Risk of End‐Stage Renal Disease in HIV‐Positive Potential Live Kidney Donors

New federal regulations allow HIV‐positive individuals to be live kidney donors; however, potential candidacy for donation is poorly understood given the increased risk of end‐stage renal disease (ESRD) associated with HIV infection. To better understand this risk, we compared the incidence of ESRD among 41 968 HIV‐positive participants of North America AIDS Cohort Collaboration on Research and Design followed for a median of 5 years with the incidence of ESRD among comparable HIV‐negative participants of National Health and Nutrition Examination III followed for a median of 14 years. We used risk associations from multivariable Cox proportional hazards regression to derive cumulative incidence estimates for selected HIV‐positive scenarios (no history of diabetes, hypertension, AIDS, or hepatitis C virus coinfection) and compared these estimates with those from similarly selected HIV‐negative scenarios. For 40‐year‐old HIV‐positive individuals with health characteristics that were similar to those of age‐matched kidney donors, viral load <400 copies/mL, and CD4⁺ count ≥500 cells/μL, the 9‐year cumulative incidence of ESRD was higher than that of their HIV‐negative peers, yet still low: 2.5 versus 1.1 per 10 000 among white women, 3.0 versus 1.3 per 10 000 among white men, 13.2 versus 3.6 per 10 000 among black women, and 15.8 versus 4.4 per 10 000 among black men. HIV‐positive individuals with no comorbidities and well‐controlled disease may be considered low‐risk kidney donor candidates.     

Discovery of Orally Active Isofuranones as Potent, Selective Inhibitors of Hematopoetic Progenitor Kinase 1

While the discovery of immune checkpoint inhibitors has led to robust, durable responses in a range of cancers, many patients do not respond to currently available therapeutics. Therefore, an urgent need exists to identify alternative mechanisms to augment the immune-mediated clearance of tumors. Hematopoetic progenitor kinase 1 (HPK1) is a serine-threonine kinase that acts as a negative regulator of T-cell receptor (TCR) signaling, to dampen the immune response. Herein we describe the structure-based discovery of isofuranones as inhibitors of HPK1. Optimization of the chemotype led to improvements in potency, selectivity, plasma protein binding, and metabolic stability, culminating in the identification of compound 24. Oral administration of 24, in combination with an anti-PD1 antibody, demonstrated robust enhancement of anti-PD1 efficacy in a syngeneic tumor model of colorectal cancer.     

Variations in pediatric HIV status disclosure between the orphanage and the community in Ethiopia

Past studies on pediatric HIV disclosure have not investigated the variations across childcare settings. This study explored pediatric HIV disclosure for children living in the community with their birthparents or relatives and those living in orphanages in Addis Ababa, Ethiopia, to highlight the variations in reasons, processes and outcomes of disclosure across childcare settings. Semi-structured interviews were conducted with children and their caregivers attending an HIV clinic in Addis Ababa, Ethiopia. Among children living in orphanages, the proportion with disclosure was significantly higher (p < 0.001) and age at disclosure was younger (p = 0.09). Although the proportions of children with unplanned disclosure were similar in orphanages and the community, there were notable differences between children’s experiences. Children living in the community often found out their status alone through exposure to antiretroviral therapy advertisements in the media, unbeknownst to their caregivers and healthcare providers and suffered silently without any support. Orphans, on the other hand, experienced unplanned disclosure after the death of their birthparents and subsequently received significant emotional support. Healthcare professionals need to consider these variations with childcare settings in disclosure processes. Practices in orphanages may be important models for developing adequate support system for caregivers and children in the community.     

Cocaine-related seizures in adults

Cocaine abuse is associated with a variety of severe acute neurologic complications. These include ischemic stroke, subarachnoid and intraparenchymal hemorrhage, syncope, seizures, and death. Eleven adult patients with cocaine-related seizures are reported. All were seen during the 1987 calendar year at the King/Drew Medical Center and Urban Comprehensive Epilepsy Program of Los Angeles. Three apparent clinical circumstances with defined methods of intake and time course after usage were identified in our cases. Seizures occurred 1) as acute provoked convulsions in patients known to have epilepsy, 2) spontaneously in otherwise normal individuals after acute snorting or "crack smoking," and 3) agonally with massive ingestion.     

Effectiveness of Integrated Best Management Practices on Mitigation of Atrazine and Metolachlor in an Agricultural Lake Watershed

The study examined the influence of land-use (cropping patterns) and integrated agricultural best management practices (BMPs) on spring herbicide levels in an agricultural watershed. Atrazine and metolachlor were applied for weed control during spring of 1998–2002, 2005, and 2007–2013. Watershed-wide mass of applied herbicides ranged from 12.7 to 209.2 g atrazine and 10.9–302.2 g metolachlor with greatest application during 1998, 2009–2010 (atrazine) and 2007–2013 (metolachlor). Spring herbicide concentrations in Beasley Lake water ranged from below detection to 3.54 μg atrazine/L and 3.01 μg metolachlor/L. Multiple linear regression analyses with cropping patterns, BMPs, rainfall and time as independent variables, showed atrazine applications were associated with increases in cotton acreage and quail buffer, while metolachlor applications increased over time. Multiple linear regressions showed lake atrazine concentrations were associated with conservation tillage, rainfall, and corn, while lake metolachlor concentrations were associated with the cumulative metolachlor application and sediment retention pond installation.     

Interpersonal Guilt and Substance Use in College Students

Background: The college years are a time for developing independence and separating from one's family, and they are also a time in which substance use often escalates. This study examined the relationships between use of substances and interpersonal guilt, an emotion that can arise from feelings about separation among college students. Methods: In total, 1865 college students completed a survey evaluating substance use and interpersonal guilt. Regular users of alcohol, cigarettes, cannabis, and other illicit drugs were compared with nonregular users of each substance. Sequential linear regression, controlling for confounding variables, examined relationships between regular use of each substance and scores on a guilt index. Results: Risky drinkers and daily smokers had significantly more interpersonal guilt than their peers who did not regularly use these substances. In contrast, regular cannabis users had significantly less guilt than nonregular cannabis users. Conclusions: These data suggest that substance use among college students may be related to interpersonal guilt and family separation issues, and this relationship may vary across substances.