The influence of clan structure on the genetic variation in a single Ghanaian village

Socioeconomic and cultural factors are thought to have an important role in influencing human population genetic structure. To explain such population structure differences, most studies analyse genetic differences among widely dispersed human populations. In contrast, we have studied the genetic structure of an ethnic group occupying a single village in north-eastern Ghana. We found a markedly skewed male population substructure because of an almost complete lack of male gene flow among Bimoba clans in this village. We also observed a deep male substructure within one of the clans in this village. Among all males, we observed only three Y-single-nucleotide polymorphism (SNP) haplogroups: E1b1a*-M2, E1b1a7a*-U174 and E1b1a8a*-U209, P277, P278. In contrast to the marked Y-chromosomal substructure, mitochondrial DNA HVS-1 sequence variation and autosomal short-tandem repeats variation patterns indicate high genetic diversities and a virtually random female-mediated gene flow among clans. On the extreme micro-geographical scale of this single Bimoba village, correspondence between the Y-chromosome lineages and clan membership could be due to the combined effects of the strict patrilocal and patrilineal structure. If translated to larger geographic scales, our results would imply that the extent of variation in uniparentally inherited genetic markers, which are typically associated with historical migration on a continental scale, could equally likely be the result of many small and different cumulative effects of social factors such as clan membership that act at a local scale. Such local scale effects should therefore be considered in genetic studies, especially those that use uniparental markers, before making inferences about human history at large.     

Suggestive association between the C825T polymorphism of the G-protein beta3 subunit gene (GNB3) and clinical improvement with antipsychotics in schizophrenia.

G-proteins are composed of alpha, beta and gamma subunits. Once activated, these subunits play a major role in the conversion of external receptor activation into intracellular signals. The functional C825T polymorphism of the beta3 subunit gene (GNB3) has recently been shown to modulate antidepressant response, with the T-allele conferring an increased signaling and being associated with favorable antidepressant response. We hypothesized that this polymorphism may be associated with response to antipsychotics in a population of 145 chronic schizophrenic patients deriving from two study-samples and being mainly treated with clozapine for up to 6 months. Overall, the C/C genotype was significantly associated with relative clinical improvement as measured by Brief Psychiatric Rating Scale (BPRS) change scores after 6 and 12 weeks (p<0.01 and p=0.03, respectively), with estimated effect sizes ranging from 4.8 to 7%. Our results further suggest that this effect is only attributable to Caucasians when compared to African-Americans. Moreover, our findings point to the role of intracellular mechanisms in antipsychotic response.     

Urinary Platinum Levels Associated with Dental Gold Alloys

Platinum concentrations were determined in 50 urine and 20 saliva samples obtained from 50 subjects who had gold dental restorations. In addition, 42 urine and 35 saliva samples were collected from subjects who did not have gold dental restorations. Subjects with gold alloys had significantly (p < .001) higher urinary platinum excretion (mean = 11.9 ± 8.5 ng/gm creatinine, range = 1.9–45.8 ng/gm creatinine) than controls (mean = 6.2 ± 3.2 ng/gm, range = 1.9–14.4 ng/gm creatinine). Mean saliva concentrations were significantly higher in subjects with dental gold alloys (526 pg/gm vs. 8.5 pg/gm; p < .001). A laboratory test with 5 commercially available dental gold/platinum alloys showed that 0.1 % sodium chloride mobilized platinum within 1 hr (i.e., 1–18 pg/ml) of its introduction. In conclusion, dental gold/platinum alloys appear to be the main source for urinary platinum excretion from the occupationally unexposed population.     

EDHF: bringing the concepts together

Endothelial cells synthesize and release vasoactive mediators in response to various neurohumoural substances (e.g. bradykinin or acetylcholine) and physical stimuli (e.g. cyclic stretch or fluid shear stress). The best-characterized endothelium-derived relaxing factors are nitric oxide and prostacyclin. However, an additional relaxant pathway associated with smooth muscle hyperpolarization also exists. This hyperpolarization was originally attributed to the release of an endothelium-derived hyperpolarizing factor (EDHF) that diffuses to and activates smooth muscle K(+) channels. More recent evidence suggests that endothelial cell receptor activation by these neurohumoural substances opens endothelial cell K(+) channels. Several mechanisms have been proposed to link this pivotal step to the subsequent smooth muscle hyperpolarization. The main concepts are considered in detail in this review.     

In an observational study elderly patients had an increased risk of falling due to home hazards

OBJECTIVE: The objective of this study was to explore the relationship between home hazards and the incidence of falls in the oldest old population. STUDY DESIGN AND SETTING: The Leiden 85-plus Study is a population-based study of all 85-year-old inhabitants of Leiden in the birth-cohort 1912-1914. Participants and general practitioners were interviewed at baseline and annually there after. We analyzed the incidence of falling in the first year dependent on the presence of home hazards at baseline. There were no exclusion criteria other than the inability to walk alone. RESULTS: During the 1-year follow-up, 44% of the participants experienced one or more falls. Participants without preceding falls (n=246) had a 4-fold risk for falls in the presence of six or seven home hazards (relative risk 3.58, 95% confidence interval 1.75-5.05) compared with those without home hazards. Participants with preceding falls (n=234) had no increased risk of falls with increasing numbers of home hazards, although they had a higher risk to fall. The data confirmed the known increased risk for falls in participants with physical impairments. CONCLUSION: We conclude that participants without a history of preceding falls have an increased risk of falling due to the presence of home hazards.     

Homocysteine, vitamin B-12, and folic acid and the risk of cognitive decline in old age: the Leiden 85-Plus study

BACKGROUND: High concentrations of homocysteine and low concentrations of vitamin B-12 and folic acid are frequently observed in subjects with dementia. OBJECTIVE: We assessed whether serum concentrations of homocysteine, vitamin B-12, or folic acid predict cognitive decline in old age. DESIGN: This was a prospective, population-based, longitudinal study of 599 subjects (Leiden 85-Plus Study, Netherlands). The subjects were administered a battery of cognitive tests (including the Mini Mental State Examination, the Stroop test, a letter digit coding test, and a word recall test) at 85 y of age and yearly thereafter until 89 y of age. Serum concentrations of homocysteine, vitamin B-12, and folic acid were measured at 85 and 89 y of age. Cross-sectional associations between serum concentrations and cognition were assessed at 85 and 89 y of age. The association between baseline serum concentrations and subsequent longitudinal cognitive decline was assessed with the use of mixed linear models. RESULTS: In the cross-sectional analyses, serum concentrations of homocysteine and folic acid were significantly associated with cognitive performance, but serum concentrations of vitamin B-12 were not. In the longitudinal analyses, there were no significant associations of serum concentrations of homocysteine, vitamin B-12, or folic acid with rate of cognitive decline. CONCLUSIONS: Elevated serum concentrations of homocysteine and reduced folic acid are associated with cognitive impairment in elderly persons but do not predict an increased rate of cognitive decline. The association of high serum concentrations of homocysteine and low folic acid with cognitive impairment in old age is likely to be a consequence of disease and not a contributory cause.     

Alcohol and Drug Use among Youth – The Interplay of Future Orientation,Parenting, and Housing Conditions

Background: Past research indicated that future orientation might protect against substance use; however, this potential had not yet been examined in the context of a multiple risk factor model that would include different parenting styles and indicators of the material situation. Additionally, past research draws primarily from a limited set of geographical regions, often using convenience samples of children and adolescents. Objectives: The current study addresses these issues by examining (in)direct relationships between substance use (alcohol, marijuana, hard drugs), future orientation, different parenting styles (authoritarian, authoritative, permissive), and family housing conditions, using a representative sample of Slovenian youth. Methods: Correlational and path analyses were used to test the proposed hypotheses. Additionally, possible mediating pathways were examined and evaluated. Results: Findings indicated a negative relation between future orientation and use of all substances. Next, future orientation fully mediated the effect of authoritative parenting on substance use. Finally, housing conditions had a direct and positive effect on authoritative parenting, a direct and an indirect effect on future orientation and only an indirect (through authoritative parenting and future orientation) effect on substance use. Conclusions: Results, besides indicating the relevance of future orientation in understanding substance use among youth, highlight the importance of authoritative parenting (that spans beyond childhood and adolescence) and housing conditions on the development of future orientation. In addition, findings highlight the importance of the material situation when examining antecedents of substance use among youth that might be missed if only direct effects are observed. Results are discussed in the context of the risk factor paradigm.     

Predicting kidney graft failure using time-dependent renal function covariates

Chronic rejection and recurrent disease are the major causes of late graft failure in renal transplantation. To assess outcome, most researchers use Cox proportional hazard analysis with time-fixed covariates. We developed a model adding time-dependent renal function covariates to improve the prediction of late graft failure. We studied 692 kidney transplants at the Leiden University Medical Center that had functioned for at least 6 months. Graft failure from chronic rejection or recurrent disease occurred in 106 patients. The reciprocal of last recorded serum creatinine (RC), the ratio of RC and RC at 6 months (RC6), and the time elapsed since last observation (TEL) were used as time-dependent covariates. Cadaveric donor transplantation, a lower RC, and a lower ratio of RC/RC6 were independently associated with graft failure. The impact of the last recorded RC was dependent on its value, TEL, and the time since transplantation. Validation of the model confirmed much higher failure predictions in those with subsequent graft failure compared with nonfailures. This study illustrates that the prediction of late graft failure could be improved significantly by using time-dependent renal function covariates.     

PLASMA FOLLISTATIN CONCENTRATIONS INCREASE FOLLOWING LIPOPOLYSACCHARIDE ADMINISTRATION IN SHEEP

1. The effect of inflammation induced by lipopolysaccharide (LPS) injection on plasma follistatin (FS) concentrations was investigated. 2. Plasma FS and tumour necrosis factor-α concentrations increase following LPS administration in ewes. 3. The rise in FS is similar, but more sustained, to that previously observed after surgery. 4. These results indicate a possible functional link between FS, inflammation and the acute-phase response.