Antibiotic Resistance Profile and Bio-Control of Multidrug-Resistant Escherichia coli Isolated from Raw Milk in Vietnam Using Bacteriophages.

E. coli is an important zoonotic pathogen capable of causing foodborne illness and bovine mastitis. Bacteriophages have been increasingly considered a promising tool to control unwanted bacteria. The aim of this study is to determine the antibiotic resistance profile of E. coli isolated from raw milk and the efficacy of phage in controlling multidrug-resistant E. coli in raw milk. Antibiotic susceptibility testing showed the highest resistance rates of E. coli isolates to co-trime (27.34%) and ampicillin (27.34%), followed by streptomycin (25.18%), tetracycline (23.02%), and the lowest resistance rates to ciprofloxacin, gentamycin, and ceftazidime, all at a rate of 2.16%. All isolates were susceptible to meropenem. Of the 139 E. coli isolates, 57 (41.01%) were resistant to at least one antibiotic, and 35 (25.18%) were classified as MDR strains. Molecular characterization indicated that 5 (3.6%) out of the 139 isolates were STEC strains carrying stx1 gene. Seven (5.04%) isolates were phenotypically identified as ESBLEC, and four isolates (2.88%) were resistant to colistin. The results of the genotypic test revealed that four out of seven ESBLEC strains carried both blaTEM and blaCTX-M-1, two harbored blaTEM, and one possessed blaCTX-M-1, while mcr-1 was detected in all four colistin-resistant E. coli isolates. In particular, one isolated E. coli strain (EM148) was determined to be a multidrug-resistant strain simultaneously carrying blaTEM, blaCTX-M-1, and mcr-1. A total of eight phages were successfully recovered from raw milk. The application of phage PEM3 significantly reduced viable counts of multidrug-resistant host EM148 in raw milk by at least 2.31 log CFU/mL at both 24 °C and 4 °C.

Temozolomide promotes matrix metalloproteinase 9 expression through p38 MAPK and JNK pathways in glioblastoma cells.

Glioblastoma (GBM) is a highly aggressive and deadly brain cancer. Temozolomide (TMZ) is the standard chemotherapeutic agent for GBM, but the majority of patients experience recurrence and invasion of tumor cells. We investigated whether TMZ treatment of GBM cells regulates matrix metalloproteinases (MMPs), which have the main function to promote tumor cell invasion. TMZ effectively killed GL261, U343, and U87MG cells at a concentration of 500 µM, and surviving cells upregulated MMP9 expression and its activity but not those of MMP2. TMZ also elevated levels of MMP9 mRNA and MMP9 promoter activity. Subcutaneous graft tumors survived from TMZ treatment also exhibited increased expression of MMP9 and enhanced gelatinolytic activity. TMZ-mediated MMP9 upregulation was specifically mediated through the phosphorylation of p38 and JNK. This then stimulates AP-1 activity through the upregulation of c-Fos and c-Jun. Inhibition of the p38, JNK, or both pathways counteracted the TMZ-induced upregulation of MMP9 and AP-1. This study proposes a potential adverse effect of TMZ treatment for GBM: upregulation of MMP9 expression potentially associated with increased invasion and poor prognosis. This study also provides valuable insights into the molecular mechanisms by which TMZ treatment leads to increased MMP9 expression in GBM cells.

Comparing the accuracy of two machine learning models in detection and classification of periapical lesions using periapical radiographs.

BACKGROUND: Previous deep learning-based studies were mainly conducted on detecting periapical lesions; limited information in classification, such as the periapical index (PAI) scoring system, is available. The study aimed to apply two deep learning models, Faster R-CNN and YOLOv4, in detecting and classifying periapical lesions using the PAI score from periapical radiographs (PR) in three different regions of the dental arch: anterior teeth, premolars, and molars. METHODS: Out of 2658 PR selected for the study, 2122 PR were used for training, 268 PR were used for validation and 268 PR were used for testing. The diagnosis made by experienced dentists was used as the reference diagnosis. RESULTS: The Faster R-CNN and YOLOv4 models obtained great sensitivity, specificity, accuracy, and precision for detecting periapical lesions. No clear difference in the performance of both models among these three regions was found. The true prediction of Faster R-CNN was 89%, 83.01% and 91.84% for PAI 3, PAI 4 and PAI 5 lesions, respectively. The corresponding values of YOLOv4 were 68.06%, 50.94%, and 65.31%. CONCLUSIONS: Our study demonstrated the potential of YOLOv4 and Faster R-CNN models for detecting and classifying periapical lesions based on the PAI scoring system using periapical radiographs.

Synthesis and crystal structures of three organoplatinum(II) complexes bearing natural aryl-olefin and quinoline derivatives.

Three organoplatinum(II) complexes bearing natural aryl-olefin and quinoline derivatives, namely, [4-meth-oxy-5-(2-meth-oxy-2-oxoeth-oxy)-2-(prop-2-en-1-yl)phen-yl](quinolin-8-olato)platinum(II), [Pt(C13H15O4)(C9H6NO)], (I), [4-meth-oxy-5-(2-oxo-2-propoxyeth-oxy)-2-(prop-2-en-1-yl)phen-yl](quinoline-2-carboxy-l-ato)platinum(II), [Pt(C15H19O4)(C10H6NO2)], (II), and chlorido-[4-meth-oxy-5-(2-oxo-2-propoxyeth-oxy)-2-(prop-2-en-1-yl)phen-yl](quinoline)-plat-inum(II), [Pt(C15H19O4)Cl(C9H7N)], (III), were synthesized and structurally characterized by IR and 1H NMR spectroscopy, and by single-crystal X-ray diffraction. The results showed that the cyclo-platinated aryl-olefin coordinates with PtII via the carbon atom of the phenyl ring and the C=Colefinic group. The deprotonated 8-hy-droxy-quinoline (C9H6NO) and quinoline-2-carb-oxy-lic acid (C10H6NO2) coordinate with the PtII atom via the N and O atoms in complexes (I) and (II) while the quinoline (C9H7N) coordinates via the N atom in (III). Moreover, the coordinating N atom in complexes (I)-(III) is in the cis position compared to the C=Colefinic group. The crystal packing is characterized by C-H⋯π, C-H⋯O [for (II) and (III)], C-H⋯Cl [for (III) and π-π [for (I)] inter-actions.

Prevalence and Antibiotic Resistance Profile of Clostridium perfringens Isolated from Pork and Chicken Meat in Vietnam.

Clostridium perfringens is one of the most important zoonotic pathogens as it can cause food poisoning in humans and necrotic enteritis in both animals and humans. Meat, especially pork and chicken meat, is considered the main vehicle for the transmission of C. perfringens from animals to humans. The purpose of this study was to determine the prevalence, toxinotype, and antimicrobial resistance profile of C. perfringens isolated from pork and chicken meat sold in Vietnam. The isolation results showed that 15/50 (30%) of pork samples and 8/50 (16%) of chicken meat samples were contaminated with C. perfringens. The isolates exhibited their highest resistance rate to tetracycline (21/23; 91.30%) and clindamycin (10/23; 43.48%). On the contrary, their lowest resistance rates were observed in response to imipenem (2/23; 8.70%) and cefoxitin (1/23; 4.35%). In particular, 34.78% (8/23) of C. perfringens isolates were identified to be multidrug-resistant strains. The results of toxin genotyping indicated that all isolates were positive for the cpa gene and belonged to type A.

Constructing B─N─P Bonds in Ultrathin Holey g-C3N4 for Regulating the Local Chemical Environment in Photocatalytic CO2 Reduction to CO.

The lack of intrinsic active sites for photocatalytic CO2 reduction reaction (CO2RR) and fast recombination rate of charge carriers are the main obstacles to achieving high photocatalytic activity. In this work, a novel phosphorus and boron binary-doped graphitic carbon nitride, highly porous material that exhibits powerful photocatalytic CO2 reduction activity, specifically toward selective CO generation, is disclosed. The coexistence of Lewis-acidic and Lewis-basic sites plays a key role in tuning the electronic structure, promoting charge distribution, extending light-harvesting ability, and promoting dissociation of excitons into active carriers. Porosity and dual dopants create local chemical environments that activate the pyridinic nitrogen atom between the phosphorus and boron atoms on the exposed surface, enabling it to function as an active site for CO2RR. The P-N-B triad is found to lower the activation barrier for reduction of CO2 by stabilizing the COOH reaction intermediate and altering the rate-determining step. As a result, CO yield increased to 22.45 µmol g-1 h-1 under visible light irradiation, which is ≈12 times larger than that of pristine graphitic carbon nitride. This study provides insights into the mechanism of charge carrier dynamics and active site determination, contributing to the understanding of the photocatalytic CO2RR mechanism.

Employer branding, organization's image and reputation, and intention to apply: the moderating role of the availability of organizational information on social media.

The topics of employer branding and organization's image and reputation have been well-researched in the literature. However, most empirical studies were conducted in Europe, Australia, or the United States, but very few were conducted in Asia, especially in Vietnam. In addition, the interaction of image and reputation with the availability of information on social media is poorly understood. Using signaling theory for building a research model, we collected data from 206 Generation Z respondents from the logistics sector in Vietnam. Our findings show that (i) employer branding has positively and significantly related to an organization's image and reputation; (ii) the organization's image and reputation had a significant effect on job seekers' intention to apply; and (iii) the interaction of image and reputation with availability of information on social media to predict the job seeker's intention to apply. The paper also presented implications for both researchers and practitioners as well as recommendations for future research.

Identification of novel phenylalanine derivatives bearing a hydroxamic acid moiety as potent quorum sensing inhibitors.

Phenylalanine derivatives are a well-known small moiety responsible for controlling the virulence factors of several bacteria. Herein, for the first time, we report novel structures of phenylalanine derivatives bearing a hydroxamic acid moiety which were designed, synthesized, and evaluated for use as quorum sensing inhibitors. Biological results reveal that six compounds showed good quorum sensing inhibitors properties with an IC50 ranging from 7.12 ± 2.11 µM-92.34 ± 2.09 µM (4NPO, a reference compound, IC50 = 29.13 ± 0.88 µM). In addition, three out of the six compounds (4a, 4c, 4h) showed strong anti-biofilm formation and CviR inhibitory activity when compared to that of 4NPO. These biological data were also confirmed by computational studies. In this series of compounds, 4h is the most promising compound for future drug development targeting quorum sensing. Our results concluded that the fragment-based drug design is a good approach for the discovery of novel quorum-sensing inhibitors in the future.

Reference Value Fibrin Monomer in Healthy Children: A Cross-Sectional Study.

The objective of this study is to determine the fibrin monomer reference intervals in healthy children. This cross-sectional study was conducted in the Hematology Department at Vietnam National Children's Hospital (April 2023 to March 2024). Children without prior history of clotting disorders or anticoagulants use hospitalized in preparation for orthopedic surgery or inguinal hernia surgery were enrolled in the study. The fibrin monomer test method was the quantitative fibrin monomer test on the STA-R system (Diagnostica Stago™, France). Eighty-six children (58 males and 28 females) were enrolled in the study. The median (interquartile range, 2.5th-97.5th) fibrin monomer value of the study subjects was 2.56 (0.11-5.93) µg/mL, with no statistically significant difference in fibrin monomer values among the age groups of 1 month to 3 years, 3 years to 13 years, and 13 years to 18 years. This is the first study conducted in Vietnam to determine reference values of fibrin monomer in children. This information can help in the diagnosis and treatment of early hypercoagulation stage and disseminated intravascular coagulation in children.

Valorization of the treatment of antibiotic and organic contents generated from an in-situ-RAS-like shrimp farming pond by using graphene-quantum-dots deposited graphitic carbon nitride photocatalysts.

In this study, we investigated the possibility of a photocatalytic system that uses graphene-quantum-dot (GQD)-deposited graphitic carbon nitride (g-C3N4) to treat tetracycline (TC) and other organic compounds generated from an in-situ-recirculatory-aquaculture-system (RAS)-like shrimp farming pond. GQDs were successfully deposited on the exfoliated g-C3N4 base through a hydrothermal treatment. The results showed that the incorporation of GQDs into the g-C3N4 enhanced its porosity without aggregating its mesoporous structure. The GQDs-deposited g-C3N4 photocatalysts revealed sheet-like structures with nanopores on their surface that facilitate photocatalysis. More than 90% of the TC was removed by the photocatalysts under UV-LED irradiation. Low loadings of GQDs over g-C3N4 resulted in a faster and more effective photocatalysis of TC, mainly driven by.O2- radicals. The photocatalysts were also applicable in the degradation of organic compounds with 27% of the total organic compounds (TOC) being removed from the wastewater of a RAS-like shrimp farming pond.

A facile paper-based chromatography coupled Au nanodendrite on nickel foam for application in separation and SERS measurement.

A simple paper-based chromatography coupling with nickel foam decorated Au nanodendrite (PP-AuND/NiF) was fabricated for simultaneous separation and surface-enhanced Raman scattering (SERS) detection of Rhodamine-6G (R6G) from a mixture of analytes. The three-dimensional porous nickel foam (NiF) was employed as a sampling diffusion platform, and AuND with a high surface active area beneficial for SERS efficiency was electro-deposited directly onto the NiF frame. The structure of AuND/NiF was characterized by X-ray diffraction and scanning electron microscopy. The AuND/NiF could detect R6G at 0.1 nM, and the enhancement factor was 1.84 x 106. The AuND/NiF was durable, with a slight signal decrease after 6 m of drop-testing. Also, upon three days of exposure to ambient air, the signal droped only 3.35 %. Subsequently, the PP-AuND/NiF was constructed by directly situating AuND/NiF on a paper strip, serving as a sample in and out to AuND/NiF. A mixture of two SERS active compounds, namely 2-Naphthalenethiol (2-NpSH) and Rhodamine 6G (R6G), was prepared in ethanol: water (1:1) solution to evaluate PP-AuND/NiF separation capability. Raman measurements along different distances of AuND/NiF were performed, and the signal of 2-NpSH was dismissed after 3.0 mm, while R6G's signals were observed throughout AuND/NiF. In general, the PP-AuND/NiF demonstrated effective separation and SERS measurement of analytes in a mixture, which could be applicable for more complex samples in the future, especially in clinical analysis.

Maternal and perinatal outcomes of hypertensive disorders in pregnancy: Insights from the National Hospital of Obstetrics and Gynecology in Vietnam.

INTRODUCTION: Hypertension is the common disorder encountered during pregnancy, complicating 5% to 10% of all pregnancies. Hypertensive disorders in pregnancy (HDP) are also a leading cause of maternal and perinatal morbidity and mortality. The majority of feto-maternal complications due to HPD have occurred in the low- and middle-income countries. However, few studies have been done to assess the feto-maternal outcomes and the predictors of adverse perinatal outcome among women with HDP in these countries. METHODS: A prospective cohort study was conducted on women with HDP who were delivered at National Hospital of Obstetrics and Gynecology, Vietnam from March 2023 to July 2023. Socio-demographic and obstetrics characteristics, and feto-maternal outcomes were obtained by trained study staff from interviews and medical records. Statistical analysis was performed using SPSS version 26.0. Bivariate and multiple logistic regressions were done to determine factors associated with adverse perinatal outcome. A 95% confidence interval not including 1 was considered statically significant. RESULTS: A total of 255 women with HDP were enrolled. Regarding adverse maternal outcomes, HELLP syndrome (3.9%), placental abruption (1.6%), and eclampsia (1.2%) were three most common complications. There was no maternal death associated with HDP. The most common perinatal complication was preterm delivery developed in 160 (62.7%) of neonates. Eight stillbirths (3.1%) were recorded whereas the perinatal mortality was 6.3%. On bivariate logistic regression, variables such as residence, type of HDP, highest systolic BP, highest diastolic BP, platelet count, severity symptoms, and birth weight were found to be associated with adverse perinatal outcome. On multiple logistic regression, highest diastolic BP, severity symptoms, and birth weight were found to be independent predictors of adverse perinatal outcome. CONCLUSION: Our study showed lower prevalence of stillbirth, perinatal mortality, and maternal complication compared to some previous studies. Regular antenatal care and early detection of abnormal signs during pregnancy help to devise an appropriate monitoring and treatment strategies for each women with HDP.

INO80 function is required for mouse mammary gland development, but mutation alone may be insufficient for breast cancer.

The aberrant function of ATP-dependent chromatin remodeler INO80 has been implicated in multiple types of cancers by altering chromatin architecture and gene expression; however, the underlying mechanism of the functional involvement of INO80 mutation in cancer etiology, especially in breast cancer, remains unclear. In the present study, we have performed a weighted gene co-expression network analysis (WCGNA) to investigate links between INO80 expression and breast cancer sub-classification and progression. Our analysis revealed that INO80 repression is associated with differential responsiveness of estrogen receptors (ERs) depending upon breast cancer subtype, ER networks, and increased risk of breast carcinogenesis. To determine whether INO80 loss induces breast tumors, a conditional INO80-knockout (INO80 cKO) mouse model was generated using the Cre-loxP system. Phenotypic characterization revealed that INO80 cKO led to reduced branching and length of the mammary ducts at all stages. However, the INO80 cKO mouse model had unaltered lumen morphology and failed to spontaneously induce tumorigenesis in mammary gland tissue. Therefore, our study suggests that the aberrant function of INO80 is potentially associated with breast cancer by modulating gene expression. INO80 mutation alone is insufficient for breast tumorigenesis.

A Cell-Adapted Live-Attenuated Vaccine Candidate Protects Pigs against the Homologous Strain VNUA-ASFV-05L1, a Representative Strain of the Contemporary Pandemic African Swine Fever Virus.

African swine fever (ASF) is a lethal and highly contagious transboundary animal disease with the potential for rapid international spread. Currently, there is no ASF vaccine commercially available. All infected animals must be isolated and culled immediately upon the confirmation of the presence of the virus. Studies leading to the rational development of protective ASF vaccines are urgently needed. Here, we generated a safe and efficacious live-attenuated vaccine (LAV) VNUA-ASFV-LAVL2 by serially passaging a field isolate (VNUA-ASFV-05L1, genotype II) in porcine alveolar macrophages (PAMs, 65 passages) and an immortalized porcine alveolar macrophage cell line (3D4/21, 55 passages). VNUA-ASFV-LAVL2 can efficiently replicate in both PAMs and 3D4/21 cells. It provides 100% protection, even with the low dose of 102 HAD50, to the vaccinated pigs against the challenge of contemporary pandemic ASFV field isolate. Pigs vaccinated with this LAV in a dose range of 102 to 105 HAD50 remained clinically healthy during both the 28-day observation period of immunization and the 28-day observation period of challenge. VNUA-ASFV-LAVL2 was eliminated from blood by 28 days post-inoculation (DPI), and from feces or oral fluids by 17 DPI. Although the vaccine strain in serum remained a safe and attenuated phenotype after five passages in swine, a reversion-to-virulence study using blood or tissue homogenates at peak viremia will be conducted in the future. ASFV-specific IgG antibodies and significant cellular immunity were detected in vaccinated pigs before the ASFV challenge. These results indicate that the VNUA-ASFV-LAVL2 strain is a safe and efficacious LAV against the genotype II ASFV strain responsible for current ASF outbreaks in Asia.

Determination of Methanol, Acetaldehyde, and Ethyl Acetate in Thousand Folds of Ethanol Sample by Headspace Gas Chromatography with Mass Spectrometry.

Alcohol beverages have been widely consumed in several parts of the world. In this study, volatile organic compounds in alcoholic beverages including acetaldehyde, ethyl acetate, methanol, and higher ethanol were investigated and evaluated using a headspace gas chromatograph equipped with a mass spectrometer. This study evaluated the suitability of the chromatographic system, linearity, limit of detection, and limit of quantification, accuracy, and precision of the single and simultaneous determination of acetaldehyde, ethyl acetate, and methanol in thousand folds of ethanol. Results showed that the acetaldehyde concentration in local beer samples and local manual product liqueur samples ranged from 4.65 to 13.22 mg/L and from 5.55 to 75.96 mg/L, respectively, but in local industrial product liqueur samples, acetaldehyde was not detected. Methanol was only detected in a few local beer samples and locally manually produced liqueur samples within low concentrations. Ethyl acetate was only detected in all local beer samples, but it was not present in local industrial product liqueur samples.

Polymer-Based Hydrogels Applied in Drug Delivery: An Overview.

Polymer-based hydrogels are hydrophilic polymer networks with crosslinks widely applied for drug delivery applications because of their ability to hold large amounts of water and biological fluids and control drug release based on their unique physicochemical properties and biocompatibility. Current trends in the development of hydrogel drug delivery systems involve the release of drugs in response to specific triggers such as pH, temperature, or enzymes for targeted drug delivery and to reduce the potential for systemic toxicity. In addition, developing injectable hydrogel formulations that are easily used and sustain drug release during this extended time is a growing interest. Another emerging trend in hydrogel drug delivery is the synthesis of nano hydrogels and other functional substances for improving targeted drug loading and release efficacy. Following these development trends, advanced hydrogels possessing mechanically improved properties, controlled release rates, and biocompatibility is developing as a focus of the field. More complex drug delivery systems such as multi-drug delivery and combination therapies will be developed based on these advancements. In addition, polymer-based hydrogels are gaining increasing attention in personalized medicine because of their ability to be tailored to a specific patient, for example, drug release rates, drug combinations, target-specific drug delivery, improvement of disease treatment effectiveness, and healthcare cost reduction. Overall, hydrogel application is advancing rapidly, towards more efficient and effective drug delivery systems in the future.

A novel n-p heterojunction Bi2S3/ZnCo2O4 photocatalyst for boosting visible-light-driven photocatalytic performance toward indigo carmine.

An innovative p-n heterojunction Bi2S3/ZnCo2O4 composite was first fabricated via a two-step co-precipitation and hydrothermal method. By controlling the weight amount of Na2S and Bi(NO3)3 precursor, different heterogeneous xBi2S3/ZnCo2O4 were synthesized (x = 0, 2, 6, 12, and 20). The p-n heterojunction Bi2S3/ZnCo2O4 was characterized by structural, optical, and photochemical properties and the photocatalyst decoloration of indigo carmine. Mott-Schottky plots proved a heterojunction formed between n-Bi2S3 and p-ZnCo2O4. Furthermore, the investigation of the photocurrent response indicated that the Bi2S3/ZnCo2O4 composite displayed an enhanced response, which was respectively 4.6 and 7.3 times (4.76 µA cm-2) greater than that of the pure Bi2S3 (1.02 µA cm-2) and ZnCo2O4 (0.65 µA cm-2). Especially the optimized p-n Bi2S3/ZnCo2O4 heterojunction with 12 wt% Bi2S3 showed the highest photocatalyst efficacy of 92.1% at 40 mg L-1 solutions, a loading of 1.0 g L-1, and a pH of 6 within 90 min of visible light illumination. These studies prove that p-n Bi2S3/ZnCo2O4 heterojunction photocatalysts can greatly boost their photocatalytic performance because the inner electric field enhances the process of separating photogenerated electron-hole pairs. Furthermore, this composite catalyst showed good stability and recyclability for environmental remediation.

Six years of the Angels Initiative: Aims, achievements, and future directions to improve stroke care worldwide.

The rate of stroke-related death and disability is four times higher in low- and middle-income countries (LMICs) than in high-income countries (HICs), yet stroke units exist in only 18% of LMICs, compared with 91% of HICs. In order to ensure universal and equitable access to timely, guideline-recommended stroke care, multidisciplinary stroke-ready hospitals with coordinated teams of healthcare professionals and appropriate facilities are essential.Established in 2016, the Angels Initiative is an international, not-for-profit, public-private partnership. It is run in collaboration with the World Stroke Organization, European Stroke Organisation, and regional and national stroke societies in over 50 countries. The Angels Initiative aims to increase the global number of stroke-ready hospitals and to optimize the quality of existing stroke units. It does this through the work of dedicated consultants, who help to standardize care procedures and build coordinated, informed communities of stroke professionals. Angels consultants also establish quality monitoring frameworks using online audit platforms such as the Registry of Stroke Care Quality (RES-Q), which forms the basis of the Angels award system (gold/platinum/diamond) for all stroke-ready hospitals across the world.The Angels Initiative has supported over 1700 hospitals (>1000 in LMICs) that did not previously treat stroke patients to become "stroke ready." Since its inception in 2016, the Angels Initiative has impacted the health outcomes of an estimated 7.46 million stroke patients globally (including an estimated 4.68 million patients in LMICs). The Angels Initiative has increased the number of stroke-ready hospitals in many countries (e.g. in South Africa: 5 stroke-ready hospitals in 2015 vs 185 in 2021), reduced "door to treatment time" (e.g. in Egypt: 50% reduction vs baseline), and increased quality monitoring substantially.The focus of the work of the Angels Initiative has now expanded from the hyperacute phase of stroke treatment to the pre-hospital setting, as well as to the early post-acute setting. A continued and coordinated global effort is needed to achieve the target of the Angels Initiative of >10,000 stroke-ready hospitals by 2030, and >7500 of these in LMICs.

The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3): an international, stepped wedge cluster randomised controlled trial.

BACKGROUND: Early control of elevated blood pressure is the most promising treatment for acute intracerebral haemorrhage. We aimed to establish whether implementing a goal-directed care bundle incorporating protocols for early intensive blood pressure lowering and management algorithms for hyperglycaemia, pyrexia, and abnormal anticoagulation, implemented in a hospital setting, could improve outcomes for patients with acute spontaneous intracerebral haemorrhage. METHODS: We performed a pragmatic, international, multicentre, blinded endpoint, stepped wedge cluster randomised controlled trial at hospitals in nine low-income and middle-income countries (Brazil, China, India, Mexico, Nigeria, Pakistan, Peru, Sri Lanka, and Viet Nam) and one high-income country (Chile). Hospitals were eligible if they had no or inconsistent relevant, disease-specific protocols, and were willing to implement the care bundle to consecutive patients (aged ≥18 years) with imaging-confirmed spontaneous intracerebral haemorrhage presenting within 6 h of the onset of symptoms, had a local champion, and could provide the required study data. Hospitals were centrally randomly allocated using permuted blocks to three sequences of implementation, stratified by country and the projected number of patients to be recruited over the 12 months of the study period. These sequences had four periods that dictated the order in which the hospitals were to switch from the control usual care procedure to the intervention implementation of the care bundle procedure to different clusters of patients in a stepped manner. To avoid contamination, details of the intervention, sequence, and allocation periods were concealed from sites until they had completed the usual care control periods. The care bundle protocol included the early intensive lowering of systolic blood pressure (target <140 mm Hg), strict glucose control (target 6·1-7·8 mmol/L in those without diabetes and 7·8-10·0 mmol/L in those with diabetes), antipyrexia treatment (target body temperature ≤37·5°C), and rapid reversal of warfarin-related anticoagulation (target international normalised ratio <1·5) within 1 h of treatment, in patients where these variables were abnormal. Analyses were performed according to a modified intention-to-treat population with available outcome data (ie, excluding sites that withdrew during the study). The primary outcome was functional recovery, measured with the modified Rankin scale (mRS; range 0 [no symptoms] to 6 [death]) at 6 months by masked research staff, analysed using proportional ordinal logistic regression to assess the distribution in scores on the mRS, with adjustments for cluster (hospital site), group assignment of cluster per period, and time (6-month periods from Dec 12, 2017). This trial is registered at Clinicaltrials.gov (NCT03209258) and the Chinese Clinical Trial Registry (ChiCTR-IOC-17011787) and is completed. FINDINGS: Between May 27, 2017, and July 8, 2021, 206 hospitals were assessed for eligibility, of which 144 hospitals in ten countries agreed to join and were randomly assigned in the trial, but 22 hospitals withdrew before starting to enrol patients and another hospital was withdrawn and their data on enrolled patients was deleted because regulatory approval was not obtained. Between Dec 12, 2017, and Dec 31, 2021, 10 857 patients were screened but 3821 were excluded. Overall, the modified intention-to-treat population included 7036 patients enrolled at 121 hospitals, with 3221 assigned to the care bundle group and 3815 to the usual care group, with primary outcome data available in 2892 patients in the care bundle group and 3363 patients in the usual care group. The likelihood of a poor functional outcome was lower in the care bundle group (common odds ratio 0·86; 95% CI 0·76-0·97; p=0·015). The favourable shift in mRS scores in the care bundle group was generally consistent across a range of sensitivity analyses that included additional adjustments for country and patient variables (0·84; 0·73-0·97; p=0·017), and with different approaches to the use of multiple imputations for missing data. Patients in the care bundle group had fewer serious adverse events than those in the usual care group (16·0% vs 20·1%; p=0·0098). INTERPRETATION: Implementation of a care bundle protocol for intensive blood pressure lowering and other management algorithms for physiological control within several hours of the onset of symptoms resulted in improved functional outcome for patients with acute intracerebral haemorrhage. Hospitals should incorporate this approach into clinical practice as part of active management for this serious condition. FUNDING: Joint Global Health Trials scheme from the Department of Health and Social Care, the Foreign, Commonwealth & Development Office, and the Medical Research Council and Wellcome Trust; West China Hospital; the National Health and Medical Research Council of Australia; Sichuan Credit Pharmaceutic and Takeda China.

Posterior reversible encephalopathy syndrome following septicemia in patient with myasthenia gravis.

Posterior reversible encephalopathy syndrome is a clinicoradiologic entity characterized by seizure, headaches, visual symptoms, impaired consciousness, and vasogenic cerebral edema of occipital and parietal lobes of the brain. Magnetic resonance imaging (MRI) is the diagnostic gold standard. The pathophysiology of posterior reversible encephalopathy syndrome is still unknown, but it is thought to be closely related to several medical conditions including hypertension, preeclampsia, eclampsia, immunosuppressive agents, transplantation, and sepsis. We report a rare case of posterior reversible encephalopathy syndrome in patient with myasthenia gravis and sepsis. A 22-year-old male was diagnosed with myasthenia gravis combined with sepsis due to pneumonia. During his recovery, the patient suffered multiple generalized convulsions and subsequent loss of consciousness. On cranial MRI, the abnormalities were observed with hyperintense within the subcortical white matter of the temporal, parietal, and bilateral occipital lobes on T2-weighted and T2 FLAIR. Reversibility of the symptoms and characteristic imaging findings led us to a diagnosis of posterior reversible encephalopathy syndrome. Early recognition and management of posterior reversible encephalopathy syndrome as a cause of encephalopathy in patients with septicemia and myasthenia gravis is necessary to prevent secondary complications in this condition.