Herpes simplex virus (HSV) infections manifest as recurrent oral or genital mucosal lesions, meningoencephalitis, corneal blindness, and perinatal disease. Subunit vaccines have advanced into the clinic without success. None were tested preclinically in male mice. We compared a single-cycle candidate vaccine deleted in HSV-2 glycoprotein D (ΔgD-2) and subunit gD-2 or gD-1 protein vaccines in a male murine skin model. The ΔgD-2 provided complete protection against 10 times the lethal dose of HSV-1 or HSV-2 clinical isolates, and no latent virus was detected, whereas gD-1- and gD-2-adjuvanted proteins provided little or no protection. Protection correlated with Fc receptor activating but not neutralizing antibody titers.

Food insecurity is defined as limited or uncertain ability to acquire nutritionally adequate and safe foods in socially acceptable ways. The United States Department of Agriculture (USDA) has divided food insecurity into two categories: low food security and very low food security. Low food security is characterized by irregular access to food, binge eating when food is available, overconsumption of energy-dense foods, obesity, and even type 2 diabetes. This type of food insecurity occurs in impoverished urban areas of high-income countries such as the United States. In contrast, very low food security is distinctly different from low food security and can lead to undernutrition and frank starvation. Very low food security is found in developing countries in both rural areas and urban slums. In these countries, food insecurity is often exacerbated by natural disasters and climate changes that compromise food availability. With a focus on the social, economic, and behavioral factors that promote obesity and cardiometabolic disease in food insecure households in the United States, this review will first define the key terms and concepts associated with food insecurity. Then, the characteristics of food insecure households and the relationship to cardiometabolic disease will be discussed. Finally, the cardiac consequences of food insecurity in developing countries will be briefly described.

Vitamin D levels in people of African descent are often described as inadequate or deficient. Whether low vitamin D levels in people of African descent lead to compromised bone or cardiometabolic health is unknown. Clarity on this issue is essential because if clinically significant vitamin D deficiency is present, vitamin D supplementation is necessary. However, if vitamin D is metabolically sufficient, vitamin D supplementation could be wasteful of scarce resources and even harmful. In this review vitamin D physiology is described with a focus on issues specific to populations of African descent such as the influence of melanin on endogenous vitamin D production and lactose intolerance on the willingness of people to ingest vitamin D fortified foods. Then data on the relationship of vitamin D to bone and cardiometabolic health in people of African descent are evaluated.

Background: The prevalence of cardiometabolic disease in Africa now rivals that of Western nations. Therefore, screening programs that lead to effective prevention of cardiometabolic disease in Africans is imperative. Most screening tests for cardiometabolic disease use triglyceride (TG) levels as a criterion. However, the failure rate of TG-based screening tests in African Americans is high. In Africans, the efficacy of TG-based screening tests is unknown. Our goal was to determine the association between hypertriglyceridemia (TG ‡ 150 mg/dL) and cardiometabolic disease in African and African-American men. Research Design and Methods: This was a cross-sectional study of 155 men (80 African immigrants, 75 African Americans) [age, 35 -9 years, mean -standard deviation (SD), body mass index (BMI) 28.5 -5.2 kg/m 2 ] who self-identified as healthy. Lipid profiles were performed. Glucose tolerance and insulin resistance was determined by oral glucose tolerance tests (OGTT) and the insulin sensitivity index (S I ), respectively. Cardiometabolic disease was defined by four possible subtypes-prediabetes, diabetes, insulin resistance, or metabolic triad [hyperinsulinemia, hyperapolipoprotein B, small low-density lipoprotein (LDL) particles]. Results: TG levels were higher in men with cardiometabolic disease than without (88 -43 versus 61 -26 mg/dL, P < 0.01). However, < 10% of men with cardiometabolic disease had TG ‡ 150 mg/dL. Even within each cardiometabolic disease subtype, the prevalence of TG ‡ 150 mg/dL was < 10%. Furthermore, TG levels in the 5% of men identified by OGTT as diabetic were £ 100 mg/dL (mean 71 -24, range 45-100 mg/dL). Conclusions: Hypertriglyceridemia is a poor marker of cardiometabolic disease in men of African descent. Therefore TG-based screening tests fail to identify both African immigrants and African-American men with cardiometabolic disease. As a consequence, the opportunity for early intervention and prevention is lost.

Herpes simplex virus 1 (HSV-1) is a leading cause of infectious blindness, highlighting the need for effective vaccines. A single-cycle HSV-2 strain with the deletion of glycoprotein D, ΔgD-2, completely protected mice from HSV-1 and HSV-2 skin or vaginal disease and prevented latency following active or passive immunization in preclinical studies. The antibodies functioned primarily by activating Fc receptors to mediate antibody-dependent cellular cytotoxicity (ADCC). The ability of ADCC to protect the immune-privileged eye, however, may differ from skin or vaginal infections. Thus, the current studies were designed to compare active and passive immunization with ΔgD-2 versus an adjuvanted gD subunit vaccine (rgD-2) in a primary lethal ocular murine model. ΔgD-2 provided significantly greater protection than rgD-2 following a two-dose vaccine regimen, although both vaccines were protective compared to an uninfected cell lysate. However, only immune serum from ΔgD-2-vaccinated, but not rgD-2-vaccinated, mice provided significant protection against lethality in passive transfer studies. The significantly greater passive protection afforded by ΔgD-2 persisted after controlling for the total amount of HSV-specific IgG in the transferred serum. The antibodies elicited by rgD-2 had significantly higher neutralizing titers, whereas those elicited by ΔgD-2 had significantly more C1q binding and Fc gamma receptor activation, a surrogate for ADCC function. Together, the findings suggest ADCC is protective in the eye and that nonneutralizing antibodies elicited by ΔgD-2 provide greater protection than neutralizing antibodies elicited by rgD-2 against primary ocular HSV disease. The findings support advancement of vaccines, including ΔgD-2, that elicit polyfunctional antibody responses. IMPORTANCE Herpes simplex virus 1 is the leading cause of infectious corneal blindness in the United States and Europe. Developing vaccines to prevent ocular disease is challenging because the eye is a relatively immune-privileged site. In this study, we compared a single-cycle viral vaccine candidate, which is unique in that it elicits predominantly nonneutralizing antibodies that activate Fc receptors and bind complement, and a glycoprotein D subunit vaccine that elicits neutralizing but not Fc receptor-activating or complement-binding responses. Only the single-cycle vaccine provided both active and passive protection against a lethal ocular challenge. These findings greatly expand our understanding of the types of immune responses needed to protect the eye and will inform future prophylactic and therapeutic strategies.

"The human brain grows rapidly in early childhood, reaching 95% of its final volume by age 6. Understanding brain growth in childhood is important both to answer neuroscience questions about anatomical changes in development, and as a comparison metric for neurological disorders. Metrics for neuroanatomical development including cortical measures pertaining to the sulci can be instrumental in early diagnosis, monitoring and intervention for neurological diseases. In this paper, we examine the development of the central sulcus in children aged 12 to 60 months from structural magnetic resonance images. The central sulcus is one of the earliest sulci to develop at the fetal stage and is implicated in diseases such as Attention Deficit Hyperactive Disorder and Williams syndrome. We investigate the relationship between the changes in the depth of the central sulcus with respect to age. In our results, we observed a pattern of depth present early on, that had been previously observed in adults. Results also reveal the presence of a rightward depth asymmetry at age 12 month at a location related to orofacial movements. That asymmetry disappears gradually, mostly between 12 and 24 months, and we suggest that it is related to the development of language skills."

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