Follicle size on day of trigger most likely to yield a mature oocyte

Funding: MRC, BBSRC and NIHR and supported by the NIHR/Wellcome Trust Imperial Clinical Research Facility and Imperial Biomedical Research Centre.Objective: To identify follicle sizes on the day of trigger most likely to yield a mature oocyte following hCG, GnRH agonist (GnRHa), or kisspeptin during IVF treatment. Design: Retrospective analysis to determine the size of follicles on day of trigger contributing most to the number of mature oocytes retrieved using generalized linear regression and random forest models applied to data from IVF cycles (2014–2017) in which either hCG, GnRHa, or kisspeptin trigger was used. Setting: HCG and GnRHa data were collected at My Duc Hospital, Ho Chi Minh City, Vietnam, and kisspeptin data were collected at Hammersmith Hospital, London, UK. Patients: Four hundred and forty nine women aged 18–38 years with antral follicle counts 4–87 were triggered with hCG (n = 161), GnRHa (n = 165), or kisspeptin (n = 173). Main outcome measure: Follicle sizes on the day of trigger most likely to yield a mature oocyte. Results: Follicles 12–19 mm on the day of trigger contributed the most to the number of oocytes and mature oocytes retrieved. Comparing the tertile of patients with the highest proportion of follicles on the day of trigger 12–19 mm, with the tertile of patients with the lowest proportion within this size range, revealed increases of 4.7 mature oocytes for hCG (P < 0.0001) and 4.9 mature oocytes for GnRHa triggering (P < 0.01). Using simulated follicle size profiles of patients with 20 follicles on the day of trigger, our model predicts that the number of oocytes retrieved would increase from a mean 9.8 (95% prediction limit 9.3–10.3) to 14.8 (95% prediction limit 13.3–16.3) oocytes due to the difference in follicle size profile alone. Conclusion: Follicles 12–19 mm on the morning of trigger administration were most likely to yield a mature oocyte following hCG, GnRHa, or kisspeptin.Publisher PDFPeer reviewe

Rapid detection of an Ebola biomarker with optical microring resonators

Ebola virus (EBOV) is a highly infectious pathogen, with a case mortality rate as high as 89%. Rapid therapeutic treatments and supportive measures can drastically improve patient outcome; however, the symptoms of EBOV disease (EVD) lack specificity from other endemic diseases. Given the high mortality and significant symptom overlap, there is a critical need for sensitive, rapid diagnostics for EVD. Facile diagnosis of EVD remains a challenge. Here, we describe a rapid and sensitive diagnostic for EVD through microring resonator sensors in conjunction with a unique biomarker of EBOV infection, soluble glycoprotein (sGP). Microring resonator sensors detected sGP in under 40 min with a limit of detection (LOD) as low as 1.00 ng/mL in serum. Furthermore, we validated our assay with the detection of sGP in serum from EBOV-infected non-human primates. Our results demonstrate the utility of a high-sensitivity diagnostic platform for detection of sGP for diagnosis of EVD

Detection of biomarkers for filoviral infection with a silicon photonic resonator platform

This protocol describes the use of silicon photonic microring resonator sensors for detection of Ebola virus (EBOV) and Sudan virus (SUDV) soluble glycoprotein (sGP). This protocol encompasses biosensor functionalization of silicon microring resonator chips, detection of protein biomarkers in sera, preparing calibration standards for analytical validation, and quantification of the results from these experiments. This protocol is readily adaptable toward other analytes, including cytokines, chemokines, nucleic acids, and viruses. For complete details on the use and execution of this protocol, please refer to Qavi et al. (2022)

Role of Esrrg in the Fibrate-Mediated Regulation of Lipid Metabolism Genes in Human ApoA-I Transgenic Mice

We have used a new ApoA-I transgenic mouse model to identify by global gene expression profiling, candidate genes that affect lipid and lipoprotein metabolism in response to fenofibrate treatment. Multilevel bioinformatical analysis and stringent selection criteria (2-fold change, 0% false discovery rate) identified 267 significantly changed genes involved in several molecular pathways. The fenofibrate-treated group did not have significantly altered levels of hepatic human APOA-I mRNA and plasma ApoA-I compared with the control group. However, the treatment increased cholesterol levels to 1.95-fold mainly due to the increase in high-density lipoprotein (HDL) cholesterol. The observed changes in HDL are associated with the upregulation of genes involved in phospholipid biosynthesis and lipid hydrolysis, as well as phospholipid transfer protein. Significant upregulation was observed in genes involved in fatty acid transport and β-oxidation, but not in those of fatty acid and cholesterol biosynthesis, Krebs cycle and gluconeogenesis. Fenofibrate changed significantly the expression of seven transcription factors. The estrogen receptor-related gamma gene was upregulated 2.36-fold and had a significant positive correlation with genes of lipid and lipoprotein metabolism and mitochondrial functions, indicating an important role of this orphan receptor in mediating the fenofibrate-induced activation of a specific subset of its target genes.National Institutes of Health (HL48739 and HL68216); European Union (LSHM-CT-2006-0376331, LSHG-CT-2006-037277); the Biomedical Research Foundation of the Academy of Athens; the Hellenic Cardiological Society; the John F Kostopoulos Foundatio

Sources of Multidrug Resistance in Patients With Previous Isoniazid-Resistant Tuberculosis Identified Using Whole Genome Sequencing: A Longitudinal Cohort Study

Background Meta-analysis of patients with isoniazid-resistant tuberculosis given standard first-line anti-tuberculosis treatment indicated an increased risk of multi-drug resistant tuberculosis (MDR-TB) emerging (8%), compared to drug-sensitive tuberculosis (0.3%). Here we use whole genome sequencing (WGS) to investigate whether treatment of patients with pre-existing isoniazid resistant disease with first-line anti-tuberculosis therapy risks selecting for rifampicin resistance, and hence MDR-TB. Methods Patients with isoniazid-resistant pulmonary TB were recruited and followed up for 24 months. Drug-susceptibility testing was performed by Microscopic observation drug-susceptibility assay (MODS), Mycobacterial Growth Indicator Tube (MGIT) and by WGS on isolates at first presentation and in the case of re-presentation. Where MDR-TB was diagnosed, WGS was used to determine the genomic relatedness between initial and subsequent isolates. De novo emergence of MDR-TB was assumed where the genomic distance was five or fewer single nucleotide polymorphisms (SNPs) whereas reinfection with a different MDR-TB strain was assumed where the distance was 10 or more SNPs. Results 239 patients with isoniazid-resistant pulmonary tuberculosis were recruited. Fourteen (14/239, 5.9%) patients were diagnosed with a second episode of tuberculosis that was multi-drug resistant. Six (6/239, 2.5%) were identified as having evolved MDR-TB de novo and six as having been re-infected with a different strain. In two cases the genomic distance was between 5-10 SNPs and therefore indeterminate. Conclusions In isoniazid-resistant TB, de novo emergence and reinfection of MDR-TB strains equally contributed to MDR development. Early diagnosis and optimal treatment of isoniazid resistant TB are urgently needed to avert the de novo emergence of MDR-TB during treatment

Effectiveness and safety of in vitro maturation of oocytes versus in vitro fertilisation in women with high antral follicle count : Study protocol for a randomised controlled trial

This work was supported by Ferring grant number 000323 and sponsored by My Duc Hospital.Peer reviewedPublisher PD

Rifampicin resistant 'Mycobacterium tuberculosis' in Vietnam, 2020–2022

Objective: We conducted a descriptive analysis of multi-drug resistant tuberculosis (MDR-TB) in Vietnam’s two largest cities, Hanoi and Ho Chi Minh city. Methods: All patients with rifampicin resistant tuberculosis were recruited from Hanoi and surrounding provinces between 2020 and 2022. Additional patients were recruited from Ho Chi Minh city over the same time period. Demographic data were recorded from all patients, and samples collected, cultured, whole genome sequenced and analysed for drug resistance mutations. Genomic susceptibility predictions were made on the basis of the World Health Organization’s catalogue of mutations in Mycobacterium tuberculosis associated with drug resistance, version 2. Comparisons were made against phenotypic drug susceptibility test results where these were available. Multivariable logistic regression was used to assess risk factors for previous episodes of tuberculosis. Results: 233/265 sequenced isolates were of sufficient quality for analysis, 146 (63 %) from Ho Chi Minh City and 87 (37 %) from Hanoi. 198 (85 %) were lineage 2, 20 (9 %) were lineage 4, and 15 (6 %) were lineage 1. 17/211 (8 %) for whom HIV status was known were infected, and 109/214 (51 %) patients had had a previous episode of tuberculosis. The main risk factor for a previous episode was HIV infection (odds ratio 5.1 (95 % confidence interval 1.3–20.0); p = 0.021). Sensitivity for predicting first-line drug resistance from whole genome sequencing data was over 90 %, with the exception of pyrazinamide (85 %). For moxifloxacin and amikacin it was 50 % or less. Among rifampicin-resistant isolates, prevalence of resistance to each non-first-line drug was < 20 %. Conclusions: Drug resistance among most MDR-TB strains in Vietnam’s two largest cities is confined largely to first-line drugs. Living with HIV is the main risk factor among patients with MDR-TB for having had a previous episode of tuberculosis

Clinical implications of reduced susceptibility to fluoroquinolones in paediatric Shigella sonnei and Shigella flexneri infections.

OBJECTIVES: We aimed to quantify the impact of fluoroquinolone resistance on the clinical outcome of paediatric shigellosis patients treated with fluoroquinolones in southern Vietnam. Such information is important to inform therapeutic management for infections caused by this increasingly drug-resistant pathogen, responsible for high morbidity and mortality in young children globally. METHODS: Clinical information and bacterial isolates were derived from a randomized controlled trial comparing gatifloxacin with ciprofloxacin for the treatment of paediatric shigellosis. Time-kill experiments were performed to evaluate the impact of MIC on the in vitro growth of Shigella and Cox regression modelling was used to compare clinical outcome between treatments and Shigella species. RESULTS: Shigella flexneri patients treated with gatifloxacin had significantly worse outcomes than those treated with ciprofloxacin. However, the MICs of fluoroquinolones were not significantly associated with poorer outcome. The presence of S83L and A87T mutations in the gyrA gene significantly increased MICs of fluoroquinolones. Finally, elevated MICs and the presence of the qnrS gene allowed Shigella to replicate efficiently in vitro in high concentrations of ciprofloxacin. CONCLUSIONS: We found that below the CLSI breakpoint, there was no association between MIC and clinical outcome in paediatric shigellosis infections. However, S. flexneri patients had worse clinical outcomes when treated with gatifloxacin in this study regardless of MIC. Additionally, Shigella harbouring the qnrS gene are able to replicate efficiently in high concentrations of ciprofloxacin and we hypothesize that such strains possess a competitive advantage against fluoroquinolone-susceptible strains due to enhanced shedding and transmission

Health services for reproductive tract infections among female migrant workers in industrial zones in Ha Noi, Viet Nam: an in-depth assessment

BACKGROUND: Rural-to-urban migration involves a high proportion of females because job opportunities for female migrants have increased in urban industrial areas. Those who migrate may be healthier than those staying in the village and they may benefit from better health care services at destination, but the 'healthy' effect can be reversed at destination due to migration-related health risk factors. The study aimed to explore the need for health care services for reproductive tract infections (RTIs) among female migrants working in the Sai Dong industrial zone as well as their services utilization. METHODS: The cross sectional study employed a mixed method approach. A cohort of 300 female migrants was interviewed to collect quantitative data. Two focus groups and 20 in-depth interviews were conducted to collect qualitative data. We have used frequency and cross-tabulation techniques to analyze the quantitative data and the qualitative data was used to triangulate and to provide more in-depth information. RESULTS: The needs for health care services for RTI were high as 25% of participants had RTI syndromes. Only 21.6% of female migrants having RTI syndromes ever seek helps for health care services. Barriers preventing migrants to access services were traditional values, long working hours, lack of information, and high cost of services. Employers had limited interests in reproductive health of female migrants, and there was ineffective collaboration between the local health system and enterprises. These barriers were partly caused by lack of health promotion programs suitable for migrants. Most respondents needed more information on RTIs and preferred to receive these from their employers since they commonly work shifts--and spend most of their day time at work. CONCLUSION: While RTIs are a common health problem among female migrant workers in industrial zones, female migrants had many obstacles in accessing RTI care services. The findings from this study will help to design intervention models for RTI among this vulnerable group such as communication for behavioural impact of RTI health care, fostered collaboration between local health care services and employer enterprises, and on-site service (e.g. local or enterprise health clinics) strengthenin

On Spatially Distributed Hydrological Ecosystem Services: Bridging the Quantitative Information Gap using Remote Sensing and Hydrological Models

One of the ways in which the CGIAR Research Program on Water, Land and Ecosystems (WLE) addresses the challenge of achieving sustainable growth is by improving our understanding of tradeoffs and synergies related to water, food, environment and energy. Essential to the success of these efforts is the availability of quantitative data on these tradeoffs and synergies, and how they vary across space and time. Specifically for the countries sharing the Mekong River, WLE Greater Mekong seeks to drive and inform research and dialogue around the rivers of the region. Hydrological EcoSystem Services (HESS) are heavily affected by intensive development across the region, such as the construction of hydropower dams and land use changes - in particular deforestation, urbanization and agricultural intensification. The full extent of such changes in the agro-ecological system is often unknown, and it is a challenge to account for tradeoffs in HESS in policy processes. As in many other areas of the world, improving governance and management of water resources and associated land and ecosystems in the Greater Mekong region is not only a matter of generating more data. Sharing of knowledge and practices is a key focus of WLE Greater Mekong, which we strive to promote by enhancing the accessibility of valuable information to a wide diversity of regional stakeholders, and promoting dialogue by facilitating the creation of communities of practice. This white paper demonstrates state-of-the-art methods for assessing different HESS and their tradeoffs under different development scenarios. It explores opportunities for spatial monitoring of HESS and predicting changes under different future scenarios, information that is essential for achieving a balanced and healthy agro-ecological system. By relying on tools in the public domain and leveraging the resulting HESS data through online information platforms, this white paper is an excellent example of current efforts supported by WLE Greater Mekong to stimulate uptake of ecosystem services assessments in decision-making processes