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STUDY QUESTION: In non-male factor infertile couples, are there any differences in the developmental outcomes between children born through ICSI and conventional IVF (cIVF)? SUMMARY ANSWER: In this preliminary study, ICSI and cIVF seem to have a comparable effect on developmental outcomes after 12 months in children born to non-male factor infertile couples. WHAT IS KNOWN ALREADY: ICSI, an invasive technique, has raised concerns about potential developmental abnormalities in children. Limited data are available regarding the developmental outcomes of ICSI-conceived infants born to non-male factor infertile couples. STUDY DESIGN, SIZE, DURATION: This prospective cohort study involved a follow-up of all children aged 12 months or older who were born from pregnancies resulting from either ICSI or cIVF as part of a previous randomized controlled trial (RCT) (NCT03428919). PARTICIPANTS/MATERIALS, SETTING, METHODS: In the original RCT, 1064 women were randomly assigned to the ICSI or cIVF groups (532 women for each group). Follow-up was conducted with 155 couples (195 children) in the ICSI group and 141 couples (185 children) in the cIVF group. The Vietnamese version of the Ages & Stages Third Edition Questionnaires (ASQ-3) and the Development Red Flags questionnaires were completed by the participants. A total of 141 (90.1%) women (177 children) in the ICSI group and 113 (80.1%) women (145 children) in the cIVF group returned fully completed questionnaires. The primary outcomes were the developmental outcomes based on responses to the ASQ-3 and the Red Flags questionnaire. MAIN RESULTS AND THE ROLE OF CHANCE: The mean age of children at follow-up was 19.5 ± 5.0 months in the ICSI group and 19.3 ± 5.5 months in the cIVF group. The mean height and weight of children in both groups were similar. The overall proportion of children with any abnormal ASQ-3 score did not differ significantly between the ICSI and cIVF groups (16.9% vs 13.1%, P = 0.34). The proportion of children with Red Flag signs was also comparable between the two groups (6.2% vs 9.2%, P = 0.36, ICSI vs cIVF, respectively). LIMITATIONS, REASONS FOR CAUTION: Despite a reasonably high follow-up response rate, there is a potential risk of sampling bias, and overall, the number of children with developmental abnormalities was very small. The study relied solely on questionnaires as screening tools, rather than incorporating additional behavioral observations or physical developmental tests; this may have affected the statistical power and the significance of between-group comparisons. WIDER IMPLICATIONS OF THE FINDINGS: The current findings contribute to the existing evidence and support the comparative safety of ICSI and cIVF regarding early childhood development. However, more extensive and prolonged follow-up data for these children are needed to draw definitive conclusions. STUDY FUNDING/COMPETING INTEREST(S): No external funding was received for this study, and no authors reported conflicting interests. TRIAL REGISTRATION NUMBER: NCT04866524 (clinicaltrials.gov).
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Spotty Liver Disease (SLD), caused by Campylobacter hepaticus or C. bilis infection in adult female chickens continues to emerge as a major disease problem in cage-free production systems. Free range production has become the predominant system in Australian egg production and SLD is widespread in these farms. Previous studies have identified having a scratch area as a key determinant for SLD occurrence. An Australia-wide survey of egg production flocks with scratch areas was conducted regarding SLD including 48 individual flocks. Descriptive information on the facilities and flock management practices was reported. The incidence of SLD, age of first outbreak, initial mortality rate, duration of elevated mortality, and magnitude and duration of any associated egg production decline are described. Recurrence of SLD in the same flock was also reported and discussed. Therapies applied were recorded and assessed across SLD severity and duration. SLD occurred in 66.7% of layer flocks whose facility included a scratch area. Recurrent SLD outbreaks occurred in 31% of flocks experiencing SLD. Antibiotic medication reduced duration of mortality and egg production decline. Antibiotic therapy was associated with reduced duration of mortality and a less severe and shorter duration of egg production drops compared to untreated flocks. PCR detection of C. hepaticus in cloacal swabs and house dust samples and a serological ELISA test were compared and evaluated as diagnostic aids or as possible predictors of SLD outbreaks. The ELISA showed substantial agreement with detection of C. hepaticus in cloacal swabs by PCR. Examining composite house dust samples by PCR for C. hepaticus DNA appeared to be the most convenient and cost-effective aid to diagnosis and as a putative predictor for SLD outbreaks.
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Criação de Animais Domésticos , Infecções por Campylobacter , Galinhas , Doenças das Aves Domésticas , Animais , Doenças das Aves Domésticas/epidemiologia , Doenças das Aves Domésticas/microbiologia , Feminino , Austrália/epidemiologia , Criação de Animais Domésticos/métodos , Infecções por Campylobacter/veterinária , Infecções por Campylobacter/epidemiologia , Infecções por Campylobacter/microbiologia , Hepatopatias/veterinária , Hepatopatias/epidemiologia , Campylobacter/isolamento & purificação , Surtos de Doenças/veterinária , Abrigo para Animais , Incidência , AntibacterianosRESUMO
BACKGROUND: Key populations are disproportionately affected by HIV, viral hepatitis (VH), and sexually transmitted infections (STIs) and face barriers to care. Peer navigation programs are widely used, but evidence supporting their use has not been synthesized. SETTING: Peer navigation programs for sex workers, men who have sex with men, people who inject drugs, prisoners, and trans and gender diverse people globally. METHODS: To inform World Health Organization guidelines, we conducted a systematic review of effectiveness, values and preferences, and cost studies published between January 2010 and May 2021. We searched CINAHL, PsycINFO, PubMed, and EMBASE; screened abstracts; and extracted data in duplicate. The effectiveness review included randomized controlled trials and comparative observational studies evaluating time to diagnosis or linkage to care, treatment initiation, treatment retention/completion, viral load, cure, or mortality. We assessed risk of bias and summarized findings in GRADE evidence profiles. Values and preferences and cost data were summarized descriptively. RESULTS: Four studies evaluated the effectiveness of peer navigators for key populations. All were focused on HIV; none were designed for VH or STIs. These studies showed mixed effects on linkage to care, treatment retention/completion, and viral load; no studies measured treatment initiation, cure, or mortality. Two values and preferences studies with community-based organization staff and health workers suggested peer navigators for key populations were acceptable and valued, although continued challenges remained. No cost studies were identified. CONCLUSIONS: Although limited, available studies provide moderate certainty evidence for benefits of HIV/VH/STI peer navigation programs for key populations. Further evaluations are needed.
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Infecções por HIV , Adesão à Medicação , Retenção nos Cuidados , Humanos , Masculino , Infecções por HIV/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Observacionais como Assunto , Populações VulneráveisRESUMO
To compare the rate of positive thyroid peroxidase antibodies (TPO Ab) between women with different polycystic ovary syndrome (PCOS) phenotypes and women without PCOS. This is a retrospective cohort study. Women with PCOS at My Duc Hospital between June 1, 2020, and March 27, 2021, were matched with non-PCOS women by age. TPO Ab (cut-off: 34 IU/mL) and thyroid-stimulating hormone (TSH) levels were measured as markers of Hashimoto thyroiditis and thyroid function, respectively. One thousand eight hundred eight infertile women were included, 904 with PCOS (mean age 29.0 ± 3.58 years) and 904 without PCOS (29.1 ± 3.4 years; controls). Women with PCOS had a higher body mass index (22.8 ± 3.84 vs. 19.9 ± 2.23 kg/m2, p < 0.001), but most were not overweight/obese. Rates of positive TPO Ab in women with versus without PCOS were 8.2% and 8.4%, respectively (p = 0.932). Rates of positive TPO Ab in patients with PCOS phenotype A, B, C, or D were not statistically different (7.5%, 2.9%, 20.0%, and 7.8%, respectively). Median TSH concentrations were similar in the PCOS and control groups (1.84 mIU/L vs. 1.78 mIU/L, respectively; p = 0.194). Based on a linear regression model, there was no correlation between either BMI or the estradiol to progesterone ratio and TPO Ab status. In a large population of infertile women with PCOS who were mostly lean patients, rates of positive TPO Ab across all four PCOS phenotypes did not differ significantly from those in women without PCOS. These findings did not support the hypothesis that PCOS is a risk factor for Hashimoto thyroiditis.
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Doença de Hashimoto , Infertilidade Feminina , Síndrome do Ovário Policístico , Humanos , Feminino , Adulto , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/epidemiologia , Estudos Retrospectivos , Tireotropina , Iodeto PeroxidaseRESUMO
INTRODUCTION: Preterm birth is the most common cause of neonatal morbidity and mortality. Women with twin pregnancies and a short cervical length are at high risk for preterm birth. Vaginal progesterone and cervical pessary have been proposed as potential strategies to reduce preterm birth in this high-risk population. Therefore, we aimed to compare the effectiveness of cervical pessary and vaginal progesterone in improving developmental outcomes of children born to women with twin pregnancies and mid-trimester short cervical length. MATERIAL AND METHODS: This was a follow-up study (NCT04295187) of all children at 24 months of age, born from women treated with cervical pessary or progesterone to prevent preterm birth in a randomized controlled trial (NCT02623881). We used a validated Vietnamese version of Ages & Stages Third Edition Questionnaires (ASQ-3) and a red flag questionnaire. In surviving children, we compared the mean ASQ-3 scores, abnormal ASQ-3 scores, the number of children with any abnormal ASQ-3 scores and red flag signs between the two groups. We reported the composite outcome of perinatal death or survival with any abnormal ASQ-3 score in offspring. These outcomes were also calculated in a subgroup of women with a cervical length ≤28 mm (<25th percentile). RESULTS: In the original randomized controlled trial, we randomized 300 women to pessary or progesterone. After counting the number of perinatal deaths and lost to follow-up, 82.8% parents in the pessary group and 82.5% parents in progesterone group returned the questionnaire. The mean ASQ-3 scores of the five skills and red flag signs did not differ significantly between the two groups. However, the percentage of children having abnormal ASQ-3 scores in fine motor skills was significantly lower in the progesterone group (6.1% vs 1.3%, P = 0.01). There were no significant differences in the composite outcome of perinatal death or survival with any abnormal ASQ-3 score in unselected women and in those with cervical length ≤28 mm. CONCLUSIONS: Cervical pessary and vaginal progesterone may have comparable effects on developmental outcomes in children at ≥24 months of age, born to women with twin pregnancies and short cervical length. However, this finding could be likely due to a lack of study power.
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Morte Perinatal , Nascimento Prematuro , Gravidez , Recém-Nascido , Feminino , Criança , Humanos , Progesterona , Gravidez de Gêmeos , Seguimentos , Nascimento Prematuro/prevenção & controle , Pessários , Colo do Útero , Administração IntravaginalRESUMO
Current quantification methods of Escherichia coli (E. coli) contamination in water samples involve long incubation, laboratory equipment and facilities, or complex processes that require specialized training for accurate operation and interpretation. To address these limitations, we have developed a microfluidic device and portable instrument prototypes capable of performing a rapid and highly sensitive bacteriophage-based assay to detect E. coli cells with detection limit comparable to traditional methods in a fraction of the time. The microfluidic device combines membrane filtration and selective enrichment using T7-NanoLuc-CBM, a genetically engineered bacteriophage, to identify 4.1 E. coli CFU in 100 mL of drinking water within 5.5 hours. The microfluidic device was designed and tested to process up to 100 mL of real-world drinking water samples with turbidities below 10 NTU. Prototypes of custom instrumentation, compatible with our valveless microfluidic device and capable of performing all of the assay's units of operation with minimal user intervention, demonstrated similar assay performance to that obtained on the benchtop assay. This research is the first step towards a faster, portable, and semi-automated, phage-based microfluidic platform for improved in-field water quality monitoring in low-resource settings.
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Bacteriófagos , Água Potável , Escherichia coli , Dispositivos Lab-On-A-Chip , LuciferasesRESUMO
STUDY QUESTION: Is there any difference in developmental outcomes in children born after capacitation IVM (CAPA IVM) compared with conventional IVF? SUMMARY ANSWER: Overall development up to 24 months of age was comparable in children born after CAPA IVM compared with IVF. WHAT IS KNOWN ALREADY: IVM has been shown to be a feasible alternative to conventional IVF in women with a high antral follicle count (AFC). In addition to live birth rate, childhood development is also a relevant metric to compare between the two approaches to ART and there are currently no data on this. STUDY DESIGN, SIZE, DURATION: This study was a follow-up of babies born to women who participated in a randomized controlled trial comparing IVM with a pre-maturation step (CAPA IVM) and IVF. Developmental assessments were performed on 231 children over 24 months of follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants in the randomized controlled trial had an indication for ART and a high AFC (≥24 follicles in both ovaries). They were randomized to undergo one cycle of either IVM (n = 273) or IVF (n = 273). Of these, 96 women and 118 women, respectively, had live births. Seventy-six women (94 children, 79.2%) and 104 women (137 children, 88.1%), respectively, completed Ages & Stages Third Edition Questionnaire assessment (ASQ-3), and underwent evaluation of Developmental Red Flags at 6, 12 and 24 months of age. MAIN RESULTS AND THE ROLE OF CHANCE: Baseline characteristics of participants in the follow-up study between the IVM and IVF groups were comparable. Overall, there were no significant differences in ASQ-3 scores at 6, 12 and 24 months between children born after IVM or IVF. The proportion of children with developmental red flags was low and did not differ between the two groups. Slightly, but significantly, lower ASQ-3 problem solving and personal-social scores in twins from the IVM versus IVF group at 6 months were still within the normal range and had caught up to the IVF group in the 12- and 24-month assessments. The number of children confirmed to have abnormal mental and/or motor development after specialist assessment was four in the IVM group and two in the IVF group (relative risk 2.91, 95% CI 0.54-15.6; P = 0.23). LIMITATIONS, REASONS FOR CAUTION: This study is an open-label follow-up of participants in a randomized controlled trial, and not all original trial subjects took part in the follow-up. The self-selected nature of the follow-up population could have introduced bias, and the sample size may have been insufficient to detect significant between-group differences in developmental outcomes. WIDER IMPLICATIONS OF THE FINDINGS: Based on the current findings at 2 years of follow-up, there does not appear to be any significant concern about the effects of IVM on childhood development. These data add to the evidence available to physicians when considering different approaches to fertility treatment, but require validation in larger studies. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by the Vietnam National Foundation for Science and Technology Development (NAFOSTED) under grant number FWO.106-YS.2017.02. L.N.V. has received speaker and conference fees from Merck, grant, speaker and conference fees from Merck Sharpe and Dohme, and speaker, conference and scientific board fees from Ferring; T.M.H. has received speaker fees from Merck, Merck Sharp and Dohme, and Ferring; R.J.N. has receives grant funding from the National Health and Medical Research Council (NHMRC) of Australia; B.W.M. has acted as a paid consultant to Merck, ObsEva and Guerbet and is the recipient of grant money from an NHMRC Investigator Grant; J.E.J.S. reports lecture fees from Ferring Pharmaceuticals, Biomérieux and Besins Female Healthcare, grants from Fund for Research Flanders (FWO) and is co-inventor on granted patents on CAPA-IVM methodology in the USA (US10392601B2) and Europe (EP3234112B1); T.D.P., M.H.N.N., N.A.N., T.T.L., V.T.T.T., N.T.N., H.L.T.H. and X.T.H.L. have no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years, and no other relationships or activities that could appear to have influenced the submitted work. TRIAL REGISTRATION NUMBER: NCT04296357 (www.clinicaltrials.gov). TRIAL REGISTRATION DATE: 5 March 2020. DATE OF FIRST PATIENT'S ENROLMENT: 7 March 2020.
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Coeficiente de Natalidade , Indução da Ovulação , Criança , Feminino , Fertilização in vitro/métodos , Seguimentos , Humanos , Nascido Vivo , Indução da Ovulação/métodos , GravidezRESUMO
Inadequate drinking water quality is among the major causes of preventable mortality, predominantly in young children. Identifying contaminated water sources remains a significant challenge, especially where resources are limited. The current methods for measuring Escherichia coli (E. coli), the WHO preferred indicator for measuring fecal contamination of water, involve overnight incubation and require specialized training. In 2016, UNICEF released a Target Product Profile (TPP) to incentivize product innovations to detect low levels of viable E. coli in water samples in the field in less than 6 h. Driven by this challenge, we developed a phage-based assay to detect and semi-quantify E. coli. We formulated a phage cocktail containing a total of 8 phages selected against an extensive bacterial strain library and recombined with the sensitive NanoLuc luciferase reporter. The assay was optimized to be processed in a microfluidic chip designed in-house and was tested against locally sourced sewage samples and on drinking water sources in Nairobi, Kenya. With this assay, combined with the microfluidic chip platform, we propose a complete automated solution to detect and semi-quantify E. coli at less than 10 MPN/100 mL in 5.5 h by minimally trained personnel.
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Bacteriófagos , Água Potável , Bactérias , Escherichia coli , Quênia , LuciferasesRESUMO
OBJECTIVE: Diabetes insipidus (DI) can be classified into 2 types: central/neurogenic DI and nephrogenic DI. Most cases of central DI occur after brain surgery, trauma, tumor, or infection. Here we report a rare case of familial central DI due to a heterozygous AVP gene mutation. METHODS: A case of familial neurogenic DI has been described with thorough clinical, laboratory, and genetic workup. PubMed and Google scholar databases were used for literature discussion. RESULTS: A 22-year-old man presented with polyuria and polydipsia. He drank about 4 gallons of water everyday and urinated large volumes very frequently. His physical examination was unremarkable. After 2 hours of water-deprivation, his serum sodium level was 147 mmol/L, serum osmolality was 302 mOsm/kg with concurrent urine osmolality of 78 mOsm/kg, vasopressin level was <0.8 pg/mL, and copeptin level was <2.8 pmol/L, suggesting neurogenic DI. His brain magnetic resonance imaging revealed the absence of the posterior pituitary bright spot but a normal anterior pituitary gland. Genetic analysis revealed a nonfunctional heterozygous mutation in the AVP gene. Further questioning revealed that his mother also had the disease and that he had been treated with desmopressin as a child; however, it was later self-stopped. The patient was reinitiated on desmopressin, which improved his symptoms. CONCLUSION: Genetic mutations in the AVP gene represent a very rare etiology of DI, and patients with DI respond well to desmopressin treatment.
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We developed a novel real-time PCR assay that simultaneously evaluates 11 major nucleos(t)ide antiviral (NA) drug resistance mutations (mt) in chronic hepatitis B patients (CHB), including L180M, M204I/V, and V207M (lamivudine [LMV] resistance), N/H238A/T (adefovir [ADF] resistance), which are circulating in Vietnam; and T184G/L, S202I, and M250V (entecavir [ETV] resistance) and A194T (tenofovir resistance), which have been recently reported in several studies across the globe. We detected drug-resistant mt in hepatitis B virus (HBV) samples using our predesigned panel of allele-specific locked-nucleic acid (LNA) probes. Our assay had a high sensitivity of 5% in a low-HBV DNA population of ≥5 × 103 IU/ml and was validated in a cohort of 130 treatment-naive children and 98 NA-experienced adults with CHB. Single-point mt for LMV and ADF resistance were detected in 57.7% and 54.1% of the child and adult samples, respectively, with rtV207M (children, 42.3%; adults, 36.7%) and rtN238T/A (children, 15.4%; adults, 16.3%) being the most frequent mt in these populations. Multiple-point mt, including rtL180M-rtM204V- rtN238A and rtL180M-rtM204I, were identified in only two children, resulting in LMV-ADF resistance and reduced ETV susceptibility. In conclusion, this assay accurately identified the mt profile of children (98.4%) and adults (91.2%) with CHB, which is comparable to established methods. This fast and sensitive screening method can be used for the detection of major NA-resistant mt circulating in developing countries, as well as providing a model for the development of similar mt-detection assays, especially for use in nonhospitalized patients who need their results within half a day, before starting treatment.
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Hepatite B Crônica , Adulto , Antivirais/farmacologia , Antivirais/uso terapêutico , Criança , DNA Viral/genética , Farmacorresistência Viral , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Humanos , Lamivudina/uso terapêutico , Mutação , Reação em Cadeia da Polimerase em Tempo RealAssuntos
Buprenorfina , Infecções por HIV , Transtornos Relacionados ao Uso de Opioides , Buprenorfina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Humanos , Manutenção , Metadona , Naloxona , Nitrilas , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Encaminhamento e Consulta , VietnãRESUMO
The high-performance liquid chromatography method coupled with diode array and mass spectrometric detector (HPLC-DAD-MS) method for quinonoid pigment identification and quantification in sea urchin samples was developed and validated. The composition and quantitative ratio of the quinonoid pigments of the shells of 16 species of sea urchins, collected in the temperate (Sea of Japan) and tropical (South-China Sea) climatic zones of the Pacific Ocean over several years, were studied. The compositions of the quinonoid pigments of sea urchins Maretia planulata, Scaphechinus griseus, Laganum decagonale and Phyllacanthus imperialis were studied for the first time. A study of the composition of the quinonoid pigments of the coelomic fluid of ten species of sea urchins was conducted. The composition of quinonoid pigments of Echinarachnius parma jelly-like egg membrane, of Scaphechinus mirabilis developing embryos and pluteus, was reported for the first time. In the case of Scaphechinus mirabilis, we have shown that the compositions of pigment granules of the shell epidermis, coelomic fluid, egg membrane, developing embryos and pluteus are different, which should enable a fuller understanding of the functions of pigments at different stages of life.
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Óvulo/química , Ouriços-do-Mar/química , Animais , Cromatografia Líquida de Alta Pressão , Embrião não Mamífero , Epiderme/química , Espectrometria de Massas , Oceano Pacífico , Pigmentos Biológicos , Quinonas/química , Ouriços-do-Mar/classificação , Ouriços-do-Mar/crescimento & desenvolvimentoRESUMO
Microbial colonisation of the gastrointestinal tract of newly hatched chicks starts at hatch, seeded from the immediate hatching environment, and quickly results in dense colonisation. The role of ecological factors in gut colonisation has been extensively investigated, as well as the role of micro- and macronutrients in supporting and selecting for bacterial species highly adapted for utilising those nutrients. However, the microbial community contained in poultry feed and its influence on colonisation and maturation of gut microbiota has not been directly addressed. In this study, we compared the microbiota found in poultry feed, with the microbiota of ileum, cecum and excreta, to identify substantial overlap in core microbiotas of the compared groups. We then investigated the microbiota present in raw feedstuffs: meat and bone meal, wheat, corn, canola, barley, soybean, millrun, sorghum, poultry oil, oats, limestone and bloodmeal from four geographically distinct feedstuff suppliers. Each of the feedstuffs had diverse microbial communities. The meat and bone meal and bloodmeal samples had the most complex and distinct microbial populations. There was substantial overlap in the phylogenetic composition found in the grain and seed samples: barley, canola, corn, millrun, oats, sorghum, soybean meal and wheat. Issues related to methodology, viability of microbial communities in the gut and feed, and the implications for biosecurity are discussed.
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BACKGROUND AND AIM: Chronic hemodialysis patients are at high risk of contracting hepatitis B (HBV) and C (HCV) virus infections. In Vietnam, the seroprevalence of HBV and HCV infections is approximately 10 and 4%, respectively. Although the chronic hemodialysis population is increasing, relatively little epidemiology is available for HBV and HCV infections in this population. To address this, we reviewed the current literature on the magnitude of these infections in the hemodialysis population in Vietnam. METHODS: Four databases were used to search for publications containing the prevalence of HBV and/or HCV infections in hemodialysis patients in Vietnam. Grey literature search was utilized to identify local publications. Prevalence and 95% confidence interval were used or calculated, and a meta-analysis was conducted on HBV and HCV prevalence for comparison. RESULTS: Sixteen studies were included in the review. The search identified knowledge gaps in the current literature. Available data show that HBV and HCV infections remain prevalent in the hemodialysis population. HBV prevalence is not different between the north and the south of Vietnam. The pattern of HCV prevalence is different, with recent reports of lower prevalence in the south than in the north, while HCV prevalence varies between hemodialysis units in the same regions. CONCLUSIONS: A national prevalence survey of hemodialysis patients would improve the reliability and generalizability of the findings. However, the review confirmed that both HBV and HCV were prevalent in hemodialysis patients. The findings support a reinforcement of infection prevention to minimize the risk of HBV and HCV transmission in hemodialysis facilities.
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OBJECTIVES: Cryptococcal meningitis (CM) remains an important cause of morbidity and mortality among immunocompromised patients. Laboratory diagnostics for CM includes antigen detection, staining and culture. Data on the performance of the Biofire® FilmArray® meningitis/encephalitis (ME) panel for detecting Cryptococcus neoformans/gattii is limited, with several reports describing false negativity for this target. METHODS: A retrospective analysis of 1384 physician-ordered ME panel tests ordered between January 2017 to October 2018 was performed. ME panel results were compared to cerebrospinal fluid (CSF) cryptococcal antigen (CrAg) and CSF culture testing and clinical significance of cryptococcal detection was determined. RESULTS: There were 34 patients positive for cryptococcal detection by either ME panel, CSF CrAg or CSF culture in 2.7% of CSF specimens tested (38/1384). Of the 34 patients positive for cryptococcal detection, 85.3% were human immunodeficiency virus positive (29/34). The ME panel detected 32/38 (84.2%) cryptococcal-positive specimens, culture detected 28/38 (73.7%) and CSF CrAg was positive in 37/38 specimens (97.4%). The ME panel had a sensitivity and specificity of 96.4% (95% CI 81.7-99.9%) and 99.6% (95% CI 99.2-99.9%) compared with culture, and 83.8% (95% CI 68.0-93.8%) and 99.9% (95% CI 99.6-100.0%) compared to CSF CrAg testing, respectively. CrAg titres were lower among ME panel-negative, culture-negative specimens compared with ME panel-positive, culture-negative specimens (reciprocal median end-point titres of 128 ± 60 vs. 1920 ± 1730, p 0.04). All five CrAg-positive, ME panel- and culture-negative specimens were obtained from previously treated CM patients. DISCUSSION: The ME panel had high correlation with CSF culture and a somewhat lower correlation with CSF CrAg testing. The potential utility of using negative ME panel test results to predict culture sterility among patients undergoing treatment for CM warrants further study.
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Cryptococcus gattii/isolamento & purificação , Cryptococcus neoformans/isolamento & purificação , Meningite Criptocócica/diagnóstico , Análise Serial de Proteínas/métodos , Adulto , Idoso , Antígenos de Fungos/líquido cefalorraquidiano , Testes Diagnósticos de Rotina/métodos , Feminino , Infecções por HIV/complicações , Humanos , Masculino , Meningite Criptocócica/microbiologia , Meningite Criptocócica/mortalidade , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex/métodos , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto JovemRESUMO
Campylobacter hepaticus was recently identified as the aetiological agent of Spotty Liver Disease (SLD). SLD causes significant health and productivity losses in the Australian egg industry and the disease is present in other countries. Following the isolation and characterization of C. hepaticus, molecular tools and refined culturing methods have been developed to identify the pathogen. It is suspected that the application of these tools will lead to identification of the pathogen in many poultry production systems throughout the world. As C. hepaticus has only recently been identified, little is known about the mechanisms of pathogenesis and, hence, new research needs to be directed towards understanding SLD epidemiology and C. hepaticus virulence mechanisms to inform efforts to develop intervention strategies.
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Infecções por Campylobacter/veterinária , Campylobacter , Galinhas , Hepatopatias/veterinária , Doenças das Aves Domésticas/microbiologia , Animais , Campylobacter/ultraestrutura , Infecções por Campylobacter/microbiologia , Infecções por Campylobacter/terapia , Fígado/microbiologia , Fígado/patologia , Fígado/ultraestrutura , Hepatopatias/microbiologia , Hepatopatias/terapia , Microscopia Eletrônica de Transmissão/veterinária , Doenças das Aves Domésticas/terapiaRESUMO
From an EtOAc-soluble fraction of the leaves of Azadirachta indica, one new lactam 28-norlimonoid named nimbandiolactam-21 (1), together with 2 known limonoids (2 and 3) were isolated. Their relative structures were elucidated based on NMR spectroscopic analysis. Nimbandiolactone-23 (2) showed the most potent α-glucosidase inhibitory activity, with an IC50 value of 38.7 µM. Compound 1 represents the first naturally occurring example of a 28-norlimonoid having the lactam moiety. The plausible biosynthetic pathway for the formation of lactam moiety in 1 was proposed.
Assuntos
Azadirachta/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Lactamas/farmacologia , Limoninas/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Concentração Inibidora 50 , Lactamas/química , Lactamas/isolamento & purificação , Limoninas/química , Limoninas/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Folhas de Planta/química , Plantas Medicinais/químicaRESUMO
Fucoidans from brown macroalgae have beneficial biomedical properties but their use as pharma products requires homogenous oligomeric products. In this study, the action of five recombinant microbial fucoidan degrading enzymes were evaluated on fucoidans from brown macroalgae: Sargassum mcclurei, Fucus evanescens, Fucus vesiculosus, Turbinaria ornata, Saccharina cichorioides, and Undaria pinnatifida. The enzymes included three endo-fucoidanases (EC 3.2.1.-GH 107), FcnA2, Fda1, and Fda2, and two unclassified endo-fucoglucuronomannan lyases, FdlA and FdlB. The oligosaccharide product profiles were assessed by carbohydrate-polyacrylamide gel electrophoresis and size exclusion chromatography. The recombinant enzymes FcnA2, Fda1, and Fda2 were unstable but were stabilised by truncation of the C-terminal end (removing up to 40% of the enzyme sequence). All five enzymes catalysed degradation of fucoidans containing α(1â4)-linked l-fucosyls. Fda2 also degraded S. cichorioides and U. pinnatifida fucoidans that have α(1â3)-linked l-fucosyls in their backbone. In the stabilised form, Fda1 also cleaved α(1â3) bonds. For the first time, we also show that several enzymes catalyse degradation of S. mcclurei galactofucan-fucoidan, known to contain α(1â4) and α(1â3) linked l-fucosyls and galactosyl-ß(1â3) bonds in the backbone. These data enhance our understanding of fucoidan degrading enzymes and their substrate preferences and may assist development of enzyme-assisted production of defined fuco-oligosaccharides from fucoidan substrates.
Assuntos
Glicosídeo Hidrolases/química , Oligossacarídeos/química , Phaeophyceae/química , Polissacarídeo-Liases/química , Polissacarídeos/química , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/isolamento & purificação , Ensaios Enzimáticos , Estabilidade Enzimática , Flavobacterium/química , Flavobacterium/genética , Glicosídeo Hidrolases/genética , Glicosídeo Hidrolases/isolamento & purificação , Polimerização , Polissacarídeo-Liases/genética , Polissacarídeo-Liases/isolamento & purificação , Engenharia de Proteínas/métodos , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Especificidade por Substrato , Sulfatos/químicaRESUMO
Background Clinical pharmacy is key to the quality use of medicines. While there are different approaches in different countries, international perspectives may inform health service development. The Vietnamese Ministry of Health introduced a legal regulation of clinical pharmacy services in December 2012. Objective To describe the services, and to explore reported barriers and facilitators in implementing clinical pharmacy activities in Vietnamese hospitals after the introduction of Vietnamese Ministry of Health legal regulation. Setting Thirty-nine hospitals in Hanoi, Vietnam, including 22 provincial and 17 district hospitals. Method A mixed methods study was utilized. An online questionnaire was sent to the hospitals. In-depth interviews were conducted with pairs of nominated pharmacists at ten of these hospitals. The questionnaire focused on four areas: facilities, workforce, policies and clinical pharmacy activities. Main outcome measure Proportion of clinical pharmacy activities in hospitals. Themes in clinical pharmacy practice. Results 34/39 (87%) hospitals had established clinical pharmacy teams. Most activities were non-patient-specific (87%) while the preliminary patient-specific clinical pharmacy services were available in only 8/39 hospitals (21%). The most common non-patient-specific activities were providing medicines information (97%), reporting adverse drug reactions (97%), monitoring medication usage (97%). The patient specific activities varied widely between hospitals and were ad hoc. The main challenges reported were: lack of workforce and qualified clinical pharmacists. Conclusion While most hospitals had hospital-based pharmacy activities, the direct patient care was limited. Training, education and an expanded work forces are needed to improve clinical pharmacy services.
Assuntos
Assistência ao Paciente/estatística & dados numéricos , Farmacêuticos/organização & administração , Serviço de Farmácia Hospitalar/organização & administração , Recursos Humanos/estatística & dados numéricos , Pesquisas sobre Atenção à Saúde , Humanos , Entrevistas como Assunto , Farmacêuticos/estatística & dados numéricos , Serviço de Farmácia Hospitalar/estatística & dados numéricos , Papel Profissional , VietnãRESUMO
To evaluate the association between the single nucleotide polymorphism (SNP) rs227493 in the MEOX2 gene and nonsyndromic cleft palate only, this research was conducted as a case-control study by comparing a nonsyndromic cleft palate only group with an independent, healthy, and unaffected control group who were both examined by specialists. Based on clinical examination and medical records, we analyzed a total of 570 DNA samples, including 277 cases and 293 controls, which were extracted from dry blood spot samples collected from both the Odonto and Maxillofacial Hospital in Ho Chi Minh City and Nguyen Dinh Chieu Hospital in Ben Tre province, respectively. The standard procedures of genotyping the specific SNP (rs2237493) for MEOX2 were performed on a StepOne Realtime PCR system with TaqMan SNP Genotyping Assays. Significant statistical differences were observed in allelic frequencies (allele T and allele G) between the non-syndromic cleft palate only and control groups in female subjects, with an allelic odds ratio of 1.455 (95% confidence interval: 1.026-2.064) and P < 0.05. These study findings suggest that nonsyndromic isolated cleft palate might be influenced by variation of MEOX2, especially SNP rs2237493 in Vietnamese females.