation pathway in hypertensive models. We hypothesized that O-GlcNAcylation is also involved in renal damage, especially development of proteinuria, associated with hypertension. Using the spontaneously hypertensive rat (SHR) model, we observed higher renal cortex O-GlcNAcylation, glutamine–fructose aminotransferase (GFAT), and O-GlcNAc transferase (OGT) protein expression, which positively correlated with proteinuria. Interestingly, this was observed in hypertensive, but not pre-hypertensive, rats. Pharmacological inhibition of GFAT decreased renal cortex O-GlcNAcylation, proteinuria, and albuminuria in SHR. Using a proximal tubule cell line, we observed that increased O-GlcNAcylation reduced megalin surface expression and albumin endocytosis in vitro, and the effects were correlated in vivo. Moreover, megalin is O-GlcNAcylated both in vitro and in vivo. In conclusion, our results demonstrate a new mechanism involved in hypertension-associated proteinuria.

A number of cancer types have shown an increased prevalence and a higher mortality rate in patients with hyperglycemic associated pathologies. Although the correlation between diabetes and cancer incidence has been increasingly reported, the underlying molecular mechanisms beyond this association are not yet fully understood. Recent studies have suggested that high glucose levels support tumor progression through multiple mechanisms that are hallmarks of cancer, including cell proliferation, resistance to apoptosis, increased cell migration and invasiveness, epigenetic regulation (hyperglycemic memory), resistance to chemotherapy and altered metabolism. Most of the above occur because hyperglycemia through hexosamine biosynthetic pathway leads to aberrant O-GlcNAcylation of many intracellular proteins that are involved in those mechanisms. Deregulated O-GlcNAcylation is emerging as a general feature of cancer. Despite strong evidence suggesting that aberrant O-GlcNAcylation is or may be involved in the acquisition of all cancer hallmarks, it remains out of the list of the next generation of emerging hallmarks. Here, we discuss some of the current understanding on how hyperglycemia affects cancer cell biology and how aberrant O-GlcNAcylation stands in this context.

Objective: The purpose of this study was to reproduce a mouse model of bone sarcomas for use in cancer research. Methods: A fresh sample of the tumor tissue was implanted subcutaneously into nude mice. When the patient-derived xenograft (PDX) reached a volume of 1500 mm3, it was harvested for re-implantation into additional mice. Histology was used to compare the morphological characteristics of different generations of sarcoma xenografts with the primary tumor. Results: Sixteen sarcoma tissue samples were engrafted into nude mice. Nine patients were diagnosed with osteosarcoma, two with chondrosarcoma, two with malignant peripheral nerve sheath tumor, one with synovial sarcoma, one with pleomorphic sarcoma, and one with Ewing’s sarcoma. PDX tumors were generated in 11 of the 16 implanted specimens (69% success rate in P1). Six P1 tumors grew sufficiently for transfer into additional mice, producing the P2 generation, and three P2 tumors established the P3 generation. Conclusion: PDX tumors generated from bone sarcomas were successfully established in immunodeficient mice and reproduced the characteristics of the primary tumor with a high degree of fidelity. The preclinical PDX model described herein may represent an important tool for translational oncology research and for evaluating therapeutic strategies for bone sarcomas. Level of Evidence I; Experimental study. RESUMO Objetivo: O propósito deste estudo foi reproduzir em camundongos um modelo de sarcomas ósseos para uso em pesquisa oncológica. Método: Amostras frescas de tecido tumoral foram implantadas por via subcutânea em camundongos Nude. Quando o xenoenxerto derivado do paciente (PDX) alcançava 1500 mm3, ele era retirado do animal e reimplantado em outros camundongos. Estudos histológicos foram realizados para comparar as características morfológicas de diferentes gerações de xenoenxertos com o tumor primário. Resultados: Dezesseis amostras de tecido sarcomatoso foram enxertadas em camundongos. Nove pacientes foram diagnosticados com osteossarcoma, dois com condrossarcoma, dois com tumor maligno de bainha de nervo periférico, um com sarcoma sinovial, um com sarcoma pleomórfico e um com sarcoma de Ewing. Foram gerados tumores PDX em 11 das 16 amostras enxertadas (taxa de sucesso de 69% em P1). Destes, seis tumores P1 cresceram o suficiente para serem transferidos para outros camundongos, dando origem à geração P2 e três dos tumores P2 estabeleceram a geração P3. Conclusões: Os tumores PDX de sarcomas ósseos foram estabelecidos com sucesso em camundongos imunodeficientes e reproduziram com alta precisão as características do tumor primário. O modelo pré-clínico de PDX descrito pode representar uma ferramenta importante para a pesquisa oncológica translacional e para avaliar estratégias terapêuticas para sarcomas ósseos. Nível de Evidência I; Estudo experimental.

Introduction Femoral shaft fractures generally occur in young adults following a high-energy trauma and are prone to delayed union/non-union. Novel therapies to stimulate bone regeneration will have to mimic some of the aspects of the biology of fracture healing; however, which are these aspects is unclear. Locked intramedullary nailing is the current treatment of choice for the stabilisation of femur shaft fractures, and it is associated with accelerated healing and increased union rates. These benefits were partially attributed to the reaming procedure, which, regardless of significantly destroying the haematoma, stimulates the healing response. To better understand how reaming influences healing, we evaluated the viability of the nucleated cell fraction and the frequency of CD146+ skeletal progenitors, which contain multipotent cells, in the post-reaming haematoma. We also screened the concentrations of inflammatory mediators and growth factors in the fracture site after reaming compared with those in the original haematoma. Methods Pre- and post-reaming haematomas were percutaneously aspirated from the fracture site of 15 patients with closed femoral shaft fractures. Cellular viability and the percentage of CD146+ progenitors were analysed by flow cytometry. The concentrations of cytokines and growth factors were determined by ELISA. Results AnnexinV/Pi analysis showed that the viability of the total nucleated cell fraction was decreased in the post-reaming haematoma. However, the procedure increased the percentage of CD146+ skeletal progenitors in the fracture site. Analysis of cytokines and growth factors in supernatants showed a decreased concentration of the inflammatory mediators IL-6, CCL-4, and MCP-1, along with an increase of anti-inflammatory IL-10, and the growth factors bFGF and PDGF-AB. Conclusion These findings support the view that the positive effects of reaming on fracture healing might result from mechanically grafting the fracture site with a population of skeletal progenitors that contain multipotent cells; transitioning the signalling environment to a less inflammatory state, and enhancing the availability of specific osteogenic and angiogenic factors. A better understanding of the requisite stimuli for optimal bone repair, considering the disturbances made by orthopaedic treatments, will be determinant for the development of innovative treatments for bone repair.

Cardiovascular disease (CVD) is the major cause of death in the UAE, causing one in every five deaths. Effective Cardiac Rehabilitation (CR) can significantly improve mortality and morbidity rates, leading to longer independent living and a reduced use of healthcare resources. The proposed project, namely Care4MyHeart, sets as an overall goal to introduce a personalized home-based CR program, enabling lifestyle behavioral change towards increased quality of life, surpassing the currently unsustainable provision of healthcare for CVD. In particular, the Care4MyHeart-Pesronalized Serious Game (C4MH-PSG) platform targets CVD patients entering Phase III, as this is where large numbers of patients, who would benefit significantly from exercise and CR, drop out. C4MH-PSG supports the key predictors for attendance to CR Phase III programs, including high program availability, ease of access to program location, high social connectivity, peer support (when peers share similar problems or/and can become peer mentors), and high self-efficacy. Within C4MH-PSG, advanced machine learning and modelling techniques are employed to propose gender- and age-specific CVD exercise programs and an autonomous helper-agent, providing informed feedback to the patient and the related physician/carer, establishing a collaborative patient-professional partnership. C4MH-PSG is realized via motion capture, exercise evaluation, physiological and lifestyle monitoring, exercise gaming, home-based human-computer interfacing, multi-parametric data modelling and advanced decision support systems. Finally, the overall concept and system are easily transferable to address other diseases/conditions (e.g., diabetes, osteoporosis, obesity), providing market opportunities for the commercialization of C4MH-PSG beyond CVD.

Affective Computing is one of the most active research topics in education. Increased interest in emotion recognition through text channels makes sentiment analysis (i.e., the Natural Language Processing task of determining the valence in texts) a state-of-the-practice tool. Considering the domain-dependent nature of sentiment analysis as well as the heterogeneity of the educational domain, development of robust sentiment classifiers requires an in-depth understanding of the effect of the teaching-learning context on model performance. This work investigates machine learning-based sentiment classification on datasets comprised of student posts in forums, pertaining to two different academic courses. Different dataset configurations were tested, aiming to compare performance: i) between single-course and multi-course classifiers, ii) between in-course and cross-course classification. A sentiment classifier was built for each course, exhibiting a fair performance. However, classification performance dramatically decreased, when the two models were transferred between courses. Additionally, classifiers trained on a mixture of courses underperformed single-course classifiers. Findings suggested that sentiment analysis is a course-dependent task and, as a rule of thumb, less but course-specific information results in more effective models than more but non-specialized information.

Red meat restriction in the diet is increasingly recommended, with vegetarian-based diets being promoted. [...]

SummaryDiabetes mellitus (DM) significantly increases the risk for cancer and cancer progression. Hyperglycemia is the defining characteristic of DM and tightly correlates with a poor prognosis in cancer patients. The hexosamine biosynthetic pathway (HBP) is emerging as a pivotal cascade linking high glucose, tumor progression and impaired immune function. Here we show that enhanced glucose flow through the HBP drives cancer progression and immune evasion by increasing O-GlcNAcylation in tumor-associated macrophages (TAMs). Increased O-GlcNAc skewed macrophage polarization to a M2-like phenotype. HBP or O-GlcNAcylation inhibition reprogrammed TAMs to an anti-tumoral phenotype. Finally, we found an upregulation of M2 markers on TAMs in DM2 patients with colorectal cancer compared to non-diabetic normoglycemic patients. Our results provide evidence for a new and targetable mechanism of cancer immune evasion in patients with hyperglycemia, advocating for strict control of hyperglycemia in cancer patients.SignificanceHyperglycemia increases O-GlcNAc levels in TAMs, programing them to a pro-tumorigenic phenotype (M2-like), contributing to cancer progression. Inhibition of O-GlcNAcylation could therefore be used to reprogram intratumoral macrophages to an anti-tumoral phenotype.

Alzheimer's disease (AD) is the most common form of dementia. Currently, there is no effective medication for the prevention or treatment of AD. This has led to the search for alternative therapeutic strategies. Coconut oil(CO) has a unique fatty acid composition that is rich in medium chain fatty acids(MCFA), a major portion of which directly reaches the liver via the portal vein, thereby bypassing the lymphatic system. Given that brain glucose hypometabolism is a major early hallmark of AD, detectable well before the onset of symptoms, ketone bodies from MCFA metabolism can potentially serve as an alternative energy source to compensate for lack of glucose utilisation in the brain. Additionally, neuroprotective antioxidant properties of CO have been attributed to its polyphenolic content. This review discusses how the metabolism of CO and MCFA may aid in compensating the glucose hypometabolism observed in the AD brain. Furthermore, we present the current evidence of the neuroprotective properties of CO on cognition, amyloid-β pathogenicity, inflammation and oxidative stress. The current review addresses the influence of CO/MCFA on other chronic disorders that are risk factors for AD, and addresses existing gaps in the literature regarding the use of CO/MCFA as a potential treatment for AD.

Background Although 2-dimensional echocardiography (2DE) is widely used to measure left ventricular ejection fraction (LVEF), the prognostic value of 2DE-derived LVEF has not been clearly demonstrated in a broad range of patients, including those acutely hospitalized as well as ambulatory patients. In particular, the prognostic value of echocardiographic LVEF has not been demonstrated for cardiovascular and heart failure hospitalizations. Purpose To determine if greater degrees of LV dysfunction are associated with progressively increasing risks of death or cardiovascular hospitalizations among patients undergoing echocardiography in hospital or outpatient settings. Methods We examined quantitative LVEFs from patient-level echocardiographic reports at 3 large hospital laboratories, which were linked to the Canadian Institute for Health Information hospitalization database and to death registries in Ontario, Canada. LVEF was categorized as Results In the echocardiographic cohort of 27,323 patients (median age 68 [IQR: 58–77], 14,828 women [31.7%]), greater reductions in LVEF were associated with higher rates of all-cause mortality, with adjusted hazard ratios (95% CI) of 1.67 (1.57, 1.77) for LVEF Cumulative incidence of CV death Conclusions Quantitative LVEF assessed by 2DE is potent prognostically and was able to stratify the risk of both death and hospitalization outcomes in a wide range of clinical settings. Patients with reduced LVEF measured on inpatient or outpatient echocardiograms, and even in the context of non-cardiac admission, should be considered an at-risk group in whom quality of care metrics could be evaluated in future studies. Acknowledgement/Funding Canadian Institutes of Health Research, Heart and Stroke Foundation, and the Ted Rogers Centre for Heart Research

CARNAUBA (Coherent X-Ray Nanoprobe Beamline) is an X-ray beamline under construction for the SIRIUS light source at LNLS (Brazilian Synchrotron Light Laboratory). The aim of the beamline is to provide multi-analytical and coherent X-ray imaging techniques based on achromatic optics in the energy range between 2 and 15 keV. Computed tomography will extend these techniques into three dimensions. Two end-stations are under development: an all-invacuum nanoprobe (SAPOTI) and a sub-microprobe (TARUMA), with a more flexible sample environment and much larger working distance. TARUMA will cover a large variety of scientific areas, from environmental, geophysical, agricultural and biological research to energy and more condensed matter related areas. Its design characteristics, with its mechanical design heavily based on precision engineering concepts and predictive modeling, are presented here, as well as some prospects on in situ, in operando and cryogenic sample environment experiments.

Purpose. This study aimed to characterize 27 Escherichia coli isolates obtained from peritoneal dialysis (PD)-related peritonitis that occurred at the University Hospital of Botucatu Medical School, Brazil, between 1997 and 2015. Methodology. These isolates were characterized regarding the occurrence of 22 virulence factor-encoding genes, antimicrobial resistance and biofilm production. We then evaluated whether these factors influenced the clinical outcome. Results. Over an 18-year period, 726 episodes of PD-related peritonitis were diagnosed, with 27 of them (3.7 %) being due to E. coli . The majority of the isolates were classified in phylogroups B1 (33.3 %), B2 (30.0 %) or F (18.0 %). fimH (100.0 %), ompT (66.7 %) and irp2 (51.9 %) were the most prevalent genes, while papA, papC, iha, sat, irp2, iucD, ireA, ibe10, ompT and kpsMTII were significantly more prevalent among isolates belonging to phylogroups B2 and F (P E. coli were identified. Virulence factor-encoding genes (alone or in combination) and antimicrobial resistance were not associated with non-resolution outcomes. However, there was a trend for the ability to produce biofilm to be associated with treatment failure, although this association was not statistically significant. Conclusion. The E. coli isolates were heterogeneous in terms of the features investigated, and were susceptible to most of the antimicrobial drugs tested, despite the unsuccessful treatment observed in more than 50.0 % of the patients. Studies including more cases could help to clarify if biofilm production can influence the outcome in patients with PD-related peritonitis.

Background: Aberrant amyloid-β (Aβ) deposition in the brain occurs two decades prior to the manifestation of Alzheimer’s disease (AD) clinical symptoms and therefore brain Aβ load measured using PET serves as a gold standard biomarker for the early diagnosis of AD. However, the uneconomical nature of PET makes blood markers, that reflect brain Aβ deposition, attractive candidates for investigation as surrogate markers. Objective:Investigation of plasma Aβ as a surrogate marker for brain Aβ deposition in cognitively normal elderly individuals. Methods: Plasma Aβ40 and Aβ42 concentrations were measured using the ultrasensitive Single Molecule Array (Simoa) assay in 95 cognitively normal elderly individuals, who have all undergone PET to assess brain Aβ deposition. Based on the standard uptake value ratios (SUVR) obtained from PET imaging, using the tracer 18F-Florbetaben, plasma Aβ was compared between 32 participants assessed to have low brain Aβ load (Aβ–, SUVR

Parkinson’s Disease (PD) is the second mostcommon neurodegenerative disorder worldwide, causing bothmotor and non-motor symptoms. In the early stages, symptomsare mild and patients may ignore their existence. As a result,they do not undergo any related clinical examination; hence delaying their PD diagnosis. In an effort to remedy such delay,analysis of data passively captured from user’s interaction withconsumer technologies has been recently explored towardsremote screening of early PD motor signs. In the current study,a smartphone-based method analyzing subjects’ fingerinteraction with the smartphone screen is developed for thequantification of fine-motor skills decline in early PD usingConvolutional Neural Networks. Experimental results from theanalysis of keystroke typing in-the-clinic data from 18 early PDpatients and 15 healthy controls have shown a classification performance of 0.89 Area Under the Curve (AUC) with 0.79/0.79sensitivity/specificity, respectively. Evaluation of thegeneralization ability of the proposed approach was made by itsapplication on typing data arising from a separate self-reportedcohort of 27 PD patients’ and 84 healthy controls’ daily usagewith their personal smartphones (data in-the-wild), achieving0.79 AUC with 0.74/0.78 sensitivity/specificity, respectively. Theresults show the potentiality of the proposed approach to processkeystroke dynamics arising from users’ natural typing activityto detect PD, which contributes to the development of digitaltools for remote pathological symptom screening.

OBJECTIVES To study the main causes of pre-donation blood donors' deferral in a Brazilian blood bank. BACKGROUND Blood donor selection is the most important process to maintain transfusion safeness. Pre-donation deferral aims to avoid the transmission of infectious diseases in the serological window, as well as to preserve blood donors' health. METHODS This was a retrospective study undertaken in a single blood centre in Curitiba, Brazil, taking into account the number of blood donations per year, the number of annual donations by gender and the total number of blood donors deferred annually prior to blood donation from 1 January 2007 to 31 December 2016. RESULTS Pre-donation blood donors' deferral ranged from 12·1 to 15·7% of donors. The main reason was related to donors' health (22·5-51·4%) followed by behavioural risk (17·6-29%). Issues related to blood donors' health diminished, and those related to behavioural risk increased with time. Blood donors deferred because of anaemia diminished with time and were more common in women than men (P

Made available in DSpace on 2022-04-28T19:42:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-07-01 Introduction COVID-19 pandemic posed major challenges in obstetric health care services. Preparedness, development, and implementation of new protocols were part of the needed response. This study aims to describe the strategies implemented and the perspectives of health managers on the challenges to face the pandemic in 16 different maternity hospitals that comprise a multicenter study in Brazil, called REBRACO (Brazilian network of COVID-19 during pregnancy). Methods Mixed-method study, with quantitative and qualitative approaches. Quantitative data on the infrastructure of the units, maternal and perinatal health indicators, modifications on staff and human resources, from January to July/2020. Also, information on total number of cases, and availability for COVID-19 testing. A qualitative study by purposeful and saturation sampling was undertaken with healthcare managers, to understand perspectives on local challenges in facing the pandemic. Results Most maternities early implemented their contingency plan. REBRACO centers reported 338 confirmed COVID-19 cases among pregnant and post-partum women up to July 2020. There were 29 maternal deaths and 15 (51.8%) attributed to COVID-19. All maternities performed relocation of beds designated to labor ward, most (75%) acquired mechanical ventilators, only the minority (25%) installed new negative air pressure rooms. Considering human resources, around 40% hired extra health professionals and increased weekly workload and the majority (68.7%) also suspended annual leaves. Only one center implemented universal screening for childbirth and 6 (37.5%) implemented COVID-19 testing for all suspected cases, while around 60% of the centers only tested moderate/severe cases with hospital admission. Qualitative results showed that main challenges experienced were related to the fear of the virus, concerns about reliability of evidence and lack of resources, with a clear need for mental health support among health professionals. Conclusion Study findings suggest that maternities of the REBRACO initiative underwent major changes in facing the pandemic, with limitations on testing, difficulties in infrastructure and human resources. Leadership, continuous training, implementation of evidence-based protocols and collaborative initiatives are key to transpose the fear of the virus and ascertain adequate healthcare inside maternities, especially in low and middle-income settings. Policy makers need to address the specificities in considering reproductive health and childbirth during the COVID-19 pandemic and prioritize research and timely testing availability. Department of Obstetrics and Gynecology University of Campinas Faculdade de Medicina de Jundiaí HU/FMJ Hospital das Clínicas de Porto Alegre Maternidade UNIMED UNIMED/BH Universidade Federal do Ceará MEAC/UFC Universidade Federal de São Paulo UNIFESP/EPM Hospital Moinhos de Vento-HMV Hospital Regional Jorge Rossmann Instituto Sócrates Guanaes Universidade Federal de São Carlos/UFSCAR Hospital Estadual Sumaré HES Universidade Federal de Minas Gerais HC/UFMG Instituto Fernandes Figueira IFF/Fiocruz Faculdade de Medicina Universidade Estadual de São Paulo Universidade Federal de Pernambuco HC/UFPE Maternidade Climério de Oliveira MCO-UFBA Santa Casa de Misericórdia do Pará Faculdade de Medicina Universidade Estadual de São Paulo

Objetivo: Traçar o perfil de pacientes com neoplasia primária de laringe em hospitais de alta complexidade oncológica no Pará na série temporal 2000-2017. Método: Estudo epidemiológico, retrospectivo realizado com a base de dados secundários provenientes do Registro Hospitalar de Câncer (RHC). Resultados: o perfil de pacientes com neoplasia maligna da laringe em serviços de alta complexidade oncológica no estado do Pará são em sua maioria: sexo masculino, maior de 40 anos, histórico de etilismo e/ou tabagismo, branco ou pardo, ensino fundamental incompleto, diagnosticados nos estágios mais avançados. Conclusão: Dessa forma, percebe-se que esta neoplasia está fortemente alicerçada na interação dos fatores ambientais e endógenos. Sobretudo, o sistema de saúde, ainda é tênue para atender aos pacientes em risco ou com a neoplasia de laringe, a começar pelos índices altos de desconhecimento presente nas bases de dados secundários sobre indicadores em saúde, o que implica na tendência de certas variáveis importantes para a predição do câncer.

IntroductionIgA nephropathy (IgAN) is the most common primary glomerulopathy worldwide. According to the Oxford Classification, changes in the kidney vascular compartment are not related with worse outcomes. This paper aims to assess the impact of thrombotic microangiopathy (TMA) in the outcomes of Brazilian patients with IgAN.Materials and methodsAnalysis of clinical data and kidney biopsy findings from patients with IgAN to assess the impact of TMA on renal outcomes.ResultsThe majority of the 118 patients included were females (54.3%); mean age of 33 years (25;43); hypertension and hematuria were observed in 67.8% and 89.8%, respectively. Median creatinine: 1.45mg/dL; eGFR: 48.8ml/min/1.73m2; 24-hour proteinuria: 2.01g; low serum C3: 12.5%. Regarding to Oxford Classification: M1: 76.3%; E1: 35.6%; S1: 70.3%; T1/T2: 38.3%; C1/C2: 28.8%. Average follow-up: 65 months. Histologic evidence of TMA were detected in 21 (17.8%) patients and those ones presented more frequently hypertension (100% vs. 61%, p ConclusionsIn this study patients with TMA had worse clinical manifestations and outcomes. In terms of histologic evidence, E1 distinguished patients with TMA from other patients. Further studies are necessary to analyze the impact of vascular lesions on IgAN prognosis.

Background Schistosoma mansoni schistosomiasis (SM) remains a public health problem in Brazil. Renal involvement is classically manifested as a glomerulopathy, most often membranoproliferative glomerulonephritis or focal and segmental glomerulosclerosis. We report a case of collapsing glomerulopathy (CG) associated with SM and high-risk APOL1 genotype (HRG). Case report A 35-year-old male was admitted for hypertension and an eight-month history of lower-limb edema, foamy urine, and increased abdominal girth. He had a recent diagnosis of hepatosplenic SM, treated with praziquantel, without clinical improvement. Laboratory tests revealed serum creatinine 1.89mg/dL, blood urea nitrogen (BUN) 24mg/dL, albumin 1.9g/dL, cholesterol 531mg/dL, low-density lipoprotein 426mg/dL, platelets 115000/mm3, normal C3/C4, antinuclear antibody (ANA), rheumatoid factor (RF), and antineutrophil cytoplasmic antibodies (ANCA), negative serologies for hepatitis C virus (HCV) and human immunodeficiency virus (HIV), HBsAg negative and AntiHBc IgG positive, no hematuria or leukocyturia, 24 hour proteinuria 6.56g and negative serum and urinary immunofixation. Kidney biopsy established the diagnosis of CG. A treatment with prednisone was started without therapeutic response, progressing to end-stage kidney disease 19 months later. Molecular genetics investigation revealed an HRG. Conclusions This is the first report of CG associated with SM in the setting of an HRG. This case highlights the two-hit model as a mechanism for CG pathogenesis, where the high-risk APOL1 genotype exerts a susceptibility role and SM infection serves as a trigger to CG., Author summary Schistosomiasis mansoni is still a public health problem in Brazil and renal involvement is described. In such cases, a glomerulopathy is the typical manifestation, most often membranoproliferative glomerulonephritis. In the current article, we report a patient with a recent diagnosis of hepatosplenic SM who was admitted for nephrotic syndrome associated with reduced renal function and hypertension. Kidney biopsy established the diagnosis of collapsing glomerulopathy (CG) and molecular genetics investigation identified a high-risk APOL1 genotype (HRG). Of note, HRG has been associated with increased risk to develop CG, and a two-hit model has been proposed for the genesis of this glomerulopathy. According to this model, a HRG represents the increased-susceptibility component, while an infection or other environmental factors could act as triggers for the development of CG. Based on those data and model, our case raises SM infection as a new trigger for this severe form of glomerulopathy. This is the first description of a case of CG associated with SM in a patient with an HRG. This case corroborates the interactive role between genetic and environmental factors in the pathogenesis of CG but also identifies SM infection as an additional trigger for its development.

Targeting kinases linked to insulin resistance (IR) and inflammation may help in reducing the risk of type 2 diabetes (T2D) and Alzheimer&rsquo, s disease (AD) in its early stages. This study aimed to determine whether DHA-rich fish oil supplementation reduces glycogen synthase kinase (GSK-3), which is linked to both IR and AD. Baseline and post-intervention plasma samples from 58 adults with abdominal obesity (Age: 51.7 &plusmn, 1.7 years, BMI: 31.9 &plusmn, 0.8 kg/m2) were analysed for outcome measures. Participants were allocated to 2 g DHA-rich fish oil capsules (860 mg DHA + 120 mg EPA) (n = 31) or placebo capsules (n = 27) per day for 12 weeks. Compared to placebo, DHA-rich fish oil significantly reduced GSK-3&beta, by &minus, 2.3 &plusmn, 0.3 ng/mL. An inverse correlation (p &lt, 0.05) was found between baseline insulin and IR and their changes following intervention only in participants with C-reactive protein levels higher than 2.4 mg/L. DHA-rich fish oil reduces GSK-3 and IR, suggesting a potential role of long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) in ameliorating AD risk.

Thermally activated delayed fluorescence (TADF) has revamped the scientific and technological interest in metal-free organic fluorescent compounds in recent years. The application of TADF emitters in organic light-emitting diodes (OLEDs) resulted in highly energy-efficient devices that promise to replace metal-complex systems based on iridium(III) and platinum(II) in a near future.

Dietary supplementation with curcumin has been previously reported to have beneficial effects in people with insulin resistance, type 2 diabetes (T2D) and Alzheimer&rsquo, s disease (AD). This study investigated the effects of dietary supplementation with curcumin on key peptides implicated in insulin resistance in individuals with high risk of developing T2D. Plasma samples from participants recruited for a randomised controlled trial with curcumin (180 mg/day) for 12 weeks were analysed for circulating glycogen synthase kinase-3 &beta, (GSK-3&beta, ) and islet amyloid polypeptide (IAPP). Outcome measures were determined using ELISA kits. The homeostasis model for assessment of insulin resistance (HOMA-IR) was measured as parameters of glycaemic control. Curcumin supplementation significantly reduced circulating GSK-3&beta, (&minus, 2.4 &plusmn, 0.4 ng/mL vs. &minus, 0.3 &plusmn, 0.6, p = 0.0068) and IAPP (&minus, 2.0 &plusmn, 0.7 ng/mL vs. 0.4 &plusmn, 0.6, p = 0.0163) levels compared with the placebo group. Curcumin supplementation significantly reduced insulin resistance (&minus, 0.1 vs. 0.01 &plusmn, 0.05, p = 0.0142) compared with placebo group. Dietary supplementation with curcumin reduced circulating levels of IAPP and GSK-3&beta, thus suggesting a novel mechanism through which curcumin could potentially be used for alleviating insulin resistance related markers for reducing the risk of T2D and AD.

Introduction:. Nonunion is a challenging condition in orthopaedics as its etiology is not fully understood. Clinical interventions currently aim to stimulate both the biological and mechanical aspects of the bone healing process by using bone autografts and surgical fixation. However, recent observations showed that atrophic nonunion tissues contain putative osteoprogenitors, raising the hypothesis that its reactivation could be explored to achieve bone repair. Methods:. Here we characterized atrophic nonunion stromal cells (NUSC) in vitro, using bone marrow stromal cells (BMSC) and osteoblasts as controls cells of the osteoblastic lineage, and evaluated its ability to form bone in vivo. Results:. NUSC had proliferative and senescence rates comparable to BMSC and osteoblasts, and homogeneously expressed the osteolineage markers CD90 and CD73. Regarding CD105 and CD146 expression, NUSC were closely related to osteoblasts, both with an inferior percentage of CD105+/CD146+ cells as compared to BMSC. Despite this, NUSC differentiated along the osteogenic and adipogenic lineages in vitro; and when transplanted subcutaneously into immunocompromised mice, new bone formation and hematopoietic marrow were established. Conclusions:. This study demonstrates that NUSC are osteogenically competent, supporting the hypothesis that their endogenous reactivation could be a strategy to stimulate the bone formation while reducing the amount of bone autograft requirements.

Parkinson's Disease (PD) is a neurodegenerative disorder with early non-motor/motor symptoms that may evade clinical detection for years after the disease onset due to their mildness and slow progression. Digital health tools that process densely sampled data streams from the daily human-mobile interaction can objectify the monitoring of behavioral patterns that change due to the appearance of early PD-related signs. In this context, touchscreens can capture micro-movements of fingers during natural typing; an unsupervised activity of high frequency that can reveal insights for users' fine-motor handling and identify motor impairment. Subjects' typing dynamics related to their fine-motor skills decline, unobtrusively captured from a mobile touchscreen, were recently explored in-the-clinic assessment to classify early PD patients and controls. In this study, estimation of individual fine motor impairment severity scores is employed to interpret the footprint of specific underlying symptoms [such as brady-/hypokinesia (B/H-K) and rigidity (R)] to keystroke dynamics that cause group-wise variations. Regression models are employed for each fine-motor symptom, by exploiting features from keystroke dynamics sequences from in-the-clinic data captured from 18 early PD patients and 15 healthy controls. Results show that R and B/H-K UPDRS Part III single items scores can be predicted with an accuracy of 78 and 70%, respectively. The generalization power of these trained regressors derived from in-the-clinic data was further tested in a PD screening problem using data harvested in-the-wild for a longitudinal period of time (mean ± std : 7 ± 14 weeks) via a dedicated smartphone application for unobtrusive sensing of their routine smartphone typing. From a pool of 210 active users, data from 13 self-reported PD patients and 35 controls were selected based on demographics matching with the ones in-the-clinic setting. The results have shown that the estimated index achieve {0.84 (R), 0.80 (B/H−K)} ROC AUC, respectively, with {sensitivity/specificity : 0.77/0.8 (R), 0.92/0.63 (B/H−K)}, on classifying PD and controls in-the-wild setting. Apparently, the proposed approach constitutes a step forward to unobtrusive remote screening and detection of specific early PD signs from mobile-based human-computer interaction, introduces an interpretable methodology for the medical community and contributes to the continuous improvement of deployed tools and technologies in-the-wild.

In the current study, we aimed to evaluate the effects of a single dose of curcumin and/or fish oil on postprandial glycaemic parameters in healthy individuals. This was a randomised, placebo-controlled and crossover study. Sixteen (n = 16) volunteers were randomised to receive placebo, curcumin (180 mg) tablets, fish oil (1.2 g long chain omega-3 polyunsaturated fatty acids) capsules and curcumin + fish oil prior to a standard meal on 4 test days separated by a week. Blood glucose, serum insulin and triglycerides were measured at intervals between 0–120 min. Difference between the treatments was measured using two-way repeated measures analysis of variance and pair-wise comparisons using Wilcoxon signed-rank or paired t-test as appropriate. Postprandial glucose concentrations were significantly lower in the curcumin (60.6%, P = 0.0007) and curcumin + fishoil group (51%, P = 0.002) groups at 60 min from baseline. Compared with placebo, area under the curve (AUC) for change in blood glucose concentration was reduced by curcumin (36%, P = 0.003) and curcumin + fishoil (30%, 0.004), but not fish oil alone (p = 0.105). Both curcumin (P = 0.01) and curcumin + fishoil (P = 0.03) treatments significantly lowered postprandial insulin (AUC) by 26% in comparison with placebo. Curcumin, but not fish oil, reduces postprandial glycaemic response and insulin demand for glucose control.

Geometrical thinking is a life-long skill, yet, despite its importance, geometry teaching and learning is fraught with difficulties. Traditional pen and pencil approaches have failed to address them. In this vein, a conceptual instructional design (ID), namely GeoArt-ID, is proposed as a radically novel, holistic approach to develop geometrical thinking using art as a source for inspiring activity content for learning geometry. The dynamic design of GeoArt-ID is based upon a framework where the synergy of multiple knowledge, i.e., Technological, Didactical, Content (TDCK) knowledge is involved. GeoArt-ID is set within an affective (a-), blended (b-) and collaborative (c-) learning environment, introducing unique quantitative metrics to express the evolution of the learner's geometrical thinking. oese metrics could be derived from the analysis of a collection of a large amount of sensorial biosignals (big data) captured via unobtrusive smart sensors during sensorimotor learning activities. Data-to-knowledge representation, considering the domains of emotion, cognitive, body gesture and geometric tasks, could be achieved via advanced signal processing and machine/deep learning. Consequently, GeoArt-ID can exhibit high adaptability, scaffolding mentally disabled students to perform geometrical thinking and reasoning for all.