Effect of Isovolemic,Isothermic Hemodialysis on Cerebral Perfusion and Vascular Stiffness Using Contrast Computed Tomography and Pulse Wave Velocity

Background

Patients undergoing hemodialysis treatment have a six-fold increased risk for stroke relative to the general population. However, the effect of hemodialysis on cerebral blood flow is poorly studied and confounding factors like blood pressure and ultrafiltration as well as temperature changes have rarely been accounted for. The aim of our study was to use state-of-the-art technology to evaluate the effect of a single dialysis session on cerebral perfusion as well as on vascular stiffness.

Methods

Chronic hemodialysis patients (7 male/3 female, mean age 58 years) were recruited. Cerebral blood flow and arterial pulse wave velocity were measured before and immediately after a hemodialysis session. To exclude effects of volume changes we kept ultrafiltration to a minimum, allowing no change in body weight. Isothermic conditions were maintained by using the GENIUS single-pass batch-dialysis system with a high-flux polysulfone dialyser. Cerebral blood flow was measured by contrast-enhanced computed tomography. Pulse wave velocity was measured using the SphygmoCor (AtCor Medical, USA) device by a single operator.

Results

This study shows for the first time that isovolemic, isothermic hemodialysis neither affected blood pressure or heart rate, nor total or regional cerebral perfusion. There was also no change in pulse wave velocity.

Conclusions

Mechanisms other than the dialysis procedure itself might be causative for the high incidence of ischemic strokes in this patient population. Moreover, the sole removal of uremic toxins does not lead to short-term effects on vascular stiffness, underlying the importance of volume control in this patient population.     

The effect of genomic information on optimal contribution selection in livestock breeding programs

Background

Long-term benefits in animal breeding programs require that increases in genetic merit be balanced with the need to maintain diversity (lost due to inbreeding). This can be achieved by using optimal contribution selection. The availability of high-density DNA marker information enables the incorporation of genomic data into optimal contribution selection but this raises the question about how this information affects the balance between genetic merit and diversity.

Methods

The effect of using genomic information in optimal contribution selection was examined based on simulated and real data on dairy bulls. We compared the genetic merit of selected animals at various levels of co-ancestry restrictions when using estimated breeding values based on parent average, genomic or progeny test information. Furthermore, we estimated the proportion of variation in estimated breeding values that is due to within-family differences.

Results

Optimal selection on genomic estimated breeding values increased genetic gain. Genetic merit was further increased using genomic rather than pedigree-based measures of co-ancestry under an inbreeding restriction policy. Using genomic instead of pedigree relationships to restrict inbreeding had a significant effect only when the population consisted of many large full-sib families; with a half-sib family structure, no difference was observed. In real data from dairy bulls, optimal contribution selection based on genomic estimated breeding values allowed for additional improvements in genetic merit at low to moderate inbreeding levels. Genomic estimated breeding values were more accurate and showed more within-family variation than parent average breeding values; for genomic estimated breeding values, 30 to 40% of the variation was due to within-family differences. Finally, there was no difference between constraining inbreeding via pedigree or genomic relationships in the real data.

Conclusions

The use of genomic estimated breeding values increased genetic gain in optimal contribution selection. Genomic estimated breeding values were more accurate and showed more within-family variation, which led to higher genetic gains for the same restriction on inbreeding. Using genomic relationships to restrict inbreeding provided no additional gain, except in the case of very large full-sib families.     

Bacteriuria amongst Pregnant Women in the Buea Health District,Cameroon: Prevalence,Predictors, Antibiotic Susceptibility Patterns and Diagnosis

Background

Bacteriuria is associated with significant maternal and foetal risks. However, its prevalence is not known in our community.

Objectives

This study was carried out to determine the prevalence and predictors of bacteriuria in pregnant women of the Buea Health District (BHD) as well as the antibiotic sensitivity patterns of bacterial isolates. It also sought to determine the diagnostic performance of the nitrite and leucocyte esterase tests in detecting bacteriuria in these women.

Methods

An observational analytic cross-sectional study was carried out amongst pregnant women attending selected antenatal care centres in Buea. We recruited 102 consenting pregnant women for the study. Demographic and clinical data were collected using structured questionnaires. Clean catch midstream urine was collected from each participant in sterile leak proof containers. Samples were examined biochemically, microscopically and by culture. Significant bacteriuria was defined as the presence of ≥10⁸ bacteria/L of cultured urine. Identification and susceptibility of isolates was performed using API 20E and ATB UR EU (08) (BioMerieux, Marcy l''Etoile, France).

Results

Significant bacteriuria was found in the urine of 24 of the 102 women tested giving a bacteriuria prevalence of 23.5% in pregnant women of the BHD. Asymptomatic bacteriuria was detected in 8(7.8%) of the women. There was no statistically significant predictor of bacteriuria. Escherichia coli were the most isolated (33%) uropathogens and were 100% sensitive to cefixime, cefoxitin and cephalothin. The nitrite and leucocyte esterase tests for determining bacteriuria had sensitivities of 8%, 20.8% and specificities of 98.7% and 80.8% respectively.

Conclusion

Bacteriuria is frequent in pregnant women in the BHD suggesting the need for routine screening by urine culture. Empiric treatment with cefixime should be instituted until results of urine culture and sensitivity are available. Nitrite and leucocyte esterase tests were not sensitive enough to replace urine culture as screening tests.     

Literature-Informed Analysis of a Genome-Wide Association Study of Gestational Age in Norwegian Women and Children Suggests Involvement of Inflammatory Pathways

BackgroundFive-to-eighteen percent of pregnancies worldwide end in preterm birth, which is the major cause of neonatal death and morbidity. Approximately 30% of the variation in gestational age at birth can be attributed to genetic factors. Genome-wide association studies (GWAS) have not shown robust evidence of association with genomic loci yet.MethodsWe separately investigated 1921 Norwegian mothers and 1199 children from pregnancies with spontaneous onset of delivery. Individuals were further divided based on the onset of delivery: initiated by labor or prelabor rupture of membranes. Genetic association with ultrasound-dated gestational age was evaluated using three genetic models and adaptive permutations. The top-ranked loci were tested for enrichment in 12 candidate gene-sets generated by text-mining PubMed abstracts containing pregnancy-related keywords.ResultsThe six GWAS did not reveal significant associations, with the most extreme empirical p = 5.1 × 10⁻⁷. The top loci from maternal GWAS with deliveries initiated by labor showed significant enrichment in 10 PubMed gene-sets, e.g., p = 0.001 and 0.005 for keywords "uterus" and "preterm" respectively. Enrichment signals were mainly caused by infection/inflammation-related genes TLR4, NFKB1, ABCA1, MMP9. Literature-informed analysis of top loci revealed further immunity genes: IL1A, IL1B, CAMP, TREM1, TFRC, NFKBIA, MEFV, IRF8, WNT5A.ConclusionOur analyses support the role of inflammatory pathways in determining pregnancy duration and provide a list of 32 candidate genes for a follow-up work. We observed that the top regions from GWAS in mothers with labor-initiated deliveries significantly more often overlap with pregnancy-related genes than would be expected by chance, suggesting that increased sample size would benefit similar studies.     

The highly diverged trypanosomal MICOS complex is organized in a nonessential integral membrane and an essential peripheral module

The mitochondrial contact site and cristae organization system (MICOS) mediates the formation of cristae, invaginations in the mitochondrial inner membrane. The highly diverged MICOS complex of the parasitic protist Trypanosoma brucei consists of nine subunits. Except for two Mic10‐like and a Mic60‐like protein, all subunits are specific for kinetoplastids. Here, we determined on a proteome‐wide scale how ablation of individual MICOS subunits affects the levels of the other subunits. The results reveal co‐regulation of TbMic10‐1, TbMic10‐2, TbMic16 and TbMic60, suggesting that these nonessential, integral inner membrane proteins form an interdependent network. Moreover, the ablation of TbMic34 and TbMic32 reveals another network consisting of the essential, intermembrane space‐localized TbMic20, TbMic32, TbMic34 and TbMic40, all of which are peripherally associated with the inner membrane. The downregulation of TbMic20, TbMic32 and TbMic34 also interferes with mitochondrial protein import and reduces the size of the TbMic10‐containing complexes. Thus, the diverged MICOS of trypanosomes contains two subcomplexes: a nonessential membrane‐integrated one, organized around the conserved Mic10 and Mic60, that mediates cristae formation, and an essential membrane‐peripheral one consisting of four kinetoplastid‐specific subunits, that is required for import of intermembrane space proteins.     

Characterization of the NADH:ubiquinone oxidoreductase (complex I) in the trypanosomatid Phytomonas serpens (Kinetoplastida)

NADH dehydrogenase activity was characterized in the mitochondrial lysates of Phytomonas serpens, a trypanosomatid flagellate parasitizing plants. Two different high molecular weight NADH dehydrogenases were characterized by native PAGE and detected by direct in-gel activity staining. The association of NADH dehydrogenase activities with two distinct multisubunit complexes was revealed in the second dimension performed under denaturing conditions. One subunit present in both complexes cross-reacted with the antibody against the 39 kDa subunit of bovine complex I. Out of several subunits analyzed by MS, one contained a domain characteristic for the LYR family subunit of the NADH:ubiquinone oxidoreductases. Spectrophotometric measurement of the NADH:ubiquinone 10 and NADH:ferricyanide dehydrogenase activities revealed their different sensitivities to rotenone, piericidin, and diphenyl iodonium.