Miracle-dz/UniFAR-FTUs huggingface dataset:
Diabetes and Pancreatic Cancer—A Dangerous Liaison Relying on Carbonyl Stress

Simple Summary Diabetic people have an increased risk of developing several types of cancers, particularly pancreatic cancer. The higher availability of glucose and/or lipids that characterizes diabetes and obesity is responsible for the increased production of highly reactive carbonyl compounds, a condition referred to as “carbonyl stress”. Also known as glycotoxins and lipotoxins, these compounds react quickly and damage various molecules in cells forming final products termed AGEs (advanced glycation end-products). AGEs were shown to markedly accelerate tumor development in an experimental model of pancreatic cancer and AGE inhibition prevented the tumor-promoting effect of diabetes. In humans, carbonyl stress has been associated with the risk of pancreatic cancer and recognized as a possible contributor to other cancers, including breast and colorectal cancer. These findings suggest that carbonyl stress is involved in cancer development and growth and may be the mechanistic link between diabetes and pancreatic cancer, thus representing a potential drug target. Abstract Both type 2 (T2DM) and type 1 (T1DM) diabetes mellitus confer an increased risk of pancreatic cancer in humans. The magnitude and temporal trajectory of the risk conferred by the two forms of diabetes are similar, suggesting a common mechanism. Carbonyl stress is a hallmark of hyperglycemia and dyslipidemia, which accompanies T2DM, prediabetes, and obesity. Accumulating evidence demonstrates that diabetes promotes pancreatic ductal adenocarcinoma (PDAC) in experimental models of T2DM, a finding recently confirmed in a T1DM model. The carbonyl stress markers advanced glycation end-products (AGEs), the levels of which are increased in diabetes, were shown to markedly accelerate tumor development in a mouse model of Kras-driven PDAC. Consistently, inhibition of AGE formation by trapping their carbonyl precursors (i.e., reactive carbonyl species, RCS) prevented the PDAC-promoting effect of diabetes. Considering the growing attention on carbonyl stress in the onset and progression of several cancers, including breast, lung and colorectal cancer, this review discusses the mechanisms by which glucose and lipid imbalances induce a status of carbonyl stress, the oncogenic pathways activated by AGEs and their precursors RCS, and the potential use of carbonyl-scavenging agents and AGE inhibitors in PDAC prevention and treatment, particularly in high-risk diabetic individuals.
Tailoring Pyro- and Orthophosphate Species to Enhance Stem Cell Adhesion to Phosphate Glasses

Phosphate-based glasses (PBGs) offer significant therapeutic potential due to their bioactivity, controllable compositions, and degradation rates. Several PBGs have already demonstrated their ability to support direct cell growth and in vivo cytocompatibility for bone repair applications. This study investigated development of PBG formulations with pyro- and orthophosphate species within the glass system (40 − x)P2O5·(16 + x)CaO·20Na2O·24MgO (x = 0, 5, 10 mol%) and their effect on stem cell adhesion properties. Substitution of phosphate for calcium revealed a gradual transition within the glass structure from Q2 to Q0 phosphate species. Human mesenchymal stem cells were cultured directly onto discs made from three PBG compositions. Analysis of cells seeded onto the discs revealed that PBG with higher concentration of pyro- and orthophosphate content (61% Q1 and 39% Q0) supported a 4.3-fold increase in adhered cells compared to glasses with metaphosphate connectivity (49% Q2 and 51% Q1). This study highlights that tuning the composition of PBGs to possess pyro- and orthophosphate species only, enables the possibility to control cell adhesion performance. PBGs with superior cell adhesion profiles represent ideal candidates for biomedical applications, where cell recruitment and support for tissue ingrowth are of critical importance for orthopaedic interventions.
Tópicos Emergentes em Insuficiência Cardíaca: O Futuro na Insuficiência Cardíaca: Telemonitoramento, Wearables , Inteligência Artificial e Ensino na Era Pós-Pandemia

Aguinaldo F. Freitas Jr.,1 Fábio S. Silveira,2,3 Germano E. Conceição-Souza,4,5 Manoel F. Canesin,6,7 Pedro V. Schwartzmann,8,9 Sabrina Bernardez-Pereira,10 Reinaldo B. Bestetti11 Hospital das Clínicas da Universidade Federal de Goiás (HC-UFG),1 Goiânia, GO Brasil Fundação Beneficência Hospital de Cirurgia (FBHC-Ebserh),2 Aracaju, SE Brasil Centro de Pesquisa Clínica do Coração,3 Aracaju, SE Brasil Hospital Alemão Oswaldo Cruz,4 São Paulo, SP Brasil Hospital Regional de São José dos Campos,5 São José dos Campos, SP Brasil Hospital Universitário Universidade Estadual de Londrina (HU-UEL),6 Londrina, PR Brasil ACTIVE Metodologias Ativas de Ensino,7 São Paulo, SP Brasil Hospital Unimed Ribeirão Preto,8 Ribeirão Preto, SP Brasil Centro Avançado de Pesquisa, Ensino e Diagnóstico (Caped),9 Ribeirão Preto, SP Brasil Hospital de Coração (HCor),10 São Paulo, SP Brasil Departamento de Medicina, Universidade de Ribeirão Preto (Unaerp),11 Ribeirão Preto, SP – Brasil Carta científica referente ao Heart Failure Summit Brazil 2020 / Departamento de Insuficiência Cardíaca – DEIC/SBC
The Potential of Honeybee Products for Biomaterial Applications

The development of biomaterials required continuous improvements in their properties for new tissue engineering applications. Implants based on biocompatible materials and biomaterial-based dressings are susceptible to infection threat; moreover, target tissues can suffer injuring inflammation. The inclusion of nature-derived bioactive compounds usually offers a suitable strategy to expand or increase the functional properties of biomaterial scaffolds and can even promote tissue healing. Honey is traditionally known for its healing property and is a mixture of phytochemicals that have a proven reputation as antimicrobial, anti-inflammatory, and antioxidant agents. This review discusses on the potential of honey and other honeybee products for biomaterial improvements. Our study illustrates the available and most recent literature reporting the use of these natural products combined with different polymeric scaffolds, to provide original insights in wound healing and other tissue regenerative approaches.
Identification of Targets from LRRK2 Rescue Phenotypes

Parkinson’s disease (PD) is an age-dependent neurodegenerative condition. Leucine-rich repeat kinase 2 (LRRK2) mutations are the most frequent cause of sporadic and autosomal dominant PD. The exact role of LRRK2 protective variants (R1398H, N551K) together with a pathogenic mutant (G2019S) in aging and neurodegeneration is unknown. We generated the following myc-tagged UAS-LRRK2 transgenic Drosophila: LRRK2 (WT), N551K, R1398H, G2019S single allele, and double-mutants (N551K/G2019S or R1398H/G2019S). The protective variants alone were able to suppress the phenotypic effects caused by the pathogenic LRRK2 mutation. Next, we conducted RNA-sequencing using mRNA isolated from dopaminergic neurons of these different groups of transgenic Drosophila. Using pathway enrichment analysis, we identified the top 10 modules (p < 0.05), with “LRRK2 in neurons in Parkinson’s disease” among the candidates. Further dissection of this pathway identified the most significantly modulated gene nodes such as eEF1A2, ACTB, eEF1A, and actin cytoskeleton reorganization. The induction of the pathway was successfully restored by the R1398H protective variant and R1398H-G2019S or N551K-G2019S rescue experiments. The oxidoreductase family of genes was also active in the pathogenic mutant and restored in protective and rescue variants. In summary, we provide in vivo evidence supporting the neuroprotective effects of LRRK2 variants. RNA sequencing of dopaminergic neurons identified upregulation of specific gene pathways in the Drosophila carrying the pathogenic variant, and this was restored in the rescue phenotypes. Using protective gene variants, our study identifies potential new targets and provides proof of principle of a new therapeutic approach that will further our understanding of aging and neurodegeneration in PD.
Characterization and distribution of viridans group streptococci isolated from infectious endophthalmitis and keratitis.

PURPOSE The aims of this study were to characterize alpha-hemolytic streptococci among isolates from cases of infectious endophthalmitis and keratitis and to determine their distributions. METHODS The sample included 27 and 35 nonduplicated isolates of alpha-hemolytic streptococci recovered from patients with infectious endophthalmitis (2002-2013) and keratitis (2008-2013), respectively. Isolates were identified by the optochin susceptibility and bile solubility tests, using a biochemical identification system. The minimum inhibitory concentration was determined by the broth microdilution method. Molecular identification was performed by analyses of three constitutive genes and the complementary multilocus sequence. The molecular epidemiology of Streptococcus pneumoniae was investigated using multilocus sequence typing, and the presence of the capsular polysaccharide-encoding gene was assessed using conventional polymerase chain reaction. Outcomes were evaluated using the patients' medical records. RESULTS Phenotypic tests differentiated S. pneumoniae from other alpha-hemolytic streptococci, consistent with later molecular identifications. Streptococcus oralis was significantly prevalent among the endophthalmitis isolates, as was S. pneumoniae in the keratitis isolates. High levels of susceptibility to antibiotics were observed, including vancomycin, cephalosporins, and fluoroquinolones. High genetic variability was detected among the 19 S. pneumoniae strains, with 15 predicted to be encapsulated. The medical records of patients with infectious endophthalmitis were reviewed (n=15/27; 56%), and final visual acuity was assessed in 12 cases (44%). Many patients progressed to a final visual acuity state of "no light perception" (6/12; 50%), "light perception" (3/12; 25%), or "hand motion" (1/12; 8%). The medical records of patients with infectious keratitis were also reviewed (n=24/35; 69%), and final visual acuity was assessed in 18 cases (51%). Similarly, most patients progressed to a final visual acuity state of "no light perception" (6/18; 33%), "light perception" (1/18; 6%), or "hand motion" (6/18; 33%). Overall, the majority of patients progressed to a final visual acuity state of "no light perception" (12/30), "light perception" (4/30), or "hand motion" (7/30). CONCLUSIONS The distribution of alpha-hemolytic streptococci in ocular infections suggested the presence of a species-specific tissue tropism. The prognoses of patients with ocular streptococcal infections were highly unfavorable, and antibiotic resistance did not contribute to the unfavorable clinical progressions and poor outcomes.
Electrochemical Biosensors for Detection of Biological Warfare Agents

This review discusses current development in electrochemical biosensors for detection of biological warfare agents. This could include bacteria, viruses and toxins that are aerosoled deliberately in air, food or water to spread terrorism and cause disease or death to humans, animals or plants. The rapid and unequivocal detection and identification of biological warfare agents is a major challenge for any government including military, health and other government agents. Reliable, specific characterization and identification of the microorganism from sampling location, either air, water, soil or others is required. This review will survey different types of electrochemical biosensors has been developed based on the following: i) Immunosensors ii) PCR (DNA base Sensor) iii) Bacteria or whole cell sensor and iv) Enzyme sensor. This article gives an overview of electrochemical biosensor for detection of biological warfare agents. Electrochemical biosensors have the advantages of sensitivity, selectivity, to operate in turbid media, and amenable to miniaturization. Recent developments in immunofiltration, flow injection, and flow-through electrochemical biosensors for bacteria, viruses, and toxin detection are reviewed. The current research and development in biosensors for biological warfare agents detection is of interest to the public as well as to the defense is also discussed.
Effectiveness of very low profile thrombectomy device in primary distal medium vessel occlusion, as rescue therapy after incomplete proximal recanalization or following iatrogenic thromboembolic events

Background Recent progress with smaller retrievers has expanded the ability to reach distal brain arteries. We herein report recanalization, bleeding complications and short-term clinical outcomes with the smallest currently known low profile thrombectomy device in patients with primary or secondary distal medium vessel occlusion (DMVO). Methods We performed a retrospective analysis of 115 patients receiving mechanical thrombectomy (MT) in DMVO using the extended Thrombolysis in Cerebral Infarction (eTICI), European Cooperative Acute Stroke Study (ECASS) II classification, The National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores at admission and discharge to evaluate outcomes. Patients were stratified into three groups: (1) primary isolated distal occlusion (n=34), (2) secondary distal occlusion after MT of a proximal vessel occlusion (n=71), or (3) during endovascular treatment of aneurysms or arteriovenous malformations (AVMs) (n=10). Results Successful distal recanalization, defined as an eTICI score of 2b67, 2c and 3, was achieved in 74.7% (86/115) of patients. More specifically, it was 70.5% (24/34), 73.2% (52/71), and 100% (10/10) of primary DMVO, secondary DMVO after proximal MT, and rescue MT during aneurysm or AVM embolization, respectively. Symptomatic intraparenchymal bleeding occurred in 6.9% (eight patients). In-hospital mortality occurred in 18.1% (19/105) of patients with stroke. The most common cause of death was large infarct, old age, and therapy limitation. Conclusion Direct or rescue MT of DMVO using a very low profile thrombectomy device is associated with a high rate of successful recanalization and a reasonable rate of symptomatic hemorrhagic complication, despite a risk of 18.1% hospital mortality in elderly patients. Further trials are needed to confirm our results and assess long-term clinical outcomes.
Effectiveness of a Novel HIV Self-Testing Service with Online Real-Time Counseling Support (HIVST-Online) in Increasing HIV Testing Rate and Repeated HIV Testing among Men Who Have Sex with Men in Hong Kong: Results of a Pilot Implementation Project

HIV self-testing (HIVST) with online real-time counseling (HIVST-online) is an evidence-based intervention to increase HIV testing coverage and to ensure linkage to care for men who have sex with men (MSM). A community-based organization (CBO) recruited 122 MSM who had ever used HIVST-online (ever-users) and another 228 new-users from multiple sources and promoted HIVST-online. A free oral fluid-based HIVST kit was sent to all the participants by mail. Experienced HIVST administrators implemented HIVST-online by providing real-time instruction, standard-of-care pre-test and post-test counseling via live-chat application. The number of HIVST-online sessions performed was documented by the administrators. The post-test evaluation was conducted 6 months after the pre-test survey. At month 6, 63.1% of ever-users and 40.4% of new-users received HIVST-online. Taking other types of HIV testing into account, 79.4% of ever-users and 58.6% of new-users being followed up at month 6 received any HIV testing during the project period. Ever-users were more likely to receive HIVST-online and any HIV testing as compared to new-users. Four HIVST-online users were screened to be HIV positive and linked to the treatment. The process evaluation of HIVST-online was positive. Implementation of HIVST-online was helpful to improve HIV testing coverage and repeated HIV testing among Chinese MSM. A larger scale implementation should be considered.
Functional Evaluation of a Rare Variant c.516G>C (p.Trp172Cys) in the GJB2 (Connexin 26) Gene Associated with Nonsyndromic Hearing Loss

Mutations in the GJB2 gene encoding transmembrane protein connexin 26 (Cx26) are the most common cause for hearing loss worldwide. Cx26 plays a crucial role in the ionic and metabolic homeostasis in the inner ear, indispensable for normal hearing process. Different pathogenic mutations in the GJB2 gene can affect all stages of the Cx26 life cycle and result in nonsyndromic autosomal recessive (DFNB1) or dominant (DFNA3) deafness and syndromes associating hearing loss with skin disorders. This study aims to elucidate the functional consequences of a rare GJB2 variant c.516G>C (p.Trp172Cys) found with high frequency in deaf patients from indigenous populations of Southern Siberia (Russia). The substitution c.516G>C leads to the replacement of tryptophan at a conserved amino acid position 172 with cysteine (p.Trp172Cys) in the second extracellular loop of Cx26 protein. We analyzed the subcellular localization of mutant Cx26-p.Trp172Cys protein by immunocytochemistry and the hemichannels permeability by dye loading assay. The GJB2 knockout HeLa cell line has been generated using CRISPR/Cas9 genome editing tool. Subsequently, the HeLa transgenic cell lines stably expressing different GJB2 variants (wild type and mutations associated with hearing loss) were established based on knockout cells and used for comparative functional analysis. The impaired trafficking of mutant Cx26-p.Trp172Cys protein to the plasma membrane and reduced hemichannels permeability support the pathogenic effect of the c.516G>C (p.Trp172Cys) variant and its association with nonsyndromic hearing loss. Our data contribute to a better understanding of the role of mutations in the second extracellular loop of Cx26 protein in pathogenesis of deafness.
Impact of a behaviourally focused nutrition education intervention on attitudes and practices related to eating habits and activity levels in Indian adolescents

Abstract Objective: To evaluate the effectiveness of a behaviourally focused nutrition education (NE) intervention based on the Health Belief Model (HBM) to improve knowledge, attitudes and practices (KAP) related to eating habits and activity levels in 10–12-year-old adolescents in Mumbai, India. Design: School-based cluster randomised controlled trial. The experimental group (EG) received weekly NE and three parent sessions over 12 weeks; no sessions were conducted for the control group (CG). The theoretical framework of HBM and focus group discussion results guided the development of behaviour change communication strategies and NE aids. KAP were measured using a validated survey instrument, administered at baseline and endline in EG and CG. Paired and independent t tests determined within-group and between-group changes in pre–post scores. Setting: Two aided and two private schools that were randomly allocated to either an EG or CG. Participants: Adolescent boys and girls (n 498; EG n 292 and CG n 206). Results: EG reported improvements in mean knowledge (39·3%), attitude (7·3 %), diet (9·6 %) and activity practice (9·4%) scores from pre to post intervention. No significant changes were observed in CG. Significant improvements in scores associated with perceived benefits, barriers and self-efficacy, breakfast and vegetable consumption, and moderate-to-vigorous activities were observed in EG. Conclusions: Integrating NE into the academic curriculum and adopting evidence-based lessons that entail targeted information delivery and participatory activities can improve knowledge, foster right attitudes and facilitate better eating and activity-related practices in Indian adolescents.
Clinical Implications of Uric Acid in Heart Failure: A Comprehensive Review

Affecting more than 26 million people worldwide and with rising prevalence, heart failure (HF) represents a major global health problem. Hence, further research is needed in order to abate poor HF outcomes and mitigate significant expenses that burden health care systems. Based on available data, experts agree that there is an urgent need for a cost-effective prognostic biomarker in HF. Although a significant number of biomarkers have already been investigated in this setting, the clinical utility of adding biomarker evaluation to routine HF care still remains ambiguous. Specifically, in this review we focused on uric acid (UA), a purine metabolism detriment whose role as cardiovascular risk factor has been exhaustingly debated for decades. Multiple large population studies indicate that UA is an independent predictor of mortality in acute and chronic HF, making it a significant prognostic factor in both settings. High serum levels have been also associated with an increased incidence of HF, thus expanding the clinical utility of UA. Importantly, emerging data suggests that UA is also implicated in the pathogenesis of HF, which sheds light on UA as a feasible therapeutic target. Although to date clinical studies have not been able to prove the benefits of xanthine oxidase in HF patients, we discuss the putative role of UA and xanthine oxidase in the pathophysiology of HF as a therapeutic target.
Parallel Synaptic Acetylcholine Signals Facilitate Large Monopolar Cell Repolarization and Modulate Visual Behavior in Drosophila

Appropriate termination of the photoresponse in image-forming photoreceptors and downstream neurons is critical for an animal to achieve high temporal resolution. Although the cellular and molecular mechanisms of termination in image-forming photoreceptors have been extensively studied in Drosophila, the underlying mechanism of termination in their downstream large monopolar cells remains less explored. Here, we show that synaptic ACh signaling, from both amacrine cells (ACs) and L4 neurons, facilitates the rapid repolarization of L1 and L2 neurons. Intracellular recordings in female flies show that blocking synaptic ACh output from either ACs or L4 neurons leads to slow repolarization of L1 and L2 neurons. Genetic and electrophysiological studies in both male and female flies determine that L2 neurons express ACh receptors and directly receive ACh signaling. Moreover, our results demonstrate that synaptic ACh signaling from both ACs and L4 neurons simultaneously facilitates ERG termination. Finally, visual behavior studies in both male and female flies show that synaptic ACh signaling, from either ACs or L4 neurons to L2 neurons, is essential for the optomotor response of the flies in high-frequency light stimulation. Our study identifies parallel synaptic ACh signaling for repolarization of L1 and L2 neurons and demonstrates that synaptic ACh signaling facilitates L1 and L2 neuron repolarization to maintain the optomotor response of the fly on high-frequency light stimulation. SIGNIFICANCE STATEMENT The image-forming photoreceptor downstream neurons receive multiple synaptic inputs from image-forming photoreceptors and various types of interneurons. It remains largely unknown how these synaptic inputs modulate the neural activity and function of image-forming photoreceptor downstream neurons. We show that parallel synaptic ACh signaling from both amacrine cells and L4 neurons facilitates rapid repolarization of large monopolar cells in Drosophila and maintains the optomotor response of the fly on high-frequency light stimulation. This work is one of the first reports showing how parallel synaptic signaling modulates the activity of large monopolar cells and motion vision simultaneously.