Antigen-specific T-cell memory is preserved in children treated for acute lymphoblastic leukemia

Despite profound T-cell immunodeficiency, most patients treated with chemotherapy do not succumb to infection. The basis for residual protective immunity in lymphopenic patients is not known. We prospectively measured T-cell numbers, thymopoiesis, and T-cell memory in 73 children undergoing a 2-year chemotherapy regimen for acute lymphoblastic leukemia (ALL) and compared them to an age-matched cohort of 805 healthy children. Most patients had profound defects in CD4 and CD8 T-cell numbers at diagnosis that did not recover during the 2 years of therapy. Thymic output and the fraction of naive T cells were significantly lower than in healthy controls. However, the remaining T-cell compartment was enriched for antigen-experienced, memory T cells defined both by phenotype and by function. This relative sparing of T-cell memory may, in part, account for the maintenance of protective immunity in lymphopenic patients treated for ALL. Moreover, because the memory T-cell compartment is least affected by ALL and its treatment, strategies to induce immunity to pathogens or tumor antigens in cancer patients may be most successful if they seek to expand pre-existing memory T cells.     

locStra: Fast analysis of regional/global stratification in whole‐genome sequencing studies

locStra is an ‐package for the analysis of regional and global population stratification in whole‐genome sequencing (WGS) studies, where regional stratification refers to the substructure defined by the loci in a particular region on the genome. Population substructure can be assessed based on the genetic covariance matrix, the genomic relationship matrix, and the unweighted/weighted genetic Jaccard similarity matrix. Using a sliding window approach, the regional similarity matrices are compared with the global ones, based on user‐defined window sizes and metrics, for example, the correlation between regional and global eigenvectors. An algorithm for the specification of the window size is provided. As the implementation fully exploits sparse matrix algebra and is written in C++, the analysis is highly efficient. Even on single cores, for realistic study sizes (several thousand subjects, several million rare variants per subject), the runtime for the genome‐wide computation of all regional similarity matrices does typically not exceed one hour, enabling an unprecedented investigation of regional stratification across the entire genome. The package is applied to three WGS studies, illustrating the varying patterns of regional substructure across the genome and its beneficial effects on association testing.     

Factitious hypoglycemia due to surreptitious administration of insulin. Diagnosis, treatment, and long-term follow-up

Ten patients had factitious hypoglycemia due to surreptitious insulin injections diagnosed and were followed for up to 15 years (median, 5 years; range, 2 months to 15 years). When available, demonstration of anti-insulin antibodies was the most helpful diagnostic test. Decreased plasma C-peptide levels corroborated the diagnosis. Young women (nine of ten) with knowledge of the medical profession or relatives with diabetes mellitus predominated in the sample. Five of the patients had a history of insulin-requiring diabetes mellitus. Two patients eventually committed suicide despite the best efforts at therapy. Only three of ten patients made a successful transition into productive life after the diagnosis of factitious hypoglycemia was established. Factitious hypoglycemia remains a difficult diagnosis to make, and the long-term outcome after the diagnosis is established is unpredictable. All efforts have to be made to confirm the diagnosis before the patients are approached. The confrontation is to be made by an experienced team of health care professionals who have gained the patient's confidence through an understanding but firm manner. Long-term therapy must be planned and initiated before the patient's discharge.     

Tailoring Interventions: Understanding Medical Practice Culture

This article describes the results of a study that used intensive direct observations of eight medical practices to assess the factors affecting the barriers and facilitators to adult immunization for influenza and pneumonia. The study aimed to describe the culture of these practices by identifying key features that facilitate or deter the immunization process. The article presents profiles of six of the eight practices describing their cultural and organizational frameworks. Six features that are critical to an understanding of the cultures of these practices, particularly as they relate to receptivity to influenza immunization for diverse practices and patient populations, are highlighted. These include policies and procedures, funding source, physician philosophy, patient receptivity to provider recommendation, and physical environment and social environment. The article also discusses strategies for applying knowledge about the culture of each practice to introduce appropriate and feasible interventions aimed at increasing immunization rates.     

The Role of Serotonin (5-HT) in Behavioral Control: Findings from Animal Research and Clinical Implications

The neurotransmitters serotonin and dopamine both have a critical role in the underlying neurobiology of different behaviors. With focus on the interplay between dopamine and serotonin, it has been proposed that dopamine biases behavior towards habitual responding, and with serotonin offsetting this phenomenon and directing the balance toward more flexible, goal-directed responding. The present focus paper stands in close relationship to the publication by Worbe et al. (2015), which deals with the effects of acute tryptophan depletion, a neurodietary physiological method to decrease central nervous serotonin synthesis in humans for a short period of time, on the balance between hypothetical goal-directed and habitual systems. In that research, acute tryptophan depletion challenge administration and a following short-term reduction in central nervous serotonin synthesis were associated with a shift of behavioral performance towards habitual responding, providing further evidence that central nervous serotonin function modulates the balance between goal-directed and stimulus-response habitual systems of behavioral control. In the present focus paper, we discuss the findings by Worbe and colleagues in light of animal experiments as well as clinical implications and discuss potential future avenues for related research.     

Economic vulnerability,violence, and sexual risk factors for HIV among female sex workers in Tijuana,Mexico

AIDS and Behavior - Economic vulnerability is often reported to underlie involvement in sex work among female sex workers (FSW), but may also create urgency in women’s work, limiting...