Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans.

Spinal cord injury results in the loss of sensory, motor, and autonomic functions, which almost always produces permanent physical disability. Thus, in the search for more effective treatments than those already applied for years, which are not entirely efficient, researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach, seeking to promote neuronal recovery after spinal cord injury. Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and, consequently, boosting functional recovery. Although the majority of experimental research has been conducted in rodents, there is increasing recognition of the importance, and need, of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans. This article is a literature review from databases (PubMed, Science Direct, Elsevier, Scielo, Redalyc, Cochrane, and NCBI) from 10 years ago to date, using keywords (spinal cord injury, cell therapy, non-human primates, humans, and bioengineering in spinal cord injury). From 110 retrieved articles, after two selection rounds based on inclusion and exclusion criteria, 21 articles were analyzed. Thus, this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans, aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

Predicted vitamin D levels and risk of depression in the SUN Project: A prospective cohort study.

The current study aimed to investigate the association between predicted vitamin D status and depression in a prospective Spanish cohort of university graduates. The SUN Project is a dynamic cohort study designed to investigate multiple aspects of health and lifestyle. Participants were asked to complete a comprehensive questionnaire consisting of 556 items, that included a validated food-frequency questionnaire. Participants initially free of depression were classified as incident cases if they reported a medical diagnosis of depression during follow-up. Serum vitamin D levels were predicted by a previously validated equation. Vitamin D deficiency was defined as vitamin D levels below 20 ng/mL. Cox models were used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (95% CI). We included 15,175 Spanish university graduates [mean (SD) age: 36.9 year (11.5)] followed-up for a median of 12.7 years. Among 192,976 person-years of follow-up, we identified 753 incident cases of depression. Participants with vitamin D deficiency had a 27% higher risk of depression as compared to those with vitamin D sufficiency (HR: 1.27, 95% CI: 1.09-1.48; p = 0.002) after adjusting for potential confounders. Furthermore, a significant effect modification by female sex was observed with higher depression risks associated with vitamin D deficiency in women than in men (p for interaction = 0.034). In educated middle-aged Spanish adults, we observed a direct association between vitamin D deficiency and the risk of depression, that was stronger among women.

Gliosarcoma associated with bilateral hippocampal sclerosis in a cat presenting complex partial seizures with orofacial involvement: A case report.

Key Clinical Message: Gliosarcoma, a rare cerebral neoplasm, has not been linked to hippocampal changes in cats. We report a case of complex partial seizures with orofacial involvement, revealing gliosarcoma concurrent with bilateral hippocampal sclerosis. Abstract: A 16-year-old neutered female domestic shorthair cat presented with acute inappetence, ataxia, disorientation, and vacant staring. Brain MRI revealed an ill-defined, round, intra-axial mass in the right piriform lobe, showing hyperintensity on T2W, T2-FLAIR, and T2*W, and hypointensity on T1W images. The lesion exhibited mass effect and contrast enhancement in its center. Bilateral hyperintensity on T2-FLAIR images and contrast enhancement were observed in the hippocampus. Brain histologic and immunohistochemical analysis revealed cerebral gliosarcoma with concurrent hippocampal sclerosis. Feline LGI1-antibody testing on the serum and/or CSF was not performed due to insufficient biomaterial. Although retrospective testing on brain tissue was considered, it ultimately proved unfeasible, preventing us from ruling out antibody-associated limbic encephalitis. In conclusion, cerebral gliosarcoma should be included in feline intracranial tumor differentials, warranting brain MRI and feline LGI1-antibody testing in cats showing complex partial seizures with orofacial involvement. In our case, the prognosis remained poor due to the presence of a high-grade glioma.

Phytate Effects on Incomplete Distal Renal Tubular Acidosis.

Background: Adults who have incomplete distal renal tubular acidosis (dRTA) may present with recurrent urolithiasis due to metabolic acidosis, leading to bone resorption, which in turn causes hypercalciuria and urine alkalinization (pH > 6.0). Oral potassium citrate is the most commonly used treatment for dRTA, but some patients cannot tolerate this treatment. The objective of this single-arm study was to evaluate the effect of phytate, an inhibitor of bone resorption, on calciuria of patients with incomplete dRTA. Methods: The calciuria levels of 16 patients who had incomplete dRTA with urolithiasis and could not tolerate potassium citrate treatment were recorded before (baseline) and after 6 months of treatment with oral calcium magnesium phytate (380 mg every 12 h). There were no dietary modifications or other treatments. Results: The baseline calciuria was 317 ± 81 mg/24 h and the level after 6 months was 221 ± 38 mg/24 h (p < 0.005). Conclusions: Our results suggest that calcium magnesium phytate should be considered as an alternative or adjunctive treatment for hypercalciuria in patients with incomplete dRTA.

Characterization model of the post COVID-19 condition based on immunological, biochemical, and cytokine markers.

Post-coronavirus disease condition (PCC) continues to affect many people globally, yet there remains a lack of diagnostic biomarkers to distinguish PCC from those recovered from acute COVID-19. This study compared biomarkers between two age- and gender-matched groups: PCC individuals and those recovered within three months of acute COVID-19 in 2020 (n = 85 each). Biomarkers were assessed 12-24 months after initial diagnosis, examining biochemical profiles, blood cell counts, coagulation status, antibody serology, lymphocyte populations, and cytokine levels. PCC individuals exhibited significant alterations in 49 of 167 markers, including K+ levels, αGAD antibodies, antithrombin III, insulin-like growth factor-binding protein 3 (IGFBP3), and interleukin-10 (IL-10). A panel of αGAD, IL-10, potassium levels, and CD16brightCD56- cell presence distinguished PCC individuals from recovered patients with >88% accuracy and <92% precision.

Safety and efficacy of electric cardioversion in the emergency department: analysis of associated factors according to gender. / Eficacia y seguridad de la cardioversión eléctrica en urgencias: factores asociados y perspectiva de sexo.

OBJECTIVE: To explore the safety and effectiveness of electric cardioversion to treat atrial fibrillation in a hospital emergency department (ED). METHODS: Retrospective observational study in a hospital ED. We reviewed episodes of atrial fibrillation in patients aged 18 years orolder treated with cardioversion in our ED or referred for scheduling of cardioversion. Clinical outcome measures were conversion to sinus rhythm, immediate adverse effects (hypotension, arrythmia, or bronchial aspiration), revisiting within 90 days for atrial fibrillation, and complications (stroke, major bleeding, heart failure, or death). We studied factors associated with recurrence and adverse effects according to sex. RESULTS: Cardioversion was used in 365 episodes (median patient age, 67 years); 38.6% were women. Cardioversion was applied in the ED in 75.1% of the episodes, and 24.9% were referred for scheduled cardioversion. Sinus rhythm was restored in 90.7% of the episodes. Emergency cardioversion was more effective than a scheduled procedure (odds ratio [OR], 4.258; 95% CI, 2.046-8.859; P < .001). No serious immediate adverse effects were reported, but 16.7% of the patients revisited for atrial fibrillation within 90 days. Factors associated with revisits were heart failure (hazard ratio [HR], 2.603; 95% CI, 1.298-5.222; P = .007), sleep apnea (HR, 2.598; 95% CI, 1.163-5.803; P = .020), and, in women, hypertension (HR, 3.706; 95% CI, 1.051-13.068; P = .042). Eleven patients developed late adverse events, including stroke (n = 2), major bleeding (n = 1), heart failure (n = 5), and death (n = 3). CONCLUSIONS: Cardioversion is a useful, effective, and safe treatment for atrial fibrillation in the ED, although there are frequent recurrences. Factors associated with recurrence differ according to sex.

OBJETIVO: Conocer la seguridad y eficacia de la cardioversión eléctrica (CVE) en la fibrilación auricular (FA) en un servicio de urgencias hospitalario (SUH). METODO: Estudio observacional y retrospectivo realizado en un SUH. Se revisaron los episodios de FA en pacientes con edad igual o mayor a 18 años a los que se les realizó CVE en el SUH o se les programó de forma diferida. Las variables resultado fueron: reversión a ritmo sinusal (RS), efectos adversos inmediatos (hipotensión, arritmia y broncoaspiración), reconsulta a 90 días por FA y desarrollo de complicaciones (ictus, hemorragia mayor, insuficiencia cardiaca y mortalidad). Se estudiaron los factores asociados a recurrencia y efectos adversos, y se analizaron las diferencias por sexo. RESULTADOS: Se incluyeron 365 episodios de CVE (67 años; 38,6% mujeres); el 75,1% se realizó en el SUH y el 24,9% se derivaron para CVE diferida. El 90,7% revirtieron a RS. La CVE urgente fue más efectiva que la diferida (OR 4,258; IC 95% 2,046-8,859; p < 0,001). No hubo efectos adversos inmediatos graves. El 16,7% de pacientes reconsultaron por FA en los 90 días posteriores. Los factores asociados a reconsulta fueron insuficiencia cardiaca (HR 2,603; IC 95% 1,298-5,222; p = 0,007), apnea del sueño (HR 2,598; IC 95% 1,163-5,803; p = 0,020) y, en mujeres, hipertensión arterial (HR 3,706;IC 95% 1,051-13,068; p = 0,042). Tras la CVE, 11 pacientes presentaron eventos adversos tardíos que incluyeron ictus (n = 2), hemorragia mayor (n = 1), insuficiencia cardiaca (n = 5) y muerte (n = 3). CONCLUSIONES: La CVE es útil, eficaz y segura para la FA en los SUH, aunque las recurrencias son frecuentes. Los factores asociados a recurrencia difieren entre sexos.

Twin study identifies early immunological and metabolic dysregulation of CD8+ T cells in multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory neurological disease of the central nervous system with a subclinical phase preceding frank neuroinflammation. CD8+ T cells are abundant within MS lesions, but their potential role in disease pathology remains unclear. Using high-throughput single-cell RNA sequencing and single-cell T cell receptor analysis, we compared CD8+ T cell clones from the blood and cerebrospinal fluid (CSF) of monozygotic twin pairs in which the cotwin had either no or subclinical neuroinflammation (SCNI). We identified peripheral MS-associated immunological and metabolic alterations indicative of an enhanced migratory, proinflammatory, and activated CD8+ T cell phenotype, which was also evident in cotwins with SCNI and in an independent validation cohort of people with MS. Together, our in-depth single-cell analysis indicates a disease-driving proinflammatory role of infiltrating CD8+ T cells and identifies potential immunological and metabolic therapeutic targets in both prodromal and definitive stages of the disease.

Circular recycling concept for silver recovery from photovoltaic cells in Ethaline deep eutectic solvent.

Reducing the number of stages, energy costs and carbon footprint of recycling processes is essential to overcome environmental challenges. The interest in replacing the acids used in traditional hydrometallurgical methods with deep eutectic solvents (DES), which are less toxic and more environmentally friendly, has been growing. The aim of this study is to estimate the potential use of this class of solvents in an ionometallurgical process of leaching and electrodeposition to recover silver as part of the recycling of solar panels, a major challenge of the years to come. In the present work, a circular recycling concept based on an iron redox shuttle was studied to leach and recover silver via electrodeposition. Different DESs were evaluated in combination with a hexahydrated iron(iii) chloride oxidizing agent. Ethaline DES has gained significant interest as it can attain a high silver leaching efficiency of 99.9% on crystallized silicon cell scraps at 75 °C. The promising results led to a comprehensive study of limits of this chemical system, focusing on the relation between the concentration of species (iron and water), the interfacial potential of silver (electrochemical measurements), and surface evolution (X-ray photoelectron spectroscopy analysis). Silver leaching was determined as a mixed control mechanism involving chemical and species diffusion dependence. The concentration of iron(iii) chloride appeared crucial, determining the kinetic of formation of a poorly soluble AgCl layer. Electrodeposition from leachate highlighted the need to use an oxygen-free atmosphere to produce high-quality silver. Finally, leaching at 75 °C and electrodeposition at 50 °C of silver from crystallized silicon cell scraps were demonstrated using Ethaline (1 : 2) + FeCl3·6H2O (0.12 mol L-1) under an argon atmosphere.

Allosteric modulation of the CXCR4:CXCL12 axis by targeting receptor nanoclustering via the TMV-TMVI domain.

CXCR4 is a ubiquitously expressed chemokine receptor that regulates leukocyte trafficking and arrest in both homeostatic and pathological states. It also participates in organogenesis, HIV-1 infection, and tumor development. Despite the potential therapeutic benefit of CXCR4 antagonists, only one, plerixafor (AMD3100), which blocks the ligand-binding site, has reached the clinic. Recent advances in imaging and biophysical techniques have provided a richer understanding of the membrane organization and dynamics of this receptor. Activation of CXCR4 by CXCL12 reduces the number of CXCR4 monomers/dimers at the cell membrane and increases the formation of large nanoclusters, which are largely immobile and are required for correct cell orientation to chemoattractant gradients. Mechanistically, CXCR4 activation involves a structural motif defined by residues in TMV and TMVI. Using this structural motif as a template, we performed in silico molecular modeling followed by in vitro screening of a small compound library to identify negative allosteric modulators of CXCR4 that do not affect CXCL12 binding. We identified AGR1.137, a small molecule that abolishes CXCL12-mediated receptor nanoclustering and dynamics and blocks the ability of cells to sense CXCL12 gradients both in vitro and in vivo while preserving ligand binding and receptor internalization.

Chemical Reactivity Parameters to Analyze Psychedelics: How Do We Explain the Potency of the Drugs?

Psychedelics are psychoactive substances that produce changes in thoughts and feelings and modifications in perceptions of reality. The most potent psychedelic is also the first semisynthetic hallucinogen (lysergic acid diethylamide). Psychedelics have been investigated for decades because of their potential therapeutic effects in the treatment of neuropsychiatric diseases and also because these drugs are useful in controlling addictions to other substances. In this investigation, we analyze 27 psychedelic molecules. These compounds are serotonergic psychedelics; that is, they are serotonin agonists. We analyze the electron transfer properties to better understand the mechanism of action of these substances. We found that the electron acceptance capacity is related to the potency of the drugs: the best electron acceptor is also the most potent drug. We also used global softness as a parameter of reactivity. Molecules with greater global softness are more polarizable and also have greater potency. These results are useful to continue our understanding of the mechanism of action of psychotropic drugs.

Genetic Variants in RANK and OPG Could Influence Disease Severity and Bone Remodeling in Patients with Early Arthritis.

The aim of this study was to identify single-nucleotide polymorphisms (SNPs) in bone remodeling-related genes associated with disease severity and bone mineral density (BMD) in early arthritis (EA) patients. For this purpose, the genotyping of 552 SNPs located in gene regions of semaphorins 4b, 4d, 4f, DKK1, 2 and 3, sclerostin, OPG, RANK and RANKL was performed using Immunochip from Illumina Inc. in 268 patients from the Princesa Early Arthritis Register Longitudinal (PEARL) study. Measurements of BMD and disease activity were chosen as outcome variables to select SNPs of interest. The relationships of SNPs with the BMD of the forearm, lumbar spine and hip (Hologic-4500 QDR) were analyzed by linear regression adjusted for age, sex, body mass index and presence of anti-citrullinated peptide antibodies (ACPAs). The association of each SNP with activity variables was analyzed by linear regression, logistic regression or ordered logistic regression according to the variable, and multivariate models were adjusted for potentially confounding variables, such as age, sex and presence of ACPAs. These analyses showed that four SNPs located in the genes coding for RANK (TNFRSF11A) and OPG (TNFRSF11B) were significantly associated with clinical variables of severity. SNP rs1805034 located in exon 6 of TNFRSF11A, which causes a non-synonymous (A/V) mutation, showed significant association with BMD and therefore may be considered as a possible biomarker of severity in RA patients. SNPs in the OPG gene showed an association with serum OPG levels and predicted disease activity after two years of follow-up.

Chronic Pain Management Approaches among Spanish Physiotherapists: Influences, Practices, Barriers, and Challenges.

This study evaluated Spanish physiotherapists' orientations toward biopsychosocial and biomedical approaches in chronic pain management through a cross-sectional survey of 447 registered professionals. Validated questionnaires assessed knowledge, attitudes, and beliefs. Multivariate analysis of covariance (MANCOVA) identified influential factors and ordinal regression determined the frequency of biopsychosocial application. Content analysis of open-ended responses explored barriers to biopsychosocial implementation. Over 50% of physiotherapists favored the biopsychosocial model, influenced by interdisciplinary work settings, advanced pain knowledge, and specific training. Comprehensive pain knowledge significantly impacted both biomedical and biopsychosocial orientations inversely. The biomedical approach was more prevalent among those with lower education levels and less pain knowledge, particularly at the beginning or over 20 years into their careers. Despite the theoretical preference for biopsychosocial among Spanish physiotherapists, practical application was infrequent, with only 9.8% always using it and 40.7% frequently. Self-reported confidence and skills were crucial determinants of biopsychosocial implementation frequency. Significant barriers included inadequate psychological skills (63.6%), coordination challenges (47.6%), time constraints (43.6%), patient misconceptions (34.2%), and systemic issues. These findings align with international research, highlighting the need to bridge the gap between theoretical knowledge and clinical practice. Addressing these challenges through targeted training and systemic reforms is crucial for improving chronic pain management globally.

Modeling and Analyzing the Availability of Technical Professional Profiles for the Success of Smart Cities Projects in Europe.

The success of developing and implementing Smart Cities (SC) projects depends on a varied set of factors, where the availability of a qualified technical workforce is a critical one. The combination of ICT requirements, like the effectiveness and quality of solutions merging IoT, cloud computing, sensors, and communications with the work from many varied disciplines (e.g., civil engineering, architecture, etc.), mixed with aspects of environmental and business sustainability, makes the management of these projects really challenging. Reports forecast a scarcity of qualified candidates, given this complexity and the growth of activity in SC projects. The European project SMACITE has addressed the requirements of the qualification of an ICT workforce with an analysis of multiples sources of information from the labor market, feedback from involved stakeholders, and the literature. The goal was the development of two occupational ICT profiles as a reference for training and for the availability of candidates for job vacancies. The result is two ICT role profiles for engineers and technicians, mapped with the European skills frameworks ESCO and EN16234. The profiles determined the whole set of requirements, including not only the technical areas and soft skills, but also additional technical areas and sustainability and managerial skills and the analysis of different sources of information. Our work has also determined which existing ESCO occupations are similar to the two reference profiles, so they are better adapted to SC projects. The training activities of SMACITE have also suggested the amount of training expected for a varied sample of candidates who want to be qualified for SC projects.

Discovery of Thiophene Derivatives as Potent, Orally Bioavailable, and Blood-Brain Barrier-Permeable Ebola Virus Entry Inhibitors.

The endemic nature of the Ebola virus disease in Africa underscores the need for prophylactic and therapeutic drugs that are affordable and easy to administer. Through a phenotypic screening employing viral pseudotypes and our in-house chemical library, we identified a promising hit featuring a thiophene scaffold, exhibiting antiviral activity in the micromolar range. Following up on this thiophene hit, a new series of compounds that retain the five-membered heterocyclic scaffold while modifying several substituents was synthesized. Initial screening using a pseudotype viral system and validation assays employing authentic Ebola virus demonstrated the potential of this new chemical class as viral entry inhibitors. Subsequent investigations elucidated the mechanism of action through site-directed mutagenesis. Furthermore, we conducted studies to assess the pharmacokinetic profile of selected compounds to confirm its pharmacological and therapeutic potential.

Discovery of new antimicrobial thiophene derivatives with activity against drug-resistant Gram negative-bacteria.

Our aim is to identify new small molecules with antimicrobial potential, especially against colistin-resistant (Col-R) Acinetobacter baumannii and Escherichia coli. After initial hits identification by fingerprint similarity, MIC of 24 heterocyclic derivatives for A. baumannii and E. coli reference strains, and bactericidal activity of selected thiophenes against Col-R strains were determined. We analyzed changes in bacterial membrane permeability and the OMPs profile. Additionally, we determined bacterial adherence to host cells and performed molecular docking studies to assess their binding to bacterial targets. The compounds' MICs ranged from 4 to >64 mg/L. Thiophene derivatives 4, 5 and 8 exhibited MIC50 values between 16 and 32 mg/L for Col-R A. baumannii and 8 and 32 mg/L for Col-R E. coli. The time-kill curve assay demonstrated that thiophenes 4 and 8 had bactericidal effects against Col-R A. baumannii and E. coli. Furthermore, treatment with them resulted in increased membrane permeabilization and reduced adherence of these isolates to host cells. Finally, the docking studies showed a stronger binding affinity to CarO1 and Omp33 of A. baumannii and OmpW and OmpC of E. coli. These findings indicate that thiophene derivatives possess antibacterial activity against Col-R A. baumannii and E. coli, suggesting that they may enhance the repertoire of drug treatments against bacteria.

Small molecule inhibitors of human LRRK2 enhance in vitro embryogenesis and microcallus formation for plant regeneration of crop and model species.

In vitro plant embryogenesis and microcallus formation are systems which are required for plant regeneration, a process during which cell reprogramming and proliferation are critical. These systems offer many advantages in breeding programmes, such as doubled-haploid production, clonal propagation of selected genotypes, and recovery of successfully gene-edited or transformed plants. However, the low proportion of reprogrammed cells in many plant species makes these processes highly inefficient. Here we report a new strategy to improve in vitro plant cell reprogramming using small molecule inhibitors of mammalian leucine rich repeat kinase 2 (LRRK2), which are used in pharmaceutical applications for cell reprogramming, but never used in plants before. LRRK2 inhibitors increased in vitro embryo production in three different systems and species, microspore embryogenesis of oilseed rape and barley, and somatic embryogenesis in cork oak. These inhibitors also promoted plant cell reprogramming and proliferation in Arabidopsis protoplast cultures. The benzothiazole derivative JZ1.24, a representative compound of the tested molecules, modified the expression of the brassinosteroid (BR)-related genes BIN2, CPD, and BAS1, correlating with an activation of BR signaling. Additionally, the LRRK2 inhibitor JZ1.24 induced the expression of the embryogenesis marker gene SERK1-like. The results suggest that the use of small molecules from the pharmaceutical field could be extended to promote in vitro reprogramming of plant cells towards embryogenesis or microcallus formation in a wider range of plant species and in vitro systems. This technological innovation would help to develop new strategies to improve the efficiency of in vitro plant regeneration, a major bottleneck in plant breeding.

Biological and Methodological Variability in Retinal Nerve Fiber Layer OCT: The Framingham Heart Study.

Objective: To explore participant-level biological attributes and scan-level methodological attributes associated with retinal nerve fiber layer (RNFL) thickness variability in a population-based sample of elderly United States adults. Design: Cross-sectional analysis using data from the Framingham Heart Study. Participants: One thousand three hundred forty-seven eyes from 825 participants with ≥1 OCT scan and axial length data were included. Methods: Three or more successive RNFL scans of each eye of each participant were obtained in a single session. Multivariable linear mixed models were employed to explore the associations between average RNFL thickness with participant-level biological attributes (age, gender, race, ethnicity, and axial length) and scan-level attributes (signal strength [SS]) as independent variables in the whole population as well as a subsample of adults with no self-reported history of glaucoma. Similar analyses were designed to assess methodological variability with average within-eye standard deviation (SD) for repeated scans as the dependent variable. Main Outcomes Measures: (1) Biological variability: average RNFL thickness, and (2) methodological variability: average within-participant SD across repeated scans. Results: Age (ß =  - 0.19 microns/year, [95% confidence interval {CI}: - 0.29, - 0.09]), female gender (ß = +1.48 microns vs. male, [95% CI: 0.09, 2.86]), axial length (ß =  - 1.24 microns/mm of greater length, [95% CI: - 1.80, - 0.67]), and SS (ß = +1.62 microns/1 unit greater SS, [95% CI: 1.16, 2.09]) were significantly associated with RNFL thickness, while race and ethnicity were not (P > 0.05). In analyses designed to assess methodological variability, higher RNFL thickness (ß = +0.02 per micron increase, [95% CI: 0.01, 0.03]), and lower SS (ß = +0.19 per 1 unit lower SS, [95% CI: 0.10, 0.27]) were significantly associated with greater RNFL variability. In adults with no self-reported history of glaucoma (n of eyes = 1165, n of participants = 712), female gender was not associated with RNFL, while African American race was associated with thicker RNFL (ß = +4.65 microns vs. Whites, [95% CI: 1.28, 8.03]). Conclusions: Retinal nerve fiber layer thickness is lower with older age, male gender, greater axial length, lower SS, and Whites (as compared with African Americans) without self-reported glaucoma. Measurement variability (SD) is higher with greater RNFL thickness and lower SS. Understanding these biological and methodological variations is important to aid in OCT interpretation. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Impact of the presence and type of cardiovascular disease on the risk of mortality in type 2 diabetic patients: The DIABET-IC trial.

INTRODUCTION: All-cause mortality and cardiovascular mortality (CVM) risk can be very high in adults with type 2 diabetes mellitus (DM2) with previous cardiovascular disease (CVD). Our objective was to determine this risk among the different clinical spectrum of CVD. MATERIAL AND METHODS: The DIABET-IC trial is a multicenter, prospective, observational, and analytical study. Consecutive subjects with DM2 attending our outpatients' clinics were recruited. Data on clinical features, lab test results, and echocardiographic measures were collected. Patients were categorized depending on the presence and type of CVD: heart failure (HF), coronary artery disease (CAD), cerebrovascular disease (CVD) and peripheral artery disease (PAD). All-cause mortality and CVM were the dependent variables analyzed. Mortality rate was expressed as deaths per 1000 patients-year. Cox proportional hazards regressions models were used to establish the mortality risk associated with every type of CVD. RESULTS: We studied a total of 1246 patients (mean age, 6.3 (SD, 9.9) years; 31.6%, female) with an initial prevalence of CVD of 59.3%. A total of 122 deaths (46 due to CVD) occurred at the 2.6-year follow-up. All-cause and MCV rates associated with the presence of PAD (85.6/1000 and 33.6/1000, respectively) and HF (72.9/1000 and 28.7/1000 respectively) were the most elevated of all. In multivariate analysis, HF increased all-cause mortality risk (HR, 1.63; CI 95% 1.03-2.58; P=.037) and the risk of CVM (HR, 3.41; 95% CI, 1.68-6.93; P=.001). CONCLUSIONS: Mortality among DM2 patients is highly increased in the presence of HF and PAD. This justifies the screening of these conditions to intensify therapeutic strategies.

Selective disruption of synaptic NMDA receptors of the hippocampal trisynaptic circuit in Aß pathology.

Synaptic dysfunction is an early feature in Alzheimer's disease (AD) pathogenesis and a major morphological correlate of memory deficits. Given the main synaptic location of N-methyl-D-aspartate receptors (NMDARs), their dysregulation has been implicated in these pathological effects. Here, to detect possible alterations in the expression and synaptic localisation of the GluN1 subunit in the brain of amyloidogenic APP/PS1 mice, we employed histoblot and SDS-digested freeze-fracture replica labelling (SDS-FRL) techniques. Histoblots showed that GluN1 expression was significantly reduced in the hippocampus in a layer-dependent manner, in the cortex and the caudate putamen of APP/PS1 transgenic mice at 12 months of age but was unaltered at 1 and 6 months. Using quantitative SDS-FRL, we unravelled the molecular organisation of GluN1 in seven excitatory synapse populations at a high spatial resolution in the CA1 and CA3 fields and the DG of the hippocampus in 12-month-old APP/PS1 mice. In the CA1 field, the labelling density for GluN1 in the excitatory synapses established on spines and interneurons, was significantly reduced in APP/PS1 mice compared to age-matched wild-type mice in the stratum lacunosum-moleculare but unaltered in the stratum radiatum. In the CA3 field, synaptic GluN1 was reduced in mossy fibre-CA3 pyramidal cell synapses but unaltered in the A/C-CA3 pyramidal cell synapses. In the DG, the density of GluN1 in granule cell-perforant pathway synapses was reduced in APP/PS1 mice. Altogether, our findings provide evidence of specific alterations of synaptic GluN1 in the trisynaptic circuit of the hippocampus in Aß pathology. This differential vulnerability in the disruption of NMDARs may be involved in the mechanisms causing abnormal network activity of the hippocampal circuit and cognitive impairment characteristic of APP/PS1 mice.

Effects of Selective and Nonselective Beta Blockers on Bone Mineral Density in Mexican Patients with Breast Cancer.

Breast cancer (BCa) is related to chronic stress and can reduce the bone mineral density (BMD) through neurochemicals related to beta-adrenergic receptor (ADRB) 1 and 2. Selective beta blockers (sBBs) and nonselective beta blockers (nsBBs) are used to treat systemic arterial hypertension (SAH) and may have osteoprotective effects, as they inhibit ADRBs. To evaluate the effects of sBBs and nsBBs on the BMD of Mexican patients with BCa. A retrospective study was conducted. We included 191 Mexican women with BCa without SAH and with SAH treated with nsBBs, sBBs, and diuretics. BMD was evaluated using a bone density scan (DEX scan). A greater average BMD (p < 0.05) was observed in patients with prior treatment with both nsBBs and sBBs (0.54 ± 0.94 and -0.44 ± 1.22, respectively) compared to patients treated with diuretics or without SAH (-1.73 ± 0.83 and -1.22 ± 0.98, respectively). Regarding the diagnosis of osteoporosis/osteopenia, no cases were observed in patients treated with nsBBs, whereas 5.6% of the patients treated with sBBs presented osteopenia. A total of 23.1% and 10.6% patients managed with diuretics or without treatment presented with osteoporosis and 61.5% and 48% patients managed with loop diuretics and without treatment presented with osteopenia, respectively (p < 0.05). Treatment with nsBBs is a promising option for the prevention and management of osteoporosis/osteopenia in Mexican patients with BCa; however, further prospective studies are needed.