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Discharges from food service establishments (FSEs) are a major source of fat, oil and grease (FOG) which cause blockages in sewer networks. Previous research has identified that current methods are unsuitable for quantifying FOG in FSE wastewater owing to interference from surfactants in detergents, and protein from food residuals which emulsify FOG. A novel quantification method, based on the dairy industry Gerber method, has been developed which negates the impact of surfactants. Moreover, the method allows free and emulsified oil to be quantified separately providing greater insight into FOG management strategies. Trials in synthetic and real FSE wastewaters indicate the novel method is more reliable than standard liquid–liquid and solid phase extraction in FOG‐rich systems. [ABSTRACT FROM AUTHOR]

Pesticide pollution of surface water is a major concern in many agricultural catchments The development of rapid and accurate methods for determining pesticide concentrations in water samples is, therefore, important. Here we describe a method for the simultaneous analysis of six pesticides (metaldehyde, quinmerac, carbetamide, metazachlor, propyzamide and pendimethalin) in natural waters by direct aqueous injection with liquid chromatography-tandem mass spectrometry. The method validation showed good linearity from 0.2 to 50.0 µg/L with correlation coefficients between 0.995 and 0.999. Method accuracy ranged from 84 to 100% and precision Relative standard deviation (RSD) from 4 to 15%. The limits of detection for the targeted pesticides ranged from 0.03 to 0.36 µg/L. No significant matrix effects on quantification were observed ( t-test). The method was tested on water samples from a small arable catchment in eastern England. Peak concentrations for the determinands ranged from 1 to 10 µg/L. [ABSTRACT FROM AUTHOR]

Ketorolac ( KET) is a nonsteroidal anti-inflammatory drug approved for the use in humans that possesses a potent analgesic activity, comparable to morphine, and could represent a useful tool to control acute pain also in animals. The clinical efficacy and pharmacokinetic profile of intravenous (IV) ketorolac tromethamine (0.5 mg/kg) were studied in 15 dogs undergoing gonadectomy. Intra-operative cardiorespiratory variables were monitored, and post-operative pain was assessed using a subjective pain score (0-24) in all dogs, whereas the pharmacokinetic profile of the drug was determined in 10 animals. During surgery, mean minimal alveolar concentration of isoflurane was 1.69 ± 0.11%, and normocapnia and spontaneous ventilation were maintained in all animals. During pain assessment, no significant differences between males and females were found, and in no case rescue analgesia was necessary. No adverse effects were reported. Serum samples were purified by solid-phase extraction and analysed by HPLC with UV-Vis detection. A large variability was observed in serum concentrations. The kinetics of ketorolac was described by a noncompartmental analysis. The elimination half-life (t½λz) and Cl B were 10.95 ± 7.06 h and 92.66 ± 84.49 mL/h/kg, respectively, and Vdss and V z were 1030.09 ± 620.50 mL/kg and 1512.25 ± 799.13 mL/kg, respectively. AUC(0→last) and MRT(0→last) were 6.08 ± 3.28 h × μg/mL and 5.59 ± 2.12 h, respectively. The results indicate that ketorolac possess good post-operative analgesic effects until about 6 h after administration in dogs undergoing moderately painful surgery. [ABSTRACT FROM AUTHOR]

Zonca, A., Ravasio, G., Gallo, M., Montesissa, C., Carli, S., Villa, R., Cagnardi, P. Pharmacokinetics of ketamine and propofol combination administered as ketofol via continuous infusion in cats. J. vet. Pharmacol. Therap. 35, 580-587. The pharmacokinetics of the extemporaneous combination of low doses of ketamine and propofol, known as 'ketofol', frequently used for emergency procedures in humans to achieve safe sedation and analgesia was studied in cats. The study was performed to assess propofol, ketamine and norketamine kinetics in six female cats that received ketamine and propofol (1:1 ratio) as a loading dose (2 mg/kg each, IV) followed by a continuous infusion (10 mg/kg/h each, IV, 25 min of length). Blood samples were collected during the infusion period and up to 24 h afterwards. Drug quantification was achieved by HPLC analysis using UV-visible detection for ketamine and fluorimetric detection for propofol. The pharmacokinetic parameters were deduced by a two-compartment bolus plus infusion model for propofol and ketamine and a monocompartmental model for norketamine. Additional data were derived by a noncompartmental analysis. Propofol and ketamine were quantifiable in most animals until 24 and 8 h after the end of infusion, respectively. Propofol showed a long elimination half-life ( t1/2λ2 7.55 ± 9.86 h), whereas ketamine was characterized by shorter half-life ( t1/2λ2 4 ± 3.4 h) owing to its rapid biotransformation into norketamine. The clinical significance of propofol's long elimination half-life and low clearance is negligible when the drug is administered as short-term and low-dosage infusion. The concurrent administration of ketamine and propofol in cats did not produce adverse effects although it was not possible to exclude interference in the metabolism. [ABSTRACT FROM AUTHOR]

The transformation process of the natural kaolinite into metakaolinite for its use as a cement addition was very much known long time ago. However, environmental policies prioritize the waste recycling as raw material by its environmental benefits. This article reports, for the first time, the scientific aspects related to the recycling of three Spanish coal mining wastes of different nature and origin, as an alternative source to obtain future pozzolans based on metakaolinite. The effect of activation conditions on the mineralogy, as well as the formation and evolution of hydrated phases formed during the pozzolanic reaction, was analyzed using different instrumental techniques such as X-ray fluorescence, X-ray diffraction, thermogravimetric analysis, infrared spectroscopy, and scanning electron microscopy. The results showed that all activated coal mining wastes exhibited high pozzolanic activity. The identification and evolution of hydrated phases with the hydration time in activated kaolin/ Ca(OH)2 system were directly related to the origin and nature of the starting coal mining waste and not to the activation temperature itself. Finally, the coal mining wastes are suitable for being used as future pozzolans. [ABSTRACT FROM AUTHOR]

A few studies provided convincing evidence of constitutive expression of type I interferons (IFNs) in humans and mice, and of the steady-state role of these cytokines under health conditions. These results were later confirmed in pigs, too. In line with this tenet, low levels of IFN-α/β can be detected in swine tissues in the absence of any specific inducer. These studies are compounded by the utmost complexity of type I IFNs (including among others 17 IFN-α genes in pigs), which demands proper research tools. This prompted us to analyse the available protocols and to develop a relevant, robust, reverse transcription (RT) real-time polymerase chain reaction (PCR) detection system for the amplification of porcine IFN-α/β genes. The adopted test procedure is user-friendly and provides the complete panel of gene expression of one subject in a microtitre plate. Also, a proper use of PCR fluorochromes (SYBR® versus EvaGreen® supermix) enables users to adopt proper test protocols in case of low-expression porcine IFN-α genes. This is accounted for by the much higher sensitivity of the test protocol with EvaGreen® supermix. Interestingly, IFN-β showed the highest frequency of constitutive expression, in agreement with its definition of 'immediate early' gene in both humans and mice. Results indicate that the outlined procedure can detect both constitutively expressed and virus-induced IFN-α/β genes, as well as the impact of environmental, non-infectious stressors on the previous profile of constitutive expression. [ABSTRACT FROM AUTHOR]

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In this study we present the addiction severity profile in a sample of 202 cocaine addicts, using the composite scores for each area of the EuropASI (European version of the ASI), which are compared with the severity ratings obtained through interviewers' subjective assessments. The results showed that the areas of the EuropASI which reflected the greatest severity according to the composite scores were, in the following order: employment/support, family/social situation, use of alcohol and psychiatric state. The results obtained with the composite scores show discrepancies with those obtained from the severity rating. Statistically significant differences were found in the areas of alcohol (Z = -6.205; p < 0.001), drugs (Z = -11.902; p < 0.001), family/social (Z = -6.915; p < 0.001) and psychiatric status (Z = -6.651; p < 0.001). The results call into question the reliability and validity of severity ratings obtained through interviewers' subjective assessments. For diagnosis and research, a more objective appraisal is recommended, using composite scores, since severity ratings depend totally on the interviewer's judgement, and do not appear to constitute a sound measure for estimating therapeutic change. [ABSTRACT FROM AUTHOR]

Length of hospital stay (LOS) is an important indicator of the hospital activity and management of health care. The skewness exhibited by this variable poses problems in statistical modeling. The aim of this work is to model the variable LOS within diagnosis-related groups (DRG) through finite mixtures of distributions. A mixture of the union of Gamma, Weibull and Lognormal families is used in the model, instead of a mixture of a unique distribution family. Some theoretical questions regarding the model, such as the identifiability and study of asymptotic properties of ML estimators, are analyzed. The EM algorithm is proposed for performing these estimators. Finally, this new proposed model is illustrated by using data from different DRGs. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aims The aims of the study were to: (1) evaluate the gastrointestinal transit, release and absorption of budesonide from tablets with a new multimatrix formulation (MMX®) designed to release the drug throughout the whole colon, and (2) assess the influence of food on budesonide bioavailability. Methods Two phase I studies, each comprising 12 healthy males, were performed. Gastrointestinal transit of 153Sm-labelled tablets containing 9 mg budesonide was evaluated by means of pharmaco-scintigraphy. The effect of food was tested by comparing plasma pharmacokinetics after intake of a high fat and high calorie breakfast with fasting controls. Results 153Sm-labelled tablets reached the ascending colon after a mean ± SD 9.8 ± 6.9 h. Initial tablet disintegration was observed in the ileum in 42% and the ascending and transverse colon in 33% of subjects. Ninety-six per cent of the dose was absorbed into the systemic circulation during passage through the whole colon including the sigmoid. Food significantly decreased C max values from 1429 ± 1014 to 1040 ± 601 pg mL−1 ( P = 0.028) and AUC values from 14 814 ± 11 254 to 13 486 ± 9369 pg h−1 mL−1 ( P = 0.008). Mean residence time and t max increased by 12–29%. There was no drug accumulation after 1 week of once daily oral administration of budesomide. Conclusions MMX®-budesonide tablets appear suitable for targeted colonic drug delivery. Transit parameters and low systemic bioavailability warrant further studies with the new formulation. [ABSTRACT FROM AUTHOR]

AIM: The purpose of this study was to assess the ability of enamel matrix derivative (EMD) to improve root coverage with a coronally advanced flap (CAF) during a 2-year follow-up. METHODS: Fifteen patients each with two single and similar bilateral Miller Class I or II gingival recessions (30 recessions) were selected. Each recession was randomly assigned to the test group (CAF+EMD) or the control group (CAF only). Clinical parameters recorded at baseline and at 6, 12 and 24 months were recession depth (R), recession width (WR), probing depth (PD), clinical attachment level (CAL) and keratinized tissue (KT). RESULTS: Reduction of R resulted in a significant CAL gain in both groups, whereas PD was not altered. In the test group, R decreased from 4.07 mm (SD+/-0.59) at baseline to 0.47 mm (SD+/-0.74) at 24 months, corresponding to a mean root coverage (MRC) of 90.67%, whereas in the control group R shrank from 4.13 mm (SD+/-0.74) at baseline to 0.60 mm (SD+/-0.83) at 24 months (MRC=86.67%). Complete root coverage was achieved at 24 months in 73.33% and 60% of the two groups. A significant KT increase was observed in both groups. CONCLUSIONS: Root coverage outcomes were similar in both groups and no statistically significant differences were found at all between them. Hence, the additional use of EMD to CAF is not justified for clinical benefits of root coverage, but as an attempt of achieving periodontal regeneration rather than repair. Copyright (c) Blackwell Munksgaard, 2005. [ABSTRACT FROM AUTHOR]

Neurodegenerative Diseases represent the most common cause of Dementia, about 5–10% of the population aged above 65 years and about 30% above 80 years. A study about Apo-E alleles, Coenzyme Q and Vitamins E as biological indicators was performed in plasma samples of patients aged from 30 to 85 years, affected by Neurodegenerative Diseases. The results were compared with control subjects of approximately the same ages as the reference group. A frequency of 21.7% of ℇ4 allele in control group was estimated, against 15.8% observed in patients. The frequency of ℇ2 and ℇ3 alleles was 13.0% and 65.2% in the control group against 10.5% and 73.7% in patients. No significant differences were observed between the frequency of ℇ3/ℇ3 genotype and ℇ3/ℇ4 genotype in the control group compared to patients' group. The frequencies observed in ℇ2/ℇ3 genotype groups were 8.7% vs 15.8% and of e2/e4 genotype 17.4% vs 5.3%. The ℇ2/ℇ2 and ℇ4/ℇ4 genotypes were not identified in any groups. Plasma CoQ_{10} concentrations were similar in patient and control groups and no differences were found even taking into account the distribution of male and female subjects in the two groups. Also, vitamin E did not provide evidence of any differences between groups and the analysis among sexes revealed that again vitamin E concentrations were similar in between subgroups. [ABSTRACT FROM AUTHOR]

Summary Background : Mesalazine (5-aminosalicylic acid, 5-ASA)-containing formulations represent a cornerstone in the treatment of inflammatory bowel diseases. Recently, a new formulation has been developed to provide selective and more homogeneous release of 5-ASA compared to traditional systems. Methods : In a first study, gastrointestinal transit was followed by gamma-scintigraphy after single-dose application of tablets containing 1200 mg mesalazine to 12 healthy male volunteers. 5-ASA release was verified by the assessment of plasma pharmacokinetics. In a second, 7-day, multiple-dose study, the steady state plasma pharmacokinetics, urinary excretion and safety profile were characterized after twice-daily tablet administration to 12 healthy volunteers. Results : Tablet erosion started after 6.9 ± 1.1 h in the ascending or transverse colon. Radioactivity spread homogeneously throughout the colon, indicating the sustained release of active 5-ASA. Plasma kinetics indicated an earlier initial absorption of 5-ASA, i.e. during transit of the small intestine and ileum. Mean C max values (350.6 ± 322.6 ng/mL) were observed during location in the ileo-caecal region. The mean relative absorption of 5-ASA was 19.9 ± 18.2% in the small intestine and ileum and 80.1 ± 18.2% in the colon. Conclusions : The administration of the new mesalazine formulation was well tolerated, and 5-ASA was continuously released along the whole colon, a favourable prerequisite for the therapy of distally located inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Purpose About 12 million people in the world live with visual impairment due to corneal diseases while there's a shortage of corneal tissue suitable for transplantation. One of the major causes of inappropriateness of corneas to be transplanted is to have a low endothelial cell density being apoptosis a key mechanism mediating cell loss. The protein Apaf‐1 is a key regulator of the mitochondrial apoptotic pathway. We have developed a family of Apaf‐1 inhibitors that have shown to be active in other apoptosis based‐pathologies. Methods We have established a corneal storage model.Corneas were preserved at 4°C for 7 days followed by a rewarming period that resembles the implant. At 4°C the endothelium was intact but not the tight junction (TJ) integrity. Throughout the rewarming, apoptosis was induced as indicated by caspase 3 activation, resulting in cell loss. Results The addition of Apaf‐1 inhibitors in the storage media reduces apoptosis activation. Caspase 3 activity was diminished; anti‐apoptotic genes were up‐regulated and pro‐apoptotic down‐regulated resulting in a reduced endothelium loss. Apaf‐1 inhibitors not only probed to be active during the rewarming period but also at 4°C: surprisingly, their presence inhibited the TJ breakdown. Integrity of TJ is known to be crucial to maintain cellular morphology and corneal transparency. Conclusion The results hereby presented demonstrate a dual role of Apaf‐1 inhibitors in preserving the cornea integrity by keeping TJ integrity and inhibiting apoptosis. The use of these inhibitors in the clinical setting could increase the availability and quality of tissue to be transplanted. Commercial interest [ABSTRACT FROM AUTHOR]

Background: Aficamten, a novel cardiac myosin inhibitor, reversibly reduces cardiac hypercontractility in obstructive hypertrophic cardiomyopathy. We present a prespecified analysis of the pharmacokinetics, pharmacodynamics, and safety of aficamten in SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM)., Methods and Results: A total of 282 patients with obstructive hypertrophic cardiomyopathy were randomized 1:1 to daily aficamten (5-20 mg) or placebo between February 1, 2022, and May 15, 2023. Aficamten dosing targeted the lowest effective dose for achieving site-interpreted Valsalva left ventricular outflow tract gradient <30 mm Hg with left ventricular ejection fraction (LVEF) ≥50%. End points were evaluated during titration (day 1 to week 8), maintenance (weeks 8-24), and washout (weeks 24-28), and included major adverse cardiac events, new-onset atrial fibrillation, implantable cardioverter-defibrillator discharges, LVEF <50%, and treatment-emergent adverse events. At week 8, 3.6%, 12.9%, 35%, and 48.6% of patients achieved 5-, 10-, 15-, and 20-mg doses, respectively. Baseline characteristics were similar across groups. Aficamten concentration increased by dose and remained stable during maintenance. During the treatment period, LVEF decreased by -0.9% (95% CI, -1.3 to -0.6) per 100 ng/mL aficamten exposure. Seven (4.9%) patients taking aficamten underwent per-protocol dose reduction for site-interpreted LVEF <50%. There were no treatment interruptions or heart failure worsening for LVEF <50%. No major adverse cardiovascular events were associated with aficamten, and treatment-emergent adverse events were similar between treatment groups, including atrial fibrillation., Conclusions: A site-based dosing algorithm targeting the lowest effective aficamten dose reduced left ventricular outflow tract gradient with a favorable safety profile throughout SEQUOIA-HCM., Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05186818.

Background: Supravalvar aortic stenosis (SVAS) is a characteristic feature of Williams-Beuren syndrome (WBS). Its severity varies: ~20% of people with Williams-Beuren syndrome have SVAS requiring surgical intervention, whereas ~35% have no appreciable SVAS. The remaining individuals have SVAS of intermediate severity. Little is known about genetic modifiers that contribute to this variability., Methods and Results: We performed genome sequencing on 473 individuals with Williams-Beuren syndrome and developed strategies for modifier discovery in this rare disease population. Approaches include extreme phenotyping and nonsynonymous variant prioritization, followed by gene set enrichment and pathway-level association tests. We next used GTEx v8 and proteomic data sets to verify expression of candidate modifiers in relevant tissues. Finally, we evaluated overlap between the genes/pathways identified here and those ascertained through larger aortic disease/trait genome-wide association studies. We show that SVAS severity in Williams-Beuren syndrome is associated with increased frequency of common and rarer variants in matrisome and immune pathways. Two implicated matrisome genes ( ACAN and LTBP4 ) were uniquely expressed in the aorta. Many genes in the identified pathways were previously reported in genome-wide association studies for aneurysm, bicuspid aortic valve, or aortic size., Conclusions: Smaller sample sizes in rare disease studies necessitate new approaches to detect modifiers. Our strategies identified variation in matrisome and immune pathways that are associated with SVAS severity. These findings suggest that, like other aortopathies, SVAS may be influenced by the balance of synthesis and degradation of matrisome proteins. Leveraging multiomic data and results from larger aorta-focused genome-wide association studies may accelerate modifier discovery for rare aortopathies like SVAS.

Background and Aims: The Marijuana Purchase Task (MPT) is increasingly used to measure cannabis reinforcing value and has potential use for cannabis etiological and regulatory research. This meta-analysis sought to evaluate for the first time the MPT's concurrent validity in relation to cannabis involvement., Methods: Electronic databases and pre-print repositories were searched for MPT studies that examined the cross-sectional relationship between frequency and quantity of cannabis use, problems, dependence, and five MPT indicators: intensity (i.e. unrestricted consumption), O max (i.e. maximum consumption), P max (i.e. price at which demand becomes elastic), breakpoint (i.e. first price at which consumption ceases), and elasticity (i.e. sensitivity to rising costs). Random effects meta-analyses of cross-sectional effect sizes were conducted, with Q tests for examining differences by cannabis variables, meta-regression to test quantitative moderators, and publication bias assessment. Moderators included sex, number of MPT prices, variable transformations, and year of publication. Populations included community and clinical samples., Results: The searches yielded 14 studies (n = 4077, median % females: 44.8%: weighted average age = 29.08 [SD = 6.82]), published between 2015 and 2022. Intensity, O max , and elasticity showed the most robust concurrent validity (|r's| = 0.147-325, ps < 0.014) with the largest significant effect sizes for quantity (|r| intensity = 0.325) and cannabis dependence (|r| O max  = 0.320, |r| intensity = 0.305, |r| elasticity = 0.303). Higher proportion of males was associated with increased estimates for elasticity-quantity and P max -problems. Higher number of MPT prices significantly altered magnitude of effects sizes for P max and problems, suggesting biased estimations if excessively low prices are considered. Methodological quality was generally good, and minimal evidence of publication bias was observed., Conclusions: The marijuana purchase task presents adequate concurrent validity to measure cannabis demand, most robustly for intensity, O max , and elasticity. Moderating effects by sex suggest potentially meaningful sex differences in the reinforcing value of cannabis., (© 2022 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Williams-Beuren syndrome is considered to be at increased risk for celiac disease, as for recent literature data and celiac disease guidelines, despite pathogenic mechanisms are still unclear. Our study analyzed the prevalence of autoimmune disorders, HLA DQ2 and/or DQ8 haplotypes, of transglutaminase antibodies and of diagnosis of celiac disease in a cohort of 93 Williams-Beuren syndrome's patients (mean age 21.26 years). Our study showed an increased prevalence of celiac disease equal to 10.8% (10/93 patients). We did not find a significant different frequency of predisposing HLA in subjects with Williams-Beuren syndrome compared to literature data in the general population (49.5% vs. 42.9%, with p > .1), nor a susceptibility to autoimmunity. This suggests that the increased prevalence of celiac disease in Williams-Beuren syndrome cannot be ascribed to HLA haplotype and may be related to other factors that still need to be identified in these patients., (© 2022 Wiley Periodicals LLC.)

Background and Aims: An early meta-analysis testing the concurrent validity of the Alcohol Purchase Task (APT), a measure of alcohol's relative reinforcing value, reported mixed associations, but predated a large number of studies. This systematic review and meta-analysis sought to: (1) estimate the relationships between trait-based alcohol demand indices from the APT and multiple alcohol indicators, (2) test several moderators and (3) analyze small study effects., Methods: A meta-analysis of 50 cross-sectional studies in four databases (n = 18 466, females = 43.32%). Sex, year of publication, number of APT prices and index transformations (logarithmic, square root or none) were considered as moderators. Small study effects were examined by using the Begg-Mazumdar, Egger's and Duval & Tweedie's trim-and-fill tests. Alcohol indicators were quantity of alcohol use, number of heavy drinking episodes, alcohol-related problems and hazardous drinking. APT indices were intensity (i.e. consumption at zero cost), elasticity (i.e. sensitivity to increases in costs), O max (i.e. maximum expenditure), P max (i.e. price associated to O max ) and breakpoint (i.e. price at which consumption ceases)., Results: All alcohol demand indices were significantly associated with all alcohol-related outcomes (r = 0.132-0.494), except P max , which was significantly associated with alcohol-related problems only (r = 0.064) . The greatest associations were evinced between intensity in relation to alcohol use, hazardous drinking and heavy drinking and between O max and alcohol use. All the tested moderators emerged as significant moderators. Evidence of small-study effects was limited., Conclusions: The Alcohol Purchase Task appears to have concurrent validity in alcohol research. Intensity and O max are the most relevant indices to account for alcohol involvement., (© 2020 Society for the Study of Addiction.)

Background and Objectives: There may be substantial overlap in the risk factors for substance use and substance use disorders (SUD). Identifying risk factors for substance use initiation is essential for understanding the etiology and natural history of SUD and to develop empirically-based preventive interventions to reduce initiation., Methods: Analyses were done on Wave 1 participants of the National Epidemiological Survey of Alcohol and Related Conditions (NESARC) (n = 43,093). Estimates of the cumulative probability of substance use initiation were obtained separately for nicotine, alcohol, cannabis, and cocaine. Survival analyses with time-varying covariates were implemented to identify risk factors for substance initiation., Results: The lifetime cumulative probabilities of substance initiation were 45.5% for nicotine, 82% for alcohol, 19.6% for cannabis, and 6.4% for cocaine. Among respondents with lifetime nicotine use, 50% had used it by age 15.3, whereas for alcohol, cannabis, and cocaine the respective ages were 17.8, 16.6, and 19.8. Previous use of another substance, being male, having a cluster B personality disorder, family history of SUD, and being separated, divorced, or widowed increased the risk of use of all the substances assessed, whereas social anxiety disorder and some personality disorders were associated with specific substances., Discussion and Conclusions: Although the age of substance use initiation varies by substance, in more than 50% of cases initiation of use occurs in the first two decades of life. Although most risk factors for substance use initiation are common across substances, some are substance-specific., Scientific Significance: This information may help in the development of empirically-based preventive interventions. (Am J Addict 2018;27:477-484)., (© 2018 American Academy of Addiction Psychiatry.)

The 1.8 Å resolution crystal structure of a conserved domain of the potential Burkholderia pseudomallei antigen and trimeric autotransporter BPSL2063 is presented as a structural vaccinology target for melioidosis vaccine development. Since BPSL2063 (1090 amino acids) hosts only one conserved domain, and the expression/purification of the full-length protein proved to be problematic, a domain-filtering library was generated using β-lactamase as a reporter gene to select further BPSL2063 domains. As a result, two domains (D1 and D2) were identified and produced in soluble form in Escherichia coli. Furthermore, as a general tool, a genomic open reading frame-filtering library from the B. pseudomallei genome was also constructed to facilitate the selection of domain boundaries from the entire ORFeome. Such an approach allowed the selection of three potential protein antigens that were also produced in soluble form. The results imply the further development of ORF-filtering methods as a tool in protein-based research to improve the selection and production of soluble proteins or domains for downstream applications such as X-ray crystallography.

Background: An extensive clinical literature has noted gender differences in the etiology and clinical characteristics of individuals with alcohol dependence (AD). Despite this knowledge, many important questions remain., Methods: Using the 2001 to 2002 National Epidemiologic Survey on Alcohol and Related Conditions (n = 43,093), we examined differences in sociodemographic characteristics, psychiatric and medical comorbidities, clinical correlates, risk factors, and treatment-utilization patterns of men (N = 2,974) and women (N = 1,807) with lifetime AD., Results: Men with lifetime AD were more likely than women to be diagnosed with any substance use disorder and antisocial personality disorder, whereas women were more likely to have mood and anxiety disorders. After adjusting for sociodemographic characteristics and gender differences in psychiatric comorbidity in the general population, AD was associated with externalizing disorders and any mood disorder among women only. Men with AD met more criteria, had longer episodes, and were younger at the age of first drink. There were no gender differences in remission rates. Women with AD were more likely to have a family and a spouse with history of alcohol use disorders. Treatment rates were low for both genders, and women were more likely to report social stigmatization as a treatment barrier., Conclusions: There are important gender differences in the psychiatric comorbidities, risk factors, clinical characteristics, and treatment-utilization patterns among individuals with lifetime AD., (Copyright © 2013 by the Research Society on Alcoholism.)

Introduction and Aims: The development and dissemination of effective treatments for cocaine dependence is an important public health priority in Europe, and especially in Spain, given the increase in treatment demand over recent years. The aim of this study was to determine the effectiveness of the Community Reinforcement Approach (CRA) for cocaine dependents at an outpatient clinic within the Spanish public health system., Design and Methods: A total of 82 cocaine-dependent patients were randomly assigned to one of two treatment conditions: Standard Treatment (n = 35) or CRA (n = 47). Dependent variables were treatment retention, cocaine abstinence and composite scores from the European version of the Addiction Severity Index at 12 month follow up., Results: Of the patients who received CRA, 55% completed 6 months of treatment, versus 40% who received Standard Treatment. At the 12 month follow up, patients assigned to the CRA condition achieved higher rates of abstinence (95.2%) by comparison with Standard Treatment (69.2%). In the CRA group, 27% of the patients achieved continuous cocaine abstinence, versus 21% in the Standard Treatment group. The CRA group also obtained lower scores than the Standard Treatment group in all Addiction Severity Index composite scores., Discussion and Conclusions: This study showed that CRA is a feasible treatment for cocaine addiction in a public community setting in Spain., (© 2010 Australasian Professional Society on Alcohol and other Drugs.)

This study compares the efficacy of the Community Reinforcement Approach (CRA) with and without an incentive program for cocaine-dependent patients in Spain. A total of 58 patients were randomly assigned to the CRA or CRA plus vouchers condition. In the CRA plus vouchers group, mean percentage of cocaine-negative samples was 97.07%, versus 79.76% in the no-voucher group. Those treated in the CRA plus vouchers condition also achieved greater improvements in psychosocial functioning than those treated in the CRA condition. The present results show that treatment outcome is better if incentives are delivered contingent upon the submission of cocaine-free urine specimens. , (© American Academy of Addiction Psychiatry.)

This study analyzed the viability of financing a voucher program for cocaine addicts in Spain through public and private donations. Of the 136 companies contacted, 52 (38%) provided donations. The difference between the benefits (15,670 Euro/ $20,371) and the costs (3734 Euro/ $4854) was 11,936 Euro/ $15,517. The type of reinforcer a company can offer, the size of the company, and the time elapsed before responding may be determining variables in a company's decision whether to collaborate.

Low participation rates constitute a serious problem faced by family drug abuse prevention programs. In this study we analyse the factors related to participation in a Life Skills Training program implemented in three schools in Spain. Participants in the study were 485 pupils aged 12 - 14 years and their respective parents. The variables that predicted participation in the program were: number of children and educational level of parents, children's drug use, family conflict, parental rearing style, relationships between parents and children and family communication. The results from Spain are similar to those found in international studies, and indicate that the families most at risk of drug use are those least likely to participate in prevention programs. There is a need for strategies to increase participation in prevention programs of the families most at risk.