Prenatal diagnosis of autosomal recessive renal tubular dysgenesis caused by variants in the ACE gene: Two fetuses with anhydramnios.

INTRODUCTION: Autosomal recessive renal tubular dysgenesis (ARRTD) is a rare genetic disorder with a very high mortality rate. The typical symptoms of the disease during pregnancy are oligohydramnios, anhydramnios, and nearly all affected fetuses die after birth or have a stillbirth in late gestation, which can adversely increase maternal risks. METHODS: Oligohydramnios/anhydramnios can make both amniocentesis for diagnostic testing and morphological evaluation via ultrasound more difficult. In cases of oligohydramnios/anhydramnios suspicious for urinary tract anomalies, amnioinfusion is a meaningful technique that facilitates sampling of amniotic fluid for genetic diagnosis. RESULTS: We report two cases of fetuses with anhydramnios and invisible urinary bladder. Clinical exome sequencing from amniotic fluid revealed a biparentally inherited homozygous pathogenic nonsense ACE variant c.2503G 〉 T [p.Glu853Ter] in proband 1 and a biparentally inherited homozygous pathogenic nonsense ACE variant c.2992C 〉 T [p.Gln998Ter] in proband 2. The prognosis was poor and the patients elected to terminate the pregnancies. Additional post-mortem histopathological examination from the renal tissue of the second fetus showed renal tubular hypoplasia. CONCLUSION: To our knowledge for the first time, we describe the prenatal diagnosis of ARRTD in Vietnam, and highlight the benefit of detecting ACE variants associated with ARRTD in fetuses with oligohydramnios/anhydramnios through amnioinfusion and amniocentesis, which improves genotype-phenotype correlations and provides valuable information for reproductive counseling.

Synthesis and biological screening of thiosemicarbazones of substituted 3-acetylcoumarins having d-glucose moiety.

Thiosemicarbazones 5a-j were synthesized with yields of 45-68% by condensation of 3-acetylcoumarins 3a-j and tetra-O-acetyl-ß-d-thiosemicarbazide 4. All obtained thiosemicarbazones were screened for anti-microorganic activities against bacteria (B. subtilis, S. aureus, S. epidermidis, E. coli, P. aeruginosa, K. pneumoniae, S. typhimurium) and fungi (A. niger, C. albicans, S. cerevisiae, and A. flavus). Some compounds had significant inhibitory activity with MICs of 0.78-3.125 µM in comparison with 5a, including 5e,h,i for S. aureus, and 5c,f,i for S. epidermidis (Gram-(+) bacteria), 5c,f,g for E.coli, 5f for K. pneumoniae, 5b,c,g for P. aeruginosa, and 5i for S. typhimurium (Gram-(-) bacteria), 5d,h,i for A. niger, 5i for A. flavus, 5b,d,e,h for C. albicans, and 5i for S. cerevisiae. Compounds exhibited excellent activity against tested microorganism with MIC = 0.78 µM, including 5h,i (against S. aureus), 5h (against C. albicans), and 5i (against S. cerevisiae).

The Role of p.Ser1105Ser (in NPHS1 Gene) and p.Arg548Leu (in PLCE1 Gene) with Disease Status of Vietnamese Patients with Congenital Nephrotic Syndrome: Benign or Pathogenic?

Background and Objectives: Congenital nephrotic syndrome (CNS), a genetic disease caused by mutations in genes on autosomes, usually occurs in the first three months after birth. A number of genetic mutations in genes, which encode for the components of the glomerular filtration barrier have been identified. We investigated mutations in NPHS1, NPHS2, PLCE1 (NPHS3), and WT1 genes that relate to the disease in Vietnamese patients. Materials and Methods: We performed genetic analysis of two unrelated patients, who were diagnosed with CNS in the Vietnam National Children's Hospital with different disease status. The entire coding region and adjacent splice sites of these genes were amplified and sequenced using the Sanger method. The sequencing data were analyzed and compared with the NPHS1, NPHS2, PLCE1, and WT1 gene sequences published in Ensembl (ENSG00000161270, ENSG00000116218, ENSG00000138193, and ENSG00000184937, respectively) using BioEdit software to detect mutations. Results: We detected a new variant p.Ser607Arg and two other (p.Glu117Lys and p.Ser1105Ser) in the NPHS1 gene, as well as two variants (p.Arg548Leu, p.Pro1575Arg) in the PLCE1 gene. No mutations were detected in the NPHS2 and WT1 genes. Patient 1, who presented a heterozygous genotype of p.Ser1105Ser and p.Arg548Leu had a mild disease status but patient 2, who presented a homozygous genotype of these alleles, had a severe phenotype. Conclusions: These results suggest that variants p.Ser1105Ser (in NPHS1 gene) and p.Arg548Leu (in PLCE1 gene) in the homozygous form might play a role in the development of the disease in patients.

Flexoelectric and size-dependent effects on hygro-thermal vibration of variable thickness fluid-infiltrated porous metal foam nanoplates.

The Galerkin-Vlasov approach based on the improved first-order shear deformation theory (i-FSDT) and nonlocal elasticity theory are proposed to investigate the free vibration response of variable-thickness fluid-infiltrated porous metal foam (FPMF) nanoplates with flexoelectricity effect resting on Pasternak elastic foundation in the hygro-thermal environment. The FPMF nanoplate thickness varies according to both the length and width directions. The novelty of the present work is to consider the influence of the nonlocal's spatial variation and flexoelectric coefficients on the free vibration behavior of the nanoplates. Based on Hamilton's principle, the governing equation of FPMF nanoplate is established. The accuracy of the proposed method is checked by comparing the obtained results with those of available work in the literature. The effects of the parameters such as the flexoelectric coefficient, nonlocal coefficient, porosity coefficient, Skempton factor, temperature and moisture, thickness variation, and various boundary conditions on the natural frequency of the nanoplate are examined.

Ductal carcinoma in situ arises from microglandular adenosis and atypical microglandular adenosis in a young woman.

Microglandular adenosis (MGA) and atypical microglandular adenosis (AMGA) are intensely rare and distinctive forms of adenosis of the breast, usually occurring in middle-aged women. Carcinoma arising in MGA is an extremely rare subtype of breast carcinoma, and most reported cases are of invasive carcinoma. Ultrasound and magnetic resonance imaging are accurate imaging modalities for diagnosing these abnormalities. Our goal in this article was to report a rare instance of ductal carcinoma in situ (DCIS) arising from MGA and AMGA in a very young Vietnamese woman who presented with a palpable mass in her right breast for 1 month. During clinical examination and imaging, suspected lesions were found and categorized as BI-RADS 4a. The final histopathological findings confirmed DCIS arising from MGA/AMGA. In this patient, the disease was detected and managed early when the lesion was localized in the duct and there were no signs of invasive ductal carcinoma.

Breastfeeding practices in urban and rural Vietnam.

BACKGROUND: The aim of this study was to describe and compare breastfeeding practices in rural and urban areas of Vietnam and to study associations with possibly influencing person and household factors. This type of study has not been conducted in Vietnam before. METHODS: Totally 2,690 children, born from 1st March 2008 to 30th June 2010 in one rural and one urban Health and Demographic Surveillance Site, were followed from birth to the age of 12 months. Information about demography, economy and education for persons and households was obtained from household surveys. Standard statistical methods including survival and regression analyses were used. RESULTS: Initiation of breastfeeding during the first hour of life was more frequent in the urban area compared to the rural (boys 40% vs. 35%, girls 49% vs. 40%). High birth weight and living in households with large number of assets significantly increased the probability for early initiation of breastfeeding. Exclusive breastfeeding at three months of age was more commonly reported in the rural than in the urban area (boys 58% vs. 46%, girls 65% vs. 53%). The duration of exclusive breastfeeding as well as of any breastfeeding was longer in the rural area than in the urban area (medians for boys 97 days vs. 81 days, for girls 102 days vs. 91 days). The percentages of children with exclusive breastfeeding lasting at least 6 months, as recommended by WHO, were low in both areas. The duration of exclusive breastfeeding was significantly shorter for mothers with three or more antenatal care visits or Caesarean section in both areas. High education level of mothers was associated with longer duration of exclusive breastfeeding in the rural area. No significant associations were found between duration of exclusive breastfeeding and mother's age, household economy indicators or household size. CONCLUSION: Intervention programs with the aim to promote breastfeeding are needed. Mothers should particularly be informed about the importance of starting breastfeeding early and to prolong exclusive breastfeeding. In order to reach the WHO recommendation of six months exclusive breastfeeding, we propose an extended maternity leave legislation to at least six months.

Clinical, Laboratory Characteristic, and Treatment of Human Toxocariasis in Northern Vietnam.

Background: We determined the occurrence frequency of Clinical signs, subclinical characteristics on positive anti-IgG Toxocara ELISA cases, and clinical response results after 1 month of albendazole-specific treatment. Methods: A number of 103 clinically treated patients were studied between 2018 and 2019 in two hospitals. Relevant data are collected from examination and medical records such as age, sex, job, resident, clinical and sub-clinical signs. Sera samples were subjected to anti-IgG Toxocara antigen using ELISA. Results: The median age of the patient was 43.6 ± 14.4 years. The most common symptom groups were the skin and mucosa (88.3%), followed by neurological symptoms (44%). There are 76.7% of patients with risk factors for contact with pet dogs and cats. The majority of eosinophils in the normal range (< 8%) accounted for 85.4%, the major results of the OD value of ELISA were in the group (≥ 0.3-< 1.5) accounted for 75.7%. The skin and mucosa lesions in toxocariasis patients related to IgE values were statistically significant (P <0.05). The effectiveness of anthelmintic treatment is low with nearly half of patients having no clinical symptoms after 1 month of post-treatment. It is statistically significant between exposure to dogs/cats and treatment outcomes on clinical symptoms (P < 0.05). Conclusion: Toxocara infections in Vietnamese people often have skin allergies and liver damage, rarely with severe neurological symptoms. The efficacy of albendazole treatment after one month is not clear. In the near future, research with a confirmatory test other than Anti-IgG Toxocara ELISA is needed to screen for inhospital diagnosis.

Isolation and genetic characterization of canine distemper virus in domestic dogs from central and northern provinces in Vietnam.

Canine distemper virus (CDV) is a pathogen causing fatal disease in a wide range of carnivores. Sequence analysis of CDV strains has been classified into several geographically-related lineages, and the evolution and emergence of these strains are not fully yet investigated. In this study, the complete H gene sequences of 15 CDV strains isolated on Vero DST cell culture from clinical samples of vaccinated domestic dogs in Vietnam were investigated. Fifteen CDV isolates belonging to Asia-1 CDV variants were predominant antigenic type circulated in Central and Northern Vietnam with notable differences regarding the region and some genetic variation, and the most closely related Asia-1 variants lineage reported in Vietnam, China, Taiwan, and Japan. All identified CDV isolates clustered into 2 novel clades Asia-1-C1 and Asia-1-C2. The major amino acid mutation variants of Vietnamese Asia-1 CDV strains were found at sites 51, 157, 159, 160, 171, 178, 186, 235, 245, 277, 288, 313, 324, 330, 337, 345, 358, 359, 365, 383, 446, 475, 517, 530, 584, 598 which include N-glycosylation sites and neutralizing epitope regions in H gene. The results of the virus neutralization titer (VNT) assay showed that the dogs vaccinated with commercial vaccines had significantly low VNT (4.89 and 12.8) against field CDV isolate strains (VNUA NA04, HN18, and NB05) isolated in northern and central Vietnam, respectively. These data may suggest the need for further research in CDV monitoring and development of preventative measures against CDV in Vietnam.

Late-Onset Ornithine Transcarbamylase Deficiency and Variable Phenotypes in Vietnamese Females With OTC Mutations.

Background: Ornithine transcarbamylase deficiency (OTCD) is an X- linked recessive disorder and the most common error of the urea cycle, caused by the mutations in the OTC gene. Due to X-inactivation, 15-20% of female carriers present symptoms of OTCD at late onset. Early diagnosis of OTCD by molecular analysis in females is highly desirable. The aim of the study was to identify the mutations in two unrelated Vietnamese girls suspected with OTCD and the carriers in their families for definitive diagnosis and proper counseling. Case Presentation: Two patients presented with an acute encephalopathy at the first admission. Biochemical tests revealed hyperammonemia, hyperlactatemia, elevated glutamine level, elevated transaminase, elevated urinary orotic and uracil acid levels, and disorder of prothrombin time. Brain magnetic resonance imaging indicated cerebral edema. Based on the clinical and laboratory results, the two patients were diagnosed with urea cycle disorders. Therefore, the two patients were managed by stopping feeding, with infused glucose, l-carnitine, l-arginine, and sodium benzoate, and with hemofiltration. The two patients were alert and recovered with normal blood ammonia levels after 72 h of treatment. The family history of patient 1 showed that her brother died at 4 days of age due to a coma and dyspnea, while her parents were asymptomatic. Variable phenotypes were observed in three generations of the patient 2's family, including asymptomatic (mother), affected female adults dying at the first symptom (grandmother and aunt), and affected males dying in the first week of life (uncle, cousin, and siblings). Whole-exome sequencing showed two mutations in the OTC gene, including one novel missense mutation, c.365A>T, in the patient 1 and one previously reported splicing mutation, c.717+1G>A, in the patient 2. The two mutations are evaluated as likely pathogenic and pathogenic, respectively, according to the recommendations of the American College of Medical Genetics and Genomics (ACMG). Genetic analyses in the families indicated the mothers were heterozygous. Conclusion: Clinical, biochemical, and molecular findings accurately diagnosed the two patients with late-onset OTCD. Our results explained the genetic causes and proposed the risk in the patients' families, which could be useful for genetic counseling and monitoring in prenatal diagnosis.

A Case of Streptococcus thoraltensis Bacteremia and Prosthetic Valve Endocarditis in a 68-Year-Old Vietnamese Man.

BACKGROUND Streptococcus thoraltensis is a rare cause of human disease. This report describes a patient with infective endocarditis caused by S. thoraltensis and complicated by ischemic stroke. CASE REPORT A 68-year-old man was admitted for a 12-day duration of fever. He had a history of severe aortic valve stenosis, for which he underwent prosthetic valve replacement, and type 2 diabetes mellitus. Echocardiography revealed vegetation attached to the right coronary cusp of the prosthetic aortic valve and rupture of the sinus of Valsalva into the right ventricle. Blood cultures were positive for S. thoraltensis. He experienced an ischemic stroke involving the vegetation of the aortic valve and died of acute heart failure. CONCLUSIONS S. thoraltensis may be considered an emerging pathogen in patients with infective endocarditis.

Timely immunization completion among children in Vietnam from 2000 to 2011: a multilevel analysis of individual and contextual factors.

BACKGROUND: Since the beginning of 2014, there have been nearly 6,000 confirmed measles cases in northern Vietnam. Of these, more than 86% had neither been immunized nor was their vaccination status confirmed. OBJECTIVE: To establish the likelihood that children under five in Vietnam had 'timely immunization completion' (2000-2011) and identify factors that account for variations in timely immunization completion. DESIGN: Secondary data from the Multiple Indicator Cluster Survey (MICS), which sampled women aged 15-49 from the 1999 Vietnamese Population and Housing Census frame, were analyzed. Multilevel analysis using Poisson regression was undertaken. RESULTS: Proportions of children under five who had timely immunization completion were low, especially for HBV dose 2 and HBV dose 3, which decreased between 2000 and 2011. Among seven vaccines used in the National Expanded Program of Immunization (EPI) in 2000, 2006, and 2011, measles dose 1 had the highest timely immunization completion at 65.3%, 66.7%, and 73.6%, respectively, and hepatitis B dose 1 had the lowest at 17.5%, 19.3%, and 45.5%, respectively. Timely immunization completion was less common among children whose mothers had relatively less household wealth, were from ethnic minorities, lived in rural areas, and had less education. At the community level, the child's region of residence was the main predictor of timely immunization completion, and the availability of hospital delivery and community prenatal care in the local community were also determinants. CONCLUSION: The EPI should include 'timely immunization completion' as a quality indicator. There should also be greater focus and targeting in rural areas, and among women who have relatively low education, belong to minority groups, and have less household wealth. Further research on this topic using multilevel analysis is needed to better understand how these factors interact.

Prostaglandin E2 activates Src signaling in lung adenocarcinoma cell via EP3.

Accumulating evidence suggests that overproduction of prostaglandin (PG) E2 attributable to induction of cyclooxygenase-2 plays an important role in the development of lung adenocarcinoma. Recently, we have reported that a PGE2 receptor, EP3 is involved in appearance of malignant phenotype of a lung adenocarcinoma cell (A549 cell). In line with our previous study, here we investigated if Src signaling could be involved in PGE2-stimulated growth of A549 cells via EP3. PGE2-dependent cell growth in A549 cell positively related to the activation of Src. A specific antagonist against EP3 abrogated the cell growth and Src activation in the cells stimulated with PGE2. Also, the inhibition of Src activity suppressed its downstream signaling related to cell growth as well as the cell growth in the cells treated with PGE2. These results indicate that PGE2-dependent activation of Src signaling via EP3 plays an important role in growth of A549 cells.

Synthesis of cholic acid based calixpyrroles and porphyrins.

New cholic acid based calix[4]pyrroles and porphyrins were prepared and their properties were studied. It was confirmed by spectral measurements that the superassembly of 5,15-bis(3α,7α,12α-trihydroxy-5ß-cholan-24-yl)-10,20-diphenylporphyrin, the best candidate for this study from the conjugates prepared, may be influenced not only by the solvent mixture composition (polar/non-polar component ratio) but by time as well.