Aripiprazole as protector against COVID-19 mortality.

The relation of antipsychotics with severe Coronavirus Disease 19 (COVID-19) outcomes is a matter of debate since the beginning of the pandemic. To date, controversial results have been published on this issue. We aimed to prove whether antipsychotics might exert adverse or protective effects against fatal outcomes derived from COVID-19. A population-based retrospective cohort study (January 2020 to November 2020) comprising inpatients (15,968 patients) who were at least 18 years old and had a laboratory-confirmed COVID-19 infection. Two sub-cohorts were delineated, comprising a total of 2536 inpatients: individuals who either had no prescription medication or were prescribed an antipsychotic within the 15 days preceding hospitalization. We conducted survival and odds ratio analyses to assess the association between antipsychotic use and mortality, reporting both unadjusted and covariate-adjusted results. We computed the average treatment effects, using the untreated group as the reference, and the average treatment effect on the treated, focusing solely on the antipsychotic-treated population. Among the eight antipsychotics found to be in use, only aripiprazole showed a significant decrease in the risk of death from COVID-19 [adjusted odds ratio (OR) = 0.86; 95% CI, 0.79-0.93, multiple-testing adjusted p-value < 0.05]. Importantly, these findings were consistent for both covariate-adjusted and unadjusted analyses. Aripiprazole has been shown to have a differentiated beneficial effect in protecting against fatal clinical outcome in COVID-19 infected individuals. We speculate that the differential effect of aripiprazole on controlling immunological pathways and inducible inflammatory enzymes, that are critical in COVID19 illness, may be associated with our findings herein.

Observation of magnet-induced star-like radiation of a plasma created from cancer cells in a laser trap.

We present a new phenomenon resulting from the interaction of magnetic beads with cancer cells in a laser trap formed on a slide containing a depression 16.5 mm in diameter and 0.78 mm of maximum depth. This phenomenon includes the apparent formation and expansion of a dark bubble that attracts and incinerates surrounding matter when it explodes, which leads to a plasma emitting intense radiation that has the appearance of a star on a microscopic scale. We have observed the star-like phenomenon for more than 4 years, and the intensity depends on the laser's power. Measuring the laser power of the dark bubble shows the entrapment of electromagnetic energy as it expands.

The mediating role of reflective functioning in the association between childhood trauma and suicide attempt.

BACKGROUND: Childhood trauma is intimately related with suicidal behaviour. Patients who have suffered childhood trauma develop impaired Reflective Functioning (RF), which refers to the capacity to understand ourselves and others in terms of intentional mental states. An improvement in RF has been associated with a reduction in suicidal attempts, but the mediating role of RF between childhood trauma and suicidal behaviour has not been addressed so far. OBJECTIVE: We aim to examine the potential mediating effect of RF among childhood trauma and suicide attempts. METHOD: We included 748 patients who had attempted suicide at least once. They were asked to complete the Reflective Functioning Questionnaire (RFQ-8), the Columbia-Suicide Severity Rating scale (CSSRS), and the Childhood Trauma Questionnaire-Short Form (CTQ-SF). We conducted linear regressions by simple mediating model to examine the role of RF in the indirect association between childhood trauma and the number of suicide attempts. RESULTS: Our results show significant indirect effects through hypo and hypermentalizing between Emotional Abuse (EA) and Sexual Abuse (SA) in childhood and the number of suicide attempts in lifetime. These results indicate that ineffective RF significantly mediates the association between childhood trauma and suicidality. CONCLUSION: This is the first study supporting the mediational role of RF in the relationship between EA and SA, and the number of suicide attempt in lifetime. These findings have important implications for reducing suicide rates and preventing future re-attempts. Further studies analysing this mediating role and focusing efforts on increasing RF-based interventions are required.

BECN1 protein expression is associated with poor survival in triple negative locally advanced breast cancer.

OBJECTIVE: The role that Beclin 1 (BECN1) plays in the development and progression of cancer mediated by autophagy, as well as its differential expression in breast cancer cell lines and mammary tumor tissue according to the molecular subtype, has been demonstrated. The objective of this study was to evaluate the association of BECN1 cytoplasmic expression with clinical and pathologic response, recurrence, disease-free survival (DFS) and overall survival (OS) in patients with locally advanced breast cancer (LABC), according to immunophenotype. PATIENTS AND METHODS: 64 patients with non-triple negative LABC and 20 patients with triple negative LABC who received preoperative chemotherapy were included in an observational, analytical and retrospective study to evaluate the cytoplasmic expression of BECN1 protein by immunohistochemistry in microarrays of breast cancer tissue obtained before treatment. Association between BECN1 and clinicopathological characteristics, clinical and pathologic response to preoperative chemotherapy and recurrence, were analyzed using Chi-square or Fisher's exact test. Postoperative DFS and OS were assessed by Kaplan-Meir curves, and the difference according to BECN1 expression was evaluated using the log-rank test. The bivariate analysis was performed using the Cox Proportional Hazards Model. A p-value of < 0.05 was considered statistically significant. RESULTS: BECN1 staining revealed positive expression in 62.5% of patients with non-triple negative and 60.0% with triple negative LABC. No association was observed between BECN1 expression and clinical or pathological response or recurrence. An association of the BECN1 expression with lower OS in triple negative breast cancer was found (HR = 5.19; 95% CI 1.12-24.02; p = 0.035). CONCLUSIONS: Results showed an association of the cytoplasmic expression of BECN1 with a lower OS, which could be a poor prognostic biomarker in triple negative LABC.

Spinogenesis in spinal cord motor neurons following pharmacological lesions to the rat motor cortex. / Espinogénesis en motoneuronas de la médula espinal tras la lesión farmacológica de la corteza motora de ratas.

INTRODUCTION: Motor function is impaired in multiple neurological diseases associated with corticospinal tract degeneration. Motor impairment has been linked to plastic changes at both the presynaptic and postsynaptic levels. However, there is no evidence of changes in information transmission from the cortex to spinal motor neurons. METHODS: We used kainic acid to induce stereotactic lesions to the primary motor cortex of female adult rats. Fifteen days later, we evaluated motor function with the BBB scale and the rotarod and determined the density of thin, stubby, and mushroom spines of motor neurons from a thoracolumbar segment of the spinal cord. Spinophilin, synaptophysin, and ß iii-tubulin expression was also measured. RESULTS: Pharmacological lesions resulted in poor motor performance. Spine density and the proportion of thin and stubby spines were greater. We also observed increased expression of the 3 proteins analysed. CONCLUSION: The clinical symptoms of neurological damage secondary to Wallerian degeneration of the corticospinal tract are associated with spontaneous, compensatory plastic changes at the synaptic level. Based on these findings, spontaneous plasticity is a factor to consider when designing more efficient strategies in the early phase of rehabilitation.

Plastic changes to dendritic spines in the cerebellar and prefrontal cortices underlie the decline in motor coordination and working memory during successful aging.

Old age is the last stage of life and by taking a multidimensional view of aging, Neuroscientists have been able to characterize pathological or successful aging. Psychomotor and cognitive performance are recognized as two major domains of successful aging, with a loss of motor coordination and working memory deficits two of the most characteristic features of elderly people. Dendritic spines in both the cerebellar and prefrontal cortices diminish in aging, yet the plastic changes in dendritic spines have not been related to behavioral performance neither the changes in the cerebellar or prefrontal cortices. As such, motor coordination and visuospatial working memory (vsWM) was evaluated here in aged, 22-month-old rats, calculating the density of spines and the proportion of the different types of spines. These animals performed erratically and slowly in a motor coordination-related paradigm, and the vsWM was resolved deficiently. Spine density was reduced in aged animals, and the proportional density of each of the spine types studied diminished in both the brain regions studied. The loss of dendritic spines and particularly, the changes in the proportional density of the different spine types could underlie, at least in part, the behavioral deficits observed during aging. To our knowledge, this is the first study of the plastic changes in different dendritic spine types that might underlie the behavioral alterations in motor and cognitive abilities associated with aging. Further neurochemical and molecular studies will help better understand the functional significance of the plastic changes to dendritic spines in both successful and pathological aging.

Effects of Local Environmental and Landscape Variables on the Taxonomic and Trophic Composition of Aquatic Insects in a Rare Forest Formation of the Brazilian Amazon.

In the present study, we analyzed a unique phytophysiognomy in the Amazon region, which is formed by savanna-like vegetation on iron-rich soil (known locally as canga) located within an iron-ore mining region. We used the habitat template theory to test the hypothesis that changes in the physical-chemical properties of streams and the physical structure of their habitats at in-stream and micro-basin (landscape) levels affect the taxonomic and trophic composition of immature aquatic insects. For this, we used a local environmental matrix composed of nine physical-chemical and structural habitat variables, together with the Habitat Integrity Index. We also calculated landscape metrics based on the area of the micro-basin, such as relief, slope, mean current flow, and vegetation cover. We divided the aquatic insects into five functional feeding groups based on their diet and food sources. Our results indicate that changes in the trophic level of the insects of the orders Ephemeroptera, Plecoptera, and Trichoptera are more easily observed than the taxonomic structure of communities. The loss of environmental integrity and vegetation cover were responsible for 84% of the variation observed in the composition of functional feeding groups (FFGs). Our study shows that aquatic insect communities in the canga and in the Amazon regions dominated by forest require specific in-stream and landscape conditions. These findings reinforce the need for the preservation of areas of canga vegetation, which not only have a unique levels of biological diversity, but are also targeted for the exploitation of their economically valuable natural resources.

Influence of multi-walled carbon nanotubes on the physico-chemical and biological responses of chitosan-based hybrid hydrogels.

Photoresponsive membranes were successfully obtained by combining chitosan (CS), poly(vinyl alcohol) (PVA) crosslinked with genipin (GEN) and filled with multi-walled carbon nanotubes (MWCNTs). It was demonstrated that adding a small quantity (0.01% w/v) of MWCNTs conferred to those nanocomposite hybrid hydrogels an outstanding photomechanical response under infrared irradiation. Moreover, it was observed that MWCNTs enhanced the crystallinity, increased the elastic modulus but did not contribute to the thermal stability of the nanocomposite hybrid hydrogels. The swelling capacity and contact angle values of these materials were modified through the addition of MWCNTs, and the offered free OH and NH2 functional groups in their current chemical structures. These functional groups - on hybrid hydrogels' surfaces - also enhanced the adhesion and proliferation of human dermal fibroblast cells, showing typical morphologies and sizes. Additionally, non-cytotoxic effects were observed for these nanocomposite hybrid hydrogels, suggesting their potential use in tissue engineering and biomedical applications. Chemical compounds studied in this article: Chitosan (PubChem CID: 71853); Polyvinyl alcohol (PubChem CID: 11199); Genipin (PubChem CID: 442424).

Vulnerability of Phyllocycla Species (Odonata: Gomphidae) to Current and Planned Anthropic Activities by the Brazilian Government.

Although most species distribution modeling (SDMs) are constructed at the species level, an appreciation of evolutionary processes has led to modeling above this level. In view of the difficulty in estimating the impacts of human actions on rare or deficient data species, we proposed a new approach to vulnerability assessment based on concepts already well established in the literature (ecological niche, niche conservatism, and extinction thresholds). We used distribution modeling to predict where species of the genus Phyllocycla (Calvert 1948) are most vulnerable to local extinctions and how the implementation of planned anthropic activities by the Brazilian government may modify the potential distribution of the genus in Brazil. We chose that genus because its conservation status is little known, especially due to the data gap about its geographical distribution. We proposed modeling the whole genus and used the niche conservatism theory to justify our methods. The anthropic activities considered in our analysis were agriculture and livestock, rural settlements, energy production installations, transportation, oil extraction, mining, and urbanization. We found that only 55.3% of the original potential distribution of Phyllocycla in Brazil remains available. The area compromised by anthropic activities comprises mainly the Cerrado and Atlantic Forest biomes, with less impact on the Amazon. However, with the implementation of activities planned by the Brazilian government, it is possible that an additional 13.6% of this area will be unavailable to species of Phyllocycla, especially in the Amazon, where interest in mining and the implementation of new hydroelectric production have increased.

Prescription drug diversion among people living with HIV: a systematic scoping review.

OBJECTIVES: Globally, people living with HIV (PLWH) are at greater risk for various infections and chronic pain, therefore, vulnerable to prescription drug diversion which might negatively impact HIV care. The study purpose is to gather evidence on prescription drug diversion among PLWH. STUDY DESIGN: This is a systematic scoping review. METHODS: Arksey and O'Malley's framework and recommendation by Levac et al. were used to guide this study. Literature was searched in PubMed, Google Scholar, EBSCOhost (Academic Search Complete, MEDLINE and Newspaper Source) and Open Access Theses and Dissertations. Studies reporting evidence of prescription drug diversion from January 1996 to July 2017 were included. Thematic content analysis was performed to summarize data on the prevalence. RESULTS: Twenty-nine studies were eligible for data synthesis. Twenty-six studies were conducted in the United States of America (USA), one study in France and two multicountry studies; one study in Kenya and Uganda and the other study in Botswana, Kenya, Malawi, South Africa; Zimbabwe, India, Thailand, Brazil and the USA. Research evidence shows high prevalence of prescription drug diversion for analgesics and antiretroviral drugs; meanwhile, stimulants and erectile dysfunction drugs were the least diverted drugs among PLWH. There is a research gap in low- to middle-income countries (LMICs) investigating prescription drug diversion among PLWH. CONCLUSION: Our findings reveal that diversion of various prescription drug classes among PWLH exists. There is lack of research in LMICs. We recommend research in LMICs where there is high HIV prevalence. PROSPERO REGISTRATION NUMBER: CRD42017074076.

Quantitative and qualitative control of antineoplastic preparations: Gravimetry versus HPLC.

This article compares gravimetry vs. high-performance liquid chromatography (HPLC) as quality control (QC) methods for paclitaxel, docetaxel and oxaliplatin preparations. We aimed at assessing the preparation method reliability in our hospital, evaluating compounding accuracy and estimating the influence of personnel training and standardized homogenization on compounding accuracy. Agreement, correlation, concordance, accuracy and precision between methods were evaluated for each drug. Conforming preparation percentages (CPs) at different tolerance limits (TLs) and compounding accuracy were calculated for each method and drug. Compounding accuracy was compared before and after personnel training and standardized homogenization implantation. SPSS v 20.0 and Ene v 2.0 were used. A total of 222 samples (58 docetaxel, 95 paclitaxel and 69 oxaliplatin) were analyzed. Gravimetry and HPLC are comparable methods. Overall CP was 81% for gravimetry at 10% TL and 85% for HPLC at 15% TL. Compounding accuracy is shown to be good for all methods and drugs. Homogenization optimization and personnel training make measurements more accurate for docetaxel and paclitaxel HPLC, but seem to worsen accuracy for docetaxel gravimetry. Gravimetry has shown to be a good alternative to HPLC for routine QC. Coupling with electronic methods should be considered in the future.

Evidence of factors influencing self-medication with antibiotics in low and middle-income countries: a systematic scoping review.

OBJECTIVES: Self-medication with antibiotics (SMA) is a practice of global concern with a higher incidence within the low- and middle-income countries (LMICs). Despite worldwide efforts to control and promote the rational use of antibiotics, the continuing practice of SMA systematically exposes individuals and communities to the risk of antibiotic resistance and a host of other antibiotic side-effects. This systematic scoping review maps evidence on the factors influencing SMA in these settings. STUDY DESIGN: Systematic scoping review. METHODS: The search strategy involved electronic databases including PubMed, Web of science, Science Direct, EBSCOhost, Google Scholar, BioMed Central, and the World Health Organization Library. PRISMA P guidelines and Arksey and O'Malley's framework were used. Thematic analysis was used to identify the factors that influence the practices of SMA in LMICs. The Mixed Method Appraisal Tool (MMAT), version 2011, was used to assess the quality of the included primary studies. RESULTS: Fifteen studies met the inclusion criteria. Studies included participants from the following LMICs: Guatemala, India, Indonesia, Kenya, Laos, Nepal, Nigeria, Pakistan, Sri Lanka, and Yemen. The findings of the review emphasized a considerable high prevalence of SMA, ranging from 8.1% to 93%, with an association with the level of education, monthly income, and gender of participants. Accessibility, affordability, and conditions of health facilities, as well as the health-seeking behavior, are factors that influence SMA in LMICs. Health conditions such as a sore throat, common cold, cough, headache, toothache, flu-like symptoms, pain relief, fever, runny nose, toothache, upper respiratory tract infections, and urinary tract infection were the major complaints that led to the practices of SMA. CONCLUSIONS: There is a considerable level of research evidence predominantly in some LMICs from Asia, with less evidence from African LMICs. Sociocultural determinants of health associated with the structure and conditions of health system as well as the health-seeking behavior are the main factors influencing SMA. Contextual and comprehensive studies on the factors influencing the non-prescribed use of antibiotics are needed to enable evidence-based strategies to correctly address the utilization of antibiotics and contain the problem of antimicrobial resistance, especially within the LMICs. PROSPERO REGISTRATION: CRD42017072954.

A dietary intervention with functional foods reduces metabolic endotoxaemia and attenuates biochemical abnormalities by modifying faecal microbiota in people with type 2 diabetes.

AIM: To study the effects of a functional food-based dietary intervention on faecal microbiota and biochemical parameters in patients with type 2 diabetes (T2D). MATERIALS AND METHODS: This placebo-controlled, randomized, double-blind study included 81 patients with T2D divided into two 3-month treatment groups: one following a reduced-energy diet with a dietary portfolio (DP) comprising high-fibre, polyphenol-rich and vegetable-protein functional foods; the other taking a placebo (P). The primary outcome was the effect of the DP on faecal microbiota. Secondary endpoints were biochemical parameters, lipopolysaccharide, branched-chain amino acids, trimethylamine N-oxide, glycosylated haemoglobin (HbA1c) and free fatty acids (FFAs). RESULTS: Patients with T2D exhibited intestinal dysbiosis characterized by an increase in Prevotella copri. Dietary intervention with functional foods significantly modified faecal microbiota compared with P by increasing alpha diversity and modifying the abundance of specific bacteria, independently of antidiabetic drugs. There was a decrease in P. copri and increases in Faecalibacterium prausnitzii and Akkermansia muciniphila, two bacterial species known to have anti-inflammatory effects. The DP group also exhibited significant reductions in areas under the curve for glucose, total and LDL cholesterol, FFAs, HbA1c (P< 0.05), triglycerides and CRP, and an increase in antioxidant activity (P< 0.01) vs. the P group. CONCLUSION: Long-term adherence to a high-fibre, polyphenol-enriched and vegetable-protein-based diet provides benefits for the composition of faecal microbiota, and may offer potential therapies for improvement of glycaemic control, dyslipidaemia and inflammation.

Chronic deltoid ligament insufficiency repair with Internal Brace™ augmentation.

BACKGROUND: Patients with chronic deltoid ligament insufficiency (CDLI) present a challenging situation. Although numerous procedures have been described, optimal treatment is still a matter of debate. While the treatment armamentarium ranges from simple ligament repair to complex reconstructions with or without realignment osteotomies, direct repair augmented with an Internal Brace™ device appears to be an attractive intermediate option. We investigated functional outcomes and complications in patients with CDLI operated on using Internal Brace™ augmentation. METHODS: A prospective study was conducted. Patients were included if they presented medial ankle pain and/or giving way, exhibited asymmetric flexible hindfoot valgus, failed conservative treatment, and had a positive MRI evaluated by an independent radiologist. Patients with stage IV flatfoot deformity, neuropathy and/or inflammatory arthritis were excluded. CDLI was confirmed intraoperatively with the arthroscopic drive-through sign. Patients were evaluated preoperatively and postoperatively using FAAM, SF-36 and grade of satisfaction. Paired t-tests were used to assess FAAM and SF-36 scores variation. RESULTS: Thirteen patients met inclusion criteria. No patient was lost to follow-up, with a mean follow-up time of 13.5 months (range 6-21). Preoperative FAAM and SF-36 scores improved from 58.7 to 75.3 and from 60.2 to 84.4 postoperatively, respectively (p<.01). Two implant failures were observed, with no apparent compromise of construct stability. No patient was re-operated. CONCLUSIONS: Our results suggest that deltoid ligament repair with Internal Brace™ augmentation in patients with CDLI is a reliable option with good functional outcomes and high satisfaction grade in short term follow-up. LEVEL OF EVIDENCE: Level IV.

Amino acid profiles of young adults differ by sex, body mass index and insulin resistance.

BACKGROUND AND AIMS: An increase in plasma branched-chain amino acids is associated with a higher risk of developing type 2 diabetes and cardiovascular diseases. However, little is known about the basal plasma amino acid concentrations in young adults. Our aim was to determine the plasma amino acid profiles of young adults and to evaluate how these profiles were modified by sex, body mass index (BMI) and insulin resistance (IR). METHODS AND RESULTS: We performed a transversal study with 608 Mexican young adults aged 19.9 ± 2.4 years who were applicants to the Universidad Autónoma de San Luis Potosí. The subjects underwent a physical examination and provided a clinical history and a blood sample for biochemical, hormonal and amino acid analyses. The women had higher levels of arginine, aspartate and serine and lower levels of α-aminoadipic acid, cysteine, isoleucine, leucine, methionine, proline, tryptophan, tyrosine, urea and valine than the men. The obese subjects had higher levels of alanine, aspartate, cysteine, ornithine, phenylalanine, proline and tyrosine and lower levels of glycine, ornithine and serine than the normal weight subjects. Subjects with IR (defined as HOMA > 2.5) had higher levels of arginine, alanine, aspartate, isoleucine, leucine, phenylalanine, proline, tyrosine, taurine and valine than the subjects without IR. Furthermore, we identified two main groups in the subjects with obesity and/or IR; one group was composed of amino acids that positively correlated with the clinical, biochemical and hormonal parameters, whereas the second group exhibited negative correlations. CONCLUSION: This study demonstrates that young adults with obesity or IR have altered amino acid profiles characterized by an increase in alanine, aspartate, proline and tyrosine and a decrease in glycine.

Efficacy and safety of eslicarbazepine-acetate in elderly patients with focal epilepsy: Case series.

PURPOSE: Eslicarbazepine-acetate (ESL) is a third generation antiepileptic drug licensed as adjunctive therapy in adults with focal seizures. Efficacy and safety of ESL have been established in real-life setting. However, data about outcomes in elderly patients are scarce. Primary endpoint was to evaluate outcomes of ESL in elderly patients. METHOD: This was a retrospective survey that included patients >65years with focal seizures who started ESL between January 2010 and July 2012 at 12 Spanish Hospitals. ESL was prescribed individually according to real-life practice. Efficacy and safety were evaluated over 1year. These patients were included within the bigger study ESLIBASE. RESULTS: We included 29 patients, most of them males (18). Mean age was 71.2 year-old and epilepsy evolution was 20 years. Eighteen were pharmacorresistant at baseline. At 12 months, the mean dose was 850mg/day, the retention rate 69%, the responder rate 62% and 24.1% were seizure-free. At 12 months, 16 patients (55.2%) had ≥1 adverse effect (AE), that led to discontinuation in 7 patients. Dizziness, nausea and ataxia were the most common AEs. The tolerability profile improved in 4/5 patients who switched from carbamazepine (CBZ) or oxcarbazepine (OXC) to ESL due to AEs. CONCLUSIONS: ESL was well-tolerated and effective in elderly patients in a real-life setting over 1year, with a dose around 800mg/day. AE effects improved in most of who switched from CBZ or OXC to ESL.

Influence of schooling and age on cognitive performance in healthy older adults.

Few studies have examined the influence of a low level of schooling on age-related cognitive decline in countries with wide social and economic inequalities by using the Cambridge Automated Neuropsychological Test Battery (CANTAB). The aim of the present study was to assess the influence of schooling on age-related cognitive decline using unbiased cognitive tests. CANTAB allows cognitive assessment across cultures and education levels with reduced interference of the examiner during data acquisition. Using two-way ANOVA, we assessed the influences of age and education on test scores of old adults (61-84 years of age). CANTAB tests included: Visual Sustained Attention, Reaction Time, Spatial Working Memory, Learning and Episodic Memory. All subjects had a minimum visual acuity of 20/30 (Snellen Test), no previous or current history of traumatic brain/head trauma, stroke, language impairment, chronic alcoholism, neurological diseases, memory problems or depressive symptoms, and normal scores on the Mini Mental State Examination (MMSE). Subjects were grouped according to education level (1 to 7 and ≥8 years of schooling) and age (60-69 and ≥70 years). Low schooling level was associated with significantly lower performance on visual sustained attention, learning and episodic memory, reaction time, and spatial working memory. Although reaction time was influenced by age, no significant results on post hoc analysis were detected. Our findings showed a significantly worse cognitive performance in volunteers with lower levels of schooling and suggested that formal education in early life must be included in the preventive public health agenda. In addition, we suggest that CANTAB may be useful to detect subtle cognitive changes in healthy aging.