Transitioning illicit drug preferences and emerging user identities in Ohio: The proliferation of methamphetamine use among African Americans

Understanding the social dynamics of local methamphetamine markets is critical to improving community health and reducing social costs associated with illicit drug use. We examine a local drug market in Summit County, Ohio, wherein methamphetamine users ascribe themselves different ethnic identities from those long associated with the drug elsewhere in the United States. Qualitative interviews with 52 study participants demonstrate that very poor and homeless White males and females are now using methamphetamine; however, even more surprising is that 31 of the participants identified themselves as poor or homeless, male or female African, Native, biracial, or multiracial Americans. The drug use trajectory of these 31 participants in particular involved a transition from a historical preference for crack to a present one for methamphetamine and, in some cases, a preference for concurrent use of methamphetamine and heroin. Many of these methamphetamine users also emphasized their ethnic identity to distinguish themselves as nonproducers of methamphetamine in comparison to Whites, who are commonly associated with methamphetamine production. Findings appear to suggest an emergent means of identity management resulting from the ethnic diversity of users in this methamphetamine market. These findings may have relevance in other communities with similar demographics and drug markets and may hold important implications for drug treatment, policy-making, and law enforcement professionals’ work associated with methamphetamine users, producers, and distributors.     

Thromboembolism in infants and children with gastrointestinal failure receiving long-term parenteral nutrition

Thromboembolism is an established complication of long-term parenteral nutrition (PN) administration which requires central venous lines in the pediatric population. Predisposing factors that increase the risk of thrombosis, as well as prophylaxis and treatment guidelines in this specific population, are not clearly defined. We performed a computerized search of PubMed, OVID databases, and pertinent articles from reference lists of related review papers. This review summarizes currently available data on the rates of thromboembolism in the pediatric population receiving long-term PN and concludes that control of factors such as location of catheter, duration of nutrition support, and prophylaxis with heparin or anticoagulants may reduce the rates of thrombosis in this patient population, although most data on the matter are inconclusive.     

Hematometrocolpos in an adolescent female treated for pelvic Ewing sarcoma

Radiation therapy is often used to achieve local control of pelvic Ewing sarcoma in children. The effects of radiation on the female reproductive tract have been well documented in adults with gynecological malignancies, but the long-term consequences of pelvic radiation in pre-pubertal or adolescent girls are not as well described. We report a case of hematometrocolpos developing in an adolescent previously treated with chemotherapy and radiation therapy for pelvic Ewing sarcoma. We describe the clinical presentation, radiographic features, gross pathology, treatment strategies, outcome, as well as putative predisposing factors and preventative interventions.     

Novel mechanism for the generation of human xeno-autoantibodies against the nonhuman sialic acid N-glycolylneuraminic acid

The nonhuman sialic acid N-glycolylneuraminic acid (Neu5Gc) is metabolically incorporated into human tissues from certain mammalian-derived foods, and this occurs in the face of an anti-Neu5Gc “xeno-autoantibody” response. Given evidence that this process contributes to chronic inflammation in some diseases, it is important to understand when and how these antibodies are generated in humans. We show here that human anti-Neu5Gc antibodies appear during infancy and correlate with weaning and exposure to dietary Neu5Gc. However, dietary Neu5Gc alone cannot elicit anti-Neu5Gc antibodies in mice with a humanlike Neu5Gc deficiency. Other postnatally appearing anti-carbohydrate antibodies are likely induced by bacteria expressing these epitopes; however, no microbe is known to synthesize Neu5Gc. Here, we show that trace exogenous Neu5Gc can be incorporated into cell surface lipooligosaccharides (LOS) of nontypeable Haemophilus influenzae (NTHi), a human-specific commensal/pathogen. Indeed, infant anti-Neu5Gc antibodies appear coincident with antibodies against NTHi. Furthermore, NTHi that express Neu5Gc-containing LOS induce anti-Neu5Gc antibodies in Neu5Gc-deficient mice, without added adjuvant. Finally, Neu5Gc from baby food is taken up and expressed by NTHi. As the flora residing in the nasopharynx of infants can be in contact with ingested food, we propose a novel model for how NTHi and dietary Neu5Gc cooperate to generate anti-Neu5Gc antibodies in humans.Sialic acids (Sias) are monosaccharides with a shared 9-carbon backbone, typically found at the terminal ends of vertebrate cell surface and secreted glycoconjugates (Schauer, 1982; Varki, 1992; Traving and Schauer, 1998; Angata and Varki, 2002; Chen and Varki, 2010). Most mammals express two common Sias, N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc). However, humans are deficient in Neu5Gc synthesis because of a human-specific mutation inactivating the CMAH gene responsible for converting CMP-Neu5Ac to CMP-Neu5Gc (Chou et al., 1998; Irie et al., 1998). All human adults have varying levels of circulating IgM, IgG, and IgA antibodies against Neu5Gc (Zhu and Hurst, 2002; Tangvoranuntakul et al., 2003; Nguyen et al., 2005; Padler-Karavani et al., 2008; Tahara et al., 2010). At the same time, dietary Neu5Gc from foods such as red meat or milk products can be metabolically incorporated into human tissues, particularly epithelia and endothelia (Tangvoranuntakul et al., 2003; Hedlund et al., 2007; Hedlund et al., 2008), through a mechanism involving macropinocytosis and delivery of free Neu5Gc to the cytosol via a lysosomal transporter (Bardor et al., 2005; Yin et al., 2006). Evidently, although the human immune system can react to this xeno-antigen, human biochemical pathways do not see it as foreign. Thus, anti-Neu5Gc antibodies represent novel “xeno-autoantibodies,” which recognize a “non-self” animal-derived antigen in the context of “self.” Indeed, we have recently demonstrated that human anti-Neu5Gc antibodies interact with metabolically incorporated Neu5Gc to promote chronic inflammation, likely contributing to tumor progression (Hedlund et al., 2008) and vascular inflammation (Pham et al., 2009).Given their potential contribution to the pathogenesis of dietary red meat–associated diseases, it is important to understand when and how anti-Neu5Gc antibodies emerge in humans. Here, we show that these antibodies emerge post-natally in humans during the first year of life. Other post-natally acquired human antibodies against foreign glycans, e.g., blood group antibodies and anti–α-Gal antibodies, are thought to be induced by commensal bacteria expressing these epitopes (Springer and Horton, 1969; Galili et al., 1988). However, although many bacteria can synthesize and express Neu5Ac (Vimr and Lichtensteiger, 2002; Vimr et al., 2004), none are known to synthesize Neu5Gc. Here, we demonstrate that dietary Neu5Gc can be incorporated by a common human commensal bacterium, providing a mechanism for generating anti-Neu5Gc antibodies during the first year of life. To our knowledge, this is the first example in which a diet-derived molecule is scavenged by resident bacteria from within the host and effectively expressed as an immunogenic antigen.