Clinical assessment of non-suicidal self-injury: A systematic review of instruments

There has been an increase in the number of assessment instruments for non-suicidal self-injury (NSSI). However, previous reviews are inconsistent and do not provide a comprehensive psychometric assessment of the instruments. This study aimed to systematically assess and compare the psychometric properties of clinically relevant instruments to measure NSSI in any population. Through a systematic review guided by COSMIN and PRISMA, two searches were conducted in English and Spanish in February 2020 in 13 databases including grey literature. Of the 7,813 initial records, 152 validations were extracted. From these, 83 instruments (22 versions or adaptations) were excluded for not measuring NSSI, having no potential clinical utility or not including psychometric properties. Finally, 26 (22 versions, 35 adaptations and 19 creations) instruments measuring NSSI were included. Predominantly, the studies were North American self-reports in English for community adolescents, adaptations or versions emanating from a small number of instruments. Twenty-six indicators were categorized to assess NSSI. The most frequent instruments are structured interviews, and their indicators were related to NSSI function and topography. Evidence of validity and reliability was positive but limited. Despite the high number of instruments and diversity of evaluations, we found no instrument with sufficient evidence for clinical assessment. Findings broadly overview NSSI assessment instruments' current use and future improvement in clinical and research settings.     

Evaluation of Bioequivalence of Highly Variable Drugs Using Clinical Trial Simulations. II: Comparison of Single and Multiple-Dose Trials Using AUC and Cmax

Purpose. Evaluating of the effects of high intrasubject variability in clearance (CL) and volume of distribution (V), on 90% confidence intervals (CIs) for AUC (Area Under the concentration Curve) in single and multiple-dose bioequivalence studies. The main methodology was Monte Carlo simulation, and we also used deterministic simulation, and examination of clinical trials. The results are compared with those previously observed for Cmax (maximum concentration.) Methods. The time course of drug concentration in plasma was simulated using a one-compartment model with log-normal statistical distributions of intersubject and intrasubject variabilities in the pharmacokinetic parameters. Both immediate-release and prolonged-release products were simulated using several levels of intrasubject variability in single-dose and multiple-dose studies. Simulations of 2000 clinical bioequivalence trials per condition (138 conditions) with 30 subjects in each crossover trial were carried out. Simulated data were compared with data from actual bioequivalence trials. Results. The current simulations for AUC show similar probabilities of failure for single-dose and multiple-dose bioequivalence studies, even with differences in the rate of absorption or fraction absorbed. AUC values from prolonged-release scenario studies are more sensitive to changes in the first order absorption rate constant ka, and to variability in CL and V than AUC from studies of immediate-release studies. Conclusions. We showed that multiple-dose designs for highly variable drugs do not always reduce intrasubject variability in either AUC or Cmax, although the behavior of AUC differs from Cmax. Single dose AUC to the last quantifiable concentration was more reliable than either single dose AUC extrapolated to infinity, or multiple dose AUC during a steady-state interval. Multiple-dose designs may not be the best solution for assessing bioequivalence of highly variable drugs.     

Discovery in space of ethanolamine,the simplest phospholipid head group

Cell membranes are a key element of life because they keep the genetic material and metabolic machinery together. All present cell membranes are made of phospholipids, yet the nature of the first membranes and the origin of phospholipids are still under debate. We report here the presence of ethanolamine in space, NH2CH2CH2OH, which forms the hydrophilic head of the simplest and second-most-abundant phospholipid in membranes. The molecular column density of ethanolamine in interstellar space is N = (1.51±0.07)× 1013 cm−2, implying a molecular abundance with respect to H2 of (0.9−1.4) × 10−10. Previous studies reported its presence in meteoritic material, but they suggested that it is synthesized in the meteorite itself by decomposition of amino acids. However, we find that the proportion of the molecule with respect to water in the interstellar medium is similar to the one found in the meteorite (10−6). These results indicate that ethanolamine forms efficiently in space and, if delivered onto early Earth, could have contributed to the assembling and early evolution of primitive membranes.

Life is based on three basic subsystems: a compartment, a metabolic machinery, and information-bearing molecules together with replication mechanisms (1, 2). Among these key elements, compartmentalization is a fundamental prerequisite in the process of the emergence and early evolution of life (3, 4). Indeed, cellular membranes encapsulate and protect the genetic material, as well as enable the metabolic activities within the cell. The membranes of all current cells are made of a bilayer of phospholipids (Fig. 1 A and B), which are composed of a polar hydrophilic head (an alcohol phosphate group combined with a head group such as ethanolamine [EtA], choline, or serine) and two nonpolar hydrophobic tails (hydrocarbon chains derived from fatty acids), as depicted in Fig. 1C.Open in a separate windowFig. 1.Structure of cellular membranes. (A) Schematic view of a cell. (B) Zoom-in view of the cell membrane, formed by a phospholipid bilayer. (C) Three-dimensional structure of the phospholipid PE, formed by a hydrophilic head composed of EtA, a phosphate group linked to glycerol, and two hydrophobic fatty-acid tails (black, red, blue, and white balls denote carbon, oxygen, nitrogen, and hydrogen atoms, respectively). (D) EtA, the molecular species detected in space and reported in this work.The process through which the first phospholipids were formed remains unknown. Initial work proposed that phospholipids could be synthesized under possible prebiotic conditions (5–7), but the availability of the precursor molecules on early Earth was questioned (3, 8). Alternatively, the building blocks of phospholipids could have been delivered from space. A broad repertoire of prebiotic molecules could have been provided to the early Earth through the bombardment of comets and meteorites (9, 10). Laboratory impact experiments (11, 12) have demonstrated that a significant fraction of the prebiotic molecules in comets and meteorites can survive both passage through the planetary atmosphere and the impact on the surface.In particular, some structural parts of phospholipids are known to be present in meteorites, such as fatty acids, alcohols, and phosphonic acids (10, 13, 14). The glycerol phosphate group has been shown to be synthesized in irradiation experiments of interstellar ice analogs (15, 16), which supports the idea that they can form in space. Regarding the different head groups of phospholipids, EtA (also known as glycinol or 2-aminoethanol, NH2CH2CH2OH; Fig. 1D) is the simplest one, and it forms the second-most-abundant phospholipid in biological membranes: phosphatidylethanolamine (PE) (see Fig. 1C). In addition, EtA has been proposed as a direct precursor of the simplest amino acid, glycine (NH2CH2COOH), in simulated archean alkaline hydrothermal vents (17), considered as one of the likely environments for the origin of life (18).EtA has been found in the Almahata Sitta meteorite (19), yet its origin is not known. A possible chemical formation route was proposed to be the thermal decomposition of amino acids under specific unusual conditions in the parent asteroid. This would limit the availability of EtA in the early Earth for the formation of phospholipids and thereafter of cell membranes. Another possibility is that EtA is formed from smaller interstellar precursors. However, the detection of EtA in the interstellar medium (ISM) has remained so far elusive (20).     

Successful Treatment of Congenital Erythropoietic Porphyria Using Matched Unrelated Hematopoietic Stem Cell Transplantation

Congenital erythropoietic porphyria (CEP), or Günther's disease, is an inborn error of metabolism produced by a deficiency of uroporphyrinogen III synthase (UROS), the fourth enzyme of the heme biosynthesis pathway. This enzymatic defect induces the accumulation of isomer I porphyrins in erythrocytes, skin, and tissues, producing various clinical manifestations. Severe cases are characterized by extreme photosensitivity, causing scarring and mutilations, and by hemolytic anemia, reducing life expectancy. CEP is caused by mutations in the UROS gene, and one of the most severe forms of the disease is associated with a cysteine to arginine substitution at residue 73 of the protein (C73R). CEP has been successfully treated only by the transplantation of hematopoietic precursors. We report the case of a male infant with severe postdelivery symptoms diagnosed with CEP and found to be homozygous for the C73R mutation. He underwent successful allogeneic bone marrow transplantation from a matched unrelated donor at 7 months of age. The hemolytic anemia was corrected and the porphyrin overproduction was significantly reduced. The patient remained asymptomatic after 1 year. This new case confirms that patients with severe CEP can benefit from early postnatal hematopoietic stem cell transplantation.     

Relationship of asthma and rhinoconjunctivitis with obesity, exercise and Mediterranean diet in Spanish schoolchildren

BACKGROUND: Although several studies have investigated the influence of diet on asthma in schoolchildren, none of them has evaluated how obesity can modify this effect. A study was undertaken to evaluate the association of various foods and a Mediterranean diet with the prevalence of asthma and rhinoconjunctivitis, adjusting for obesity and exercise. METHODS: A cross-sectional study was performed in 20 106 schoolchildren aged 6-7 years from eight Spanish cities. Using the ISAAC phase III questionnaire, parents reported chest and nose symptoms, food intake, weight, height and other factors, including exercise. A Mediterranean diet score was developed. A distinction was made between current occasional asthma (COA) and current severe asthma (CSA). RESULTS: Independent of the amount of exercise, each Mediterranean score unit had a small but protective effect on CSA in girls (adjusted OR 0.90, 95% CI 0.82 to 0.98). Exercise was a protective factor for COA and rhinoconjunctivitis in girls and boys (the more exercise, the more protection). Obesity was a risk factor for CSA in girls (adjusted OR 2.35, 95% CI 1.51 to 3.64). Individually, a more frequent intake (1-2 times/week and>or=3 times/week vs never/occasionally) of seafood (adjusted ORs 0.63 (95% CI 0.44 to 0.91) and 0.53 (95% CI 0.35 to 0.80)) and cereals (adjusted OR 0.56 (95% CI 0.30 to 1.02) and 0.39 (95% CI 0.23 to 0.68)) were protective factors for CSA, while fast food was a risk factor (adjusted ORs 1.64 (95% CI 1.28 to 2.10) and 2.26 (95% CI 1.09 to 4.68)). Seafood (adjusted ORs 0.74 (95% CI 0.60 to 0.92) and 0.67 (95% CI 0.53 to 0.85)) and fruit (adjusted ORs 0.76 (95% CI 0.60 to 0.97) and 0.71 (95% CI 0.57 to 0.88)) were protective factors for rhinoconjunctivitis. CONCLUSIONS: A Mediterranean diet has a potentially protective effect in girls aged 6-7 years with CSA. Obesity is a risk factor for this type of asthma only in girls.