Strategies of adoptive T -cell transfer to treat refractory viral infections post allogeneic stem cell transplantation.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) can expose patients to a transient but marked immunosuppression, during which viral infections are an important cause of morbidity and mortality. Adoptive transfer of virus-specific T cells is an attractive approach to restore protective T -cell immunity in patients with refractory viral infections after allogeneic HSCT. OBJECTIVES: This narrative review summarizes clinical evidence and developments of almost 30 years of adoptive T -cell transfer. The review is based on evidence extracted from PubMed searches and the clinical and experimental work of the authors. CONTENT: Viral infections after HSCT are frequently caused by the endogenous reactivation of persistent pathogens such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus (AdV). Current antiviral medication is not satisfactory and does not treat the underlying pathophysiology which is the lack of specific T -cell immunity. Adoptive transfer of virus-specific T cells could be a potentially curative, pathogen-specific, and non-toxic treatment providing long-term immunity against the virus. The isolation of virus-specific T cells from a healthy donor and infusion into a recipient is known as adoptive T -cell transfer and has been performed in many patients using different treatment protocols. Based on basic research, new isolation protocols aim at a safe and fast availability of cellular products for adoptive T -cell transfer. We summarize preclinical and clinical data on each of the main pathogens and on the technical approaches currently available to target either single antigens or even multiple pathogens. CONCLUSION: Cellular therapy is considered as one of the major recent breakthroughs in medicine. Translation of this individualized treatment into first-line clinical routine is still limited. Main hurdles are availability of the technique, limited compatibility of classical phase III designs with cellular therapy, and regulatory restrictions. Multinational efforts are required to clarify the status of cellular treatment in first-line clinical routine with the overall objective to strengthen evidence-based treatment guidelines for the treatment of refractory viral infections post HSCT.

Shifts in ovine cardiopulmonary microRNA expression in late gestation and the perinatal period.

BACKGROUND: MicroRNAs (miRNAs) have been identified as important contributors to the regulation of early fetal cardiopulmonary development. However, miRNA expression profiles during late gestation and the early neonatal period are not fully elaborated in large mammals such as sheep (ovis aries). The aim of this study was to sequence miRNA from cardiopulmonary tissues in late gestation and neonate sheep to identify changes in miRNA expression. METHODS: Illumina HiSeq next-generation deep sequencing (NGS) was performed on ovine tissues from the left (LV) and right ventricles (RV), lungs and pulmonary artery (PA) of preterm fetuses (128 days), near-term fetuses (140 days) (term = 148 days) and neonatal lambs (5 days). NGS reads were mapped to the sheep genome (OviAri) and published miRNA sequences. RESULTS: Of 1345 cardiopulmonary miRNAs that were sequenced, relatively few major shifts in miRNA expression were detected with increased age from near term to neonates, and were confirmed by quantitative real-time PCR: bta-miR-146a (lung), bta-miR-22-3p (lung, LV), hsa-miR-335* (lung, PA), and miR-210 (lung, PA, LV). CONCLUSIONS: Sequencing of miRNA led to identification of four predominant miRNA in ovine cardiopulmonary tissues which alter expression during late gestation and the early neonatal period, concurrent with important functional changes in heart and lungs.

Impact of the revised Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) food package policy on fruit and vegetable prices.

Obesity is generally inversely related to income among women in the United States. Less access to healthy foods is one way lower income can influence dietary behaviors and body weight. Federal food assistance programs, such as the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), are an important source of healthy food for low-income populations. In 2009, as part of a nationwide policy revision, WIC added a fruit and vegetable (F/V) voucher to WIC food packages. This quasi-experimental study determined whether F/V prices at stores authorized to accept WIC (ie, WIC vendors) decreased after the policy revision in seven Illinois counties. It also examined cross-sectional F/V price variations by store type and neighborhood characteristics. Two pre-policy observations were conducted in 2008 and 2009; one post-policy observation was conducted in 2010. Small pre- to post-policy reductions in some F/V prices were found, particularly for canned fruit and frozen vegetables at small stores. Compared with chain supermarkets, mass merchandise stores had lower prices for fresh F/V and frozen F/V and small stores and non-chain supermarkets had higher canned and frozen F/V prices, but lower fresh F/V prices. Limited price differences were found across neighborhoods, although canned vegetables were more expensive in neighborhoods with higher concentrations of either Hispanics or blacks and fresh F/V prices were lower in neighborhoods with more Hispanics. Results suggest the WIC policy revision contributed to modest reductions in F/V prices. WIC participants' purchasing power can differ depending on the type and neighborhood of the WIC vendor used.

Fruit and vegetable availability and selection: federal food package revisions, 2009.

BACKGROUND: With nearly 49,000 authorized retailers nationwide, a policy change that added fruits and vegetables (FV) to the U.S. Department of Agriculture's Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) food packages in 2009 had the potential to expand neighborhood FV availability. PURPOSE: This study examined changes in availability and selection of commonly consumed and culturally specific FV at authorized retailers (WIC vendors) before and after implementation of the revised WIC food packages. METHODS: Quasi-experimental, one-group design with two pre-policy observations and one post-policy observation. Trained observers assessed a list of fresh, frozen, and canned FV at each vendor in seven northern Illinois counties. Eight indices of FV availability and selection were derived. Multiple regression estimated relationships. Data were collected in 2008-2010 and analyzed in 2011. RESULTS: Overall, availability and selection of commonly consumed fresh FV and availability of African-American culturally specific fresh FV improved after implementation of the new policy. Modest improvements in the overall availability of canned low-sodium vegetables and frozen FV were observed. Changes differed by vendor type (large vendor, small vendor, and pharmacy). Changes in availability or selection did not differ by neighborhood characteristics (population density, median household income, racial/ethnic composition). CONCLUSIONS: Expansion of WIC foods was associated with small positive externalities on the food environment. Larger subsidies to create more demand and more-substantial stocking requirements for retailers may yield significantly larger improvements and thus warrant further investigation. Approaches targeting rural, low-income, and racial/ethnic minority neighborhoods also may be needed.

Weight misperceptions and racial and ethnic disparities in adolescent female body mass index.

This paper investigated weight misperceptions as determinants of racial/ethnic disparities in body mass index (BMI) among adolescent females using data from the National Survey of Youth 1997. Compared to their white counterparts, higher proportions of black and Hispanic adolescent females underperceived their weight status; that is, they misperceived themselves to have lower weight status compared to their clinically defined weight status. Compared to their black counterparts, higher proportions of white and Hispanic adolescent females misperceived themselves to be heavier than their clinical weight status. Oaxaca-Blinder decomposition analysis showed that accounting for weight misperceptions, in addition to individual and contextual factors, increased the total explained portion of the black-white female BMI gap from 44.7% to 54.3% but only slightly increased the total explained portion of the Hispanic-white gap from 62.8% to 63.1%. Weight misperceptions explained 13.0% of the black-white female BMI gap and 3.3% of the Hispanic-white female BMI gap. The regression estimates showed that weight underperceptions were important determinants of adolescent female BMI, particularly among black and Hispanic adolescents. Education regarding identification and interpretation of weight status may play an important role to help reduce the incidence and racial disparity of female adolescent obesity.

Ethnic disparities in adolescent body mass index in the United States: the role of parental socioeconomic status and economic contextual factors.

This paper examined the importance of household and economic contextual factors as determinants of ethnic disparities in adolescent body mass index (BMI). Individual-level data from the National Longitudinal Survey of Youth 1997 for the years 1997 through 2000 were combined with economic contextual data on food prices, outlet density and median household income. The Oaxaca-Blinder decomposition method was used to examine the factors that could help explain ethnic disparities in BMI. Ethnic differences in household demographic, parental socioeconomic status (SES), and economic contextual factors explained the majority of the male black-white (63%), male Hispanic-white (78%) and female Hispanic-white (62%) BMI gaps but less than one-half of the female black-white BMI gap (44%). We found that adding the economic contextual factors increased the explained portion of the ethnic BMI gap for both female and male adolescents: the economic contextual factors explained 28% and 38% of the black-white and Hispanic-white BMI gaps for males and 13% and 8% of the black-white and Hispanic-white BMI gaps for females, respectively. Parental SES was more important in explaining the Hispanic-white BMI gap than the black-white BMI gap for both genders, whereas neighborhood economic contextual factors were more important in explaining the male BMI gap than the female BMI gap for both black-white and Hispanic-white ethnic disparities. A significantly large portion of the ethnic BMI gap, however, remained unexplained between black and white female adolescents.

Lung natural helper cells are a critical source of Th2 cell-type cytokines in protease allergen-induced airway inflammation.

Overproduction of cytokines by T helper 2 (Th2) cells in the lung is thought to be a cause of asthma. Here we report that innate lymphocytes termed lung natural helper (LNH) cells are a T cell-independent source of Th2 cell-type cytokines in protease allergen-treated lungs. LNH (Lin(-)Sca-1(+)c-kit(+/lo)CD25(+)CD127(+)) cells, when stimulated by IL-33 plus IL-2, IL-7, or thymic stroma lymphopoietin (TSLP), produced large amounts of IL-5 and IL-13. Intranasal administration of protease allergen papain induced eosinophil infiltration and mucus hyperproduction in the lung of wild-type and Rag1(-/-) mice, but not in Rag2(-/-)Il2rg(-/-) mice that lack LNH cells. LNH cell depletion inhibited papain-induced airway inflammation in Rag1(-/-) mice whereas adoptive transfer of LNH cells enabled Rag2(-/-)Il2rg(-/-) mice to respond to papain. Treatment of lung explants with papain induced IL-33 and TSLP production by stroma cells and IL-5 and IL-13 production by LNH cells. Thus, LNH cells are critical for protease allergen-induced airway inflammation.

Religion and intimate partner violence in Chile: macro- and micro-level influences.

The Catholic Church has had a strong influence on the Chilean legal and social landscape in ways that have adversely affected victims of intimate partner violence; e.g., it succeeded until just five years ago in blocking efforts to legalize divorce. At the same time, quantitative studies based on survey data from the United States and other countries show a generally favorable influence of religion on health and many other domains of life, including intimate partner violence. The present study explores the puzzle posed by these seemingly opposing macro- and micro-level forces. Results based on data from the 2005 Survey of Student Well-Being, a questionnaire on gender-based violence administered to students at a large public university in Chile, show that moderate or low levels of religiosity are associated with reduced vulnerability to violence, but high levels are not. This non-linearity sheds light on the puzzle, because at the macro level the religious views shaping Chile's legal and social environment have been extreme.