Control of Blood Pressure and Risk Attenuation: Post Trial Follow-Up of Randomized Groups

Background

Evidence on long term effectiveness of public health strategies for lowering blood pressure (BP) is scarce. In the Control of Blood Pressure and Risk Attenuation (COBRA) Trial, a 2 x 2 factorial, cluster randomized controlled trial, the combined home health education (HHE) and trained general practitioner (GP) intervention delivered over 2 years was more effective than no intervention (usual care) in lowering systolic BP among adults with hypertension in urban Pakistan. However, it was not clear whether the effect would be sustained after the cessation of intervention. We conducted 7 years follow-up inclusive of 5 years of post intervention period of COBRA trial participants to assess the effectiveness of the interventions on BP during extended follow-up.

Methods

A total of 1341 individuals 40 years or older with hypertension (systolic BP 140 mm Hg or greater, diastolic BP 90 mm Hg or greater, or already receiving treatment) were followed by trained research staff masked to randomization status. BP was measured thrice with a calibrated automated device (Omron HEM-737 IntelliSense) in the sitting position after 5 minutes of rest. BP measurements were repeated after two weeks. Generalized estimating equations (GEE) were used to analyze the primary outcome of change in systolic BP from baseline to 7- year follow-up. The multivariable model was adjusted for clustering, age at baseline, sex, baseline systolic and diastolic BP, and presence of diabetes.

Findings

After 7 years of follow-up, systolic BP levels among those randomised to combined HHE plus trained GP intervention were significantly lower (2.1 [4.1–0.1] mm Hg) compared to those randomised to usual care, (P = 0.04). Participants receiving the combined intervention compared to usual care had a greater reduction in LDL-cholesterol (2.7 [4.8 to 0.6] mg/dl.

Conclusions

The benefit in systolic BP reduction observed in the original cohort assigned to the combined intervention was attenuated but still evident at 7- year follow-up. These findings highlight the potential for scaling-up simple strategies for cardiovascular risk reduction in low- and middle- income countries.

Trial Registration

ClinicalTrials.gov NCT00327574     

Green synthesis of zinc nanoparticles using Lavandula angustifolia Vera. Extract by microwave method and its prophylactic effects on Toxoplasma gondii infection

BackgroundToday, a suitable vaccine has not yet been discovered to prevent Toxoplasma gondii infection. Therefore, prophylaxis can be suggested as the preferred approach to prevent toxoplasmosis. This study aims to evaluate the prophylactic effects of synthesized zinc nanoparticles (ZnNPs) using Lavandula angustifolia Vera., by microwave method on chronic toxoplasmosis in mice.MethodsBALB/c Mice orally administrated with ZnNPs the doses of 32.5, 75, 150 mg/kg/day for two weeks. On the 15th day, the mice were intraperitoneally infected with the Tehran strain of T. gondii (25 tissue cysts). The mean diameter and the numbers of brain tissue cysts, as well as the mRNA levels of inducible nitric oxide synthesize (iNOs), and interferon-gamma (IFN-γ) in mice of each experimental group were evaluated.ResultsThe synthesized ZnNPs represent a spherical form with a size ranging from 30 to 80 nm. The results revealed that oral administration of Zn NPs at the doses of 32.5 (p < 0.001) and 75 mg/kg/day (p < 0.001) for 14 days significantly reduced the mean number and diameter of the brain tissue cysts in tested mice. No T. gondii tissue cyst was observed after oral administration of Zn NPs at the doses of 150 mg/kg. Based on the results of Real-time PCR analysis, the expression level of IFN-γ and iNOs was significantly increased (p < 0.001) in mice treated with 32.5, 75, 150 mg/kg/day for two weeks.ConclusionThe obtained findings of the current investigation exhibit the significant prophylactic effects of ZnNPs against chronic toxoplasmosis in mice; so that oral administration of ZnNPs the doses 32.5, 75, 150 mg/kg reduced the parasite load and even completely controlled the infection in mice. The results show that the ZnNPs had strengthened the innate immune system which could be the reason for its strong prophylactic effects. However, further in vivo and clinical investigations are required to confirm these results as well as other possible mechanisms that can trigger these pharmacological properties.     

Selective localization of Mfn2 near PINK1 enables its preferential ubiquitination by Parkin on mitochondria

Mutations in Parkin and PINK1 cause early-onset familial Parkinson''s disease. Parkin is a RING-In-Between-RING E3 ligase that transfers ubiquitin from an E2 enzyme to a substrate in two steps: (i) thioester intermediate formation on Parkin and (ii) acyl transfer to a substrate lysine. The process is triggered by PINK1, which phosphorylates ubiquitin on damaged mitochondria, which in turn recruits and activates Parkin. This leads to the ubiquitination of outer mitochondrial membrane proteins and clearance of the organelle. While the targets of Parkin on mitochondria are known, the factors determining substrate selectivity remain unclear. To investigate this, we examined how Parkin catalyses ubiquitin transfer to substrates. We found that His433 in the RING2 domain contributes to the catalysis of acyl transfer. In cells, the mutation of His433 impairs mitophagy. In vitro ubiquitination assays with isolated mitochondria show that Mfn2 is a kinetically preferred substrate. Using proximity-ligation assays, we show that Mfn2 specifically co-localizes with PINK1 and phospho-ubiquitin (pUb) in U2OS cells upon mitochondrial depolarization. We propose a model whereby ubiquitination of Mfn2 is efficient by virtue of its localization near PINK1, which leads to the recruitment and activation of Parkin via pUb at these sites.     

Reduced Axoplasmic Somatostatin Transport in Hypothyroid Rats

The effect of hypothyroidism on neuronal function was studied by measuring axoplasmic transport of immunoreactive somatostatin in rat sciatic nerve by the ligation technique. Accumulation of immunoreactive somatostatin proximal to a ligature was linear up to 8 h in normal, in thyroidectomized, and in parathyroidectomized rats. The transport rate was decreased by 38% in thyroidectomized rats as compared to normal rats and was unchanged in parathyroidectomized rats. Sciatic nerve content of somatostatin in hypothyroid rats did not differ from control. Reduced accumulation of immunoreactive somatostatin in hypothyroid rats may be due to a decrease in somatostatin synthesis or in axoplasmic transport, or to an increase in the degradation rate of the peptide.     

Aspartate aminotransferase allozyme variation in a germplasm collection of the domesticated lentil (Lens culinaris)

Summary Variation at a polymorphic Aspartate aminotransferase locus was assayed in a sample of 298 accessions from the ICARDA germplasm collection of the domesticated lentil (Lens culinaris). Two alleles Aat-1 ^F and Aat-1 ^S were detected with global frequencies of 0.51 and 0.49, respectively. Fifty-nine percent of accessions were polymorphic for both alleles. The frequency of outcrossing was estimated from the observed heterozygosity to be about 1%. This is higher than direct estimates of outcrossing and implicates selection in favour of heterozygous gene combinations. Significant variation in allele frequency and in the occurrence of polymorphic accessions was observed between countries or geographic areas. Significant associations were observed between the allozymes and agronomic characters. In particular high frequency of Aat-1 ^F appeared to be associated with late flowering and maturity and low yield.     

崇明东滩湿地芦苇种群内功能性状及生态对策变异分析

植物种群功能性状及生态对策变异对其自身环境适应能力及群落结构具有重要影响。该文基于崇明东滩湿地芦苇(Phragmites australis)种群内3个小种群不同发育时期分株集合的多项性状指标,分析了其性状及生态对策变异,并基于CSR、LHS生态对策体系,对各小种群的生态对策进行了排序。结果表明, 3个芦苇小种群的21项性状指标及C、R对策得分均存在显著差异。在LHS体系中,以比叶面积(11.5 mm2/mg)、株高(175 cm)和花序干质量(4 g)为分界线,可对3个小种群进行区分。处于生殖生长期的芦苇分株具有更大的植株大小、更高的叶片干物质含量及S对策得分,而处于营养生长期的分株则具有较小的植株大小、较大的比叶面积及R对策得分。总体而言,崇明东滩湿地3个芦苇小种群间及各小种群内处于不同生长发育阶段的分株集合间,都存在显著的性状差异及生态对策差异,且二者的差异模式基本吻合。芦苇种内性状及生态对策变异特征,可为该区芦苇种群的生态保育和恢复实践提供重要的理论参考和技术支撑。     

A novel homozygous frameshift variant in the <Emphasis Type="Italic">MCPH1 gene causes</Emphasis> primary microcephaly in a consanguineous Saudi family

Primary microcephaly (MCPH) is a rare developmental defect characterized by impaired cognitive functions, retarded neurodevelopment and reduced brain size. It is genetically heterogeneous and so far more than 17 genes associated with this disease have been identified. Primary microcephaly type 1 (MCPH1) gene encodes a protein called microcephalin, which is implicated in chromosome condensation and DNA damage induced cellular responses. It is suggested to play a role in neurogenesis and regulation of the size of the cerebral cortex. Whole exome sequencing revealed a novel, homozygous frameshift mutation (c.373_374delAA) in MCPH1 gene in exon 5 resulting in frameshift change from p.Lys125Glusfs*7. Our report presents the results of the simultaneous analysis of the trio exome data of both unaffected parents and their affected son. A homozygous frameshift variant in the MCPH1 gene was identified as a plausible candidate causal variant for the clinical phenotype in this family.     

Characterization and bioscreening of a new triterpenoid and a flavanone isolated from Salvia nubicola

A new epimeric lupane triterpenoid, 3alpha-hydroxy-20-oxo-30-norlupane (1), and a new flavanone (nubatin; 3) have been isolated from Salvia nubicola collected from Quetta, Pakistan. The structures of these constituents were elucidated with the aid of spectroscopic techniques, including two-dimensional NMR and NOE experiments. Both the metabolites were found to be moderately bio-active.