Grandmothers’ Productivity and the HIV/AIDS Pandemic in sub-Saharan Africa

The human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) pandemic has left large numbers of orphans in sub-Saharan Africa. Botswana has an HIV prevalence rate of approximately 40% in adults. Morbidity and mortality are high, and in a population of a 1.3 million there are nearly 50,000 children who have lost one or both parents to HIV/AIDS. The extended family, particularly grandparents, absorbs much of the childrearing responsibilities. This creates large amounts of additional work for grandmothers especially. The embodied capital model and the grandmother hypothesis are both derived from life history theory within evolutionary ecology, and both predict that one important factor in the evolution of the human extended family structure is that postreproductive individuals such as grandmothers provide substantial support to their grandchildren's survival. Data collected in the pre-pandemic context in a traditional multi-ethnic community in the Okavango Delta of Botswana are analyzed to calculate the amount of work effort provided to a household by women of different ages. Results show that the contributions of older and younger women to the household in term of both productivity and childrearing are qualitatively and quantitatively different. These results indicate that it is unrealistic to expect older women to be able to compensate for the loss of younger women's contributions to the household, and that interventions be specifically designed to support older women based on the type of activities in which they engage that affect child survival, growth, and development.     

Wnt/β-catenin signaling is involved in the induction and maintenance of primitive hematopoiesis in the vertebrate embryo

The formation of primitive (embryonic) blood in vertebrates is mediated by spatio-temporally restricted signaling between different tissue layers. In Xenopus, in which primitive blood originates in the ventral blood island, this involves the secretion of bone morphogenetic protein (BMP) ligands by the ectoderm that signal to the underlying mesoderm during gastrulation. Using novel transgenic reporter lines, we report that the canonical Wnt/β-catenin pathway is also activated in the blood islands in Xenopus. Furthermore, Wnt-reporter activity was also detected in the blood islands of the mouse yolk sac. By using morpholino-mediated depletion in Xenopus, we identified Wnt4 as the ligand that is expressed in the mesoderm of the ventral blood island and is essential for the expression of hematopoietic and erythroid marker genes. Injection of an inducible Wnt-interfering construct further showed that, during gastrulation, Wnt/β-catenin signaling is required both in the mesoderm and in the overlying ectoderm for the formation of the ventral blood island. Using recombination assays with embryonic explants, we document that ectodermal BMP4 expression is dependent on Wnt4 signals from the mesoderm. Our results thus reveal a unique role for Wnt4-mediated canonical signaling in the formation and maintenance of the ventral blood island in Xenopus.     

The relationship between the production and the anti-gonadotrophic action of prostaglandin F2α in luteal cells from the marmoset monkey (Callithrix jacchus) in the early and mid-luteal phase

To address the potential luteolytic role for prostaglandin F_2α (PGF_2α) in the corpus luteum of the common marmoset monkey (Callithrix jacchus), the ability of marmoset luteal cells, maintained in monolayer culture, to produce PGF_2α was determined in vitro in the presence and absence of human chorionic gonadotrophin (hCG) and other established pharmacological modulators of PGF_2α synthesis. We also assessed the effects of the PGF_2α analogue, cloprostenol, on progesterone output from luteal cells isolated in the early luteal phase versus the mid-luteal phase (days 3 and 14 post ovulation, respectively). Cloprostenol had no effect on progesterone output from luteal cells isolated on day 3 of the luteal phase, whereas it significantly inhibited both basal and hCG-stimulated progesterone synthesis by day 14 luteal cells during the culture period 48-72 h (P < 0.001). Intra-luteal PGF_2α concentrations were 5-fold higher in luteal cells isolated in the early luteal phase than in mid-luteal phase cells (16.5 ± 3.5 versus 3.5 ± 0.6 pmol/10⁵ cells). While PGF_2α production was unaffected by hCG in vitro, it was decreased by indomethacin (1000 ng/ml) (P < 0.05) and stimulated by the calcium ionophore A23187 (10 μmol/l) (P < 0.05) in luteal cells from both stages of the luteal phase. Phospholipase A₂ did not influence PGF_2α production by day 3 luteal cells whereas at 10 IU/ml, it significantly stimulated PGF_2α production by day 14 luteal cells (P < 0.05). Hence, the timing of luteolysis in the common marmoset monkey appears to involve changes in both the luteal cell response to and production of PGF_2α.     

Alcohol metabolites and lipopolysaccharide： Roles in the development and/or progression of alcoholic liver disease

The onset of alcoholic liver disease (ALD) is initiated by different cell types in the liver and a number of different factors including: products derived from ethanol- induced inflammation, ethanol metabolites, and the indirect reactions from those metabolites. Ethanol oxidation results in the production of metabolites that have been shown to bind and form protein adducts,and to increase inflammatory, fibrotic and cirrhotic responses. Lipopolysaccharide (LPS) has many deleterious effects and plays a significant role in a number of disease processes by increasing inflammatory cytokine release. In ALD, LPS is thought to be derived from a breakdown in the intestinal wall enabling LPS from resident gut bacterial cell walls to leak into the blood stream. The ability of adducts and LPS to independently stimulate the various cells of the liver provides for a two-hit mechanism by which various biological responses are induced and result in liver injury. Therefore,the purpose of this article is to evaluate the effects of a two-hit combination of ethanol metabolites and LPS on the cells of the liver to increase inflammation inflammation and fibrosis, and play a role in the development and/or progression of ALD.     

The electrocardiogram in right ventricular cardiomyopathy/dysplasia. How can the electrocardiogram assist in understanding the pathologic and functional changes of the heart in this disease?

The electrocardiogram (ECG) provides important information to aid in the diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). The ECG changes may be explained by the pathophysiology of the disease. The proximity of the right ventricle (RV) to the anterior chest leads (V₁ to V₄) explains why the characteristic ECG abnormalities are most prominent in those lends. The specific ECG abnormalities reflect the pathophysiology of the disease including T-wave inversion due to scarring of the free wall of the RV, prolonged S-wave duration due to slow depolarization of the terminal part of the QRS because the RV is the last part of the heart to undergo depolatization, and epsilon waves due to slow conduction in the RV. The extent of ECG abnormalities correlate with the degree of structural change in the RV.     

Gastroenterology in the next century:megatrends in science and practice

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Interplay between the renin-angiotensin system,the canonical WNT/β-catenin pathway and PPARγ in hypertension

Purpose of Review

Heterogeneous causes can determinate hypertension.

Recent Findings

The renin-angiotensin system (RAS) has a major role in the pathophysiology of blood pressure. Angiotensin II and aldosterone are overexpressed during hypertension and lead to hypertension development and its cardiovascular complications. In several tissues, the overactivation of the canonical WNT/β-catenin pathway leads to inactivation of peroxisome proliferator-activated receptor gamma (PPARγ), while PPARγ stimulation induces a decrease of the canonical WNT/β-catenin pathway. In hypertension, the WNT/β-catenin pathway is upregulated, whereas PPARγ is decreased. The WNT/β-catenin pathway and RAS regulate positively each other during hypertension, whereas PPARγ agonists can decrease the expression of both the WNT/β-catenin pathway and RAS.

Summary

We focus this review on the hypothesis of an opposite interplay between PPARγ and both the canonical WNT/β-catenin pathway and RAS in regulating the molecular mechanism underlying hypertension. The interactions between PPARγ and the canonical WNT/β-catenin pathway through the regulation of the renin-angiotensin system in hypertension may be an interesting way to better understand the actions and the effects of PPARγ agonists as antihypertensive drugs.

     

Association between the α-adducin gene and hypertension in the HyperGEN study

This report from the HyperGEN Study, one of four networks participating in the NHLBI-sponsored Family Blood Pressure Program, presents the results of an association study based on 822 white and 572 black subjects (cases and controls) participating in the HyperGEN Network from five geographically diverse field centers. All cases met the Joint National Committee on Detection and Treatment of High Blood Pressure (JNC VI) criteria for hypertension (Stage I or higher). Each subject was clinically examined for risk factors for hypertension as well as genotyped for the point mutation Gly460Trp at the α-adducin locus on chromosome 4p. In the white group, the prevalence of genotypes with one or more Trp alleles was 26% in normotensives, versus 33% in hypertensives randomly selected from the population, and 39% among the multiply affected hypertensive sibships. Overall, in whites, the Trp allele significantly increased the odds of hypertension (P = .0056), with an odds ratio (OR) of 1.73 (95% confidence interval [CI] = 1.17, 2.54). The α-adducin gene remained a significant independent predictor of hypertension in a multivariate logistic model even after correcting for other risk factors for hypertension, including gender, age, body mass index (BMI), smoking, LDL cholesterol, triglycerides, urine sodium (Na), and urine potassium (K), (OR = 1.55, 95% CI = 1.03, 2.34). Through the use of regression trees, several gene-by-environment interactions were implicated, suggesting that α-adducin appears to be a particularly important risk factor (OR = 4.2) for older (age > 60.5 years), less lean (BMI < 25.8 kg/m²) subjects with moderately high triglycerides (between 145.5 and 218.5 mg/dL). In the black group, the relationship was less clear. Overall, it was protective against hypertension. The prevalence of genotypes with one or more Trp alleles was 24% among normotensive versus 11% in hypertensive black subjects randomly selected from the population, and 13% among multiply affected hypertensive sibships, resulting in an OR of 0.48 (P = .0231; 95% CI = 0.25, 0.90). However, the Trp genotype was no longer a significant independent predictor of hypertension risk in the multivariate logistic model (OR = 0.79; 95% CI = 0.37, 1.67), suggesting that it may be operating through one or more of these other factors. Thus, we conclude that the α-adducin gene is a significant, independent risk factor for hypertension in whites, but not in blacks, and may play a particularly important role for subjects with certain constellations of other risk factors.     

Cardiac rehabilitation and exercise therapy in the elderly: Should we invest in the aged?

Coronary heart disease (CHD) is the leading cause of death worldwide and becomes increasingly prevalent among patients aged 65 years and older. Elderly patients are at a higher risk for complications and accelerated physical deconditioning after a cardiovascular event, especially compared to their younger counterparts. The last few decades were privy to multiple studies that demonstrated the beneficial effects of cardiac rehabilitation (CR) and exercise therapy on mortality, exercise capacity, psychological risk factors, inflammation, and obesity among patients with CHD. Unfortunately, a significant portion of the available data in this field pertains to younger patients. A viable explanation is that older patients are grossly underrepresented in these programs for multiple reasons starting with the patient and extending to the physician. In this article, we will review the benefits of CR programs among the elderly, as well as some of the barriers that hinder their participation.     

Maternal Obesity and Cardiac Development in the Offspring: Study in Human Neonates and Minipigs

Objectives

The aim of this study was to investigate the consequences of maternal overweight on cardiac development in offspring in infants (short term) and minipigs (short and longer term).