Suicidal Behavior and Its Relationship with Postmortem Forensic Toxicological Findings.

Suicide affects all sociodemographic levels, age groups, and populations worldwide. The factors that can increase the risk of suicidal tendencies are widely studied. The aim of this study was to analyze the types and combinations of toxics found in fatal suicide victims with different suicide mechanisms. A total of 355 autopsies were retrospectively studied, and 26 toxics were determined and related to mechanisms of suicide. Hanging (55%), drug overdose (22.7%), and jumping from a height (17.8%) were most represented suicide mechanisms with positive toxicology. Hanging was the most represented in men (50.3%; p = 0.019), while jumping from a height was more represented in women (29.7%, p = 0.028). Drugs of abuse were the most frequent toxics found in men (55.5%; p < 0.001), while medicines were the most frequent type found in women (70.3%, p < 0.001). Alcohol, nordiazepam, cocaine, and venlafaxine were the most consumed toxics. Benzodiazepines and venlafaxine were found in suicides involving drug overdose, hanging, and jumping from a height. In conclusion, most suicides were associated with drug abuse in men. Hanging was more represented in men and jumping from a height in women. Alcohol was present in combination with other toxics and medicines. The toxicological analysis is fundamental to understanding consumption patterns and establishing strategies and protocols for detecting and preventing suicide.

Operative Treatment of Ankle Fractures: Predictive Factors Affecting Outcome.

Purpose Surgical management of ankle fractures has been extensively studied in literature but studies investigating validated clinical results are lacking and controversial. The purpose of this study was to evaluate functional and health-related quality of life (HRQL) outcomes after surgically treated ankle fractures and to detect some of their predictors. Methods Two hundred sixty-six skeletally mature patients who underwent surgery for an isolated ankle fracture from 2006 to 2017 were retrospectively identified from our hospital records and included in the study. All patients were evaluated at one, three, six and 12 months post-injury with clinical and radiographic examination. Outcome measures recorded at final two years minimum follow-up included patient-reported pain, patient satisfaction, functional (American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score) and quality of life (Short Form (SF) 36 score) status. Results Patient satisfaction score was 8.4 out of 10, Visual Analogue Scale mean score was 2.3, complication rate was 36.5% and mean AOFAS ankle-hindfoot score was 87.3. Mean SF36-physical summary score was 77.9 and SF36-mental summary score was 81.1. The injury demonstrated a significant effect on physical function, role-physical, bodily pain and social functioning SF-36 subdomains. Functional outcome was significantly related to occupation, syndesmotic lesion, number of fractured malleoli and delay to surgery. Main predictors of quality of life were age, occupation, cause of injury, syndesmotic lesion, number of fractured malleoli and waiting time to surgery. Conclusions Ankle fractures have a considerable impact on functional and quality of life status of patients. Occupation, presence of syndesmotic injury, Pott's classification and surgery delay must be considered as predictors of final outcome.

Muerte súbita en embarazada por embolia trofoblástica vs. tiroiditis vs. canalopatía / Sudden death in pregnancy caused by trophoblastic embolism vs. thyroiditis vs. channelopathy

Mujer de 43 años, gestante de 37 semanas con controles periódicos normales que fallece súbitamente tras cuadro de náuseas y vómitos. Se realiza autopsia forense con estudio histopatológico de todos los órganos (maternos y fetales), toxicológico y genético. Los hallazgos fundamentales fueron: múltiples émbolos trofoblásticos en pulmón; extensa tiroiditis linfocitaria crónica e hipofisitis focal. El análisis genético demostró un polimorfismo en el gen SCN5A del canal del sodio. Se plantean 3 posibles causas de muerte: 1) embolismo trofoblástico; 2) arritmia por alteración electrolítica asociada a hipotiroidismo y potenciada por las náuseas y los vómitos, y 3) síndrome de QT largo por hipertiroidismo y polimorfismo en el gen SCN5A. Este caso es ilustrativo de que la determinación de la causa de la muerte durante el embarazo o puerperio puede ser muy compleja, por lo que la autopsia debe ser exhaustiva incluyendo el estudio histopatológico de los órganos endocrinos, análisis genético y análisis bioquímico

A 43-year-old, 37-week-pregnant woman with normal periodic controls dies suddenly after nausea and vomiting. A complete forensic autopsy is performed with histopathological study of all organs (maternal and foetal), and toxicological and genetic analysis. The main findings were: multiple trophoblastic embolism in the lung; extensive chronic lymphocytic thyroiditis; and focal hypophysitis. Genetic analysis demonstrated a polymorphism in the SCN5A gene of the sodium channel. There are three possible causes of death: 1) trophoblastic embolism; 2) arrhythmia due to electrolyte disturbance associated with hypothyroidism and enhanced by nausea and vomiting; 3) long QT syndrome due to hyperthyroidism and polymorphism in the SCN5A gene. This case illustrates that determination of cause of death during pregnancy or puerperium can be very complex, so the autopsy must be exhaustive including histopathological study of the endocrine organs, and genetic and biochemical analysis

Correlation of ISO 16840-2:2007 impact damping and hysteresis measures for a sample of wheelchair seating cushions.

Hysteresis and impact damping measures were made on 37 wheelchair seating cushions according to ISO 16840-2:2007 Wheelchair seating-Part 2: Determination of physical and mechanical characteristics of devices intended to manage tissue integrity-seat cushions. These measures were then correlated using Spearman and Pearson correlations to investigate the relationship between them. Correlations were also conducted on the subset of cushions comprising only those with planar foam construction. Correlation between the hysteresis measures (h250 and h500) and the mean number of rebounds greater in amplitude than 10% of the peak acceleration amplitude (R10%) were weak, as were the correlations between the hysteresis measures and the mean peak first rebound acceleration (aa). Correlations between hysteresis and the mean peak second rebound acceleration (a2), and also hysteresis and the ratio of first and second peak (a2:aa) however were moderate. Results demonstrate that the relationship between these two measures is complex. The assertion implicit in ISO 16840-2:2007 is that the two measures are related, but this study shows that these should not be assumed to be equivalent or used interchangeably.

Development and bioorthogonal activation of palladium-labile prodrugs of gemcitabine.

Bioorthogonal chemistry has become one of the main driving forces in current chemical biology, inspiring the search for novel biocompatible chemospecific reactions for the past decade. Alongside the well-established labeling strategies that originated the bioorthogonal paradigm, we have recently proposed the use of heterogeneous palladium chemistry and bioorthogonal Pd(0)-labile prodrugs to develop spatially targeted therapies. Herein, we report the generation of biologically inert precursors of cytotoxic gemcitabine by introducing Pd(0)-cleavable groups in positions that are mechanistically relevant for gemcitabine's pharmacological activity. Cell viability studies in pancreatic cancer cells showed that carbamate functionalization of the 4-amino group of gemcitabine significantly reduced (>23-fold) the prodrugs' cytotoxicity. The N-propargyloxycarbonyl (N-Poc) promoiety displayed the highest sensitivity to heterogeneous palladium catalysis under biocompatible conditions, with a reaction half-life of less than 6 h. Zebrafish studies with allyl, propargyl, and benzyl carbamate-protected rhodamines confirmed N-Poc as the most suitable masking group for implementing in vivo bioorthogonal organometallic chemistry.

Extracellular palladium-catalysed dealkylation of 5-fluoro-1-propargyl-uracil as a bioorthogonally activated prodrug approach.

A bioorthogonal organometallic reaction is a biocompatible transformation undergone by a synthetic material exclusively through the mediation of a non-biotic metal source; a selective process used to label biomolecules and activate probes in biological environs. Here we report the in vitro bioorthogonal generation of 5-fluorouracil from a biologically inert precursor by heterogeneous Pd(0) catalysis. Although independently harmless, combined treatment of 5-fluoro-1-propargyl-uracil and Pd(0)-functionalized resins exhibits comparable antiproliferative properties to the unmodified drug in colorectal and pancreatic cancer cells. Live-cell imaging and immunoassay studies demonstrate that the cytotoxic activity of the prodrug/Pd(0)-resin combination is due to the in situ generation of 5-fluorouracil. Pd(0)-resins can be carefully implanted in the yolk sac of zebrafish embryos and display excellent biocompatibility and local catalytic activity. The in vitro efficacy shown by this masking/activation strategy underlines its potential to develop a bioorthogonally activated prodrug approach and supports further in vivo investigations.

ISO 16840-2:2007 load deflection and hysteresis measurements for a sample of wheelchair seating cushions.

Load deflection and hysteresis measurements were made on 37 wheelchair seating cushions according to ISO 16840-2:2007. Load deflection plots for all 37 cushions are reported and fundamental aspects of graph interpretation discussed. ISO hysteresis data are also reported and interpretation discussed.