Determinants of ventricular arrhythmias in sickle cell anemia: toward better prevention of sudden cardiac death.

Sudden death is 1 of the leading causes of death in adults with sickle cell anemia (SCA) but its etiology remains mostly unknown. Ventricular arrhythmia (VA) carries an increased risk of sudden death; however, its prevalence and determinants in SCA are poorly studied. This study aimed to identify the prevalence and predictors of VA in patients with SCA. From 2019 to 2022, 100 patients with SCA were referred to the physiology department to specifically analyze cardiac function and prospectively included in the DREPACOEUR registry. They underwent a 24-hour electrocardiogram monitoring (24h-Holter), transthoracic echocardiography, and laboratory tests on the same day. The primary end point was the occurrence of VA, defined as sustained or nonsustained ventricular tachycardia (VT), >500 premature ventricular contractions (PVCs) on 24h-Holter, or a recent history of VT ablation. The mean patient age was 46 ± 13 years, and 48% of the patients were male. Overall, VA was observed in 22 (22%) patients. Male sex (81% vs 34%; P = .02), impaired global longitudinal strain (GLS): -16% ± 1.9% vs -18.3% ± 2.7%; P = .02), and decreased platelet count (226 ± 96 giga per liter [G/L] vs 316 ± 130 G/L) were independently associated with VA. GLS correlated with PVC load every 24 hours (r = 0.39; P < .001) and a cutoff of -17.5% could predict VA with a sensitivity of 82% and a specificity of 63%. VAs are common in patients with SCA, especially in men. This pilot study uncovered GLS as a valuable parameter for improving rhythmic risk stratification.

Effects of a comprehensive brain computed tomography deep learning model on radiologist detection accuracy.

OBJECTIVES: Non-contrast computed tomography of the brain (NCCTB) is commonly used to detect intracranial pathology but is subject to interpretation errors. Machine learning can augment clinical decision-making and improve NCCTB scan interpretation. This retrospective detection accuracy study assessed the performance of radiologists assisted by a deep learning model and compared the standalone performance of the model with that of unassisted radiologists. METHODS: A deep learning model was trained on 212,484 NCCTB scans drawn from a private radiology group in Australia. Scans from inpatient, outpatient, and emergency settings were included. Scan inclusion criteria were age ≥ 18 years and series slice thickness ≤ 1.5 mm. Thirty-two radiologists reviewed 2848 scans with and without the assistance of the deep learning system and rated their confidence in the presence of each finding using a 7-point scale. Differences in AUC and Matthews correlation coefficient (MCC) were calculated using a ground-truth gold standard. RESULTS: The model demonstrated an average area under the receiver operating characteristic curve (AUC) of 0.93 across 144 NCCTB findings and significantly improved radiologist interpretation performance. Assisted and unassisted radiologists demonstrated an average AUC of 0.79 and 0.73 across 22 grouped parent findings and 0.72 and 0.68 across 189 child findings, respectively. When assisted by the model, radiologist AUC was significantly improved for 91 findings (158 findings were non-inferior), and reading time was significantly reduced. CONCLUSIONS: The assistance of a comprehensive deep learning model significantly improved radiologist detection accuracy across a wide range of clinical findings and demonstrated the potential to improve NCCTB interpretation. CLINICAL RELEVANCE STATEMENT: This study evaluated a comprehensive CT brain deep learning model, which performed strongly, improved the performance of radiologists, and reduced interpretation time. The model may reduce errors, improve efficiency, facilitate triage, and better enable the delivery of timely patient care. KEY POINTS: • This study demonstrated that the use of a comprehensive deep learning system assisted radiologists in the detection of a wide range of abnormalities on non-contrast brain computed tomography scans. • The deep learning model demonstrated an average area under the receiver operating characteristic curve of 0.93 across 144 findings and significantly improved radiologist interpretation performance. • The assistance of the comprehensive deep learning model significantly reduced the time required for radiologists to interpret computed tomography scans of the brain.

Effects of dietary hydrolysate supplementation on growth, body composition, hematological responses, and liver histology of juvenile giant trevally (Caranx ignobilis Forsskal, 1775).

A feeding study was conducted to investigate how fish protein hydrolysate (FPH) supplementation affected the growth, feed utilization, body composition, and hematology of juvenile giant trevally (Caranx ignobilis Forsskal, 1775). Seven isonitrogenous (52% protein) and isocaloric diets (10% lipid) were formulated, wherein shrimp hydrolysate (SH) and tuna hydrolysate (TH) were used to replace fishmeal at inclusion levels of 0 (control), 30, 60, and 90 g/kg and labeled as control, SH30, SH60, SH90, TH30, TH60, and TH90, respectively. Each diet was fed to triplicate groups of juvenile giant trevally for 8 weeks. The results showed higher final body weight and specific growth rate in fish fed SH30, SH60, TH30, and TH60 than fed control diet. No difference was observed in feed intake, but reduced feed conversion ratio (FCR) was found in fish fed SH30, SH60, TH30, and TH60, demonstrating these diets improved feed utilization. TH90 caused deposition of lipid droplet in the hepatocyte, a sign of liver damage. Total monounsaturated fatty acids, polyunsaturated fatty acids (PUFA), and highly unsaturated fatty acids in fish were not affected by FPH supplementation. Fish fed TH30 showed lower ∑n - 3 PUFA than the fish fed remaining dietary treatments. The elevated serum protein was seen in fish fed control, SH30, SH60, and TH30, demonstrating that these diets were beneficial for the innate immune response in giant trevally. The results indicate that TH and SH could be incorporated into diets of giant trevally at 30-60 g/kg, replacing 7%-13% fishmeal with enhanced growth and health benefits.

iNSP-GCAAP: Identifying nonclassical secreted proteins using global composition of amino acid properties.

Nonclassical secreted proteins (NSPs) refer to a group of proteins released into the extracellular environment under the facilitation of different biological transporting pathways apart from the Sec/Tat system. As experimental determination of NSPs is often costly and requires skilled handling techniques, computational approaches are necessary. In this study, we introduce iNSP-GCAAP, a computational prediction framework, to identify NSPs. We propose using global composition of a customized set of amino acid properties to encode sequence data and use the random forest (RF) algorithm for classification. We used the training dataset introduced by Zhang et al. (Bioinformatics, 36(3), 704-712, 2020) to develop our model and test it with the independent test set in the same study. The area under the receiver operating characteristic curve on that test set was 0.9256, which outperformed other state-of-the-art methods using the same datasets. Our framework is also deployed as a user-friendly web-based application to support the research community to predict NSPs.

Variation and impact of polygenic hematologic traits in monogenic sickle cell disease.

Several of the complications observed in sickle cell disease (SCD) are influenced by variation in hematologic traits (HT), such as fetal hemoglobin (HbF) level and neutrophil count. Previous large-scale genome-wide association studies carried out in largely healthy individuals have identified thousands of variants associated with HT, which have then been used to develop multi-ancestry polygenic trait scores (PTS). Here, we tested whether these PTS associate with HT in SCD patients and if they can improve statistical models associated with SCD-related complications. In 2,056 SCD patients, we found that the PTS predicted less HT variance than in non-SCD individuals of African ancestry. This was particularly striking at the Duffy/DARC locus, where we observed an epistatic interaction between the SCD genotype and the Duffy null variant (rs2814778) that led to a two-fold weaker effect on neutrophil count. PTS for these HT which are measured as part of routine practice were not associated with complications in SCD. In contrast, we found that a simple PTS for HbF that includes only six variants explained a large fraction of the phenotypic variation (20.5-27.1%), associated with acute chest syndrome and stroke risk, and improved the statistical modeling of the vaso-occlusive crisis rate. Using Mendelian randomization, we found that increasing HbF by 4.8% reduces stroke risk by 39% (P=0.0006). Taken together, our results highlight the importance of validating PTS in large diseased populations before proposing their implementation in the context of precision medicine initiatives.

Maternal social support during and after pregnancy and child cognitive ability: examining timing effects in two cohorts.

BACKGROUND: Maternal anxiety, depression, and stress during and after pregnancy are negatively associated with child cognitive development. However, the contribution of positive maternal experiences, such as social support, to child cognitive development has received less attention. Furthermore, how maternal experience of social support during specific developmental periods impacts child cognitive development is largely unknown. METHODS: Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 5784) and the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction study (PREDO; n = 420), we investigated the associations between maternal perceived social support during and after pregnancy and child's general cognitive ability at 8 years of age, assessed with the Wechsler Intelligence Scale for Children (WISC). Bayesian relevant life course modeling was used to investigate timing effects of maternal social support on child cognitive ability. RESULTS: In both cohorts, higher maternal perceived social support during pregnancy was associated with higher performance on the WISC, independent of sociodemographic factors and concurrent maternal symptoms of depression and anxiety. In ALSPAC, pregnancy emerged as a sensitive period for the effects of perceived social support on child cognitive ability, with a stronger effect of social support during pregnancy than after pregnancy on child cognitive ability. CONCLUSIONS: Our findings, supported from two prospective longitudinal cohorts, suggest a distinct role of maternal perceived social support during pregnancy for cognitive development in children. Our study suggests that interventions aimed at increasing maternal social support during pregnancy may be an important strategy for promoting maternal and child well-being.

Sex differences in quality of life of patients following percutaneous coronary intervention in Vietnam.

PURPOSE: Data regarding the health-related quality of life (HRQoL) in men and women after percutaneous coronary intervention (PCI) in low-and-middle incomes countries remains scarce. To investigate sex difference in the HRQoL at 30 days and 12 months post PCI in Vietnam. METHODS: We used data from a single percutaneous coronary registry established in the Vietnam National Heart Institute. The HRQoL was measured using the EQ-5D-3L instrument via telephone interviews, and information about demographics, clinical presentation and procedures was obtained through face-to-face interviews and medical records. The HRQoL between men and women were compared using independent samples t tests, the Mann-Whitney U test or univariate/multivariate logistic regression. RESULTS: There were 866 patients included in this cohort, with the proportion of women being nearly half of men (32.1 vs 67.9%). Women were 3.5 years older, had lower income and educational levels but greater prevalence of cardiovascular risk factors. At 30 days, women significantly had more problems in mobility, personal care and pain/discomfort compared to men. At 12 months, women had more problem than men in usual activity. The geometric means of HRQoL was lower in women at 30 days, but not in 12 months. From 30 days to 12 months after discharge, women showed better recovery in mobility compared to men, but not in other dimensions. CONCLUSIONS: In this first insight of sex differences in HRQoL following PCI in Vietnam, women appeared to have worse quality of life, especially at 30 days after discharge but they showed better recovery in mobility at 12 months compared to men.

Nurses' perceptions about patient safety culture in public hospital in Vietnam.

AIM: This paper is aimed to assess nurses' perceptions of patient safety culture in four public general hospitals in Hanoi, Vietnam. BACKGROUND: Patient safety culture is a vital component in ensuring high quality and safe patient care. Assessment of nurses' perceptions on existing hospital patient safety culture (PSC) is the first step to promote PSC. METHODS: The cross-sectional study surveyed 705 nurses utilizing the validated Hospital Survey on Patient Safety Culture (HSOPSC) in an online format. RESULTS: The average positive response rate was high at 72.8 % and varied from 52.9 % to 93.4 %. The strongest areas are teamwork within units (93.7 %) and supervisor/manager expectations and actions promoting patient safety (85.0 %). The areas for improvement are staffing (52.9 %) and non-punitive response to error (57.6 %). The communication openness, staffing, frequency of events reported, lengths of services in hospital and unit are significant factors that predict the overall patient safety grade. CONCLUSIONS: Initiatives are necessary to improve response to errors, staffing, and error reporting. Nurse managers could develop and implement interventions and program to improve patient safety, including providing education related to patient safety culture, encouraging staff to notify incidents and avoiding punitive responses.

A review on management practices, environmental impacts, and human exposure risks related to electrical and electronic waste in Vietnam: findings from case studies in informal e-waste recycling areas.

Electrical and electronic waste (e-waste) has become a global concern, especially in developing countries. In this review, we conducted a literature survey of e-waste management practices, processing activities, and adverse effects in Vietnam, an emerging country in Southeast Asia, by gathering data from peer-reviewed articles published between 2009 and 2021. This is the first review paper to comprehensively discuss management and research aspects regarding e-waste in an Asian developing country. Due to the lack of an effective management and recycling system, a certain portion of Vietnamese e-waste has been processed by informal sectors without appropriate recycling and pollution control technology, resulting in localized contamination and human exposure to toxic chemicals. Primitive processing activities, such as manual dismantling, open burning, and plastic recycling, have been identified as important contributors to the environmental emission and human exposure to toxic elements (notably As, Mn, Ni, Pb, Zn) and organic pollutants like flame retardants, PAHs, PCBs, and dioxin-related compounds. Informal e-waste processing from these small-scale workshops can release pollutants at similar levels compared to large-scale facilities in developed countries. This fact suggests an urgent need to develop management best practices for e-waste in Vietnam as well as other emerging and developing countries, in order to increase recycling efficiency and minimize their adverse impacts on environmental and human health.

Country data on AMR in Vietnam in the context of community-acquired respiratory tract infections: links between antibiotic susceptibility, local and international antibiotic prescribing guidelines, access to medicines and clinical outcome.

BACKGROUND: Antimicrobial resistance (AMR) is one of the biggest threats to global public health. Selection of resistant bacteria is driven by inappropriate use of antibiotics, amongst other factors. COVID-19 may have exacerbated AMR due to unnecessary antibiotic prescribing. Country-level knowledge is needed to understand options for action. OBJECTIVES: To review the current situation with respect to AMR in Vietnam and initiatives addressing it. Identifying areas where more information is required will provide a call to action to minimize any further rises in AMR within Vietnam and improve patient outcomes. METHODS: National initiatives to address AMR in Vietnam, antibiotic use and prescribing, and availability of susceptibility data, in particular for the key community-acquired respiratory tract infection (CA-RTI) pathogens Streptococcus pneumoniae and Haemophilus influenzae, were identified. National and international antibiotic prescribing guidelines for CA-RTIs (community-acquired pneumonia, acute otitis media and acute bacterial rhinosinusitis) commonly used locally were also reviewed, plus local antibiotic availability. Insights from clinicians in Vietnam were sought to contextualize this information. CONCLUSIONS: In Vietnam there have been some initiatives addressing AMR; Vietnam was the first country in the Western Pacific Region to develop a national action plan to combat AMR, which according to the WHO is being implemented. Vietnam also has one of the highest rates of AMR in Asia due, in part, to the overuse of antimicrobial drugs, both in the animal health sector and in humans in both hospitals and the community. In addition, despite a 2005 law requiring antibiotic prescription, there is unrestricted access to over-the-counter antibiotics. Several global surveillance studies provide antibiotic susceptibility data for CA-RTI pathogens in Vietnam including Survey of Antibiotic Resistance (SOAR) and SENTRY (small isolate numbers only). For management of the common CA-RTIs in Vietnam there are several country-specific local antibiotic prescribing guidelines and in addition, there is a range of international guidelines referred to, but these may have been created based on pathogen resistance patterns that might be very different to those in Vietnam. Expert clinician opinion confirms the high resistance rates among common respiratory pathogens. A more standardized inclusive approach in developing local guidelines, using up-to-date surveillance data of isolates from community-acquired infections in Vietnam, could make management guideline use more locally relevant for clinicians. This would pave the way for a higher level of appropriate antibiotic prescribing and improved adherence. This would, in turn, potentially limit AMR development and improve clinical outcomes for patients.

Formation of the quasi-planar B56 boron cluster: topological path from B12 and disk aromaticity.

Formation and stability of the B56 boron cluster were investigated using a topological approach and the disk aromaticity model. An extensive global energy minimum search for the B56 system which was carried out by means of the Mexican Enhanced Genetic Algorithm (MEGA) in conjunction with density functional theory computations, confirms a quasi-planar structure as its energetically most stable isomer. Such a structural motif is derived by applying a topological leapfrog operation to a B12 form. Its high thermodynamic stability can be explained by the disk aromaticity model in which the delocalization of its π orbitals can be assigned to the levels of a particle in a circular box with the [(1σ)2 (1π)4 (1δ)4 (1φ)4 (2σ)2 (1γ)4 (2π)4 (2δ)4 (1η)4 (2φ)4 (1θ)2] electronic configuration. This π delocalization is confirmed by other delocalization indices. While the B56 has a similar electron delocalization to that of the quasi-planar B50, they have opposite magnetic ring current properties because of the symmetry selection rules of their HOMO-LUMO electronic transitions. The π delocalization in the boron clusters is larger at long distances as compared to carbon clusters at similar sizes, but such a trend is reversed at shorter distances.

Assessing the discriminative ability of the respiratory exchange ratio to detect hyperlactatemia during intermediate-to-high risk abdominal surgery.

BACKGROUND: A mismatch between oxygen delivery (DO2) and consumption (VO2) is associated with increased perioperative morbidity and mortality. Hyperlactatemia is often used as an early screening tool, but this non-continuous measurement requires intermittent arterial line sampling. Having a non-invasive tool to rapidly detect inadequate DO2 is of great clinical relevance. The respiratory exchange ratio (RER) can be easily measured in all intubated patients and has been shown to predict postoperative complications. We therefore aimed to assess the discriminative ability of the RER to detect an inadequate DO2 as reflected by hyperlactatemia in patients having intermediate-to-high risk abdominal surgery. METHODS: This historical cohort study included all consecutive patients who underwent intermediate-to-high risk surgery from January 1st, 2014, to April 30th, 2019 except those who did not have RER and/or arterial lactate measured. Blood lactate levels were measured routinely at the beginning and end of surgery and RER was calculated at the same moment as the blood gas sampling. The present study tested the hypothesis that RER measured at the end of surgery could detect hyperlactatemia at that time. A receiver operating characteristic (ROC) curve was constructed to assess if RER calculated at the end of the surgery could detect hyperlactatemia. The chosen RER threshold corresponded to the highest value of the sum of the specificity and the sensitivity (Youden Index). RESULTS: Among the 996 patients available in our study cohort, 941 were included and analyzed. The area under the ROC curve was 0.73 (95% CI: 0.70 to 0.76; p < 0.001), with a RER threshold of 0.75, allowing to discriminate a lactate > 1.5 mmol/L with a sensitivity of 87.5% and a specificity of 49.5%. CONCLUSION: In mechanically ventilated patients undergoing intermediate to high-risk abdominal surgery, the RER had moderate discriminative abilities to detect hyperlactatemia. Increased values should prompt clinicians to investigate for the presence of hyperlactatemia and treat any potential causes of DO2/VO2 mismatch as suggested by the subsequent presence of hyperlactatemia.

Incidental finding of elevated pulmonary arterial pressures during liver transplantation and postoperative pulmonary complications.

BACKGROUND: In patients with end stage liver disease (ESLD) scheduled for liver transplantation (LT), an intraoperative incidental finding of elevated mean pulmonary arterial pressure (mPAP) may be observed. Its association with patient outcome has not been evaluated. We aimed to estimate the effects of an incidental finding of a mPAP > 20 mmHg during LT on the incidence of pulmonary complications. METHODS: We examined all patients who underwent a LT at Paul-Brousse hospital between January 1,2015 and December 31,2020. Those who received: a LT due to acute liver failure, a combined transplantation, or a retransplantation were excluded, as well as patients for whom known porto-pulmonary hypertension was treated before the LT or patients who underwent a LT for other etiologies than ESLD. Using right sided pulmonary artery catheterization measurements made following anesthesia induction, the study cohort was divided into two groups using a mPAP cutoff of 20 mmHg. The primary outcome was a composite of pulmonary complications. Univariate and multivariable logistic regression analyses were performed to identify variables associated with the primary outcome. Sensitivity analyses of multivariable models were also conducted with other mPAP cutoffs (mPAP ≥ 25 mmHg and ≥ 35 mmHg) and even with mPAP as a continuous variable. RESULTS: Of 942 patients who underwent a LT, 659 met our inclusion criteria. Among them, 446 patients (67.7%) presented with an elevated mPAP (mPAP of 26.4 ± 5.9 mmHg). When adjusted for confounding factors, an elevated mPAP was not associated with a higher risk of pulmonary complications (adjusted OR: 1.16; 95%CI 0.8-1.7), nor with 90 days-mortality or any other complications. In our sensitivity analyses, we observed a lower prevalence of elevated mPAP when increasing thresholds (235 patients (35.7%) had an elevated mPAP when defined as ≥ 25 mmHg and 41 patients (6.2%) had an elevated mPAP when defined as ≥ 35 mmHg). We did not observe consistent association between a mPAP ≥ 25 mmHg or a mPAP ≥ 35 mmHg and our outcomes. CONCLUSION: Incidental finding of elevated mPAP was highly prevalent during LT, but it was not associated with a higher risk of postoperative complications.

Intraoperative measurement of the respiratory exchange ratio predicts postoperative complications after liver transplantation.

BACKGROUND: During surgery, any mismatch between oxygen delivery (DO2) and consumption (VO2) can promote the development of postoperative complications. The respiratory exchange ratio (RER), defined as the ratio of carbon dioxide (CO2) production (VCO2) to VO2, may be a useful noninvasive tool for detecting inadequate DO2. The primary objective of this study was to test the hypothesis that RER measured during liver transplantation may predict postoperative morbidity. Secondary objectives were to assess the ability of other variables used to assess the DO2/VO2 relationship, including arterial lactate, mixed venous oxygen saturation, and veno-arterial difference in the partial pressure of carbon dioxide (VAPCO2gap), to predict postoperative complications. METHODS: This retrospective study included consecutive adult patients who underwent liver transplantation for end stage liver disease from June 27th, 2020, to September 5th, 2021. Patients with acute liver failure were excluded. All patients were routinely equipped with a pulmonary artery catheter. The primary analysis was a receiver operating characteristic (ROC) curve constructed to investigate the discriminative ability of the mean RER measured during surgery to predict postoperative complications. RER was calculated at five standardized time points during the surgery, at the same time as measurement of blood lactate levels and arterial and mixed venous blood gases, which were compared as a secondary analysis. RESULTS: Of the 115 patients included, 57 developed at least one postoperative complication. The mean RER (median [25-75] percentiles) during surgery was significantly higher in patients with complications than in those without (1.04[0.96-1.12] vs 0.88[0.84-0.94]; p < 0.001). The area under the ROC curve was 0.87 (95%CI: 0.80-0.93; p < 0.001) with a RER value (Youden index) of 0.92 giving a sensitivity of 91% and a specificity of 74% for predicting the occurrence of postoperative complications. The RER outperformed all other measured variables assessing the DO2/VO2 relationship (arterial lactate, SvO2, and VAPCO2gap) in predicting postoperative complications. CONCLUSION: During liver transplantation, the RER can reliably predict postoperative complications. Implementing this measure intraoperatively may provide a warning for physicians of impending complications and justify more aggressive optimization of oxygen delivery. Further studies are required to determine whether correcting the RER is feasible and could reduce the incidence of complications.

Human health risk of mercury in street dust: A case study of children in the vicinity of compact fluorescence lamp factory, Hanoi, Vietnam.

Urban dust has been contaminated with toxic heavy metals from various diffused sources. On August 28, 2019, the compact fluorescence lamp (CFL) factory that generates light for Rang Dong Light Source and Vacuum Flask in Hanoi City in Vietnam was accidentally fired. The assessment for Hg contamination and its human health impact 2 months after the incident was conducted in autumn 2019. The heavy Hg pollution is still found near CFL. Additionally, localized Hg pollution by air and wind direction was identified at sites in the northeast direction from CFL. Namely, in the area located downstream of the southwest monsoon wind, Hg had a trend higher than other directions. The hazard quotient (HQ) and the hazard index (HI) were evaluated by four routes of Hg exposure pathways. The HI values for children and adults in the most polluted site (Site 15) were 0.968 and 0.468, respectively. This meant that children who lived around this site and commuted to schools were the most at risk regarding the potential adverse health effects of Hg in street dust around the polluted areas. This study also showed that Hg levels were affected by wind direction and that the higher Hg levels in the most polluted sites resulted from the wind flow to the sites. This study revealed that street dust may be a useful tool for the assessment of human and environmental health.

Establishment of an in-house real-time RT-PCR assay for the detection of severe acute respiratory syndrome coronavirus 2 using the first World Health Organization international standard in a resource-limited country.

BACKGROUND: The COVID-19 pandemic caused by SARS-CoV-2 remains public health burdens and many unresolved issues worldwide. Molecular assays based on real-time RT-PCR are critical for the detection of SARS-CoV-2 in clinical specimens from patients suspected of COVID-19. OBJECTIVE: We aimed to establish and validate an in-house real-time RT-PCR for the detection of SARS-CoV-2. METHODOLOGY: Primers and probes sets in our in-house real-time RT-PCR assay were designed in conserved regions of the N and E target genes. Optimized multiplex real-time RT-PCR assay was validated using the first WHO International Standard (NIBSC code: 20/146) and evaluated clinical performance. RESULTS: The limit of detection validated using the first WHO International Standard was 159 IU/ml for both E and N target genes. The evaluation of clinical performance on 170 clinical samples showed a positive percent agreement of 100% and the negative percent agreement of 99.08% for both target genes. The Kappa value of 0.99 was an excellent agreement, the strong correlation of Ct values observed between two tests with r2  = 0.84 for the E gene and 0.87 for the N gene. Notably, we assessed on 60 paired saliva and nasopharyngeal samples. The overall agreement was 91.66%, and Kappa value of 0.74 showed a high agreement between two types of samples. When using nasopharyngeal swabs as the reference standard, positive percent agreement, and negative percent agreement were 91.83% and 90.90%, respectively. CONCLUSION: In the present study, we established and validated an in-house real-time RT-PCR for molecular detection of SARS-CoV-2 in a resource-limited country.

Study on the co-infection of children with severe community-acquired pneumonia.

BACKGROUD: Pneumonia is one of the leading causes of death in children under 5 years old. Viruses have historically been the most common cause of community-acquired pneumonia in children. Co-infections in severe pneumonia are more concern by clinicians. METHOD: It was a perspective and descriptive study. Real-time polymerase chain reaction (RT-PCR) is a modern test that was used to detect many new pathogens, including microbiological co-infections. RT-PCR technique was used in this study to investigate the causes of severe pneumonia. RESULTS: Through the analysis of nasopharyngeal aspiration samples from 95 children with severe community-acquired pneumonia, the positive RT-PCR rate was 90.5%. Viral-bacterial co-infection accounted for the highest proportion (43.1%), followed by bacterial co-infection (33.7%), viral infection (7.4%), bacterial infection (6.3%) and the remaining 9.5% was unknown. In the co-infections groups, the five main bacteria species detected by PCR were Streptococcus pneumoniae, Haemophilus influenzae, MRSA, Moraxella catarrhalis and Mycoplasma pneumoniae. CONCLUSION: Antibiotic treatment should focus on detected microbes in cases of severe pneumonia for having a good result.

Traditional Vietnamese medicine Kovir capsule in patients with mild COVID-19: A double-blind randomized controlled trial.

Kovir capsule, a polyherbal medicine developed from Ren Shen Bai Du San formulation, has been used in various diseases including respiratory infections. A randomized, placebo-controlled, double-blind study was conducted to evaluate the safety and efficacy of Kovir capsule (TD0069) in the treatment of mild COVID-19 patients. Patients aged from 18 to 65 years who were PCR-confirmed with SARS-CoV-2 and had the mild disease were recruited and randomized to either Kovir capsule (34 patients) or placebo (32 patients) for up to 14 days or until discharge. Efficacy outcomes were time to viral clearance, daily viral load, time to symptom resolution, daily symptom score based on 16 pre-defined symptoms, and progression to severe/critical COVID-19. Safety outcomes were adverse events. Viral load decreased over time similarly in the two groups. Viral clearance time was also similar in both groups (median: 8 days). Kovir group had a more rapid decrease of symptom score and significantly lower time to symptom resolution than placebo (median: 4 vs. 7 days). Two patients in the placebo group developed severe COVID-19. No patient experienced adverse events. Kovir capsule is safe and can improve symptom resolution in mild COVID-19 patients. A large-scale trial is required to confirm these findings.

Unraveling the history of the genus Gallus through whole genome sequencing.

The genus Gallus is distributed across a large part of Southeast Asia and has received special interest because the domestic chicken, Gallus gallus domesticus, has spread all over the world and is a major protein source for humans. There are four species: the red junglefowl (G. gallus), the green junglefowl (G. varius), the Lafayette's junglefowl (G. lafayettii) and the grey junglefowl (G. sonneratii). The aim of this study is to reconstruct the history of these species by a whole genome sequencing approach and resolve inconsistencies between well supported topologies inferred using different data and methods. Using deep sequencing, we identified over 35 million SNPs and reconstructed the phylogeny of the Gallus genus using both distance (BioNJ) and maximum likelihood (ML) methods. We observed discrepancies according to reconstruction methods and genomic components. The two most supported topologies were previously reported and were discriminated by using phylogenetic and gene flow analyses, based on ABBA statistics. Terminology fix requested by the deputy editor led to support a scenario with G. gallus as the earliest branching lineage of the Gallus genus, instead of G. varius. We discuss the probable causes for the discrepancy. A likely one is that G. sonneratii samples from parks or private collections are all recent hybrids, with roughly 10% of their autosomal genome originating from G. gallus. The removal of those regions is needed to provide reliable data, which was not done in previous studies. We took care of this and additionally included two wild G. sonneratii samples from India, showing no trace of introgression. This reinforces the importance of carefully selecting and validating samples and genomic components in phylogenomics.

Cardiovascular phenotypes predict clinical outcomes in sickle cell disease: An echocardiography-based cluster analysis.

This study sought to link cardiac phenotypes in homozygous Sickle Cell Disease (SCD) patients with clinical profiles and outcomes using cluster analysis. We analyzed data of 379 patients included in the French Etendard Cohort. A cluster analyses was performed based on echocardiographic variables, and the association between clusters, clinical profiles and outcomes was assessed. Three clusters were identified. Cluster 1 (n = 123) patients had the lowest cardiac output, mild left cardiac cavities remodeling, mild diastolic dysfunction, and higher tricuspid regurgitation velocity (TRV). They were predominantly female and displayed the most altered functional limitation. Cluster 2 (n = 102) patients had the highest cardiac output and the most remodeled cardiac cavities. Diastolic function and TRV were similar to cluster 1. These patients had a higher blood pressure and a severe hemolytic anemia. Cluster 3 (n = 154) patients had mild left cardiac cavities remodeling, normal diastolic function and lowest TRV values. They were younger with the highest hemoglobin value. Right heart catheterization was performed in 94 patients. Cluster 1 (n = 33) included the majority of pre-capillary PH whilst cluster 2 (n = 34) included post-capillary PH. No PH was found in cluster 3 (n = 27). After a follow-up of 11.4 ± 2 years, death occurred in 41 patients (11%). Cluster 2 patients had the worst prognosis with a 19% mortality rate versus 12% in cluster 1 and 5% in cluster 3 (p log-rank = 0.003). Cluster analysis of echocardiography variables identified three hemodynamic and clinical phenotypes among SCD patients, each predicting a different prognosis.