Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case-control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 x 10(-13)) and African ancestries (rs2066702; P = 2.2 x 10(-9)). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit-hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.Peer reviewe

Cefazolin potency against methicillin-resistant Staphylococcus aureus: a microbiologic assessment in support of a novel drug delivery system for skin and skin structure infections

David P Nicolau,1 Barry N Silberg2 1Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA; 2Department of Surgery, Sonoma West Medical Center, Sebastopol, CT, USA Introduction: Despite aggressive medical and surgical management, the resolution of skin and skin structure infections is often difficult due to insufficient host response, reduced drug penetration, and a high prevalence of resistance organisms such as methicillin-resistant Staphylococcus aureus (MRSA). As a result of these factors, conventional management often consists of prolonged broad-spectrum systemic antimicrobials. An alternative therapy in development, ultrasonic drug dispersion (UDD), uses a subcutaneous injection followed by external transcutaneous ultrasound to deliver high tissue concentrations of cefazolin with limited systemic exposure. While it is postulated that these high concentrations may be suitable to treat more resistant organisms such as MRSA, the cefazolin minimum inhibitory concentration (MIC) distribution for this organism is currently unknown. Materials and methods: We assessed the potency of cefazolin against a collection of 1,239 MRSA from 42 US hospitals using Clinical Laboratory Standard Institute-defined broth microdilution methodology. Results: The cefazolin MIC inhibiting 50% of the isolates was 64 mg/L; 81% had MICs ≤128 and nearly all (99.9%) had MICs ≤512 mg/L. Conclusion: The overwhelming majority of MRSA had cefazolin MICs that were considerably lower than achievable tissue concentrations (≥1,000 mg/L) using this novel drug delivery system. While the currently defined cefazolin MRSA phenotypic profile precludes the use of parenteral administration, techniques that deliver local exposures in excess of these inhibitory concentrations may provide a novel treatment strategy for skin and skin structure infections. Keywords: methicillin-resistant, Staphylococcus aureus, ultrasonic, infection, cefazoli

Cefazolin potency against methicillin-resistant Staphylococcus aureus: a microbiologic assessment in support of a novel drug delivery system for skin and skin structure infections [Erratum]

Nicolau DP, Silberg BN. Infect Drug Resist. 2017;10:227–230.Page 227, affiliations list, the text “Department of Surgery, Sonoma West Medical Center, Sebastopol, CT, USA” should read “Department of Surgery, Sonoma West Medical Center, Sebastopol, CA, USA”. Read the original articl

Raised by depressed parents: is it an environmental risk?

The mechanisms explaining how parental depression compromises healthy child development are complex and multifaceted, with genetic and environmental pathways intertwined. Reexamination of whether and how maternal and paternal depression serve as environmental risk factors is important because such an investigation can be helpful to identify modifiable mechanisms that are accessible to interventions. We review studies that have employed designs that isolate the effects of the environment from genetic influences, including adoption studies and children of twins studies. Findings indicate that maternal depression is an environmental risk factor for the emotional, behavioral, and neurobiological development of children. Although more studies are needed, preliminary findings suggest that paternal depression appears to be a weaker environmental risk as compared to maternal depression, at least during infancy and toddlerhood. Implications for theory and future research are discussed. © 2014, Springer Science+Business Media New York