Low-calorie diet-induced weight loss is associated with altered brain connectivity and food desire in obesity.

OBJECTIVE: The main objective of this study is to better understand the effects of diet-induced weight loss on brain connectivity in response to changes in glucose levels in individuals with obesity. METHODS: A total of 25 individuals with obesity, among whom 9 had a diagnosis of type 2 diabetes, underwent functional magnetic resonance imaging (fMRI) scans before and after an 8-week low-calorie diet. We used a two-step hypereuglycemia clamp approach to mimic the changes in glucose levels observed in the postprandial period in combination with task-mediated fMRI intrinsic connectivity distribution (ICD) analysis. RESULTS: After the diet, participants lost an average of 3.3% body weight. Diet-induced weight loss led to a decrease in leptin levels, an increase in hunger and food intake, and greater brain connectivity in the parahippocampus, right hippocampus, and temporal cortex (limbic-temporal network). Group differences (with vs. without type 2 diabetes) were noted in several brain networks. Connectivity in the limbic-temporal and frontal-parietal brain clusters inversely correlated with hunger. CONCLUSIONS: A short-term low-calorie diet led to a multifaceted body response in patients with obesity, with an increase in connectivity in the limbic-temporal network (emotion and memory) and hormone and eating behavior changes that may be important for recovering the weight lost.

Clinical and Diagnostic Features of West Nile Virus Neuroinvasive Disease in New York City.

West Nile virus (WNV) neuroinvasive disease (WNND) occurs in approximately 1 percent of WNV-infected patients and typically presents as encephalitis, meningitis, or acute flaccid paralysis (AFP). WNND remains a difficult inpatient diagnosis, creating significant challenges for prognostication and therapy selection. We characterized the clinical and diagnostic features of WNND cases at two major academic medical centers in New York City in routine clinical practice. We retrospectively reviewed the charts of thirty-six patients with WNND, including twenty-six encephalitis, four meningitis, and six AFP cases. The most common presenting symptoms were fever (86.1%) and gastrointestinal symptoms (38.9%) in addition to altered mental status (72.2%), lethargy (63.9%), gait disturbances (46.2%), and headache (44.4%). Fourteen (48.3%) patients displayed acute magnetic resonance imaging (MRI) findings, particularly T2 hyperintensities in the bilateral thalami, brainstem, and deep white matter. New York State Department of Health WNV CSF IgM testing was utilized for diagnosis in 58.3% of patients; however, just 38.1% had the result by discharge, compared to 85.6% of those who underwent serum IgM testing. The median length of stay was 13.5 days, 38.9% were intubated, and three patients (8.9%) died during acute hospitalization. Our findings underscore the morbidity, mortality, and diagnostic challenges of WNND, suggesting the potential utility of serum IgM testing in combination with confirmatory CSF testing to expedite diagnosis in the acute setting.

Age-specific prevalence of IgG against measles/rubella and the impact of routine and supplementary immunization activities: A multistage random cluster sampling study with mathematical modelling.

BACKGROUND: Vietnam continues to have measles and rubella outbreaks following supplementary immunization activities (SIA) and routine immunization despite both having high reported coverage. To evaluate immunization activities, age-specific immunity against measles and rubella, and the number of averted Congenital Rubella Syndrome (CRS) cases, must be estimated. METHODS: Dried blood spots were collected from 2091 randomly selected individuals aged 1-39 years. Measles and rubella virus-specific immunoglobulin G (IgG) were measured by enzyme immunoassay. Results were considered positive at ≥120 mIU/mL for measles and ≥10 IU/mL for rubella. The number of CRS cases averted by immunization since 2014 were estimated using mathematical modelling. RESULTS: Overall IgG seroprevalence was 99.7% (95%CI: 99.2-99.9) for measles and 83.6% (95%CI: 79.3-87.1) for rubella. Rubella IgG seroprevalence was higher among age groups targeted in the SIA than in non-targeted young adults (95.4% [95%CI: 92.9-97.0] vs 72.4% [95%CI: 63.1-80.1]; P < 0.001). The estimated number of CRS cases averted in 2019 by immunization activities since 2014 ranged from 126 (95%CI: 0-460) to 883 (95%CI: 0-2271) depending on the assumed postvaccination reduction in the force of infection. CONCLUSIONS: The results suggest the SIA was effective, while young adults born before 1998 who remain unprotected for rubella require further vaccination.

Poorly Differentiated Hepatocellular Carcinoma Cells Avoid Apoptosis by Interacting with T Cells via CD40-CD40L Linkage.

Hepatocellular carcinoma (HCC) was associated with increased soluble CD40 levels in a previous study. This study aimed to investigate CD40's role in liver tumor progression. CD40 levels were examined in HCC patient tissues and various HCC cell lines, and their interaction with CD4+T cells was studied. RNA sequencing analysis was performed to explore the mechanisms of CD40 induction. Poorly differentiated HCC tumor tissues exhibited high membrane-bound CD40 expression, in contrast to nontumor areas. Poorly differentiated HCC cell lines showed high expression of membrane-bound CD40 with low CD40 promoter methylation, which was opposite of well-differentiated ones. Solely modulating CD40 expression in HCC cells exerted no direct consequences on cell growth or appearance. Interestingly, HLFs co-cultured with activated (CD40 ligand+) CD4+ T cells increased CD40 levels and showed a modest 3.2% dead cells, then increased to 10.9% underwent preneutralizing CD40 condition, whereas preblocking both CD40 and integrin α5ß1 concomitantly caused only 1.9% cell death. RNA sequencing of co-cultured HLFs with activated CD4+ T cells revealed the up-regulation of interferon and immune-response pathways. Increased interferon-γ levels in the activated T-cell media stimulated the Janus kinase/signal transducer and activator of transcription 3 pathway, resulting in increased CD40 expression in HLF. Collectively, CD40 expression in poorly differentiated HCC cells prevents cell death by interacting with CD40 ligand in activated T cells. Targeting CD40 may represent a promising anticancer therapy.

Tailoring the Photophysical Properties of a Homoleptic Iron(II) Tetra N-Heterocyclic Carbene Complex by Attaching an Imidazolium Group to the (C∧N∧C) Pincer Ligand─A Comparative Study.

We here report the synthesis of the homoleptic iron(II) N-heterocyclic carbene (NHC) complex [Fe(miHpbmi)2](PF6)4 (miHpbmi = 4-((3-methyl-1H-imidazolium-1-yl)pyridine-2,6-diyl)bis(3-methylimidazol-2-ylidene)) and its electrochemical and photophysical properties. The introduction of the π-electron-withdrawing 3-methyl-1H-imidazol-3-ium-1-yl group into the NHC ligand framework resulted in stabilization of the metal-to-ligand charge transfer (MLCT) state and destabilization of the metal-centered (MC) states. This resulted in an improved excited-state lifetime of 16 ps compared to the 9 ps for the unsubstituted parent compound [Fe(pbmi)2](PF6)2 (pbmi = (pyridine-2,6-diyl)bis(3-methylimidazol-2-ylidene)) as well as a stronger MLCT absorption band extending more toward the red spectral region. However, compared to the carboxylic acid derivative [Fe(cpbmi)2](PF6)2 (cpbmi = 1,1'-(4-carboxypyridine-2,6-diyl)bis(3-methylimidazol-2-ylidene)), the excited-state lifetime of [Fe(miHpbmi)2](PF6)4 is the same, but both the extinction and the red shift are more pronounced for the former. Hence, this makes [Fe(miHpbmi)2](PF6)4 a promising pH-insensitive analogue of [Fe(cpbmi)2](PF6)2. Finally, the excited-state dynamics of the title compound [Fe(miHpbmi)2](PF6)4 was investigated in solvents with different viscosities, however, showing very little dependency of the depopulation of the excited states on the properties of the solvent used.

How Rigidity and Conjugation of Bidentate Ligands Affect the Geometry and Photophysics of Iron N-Heterocyclic Complexes: A Comparative Study.

Two iron complexes featuring the bidentate, nonconjugated N-heterocyclic carbene (NHC) 1,1'-methylenebis(3-methylimidazol-2-ylidene) (mbmi) ligand, where the two NHC moieties are separated by a methylene bridge, have been synthesized to exploit the combined influence of geometric and electronic effects on the ground- and excited-state properties of homoleptic FeIII-hexa-NHC [Fe(mbmi)3](PF6)3 and heteroleptic FeII-tetra-NHC [Fe(mbmi)2(bpy)](PF6)2 (bpy = 2,2'-bipyridine) complexes. They are compared to the reported FeIII-hexa-NHC [Fe(btz)3](PF6)3 and FeII-tetra-NHC [Fe(btz)2(bpy)](PF6)2 complexes containing the conjugated, bidentate mesoionic NHC ligand 3,3'-dimethyl-1,1'-bis(p-tolyl)-4,4'-bis(1,2,3-triazol-5-ylidene) (btz). The observed geometries of [Fe(mbmi)3](PF6)3 and [Fe(mbmi)2(bpy)](PF6)2 are evaluated through L-Fe-L bond angles and ligand planarity and compared to those of [Fe(btz)3](PF6)3 and [Fe(btz)2(bpy)](PF6)2. The FeII/FeIII redox couples of [Fe(mbmi)3](PF6)3 (-0.38 V) and [Fe(mbmi)2(bpy)](PF6)2 (-0.057 V, both vs Fc+/0) are less reducing than [Fe(btz)3](PF6)3 and [Fe(btz)2(bpy)](PF6)2. The two complexes show intense absorption bands in the visible region: [Fe(mbmi)3](PF6)3 at 502 nm (ligand-to-metal charge transfer, 2LMCT) and [Fe(mbmi)2(bpy)](PF6)2 at 410 and 616 nm (metal-to-ligand charge transfer, 3MLCT). Lifetimes of 57.3 ps (2LMCT) for [Fe(mbmi)3](PF6)3 and 7.6 ps (3MLCT) for [Fe(mbmi)2(bpy)](PF6)2 were probed and are somewhat shorter than those for [Fe(btz)3](PF6)3 and [Fe(btz)2(bpy)](PF6)2. [Fe(mbmi)3](PF6)3 exhibits photoluminescence at 686 nm (2LMCT) in acetonitrile at room temperature with a quantum yield of (1.2 ± 0.1) × 10-4, compared to (3 ± 0.5) × 10-4 for [Fe(btz)3](PF6)3.

The ability of a 3-gene host signature in blood to distinguish tuberculous meningitis from other brain infections.

BACKGROUND: Tuberculous meningitis (TBM) is difficult to diagnose. We investigated whether a 3-gene host response signature in blood can distinguish TBM from other brain infections. METHODS: The expression of 3 genes (Dual specificity phosphatase 3- DUSP3, Guanylate-binding protein- GBP5, Krupple-like factor 2- KLF2) was analysed by RNA sequencing of archived whole blood from four cohorts of Vietnamese adults: 281 with TBM; 279 with pulmonary tuberculosis; 50 with other brain infections; and 30 healthy controls. 'TB scores' (combined 3-gene expression) were calculated following published methodology and discriminatory performance compared using area under a receiver operator characteristic curve (AUC). RESULTS: GBP5 was upregulated in TBM compared to other brain infections (p < 0.001), with no difference in DUSP3 and KLF2 expression. The diagnostic performance of GBP5 alone (AUC 0.74 (95% CI 0.67-0.81)) was slightly better than the 3-gene TB score (AUC 0.66, 95% CI 0.58-0.73) in TBM. Both GBP5 expression and TB score were higher in HIV-positive participants (P < 0.001), with good diagnostic performance of GBP5 alone (AUC 0.86, 95% CI 0.80-0.93). CONCLUSION: The 3-gene host signature in whole blood has the ability to discriminate TBM from other brain infections, including in HIV-positive individuals. Validation in large prospective diagnostic study is now required.

A humanized orthotopic mouse model for preclinical evaluation of immunotherapy in Ewing sarcoma.

The advent of novel cancer immunotherapy approaches is revolutionizing the treatment for cancer. Current small animal models for most cancers are syngeneic or genetically engineered mouse models or xenograft models based on immunodeficient mouse strains. These models have been limited in evaluating immunotherapy regimens due to the lack of functional human immune system. Development of animal models for bone cancer faces another challenge in the accessibility of tumor engraftment sites. Here, we describe a protocol to develop an orthotopic humanized mouse model for a bone and soft tissue sarcoma, Ewing sarcoma, by transplanting fresh human cord blood CD34+ hematopoietic stem cells into young NSG-SGM3 mice combined with subsequent Ewing sarcoma patient derived cell engraftment in the tibia of the humanized mice. We demonstrated early and robust reconstitution of human CD45+ leukocytes including T cells, B cells, natural killer cells and monocytes. Ewing sarcoma xenograft tumors successfully orthotopically engrafted in the humanized mice with minimal invasive procedures. We validated the translational utility of this orthotopic humanized model by evaluating the safety and efficacy of an immunotherapy antibody, magrolimab. Treatment with magrolimab induces CD47 blockade resulting in significantly decreased primary tumor growth, decreased lung metastasis and prolonged animal survival in the established humanized model. Furthermore, the humanized model recapitulated the dose dependent toxicity associated with the CD47 blockade as observed in patients in clinical trials. In conclusion, this orthotopic humanized mouse model of Ewing sarcoma represents an improved platform for evaluating immunotherapy in bone and soft tissue sarcoma, such as Ewing sarcoma. With careful design and optimization, this model is generalizable for other bone malignancies.

Validation of the accuracy of the modified World Federation of Neurosurgical Societies subarachnoid hemorrhage grading scale for predicting the outcomes of patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Evaluating the prognosis of patients with aneurysmal subarachnoid hemorrhage (aSAH) who may be at risk of poor outcomes using grading systems is one way to make a better decision on treatment for these patients. This study aimed to compare the accuracy of the modified World Federation of Neurosurgical Societies (WFNS), WFNS, and Hunt and Hess (H&H) Grading Scales in predicting the outcomes of patients with aSAH. METHODS: From August 2019 to June 2021, we conducted a multicenter prospective cohort study on adult patients with aSAH in three central hospitals in Hanoi, Vietnam. The primary outcome was the 90-day poor outcome, measured by a score of 4 (moderately severe disability) to 6 (death) on the modified Rankin Scale (mRS). We calculated the areas under the receiver operator characteristic (ROC) curve (AUROCs) to determine how well the grading scales could predict patient prognosis upon admission. We also used ROC curve analysis to find the best cut-off value for each scale. We compared AUROCs using Z-statistics and compared 90-day mean mRS scores among intergrades using the pairwise multiple-comparison test. Finally, we used logistic regression to identify factors associated with the 90-day poor outcome. RESULTS: Of 415 patients, 32% had a 90-day poor outcome. The modified WFNS (AUROC: 0.839 [95% confidence interval, CI: 0.795-0.883]; cut-off value≥2.50; PAUROC<0.001), WFNS (AUROC: 0.837 [95% CI: 0.793-0.881]; cut-off value≥3.5; PAUROC<0.001), and H&H scales (AUROC: 0.836 [95% CI: 0.791-0.881]; cut-off value≥3.5; PAUROC<0.001) were all good at predicting patient prognosis on day 90th after ictus. However, there were no significant differences between the AUROCs of these scales. Only grades IV and V of the modified WFNS (3.75 [standard deviation, SD: 2.46] vs 5.24 [SD: 1.68], p = 0.026, respectively), WFNS (3.75 [SD: 2.46] vs 5.24 [SD: 1.68], p = 0.026, respectively), and H&H scales (2.96 [SD: 2.60] vs 4.97 [SD: 1.87], p<0.001, respectively) showed a significant difference in the 90-day mean mRS scores. In multivariable models, with the same set of confounding variables, the modified WFNS grade of III to V (adjusted odds ratio, AOR: 9.090; 95% CI: 3.494-23.648; P<0.001) was more strongly associated with the increased risk of the 90-day poor outcome compared to the WFNS grade of IV to V (AOR: 6.383; 95% CI: 2.661-15.310; P<0.001) or the H&H grade of IV to V (AOR: 6.146; 95% CI: 2.584-14.620; P<0.001). CONCLUSIONS: In this study, the modified WFNS, WFNS, and H&H scales all had good discriminatory abilities for the prognosis of patients with aSAH. Because of the better effect size in predicting poor outcomes, the modified WFNS scale seems preferable to the WFNS and H&H scales.

High-flow nasal cannula therapy in patients with COVID-19 in intensive care units in a country with limited resources: a single-center experience.

OBJECTIVE: This study was performed to determine the outcomes of patients with coronavirus disease 2019 (COVID-19) who developed hypoxemic respiratory failure necessitating high-flow nasal cannula (HFNC) therapy and to identify the predictors of HFNC therapy success. METHODS: This retrospective observational study involved all patients treated with HFNC therapy at a center for COVID-19 in Viet Nam from August to October 2021. RESULTS: The study recruited 302 patients. Of these 302 patients, 171 (56.6%) underwent successful HFNC therapy, and the all-cause mortality rate was 33.44%. Non-critical COVID-19 and a higher respiratory rate-oxygenation (ROX) index at 48 hours after initiating HFNC therapy were independently correlated with HFNC therapy success. The statistically significant predictors of HFNC therapy success were younger age, non-critical COVID-19, a higher platelet count when starting HFNC therapy, and a higher ROX index at 24, 36, and 48 hours after HFNC therapy initiation. CONCLUSIONS: HFNC therapy appears to be effective in patients with COVID-19 who develop respiratory failure requiring respiratory support. Non-critical COVID-19 and a higher ROX index measured 48 hours after HFNC therapy initiation might serve as predictive factors for the success of HFNC therapy.

Sex disparity in stroke outcomes in a multicenter prospective stroke registry in Vietnam.

BACKGROUND: Although men have a higher rate of stroke than women, it is not clear whether women have a worse outcome after adjusting for confounders such as vascular risk factors, age, stroke severity, and reperfusion therapy. We evaluated sex differences on 90-day functional outcomes after stroke in a multicenter study in Vietnam. METHODS: We recruited patients presenting with ischemic or hemorrhagic stroke at 10 stroke centers in Vietnam for a period of 1 month from 1 August 2022 to 31 August 2022. We reviewed the patient's clinical demographics, time from symptom onset to hospital admission, stroke classification, stroke subtype, stroke severity, characteristics of reperfusion therapy, and 90-day clinical outcome. We compared functional outcomes and predisposing factors at day 90 between men and women after an ischemic and hemorrhagic stroke. Poor outcome was defined as modified Rankin Scale 3-6. RESULTS: There were 2300 stroke patients included. Men accounted for 61.3% (1410) of participants. Compared to men, women were older (67.7 ± 13.9 vs 63.7 ± 13.3, P < 0.001), had a higher rate of diabetes mellitus (21.1% vs 15.3%, P < 0.001), a lower rate of tobacco use (1.0 % vs 23.6%, P < 0.001), and a lower body mass index (21.4 ± 2.70 vs 22.0 ± 2.72, P < 0.001). There was a higher rate of intracranial hemorrhage (ICH) in men (21.3% vs 15.6%, P = 0.001), whereas the rate of subarachnoid hemorrhage was higher in women (6.2% vs 3.0%, P < 0.001). For ischemic stroke, door-to-needle time (36.9 ± 17.6 vs 47.8 ± 35.2 min, P = 0.04) and door-to-recanalization time (113.6 ± 51.1 vs 134.2 ± 48.2, P = 0.03) were shorter in women. There was no difference in 90-day functional outcomes between sexes. Factors associated with poor outcomes included age ⩾50 years (adjusted odds ratio (aOR): 1.75; 95% confidence interval (CI): 1.16-2.66), history of stroke (aOR: 1.50; 95% CI: 1.15-1.96), large artery atherosclerosis (aOR: 5.19; 95% CI: 3.90-6.90), and cardioembolism (aOR: 3.21; 95% CI: 1.68-6.16). Factors associated with mortality in patients with acute ischemic stroke included a history of coronary artery disease (aOR: 3.04; 95% CI: 1.03-8.92), large artery atherosclerosis (aOR: 3.37; 95% CI: 2.11-5.37), and cardioembolism (aOR: 3.15; 95% CI: 1.20-8.27). CONCLUSION: There were no sex differences in the clinical outcome of stroke and ischemic stroke in this prospective cohort of hospitalized Vietnamese patients.

Predictive validity of the prognosis on admission aneurysmal subarachnoid haemorrhage scale for the outcome of patients with aneurysmal subarachnoid haemorrhage.

This multicentre prospective cohort study aimed to compare the accuracy of the PAASH, WFNS, and Hunt and Hess (H&H) scales in predicting the outcomes of adult patients with aneurysmal SAH presented to three central hospitals in Hanoi, Vietnam, from August 2019 to June 2021. Of 415 eligible patients, 32.0% had a 90-day poor outcome, defined as an mRS score of 4 (moderately severe disability) to 6 (death). The PAASH, WFNS and H&H scales all have good discriminatory abilities for predicting the 90-day poor outcome. There were significant differences in the 90-day mean mRS scores between grades I and II (p = 0.001) and grades II and III (p = 0.001) of the PAASH scale, between grades IV and V (p = 0.026) of the WFNS scale, and between grades IV and V (p < 0.001) of the H&H scale. In contrast to a WFNS grade of IV-V and an H&H grade of IV-V, a PAASH grade of III-V was an independent predictor of the 90-day poor outcome. Because of the more clearly significant difference between the outcomes of the adjacent grades and the more strong effect size for predicting poor outcomes, the PAASH scale was preferable to the WFNS and H&H scales.

Monitoring the effects of urbanization and flood hazards on sandy ecosystem services.

Urbanization, storms, and floods have compromised the benefits derived from various types of sand dune landscapes, particularly in developing countries located in humid monsoon tropical regions. One pertinent question is which driving forces have had a dominant impact on the contributions of sand dune ecosystems to human well-being. Has the decline in sand dune ecosystem services (ES) been primarily due to urbanization or flooding hazards? This study aims to address these issues by developing a Bayesian Belief Network (BBN) to analyze six different sand dune landscapes worldwide. The study uses various data types, including multi-temporal and -sensor remote sensing (SAR and optical data), expert knowledge, statistics, and GIS to analyze the trends in sand dune ecosystems. A support tool based on probabilistic approaches was developed to assess changes in ES over time due to the effects of urbanization and flooding. The developed BBN has the potential to assess the ES values of sand dunes during both rainy and dry seasons. The study calculated and tested the ES values in detail over six years (from 2016 to 2021) in Quang Nam province, Vietnam. The results showed that urbanization has led to an increase in the total ES values since 2016, while floods only had a minimal impact on dune ES values during the rainy season. The fluctuations of ES values were found to be more significant due to urbanization than floods. The study's approach can be useful in future research on coastal ecosystems.

Factors related to intracerebral haematoma in patients with aneurysmal subarachnoid haemorrhage in Vietnam: a multicentre prospective cohort study.

OBJECTIVES: To investigate the impact of intracerebral haematoma (ICH) on the outcomes and the factors related to an ICH in patients with aneurysmal subarachnoid haemorrhage (aSAH) in a low- and middle-income country. DESIGN: A multicentre prospective cohort study. SETTING: Three central hospitals in Hanoi, Vietnam. PARTICIPANTS: This study included all patients (≥18 years) presenting with aSAH to the three central hospitals within 4 days of ictus, from August 2019 to June 2021, and excluded patients for whom the admission Glasgow Coma Scale was unable to be scored or patients who became lost at 90 days of follow-up during the study. OUTCOME MEASURES: The primary outcome was ICH after aneurysm rupture, defined as ICH detected on an admission head CT scan. The secondary outcomes were 90-day poor outcomes and 90-day death. RESULTS: Of 415 patients, 217 (52.3%) were females, and the median age was 57.0 years (IQR: 48.0-67.0). ICH was present in 20.5% (85/415) of patients with aSAH. There was a significant difference in the 90-day poor outcomes (43.5% (37/85) and 29.1% (96/330); p=0.011) and 90-day mortality (36.5% (31/85) and 20.0% (66/330); p=0.001) between patients who had ICH and patients who did not have ICH. The multivariable regression analysis showed that systolic blood pressure (SBP) ≥140 mm Hg (adjusted odds ratio (AOR): 2.674; 95% CI: 1.372 to 5.214; p=0.004), World Federation of Neurosurgical Societies (WFNS) grades II (AOR: 3.683; 95% CI: 1.250 to 10.858; p=0.018) to V (AOR: 6.912; 95% CI: 2.553 to 18.709; p<0.001) and a ruptured middle cerebral artery (MCA) aneurysm (AOR: 3.717; 95% CI: 1.848 to 7.477; p<0.001) were independently associated with ICH on admission. CONCLUSIONS: In this study, ICH was present in a substantial proportion of patients with aSAH and contributed significantly to a high rate of poor outcomes and death. Higher SBP, worse WFNS grades and ruptured MCA aneurysms were independently associated with ICH on admission.

Characterization of neurotropic HPAI H5N1 viruses with novel genome constellations and mammalian adaptive mutations in free-living mesocarnivores in Canada.

The GsGd lineage (A/goose/Guangdong/1/1996) H5N1 virus was introduced to Canada in 2021/2022 through the Atlantic and East Asia-Australasia/Pacific flyways by migratory birds. This was followed by unprecedented outbreaks affecting domestic and wild birds, with spillover into other animals. Here, we report sporadic cases of H5N1 in 40 free-living mesocarnivore species such as red foxes, striped skunks, and mink in Canada. The clinical presentations of the disease in mesocarnivores were consistent with central nervous system infection. This was supported by the presence of microscopic lesions and the presence of abundant IAV antigen by immunohistochemistry. Some red foxes that survived clinical infection developed anti-H5N1 antibodies. Phylogenetically, the H5N1 viruses from the mesocarnivore species belonged to clade 2.3.4.4b and had four different genome constellation patterns. The first group of viruses had wholly Eurasian (EA) genome segments. The other three groups were reassortant viruses containing genome segments derived from both North American (NAm) and EA influenza A viruses. Almost 17 percent of the H5N1 viruses had mammalian adaptive mutations (E627 K, E627V and D701N) in the polymerase basic protein 2 (PB2) subunit of the RNA polymerase complex. Other mutations that may favour adaptation to mammalian hosts were also present in other internal gene segments. The detection of these critical mutations in a large number of mammals within short duration after virus introduction inevitably highlights the need for continually monitoring and assessing mammalian-origin H5N1 clade 2.3.4.4b viruses for adaptive mutations, which potentially can facilitate virus replication, horizontal transmission and posing pandemic risks for humans.

Dimethyl Itaconate Inhibits Melanogenesis in B16F10 Cells.

Itaconate is a metabolite produced to counteract and resolve pro-inflammatory responses when macrophages are challenged with intracellular or extracellular stimuli. In the present study, we have observed that dimethyl itaconate (DMI) inhibits melanogenesis in B16F10 cells. DMI inhibits microphthalmia-associated transcription factor (MITF) and downregulates the expression of MITF target genes, such as tyrosinase (TYR), tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2). DMI also decreases the level of melanocortin 1 receptor (MC1R) and the production of α-melanocyte stimulating hormone (α-MSH), resulting in the inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) and MITF activities. The structure-activity relationship (SAR) study illustrates that the α,ß-unsaturated carbonyl moiety in DMI, a moiety required to target KELCH-like ECH-associated protein 1 (KEAP1) to activate NF-E2-related factor 2 (NRF2), is necessary to inhibit melanogenesis and knocking down Nrf2 attenuates the inhibition of melanogenesis by DMI. Together, our study reveals that the MC1R-ERK1/2-MITF axis regulated by the KEAP1-NRF2 pathway is the molecular target responsible for the inhibition of melanogenesis by DMI.

Sequential Organ Failure Assessment (SOFA) Score for predicting mortality in patients with sepsis in Vietnamese intensive care units: a multicentre, cross-sectional study.

OBJECTIVES: To compare the accuracy of the Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) Scores in predicting mortality among intensive care unit (ICU) patients with sepsis in a low-income and middle-income country. DESIGN: A multicentre, cross-sectional study. SETTING: A total of 15 adult ICUs throughout Vietnam. PARTICIPANTS: We included all patients aged ≥18 years who were admitted to ICUs for sepsis and who were still in ICUs from 00:00 to 23:59 of the specified study days (ie, 9 January, 3 April, 3 July and 9 October of the year 2019). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was hospital all-cause mortality (hospital mortality). We also defined the secondary outcome as all-cause deaths in the ICU (ICU mortality). RESULTS: Of 252 patients, 40.1% died in hospitals, and 33.3% died in ICUs. SOFA Score (areas under the receiver operating characteristic curve (AUROC): 0.688 (95% CI 0.618 to 0.758); cut-off value≥7.5; PAUROC<0.001) and APACHE II Score (AUROC: 0.689 (95% CI 0.622 to 0.756); cut-off value ≥20.5; PAUROC<0.001) both had a poor discriminatory ability for predicting hospital mortality. However, the discriminatory ability for predicting ICU mortality of SOFA (AUROC: 0.713 (95% CI 0.643 to 0.783); cut-off value≥9.5; PAUROC<0.001) was fair and was better than that of APACHE II Score (AUROC: 0.672 (95% CI 0.603 to 0.742); cut-off value≥18.5; PAUROC<0.001). A SOFA Score≥8 (adjusted OR (AOR): 2.717; 95% CI 1.371 to 5.382) and an APACHE II Score≥21 (AOR: 2.668; 95% CI 1.338 to 5.321) were independently associated with an increased risk of hospital mortality. Additionally, a SOFA Score≥10 (AOR: 2.194; 95% CI 1.017 to 4.735) was an independent predictor of ICU mortality, in contrast to an APACHE II Score≥19, for which this role did not. CONCLUSIONS: In this study, SOFA and APACHE II Scores were worthwhile in predicting mortality among ICU patients with sepsis. However, due to better discrimination for predicting ICU mortality, the SOFA Score was preferable to the APACHE II Score in predicting mortality.Clinical trials registry - India: CTRI/2019/01/016898.

Knowledge and medication adherence of oral anticoagulant-taking patients in Vietnam.

Background: Oral anticoagulants for venous thromboembolism are not thoroughly managed in ambulatory settings in low-/middle-income countries, primarily because of patients' neglect of medication knowledge and adherence. Objectives: This study was conducted to investigate patient knowledge, adherence, and the associated factors at a Vietnamese tertiary hospital, serving as a reference for educational programs in other local and regional health care facilities. Methods: A randomly recruited cross-sectional study was conducted on patients using vitamin K antagonists (VKA) or direct oral anticoagulants (DOAC). The primary and secondary outcomes were the knowledge score (in percent) and adherence to oral anticoagulants. Student's t-tests or chi-squared tests were used to compare the crude differences in mean or proportion between patients taking VKA and DOAC. Regression models were conducted to adjust the potential confounders and determine factors associated with patient knowledge and adherence. Results: A total of 199 patients were included. After adjusting for potential confounders, patients receiving a DOAC had similar knowledge scores and levels of adherence compared with those taking VKA, with both groups being suboptimal. Previous counseling was associated with higher knowledge. Better medication knowledge, female sex, and no history of venous thromboembolism were associated with better adherence. Conclusion: Good knowledge and adherence of oral anticoagulant-taking patients remain limited in Southeast Asian clinical practice. Further studies in similar settings should examine the associations between these factors and the effectiveness of the regimens. More effective measures targeting patient knowledge and adherence should be implemented to optimize anticoagulation therapy, improve the patients' outcomes, and mitigate the associated adverse effects.

Post-stroke depression in Vietnamese patients is associated with decreased sleep quality and increased fatigue: a one-institution cross-sectional analysis.

PURPOSE: This study aimed to determine the prevalence of post-stroke depression (PSD) during the first year and its associated factors, especially focusing on sleep quality and fatigue severity. METHODS: A cross-sectional study was conducted among stroke patients in Vietnam's National Geriatric Hospital. Data were collected by using standardized questionnaires for interviewing and evaluating patients at the research site. Several covariables were presented including demographics, stroke-related characteristics, activities of daily living, post-stroke fatigue, and sleep quality (Pittsburgh Sleep Quality Index [PSQI] scale). PSD was assessed as an outcome variable through the Patient Health Questionnaire-9 scale. To summarize sociodemographic and clinical variables, descriptive statistics were performed. A logistic regression model was used to explore the factors related to PSD. RESULTS: Of 157 patients with stroke, mean age 73.1 (± 9.6), PSD was present in 60 patients (38%). The global score and all PSQI components of participants with PSD showed worse levels than those without depression. Furthermore, the prevalence of PSD was higher in patients with low IADL scores and functional disability at high levels. In the multivariate logistic regression analysis, the patients with PSD showed higher Fatigue Severity Scale (FSS) scores (OR = 4.11; 95% CI = 1.39; 12.19) and higher scores in two domains of the PSQI scale including subjective sleep quality (OR = 3.03; 95% CI = 1.21; 7.58) and sleep disturbance (OR = 5.22; 95% CI = 1.33; 20.47). CONCLUSION: There is a significant prevalence of depression following stroke. Furthermore, post-stroke fatigue and two PSQI scale components (subjective sleep quality and sleep disturbance) were shown to be associated with PSD. This finding may guide early screening and intervention strategies to address depression following stroke.