Circulation of human respiratory syncytial virus and new ON1 genotype in northern Viet Nam, 2017–2020

@#Objective: Human respiratory syncytial virus (RSV) is a primary cause of paediatric severe acute respiratory infection (SARI) worldwide, especially in developing countries. We investigated the genetic characteristics of RSV in northern Viet Nam to determine the prevalence and distribution of subtypes as well as the diversity and transmission patterns of genotypes. Methods: In two facilities, from January 2017 to December 2020, 1563 clinical specimens were collected from paediatric patients hospitalized with SARI and tested for RSV. Selected positive samples underwent sequencing analysis targeting the second hypervariable region of the G gene using next-generation sequencing. Results: The RSV positivity rate was 28.02% (438/1563 samples), and prevalence was highest in children aged <1 year (43.84%; 192/438). Subtype RSV-A accounted for 53.42% (234/438) of cases, RSV-B for 45.89% (201/438), and there was coinfection in 0.68% (3/438). Both subtypes cocirculated and peaked during August–September in each year of the study. Phylogenetic analysis showed that RSV-A samples belonged to the ON1 genotype, which has three subgenotypes: ON1.1, ON1.2 and ON1.3. However, we did not find the 72-nucleotide duplication in the second hypervariable region of the G gene, a characteristic of genotype ON1, in any RSV-A samples. RSV-B samples belonged to genotype BA9. Discussion: Our results provide additional molecular characterization of RSV infections in Viet Nam. Specially, our study is the first to report the absence of the 72-nucleotide duplication in the G gene of RSV-A genotype ON1 in Viet Nam, which may help in understanding the genetic evolution of RSV and be useful for vaccine development in the future.

Inhibitory Activity of PTP1B and α-Glucosidase by Compounds from Whole Plants of Houttuynia cordata Thunb

In this study, twenty known compounds were isolated from Houttuynia cordata Thunb., including four megastigmanes (1‒4), four phenolics (5, 6, 9, and 10), one tetrahydro-2-one derivative (12), four coumarins (7, 13, 14, and 16), six caffeic acid derivatives (8, 11, 15, 17, 18, and 19), and one triterpenoid (20). Their chemical structures were established using NMR spectra and comparison with literature. The anti-diabetic activity of the isolated compounds was assessed by investigating their inhibitory effects on protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase. The results revealed that ginnalin A (10) and 3-(4′-hydroxyphenyl)-2-propenoic acid (4′′-carboxyl)-phenyl ester (13) exhibited significant inhibitory effects on both PTP1B and α-glucosidase with IC 50 values of 7.9 ‒ 37.6 and 13.9 ‒ 31.9 μM, respectively. In the kinetic study, these two compounds showed noncompetitive-type PTP1B and α-glucosidase inhibition, with K i values of 35.6 and 7.3 μM for PTP1B and 13.9 and 31.0 μM for α-glucosidase, respectively. These findings highlight the potential of the isolated compounds as candidates for the development of novel therapeutic agents for diabetes.

Anti-inflammatory and Cytotoxic Activities of Phenolic Compoundsfrom Broussonetia kazinoki

The phytochemical investigation of Broussonetia kazinoki roots led to the isolation of ten compounds, including six flavonoids (1–6), two lignans (7 and 8), and two coumarins (9 and 10) by comparing their 1H and 13C NMR spectra with reference values. To the best of our knowledge, compounds 9 and 10 were isolated from this plant for the first time. Among the ten isolates, compounds 2, 4, and 6 exhibited inhibitory effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophage RAW264.7 cells with IC50 values of 11.98, 10.16, and 24.06 μM, respectively. Furthermore, compounds 2, 4, and 6 reduced LPS-induced inducible nitric oxide synthase (iNOS) expression in a dose-dependent manner. Pre-incubation of cells with these compounds also significantly suppressed LPS-induced COX-2 protein expression. Compounds 2, 4, and 6 also showed cytotoxic activity against HL-60 cells with IC50 values ranging between 46.43 and 94.06 μM.

Anti-inflammatory and Cytotoxic Activities of Phenolic Compoundsfrom Broussonetia kazinoki

The phytochemical investigation of Broussonetia kazinoki roots led to the isolation of ten compounds, including six flavonoids (1–6), two lignans (7 and 8), and two coumarins (9 and 10) by comparing their 1H and 13C NMR spectra with reference values. To the best of our knowledge, compounds 9 and 10 were isolated from this plant for the first time. Among the ten isolates, compounds 2, 4, and 6 exhibited inhibitory effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophage RAW264.7 cells with IC50 values of 11.98, 10.16, and 24.06 μM, respectively. Furthermore, compounds 2, 4, and 6 reduced LPS-induced inducible nitric oxide synthase (iNOS) expression in a dose-dependent manner. Pre-incubation of cells with these compounds also significantly suppressed LPS-induced COX-2 protein expression. Compounds 2, 4, and 6 also showed cytotoxic activity against HL-60 cells with IC50 values ranging between 46.43 and 94.06 μM.

Missed detections of influenza A(H1)pdm09 by real-time RT–PCR assay due to haemagglutinin sequence mutation, December 2017 to March 2018, northern Viet Nam

Introduction@#There are two methods of reverse transcription polymerase chain reaction (RT–PCR) that have been the common methods to detect influenza infections: conventional and real-time RT–PCR. From December 2017 to March 2018, several missed diagnoses of influenza A(H1)pdm09 using real-time RT–PCR were reported in northern Viet Nam. This study investigated how these missed detections occurred to determine their effect on the surveillance of influenza.@*Methods@#The haemagglutinin (HA) segments of A(H1N1)pdm09 from both real-time RT-PCR positive and negative samples were isolated and sequenced. The primer and probe sets in the HA gene were checked for mismatches, and phylogenetic analyses were performed to determine the molecular epidemiology of these viruses.@*Results@#There were 86 positive influenza A samples; 32 were A(H1)pdm09 positive by conventional RT–PCR but were negative by real-time RT–PCR. Sequencing was conducted on 23 influenza (H1N1)pdm09 isolates that were recovered from positive samples. Eight of these were negative for A(H1)pdm09 by real-time RT–PCR. There were two different mismatches in the probe target sites of the HA gene sequences of all isolates (n = 23) with additional mismatches only at position 7 (template binding site) identified for all eight negative real-time RT–PCR isolates. The prime target sites had no mismatches. Phylogenetic analysis of the HA gene showed that both the positive and negative real-time RT–PCR isolates were grouped in clade 6B.1; however, the real-time RT–PCR negative viruses were located in a subgroup that referred to substitution I295V.@*Conclusion@#Constant monitoring of genetic changes in the circulating influenza A(H1N1)pdm09 viruses is important for maintaining the sensitivity of molecular detection assays.

Seroprevalence survey of avian influenza A(H5N1) among live poultry market workers in northern Viet Nam, 2011

Objective:Highly pathogenic avian influenza A(H5N1) is endemic in poultry in Viet Nam. The country has experienced the third highest number of human infections with influenza A(H5N1) in the world. A study in Hanoi in 2001, before the epizootic that was identified in 2003, found influenza A(H5N1) specific antibodies in 4% of poultry market workers (PMWs). We conducted a seroprevalence survey to determine the seroprevalence of antibodies to influenza A(H5N1) among PMWs in Hanoi, Thaibinh and Thanhhoa provinces.Methods:We selected PMWs from five markets, interviewed them and collected blood samples. These were then tested using a horse haemagglutination inhibition assay and a microneutralization assay with all three clades of influenza A(H5N1) viruses that have circulated in Viet Nam since 2004.Results:The overall seroprevalence was 6.1% (95% confidence interval: 4.6–8.3). The highest proportion (7.2%) was found in PMWs in Hanoi, and the majority of seropositive subjects (70.3%) were slaughterers or sellers of poultry.Discussion:The continued circulation and evolution of influenza A(H5N1) requires comprehensive surveillance of both human and animal sites throughout the country with follow-up studies on PMWs to estimate the risk of avian–human transmission of influenza A(H5N1) in Viet Nam.

Nerve function impairment in leprosy reaction

Background: Nerve damage in leprosy reaction occurs very quickly, that can lead to paralysis for many peripheral nerves within 24 hours. Objective: To survey nerve function impairment in leprosy reactions. Subjects and method: 285 new leprosy patients treated from 1996 to 2000 at 22 districts in Ho Chi Minh city had leprosy reaction and estimated nerve functions. This was retrospective cross-section descriptive study. Results: This study included 70.2% men, age 15-45 years (71.9%) and most patients were manual laborers. There were 83.5% multibacillary (MB) and 16.5% paucibacillary (PB). 86.3% Reversal Reaction (RR), Erythemal Nodosum Leprosy (ENL) 13% and both 0.7%. 53% of leprosy reaction happened during Multi-Drug Treatment (MDT), at diagnosis 37.5%, before MDT 7.7% and after MDT 1.8%. Nerve function impairment was 38.2% in leprosy reaction; men had impaired nerve function 1.7 times higher than women (p<0.05). Nerve function impairment in RR and ENL as well as MB and PB were the same (p>0.05). MB (42%) has impaired nerve function higher than PB (26.1%) in RR (p<0.05, OR = 2.05). Conclusions: Leprosy reaction happened to men more frequent than women, essentially in MB and during MDT. One third of cases had nerve function impairment in leprosy reaction and also had a link between sex and nerve function impairment. MB was 2 times the impaired nerve function higher than PB in RR.

Detection and genotyping of hepatitis C (HCV) and G (HGV) co-existing in viral hepatitis patients admitted to hospitals in Ha Noi

Background: Hepatitis C Virus (HCV) is one of thecauses resulting in chronic hepatitis, cirrhosis and primary hepatocarcinoma. In Viet Nam, HCV-infected people are on the increase. The co-existence of HCV and G (HGV) in Viet Nam and their accurate genotyping needs to be clarified. Objective: To detect and molecularly genotype HCV and HGV from 4 serum isolates. Materials: This study consisted of 4 anti-HCV positive [HCV(+)] serum isolates. Method: To extract genomic RNA, perform RT-PCR, 5\u2019UTR fragment of 295 nucleotides for HCV, genomic RNAs from HCV(+) (confirmed by RT-PCR) as samples for RT-PCR for HGV to obtain 260 bp 5\u2019UTR. All of them were cloned and sequenced for analysis. Results: HCV products and HCV + HGV products obtained from samples, respectively; suggested that the co-existence of HCV and HGV could occur in a patient. Base on Gen Back and analysis, we showed that three nucleotide strains of HCV (HCV-H1VN, HCV-H2VN, HCV-H3VN) belongs to genotype 1a of the group 1a/1b, commonly found in East and Southeast Asia. HGV of Viet Nam [HGV-(Han9)VN strain] was identified to belong to type 2; one of five HGV types existing in the world. Conclusions: Three HCV isolates were genotype 1a; one HGV isolate belonged to genotype 2. Detection and genotyping of co-existence of HCV and HGV contributed the development of a multiplex-PCR/RT-PCR for screening blood-transmitted viral hepatitis.

The prevalence of deltoid contracture in some areas of Viet Nam in 2006-2007

Background: Deltoid contracture can be a congenital or acquired condition. There were not any reports on deltoid contracture in English literature until 1960. In 2005 there were 170 children presented at the Viet Nam Pediatric Institute with deltoid contracture. These children came from different provinces, nationwide. The numbers of children who have this condition is increasing, but there were few studies on this problem in Viet Nam. Objectives: To identify the prevalence of deltoid contracture in Viet Nam in 2006-2007. Subjects and method: A cross-sectional study was done in 8 provinces representing for 3 geographic regions of Viet Nam., included Ha Noi, Ha Tay, Thanh Hoa and Lang son in Northern, Ha Tinh and Da Nang in Central and Tien Giang and Can Tho in the Southern region. 29,696 people aged from 1 to 60 years old at the baseline were involved in the study. The subjects were examined to identify the deltoid contracture based on defined criteria. Results: The prevalence of disease was 0.65% (0.83% in men and 0.51% in women). The rate was highest in the group of 6-10 years of age (1.81%). The prevalence was 0.82% in rural and 0.31% in urban area. Cases were found in all but 4 provinces (Da Nang, Tien Giang, Can Tho and Ha Noi) Conclusion: The prevalence of Deltoid contracture in Viet Nam was 0.65% in 2006-2007. It was more likely to occur in men than in women, in age group of 6 \u2013 10 than in other groups and in rural than in urban area.

THE RISK FACTORS OF THE DELTOID CONTRACTURE OF LOCAL PEOPLE IN VIETNAM

Background: Deltoid contracture can be congenital or acquired. A cross-sectional study has been done in 8 provinces representing three regions in Vietnam. These are Ha Noi, HaTay, Thanh Hoa and Lang Son in the North, Ha Tinh and Da Nang provinces in the central, Tien Giang and Can Tho provinces in the South of Vietnam. Objective: To identify the risk factors of Deltoid contracture in Vietnam from 2006 - 2007. Subject and Method: 29696 people aged from 1 to 60 years old at the time of the survey were examined to diagnose the Deltoid contracture as well as being interviewed by structured questionnaire. Results: There was significant association between contracture of Deltoid muscle and some factors. These are antibiotics injection into the Delta muscle at 0 - 5 years old: OR = 2.93 (1.435,8); Antibiotics type (streptomycin) was injected at 0-5 years old: OR = 45.2 (13.1 - 167); having cicatrix: OR = 73.4 (46.1 - 116.9). There was no significant association between Deltoid fibrosis and vaccination (position and administration). Logistic regression was done to find that antibiotics injection into Delta muscle at 6 - 10 years old and antibiotics type (streptomycin) were significantly associated with Deltoid contracture. Conclusion: Risk factors of Deltoid contracture in this study were antibiotic injection at aged 0 - 5 years old, antibiotic type (Streptomycin) and having cicatrix. There was no significant association between Deltoid fibrosis and vaccination (position and administration).

Evaluation of microbial contamination in shrimp paste

Background: Food-born bacteria can be present in raw materials or contaminated foods during process and storage. Shrimp paste is a popular food in Viet Nam, but there are no studies on the hygiene and safety of this food. Objectives: To identify the microbial contamination of commercial shrimp paste available in Ha Noi City. Materials and method: A total of 50 shrimp paste samples were collected randomly from markets around Ha Noi City. Enumeration and isolation methods were used to determine the microbial contamination in these samples. Results: 100% of the samples were contaminated with Clostridium perfringens and Candida albicans. 10% of samples were contaminated with Coliform. Other pathogenic bacteria, including Escherichia coli, Salmonella, Staphylococcus aureus, Vibrio parahaemolyticus and Vibrio cholerae were not found in shrimp paste samples. Conclusion: Evaluation of microbial contamination in popular foods such as shrimp paste should be done regularly to prevent food-born diseases in the community.

Evaluation of dipstick kit for detection of vibrio cholerae 01

Background:The kit Crystal VC is a Lateral Flow Imunochromatographic test for the qualitative determination of Lipopolysacharide (LPS) antigen of both V cholerae 01 and 0139, from stool specimens, using monoclonal antibodies specific to V. cholerae 01 and 0139 LPS. It does not include culturing the specimen and is performed without the need for sophisticated laboratory equipment. \r\n', u'Objectives: To evaluate the dipstick kit for detection of V. cholerae 01. Subjects and methods: A total of 65 stool specimens from diarrhea patients were tested to determine V. cholerae 01 by Crystal VC kit. \r\n', u'Results: The sensitivity of the 01 dipstick compared to culture was 93.7%, with a specificity of 87.7%. Crystal VC kit is simple, sensitivity, specific and does not require culturing procedures, making it suitable for direct detection of V. cholerae in clinical specimens. Also, the test only requires 10 minutes to complete.\r\n', u'Conclusions: The dipsticks test may be helpful in confirming clinically suspected cholera cases, especially during the start of an outbreak. Once a cholera outbreak has been confirmed, large scale preventive measures could be mobilized to minimize morbidity and mortality. \r\n', u'

Major enteropathogenic bacteria isolated in Hai Phong pediatric hospital from diarrhea patients

Background: Diarrhea is a leading cause of death in children under 5 years old, especially in developing countries. About 12.600 children die because of diarrhea everyday in Asia, Africa and Latin-America. Objective: To identify the main organism that causes diarrhea in children under 5 years old. Subject and Method: The etiology agents of diarrheal children under 5 years old admitted to the Pediatric Hospital in Hai Phong city were studied in the period from September 2006 to August 2007. A total of 968 children were examined for diarrheagenic Escherichia coli (DEC), Salmonella, Shigella, Vibrio, Aeromonas, Campylobacter, these pathogens as being significant bacteria associated with diarrhea. A total of 212 out of 968 cases were positive for bacteria. Result: The main pathogens were diarrheagenic Eschierichiacoli 153 (15.7%), Salmonella 12 (1.24%), Shigella 32 (3.3%). Vibirio paraheamolyticus 1(0.1%), Aeromonas 8 (0.8%), Campylobacter 6(0.6%) from rectal swabs and no Vibrio cholerae was found. The multiplex PCR assays for the identification of DEC was developed. DEC was classified into 6 categories with frequencies of EPEC 3.9%, ETEC 4.4%, EIEC 0.6%, EAggEC 6.7%, DAEC 0.1%, no EHEC was identified. Conclusion: An analysis of incidence of enteropathogens with respect to seasonal variant demonstrated that the frequencies of isolation of etiology agents mainly in July, August and September. This study also showed that diarrheagenic- Escherichia coli is the main organism causing diarrhea in children under 5 years old.

Surveillance for Vibrio cholerae 01 and vibriophages in surface water - the factors for prediction of cholera outbreaks

Background: In countries that cholera outbreaks commonly occurs, surveillance of surface water is important to control the epidemics. Kappa phage (K139) of Vibrio cholerae is related to epidemic El Tor and O139 strains in various countries. Objectives: To study the relationships between V. cholerae 01 and vibriophages in surface water in Thai Binh and Hai Phong city and to determine the predictors of cholera outbreaks. Subjects and method: Total of 82 water samples were collected by shrimp swab method in Hai Phong and Thai Binh in June and September 2007, where cholera outbreaks occurred. The enriched culture method and direct peR were applied to define the relationships between vibriophages and V. cholerae 01 in surface water. Results: The rates of detecting kappa junction with chromosomes of V. cholerae 01 in Hai Phong and Thai Binh were 10% and 15% in June 2007, 35% and 41% in September 2007. The rates of detecting vibriophages in Hai Phong and Thai Binh were 15% and 15% in June 2007, 25% and 36% in September 2007. The rates of Fs1 and Fs2 detected by PCR method were 70% and 100% in Hai Phong at June and September 2007, and were 57% and 100% in Thai Binh at June and September 2007, respectively. V. cholerae 01, O139 weren\u2019t found in water samples. Conclusion: The presences of vibriophages (kappa phage and fs1 fs2) in surface water contaminated with V. cholerae 01 were dependent on the ability of the vibriophages to infect and lyse these bacteria. Vibriophages played a role in the transfer of cholera toxin and pathogenic factors. Surveillance by detecting V. cholerae 01 and vibriophages in surface water may be a feasible means of predicting outbreaks of cholera before a significant number of cases occur.

Classification of vibriophages isolated from environment surface water samples in Thai Binh

Background: Classification of vibriophages has been applied for epidemiological surveillance of cholera, but in Vietnam, there was virtually no knowledge about it. It is very important to determine whether the strains have common origin or different origins.Objectives: To classify vibriophages isolated from environmental surface water samples in Thai Binh in order to monitor cholera outbreaks. Subjects and method: Three vibriophages (84, 87, and 811) were collected from surface water samples in Thai Binh in 2006. Electronic microscopy was used to compare the size and morphology of Vibrio phages. Also, the structures of genomic DNA of vibriophages were compared by hind III digestion pattern and Southern blotting. Results: Vibriophages S4 and S11 isolated from Thai Binh were similar to kappa phage (a phage produced by V. cholerae 01 EI Tor strain), phage IV (a phage produced by V. cholerae 01 classical strain) in term of morphology and genome and were the same shape and DNA dimension of phage 1823 isolated from V. cholerae O139 strain in India and Bangladesh. Conclusion: Phage 84, 81 isolated from Thai Binh were new kinds of vibriophage isolated in Viet Nam. These findings were very useful for supervising and controlling cholera outbreaks in Vietnam.

Multiplex PCR assay for direct detection of diarrheagenic escherichia coli from clinical stool specimens

Background: To distinguish the different types of pathogenic E. coli with other non-pathogenic E.coli in the intestine is extremely important in diagnosis. Up to date there are at least six types of E. coli that causes diarrhea. Objectives: We have designed a multiplex PCR assay for the direct detection of 6 categories of diarrheagenic Escherichia coli. Subjects and method: This techniques proved to be specific and rapid for detecting virulence genes from Shiga toxin-producing (stx and eae), enteropathoogenic (eae), enterotoxigenic (elt, est), ennteroinvasive (ipaH), enteroaggregative (aggR), and diffuse adherent (daaE) Esscherichia coli. The technique was applied to 295 clinical stool specimens. Results: The highest prevalence is EAggEC with 51 positive samples.(17.29%), 48 EIEC (16.27%), 17 EPEC (5.76%), 8 ETEC (LT) (2.71%), 5 ETEC (ST) (1.69%), 1 DAEC (0.34%), no STEC positive and 19 mix infections (6.44%). Conclusion: Multiplex PCR assay is a quick and highly accuurate technique. It is not only specific but can also amplify 7 virulence genes of diarrrheagenic E.coli at the same time. This method would offer an effective alternative to traditional culture methods for the identification and differentiation of human diarrhaegenic Escherichia coli.

Symptoms of human cysticercosis for diagnosis

Background: People were infected with Cysticercus by either eating Taenia solium eggs from the environment or from proglottids in intestines. These eggs hatched to larvae in muscular and cerebral tissue, which causes specific symptoms. \r\n', u'Objectives: To determine symptoms of human cysticercosis. \r\n', u'Subjects and methods: Clinical and para-clinical processes were conducted on 30 cysticercosis patients, of which 21 were male (70%) and 9 female (30%).\r\n', u'Results and conclusion: The main symptoms were headache in 29 patients (96.7%), subcutaneous cysts in 28 patients (93.3%), epilepsy in 14 patients (46.7%), positive ELISA (antigen of T.solium) with samples in 28 (93.3%) and positive ELISA with CSF samples (73.3%), living cysts in the brain were discovered in 25 patients (83.3%) by CT scanner and eosinophylia in 24 patients (80%). Cysticercus nodules were collected from 28 patients in this study; the species were identified by molecular method. A portion of 652 bp of mitochondrial-encoded cytochrome oxidase b (cob) and 217 amino-acid was amplified by Polymerase Chain Reaction (PCR) and sequenced. The nucleotide sequence was comparatively aligned with the known corresponding sequences of Taenia solium Chinese (TsoCN1). Molecular-based analysis revealed that the Cysticercus from the patients in this study was identified as Taenia solium. There is absolute nucleotide and amino-acid similarity between Taenia solium Chinese (hemogeny 99.1-99.8% of nucleotide and 100% of amino acid).\r\n', u'

Endovascular laser He-Ne and micro frequency electromagnetic stimulation in treatment of Parkinson in the Center for Biomedical Physic

Parkinson is popular disease caused by degeneration of central nervous system. 17 patients received the specific drug therapy but had no effect. They then received the endovascular laser He - We in combination with micro frequency electromagnetic stimulation. The results have shown that the disease’ s symptoms were remised and dosage of current drugs was reduced. The method found simply, easy to implement and no effects on the cardiovascular system

The situation of occupational accident in the construction facility cause and solution for prevention

The study on the document and field minutes and direct interview of workers, managers in the Ha noi General Construction company during 1991-1999 have shown that there were72 accidents with 104 persons with injuries in which 23 death, 53 moderate and severe injuries, 28 mild injuries, fall from high accounted for high rate (36,6%), the main cause (89%) of the accident that procedure and regulation of safe work were not obeyed properly.

Prevalence of orodental diseases in pupils with ages of 12 in secondary schools, Cau Giay district and risk factors

We undertake this study to create a base for expanding the school dental program in the whole country of Vietnam, firstly in Hanoi capital and Cau Giay district just established. Our research scope is of 9,512 pupils selected accidentally from several Secondary schools located in Cau giay district in Feb 1998. Followings are the minitial results of our research: 1. The proportion of carries to 12 years old pupils in Cau Giay district is 37.9% in which there are no difference between the boys and girls. 2. The proportion of periodontosis is 77.9%, in which the boys is more than the girls with p< 0.05. 3. Eating candy and other sweets too much is a causative for carries (with OR= 5.7) and for periodontosis (with OR= 4.28) 4. Infrequent tooth brush also is a causative agent for carries (with OR = 4.58) and periodontositis (with OR=3.87)