Outcome of emergency neurosurgery in patients with refractory and super-refractory status epilepticus: a systematic review and individual participant data meta-analysis.

Background: Refractory (RSE) and super-refractory status epilepticus (SRSE) are serious neurological conditions requiring aggressive management. Beyond anesthetic agents, there is a lack of evidence guiding management in these patients. This systematic review and individual participant data meta-analysis (IPDMA) seeks to evaluate and compare the currently available surgical techniques for the acute treatment of RSE and SRSE. Methods: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Individual Participant Data (PRISMA-IPD). Only patients who underwent surgery while in RSE and SRSE were included. Descriptive statistics were used to compare various subgroups. Multivariable logistic regression models were constructed to identify predictors of status epilepticus (SE) cessation, long-term overall seizure freedom, and favorable functional outcome (i.e., modified Rankin score of 0-2) at last follow-up. Results: A total of 87 studies including 161 participants were included. Resective surgery tended to achieve better SE cessation rate (93.9%) compared to non-resective techniques (83.9%), but this did not reach significance (p = 0.071). Resective techniques were also more likely to achieve seizure freedom (69.1% vs. 34.4%, p = <0.0001). Older age at SE (OR = 1.384[1.046-1.832], p = 0.023) was associated with increased likelihood of SE cessation, while longer duration of SE (OR = 0.603[0.362-1.003], p = 0.051) and new-onset seizures (OR = 0.244[0.069-0.860], p = 0.028) were associated with lower likelihood of SE cessation, but this did not reach significance for SE duration. Only shorter duration of SE prior to surgery (OR = 1.675[1.168-2.404], p = 0.0060) and immediate termination of SE (OR = 3.736 [1.323-10.548], p = 0.014) were independently associated with long-term seizure status. Rates of favorable functional outcomes (mRS of 0-2) were comparable between resective (44.4%) and non-resective (44.1%) techniques, and no independent predictors of outcome were identified. Conclusion: Our findings suggest that emergency neurosurgery may be a safe and effective alternative in patients with RSE/SRSE and may be considered earlier during the disease course. However, the current literature is limited exclusively to small case series and case reports with high risk of publication bias. Larger clinical trials assessing long-term seizure and functional outcomes are warranted to establish robust management guidelines.

Prognostic values of serum lactate-to-bicarbonate ratio and lactate for predicting 28-day in-hospital mortality in children with dengue shock syndrome.

This study aimed to assess the clinical utility of blood lactate-to-bicarbonate (L/B) ratio, as a prognostic factor for 28-day in-hospital mortality in children with dengue shock syndrome (DSS), admitted to the pediatric intensive care unit (PICU). This single-center retrospective study was conducted at a tertiary children hospital in southern Vietnam from 2013 to mid-2022. Prognostic models for DSS mortality were developed, using a predefined set of covariates in the first 24 hours of PICU admission. Area under the curves (AUCs), multivariable logistic and Least Absolute Shrinkage and Selection Operator (LASSO) regressions, bootstrapping and calibration slope were performed. A total of 492 children with DSS and complete clinical and biomarker data were included in the analysis, and 26 (5.3%) patients died. The predictive values for DSS mortality, regarding lactate showing AUC 0.876 (95% CI, 0.807-0.944), and that of L/B ratio 0.867 (95% CI, 0.80-0.934) (P values of both biomarkers < .001). The optimal cutoff point of the L/B ratio was 0.25, while that of lactate was 4.2 mmol/L. The multivariable model showed significant clinical predictors of DSS fatality including severe bleeding, cumulative amount of fluid infused and vasoactive-inotropic score (>30) in the first 24 hours of PICU admission. Combined with the identified clinical predictors, the L/B ratio yielded higher prognostic values (odds ratio [OR] = 8.66, 95% confidence interval [CI], 1.96-38.3; P < .01) than the lactate-based model (OR = 1.35, 95% CI, 1.15-1.58; P < .001). Both the L/B and lactate models showed similarly good performances. Considering that the L/B ratio has a better prognostic value than the lactate model, it may be considered a potential prognostic biomarker in clinical use for predicting 28-day mortality in PICU-admitted children with DSS.

BaHf0.05Ti0.95O3 Ceramics from Sol-Gel and Solid-State Processes: Application to the Modelling of Piezoelectric Energy Harvesters.

A typical piezoelectric energy harvester is a bimorph cantilever with two layers of piezoelectric material on both sides of a flexible substrate. Piezoelectric layers of lead-based materials, typically lead zirconate titanate, have been mainly used due to their outstanding piezoelectric properties. However, due to lead toxicity and environmental problems, there is a need to replace them with environmentally benign materials. Here, our main efforts were focused on the preparation of hafnium-doped barium titanate (BaHfxTi1-xO3; BHT) sol-gel materials. The original process developed makes it possible to obtain a highly concentrated sol without strong organic complexing agents. Sol aging and concentration can be controlled to obtain a time-stable sol for a few months at room temperature, with desired viscosity and colloidal sizes. Densified bulk materials obtained from this optimized sol are compared with a solid-state synthesis, and both show good electromechanical properties: their thickness coupling factor kt values are around 53% and 47%, respectively, and their converse piezoelectric coefficient d33∗ values are around 420 and 330 pm/V, respectively. According to the electromechanical properties, the theoretical behavior in a bimorph configuration can be simulated to predict the resonance and anti-resonance frequencies and the corresponding output power values to help to design the final device. In the present case, the bimorph configuration based on BHT sol-gel material is designed to harvest ambient vibrations at low frequency (<200 Hz). It gives a maximum normalized volumetric power density of 0.03 µW/mm3/Hz/g2 at 154 Hz under an acceleration of 0.05 m/s2.

Analytical validation and clinical utilization of K-4CARE™: a comprehensive genomic profiling assay with personalized MRD detection.

Background: Biomarker testing has gradually become standard of care in precision oncology to help physicians select optimal treatment for patients. Compared to single-gene or small gene panel testing, comprehensive genomic profiling (CGP) has emerged as a more time- and tissue-efficient method. This study demonstrated in-depth analytical validation of K-4CARE, a CGP assay that integrates circulating tumor DNA (ctDNA) tracking for residual cancer surveillance. Methods: The assay utilized a panel of 473 cancer-relevant genes with a total length of 1.7 Mb. Reference standards were used to evaluate limit of detection (LOD), concordance, sensitivity, specificity and precision of the assay to detect single nucleotide variants (SNVs), small insertion/deletions (Indels), gene amplification and fusion, microsatellite instability (MSI) and tumor mutational burden (TMB). The assay was then benchmarked against orthogonal methods using 155 clinical samples from 10 cancer types. In selected cancers, top tumor-derived somatic mutations, as ranked by our proprietary algorithm, were used to detect ctDNA in the plasma. Results: For detection of somatic SNVs and Indels, gene fusion and amplification, the assay had sensitivity of >99%, 94% and >99% respectively, and specificity of >99%. Detection of germline variants also achieved sensitivity and specificity of >99%. For TMB measurement, the correlation coefficient between whole-exome sequencing and our targeted panel was 97%. MSI analysis when benchmarked against polymerase chain reaction method showed sensitivity of 94% and specificity of >99%. The concordance between our assay and the TruSight Oncology 500 assay for detection of somatic variants, TMB and MSI measurement was 100%, 89%, and 98% respectively. When CGP-informed mutations were used to personalize ctDNA tracking, the detection rate of ctDNA in liquid biopsy was 79%, and clinical utility in cancer surveillance was demonstrated in 2 case studies. Conclusion: K-4CARE™ assay provides comprehensive and reliable genomic information that fulfills all guideline-based biomarker testing for both targeted therapy and immunotherapy. Integration of ctDNA tracking helps clinicians to further monitor treatment response and ultimately provide well-rounded care to cancer patients.

Extracorporeal life support and continuous renal replacement therapy in a patient with Enterovirus A71 associated cardiopulmonary failure: A case report.

RATIONALE: Hand-foot-mouth disease (HFMD) caused by Enterovirus A71, complicated by cardiopulmonary failure, is associated with a high mortality rate despite intensive treatment. To date, there is a paucity of clinical management data, regarding the use of extracorporeal life support (VA-ECMO) for Enterovirus-A71 associated cardiopulmonary failure reported. PATIENT CONCERNS: The patient in this study presented with severe HFMD complicated by cardiopulmonary failure, polymorphic ventricular tachycardia, and cardiac arrest. DIAGNOSES: Clinical presentations, laboratory data, and polymerase chain reaction (PCR) results from rectal swabs were used to confirm the diagnosis of severe HFMD caused by Enterovirus A71. INTERVENTIONS: The patient was managed with chest compression and an automatic external defibrillator, mechanical ventilation, intravenous immunoglobulin (IVIG), continuous renal replacement therapy (CRRT) and inotrope (milrinone). The patient did not respond to these interventions and subsequently required further management with VA-ECMO. OUTCOMES: The patient achieved a favorable outcomes. LESSONS: Our study highlights that extracorporeal membrane oxygenation and CRRT can enhance the survival outcomes of patients with severe HFMD with cardiopulmonary failure complications. Furthermore, we propose specific indications for the initiation of VA-ECMO.

IgG Antibody Responses to Epstein-Barr Virus in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Their Effective Potential for Disease Diagnosis and Pathological Antigenic Mimicry.

Background and Objectives: The diagnosis and pathology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remain under debate. However, there is a growing body of evidence for an autoimmune component in ME/CFS caused by the Epstein-Barr virus (EBV) and other viral infections. Materials and Methods: In this work, we analyzed a large public dataset on the IgG antibodies to 3054 EBV peptides to understand whether these immune responses could help diagnose patients and trigger pathological autoimmunity; we used healthy controls (HCs) as a comparator cohort. Subsequently, we aimed at predicting the disease status of the study participants using a super learner algorithm targeting an accuracy of 85% when splitting data into train and test datasets. Results: When we compared the data of all ME/CFS patients or the data of a subgroup of those patients with non-infectious or unknown disease triggers to the data of the HC, we could not find an antibody-based classifier that would meet the desired accuracy in the test dataset. However, we could identify a 26-antibody classifier that could distinguish ME/CFS patients with an infectious disease trigger from the HCs with 100% and 90% accuracies in the train and test sets, respectively. We finally performed a bioinformatic analysis of the EBV peptides associated with these 26 antibodies. We found no correlation between the importance metric of the selected antibodies in the classifier and the maximal sequence homology between human proteins and each EBV peptide recognized by these antibodies. Conclusions: In conclusion, these 26 antibodies against EBV have an effective potential for disease diagnosis in a subset of patients. However, the peptides associated with these antibodies are less likely to induce autoimmune B-cell responses that could explain the pathogenesis of ME/CFS.

Possible Concomitant Aggressive NK Cell Leukemia and EBV-positive T-cell lymphoma; Using the online beta version of WHO-HAEM5 and videoconferencing software to make diagnoses accessible in an emerging economy.

BACKGROUND: Using the World Health Organization Classification 5th edition (beta version online; WHO-HAEM5bv) in emerging economies is key to global healthcare equity. Although there may be ongoing updates, hesitancy in accepting and reporting these diagnoses in publication conflicts with the WHO's commitment to global accessibility. Aggressive NK cell leukemia (ANKL) and systemic EBV-positive T-cell lymphoma of childhood (SEBVTCL) with CD4-positive immunophenotype are both rare entities, are most described in Asians and East Asians, are associated with prior systemic chronic active EBV disease (CAEBV), and presentation with Hemophagocytic Lymphohistiocytosis (HLH). Recognizing and diagnosing any one of these entities requires not only training and experience in hematopathology, but good cooperation between clinical physicians and all areas of the laboratory. We describe a 30-year-old woman who presented to a Vietnam hospital and was rapidly diagnosed with ANKL, SEBVTCL, and HLH using WHO-HAEM5bv essential criteria, aided by expert consultation from a United States (US) board certified hematopathologist in real-time using video conferencing software. METHODS: Zoom™ videoconferencing software; Immunohistochemistry; flow cytometric immunophenotyping; polymerase chain reaction (PCR), Next Generation Sequencing (NGS). RESULTS: At the time of hospital admission, automated complete blood count (CBC) with differential count showed slight anemia, slight lymphocytosis, and moderate thrombocytopenia. HIV serology was negative. Whole blood PCR for EBV was positive showing 98,000 copies/ml. A lymph node biopsy revealed histology and immunohistochemistry consistent with the online beta version WHO-HAEM5 classification of SEBVTCL arising in CAEBV. Blood and bone marrow studies performed for staging revealed no histologic or immunohistochemical evidence of T-cell lymphoma in the bone marrow core, however, atypical blood smear lymphocyte morphology and blood immunophenotyping by flow cytometry were consistent with WHO-HAEM5 classification of ANKL. NGS revealed no evidence of genetic variant(s) associated with HLH in Vietnam. All laboratory studies were performed at Blood Transfusion Hematology Hospital (BTHH) in Ho Chi Minh City Vietnam. CONCLUSION: Although Vietnam, an emerging economy, currently lacks the laboratory infrastructure to more rigorously confirm a rare synchronous presentation of two distinct EBV-driven T/NK cell neoplasms, these two concomitant diagnoses were made using only laboratory techniques available in Vietnam with the help of WHO-HAEM5bv and real-time video consultation by a US hematopathologist.

Improvement in neoantigen prediction via integration of RNA sequencing data for variant calling.

Introduction: Neoantigen-based immunotherapy has emerged as a promising strategy for improving the life expectancy of cancer patients. This therapeutic approach heavily relies on accurate identification of cancer mutations using DNA sequencing (DNAseq) data. However, current workflows tend to provide a large number of neoantigen candidates, of which only a limited number elicit efficient and immunogenic T-cell responses suitable for downstream clinical evaluation. To overcome this limitation and increase the number of high-quality immunogenic neoantigens, we propose integrating RNA sequencing (RNAseq) data into the mutation identification step in the neoantigen prediction workflow. Methods: In this study, we characterize the mutation profiles identified from DNAseq and/or RNAseq data in tumor tissues of 25 patients with colorectal cancer (CRC). Immunogenicity was then validated by ELISpot assay using long synthesis peptides (sLP). Results: We detected only 22.4% of variants shared between the two methods. In contrast, RNAseq-derived variants displayed unique features of affinity and immunogenicity. We further established that neoantigen candidates identified by RNAseq data significantly increased the number of highly immunogenic neoantigens (confirmed by ELISpot) that would otherwise be overlooked if relying solely on DNAseq data. Discussion: This integrative approach holds great potential for improving the selection of neoantigens for personalized cancer immunotherapy, ultimately leading to enhanced treatment outcomes and improved survival rates for cancer patients.

Falls Among Older Adults During the COVID-19 Pandemic: A Multicenter Cross-Sectional Study in Vietnam.

Purpose: We aimed to investigate the prevalence and factors associated with falls in older adult outpatients during the coronavirus disease (COVID-19) pandemic in Vietnam. Patients and Methods: From February 2022 to June 2022, this cross-sectional study included 814 patients (aged ≥60 years; mean age 71.8 ± 7.3 years; women, 65.2%) attending three geriatric clinics for a comprehensive geriatric assessment. Self-reported fall events in the past 12 months and post-COVID-19 falls were assessed. Factors associated with falls were determined using logistic regression analysis. Results: In total, 188 patients (23.1%) had falls (single fall, 75.5%; recurrent falls, 24.5%). The most frequent location, time, and circumstance of falls were the bedroom (43.1%), morning (54.3%), and dizziness (34.6%), respectively. Most patients experienced health issues after falls (bruise/grazes, 53.7%; fracture, 12.8%; immobility, 9.6%; hospital admission, 14.9%). In the adjusted model, factors associated with falls were being underweight (odds ratio [OR] 2.50, 95% confidence interval [CI] 1.37-4.56, P = 0.003), limitations in instrumental activities of daily living (OR 2.03, 95% CI 1.05-3.95, P = 0.036), poor sleep quality (OR 1.83, 95% CI 1.10-3.05, P = 0.020), and fear of falling (OR 3.45, 95% CI 2.23-5.33, P <0.001). Among 357 COVID-19 infected patients, post-COVID-19 falls occurred in 35 patients (9.8%) and were associated with fear of falling (OR 3.14, 95% CI 1.18-8.40, P = 0.023) and post-COVID-19 lower limb weakness (OR 2.55, 95% CI 1.07-6.10, P = 0.035). Conclusion: Our study found a substantial prevalence of falls among older outpatients during the COVID-19 pandemic in Vietnam. Management of factors associated with falls may be needed to reduce the burden of falls in the older population.

Effects of process parameters in microwave-assisted extraction on the anthocyanin-enriched extract from Rhodomyrtus tomentosa (Ait.) Hassk and its storage conditions on the kinetic degradation of anthocyanins in the extract.

Rhodomyrtus tomentosa (Ait.) Hassk (RTH) is a plant distributed mainly in Southeast Asia that has long been used as a food or a folk remedy for various ailments. Anthocyanins extracted from RTH have received the attention of researchers as well as manufacturers in exploiting the application of this plant for commercial purposes. Several extraction methods have been performed, however, concerns about new extraction methods, extraction conditions as well as stability of anthocyanins during storage are issues that need to be evaluated. In this study, the process of extracting anthocyanins by microwave method and the stability of anthocyanins in RTH extraction were investigated. For the extraction method, the influence of solvent concentration (30-70%), application ratio (10:1-1:1 mL/g), microwave power (100-500W), and time (1-9 min) have been evaluated. A first-order kinetic model was also used to evaluate the variation of anthocyanin content during storage at different conditions, including 5 °C (refrigerator), 30 °C (room temperature), and 45 °C (incubator). The study results showed that the anthocyanin content had the greatest value of 137.54 mg/L when extracted with 50% ethanol solvent with the material/solvent ratio of 1:3 (g/ml) microwave power is 200W for 5 min. The first-order decomposition kinetics model showed that the t1/2 values of the RTH extract were 69.64, 28.66, and 19.8, respectively, for the storage temperatures of 5 °C, 30 °C, and 45 °C, respectively. During storage, anthocyanin content tends to decrease more rapidly under high-temperature conditions. In addition, a close correlation between anthocyanin content and antioxidant capacity was recorded at a high significance level R2 > 0.98.

Clinical and laboratory factors associated with neonatal sepsis mortality at a major Vietnamese children's hospital.

Sepsis is a major cause of neonatal mortality and children born in low- and middle-income countries (LMICs) are at greater risk of severe neonatal infections than those in higher-income countries. Despite this disparity, there are limited contemporaneous data linking the clinical features of neonatal sepsis with outcome in LMICs. Here, we aimed to identify factors associated with mortality from neonatal sepsis in Vietnam. We conducted a prospective, observational study to describe the clinical features, laboratory characteristics, and mortality rate of neonatal sepsis at a major children's hospital in Ho Chi Minh City. All in-patient neonates clinically diagnosed with probable or culture-confirmed sepsis meeting inclusion criteria from January 2017 to June 2018 were enrolled. We performed univariable analysis and logistic regression to identify factors independently associated with mortality. 524 neonates were recruited. Most cases were defined as late-onset neonatal sepsis and were hospital-acquired (91.4% and 73.3%, respectively). The median (IQR) duration of hospital stay was 23 (13-41) days, 344/524 (65.6%) had a positive blood culture (of which 393 non-contaminant organisms were isolated), and 69/524 (13.2%) patients died. Coagulase-negative staphylococci (232/405; 57.3%), Klebsiella spp. (28/405; 6.9%), and Escherichia coli (27/405; 6.7%) were the most isolated organisms. Sclerema (OR = 11.4), leukopenia <4,000/mm3 (OR = 7.8), thrombocytopenia <100,000/mm3 (OR = 3.7), base excess < -20 mEq/L (OR = 3.6), serum lactate >4 mmol/L (OR = 3.4), extremely low birth weight (OR = 3.2), and hyperglycaemia >180 mg/dL (OR = 2.6) were all significantly (p<0.05) associated with mortality. The identified risk factors can be adopted as prognostic factors for the diagnosis and treatment of neonatal sepsis and enable early risk stratification and interventions appropriate to reduce neonatal sepsis in LMIC settings.

Characterizing the spatial distribution of coral reefs in the South-Central Coast region of Viet Nam using Planetscope imagery.

This study aims to understand the spatial distribution of coral reefs in the central region of Viet Nam. We classified live coral cover in Son Tra Peninsula (ST) and Cu Lao Cham Island (CLC) in the South-Central Coast Region of Viet Nam using the Maximum Likelihood Classifier on 3 m Planetscope imagery. Confusion matrices and the accuracy of the classifier were assessed using field data (1,543 and 1,560 photographs in ST and CLC, respectively). The results showed that the reef's width ranged from 30 to 300 m across the study site, and we were able to detect live coral cover across a depth gradient of 2 to 6 m below the sea surface. The overall accuracies of the classifier (the Kappa coefficient) were 76.78% (0.76) and 78.08% (0.78) for ST and CLC, respectively. We found that 60.25% of coral reefs in ST were unhealthy and the live coral cover was less than 50%, while 25.75% and 11.46% of those in CLC were in good and excellent conditions, respectively. This study demonstrates the feasibility of utilizing Planetscope imagery to monitor shallow coral reefs of small islands at a high spatial resolution of 3 m. The results of this study provide valuable information for coral reef protection and conservation.

The endemic Helicobacter pylori population in Southern Vietnam has both South East Asian and European origins.

BACKGROUND: The burden of Helicobacter pylori-induced gastric cancer varies based on predominant H. pylori population in various geographical regions. Vietnam is a high H. pylori burden country with the highest age-standardized incidence rate of gastric cancer (16.3 cases/100,000 for both sexes) in Southeast Asia, despite this data on the H. pylori population is scanty. We examined the global context of the endemic H. pylori population in Vietnam and present a contextual and comparative genomics analysis of 83 H. pylori isolates from patients in Vietnam. RESULTS: There are at least two major H. pylori populations are circulating in symptomatic Vietnamese patients. The majority of the isolates (~ 80%, 66/83) belong to the hspEastAsia and the remaining belong to hpEurope population (~ 20%, 17/83). In total, 66 isolates (66/83) were cagA positive, 64 were hspEastAsia isolates and two were hpEurope isolates. Examination of the second repeat region revealed that most of the cagA genes were ABD type (63/66; 61 were hspEastAsia isolates and two were hpEurope isolates). The remaining three isolates (all from hspEastAsia isolates) were ABC or ABCC types. We also detected that 4.5% (3/66) cagA gene from hspEastAsia isolates contained EPIYA-like sequences, ESIYA at EPIYA-B segments. Analysis of the vacA allelic type revealed 98.8% (82/83) and 41% (34/83) of the strains harboured the s1 and m1 allelic variant, respectively; 34/83 carried both s1m1 alleles. The most frequent genotypes among the cagA positive isolates were vacA s1m1/cagA + and vacA s1m2/cagA + , accounting for 51.5% (34/66) and 48.5% (32/66) of the isolates, respectively. CONCLUSIONS: There are two predominant lineages of H. pylori circulating in Vietnam; most of the isolates belong to the hspEastAsia population. The hpEurope population is further divided into two smaller clusters.

Opportunistic DF-AF Selection Relaying in Hybrid Wireless and Power Line Communication for Indoor IoT Networks.

This manuscript investigates the system performance of hybrid wireless and power line communication networks for indoor Internet of Things applications. Differentiating itself from the existing literature, the performance of the direct link and dual-hop energy harvesting relay-aided links is analyzed under the condition of indoor fading modeled by log-normal distribution. Moreover, the manuscript presents the analytical expressions of the successful transmission probability of the deployed opportunistic decode-and-forward and amplify-and-forward relay selection scheme, and validates them with Monte Carlo simulations. Moreover, the impact of different system parameters on the successful transmission probability is revealed. For the considered hybrid system, in general, the opportunistic decode-and-forward relaying scheme outperforms the opportunistic amplify-and-forward relaying scheme. As importantly, increasing the source to relay distance and power splitting ratio over certain limits significantly deteriorates the system performance, indicated by the decrease in the successful transmission probability.

Vascular control of kidney epithelial transporters.

A major pathway in hypertension pathogenesis involves direct activation of ANG II type 1 (AT1) receptors in the kidney, stimulating Na+ reabsorption. AT1 receptors in tubular epithelia control expression and stimulation of Na+ transporters and channels. Recently, we found reduced blood pressure and enhanced natriuresis in mice with cell-specific deletion of AT1 receptors in smooth muscle (SMKO mice). Although impaired vasoconstriction and preserved renal blood flow might contribute to exaggerated urinary Na+ excretion in SMKO mice, we considered whether alterations in Na+ transporter expression might also play a role; therefore, we carried out proteomic analysis of key Na+ transporters and associated proteins. Here, we show that levels of Na+-K+-2Cl- cotransporter isoform 2 (NKCC2) and Na+/H+ exchanger isoform 3 (NHE3) are reduced at baseline in SMKO mice, accompanied by attenuated natriuretic and diuretic responses to furosemide. During ANG II hypertension, we found widespread remodeling of transporter expression in wild-type mice with significant increases in the levels of total NaCl cotransporter, phosphorylated NaCl cotransporter (Ser71), and phosphorylated NKCC2, along with the cleaved, activated forms of the α- and γ-epithelial Na+ channel. However, the increases in α- and γ-epithelial Na+ channel with ANG II were substantially attenuated in SMKO mice. This was accompanied by a reduced natriuretic response to amiloride. Thus, enhanced urinary Na+ excretion observed after cell-specific deletion of AT1 receptors from smooth muscle cells is associated with altered Na+ transporter abundance across epithelia in multiple nephron segments. These findings suggest a system of vascular-epithelial in the kidney, modulating the expression of Na+ transporters and contributing to the regulation of pressure natriuresis.NEW & NOTEWORTHY The use of drugs to block the renin-angiotensin system to reduce blood pressure is common. However, the precise mechanism for how these medications control blood pressure is incompletely understood. Here, we show that mice lacking angiotensin receptors specifically in smooth muscle cells lead to alternation in tubular transporter amount and function. Thus, demonstrating the importance of vascular-tubular cross talk in the control of blood pressure.

Angiotensin receptors in the kidney and vasculature in hypertension and kidney disease.

Kidney disease, blood pressure determination, hypertension pathogenesis, and the renin-angiotensin system (RAS) are inextricably linked. Hence, understanding the RAS is pivotal to unraveling the pathophysiology of hypertension and the determinants to maintaining normal blood pressure. The RAS has been the subject of intense investigation for over a century. Moreover, medications that block the RAS are mainstay therapies in clinical medicine and have been shown to reduce morbidity and mortality in patients with diabetes, cardiovascular, and kidney diseases. The main effector peptide of the RAS is the interaction of the octapeptide- Ang II with its receptor. The type 1 angiotensin receptor (AT1R) is the effector receptor for Ang II. These G protein-coupled receptors (GPCRs) are ubiquitously expressed in a variety of cell lineages and tissues relevant to cardiovascular disease throughout the body. The advent of cell specific deletion of genes using Cre LoxP technology in mice has allowed for the identification of discreet actions of AT1Rs in blood pressure control and kidney disease. The kidney is one of the major targets of the RAS, which is responsible in maintaining fluid, electrolyte balance, and blood pressure. In this review we will discuss the role of AT1Rs in the kidney, vasculature, and immune cells and address their effects on hypertension and kidney disease.

Direct Actions of AT1 (Type 1 Angiotensin) Receptors in Cardiomyocytes Do Not Contribute to Cardiac Hypertrophy.

Activation of AT1 (type 1 Ang) receptors stimulates cardiomyocyte hypertrophy in vitro. Accordingly, it has been suggested that regression of cardiac hypertrophy associated with renin-Ang system blockade is due to inhibition of cellular actions of Ang II in the heart, above and beyond their effects to reduce pressure overload. We generated 2 distinct mouse lines with cell-specific deletion of AT1A receptors, from cardiomyocytes. In the first line (C-SMKO), elimination of AT1A receptors was achieved using a heterologous Cre recombinase transgene under control of the Sm22 promoter, which expresses in cells of smooth muscle lineage including cardiomyocytes and vascular smooth muscle cells of conduit but not resistance vessels. The second line (R-SMKO) utilized a Cre transgene knocked-in to the Sm22 locus, which drives expression in cardiac myocytes and vascular smooth muscle cells in both conduit and resistance arteries. Thus, although both groups lack AT1 receptors in the cardiomyocytes, they are distinguished by presence (C-SMKO) or absence (R-SMKO) of peripheral vascular responses to Ang II. Similar to wild-types, chronic Ang II infusion caused hypertension and cardiac hypertrophy in C-SMKO mice, whereas both hypertension and cardiac hypertrophy were reduced in R-SMKOs. Thus, despite the absence of AT1A receptors in cardiomyocytes, C-SMKOs develop robust cardiac hypertrophy. By contrast, R-SMKOs developed identical levels of hypertrophy in response to pressure overload-induced by transverse aortic banding. Our findings suggest that direct activation of AT1 receptors in cardiac myocytes has minimal influence on cardiac hypertrophy induced by renin-Ang system activation or pressure overload.

Study protocol: The clinical features, epidemiology, and causes of paediatric encephalitis in southern Vietnam.

Encephalitis is a major cause of morbidity and mortality worldwide. The clinical syndrome of encephalitis consists of altered mental status, seizures, neurologic signs, and is often accompanied by fever, headache, nausea, and vomiting. The encephalitis in children has been known that more common than in adult, with the incidence rate of infants was 3.9 times higher than that of people 20-44 years of age. The reported incidence of hospitalization attributed to paediatric encephalitis ranged from 3 to 13 admissions per 100,000 children per year with the overall mortality ranging from 0 to 7%. There are however more than 100 pathogens that can cause encephalitis and accurate diagnosis is challenging. Over 50% of patients with encephalitis are left undiagnosed despite extensive laboratory investigations. Furthermore, recent studies in high-income settings have suggested autoimmune encephalitis has now surpassed infectious aetiologies, mainly due to increased awareness and diagnostic capacity, which further challenges routine diagnosis and clinical management, especially in developing countries. There are limited contemporary data on the causes of encephalitis in children in Vietnam. Improving our knowledge of the causative agents of encephalitis in this resource-constrained setting remains critical to informing case management, resource distribution and vaccination strategy. Therefore, we conduct a prospective observational study to characterise the clinical, microbiological, and epidemiological features of encephalitis in a major children's hospital in southern Vietnam. Admission clinical samples will be collected alongside meta clinical data and from each study participants. A combination of classical assays (serology and PCR) and metagenomic next-generation sequencing will used to identify the causative agents. Undiagnosed patients with clinical presentations compatible with autoimmune encephalitis will then be tested for common forms of the disease. Finally, using direct- and indirect costs, we will estimate the economic burden of hospitalization and seven days post hospital discharge of paediatric encephalitis in our setting.

Microbiome dataset analysis from a shrimp pond in Ninh Thuan, Vietnam using shotgun metagenomics.

Vietnam is one of the top shrimp producing and exporting countries in the world [1]. However, viral and bacterial epidemic diseases cause severe damages to shrimp farming, resulting in millions of US dollars losses annually [2]. Furthermore, inappropriate use of antibiotics in shrimp rearing lead to increased emergence of drug resistant pathogens [3]. Current practices for water quality control, mostly based on chemical and physical parameters; neglected biological criteria necessary for maintaining pond health. Ninh Thuan is a region situated in the South Central Coast of Vietnam. Due to its geographic location, a large part of this region is dedicated to shrimp (Litopenaeus vannamei) post-larvae production and rearing. This article presents a microbiome dataset from two water samples collected in a shrimp rearing pond in Ninh Thuan. We used Oxford Nanopore Technologies (ONT) for metagenomic sequencing of the samples to characterize microbial communities and antibiotic resistance profiles. The metagenome dataset generated will provide an understanding and comparison framework of the microbial diversity and functionality among shrimp ponds with potential application in health management and shrimp rearing industry.

Transoral robotic surgery and neck dissection for HPV-positive oropharyngeal carcinoma: Importance of nodal count in survival.

BACKGROUND: In this study we determine the survival in patients with HPV-positive oropharyngeal carcinoma treated with transoral robotic surgery (TORS), neck dissection and risk-adapted adjuvant therapy. METHODS: We retrospectively identified 122 patients with HPV-positive oropharyngeal carcinoma treated with TORS and neck dissection between 2011 and 2018. Survival probability was calculated. We determined the effect of the type of neck dissection performed (modified radical neck dissection-MRND vs. selective neck dissection - SND), extranodal extension (ENE), margin status, and presence of ≥ 5 metastatic nodes on survival. RESULTS: Our patient population had a five-year overall survival of 91.0% (95% C.I. 85-97%). The five-year probability of recurrence or cancer-associated death was 0.0977 (95% C.I. 0.0927-0.1027). The five-year probability of cancer-associated death was 0.0528 (95% C.I. 0.048-0.0570). All patients who died of their disease had distant metastasis. Our PEG dependence rate was 0%. Patients with ENE and positive margins who underwent adjuvant chemoradiation did not have worse survival. Presence of ≥ 5 metastatic nodes portended worse survival after controlling for age, positive ENE and margins. Low yield (<18 nodes) on neck dissection worsened DFS on multivariable analysis. Furthermore, patients who underwent SND did not have worse OS than those who underwent MRND. CONCLUSION: Our study demonstrates that surgery could be simplified by performing TORS with SND rather than MRND. The one true poor prognostic factor in HPV-positive oropharyngeal carcinoma patients who undergo surgery is high nodal burden. Patients with high nodal burden are much more likely to die from their disease.