Considerations for Studying Sex as a Biological Variable in Spinal Cord Injury

In response to NIH initiatives to investigate sex as a biological variable in preclinical animal studies, researchers have increased their focus on male and female differences in neurotrauma. Inclusion of both sexes when modeling neurotrauma is leading to the identification of novel areas for therapeutic and scientific exploitation. Here, we review the organizational and activational effects of sex hormones on recovery from injury and how these changes impact the long-term health of spinal cord injury (SCI) patients. When determining how sex affects SCI it remains imperative to expand outcomes beyond locomotor recovery and consider other complications plaguing the quality of life of patients with SCI. Interestingly, the SCI field predominately utilizes female rodents for basic science research which contrasts most other male-biased research fields. We discuss the unique caveats this creates to the translatability of preclinical research in the SCI field. We also review current clinical and preclinical data examining sex as biological variable in SCI. Further, we report how technical considerations such as housing, size, care management, and age, confound the interpretation of sex-specific effects in animal studies of SCI. We have uncovered novel findings regarding how age differentially affects mortality and injury-induced anemia in males and females after SCI, and further identified estrus cycle dysfunction in mice after injury. Emerging concepts underlying sexually dimorphic responses to therapy are also discussed. Through a combination of literature review and primary research observations we present a practical guide for considering and incorporating sex as biological variable in preclinical neurotrauma studies

A comparison of the hypoglycemic effect of insulin with systemic venous and portal venous administration

The hyperglycemic effect of insulin by prolonged intraportal and systemic infusion was measured in unanesthetized dogs with a modified portacaval transposition. There was no significant difference in response with the two routes of administration. The relation of these results to research directed to surgical therapy of diabetes is discussed. © 1963 W. B. Saunders Company

Development and validation of new disease-specific measures of somatization and comorbidity in IBS

To create and validate empirically derived questionnaires that measure non-gastrointestinal symptoms and disorders that co-exist with irritable bowel syndrome (IBS)

Socioecological Factors Related to Hazardous Alcohol use among Female Sex Workers in Lilongwe, Malawi: A Mixed Methods Study

Background: Alcohol use is pervasive among female sex workers (FSW) placing them at increased risk of violence and sexual risk behaviors. FSW often live and work where alcohol is highly normative. Objective: To understand the socioecological influences on hazardous alcohol use among FSW in Malawi. Methods: In 2014, 200 FSW identified through venue-based sampling in Lilongwe, Malawi, completed a quantitative behavioral survey, with a sub-sample participating in qualitative interviews. Multivariable log-binomial regression was used to identify associations between hazardous alcohol use (AUDIT score ≥ 7) and time in sex work, clients per week, unprotected sex, alcohol use with clients, and living environment. Qualitative interviews enhanced findings from quantitative data and identify emergent themes around socioecological influences on alcohol use. Results: Over 50% reported hazardous alcohol use and lived in an alcohol-serving venue. Hazardous alcohol use was associated with sex work duration of ≥2 years (aPR: 1.30; 95%CI: 1.02,1.65) and alcohol use at last sex with a client (aPR: 1.29; 95%CI: 1.06,1.57). FSW perceived alcohol as a facilitator for sex work by reducing inhibitions and attracting clients, but acknowledged alcohol leads to violence and/or unprotected sex. Despite these risks and a motivation to reduce use, FSW feared that refusing to drink would be tantamount to turning away clients. Conclusions: Although FSW recognized alcohol-related risks, the norms and power dynamics of sex work perpetuated hazardous alcohol use. Multilevel interventions are needed to collectively change norms around drinking and sex work that will enable FSW to reduce alcohol consumption when engaging in their work

Centerscope

Centerscope, formerly Scope, was published by the Boston University Medical Center "to communicate the concern of the Medical Center for the development and maintenance of improved health care in contemporary society.

Social Networking Technology, Social Network Composition, and Reductions in Substance Use Among Homeless Adolescents

Peer-based prevention programs for homeless youth are complicated by the potential for reinforcing high-risk behaviors among participants. The goal of this study is to understand how homeless youth could be linked to positive peers in prevention programming by understanding where in social and physical space positive peers for homeless youth are located, how these ties are associated with substance use, and the role of social networking technologies (e.g., internet and cell phones) in this process. Personal social network data were collected from 136 homeless adolescents in Los Angeles, CA. Respondents reported on composition of their social networks with respect to: home-based peers and parents (accessed via social networking technology; e.g., the internet, cell phone, texting), homeless peers and agency staff (accessed face-to-face) and whether or not network members were substance-using or non-substance-using. Associations between respondent’s lifetime cocaine, heroin, and methamphetamine use and recent (previous 30 days) alcohol and marijuana use were assessed by the number of non-substance-using versus substance-using ties in multivariate linear regression models. 43% of adolescents reported a non-substance-using home-based tie. More of these ties were associated with less recent alcohol use. 62% of adolescents reported a substance-using homeless tie. More of these ties were associated with more recent marijuana use as well as more lifetime heroin and methamphetamine use. For homeless youth, who are physically disconnected from positive peers, social networking technologies can be used to facilitate the sorts of positive social ties that effective peer-based prevention programs require

Design, synthesis and antibacterial properties of pyrimido[4,5-b]indol-8-amine inhibitors of DNA gyrase

According to the World Health Organization (WHO), approximately 1.7 million deaths per year are caused by tuberculosis infections. Furthermore, it has been predicted that, by 2050, antibacterial resistance will be the cause of approximately 10 million deaths annually if the issue is not tackled. As a result, novel approaches to treating broad-spectrum bacterial infections are of vital importance. During the course of our wider efforts to discover unique methods of targeting multidrug-resistant (MDR) pathogens, we identified a novel series of amide-linked pyrimido[4,5-b]indol-8-amine inhibitors of bacterial type II topoisomerases. Compounds from the series were highly potent against gram-positive bacteria and mycobacteria, with excellent potency being retained against a panel of relevant Mycobacterium tuberculosis drug-resistant clinical isolates

Using Genomic Sequencing for Classical Genetics in E. coli K12

We here develop computational methods to facilitate use of 454 whole genome shotgun sequencing to identify mutations in Escherichia coli K12. We had Roche sequence eight related strains derived as spontaneous mutants in a background without a whole genome sequence. They provided difference tables based on assembling each genome to reference strain E. coli MG1655 (NC_000913). Due to the evolutionary distance to MG1655, these contained a large number of both false negatives and positives. By manual analysis of the dataset, we detected all the known mutations (24 at nine locations) and identified and genetically confirmed new mutations necessary and sufficient for the phenotypes we had selected in four strains. We then had Roche assemble contigs de novo, which we further assembled to full-length pseudomolecules based on synteny with MG1655. This hybrid method facilitated detection of insertion mutations and allowed annotation from MG1655. After removing one genome with less than the optimal 20- to 30-fold sequence coverage, we identified 544 putative polymorphisms that included all of the known and selected mutations apart from insertions. Finally, we detected seven new mutations in a total of only 41 candidates by comparing single genomes to composite data for the remaining six and using a ranking system to penalize homopolymer sequencing and misassembly errors. An additional benefit of the analysis is a table of differences between MG1655 and a physiologically robust E. coli wild-type strain NCM3722. Both projects were greatly facilitated by use of comparative genomics tools in the CoGe software package (http://genomevolution.org/)

Regulation of skeletal muscle oxidative capacity and insulin signaling by the Mitochondrial Rhomboid Protease PARL

Type 2 diabetes mellitus (T2DM) and aging are characterized by insulin resistance and impaired mitochondrial energetics. In lower organisms, remodeling by the protease pcp1 (PARL ortholog) maintains the function and lifecycle of mitochondria. We examined whether variation in PARL protein content is associated with mitochondrial abnormalities and insulin resistance. PARL mRNA and mitochondrial mass were both reduced in elderly subjects and in subjects with T2DM. Muscle knockdown of PARL in mice resulted in malformed mitochondrial cristae, lower mitochondrial content, decreased PGC1&alpha; protein levels, and impaired insulin signaling. Suppression of PARL protein in healthy myotubes lowered mitochondrial mass and insulin-stimulated glycogen synthesis and increased reactive oxygen species production. We propose that lower PARL expression may contribute to the mitochondrial abnormalities seen in aging and T2DM.<br /