Low-dose intravenous recombinant tissue plasminogen activator in acute ischemic stroke without large vessel occlusion screened by 3T MRI.

OBJECTIVE: Globally, there are more than six million deaths due to cerebrovascular disease, which is the second leading cause of death. Although the imaging findings of magnetic resonance imaging (MRI) are more accurate than computed tomography for acute ischemic stroke (AIS), it is uncommon in recombinant tissue plasminogen activator (rTPA) treatment. Alteplase is not only strongly recommended treatment for acute ischemic stroke within 4.5 hours, but also decreases the disability and mortality rate. Besides, low-dose rTPA was associated with significant reductions in symptomatic intracerebral hemorrhage (sICH), compared with standard one. However, the benefits of low-dose rTPA for the treatment of AIS without large vessel occlusion (LVO) have not been fully demonstrated. We evaluated whether the low-dose rTPA in AIS without LVO could improve prognosis in patients three months post-treatment. PATIENTS AND METHODS: This was a cross-sectional study on patients with AIS treated within 4.5 hours of symptom onset admitted to Can Tho S.I.S General Hospital between February 2019 and July 2021. The eligibility criteria were patients aged > 18 years treated with low-dose rTPA (0.6 mg/kg) and screened by 3T MRI. Patients with a pre-hospital modified Rankin score (mRS) ≥ 2 points, intracranial hemorrhage, LVO, or ≥ 3 microbleeds on brain MRI were excluded. The primary outcomes were the favorable outcome rate at three months and safety, which were evaluated by the rates of intracranial hemorrhage and mortality at three months. RESULTS: This study enrolled 92 eligible patients between February 2019 and July 2021. Their National Institute of Health Stroke Scale (NIHSS) scores were 7.5 ± 3.7 at admission, 3.3 ± 3.5 at discharge or seven days after discharge, and 2.2 ± 2.8 at three months. Their mRS were 2.9 ± 0.8 at admission, 1.4 ± 1.3 at discharge or seven days after discharge, and 1.1 ± 1.1 at three months. Elevated cardiac enzymes, age ≥ 75 years, and body mass index ≥ 25 were associated with increased poor outcomes at three months. While AIS was more common in men than women, a similar number of men (33.3%) and women had poor mRS. Three patients had complications associated with low-dose rTPA treatment: one (1.1%) had intracranial hemorrhage, one (1.1%) had new infarcts, and one (1.1%) had gastrointestinal bleeding. No deaths occurred within three months. CONCLUSIONS: Our study indicates the efficacy and safety of low-dose rTPA treatment for AIS without LVO within 4.5 hours. Patient selection for rTPA by 3T MRI decreased complications and mortality.

The growth of pediatric neurosurgery in southern Vietnam and the first separation of pygopagus twins: case report.

Conjoined twins are a rare congenital abnormality with an estimated incidence of 1:50,000 pregnancies and 1:200,000 live births. Pygopagus twins are characterized by sacrococcygeal fusion that is commonly associated with perineal and spinal abnormalities. Management of this complex disease requires a well-developed surgical system with multidisciplinary capacity and expertise.A decade ago there were no dedicated pediatric neurosurgeons in southern Vietnam. This has changed within a few short years; there are now 10 dedicated pediatric neurosurgeons with continually expanding technical capacity. In August 2017 a multidisciplinary surgical and anesthetic team successfully separated female pygopagus twins with fused sacrum and spinal cord with associated myelomeningocele defect.The authors present here the first successful separation of pygopagus twins in Vietnam as a representative case of gradual and sustainable pediatric neurosurgical scale-up.

A novel anti-inflammatory compound, artonkin-4'-O-glucoside, from the leaves of Artocarpus tonkinensis suppresses experimentally induced arthritis.

Artocarpus tonkinenesis (Moraceae) has been used in Vietnamese traditional medicine for the treatment of backache and joint diseases since many 100 years. We have previously shown that a crude extract of A. tonkinensis elicited anti-inflammatory effects in rat collagen-induced arthritis (CIA), with significant improvement of disease symptoms. However, the pharmacological basis of the bioactivity of A. tonkinensis extract is not known. In the present study, we have isolated four individual active components from A. tonkinensis extract by reverse phase high-pressure liquid chromatography. The structures of the compounds were determined by nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry and their biological effects investigated. A novel biologically active flavonoid glucoside (5-hydroxy-8-hydroxymethyl-8-methyl-2-[4-(3,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-2-yloxy)-phenyl]-8H-pyrano[3,2-g]chromen-4-one) with an average molecular mass of 514.49 Da was isolated.We have named the compound artonkin-4'-O-glucoside. The name 'artonkin' for the novel flavonoid part of the compound was coined from the Latin name of its source Artocarpus tonkinensis. The three other active flavonoid glucosides isolated and characterized were alphitonin-4-O-beta-D-glucoside, maesopsin-4-O-beta-D-glucoside and kaempherol-3-O-beta-D-glucoside. All four compounds were found to cause anti-inflammatory effect with different potencies. The anti-inflammatory effects demonstrated in the rat model of arthritis correlate well with the inhibition of mitogen-induced T-cell proliferation. Furthermore, the compounds inhibit production of cytokines, such as tumour necrosis factor-a and interferon-c, in mitogen-stimulated T cells in a concentration-dependent manner. We postulate that the isolated flavonoids suppress T-cell proliferation as well as cytokine expression and thereby contribute to an amelioration of arthritis severity in CIA.

CDX2 promotes anchorage-independent growth by transcriptional repression of IGFBP-3.

CDX2 is a Drosophila caudal-related homeobox transcription factor that is important for the establishment and maintenance of intestinal epithelial cells. We have reported that CDX2 promotes tumorigenicity in a subset of human colorectal cancer cell lines. Here, we present evidence that CDX2 negatively regulates the well-documented growth inhibitor insulin-like growth factor binding protein-3 (IGFBP-3). Specifically, CDX2 binds to the IGFBP-3 gene promoter and can repress IGFBP-3 transcription, protein expression and secretion. Furthermore, inhibition of IGFBP-3 partially rescues the decreased anchorage-independent growth phenotype observed in CDX2 knockout cells. These data demonstrate for the first time that (1) CDX2 can function as a transcriptional repressor, and (2) one mechanism by which CDX2 promotes anchorage-independent growth is by transcriptional repression of IGFBP-3.

CDX2 does not suppress tumorigenicity in the human gastric cancer cell line MKN45.

CDX2 is a Drosophila caudal-related homeobox transcription factor that is expressed specifically in the intestine. In mice, ectopic expression of CDX2 in the gastric mucosa gives rise to intestinal metaplasia and in one model, gastric carcinoma. In humans, increased CDX2 expression is associated with gastric intestinal metaplasia and tubular adenocarcinomas. These patterns of expression have shown that CDX2 is important for the initiation of intestinal metaplasia in the gastric mucosa, but the role of CDX2 in established gastric cancer remains unclear. We sought to determine whether CDX2 contributes to tumorigenic potential in established gastric cancer. The CDX2 gene in MKN45 gastric carcinoma cells was disrupted using targeted homologous recombination. The resulting CDX2-/- cells are essentially identical to their parental cells, with the exception of CDX2 ablation. We found no significant differences in the proliferation of CDX2-/- cells compared to CDX2+/+ cells, in vitro or in vivo. Molecular analyses show that loss of CDX2 predominantly altered the expression of genes involved in intestinal glandular differentiation and adhesion. However, there were no microscopic differences in tumor differentiation. We conclude that disruption of CDX2 in MKN45 cells does not significantly affect their tumorigenic potential.

CDX2 has tumorigenic potential in the human colon cancer cell lines LOVO and SW48.

CDX2 is a Drosophila caudal-related homeobox transcription factor that is important for the establishment and maintenance of intestinal epithelial cells. CDX2 is a marker of colon cancer, with strong staining in up to 90% of colonic adenocarcinomas. CDX2 heterozygous-null mice develop colonic neoplasms, which have suggested that CDX2 is a tumor suppressor. However, CDX2 has not been reported to affect xenograft growth. Furthermore, CDX2 is rarely mutated in colon cancer, which has led to suggestions that it may play only a minor role as a tumor suppressor in colon cancer. To understand the functional contributions of CDX2 to colon cancer, we disrupted CDX2 in LOVO and SW48 human colon cancer cell lines by targeted homologous recombination. Consistent with the literature, disruption of CDX2 enhanced anchorage-dependent cell proliferation. However, homozygous loss of CDX2 led to significant inhibition of anchorage-independent growth in LOVO cells, and cell lethality in SW48 cells. Further analyses revealed that disruption of CDX2 led to anchorage-independent G1 to S growth arrest and anoikis. In vivo xenograft studies confirmed that disruption of CDX2 inhibited LOVO tumor growth. These data demonstrate that CDX2 mediates anchorage-independent growth and survival. Thus, CDX2 has tumorigenic potential in the human colon cancer cell lines LOVO and SW48.

Expression of the gut-enriched Krüppel-like factor (Krüppel-like factor 4) gene in the human colon cancer cell line RKO is dependent on CDX2.

Gut-enriched Krüppel-like factor (GKLF or KLF4) is a zinc finger-containing, epithelial-specific transcription factor, that functions as a suppressor of cell proliferation. We previously showed that GKLF expression is decreased in intestinal and colonic adenomas, respectively, from multiple intestinal neoplasia (Min) mice and familial adenomatous polyposis (FAP) patients. This study shows that GKLF is induced upon activation of the adenomatous polyposis coli (APC) gene. However, among several human colon cancer cell lines surveyed, expression of GKLF is lowest in RKO, a line with wild-type APC and beta-catenin. RKO contains a mutated allele that encodes the putative tumor suppressor homeodomain protein, CDX2. We show that wild-type CDX2 activates the GKLF promoter and that the mutated CDX2 has a dominant negative effect on wild-type function. Our results may help explain the exceedingly low levels of GKLF expression detected in this cell line, which may in turn contribute to the tumor phenotype.

Krüppel-like factor 4 (gut-enriched Krüppel-like factor) inhibits cell proliferation by blocking G1/S progression of the cell cycle.

Krüppel-like factor 4 (KLF4) is an epithelial cell-enriched, zinc finger-containing transcription factor, the expression of which is associated with growth arrest. Previous studies show that constitutive expression of KLF4 inhibits DNA synthesis but the manner by which KLF4 exerts this effect is unclear. In the present study, we developed a system in which expression of KLF4 is controlled by a promoter that is induced upon treatment of cells containing the receptors for the insect hormone, ecdysone, with ponasterone A, an ecdysone analogue. The rate of proliferation of a stably transfected colon cancer cell line, RKO, was significantly decreased following addition of ponasterone A when compared with untreated cells. Flow cytometric analyses indicated that the inducible expression of KLF4 caused a block in the G(1)/S phase of the cell cycle. A similar block was observed when ecdysone receptor-containing RKO cells were infected with a replication-defective recombinant adenovirus containing an inducible KLF4 and treated with ponasterone A. Results of these studies provide evidence that the inhibitory effect of KLF4 on cell proliferation is mainly exerted at the G(1)/S boundary of the cell cycle.

The epidemiology and disease burden of rotavirus in Vietnam: sentinel surveillance at 6 hospitals.

The disease burden of rotavirus diarrhea in Vietnam was assessed by surveillance of children <5 years old who were hospitalized for diarrhea at 3 centers in the north and 3 centers in the south. Rotavirus was identified in 56% (range, 47%-60%) of the 5768 patients surveyed between July 1998 and June 2000. G-typing of the first 224 strains indicated that only 2% were non-typeable, 9% were in mixed infections, and the remainder were of the common serotypes G1, G2, G3, G4, and G9. In Vietnam, diarrhea accounts for 9880 deaths per year, which is approximately 15% of all deaths among children <5 years old, or 6.5 deaths per 1000 children. If even 50% of these diarrhea-related deaths in Vietnam were due to rotavirus, the number would represent 4%-8% of all deaths among children <5 years old, 2700-5400 rotavirus-related deaths per year, and 1 death per 280-560 children during the first 5 years of life. Thus, the disease burden of rotavirus in Vietnam is substantial, and programs to encourage the use of oral rehydration should be encouraged while efforts to develop vaccines continue.

Decreased expression of the gut-enriched Krüppel-like factor gene in intestinal adenomas of multiple intestinal neoplasia mice and in colonic adenomas of familial adenomatous polyposis patients.

Gut-enriched Krüppel-like factor (GKLF) is a zinc finger-containing transcription factor, the expression of which is associated with growth arrest. We compared Gklf expression in intestinal and colonic adenomas to normal mucosa in multiple intestinal neoplasia (Min) mice and familial adenomatous polyposis (FAP) patients, respectively, using semi-quantitative RT-PCR. In Min mice, the level of Gklf transcript is highest in normal-appearing intestinal tissues and decreases as the size of the adenoma increases. In FAP patients, the level of GKLF transcript is lower in adenomas compared to paired normal-appearing mucosa from the same patient or normal colonic mucosa from control individuals without FAP. The possibility of DNA methylation as a cause for the decreased expression of Gklf in adenomas of Min mice was investigated by methylation-specific PCR. Results indicate that the Gklf gene is not methylated in either normal or tumorous tissues. The findings of our study are therefore consistent with the potential role of GKLF as a negative growth regulator of gut epithelial cells.

The gut-enriched Kruppel-like factor (Kruppel-like factor 4) mediates the transactivating effect of p53 on the p21WAF1/Cip1 promoter.

An important mechanism by which the tumor suppressor p53 maintains genomic stability is to induce cell cycle arrest through activation of the cyclin-dependent kinase inhibitor p21(WAF1/Cip1) gene. We show that the gene encoding the gut-enriched Krüppel-like factor (GKLF, KLF4) is concurrently induced with p21(WAF1/Cip1) during serum deprivation and DNA damage elicited by methyl methanesulfonate. The increases in expression of both Gklf and p21(WAF1/Cip1) due to DNA damage are dependent on p53. Moreover, during the first 30 min of methyl methanesulfonate treatment, the rise in Gklf mRNA level precedes that in p21(WAF1/Cip1), suggesting that GKLF may be involved in the induction of p21(WAF1/Cip1). Indeed, GKLF activates p21(WAF1/Cip1) through a specific Sp1-like cis-element in the p21(WAF1/Cip1) proximal promoter. The same element is also required by p53 to activate the p21(WAF1/Cip1) promoter, although p53 does not bind to it. Potential mechanisms by which p53 activates the p21(WAF1/Cip1) promoter include a physical interaction between p53 and GKLF and the transcriptional induction of Gklf by p53. Consequently, the two transactivators cause a synergistic induction of the p21(WAF1/Cip1) promoter activity. The physiological relevance of GKLF in mediating p53-dependent induction of p21(WAF1/Cip1) is demonstrated by the ability of antisense Gklf oligonucleotides to block the production of p21(WAF1/Cip1) in response to p53 activation. These findings suggest that GKLF is an essential mediator of p53 in the transcriptional induction of p21(WAF1/Cip1) and may be part of a novel pathway by which cellular responses to stress are modulated.

The epidemiology of typhoid fever in the Dong Thap Province, Mekong Delta region of Vietnam.

A population-based surveillance for typhoid fever was conducted in three rural communes of Dong Thap Province in southern Vietnam (population 28,329) for a 12-month-period starting on December 4, 1995. Cases of typhoid fever were detected by obtaining blood for culture from residents with fever > or = 3 days. Among 658 blood cultures, 56 (8.5%) were positive for Salmonella typhi with an overall incidence of 198 per 10(5) population per year. The peak occurrence was at the end of the dry season in March and April. The attack rate was highest among 5-9 year-olds (531/10(5)/year), and lowest in > 30 year-olds (39/10(5)/year). The attack rate was 358/10(5)/year in 2-4 year-olds. The isolation of S. typhi from blood cultures was highest (17.4%) in patients with 5 to 6 days of fever. Typhoid fever is highly endemic in Vietnam and is a significant disease in both preschool and school-aged children.

The biology of the mammalian Krüppel-like family of transcription factors.

Recent advances in molecular cloning have led to the identification of a large number of mammalian zinc finger-containing transcription factors that exhibit homology to the Drosophila melanogaster protein, Krüppel. Although the amino acid sequences in the zinc finger domains of these Krüppel-like factors (KLFs) are closely related to one another, the regions outside the zinc fingers of the proteins are usually unique. KLFs display seemingly different and broad biological properties with each functioning as an activator of transcription, a repressor or both. This review article provides a current phylogenetic classification of the identified KLFs to date. More importantly, the currently known biological activities of the KLFs in regulating transcription, cell proliferation, differentiation and development are summarized and compared. Further characterization of this interesting protein family should provide additional insights into the their respective regulatory role in various important biological processes.

The situation of malaria along the Vietnam-Lao PDR border and some related factors.

This was a descriptive cross sectional study. It was done in 4 communes along the Vietnam-Lao PDR border of two mountainous provinces: Sonla and Nghean. The cluster multistage sampling technique was applied to choose the study sites. The results of the study show: Among the 2,441 persons given blood tests to find malaria parasites, 0.7% of them carry malaria parasite, of whom 0.6% carry P. falciparum and 0.1% carry P. vivax. The malaria morbidity in the year was 6.9%. The mortality due to malaria is 1.59 per 100,000 population per year. Among the 106 hamlet motivators being interviewed, only 75.5% knew that malaria is transmitted by mosquitos, 71.7% knew that malaria patients are a source of transmission, over 50% of the motivators have mistaken understanding about the living environment of malaria mosquitos. Most of them have had mistakes in diagnosis, treatment of malaria, mosquito-killing spraying. Among the 729 adults being interviewed, 59.0% did not know about the causes of malaria, 30.7% did not take part in malaria control activities. Only 69.3% of the adults regularly sleep inside mosquito nets, 68% of adults buy medicine to cure malaria, 39.9% referred patients to health facilities for cure, and 25% use forest herbs to cure malaria. The factors that increased the malaria morbidity in communes along Vietnam-Lao PDR border have been identified.

Occupational exposure and chronic respiratory symptoms--a population based study in Vietnam.

In order to investigate the relationship between occupational exposure to dust/chemicals (toxic gases/fumes) and chronic respiratory symptoms in Vietnam, the questionnaire standardized by the American Thoracic Society was applied to 368 subjects living in Ha Thai district of Vietnam. According to the results of multiple logistic regression analyses, the odds ratios of chronic respiratory symptoms by occupational exposure are over unity, except for the relationship between chronic cough and occupational exposure to chemicals. Especially for chronic breathlessness, significantly higher odds ratios are observed among people with a history of occupational exposure to dust or chemicals: 2.925 (95% CI: 1.130-7.574) for dust, and 3.721 (95% CI: 1.412-9.803) for chemicals. As for the interaction between occupational exposure to dust and cigarette smoking, it is considered that occupational exposure leads to an increase in chronic respiratory symptoms independent of the effects of cigarette smoking.

Long-term evaluation of immune status in leprosy patients undergoing multiple drug therapy.

A long-term survey of leprosy patients of all clinical types, starting at the time of diagnosis, was carried out to monitor clinical, bacteriological and immunological parameters at regular intervals during multiple drug therapy (MDT). The patients were assigned to two groups for treatment following WHO guidelines: paucibacillary (PB) and multibacillary (MB). Immunoglobulin levels, specific antibodies, skin-test responses to different soluble mycobacterial antigens (new tuberculins), and in vitro proliferative responses to mitogens and to antigens were measured during treatment, as were clinical changes, the bacterial index, and clinical improvement. No exact relations between disease activity and IgM antibody levels, both IgM immunoglobulin and specific IgM antibody to a species-specific antigen (ND-O-BSA), could be seen for MB patients. Changes in in vitro cell-mediated immunity and skin-test response seemed to be more directly related to the bacterial load and could reflect the improvement of bacteriological and clinical parameters during MDT.

Use of a yeast site-specific recombinase to generate embryonic mosaics in Drosophila.

An efficient method for generating embryonic mosaics using a yeast site-specific recombinase (FLP), under the control of a heat shock promoter, is described. FLP-recombinase can promote mitotic exchange between homologous chromosomes that contain FRT (FLP Recombination Target) sequences. To demonstrate the efficiency of FLP-recombinase to generate embryonic mosaics, clones of the recessive and cell autonomous mutation armadillo (arm), detected by their ability to differentiate ectopic denticles in the naked cuticle of each abdominal segment, have been induced. We have analyzed the parameters of FLP-recombinase induced embryonic mitotic recombination and have demonstrated that clones can be efficiently induced during the postblastoderm mitotic divisions. We discuss applications of this technique for the analyses of the roles of various mutations during embryonic patterning.

Freeze-etching and freeze-fracture structural features of cell envelopes in mycobacteria and leprosy derived corynebacteria.

The structural properties of the cell wall and cell membrane of several mycobacteria and of Leprosy Derived Corynebacteria are investigated by freeze-etching and freeze-fracture. In all cases the freeze-fracture split the cell wall in two asymmetric halves. The cell wall fracture faces of the mycobacteria are characterized by a filamentous network which vary with respect to the amount and complexity among microorganism of the same species and even more of different species. In LDC the structure organization of the cell wall and cell membrane differs from that of mycobacteria. The most stricking difference is the presence on the fracture faces of the LDC cell wall of different classes of particulated entities of yet unknown nature. In the mycobacteria and LDC the periseptal annuli likely provide a potential frame for cell envelope and cell membrane assembly.

The humoral antibody response to Shigella dysenteriae type 1 infection, as determined by ELISA.

An enzyme-linked immunosorbent assay (ELISA) for determining the class-specific humoral antibody response to the lipopolysaccharide antigen from Shigella dysenteriae serotype 1 bacteria has been tested. Two or more serum samples from each of 60 persons infected with this organism during a dysentery outbreak in a boarding school for young men near Haiphong, Viet Nam, and single serum samples from 39 healthy Vietnamese and from 20 healthy Swedes were included in the study. Comparison of the titres in the sera from the patients and the Vietnamese controls showed that the patients had significantly elevated IgA titres in sera collected 10, 30 and 45 days after onset of infection, and significantly elevated IgG titres in sera collected 30, 45 and 180 days after the onset. The titres in the patients' sera, compared with those in the Swedish controls, were significantly elevated for IgA and IgM as well as IgG in the samples collected after 10, 30, 45 and 180 days. The use of rabbit antisera, specific for enteropathogenic bacteria, and absorption experiments with human sera indicated that the S. dysenteriae type 1 lipopolysaccharide antigen is specific with respect to the O-antigenic polysaccharide chain.