Impulsivity in fatal suicide behaviour: A systematic review and meta-analysis of psychological autopsy studies.

Our aim is to review and perform a meta-analysis on the role of impulsivity in fatal suicide behaviour. We included papers who used psychological autopsy methodology, assessed adult death by suicide, and included assessment of impulsivity. We excluded papers about assisted suicide, terrorist suicide, or other cause of death other than suicide or postmortem diagnosis made only from medical records or database. 97 articles were identified. 33 were included in the systematic review and nine in the meta-analysis. We found that people who die by suicide with high impulsivity are associated with younger age, substance abuse, and low intention to die, whereas those with low impulsivity were associated with older age, depression, schizophrenia, high intention to die and low social support. In the meta-analysis, suicide cases had higher impulsivity scores than living controls (Hedges' g = 0.59, 95 % CI [0.28, 0.89], p=.002). However, studies showed heterogeneity (Q = 90.86, p<.001, I2=89.0 %). Impulsivity-aggressiveness interaction was assessed through meta-regression (ß=0.447, p=.045). Individuals with high impulsivity would be exposed to a higher risk of fatal suicide behaviour, aggressiveness would play a mediating role. People who die by suicide with high and low impulsivity display distinct characteristics, which may reflect different endophenotypes leading to suicide by different pathways.

Safety of fluoroquinolones / Seguridad de las fluoroquinolonas

Fluoroquinolones (FQs) are one of the most commonly prescribed classes of antibiotics. Although they were initially well tolerated in randomized clinical trials, subsequent epidemiological studies have reported an increased risk of threatening, severe, long-lasting, disabling and irreversible adverse effects (AEs), related to neurotoxicity and collagen degradation, such as tendonitis, Achilles tendon rupture, aortic aneurysm, and retinal detachment. This article reviews the main potentially threatening AEs, the alarms issued by regulatory agencies and therapeutic alternatives. (AU)

Las fluoroquinolonas son una de las clases de antibióticos más prescritas. Aunque inicialmente fueron bien toleradas en ensayos clínicos aleatorizados, estudios epidemiológicos posteriores han informado de un mayor riesgo de efectos adversos efectos adversos amenazantes, graves, duraderos, incapacitantes e irreversibles, relacionados con la neurotoxicidad y la degradación del colágeno, como tendinitis, rotura del tendón de Aquiles, aneurisma aórtico y desprendimiento de retina. Este artículo repasa los principales efectos adversos potencialmente amenazadores, las alarmas emitidas por las agencias reguladoras y las alternativas terapéuticas. (AU)

In Vivo Detection of Staphylococcus aureus Infections Using Radiolabeled Antibodies Specific for Bacterial Toxins.

Purpose: The Gram-positive Staphylococcus aureus bacterium is one of the leading causes of infection in humans. The lack of specific noninvasive techniques for diagnosis of staphylococcal infection together with the severity of its associated complications support the need for new specific and selective diagnostic tools. This work presents the successful synthesis of an immunotracer that targets the α-toxin released by S. aureus. Methods: [89Zr]Zr-DFO-ToxAb was synthesized based on radiolabeling an anti-α-toxin antibody with zirconium-89. The physicochemical characterization of the immunotracer was performed by high-performance liquid chromatography (HPLC), radio-thin layer chromatography (radio-TLC), and electrophoretic analysis. Its diagnostic ability was evaluated in vivo by positron emission tomography/computed tomography (PET/CT) imaging in an animal model of local infection-inflammation (active S. aureus vs. heat-killed S. aureus) and infective osteoarthritis. Results: Chemical characterization of the tracer established the high radiochemical yield and purity of the tracer while maintaining antibody integrity. In vivo PET/CT image confirmed the ability of the tracer to detect active foci of S. aureus. Those results were supported by ex vivo biodistribution studies, autoradiography, and histology, which confirmed the ability of [89Zr]Zr-DFO-ToxAb to detect staphylococcal infectious foci, avoiding false-positives derived from inflammatory processes. Conclusions: We have developed an immuno-PET tracer capable of detecting S. aureus infections based on a radiolabeled antibody specific for the staphylococcal alpha toxins. The in vivo assessment of [89Zr]Zr-DFO-ToxAb confirmed its ability to selectively detect staphylococcal infectious foci, allowing us to discern between infectious and inflammatory processes.

Gene expression reprogramming of Pseudomonas alloputida in response to arginine through the transcriptional regulator ArgR.

Different bacteria change their life styles in response to specific amino acids. In Pseudomonas putida (now alloputida) KT2440, arginine acts both as an environmental and a metabolic indicator that modulates the turnover of the intracellular second messenger c-di-GMP, and expression of biofilm-related genes. The transcriptional regulator ArgR, belonging to the AraC/XylS family, is key for the physiological reprogramming in response to arginine, as it controls transport and metabolism of the amino acid. To further expand our knowledge on the roles of ArgR, a global transcriptomic analysis of KT2440 and a null argR mutant growing in the presence of arginine was carried out. Results indicate that this transcriptional regulator influences a variety of cellular functions beyond arginine metabolism and transport, thus widening its regulatory role. ArgR acts as positive or negative modulator of the expression of several metabolic routes and transport systems, respiratory chain and stress response elements, as well as biofilm-related functions. The partial overlap between the ArgR regulon and those corresponding to the global regulators RoxR and ANR is also discussed.

Fixed dental prosthesis on six zirconia implants for an anterior maxillary rehabilitation: case report with 10-year follow-up.

This article reports a case of maxillary rehabilitation with an implant-supported fixed partial denture on six zirconia implants. A female patient with impacted maxillary canines attended our dental clinic seeking a metal-free maxillary restoration. After the extraction of both impacted maxillary canines and the placement of autogenous bone graft, six one-piece zirconia implants with conical abutments were placed in the anterior maxillary region. Two zirconia fixed dental prosthesis with porcelain veneering, separated at the mid-line, were placed on these zirconia implants. The ten-year follow-up monitored the adequate evolution of both implants and restorations with no signs of peri-implant disease.

Isolation of goat milk small extracellular vesicles by novel combined bio-physical methodology.

Introduction: Goat milk is notable as a cost-effective source of exosomes, also known as small extracellular vesicles (sEVs). These nanoparticle-like structures are naturally secreted by cells and have emerged as potential diagnostic agents and drug delivery systems, also supported by their proven therapeutic effects. However, the complexity of goat milk and the lack of standardized protocols make it difficult to isolate pure sEVs. This work presents an optimized approach that combines well-established physical isolation methods with the biological treatment of milk with rennet. Methods: sEVs derived from goat milk were purified using a methodology that combines differential ultracentrifugation, rennet, and size-exclusion chromatography. This novel strategy was compared with two of the main methodologies developed for isolating extracellular vesicles from bovine and human milk by means of physico-chemical characterization of collected vesicles using Transmission Electron Microscopy, Western blot, Bradford Coomassie assay, Dynamic Light Scattering, Nanoparticle Tracking Analysis and Zeta Potential. Results: Vesicles isolated with the optimized protocol had sEV-like characteristics and high homogeneity, while samples obtained with the previous methods were highly aggregated, with significant residual protein content. Discussion: This work provides a novel biophysical methodology for isolating highly enriched goat milk sEVs samples with high stability and homogeneity, for their further evaluation in biomedical applications as diagnostic tools or drug delivery systems.

Quality of Life, Pedobarographic Parameters, and Foot Disorders in Patients with Extreme Obesity: Preliminary Results on Changes After Bariatric Surgery with Gastric Bypass.

PURPOSE: Obesity is a growing health problem that affects a high percentage of the population. In podiatry context, few studies have addressed obesity because most pedobarographic systems are unable to bear the weight of patients with obesity, making it difficult to examine and manage these patients. The objective of this study was analyzed the sociodemographic characteristics, quality of life, foot disorders, and pedobarographic parameters of patients with extreme obesity who are candidates for bariatric surgery and determine the changes after weight loss post-surgery. MATERIALS AND METHODS: We conducted a foot examination, a pedobarographic study using a Podoprint® pressure platform, and a quality of life questionnaire (EQ-5D) on 23 patients with extreme obesity and analyzed the changes 12-18 months after surgery in 11 of them. RESULTS: We observed foot disorders, high plantar pressure, greater rearfoot contact, flat footprint, asymmetries, and alterations in toe contact. Almost 73.9% of participants said they had foot pain, 56.5% said they had impaired mobility, and more than 40% said they had limitations in carrying out daily activities and suffered from anxiety. After weight loss, we observed improved quality of life; more foot disorders; changes in total contact area, plantar pressures, barycenter, contact time, and footprint; decreased pain perception, walking problems and anxiety situations. Moreover, medication decreased, but they need to take more vitamins and calcium. CONCLUSION: Weight loss improved the quality of life of the participating patients but altered their foot disorders. All parameters need regular reassessment to detect changes and modify initially prescribed treatments.

Becoming settlers: Elements and mechanisms for surface colonization by Pseudomonas putida.

Pseudomonads are considered to be among the most widespread culturable bacteria in mesophilic environments. The evolutive success of Pseudomonas species can be attributed to their metabolic versatility, in combination with a set of additional functions that enhance their ability to colonize different niches. These include the production of secondary metabolites involved in iron acquisition or having a detrimental effect on potential competitors, different types of motility, and the capacity to establish and persist within biofilms. Although biofilm formation has been extensively studied using the opportunistic pathogen Pseudomonas aeruginosa as a model organism, a significant body of knowledge is also becoming available for non-pathogenic Pseudomonas. In this review, we focus on the mechanisms that allow Pseudomonas putida to colonize biotic and abiotic surfaces and adapt to sessile life, as a relevant persistence strategy in the environment. This species is of particular interest because it includes plant-beneficial strains, in which colonization of plant surfaces may be relevant, and strains used for environmental and biotechnological applications, where the design and functionality of biofilm-based bioreactors, for example, also have to take into account the efficiency of bacterial colonization of solid surfaces. This work reviews the current knowledge of mechanistic and regulatory aspects of biofilm formation by P. putida and pinpoints the prospects in this field.

Pandemics and Suicide Rates in Spain: From the Spanish Flu to COVID-19.

Objective: The aim of this study was to examine suicide rates in Spain during the COVID-19 pandemic and the influenza pandemic of 1918-1920.Methods: Data on deaths by cause for the periods 1910-1925 and 2016-2020 were obtained from the National Statistics Institute of Spain.Results: During the Spanish influenza pandemic, a peak of deaths in 1918 due to influenza, acute bronchitis, pneumonia, and other respiratory diseases coincided with an increase in suicides (from 5.9 in 1917 to 6.6 per 100,000 population in 1918). The pattern was repeated in the COVID-19 pandemic during 2020, with an increase in suicides from 7.8 in 2019 to 8.3 per 100,000 population in 2020. In both cases, the male:female suicide ratio was reduced in similar proportion, with a higher net increase in the number of suicides among males but a higher percentage increase among females.Conclusions: Albeit limited, there is evidence that the pandemics may have affected suicide rates. However, the effect was most likely due to precipitation of different diathesis-stressor factors in each setting, given the different historical contexts.

Subcutaneous anti-COVID-19 hyperimmune immunoglobulin for prevention of disease in asymptomatic individuals with SARS-CoV-2 infection: a double-blind, placebo-controlled, randomised clinical trial.

Background: Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141. Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, -3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; -9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19. Funding: Grifols.

Biomonitoring of potentially toxic elements through oysters (Saccostrea palmula and Crassostrea corteziensis) from coastal lagoons of Southeast Gulf of California, Mexico: health risk assessment.

The coastal lagoons of the Gulf of California support important traditional fisheries and mollusc cultures (generally oysters) and receive important volumes of agricultural, industrial and urban effluents, consumption of the oysters could pose risk to human health. The concentrations of arsenic (As), cadmium (Cd), copper (Cu), iron (Fe), lead (Pb), and zinc (Zn) in the oysters Saccostrea palmula and Crassostrea corteziensis, from four coastal lagoons (Altata, AL; Macapule, ML; Navachiste, NL; El Colorado, ECL) in the Southeast Gulf of California, were seasonally evaluated (summer 2019-spring 2020). The order of magnitude of potentially toxic elements concentrations in the soft tissue in both oyster species and at all sites was Zn > Fe > Cu > As > Cd > Pb. Cadmium, Cu, Pb, and Zn exceeded the maximum permissible limits in more than one sampling site. The highest concentrations (mg kg-1, wet weight) of As (4.2 ± 1.1, spring) and Cd (3.3 ± 0.7, autumn) were registered in S. palmula et al. and NL sampling sites, respectively. Crassostrea corteziensis presented higher levels of Cu (40.5 ± 6.7, spring), Pb (2.0 ± 0.4, spring), and Zn (96.9 ± 20.4, spring) in ECL and Fe (62.2 ± 25.4, autumn) in ML. The hazard quotient (HQ) values exceeded the safe level of 1 for Cd in S. palmula and C. corteziensis in NL for children (~ 16 kg weight). In addition, in children, the hazard index (HI) values in both species of oysters ranged from 0.7 to 2.1 and 0.6 to 1.9, respectively. On the other hand, the intake of the studied elements through the consumption of oysters would not induce adverse effects to human health (men and women weighing 70 and 60 kg, respectively); HQ and HI values were < 1.

Evolución satisfactoria de un paciente adulto con malaria grave y complicada por Plasmodium falciparum / Satisfactory course of an adult patient with severe complicated Plasmodium falciparum malaria

Introducción: La malaria continúa siendo un importante problema de salud a nivel mundial, su diagnóstico temprano y tratamiento inmediato son fundamentales para prevenir las complicaciones y la muerte. Objetivo: Reportar el caso de un paciente cubano procedente de República de Guinea, que presentó malaria complicada por Plasmodium falciparum, el cual fue hospitalizado en el Instituto de Medicina Tropical Pedro Kourí (IPK). Caso clínico: Paciente masculino, cubano, de piel negra, 63 años de edad, profesión marinero mercante. Sin antecedentes patológicos personales. Llegó al IPK en camilla, con cierto deterioro de la conciencia, debilidad generalizada, dificultad respiratoria y compromiso del ritmo diurético. Ingresó en la Unidad de Cuidados Intensivos donde recibió tratamiento con los antipalúdicos artesunato y primaquina. La parasitemia fue descendiendo en el decursar de los días. El paciente sobrevivió y egresó satisfactoriamente a los 16 días posteriores a su ingreso. Fue debidamente notificado a las autoridades del Ministerio de Salud Pública de Cuba, lo que constituye un procedimiento obligatorio del Sistema Nacional de Vigilancia de Enfermedades Transmisibles en Cuba. Conclusión: La rapidez en el diagnóstico, así como el tratamiento integral, eficaz y oportuno, fue de importancia vital y condujo a un buen desenlace de la enfermedad.

Introduction: Malaria continues to be a major health problem worldwide, its early diagnosis and prompt treatment are critical to prevent complications and death. Objective: To report the case of a Cuban patient from the Republic of Guinea, who presented with complicated Plasmodium falciparum malaria, who was hospitalized at the Institute of Tropical Medicine Pedro Kourí (IPK). Clinical case: Male patient, Cuban, black-skinned, 63 years old, occupation: merchant seaman. No personal pathological history. He arrived at the IPK on a stretcher, with some deterioration of consciousness, generalized weakness, respiratory distress and diuretic rhythm compromise. He was admitted to the Intensive Care Unit where he received treatment with the antimalarial drugs artesunate and primaquine. Parasitemia decreased over the days. The patient survived and was discharged satisfactorily 16 days after admission. This case was duly notified to the authorities of the Ministry of Public Health of Cuba, which is a mandatory procedure of the National Surveillance System of Communicable Diseases in Cuba. Conclusion: Prompt diagnosis, as well as a comprehensive, effective, and timely treatment was vital and led to a good disease outcome.

Dual-labeled nanoparticles based on small extracellular vesicles for tumor detection.

BACKGROUND: Small extracellular vesicles (sEVs) are emerging natural nanoplatforms in cancer diagnosis and therapy, through the incorporation of signal components or drugs in their structure. However, for their translation into the clinical field, there is still a lack of tools that enable a deeper understanding of their in vivo pharmacokinetics or their interactions with the cells of the tumor microenvironment. In this study, we have designed a dual-sEV probe based on radioactive and fluorescent labeling of goat milk sEVs. RESULTS: The imaging nanoprobe was tested in vitro and in vivo in a model of glioblastoma. In vitro assessment of the uptake of the dual probe in different cell populations (RAW 264.7, U87, and HeLa) by optical and nuclear techniques (gamma counter, confocal imaging, and flow cytometry) revealed the highest uptake in inflammatory cells (RAW 264.7), followed by glioblastoma U87 cells. In vivo evaluation of the pharmacokinetic properties of nanoparticles confirmed a blood circulation time of ~ 8 h and primarily hepatobiliary elimination. The diagnostic capability of the dual nanoprobe was confirmed in vivo in a glioblastoma xenograft model, which showed intense in vivo uptake of the SEV-based probe in tumor tissue. Histological assessment by confocal imaging enabled quantification of tumor populations and confirmed uptake in tumor cells and tumor-associated macrophages, followed by cancer-associated fibroblasts and endothelial cells. CONCLUSIONS: We have developed a chemical approach for dual radioactive and fluorescent labeling of sEVs. This methodology enables in vivo and in vitro study of these vesicles after exogenous administration. The dual nanoprobe would be a promising technology for cancer diagnosis and a powerful tool for studying the biological behavior of these nanosystems for use in drug delivery.

Improvement of fitness and biocontrol properties of Pseudomonas putida via an extracellular heme peroxidase.

The extracellular 373-kDa PehA heme peroxidase of Pseudomonas putida KT2440 has two enzymatic domains which depend on heme cofactor for their peroxidase activity. A null pehA mutant was generated to examine the impact of PehA in rhizosphere colonization competence and the induction of plant systemic resistance (ISR). This mutant was not markedly hampered in colonization efficiency. However, increase in pehA dosage enhanced colonization fitness about 30 fold in the root and 900 fold in the root apex. In vitro assays with purified His-tagged enzymatic domains of PehA indicated that heme-dependent peroxidase activity was required for the enhancement of root tip colonization. Evaluation of live/dead cells confirmed that overexpression of pehA had a positive effect on bacterial cell viability. Following root colonization of rice plants by KT2440 strain, the incidence of rice blast caused by Magnaporthe oryzae was reduced by 65% and the severity of this disease was also diminished in comparison to non-treated plants. An increase in the pehA dosage was also beneficial for the control of rice blast as compared with gene inactivation. The results suggest that PehA helps P. putida to cope with the plant-imposed oxidative stress leading to enhanced colonization ability and concomitant ISR-elicitation.

Decision aids linked to the recommendations in clinical practice guidelines: results of the acceptability of a decision aid for patients with generalized anxiety disorder.

BACKGROUND: Generalized anxiety disorder (GAD) is one of the most prevalent mental health problems. Patients with GAD have unmet needs related to the information received about their disorder, its treatments and their participation in the decision-making process. The aim of this study is to develop and assess the acceptability of a patient decision aid (PtDA) for patients with GAD. METHOD: The PtDA was developed following the International Patient Decision Aid Standards. The recommendations of the Spanish clinical practice guideline (CPG) for patients with GAD were used as the basis. The first prototype was developed by an expert committee, further improvements were made with patients (n = 2), clinical experts (n = 13) and the project management group (n = 7). The acceptability of this second draft was assessed by patients non-involved in the previous phases (n = 11). RESULTS: The final PtDA version included a brief description of GAD and its treatments. Most participants agreed that the PtDA was easy to use, visually appealing and useful. At least half of the participants learned new things about treatments and adverse effects. CONCLUSIONS: A PtDA was developed for patients with GAD based on recommendations from the Spanish CPG. It was improved and accepted by patients and clinical experts involved. An evaluation of its effectiveness on the shared decision-making process during the clinical encounter is planned.

Leucodistrofia metacromática del adulto: reporte de caso / Adult-onset metachromatic leukodystrophy

RESUMEN INTRODUCCIÓN: La leucodistrofia metacromática (LDM) es una enfermedad poco frecuente que se caracteriza por desmielinización progresiva a nivel del sistema nervioso central y periférico. En la mayoría de los casos, es causada por una actividad deficiente de la enzima arilsulfatasa-A. Pertenece al grupo de las leucodistrofias, que son trastornos hereditarios de la sustancia blanca asociados con una variabilidad fenotípica y una heterogeneidad genética importante. El fenotipo de la LDM suele relacionarse con la edad de presentación, que puede variar desde la infancia hasta la adultez. Cuando se presenta en la edad adulta, puede debutar con manifestaciones neuropsiquiátricas, lo que lleva con frecuencia a diagnósticos erróneos. REPORTE DE CASO: Se presenta el caso de una paciente adulta que debutó con un cuadro clínico caracterizado por cambios comportamentales progresivos, con posterior inicio de manifestaciones clínicas motoras. El diagnóstico de LDM se sospechó a partir de la clínica y los hallazgos típicos en la resonancia magnética (RM) cerebral, y se confirmó con la detección de actividad deficiente de la arilsulfatasa-A (ARSA) y la secuenciación del gen ARSA que confirmó la mutación en estado homocigoto, compatible con este diagnóstico. DISCUSIÓN: Destacamos en este caso la importancia de la sospecha clínica, el reconocimiento temprano y el manejo multidisciplinario como factores pronósticos del curso de la enfermedad, ya que en la actualidad no hay tratamiento definitivo para la enfermedad.

ABSTRACT INTRODUCTION: Metachromatic leukodystrophy (MLD) is an infrequent disease characterized by progressive demyelination of the central and peripheral nervous system. In most cases, it is caused by deficient activity of arylsulfatase-A. It belongs to the group of leukodystrophies, which are inherited white matter disorders that can be associated with significant phenotypic variability and genetic heterogeneity. The phenotype in MLD is usually related to the age of onset, which can vary from childhood to adulthood. Adult-onset MLD can debut with neuropsychiatry symptoms, which can often lead to misdiagnosis. CASE REPORT: We report the case of an adult female patient who presented with progressive behavioral changes, followed by motor manifestations. MLD was initially suspected based on the clinical presentation and the characteristic findings on brain magnetic resonance imaging (MRI), with subsequent confirmation by detection of deficient arylsulfatase-A (ARSA) activity and ARSA gene sequencing, which demonstrated homozygosity, compatible with this diagnosis. DISCUSSION: We highlight the importance of clinical suspicion, early recognition and multidisciplinary management as a prognostic factor for the course of the disease, since there is currently no definitive treatment for the disease.