Co-occurrences of substance use and other potentially addictive behaviors: epidemiological results from the Psychological and Genetic Factors of the Addictive Behaviors (PGA) Study

Background and aims: Changes in the nomenclature of addictions suggest a significant shift in the conceptualization of addictions, where non-substance related behaviors can also be classified as addictions. A large amount of data provides empirical evidence that there are overlaps of different types of addictive behaviors in etiology, phenomenology, and in the underlying psychological and biological mechanisms. Our aim was to investigate the co-occurrences of a wide range of substance use and behavioral addictions. Methods: The present epidemiological analysis was carried out as part of the Psychological and Genetic Factors of the Addictive Behaviors (PGA) Study, where data were collected from 3,003 adolescents and young adults (42.6% males; mean age 21 years). Addictions to psychoactive substances and behaviors were rigorously assessed. Results: Data is provided on lifetime occurrences of the assessed substance uses, their co-occurrences, the prevalence estimates of specific behavioral addictions , and co-occurrences of different substance use and potentially addictive behaviors. Associations were found between (i) smoking and problematic Internet use, exercising, eating disorders, and gambling (ii) alcohol consumption and problematic Internet use, problematic online gaming, gambling, and eating disorders, and (iii) cannabis use and problematic online gaming and gambling. Conclusions: The results suggest a large overlap between the occurrence of these addictions and behaviors and underlies the importance of investigating the possible common psychological, genetic and neural pathways. These data further support concepts such as the Reward Deficiency Syndrome and the component model of addictions that propose a common phenomenological and etiological background of different addictive and related behaviors

Metabolic stress-induced microRNA and mRNA expression profiles of human fibroblasts

Metabolic and oxidative stresses induce physiological adaptation processes, disrupting a finely tuned, coordinated network of gene expression. To better understand the interplay between the mRNA and miRNA transcriptomes, we examined how two distinct metabolic stressors alter the expression profile of human dermal fibroblasts.Primary fibroblast cultures were obtained from skin biopsies of 17 healthy subjects. Metabolic stress was evoked by growing subcultured cells in glucose deprived, galactose enriched (GAL) or lipid reduced, cholesterol deficient (RL) media, and compared to parallel-cultured fibroblasts grown in standard (STD) medium. This was followed by mRNA expression profiling and assessment of >1000 miRNAs levels across all three conditions. The miRNA expression levels were subsequently correlated to the mRNA expression profile.Metabolic stress by RL and GAL both produced significant, strongly correlated mRNA/miRNA changes. At the single gene level four miRNAs (miR-129-3p, miR-146b-5p, miR-543 and miR-550a) showed significant and comparable expression changes in both experimental conditions. These miRNAs appeared to have a significant physiological effect on the transcriptome, as nearly 10% of the predicted targets reported changes at mRNA level. The two distinct metabolic stressors induced comparable changes in the miRNome profile, suggesting a common defensive response of the fibroblasts to altered homeostasis. The differentially expressed miR-129-3p, miR-146b-5p, miR-543 and miR-550a regulated multiple genes (e.g. NGEF, NOVA1, PDE5A) with region- and age-specific transcription in the human brain, suggesting that deregulation of these miRNAs might have significant consequences on CNS function. The overall findings suggest that analysis of stress-induced responses of peripheral fibroblasts, obtained from patients with psychiatric disorders is a promising avenue for future research endeavors. © 2013 Elsevier Inc

FOXN3 and GDNF polymorphisms as common genetic factors of substance use and addictive behaviors

Epidemiological and phenomenological studies suggest shared underpinnings between multiple addictive behaviors. The present genetic association study was conducted as part of the Psychological and Genetic Factors of Addictions study (n = 3003) and aimed to investigate genetic overlaps between different substance use, addictive, and other compulsive behaviors. Association analyses targeted 32 single-nucleotide polymorphisms, potentially addictive substances (alcohol, tobacco, cannabis, and other drugs), and potentially addictive or compulsive behaviors (internet use, gaming, social networking site use, gambling, exercise, hair-pulling, and eating). Analyses revealed 29 nominally significant associations, from which, nine survived an FDRbl correction. Four associations were observed between FOXN3 rs759364 and potentially addictive behaviors: rs759364 showed an association with the frequency of alcohol consumption and mean scores of scales assessing internet addiction, gaming disorder, and exercise addiction. Significant associations were found between GDNF rs1549250, rs2973033, CNR1 rs806380, DRD2/ANKK1 rs1800497 variants, and the “lifetime other drugs” variable. These suggested that genetic factors may contribute similarly to specific substance use and addictive behaviors. Specifically, FOXN3 rs759364 and GDNF rs1549250 and rs2973033 may constitute genetic risk factors for multiple addictive behaviors. Due to limitations (e.g., convenience sampling, lack of structured scales for substance use), further studies are needed. Functional correlates and mechanisms underlying these relationships should also be investigated

Association between Age and the 7 Repeat Allele of the Dopamine D4 Receptor Gene

Longevity is in part (25%) inherited, and genetic studies aim to uncover allelic variants that play an important role in prolonging life span. Results to date confirm only a few gene variants associated with longevity, while others show inconsistent results. However, GWAS studies concentrate on single nucleotide polymorphisms, and there are only a handful of studies investigating variable number of tandem repeat variations related to longevity. Recently, Grady and colleagues (2013) reported a remarkable (66%) accumulation of those carrying the 7 repeat allele of the dopamine D4 receptor gene in a large population of 90-109 years old Californian centenarians, as compared to an ancestry-matched young population. In the present study we demonstrate the same association using continuous age groups in an 18-97 years old Caucasian sample (N = 1801, p = 0.007). We found a continuous pattern of increase from 18-75, however frequency of allele 7 carriers decreased in our oldest age groups. Possible role of gene-environment interaction effects driven by historical events are discussed. In accordance with previous findings, we observed association preferentially in females (p = 0.003). Our results underlie the importance of investigating non-disease related genetic variants as inherited components of longevity, and confirm, that the 7-repeat allele of the dopamine D4 receptor gene is a longevity enabling genetic factor, accumulating in the elderly female population

Patients with an Open Abdomen in Asian, American and European Continents: A Comparative Analysis from the International Register of Open Abdomen (IROA)

Background: International register of open abdomen (IROA) enrolls patients from several centers in American, European, and Asiatic continent. The aim of our study is to compare the characteristics, management and clinical outcome of adult patients treated with OA in the three continents. Material and methods: A prospective analysis of adult patients enrolled in the international register of open abdomen (IROA). Trial registration: NCT02382770. Results: 1183 patients were enrolled from American, European and Asiatic Continent. Median age was 63 years (IQR 49–74) and was higher in the European continent (65 years, p < 0.001); 57% were male. The main indication for OA was peritonitis (50.6%) followed by trauma (15.4%) and vascular emergency (13.5%) with differences among the continents (p < 0.001). Commercial NPWT was preferred in America and Europe (77.4% and 52.3% of cases) while Barker vacuum pack (48.2%) was the preferred temporary abdominal closure technique in Asia (p < 0.001). Definitive abdominal closure was achieved in 82.3% of cases in America (fascial closure in 90.2% of cases) and in 56.4% of cases in Asia (p < 0.001). Prosthesis were mostly used in Europe (17.3%, p < 0.001). The overall entero-atmospheric fistula rate 2.5%. Median open abdomen duration was 4 days (IQR 2–7). The overall intensive care unit and hospital length-of-stay were, respectively, 8 and 11 days (no differences between continents). The overall morbidity and mortality rates for America, Europe, and Asia were, respectively, 75.8%, 75.3%, 91.8% (p = 0.001) and 31.9%, 51.6%, 56.9% (p < 0.001). Conclusion: There is no uniformity in OA management in the different continents. Heterogeneous adherence to international guidelines application is evident. Different temporary abdominal closure techniques in relation to indications led to different outcomes across the continents. Adherence to guidelines, combined with more consistent data, will ultimately allow to improving knowledge and outcome

A proposal for a CT driven classification of left colon acute diverticulitis

Computed tomography (CT) imaging is the most appropriate diagnostic tool to confirm suspected left colonic diverticulitis. However, the utility of CT imaging goes beyond accurate diagnosis of diverticulitis; the grade of severity on CT imaging may drive treatment planning of patients presenting with acute diverticulitis. The appropriate management of left colon acute diverticulitis remains still debated because of the vast spectrum of clinical presentations and different approaches to treatment proposed. The authors present a new simple classification system based on both CT scan results driving decisions making management of acute diverticulitis that may be universally accepted for day to day practice

Novel Textbook Outcomes following emergency laparotomy:Delphi exercise

Background: Textbook outcomes are composite outcome measures that reflect the ideal overall experience for patients. There are many of these in the elective surgery literature but no textbook outcomes have been proposed for patients following emergency laparotomy. The aim was to achieve international consensus amongst experts and patients for the best Textbook Outcomes for non-trauma and trauma emergency laparotomy. Methods: A modified Delphi exercise was undertaken with three planned rounds to achieve consensus regarding the best Textbook Outcomes based on the category, number and importance (Likert scale of 1–5) of individual outcome measures. There were separate questions for non-trauma and trauma. A patient engagement exercise was undertaken after round 2 to inform the final round. Results: A total of 337 participants from 53 countries participated in all three rounds of the exercise. The final Textbook Outcomes were divided into ‘early’ and ‘longer-term’. For non-trauma patients the proposed early Textbook Outcome was ‘Discharged from hospital without serious postoperative complications (Clavien–Dindo ≥ grade III; including intra-abdominal sepsis, organ failure, unplanned re-operation or death). For trauma patients it was ‘Discharged from hospital without unexpected transfusion after haemostasis, and no serious postoperative complications (adapted Clavien–Dindo for trauma ≥ grade III; including intra-abdominal sepsis, organ failure, unplanned re-operation on or death)’. The longer-term Textbook Outcome for both non-trauma and trauma was ‘Achieved the early Textbook Outcome, and restoration of baseline quality of life at 1 year’. Conclusion: Early and longer-term Textbook Outcomes have been agreed by an international consensus of experts for non-trauma and trauma emergency laparotomy. These now require clinical validation with patient data.</p

Knowledge, awareness, and attitude towards infection prevention and management among surgeons: identifying the surgeon champion

Abstract Despite evidence supporting the effectiveness of best practices of infection prevention and management, many surgeons worldwide fail to implement them. Evidence-based practices tend to be underused in routine practice. Surgeons with knowledge in surgical infections should provide feedback to prescribers and integrate best practices among surgeons and implement changes within their team. Identifying a local opinion leader to serve as a champion within the surgical department may be important. The “surgeon champion” can integrate best clinical practices of infection prevention and management, drive behavior change in their colleagues, and interact with both infection control teams in promoting antimicrobial stewardship.https://deepblue.lib.umich.edu/bitstream/2027.42/145433/1/13017_2018_Article_198.pd

Multivariate Analysis of Dopaminergic Gene Variants as Risk Factors of Heroin Dependence

BACKGROUND: Heroin dependence is a debilitating psychiatric disorder with complex inheritance. Since the dopaminergic system has a key role in rewarding mechanism of the brain, which is directly or indirectly targeted by most drugs of abuse, we focus on the effects and interactions among dopaminergic gene variants. OBJECTIVE: To study the potential association between allelic variants of dopamine D2 receptor (DRD2), ANKK1 (ankyrin repeat and kinase domain containing 1), dopamine D4 receptor (DRD4), catechol-O-methyl transferase (COMT) and dopamine transporter (SLC6A3) genes and heroin dependence in Hungarian patients. METHODS: 303 heroin dependent subjects and 555 healthy controls were genotyped for 7 single nucleotide polymorphisms (SNPs) rs4680 of the COMT gene; rs1079597 and rs1800498 of the DRD2 gene; rs1800497 of the ANKK1 gene; rs1800955, rs936462 and rs747302 of the DRD4 gene. Four variable number of tandem repeats (VNTRs) were also genotyped: 120 bp duplication and 48 bp VNTR in exon 3 of DRD4 and 40 bp VNTR and intron 8 VNTR of SLC6A3. We also perform a multivariate analysis of associations using Bayesian networks in Bayesian multilevel analysis (BN-BMLA). FINDINGS AND CONCLUSIONS: In single marker analysis the TaqIA (rs1800497) and TaqIB (rs1079597) variants were associated with heroin dependence. Moreover, -521 C/T SNP (rs1800955) of the DRD4 gene showed nominal association with a possible protective effect of the C allele. After applying the Bonferroni correction TaqIB was still significant suggesting that the minor (A) allele of the TaqIB SNP is a risk component in the genetic background of heroin dependence. The findings of the additional multiple marker analysis are consistent with the results of the single marker analysis, but this method was able to reveal an indirect effect of a promoter polymorphism (rs936462) of the DRD4 gene and this effect is mediated through the -521 C/T (rs1800955) polymorphism in the promoter