Characteristics of Hidden Status Among Users of Crack, Powder Cocaine, and Heroin in Central Harlem

This article analyzes hidden status among crack, powder cocaine, and heroin users and setters, in contrast to more accessible users/sellers. Several sampling strategies acquired 657 users (N=559) and sellers (N=98). Indicators of hidden status were those who (1) paid rent in full in the last 30 days, (2) used nonstreet drug procurement. (3) had legal jobs, and (4) earned $1,000 or more in legal income in the last 30 days. Nearly half had at least one indicator: approximately 16% of users/sellers had two to four indicators. In logistic regression analyses, those who had not panhandled in the last 30 days, those who had used powder cocaine in the last 30 days, and those never arrested were the most likely to have hidden status, whether the analysis predicted those having any indicators or those having two to four indicators. The four indicators begin to operationally define hidden status among users of cocaine and heroin.     

Education review: Crossing borders--delivering health information management education across state lines

Since its inception in 1992, the associate degree program in health information management (HIM) of the University of Alaska Southeast has been distance delivered across the state; it was the first distance degree program to be approved by the university's Board of Regents. In the spring of 1995, the HIM program was selected to be part of a pilot brokering project of the Western Interstate Consortium on Higher Education, in which member institutions would offer programs to or receive programs from other member institutions. The university's HIM program was selected by New Mexico and Wyoming, and classes for two groups of Wyoming students were initiated in the fall of 1995. The article summarizes the results of the project for the HIM program and future plans. It also provides an overview of some of the challenges facing institutions with out-of-state or multistate program delivery.     

The Variation in Arrestees' Disclosure of Recent Drug Use Across Locations, Drugs, and Demographic Characteristics

This study provides a comprehensive multivariate analysis of drug use disclosure among arrestees interviewed between 2000 and 2001 at 37 sites across the U.S. served by the Arrestee Drug Abuse Monitoring (ADAM) Program. Rates varied widely by drug and across sites. The marijuana disclosure rate varied from 68% in Fort Lauderdale to 93% in Spokane. The cocaine/crack disclosure rate varied from 28% in Chicago to 70% in Kansas City. Moreover, covariates of disclosure differed across drugs. This wide variation in disclosure suggests extreme caution be used when comparing self-reports of prevalence across drugs, locations, and individual characteristics - certainly at least for arrestees.     

Mitogen-activated protein kinases, inhibitory-kappaB kinase, and insulin signaling in human omental versus subcutaneous adipose tissue in obesity

MAPKs and inhibitory-kappaB kinase (IKK) were suggested to link various conditions thought to develop in adipose tissue in obesity (oxidative, endoplasmic reticulum stress, inflammation) with insulin resistance. Yet whether in obesity these kinases are affected in a fat-depot-differential manner is unknown. We assessed the expression and phosphorylation of these kinases in paired omental and abdominal-sc fat biopsies from 48 severely obese women (body mass index > 32 kg/m(2)). Protein and mRNAs of p38MAPK, ERK, c-Jun kinase-1, and IKKbeta were increased 1.5-2.5-fold in omental vs. sc fat. The phosphorylated (activated) forms of these kinases were also increased to similar magnitudes as the total expression. However, phosphorylation of insulin receptor substrate-1 on Ser312 (equivalent of murine Ser307) was not increased in omental, compared with sc, fat. Consistently, fat tissue fragments stimulated with insulin demonstrated that tyrosine phosphorylation and signal transduction to Akt/protein kinase B in omental fat was not inferior to that observable in sc fat. Comparison with lean women (body mass index 23.2 +/- 2.9 kg/m(2)) revealed similar ERK2 and IKKbeta expression and phosphorylation in both fat depots. However, as compared with lean controls, obese women exhibited 480 and 270% higher amount of the phosphorylated forms of p38MAPK and c-Jun kinase, respectively, in omental, but not sc, fat, and this expression level correlated with clinical parameters of glycemia and insulin sensitivity. Increased expression of stress-activated kinases and IKK and their phosphorylated forms in omental fat occurs in obesity, potentially contributing to differential roles of omental and sc fat in the pathophysiology of obesity.     

Immediate antiviral therapy appears to restrict resting CD4+ cell HIV-1 infection without accelerating the decay of latent infection

HIV type 1 (HIV-1) persists within resting CD4(+) T cells despite antiretroviral therapy (ART). To better understand the kinetics by which resting cell infection (RCI) is established, we developed a mathematical model that accurately predicts (r = 0.65, P = 2.5 × 10(-4)) the initial frequency of RCI measured about 1 year postinfection, based on the time of ART initiation and the dynamic changes in viremia and CD4(+) T cells. In the largest cohort of patients treated during acute seronegative HIV infection (AHI) in whom RCI has been stringently quantified, we found that early ART reduced the generation of latently infected cells. Although RCI declined after the first year of ART in most acutely infected patients, there was a striking absence of decline when initial RCI frequency was less than 0.5 per million. Notably, low-level viremia was observed more frequently as RCI increased. Together these observations suggest that (i) the degree of RCI is directly related to the availability of CD4(+) T cells susceptible to HIV, whether viremia is controlled by the immune response and/or ART; and (ii) that two pools of infected resting CD4(+) T cells exist, namely, less stable cells, observable in patients in whom viremia is not well controlled in early infection, and extremely stable cells that are established despite early ART. These findings reinforce and extend the concept that new approaches will be needed to eradicate HIV infection, and, in particular, highlight the need to target the extremely small but universal, long-lived latent reservoir.     

Gremlin 1 depletion in vivo causes severe enteropathy and bone marrow failure

The intestinal epithelium is perpetually renewed from a stem cell niche in the base of crypts to maintain a healthy bowel mucosa. Exit from this niche and maturation of epithelial cells requires tightly controlled gradients in BMP signalling, progressing from low BMP signalling at the crypt base to high signalling at the luminal surface. The BMP antagonist gremlin 1 (Grem1) is highly expressed by subepithelial myofibroblasts adjacent to the intestinal crypts but its role in regulating the stem cell niche and epithelial renewal in vivo has not been explored. To explore the effects of Grem1 loss in adulthood following normal growth and development, we bred mice (ROSA26CreER-Grem1 ^flx/flx) in which Grem1 could be deleted by tamoxifen administration. While Grem1 remained intact, these mice were healthy, grew normally, and reproduced successfully. Following Grem1 depletion, the mice became unwell and were euthanised (at 7–13 days). Post-mortem examination revealed extensive mucosal abnormalities throughout the small and large intestines with failure of epithelial cell replication and maturation, villous atrophy, and features of malabsorption. Bone marrow hypoplasia was also observed with associated early haematopoietic failure. These results demonstrate an essential homeostatic role for gremlin 1 in maintaining normal bowel epithelial function in adulthood, suggesting that abnormalities in gremlin 1 expression can contribute to enteropathies. We also identified a previously unsuspected requirement for gremlin 1 in normal haematopoiesis. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.