Community-Based Accompaniment and Psychosocial Health Outcomes in HIV-Infected Adults in Rwanda: A Prospective Study

We examined whether the addition of community-based accompaniment to Rwanda’s national model for antiretroviral treatment (ART) was associated with greater improvements in patients’ psychosocial health outcomes during the first year of therapy. We enrolled 610 HIV-infected adults with CD4 cell counts under 350 cells/μL initiating ART in one of two programs. Both programs provided ART and required patients to identify a treatment buddy per national protocols. Patients in one program additionally received nutritional and socioeconomic supplements, and daily home-visits by a community health worker (“accompagnateur”) who provided social support and directly-observed ingestion of medication. The addition of community-based accompaniment was associated with an additional 44.3 % reduction in prevalence of depression, more than twice the gains in perceived physical and mental health quality of life, and increased perceived social support in the first year of treatment. Community-based accompaniment may represent an important intervention in HIV-infected populations with prevalent mental health morbidity.     

Narrowband Ultraviolet B Light in Langerhans Cell Histiocytosis: A Case Report

Langerhans cell histiocytosis (LCH) (previously called eosinophilic granuloma, Hand–Schüller–Christian syndrome, Letterer–Siwe disease, and Hashimoto–Pritzker disease) is a rare, heterogeneous disorder with highly variable presentation. LCH commonly affects the skin, as well as internal organs. Because the skin lesions appear benign, and LCH is unfamiliar to most physicians, diagnosis is often delayed. Treatment is controversial, with further clinical study needed. For persons with extensive, skin‐limited disease, the existing topical therapies are impractical. We present a child with cutaneous LCH lesions that responded to ultraviolet light phototherapy with minimal adverse effects or patient discomfort.     

Epigenome‐wide DNA methylation changes with development of arsenic‐induced skin lesions in Bangladesh: A case–control follow‐up study

Studies have found an association between aberrant DNA methylation and arsenic‐induced skin lesions. However, little is known about DNA methylation changes over time in people who develop arsenic‐induced skin lesions. We sought to investigate epigenome‐wide changes of DNA methylation in people who developed arsenic‐induced skin lesions in a 10‐year period. In 2009–2011, we conducted a follow‐up study of 900 skin lesion cases and 900 controls and identified 10 people who developed skin lesions since a baseline survey in 2001–2003. The 10 cases (“New Cases”) were matched with 10 controls who did not have skin lesions at baseline or follow‐up (“Persistent Controls”). Drinking water and blood samples were collected, and skin lesion was diagnosed by the same physician at both time points. We measured DNA methylation in blood using Infinium HumanMethylation450K BeadChip, followed by quantitative validation using pyrosequencing. Two‐sample t‐tests were used to compare changes in percent methylation between New Cases and Persistent Controls. Six CpG (cytosine‐phosphate‐guanine) sites with greatest changes of DNA methylation over time among New Cases were further validated with a correlation of 93% using pyrosequencing. One of the validated CpG site (cg03333116; change of %methylation was 13.2 in New Cases versus ?0.09 in Persistent Controls; P < 0.001) belonged to the RHBDF1 gene, which was previously reported to be hypermethylated in arsenic‐exposed cases. We examined DNA methylation changes with the development of arsenic‐induced skin lesions over time but nothing was statistically significant given the small sample size of this exploratory study and the high dimensionality of data. Environ. Mol. Mutagen. 55:449–456, 2014. © 2014 Wiley Periodicals, Inc.     

Coincident plasma ACTH and corticosterone time series: Comparisons between young and old rats

Senescence is accompanied by a reduced ability to respond to a variety of physical and behavioral stressors. A sizable literature has been devoted to the interplay between hypothalamic-pituitary-adrenocortical axis dysfunction and senescence; yet, the precise interactions remain an enigma. Adrenocorticotropic hormone (ACTH) is secreted in pulsatile bursts generating complex signals in the plasma compartment that must be “read” by adrenocortical cells in order to initiate appropriate secretory responses. We have previously demonstrated subtle differences between young and old rats in the pattern of fluctuations in plasma ACTH concentrations over time, despite no difference in mean levels. The present work addressed the physiological significance of these differences in the plasma ACTH signal by analyzing the corresponding plasma corticosterone concentration time series and the relationship between these two hormones over time. Time series of integrated 10-min ACTH and corticosterone concentrations were collected over 4 h at the time of diurnal activation and analyzed in the time and frequency domains. The time of onset of the diurnal surge occurred 20 min later in old rats, and the ratio of corticosterone to ACTH was less at the time of onset and peak of the diurnal surge. Corticosterone levels were lower in old rats and mean ACTH and corticosterone levels were correlated in young but not old rats, as were maximum levels of the two hormones. Cross-correlation of ACTH and corticosterone time series and comparison of spectra were consistent with smoother fluctuations in plasma corticosterone in old animals with less variability at time scales less than 55 min. We conclude that age may be associated with a delay in diurnal activation of the HPA axis, a loss of sensitivity of adrenal corticosterone secretion to plasma ACTH levels, and a relative loss of high frequency variability in the corticosterone signal, as seen in many physiological systems with age.     

Analysis of variable (diversity) joining recombination in DNAdependent protein kinase (DNA-PK)-deficient mice reveals DNA-PK-independent pathways for both signal and coding joint formation

Previous studies have suggested that ionizing radiation causes irreparable DNA double-strand breaks in mice and cell lines harboring mutations in any of the three subunits of DNA-dependent protein kinase (DNA-PK) (the catalytic subunit, DNA-PKcs, or one of the DNA-binding subunits, Ku70 or Ku86). In actuality, these mutants vary in their ability to resolve double-strand breaks generated during variable (diversity) joining [V(D)J] recombination. Mutant cell lines and mice with targeted deletions in Ku70 or Ku86 are severely compromised in their ability to form coding and signal joints, the products of V(D)J recombination. It is noteworthy, however, that severe combined immunodeficient (SCID) mice, which bear a nonnull mutation in DNA-PKcs, are substantially less impaired in forming signal joints than coding joints. The current view holds that the defective protein encoded by the murine SCID allele retains enough residual function to support signal joint formation. An alternative hypothesis proposes that DNA-PKcs and Ku perform different roles in V(D)J recombination, with DNA-PKcs required only for coding joint formation. To resolve this issue, we examined V(D)J recombination in DNA-PKcs-deficient (SLIP) mice. We found that the effects of this mutation on coding and signal joint formation are identical to the effects of the SCID mutation. Signal joints are formed at levels 10-fold lower than in wild type, and one-half of these joints are aberrant. These data are incompatible with the notion that signal joint formation in SCID mice results from residual DNA-PKcs function, and suggest a third possibility: that DNA-PKcs normally plays an important but nonessential role in signal joint formation.     

Increased human leukocyte antigen-G expression at the maternal–fetal interface is associated with preterm birth

Objective: The maternal–fetal interface must modulate immune function to allow tolerance of fetal cells while still reacting to pathogens to suppress infection. Human leukocyte antigen-G (HLA-G) is a class Ib major histocompatibility complex protein involved in maternal–fetal tolerance. We posited that alterations in placental HLA-G expression predispose women to preterm birth. The aim of this study was to compare HLA-G expression in the maternal–fetal interface of term versus preterm human placentas.

Methods: We performed a cross-sectional study of specimens from the basal plate of the human placenta from women enrolled in a tissue specimen and clinical data consortium. Immunohistochemistry with digital microscopic analysis was used to quantify HLA-G protein expression in the basal plate from preterm and term placentas.

Results: Preterm birth <37 weeks occurred in 29.5% of 149 singleton pregnancies. HLA-G-positive cells occupied one-third of the basal plates, and the HLA-G-positive area was increased by 14% in placentas from preterm births than in those from term births (32.1% in term placentas versus 36.6% in preterm placentas).

Conclusion: Although HLA-G is required for maternal tolerance of the semi-allogeneic fetus, higher levels of HLA-G expression at the maternal–fetal interface is associated with preterm birth.