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Background Vietnam has been experiencing an epidemiologic transition to that of a lower-middle income country with an increasing prevalence of non-communicable diseases. The key risk factors for cardiovascular disease (CVD) are either on the rise or at alarming levels in Vietnam, particularly hypertension (HTN). Inasmuch, the burden of CVD will continue to increase in the Vietnamese population unless effective prevention and control measures are put in place. The objectives of the proposed project are to evaluate the implementation and effectiveness of two multi-faceted community and clinic-based strategies on the control of elevated blood pressure (BP) among adults in Vietnam via a cluster randomized trial design. Methods Sixteen communities will be randomized to either an intervention (8 communities) or a comparison group (8 communities). Eligible and consenting adult study participants with HTN (n = 680) will be assigned to intervention/comparison status based on the community in which they reside. Both comparison and intervention groups will receive a multi-level intervention modeled after the Vietnam National Hypertension Program including education and practice change modules for health care providers, accessible reading materials for patients, and a multi-media community awareness program. In addition, the intervention group only will receive three carefully selected enhancements integrated into routine clinical care: (1) expanded community health worker services, (2) home BP self-monitoring, and (3) a “storytelling intervention,” which consists of interactive, literacy-appropriate, and culturally sensitive multi-media storytelling modules for motivating behavior change through the power of patients speaking in their own voices. The storytelling intervention will be delivered by DVDs with serial installments at baseline and at 3, 6, and 9 months after trial enrollment. Changes in BP will be assessed in both groups at several follow-up time points. Implementation outcomes will be assessed as well. Discussion Results from this full-scale trial will provide health policymakers with practical evidence on how to combat a key risk factor for CVD using a feasible, sustainable, and cost-effective intervention that could be used as a national program for controlling HTN in Vietnam. Trial registration ClinicalTrials.gov NCT03590691. Registered on July 17, 2018. Protocol version: 6. Date: August 15, 2019.

The soil-geogrid interaction process was analyzed by the Particle Image Velocimetry furthermore spatial discretization scheme in finite element method to understand about the dilatancy mechanism and shear strain distribution during unloading-reloading process. In this test the geogrid was pushed back and forth at three stages of pullout test: before peak, at peak and at residual part to simulate the seismic activities. Results showed that the shear strain concentrated in front of transverse ribs and upper apart of pullout box. The dilative behavior appears in front of transverse ribs and contractive behavior exits at behind of these bars. The alternative soil dilatancy-contraction distribution in between the two transverse ribs can be seen throughout the length of geogrid.

It is considered that the pullout resistance is more affected by the transverse elements than the longitudinal elements. In this study a square and a circle opening type and a plate are tested of pullout resistance in Toyoura sand during the unloading-reloading process through a series of laboratory model tests. The results show that unloading-reloading process reduces the pullout resistance of both two types of geogrid and a plate at peak value and at the residual part. But the pullout resistance of the square geogrid type in this study is decreased more as well as less stable than that of the other two. Moreover, the square geogrid type takes larger displacement to reach to the peak values of pullout resistance than the circle and plate ones do. To discuss the effects, all of the deformation of soil around geogrid is observed while it is pulled out. The PIV analysis shows the mechanism and effects of transverse ribs on the pullout resistance.

The nucleoprotein genes of 49 measles virus (MV) strains circulating in Russia between 2000 and 2006 and in Vietnam in 2003 were analyzed by genotype-specific PCR and the results were compared with their sequences. The sequences revealed the presence of genotypes H1 and H2 in the center (Nha Trang) and the north (Hanoi) of Vietnam, respectively. The relative diversity of the H2 strains suggested an endemic circulation of these viruses in the capital. In contrast genotype H1 strains from Nha Trang were homogenous genetically, which may indicate a recent importation. The strains obtained from 12 different regions of the Russian Federation were assigned to the genotypes H1, D4, and D6. Most strains (81.4%) were correctly genotyped by a multiplex PCR method which was sensitive to genotype-specific mutations [Kremer et al. (2004): J Clin Microbiol 42: 3017-3022]. Ambiguous or negative results for some clade H and genotype D6 strains were due to point mutations in the type-specific primer binding sites. After exchanging a single nucleotide in both the clade H- and the genotype D6-specific primers, all strains were assigned correctly to their genotype. A simplified procedure for use in Vietnam was developed to distinguish directly between genotypes H1 and H2 and any non-H genotype. These results demonstrate that our multiplex PCR method can be adapted easily to new sequence variants or specific epidemiological situations, and thus be very useful for rapid genotyping of large number of samples even in laboratories which do not have sequencing facilities.

Targeted cDNA differential display (TcDD) was developed to study expression of a different selected gene families especially those at low copy numbers per cell. This method is an adaptation of our previously described targeted genomic differential display method (TGDD). In TcDD, the expression of genes containing target sequences such as CAG repeating sequences or genes encoding for zinc-finger binding proteins were followed in an experimental rat model with salt-induced hypertension. DNA sequencing experiments demonstrated that the effectiveness of targeting was greater than 99%.

The high affinity (kd= approximately 10(-15)M) of streptavidin and avidin for biotin is key to a large number of biological applications and is essentially irreversible unless the complex is exposed to harsh conditions (e.g. heat (100 degrees C for 10 min)), detergents, and/or denaturants which damage macromolecules. Thus, high binding affinity becomes a disadvantage when a biotinylated target must be released for further processing. This work describes relatively mild conditions that release biotin and mono- and bis-biotinylated macromolecules from immobilized streptavidin on monodispersed magnetic beads.

DNA methylation changes could provide a mechanism for DNA plasticity and dynamism for short-term adaptation, enabling a type of cell memory to register cellular history under different environmental conditions. Some environmental insults may also result in pathological methylation with corresponding alteration of gene expression patterns. Evidence from several studies has suggested that in schizophrenia and bipolar disorder, mRNA of the reelin gene (RELN), which encodes a protein necessary for neuronal migration, axonal branching, synaptogenesis, and cell signaling, is severely reduced in post-mortem brains. Therefore, we investigated the methylation status of the RELN promoter region in schizophrenic patients and normal controls as a potential mechanism for down regulation of its expression. Ten post-mortem frontal lobe brain samples from male schizophrenic patients and normal controls were obtained from the Harvard Brain Tissue Resources Center. DNA was extracted using a standard phenol–chloroform DNA extraction protocol. To evaluate differences between patients and controls, we applied methylation specific PCR (MSP) using primers localized to CpG islands flanking a potential cyclic AMP response element (CRE) and a stimulating protein-1 (SP1) binding site located in the promoter region. For each sample, DNA extraction, bisulfite treatment, and MSP were independently repeated at least four times to accurately determine the methylation status of the target region. Forty-three PCR trials were performed on the test and control samples. MSP analysis of the RELN promoter revealed an unmethylated signal in all reactions (43 of 43) using DNA from the frontal brain tissue, derived from either the schizophrenic patients or normal controls indicating that this region of the RELN promoter is predominantly unmethylated. However, we observed a distinct methylated signal in 73% of the trials (16 of 22) in schizophrenic patients compared with 24% (5 of 21) of controls. Thus, the hypermethylation of the CpG islands flanking a CRE and SP1 binding site observed at a significantly higher level (t = −5.07, P = 0.001) may provide a mechanism for the decreased RELN expression, frequently observed in post-mortem brains of schizophrenic patients. We also found an inverse relationship between the level of DNA methylation using MSP analysis and the expression of the RELN gene using semi-quantitative RT-PCR. Despite the small sample size, these studies indicate that promoter hypermethylation of the RELN gene could be a significant contributor in effecting epigenetic alterations and provides a molecular basis for the RELN gene hypoactivity in schizophrenia. Further studies with a larger sample set would be required to validate these preliminary observations. © 2005 Wiley-Liss, Inc.

To the Editor: Clozapine is an antipsychotic that exhibits a unique pharmacodynamic profile. It has a strong affinity for dopaminergic D4 receptors, weak activity at D2 receptors, and potent serotonergic, noradrenergic, histaminic, and muscarinic receptor antagonism.1 Some of the side effects of clozapine, such as agranulocytosis,2 are well recognized as life-threatening complications. We present a case in which constipation, a common and often considered nuisance side effect of clozapine, progressed to life-threatening proportions. Case report. Mr A is a 50-year-old man with a long history of smoking, schizophrenia, and hypertension who was admitted to the hospital after presenting to the emergency department from a free-standing psychiatric hospital with concerns of abdominal distention, constipation, and altered mental status. The psychiatry service was consulted to manage the patient’s psychiatric medications and delirium. During his 4-day hospitalization at the psychiatric facility for psychotic decompensation, Mr A had continued to receive his scheduled home medications, which included clozapine 200 mg once in the afternoon and 400 mg at bedtime and once-daily dosages of solifenacin 5 mg, lisinopril 10 mg, omeprazole 20 mg, ferrous sulfate 325 mg, and valproate extended release 2,000 mg. In addition, he had received a total of 120 mg of olanzapine for psychosis and agitation over the 4 days prior to transfer. In the emergency department, Mr A’s vital signs were stable. Physical examination was notable for significant abdominal distension. Mental status evaluation displayed disorientation, behavioral disinhibition, and unintelligible speech. A kidney-ureter-bladder x-ray (KUB) demonstrated a large stool burden and a prominent 11-cm dilation of the transverse colon (Figure 1). Laboratory workup was fairly unremarkable outside of a mild hypernatremia (147 mmol/L), slightly decreased glomerular filtration rate (54 mL/min/1.73 m2), and an elevated non-trough valproate level (18 mg/L). The hypernatremia and acute kidney injury resolved quickly with intravenous fluids, and the free-valproate level normalized (12 mg/L) with a decrease in valproate dose to 500 mg twice daily. Figure 1. Kidney-Ureter-Bowel X-Ray Highlighting Distended Transverse Colon Diameter Plans to manage his partial ileus included decreasing the clozapine dose, minimizing exposure to other anticholinergic medications, discontinuing ferrous sulfate, obtaining a consultation with a gastroenterologist, and initiating an aggressive bowel care management regimen (polyethylene glycol, docusate sodium 50 mg and sennosides 8.6 mg [Senna-S], and bisacodyl). Despite these measures, Mr A continued to exhibit significant constipation and delirium. Asenapine was subsequently initiated because it has both minimal anticholinergic properties and antipsychotic efficacy. It was cross-titrated with a gradually decreasing clozapine dose. The patient’s constipation eventually improved, and he was able to tolerate a general diet. With a reduction in his clozapine dosage and an asenapine dose of 15 mg twice daily, his delirium resolved and he exhibited minimal active symptoms of psychosis. He was subsequently transferred back to the psychiatric hospital on clozapine 50 mg daily (with a plan to gradually taper off completely), asenapine 15 mg twice daily, valproate 500 mg twice daily, polyethylene glycol 68 g three times daily, Senna-S 3 tablets twice daily, and bisacodyl 10 mg daily. Constipation has been reported to be one of the most common side effects associated with clozapine, affecting 1 of every 3 patients taking the drug.3 Clozapine’s induction of gastrointestinal hypomotility, most likely a consequence of the medication’s antagonist action on muscarinic and serotonergic receptors, has the potential to lead to significant medical complications. This patient’s presentation may have been further exacerbated by elevated clozapine levels due to pharmacokinetic mechanisms secondary to the recent cessation of smoking and the coadministration of omeprazole. In addition, the chronic and acute administration of other medications commonly associated with constipation (ferrous sulfate, olanzapine, solifenacin) may have further increased the risk of gastrointestinal dysfunction in this patient. The recognition of clozapine’s inherent properties to disrupt gastrointestinal motility coupled with the potential for drug interactions (pharmacokinetic and pharmacodynamic) requires clinical vigilance on the part of the consultation-liaison psychiatrist. This recognition may prevent the deleterious and commonly unappreciated adverse effect of clozapine-induced gastrointestinal dysmotilty and its associated morbidity and mortality.

Increasing evidence links genomic and epigenomic instability, including multiple fragile sites regions to neuropsychiatric diseases including schizophrenia and autism. Cancer is the only other disease associated with multiple fragile site regions, and genome and epigenomic instability is a characteristic of cancer. Research on cancer is far more advanced than research on neuropsychiatric disease; hence, insight into neuropsychiatric disease may be derived from cancer research results. Towards this end, this article will review the evidence linking schizophrenia and other neuropsychiatric diseases (especially autism) to genomic and epigenomic instability, and fragile sites. The results of studies on genetic, epigenetic and environmental components of schizophrenia and autism point to the importance of the folate-methionine-transulfuration metabolic hub that is diseases also perturbed in cancer. The idea that the folate-methionine-transulfuration hub is important in neuropsychiatric is exciting because this hub present novel targets for drug development, suggests some drugs used in cancer may be useful in neuropsychiatric disease, and raises the possibility that nutrition interventions may influence the severity, presentation, or dynamics of disease.

Exon-specific anti-dystrophin antibodies are used to monitor the success of treatments for Duchenne muscular dystrophy that aim to restore the missing dystrophin protein. Dystrophin is a large cytoskeletal protein encoded by 79 exons and expressed mainly in muscle. Most cases of Duchenne and Becker muscular dystrophies are caused by genetic deletion of one or more exons. In-frame deletions permit some synthesis of internally-deleted dystrophin and cause the milder Becker form, while out-of-frame deletions in the severe Duchenne form result in early stop-codons and no functional dystrophin synthesis. In this study, we describe the production of ten new monoclonal antibodies against a rod region encoded by exons 55–59 and their mapping to specific dystrophin exons, thus filling a major gap in the spectrum of available antibodies. The antibodies have already been applied in a published clinical trial of a drug treatment for Duchenne muscular dystrophy.

This entry reviews the types of physical map that can be constructed, the methods used to construct them and their most likely current use. In particular, the emphasis is on the construction of genomic restriction maps and ordering overlapping libraries using top-down mapping approaches to enable de novo genome sequencing and for gap filling in sequencing projects. Also explored is the use of these approaches in functional studies. Keywords: Alu Repeat; Bacterial Artificial Chromosome (BAC); Cloneless Library; Comparative Genomic Hybridization (CGH); Expressed Sequence Tag (EST); Fluorescence In Situ Hybridization (FISH); Inter-Alu PCR; Jumping Libraries; Kpn Repeat; Linking Libraries; Locus; Long Interspersed Repeat Elements (LINEs); Multiplex Analysis; P1-derived Artificial Chromosomes (PAC); Polonies; Polymerase Chain Reaction (PCR); Polymorphism Link-up; Pulsed Field Gel (PFG) Electrophoresis; Radiation Hybrid Maps; RARE (RecA-assisted Restriction Endonuclease) Cleavage; Retroposons; Sequence-tagged Restriction Site (STAR); Sequence-tagged Site (STS); Short Interspersed Repeat Elements (SINEs); Yeast Artificial Chromosome (YAC)

An understanding of genome function within the context of human cells requires new methodology. This article describes comparative approaches that are used for genomes and genes in situ. However, the major focus of the article is on differential display (DD) and subtractive hybridization (SH) because these two methods are most accessible to a large number of researchers. The basic principles of these methods are described along with some fundamental reminders about the important factors that must be kept in mind for successful experiments.

The goal of these experiments was to understand DNA changes relevant to schizophrenia. This work compared DNA of monozygotic (MZ) twins surrounding (CAG)n repeating sequences, and characterized the relationship between fragile sites and schizophrenia. Twelve twin-pairs, previously classified as MZ and 18 unrelated sib-pairs, from seven families were studied. Eight twin-pairs were affected by schizophrenia, four concordantly and four discordantly. DNA comparisons were made using profiles of electrophoretic size fractionations of PCR amplified (CAG)n containing genomic fragments. These profiles were generated by a new method, developed by us, called targeted genomic differential display (TGDD). Surprisingly, the number of peak profile differences in MZ twin-pairs discordant for schizophrenia was greater than the concordantly ill twins and the well twins and, in some cases, overlapped the range of sib-pairs. These results might mean that some twins were not MZ but it was not possible to definitively test these samples for zygosity. Alternatively, the results might be explained as an increased mutation rate (or genomic instability) around (CAG)n sites in individuals afflicted with schizophrenia. Also, we uncovered an association of schizophrenia (i.e., a linkage of chromosomal abnormalities and gene localizations) with fragile sites spread throughout the genome (χ2, P = 0.001). Furthermore, it appears that an increasing number of genes linked to schizophrenia are associated with (CAG)n sequences. Fragile sites and (CAG)n repeat sequences are known to be unstable. We speculate the association of genomic instability with schizophrenia accounts for seemingly disparate biological and environmental factors that influence disease occurrence. © 2003 Wiley-Liss, Inc.

Publisher Summary This chapter presents an overview on analyzing genomic DNA discordance between monozygotic twins. The chapter illustrates that monozygotic (MZ) or "identical" twins result from the fertilization of one ovum by one sperm. Intra-uterine environmental differences in the allocation of cells in the placental vascular supply to each twin, and stochastic developmental events, may lead to major phenotypic discordance within a MZ twin pair. Application of new molecular techniques to MZ twins reveals that they do not possess identical genomes when individual loci are established. Therefore, it is important to reassess the role of genomic differences between MZ twins in producing phenotypic discordances. For example, the study of MZ twins is particularly valuable when only one twin is affected by disease, because a comparison of the almost identical genomes can lead to the identification of genetic abnormalities.