Predictors of depression recovery in HIV-infected individuals managed through measurement-based care in infectious disease clinics

Treatment of comorbid chronic disease, such as depression, in people living with HIV/AIDS (PLWHA) increasingly falls to HIV treatment providers. Guidance in who will best respond to depression treatment and which patient-centered symptoms are best to target is limited

In Populo

While the Latin phrase in vitro and in vivo are well understood in the medical literature, neither term accurately describes the science performed at the level of the population by epidemiologists and others. In particular, results in a single organism can differ broadly from results in a population, for reasons from random error to herd immunity. We suggest that in populo, meaning literally “in the people”, can fill this gap in the literature, and urge its wide adoption

Evidence That the P\u3csub\u3ei\u3c/sub\u3e Release Event Is the Rate-Limiting Step in the Nitrogenase Catalytic Cycle

Nitrogenase reduction of dinitrogen (N2) to ammonia (NH3) involves a sequence of events that occur upon the transient association of the reduced Fe protein containing two ATP molecules with the MoFe protein that includes electron transfer, ATP hydrolysis, Pi release, and dissociation of the oxidized, ADP-containing Fe protein from the reduced MoFe protein. Numerous kinetic studies using the nonphysiological electron donor dithionite have suggested that the rate-limiting step in this reaction cycle is the dissociation of the Fe protein from the MoFe protein. Here, we have established the rate constants for each of the key steps in the catalytic cycle using the physiological reductant flavodoxin protein in its hydroquinone state. The findings indicate that with this reductant, the rate-limiting step in the reaction cycle is not protein–protein dissociation or reduction of the oxidized Fe protein, but rather events associated with the Pi release step. Further, it is demonstrated that (i) Fe protein transfers only one electron to MoFe protein in each Fe protein cycle coupled with hydrolysis of two ATP molecules, (ii) the oxidized Fe protein is not reduced when bound to MoFe protein, and (iii) the Fe protein interacts with flavodoxin using the same binding interface that is used with the MoFe protein. These findings allow a revision of the rate-limiting step in the nitrogenase Fe protein cycle

The Depression Treatment Cascade in Primary Care: A Public Health Perspective

Major depressive disorder (MDD) is common and costly. Primary care remains a major access point for depression treatment, yet the successful clinical resolution of depression in primary care is uncommon. The clinical response to depression suffers from a “treatment cascade”: the affected individual must access health care, be recognized clinically, initiate treatment, receive adequate treatment, and respond to treatment. Major gaps currently exist in primary care at each step along this treatment continuum. We estimate that 12.5% of primary care patients have had MDD in the past year; of those with MDD, 47% are recognized clinically, 24% receive any treatment, 9% receive adequate treatment, and 6% achieve remission. Simulations suggest that only by targeting multiple steps along the depression treatment continuum (e.g. routine screening combined with collaborative care models to support initiation and maintenance of evidence-based depression treatment) can overall remission rates for primary care patients be substantially improved

Chlamydia Prevalence Trends among Women and Men Entering the National Job Training Program from 1990 Through 2012

Background Evaluating chlamydia prevalence trends from sentinel surveillance is important for understanding population disease burden over time. However, prevalence trend estimates from surveillance data may be misleading if they do not account for changes in risk profiles of individuals who are screened (case mix) and changing performance of the screening tests used. Methods We analyzed chlamydia screening data from a sentinel surveillance population of 389,555 young women (1990-2012) and 303,699 young men (2003-2012) entering the US National Job Training Program. This period follows the introduction of national chlamydia screening programs designed to prevent transmission and reduce population disease burden. After ruling out bias due to case mix, we used an expectation-maximization-based maximum likelihood approach to account for measurement error from changing screening tests, and generated minimally biased long-term chlamydia prevalence trend estimates among youth and young adults in this sentinel surveillance population. Results Adjusted chlamydia prevalence among women was high throughout the study period, but fell from 20% in 1990 to 12% in 2003, and remained between 12% and 14% through 2012. Adjusted prevalence among men was steady throughout the study period at approximately 7%. For both women and men, adjusted prevalence was highest among Black and American Indian youth and young adults, and in the Southern and Midwestern regions of the United States throughout the study period. Conclusions Our minimally biased trend estimates provide support for an initial decrease in chlamydia prevalence among women soon after the introduction of national chlamydia screening programs. Constant chlamydia prevalence in more recent years suggests that screening may not be sufficient to further reduce chlamydia prevalence among high-risk youth and young adults

Factors Associated with Change in Sexual Transmission Risk Behavior over 3 Years among HIV-Infected Patients in Tanzania.

The reduction of HIV transmission risk behaviors among those infected with HIV remains a major global health priority. Psychosocial characteristics have proven to be important correlates of sexual transmission risk behaviors in high-income countries, but little attention has focused on the influence of psychosocial and psychological factors on sexual transmission risk behaviors in African cohorts. The CHAT Study enrolled a representative sample of 499 HIV-infected patients in established HIV care and 267 newly diagnosed HIV-infected individuals from the Kilimanjaro Region of Tanzania. Participants completed in-person interviews every 6 months for 3 years. Using logistic random effects models to account for repeated observations, we assessed sociodemographic, physical health, and psychosocial predictors of self-reported unprotected sexual intercourse. Among established patients, the proportion reporting any recent unprotected sex was stable, ranging between 6-13% over 3 years. Among newly diagnosed patients, the proportion reporting any unprotected sex dropped from 43% at baseline to 11-21% at 6-36 months. In multivariable models, higher odds of reported unprotected sex was associated with female gender, younger age, being married, better physical health, and greater post-traumatic stress symptoms. In addition, within-individual changes in post-traumatic stress over time coincided with increases in unprotected sex. Changes in post-traumatic stress symptomatology were associated with changes in sexual transmission risk behaviors in this sample of HIV-infected adults in Tanzania, suggesting the importance of investing in appropriate mental health screening and intervention services for HIV-infected patients, both to improve mental health and to support secondary prevention efforts

Unraveling the interactions of the physiological reductant flavodoxin with the different conformations of the Fe protein in the nitrogenase cycle

Nitrogenase reduces dinitrogen (N2) to ammonia in biological nitrogen fixation. The nitrogenase Fe protein cycle involves a transient association between the reduced, MgATP-bound Fe protein and the MoFe protein and includes electron transfer, ATP hydrolysis, release of Pi, and dissociation of the oxidized, MgADP-bound Fe protein from the MoFe protein. The cycle is completed by reduction of oxidized Fe protein and nucleotide exchange. Recently, a kinetic study of the nitrogenase Fe protein cycle involving the physiological reductant flavodoxin reported a major revision of the rate-limiting step from MoFe protein and Fe protein dissociation to release of Pi. Because the Fe protein cannot interact with flavodoxin and the MoFe protein simultaneously, knowledge of the interactions between flavodoxin and the different nucleotide states of the Fe protein is critically important for understanding the Fe protein cycle. Here we used time-resolved limited proteolysis and chemical cross-linking to examine nucleotide-induced structural changes in the Fe protein and their effects on interactions with flavodoxin. Differences in proteolytic cleavage patterns and chemical cross-linking patterns were consistent with known nucleotide-induced structural differences in the Fe protein and indicated that MgATP-bound Fe protein resembles the structure of the Fe protein in the stabilized nitrogenase complex structures. Docking models and cross-linking patterns between the Fe protein and flavodoxin revealed that the MgADP-bound state of the Fe protein has the most complementary docking interface with flavodoxin compared with the MgATP-bound state. Together, these findings provide new insights into the control mechanisms in protein–protein interactions during the Fe protein cycle. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc

Prevalence of Psychological Trauma and Association with Current Health and Functioning in a Sample of HIV-infected and HIV-uninfected Tanzanian Adults

In high income nations, traumatic life experiences such as childhood sexual abuse are much more common in people living with HIV/AIDS (PLWHA) than the general population, and trauma is associated with worse current health and functioning. Virtually no data exist on the prevalence or consequences of trauma for PLWHA in low income nations. We recruited four cohorts of Tanzanian patients in established medical care for HIV infection (n = 228), individuals newly testing positive for HIV (n = 267), individuals testing negative for HIV at the same sites (n = 182), and a random sample of community-dwelling adults (n = 249). We assessed lifetime prevalence of traumatic experiences, recent stressful life events, and current mental health and health-related physical functioning. Those with established HIV infection reported a greater number of childhood and lifetime traumatic experiences (2.1 and 3.0 respectively) than the community cohort (1.8 and 2.3). Those with established HIV infection reported greater post-traumatic stress disorder (PTSD) symptomatology and worse current health-related physical functioning. Each additional lifetime traumatic experience was associated with increased PTSD symptomatology and worse functioning. This study is the first to our knowledge in an HIV population from a low income nation to report the prevalence of a range of potentially traumatic life experiences compared to a matched community sample and to show that trauma history is associated with poorer health-related physical functioning. Our findings underscore the importance of considering psychosocial characteristics when planning to meet the health needs of PLWHA in low income countries