Background Low- and middle-income countries continue to experience a large burden of stunting; 148 million children were estimated to be stunted, around 30–40% of all children in 2011. In many of these countries, foetal growth restriction (FGR) is common, as is subsequent growth faltering in the first 2 years. Although there is agreement that stunting involves both prenatal and postnatal growth failure, the extent to which FGR contributes to stunting and other indicators of nutritional status is uncertain. Methods Using extant longitudinal birth cohorts (n = 19) with data on birth-weight, gestational age and child anthropometry (12–60 months), we estimated study-specific and pooled risk estimates of stunting, wasting and underweight by small-for-gestational age (SGA) and preterm birth. Results We grouped children according to four combinations of SGA and gestational age: adequate size-for-gestational age (AGA) and preterm; SGA and term; SGA and preterm; and AGA and term (the reference group). Relative to AGA and term, the OR (95% confidence interval) for stunting associated with AGA and preterm, SGA and term, and SGA and preterm was 1.93 (1.71, 2.18), 2.43 (2.22, 2.66) and 4.51 (3.42, 5.93), respectively. A similar magnitude of risk was also observed for wasting and underweight. Low birthweight was associated with 2.5–3.5-fold higher odds of wasting, stunting and underweight. The population attributable risk for overall SGA for outcomes of childhood stunting and wasting was 20% and 30%, respectively. Conclusions This analysis estimates that childhood undernutrition may have its origins in the foetal period, suggesting a need to intervene early, ideally during pregnancy, with interventions known to reduce FGR and preterm birth.

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The immunoreceptor PD-1 is significantly up-regulated on exhausted CD8 ؉ T cells during chronic viral infections such as HIV-1. However, it remains unknown whether PD-1 expression on CD8 ؉ T cells differs between typical progressors (TPs) and long-term nonprogressors (LTNPs). In this report, we examined PD-1 expression on HIV-specific CD8 ؉ T cells from 63 adults with chronic HIV infection. We found that LTNPs exhibited functional HIV-specific memory CD8 ؉ T cells with markedly lower PD-1 expression. TPs, in contrast, showed significantly up-regulated PD-1 expression that was closely correlated with a reduction in CD4 T-cell number and an elevation in plasma viral load. Importantly, PD-1 up-regulation was also associated with reduced perforin and IFN-␥ production, as well as decreased HIV-specific effector memory CD8 ؉ T-cell proliferation in TPs but not LTNPs. Blocking PD-1/PD-L1 interactions efficiently restored HIV-specific CD8 ؉ T-cell effector function and proliferation. Taken together, these findings confirm the hypothesis that high PD-1 up-regulation mediates HIV-specific CD8 ؉ T-cell exhaustion. IntroductionCD8 ϩ T cells play a critical role in clearing human immunodeficiency virus (HIV) infection in vivo. 1 In general, typical progressors (TPs) have insufficient CD8 ϩ T-cell responses to HIV and fail to maintain durable control of the HIV load, whereas long-term nonprogressors (LTNPs) preferentially maintain functional HIVspecific CD8 ϩ T cells that can persistently control viral replication. [2][3][4][5][6][7][8][9][10] During the CD8 ϩ T-cell response to HIV, there is a complex process of memory CD8 ϩ T-cell differentiation. 11 On the basis of CD45RA and CCR7 surface marker expression and relative function, 4 subpopulations of memory CD8 ϩ T cells are proposed to exist: naive CD45RA ϩ CCR7 ϩ T cells, central memory CD45RA Ϫ CCR7 ϩ T (T CM ) cells, effector memory CD45RA Ϫ CCR7 Ϫ T (T EM ) cells, and terminally differentiated effector CD45RA ϩ CCR7 Ϫ T (T EM RA) cells. [12][13][14][15] The T CM subpopulation readily differentiates into proliferating effector cells and homes to T-cell areas of the secondary lymphoid organs, but it has little or no effector function. The T EM subset has selectively lost constitutive CCR7 expression and produces high levels of perforin, IFN-␥, and IL-4 within hours of antigenic stimulation. The T EM RA subset, the T EM subpopulation that expresses CD45RA, can produce high levels of perforin. Thus, T EM cells are characterized by rapid effector function. Champagne et al 16 have demonstrated that chronic HIV-1 infection affects the differentiation pattern of different CD8 ϩ T-cell subsets; however, the molecular mechanisms of how this process occurs remain undefined.Memory T-cell responses are an important component of protective immunity against viral infection. However, memory T-cell responses generated during chronic viral infection often show defects in antiviral function and skewed differentiation of the memory T-cell subsets. [16][17][18] For example, the proportion ...

In vivo vagus nerve stimulation holds great promise in regulating food intake for obesity treatment. Here we present an implanted vagus nerve stimulation system that is battery-free and spontaneously responsive to stomach movement. The vagus nerve stimulation system comprises a flexible and biocompatible nanogenerator that is attached on the surface of stomach. It generates biphasic electric pulses in responsive to the peristalsis of stomach. The electric signals generated by this device can stimulate the vagal afferent fibers to reduce food intake and achieve weight control. This strategy is successfully demonstrated on rat models. Within 100 days, the average body weight is controlled at 350 g, 38% less than the control groups. This work correlates nerve stimulation with targeted organ functionality through a smart, self-responsive system, and demonstrated highly effective weight control. This work also provides a concept in therapeutic technology using artificial nerve signal generated from coordinated body activities.

Skin wound healing is a major health care issue. While electric stimulations have been known for decades to be effective for facilitating skin wound recovery, practical applications are still largely limited by the clumsy electrical systems. Here, we report an efficient electrical bandage for accelerated skin wound healing. On the bandage, an alternating discrete electric field is generated by a wearable nanogenerator by converting mechanical displacement from skin movements into electricity. Rat studies demonstrated rapid closure of a fullthickness rectangular skin wound within 3 days as compared to 12 days of usual contraction-based healing processes in rodents. From in vitro studies, the accelerated skin wound healing was attributed to electric field-facilitated fibroblast migration, proliferation, and transdifferentiation. This selfpowered electric-dressing modality could lead to a facile therapeutic strategy for nonhealing skin wound treatment.