Discovery of Alkyl Triphenylphosphonium Pinostrobin Derivatives as Potent Anti-Breast Cancer Agents.

Pinostrobin demonstrated anticancer properties, but its hydrophobic feature led to a reduction in bioavailability. The mitochondria-targeted approach successfully synthesized eight new alkyl triphenylphosphonium pinostrobin derivatives (1-8) with good yield in this study. Seven compounds (1-3, 5-8) showed greater cytotoxic potency against the human MCF-7 breast cancer cell line than pinostrobin. Molecular docking studies were performed with two important targets in hormone-dependent anticancer strategies, estrogen receptor α (ERα) ligand binding domains, 3ERT (antagonist recognition and antiproliferative function), and 1GWR (agonist recognition and pro-proliferative function). In addition, the MD simulation study of the two most potent compounds (2 and 3) complexed with both ERα forms suggested that compounds 2 and 3 could serve as favourable antagonists. Furthermore, the in silico ADMET prediction indicated that compounds 2 and 3 could be potential drug candidates.

A comparison between the enzymatic oxidation method and headspace gas chromatography with a flame ionization detector in the determination of postmortem blood ethanol.

Ethanol is the most commonly encountered substance in forensic toxicology. Determining blood alcohol concentration (BAC) in autopsies accounts for the majority of work in forensic diagnosis. The most common method to assess BAC is the enzymatic oxidation method because of its low cost, easy operation, and high throughput. Still, the elevated lactate and lactate dehydrogenase (LDH) levels in postmortem blood may affect accuracy. This study uses headspace gas chromatography with a flame ionization detector (HS-GC/FID) to assess the interference of lactate and LDH levels on BAC in 110 autopsied blood samples determined by the enzymatic oxidation method. The results showed that lactate and LDH levels in postmortem blood were higher than in normal blood. There was a weak correlation between the lactate levels and BAC difference (r = 0.23, p < 0.05) and a strong correlation between LDH levels and BAC difference (r = 0.67, p < 0.001). The differentiation of BAC between the enzymatic oxidation method and HS-GC/FID was significant (p < 0.001), confirming the interference significantly. All postmortem blood samples with lactate and LDH levels higher than regular lead to a positive error in determining BAC by enzymatic oxidation method. The study results suggest that the HS-GC/FID method should be used to determine BAC in postmortem blood samples instead of the enzymatic oxidation method to avoid mistakes in forensic diagnosis.

Therapeutic plasma exchange and continuous renal replacement therapy in pediatric dengue-associated acute liver failure: A case series from Vietnam.

BACKGROUND AND OBJECTIVES: Paediatric dengue-associated acute liver failure (PALF) is a rare and fatal complication. To date, clinical data regarding the combination of therapeutic plasma exchange (TPE) and continuous renal replacement therapy (CRRT) for the treatment of dengue-associated PALF are limited. METHODS: We conducted a single-center, retrospective study of all children with dengue-associated PALF admitted to the paediatric intensive care unit of Children Hospital No.2, Vietnam, who were treated with TPE+CRRT between January 2021 and March 2022. The main study outcomes were in-hospital survival, normalisation of hepatic function, and hepatic encephalopathy improvement. RESULTS: Twelve patients aged from 06 to 12 years underwent TPE+CRRT procedures. Among them, three (25 %) patients died of severe sepsis and septic shock confirmed by Enterobacteriaceae spp. haemocultures (stable on maintenance treatment of COVID-19-associated MIS-C with low dose of oral steroids on hospital admission), acute respiratory distress syndrome (ARDS), and clinically apparent intracranial haemorrhage. Nine patients (75 %) survived. The paediatric mortality risk score improved significantly at discharge compared with PICU admission (P < 0.01). Markedly, all twelve patients were diagnosed with hepatoencephalopathy of grades III and IV on PICU admission. After the combined TPE+CRRT interventions, there were substantial improvements in liver transaminases levels, coagulation profiles, and metabolic biomarkers. Normal neurological functions were observed in nine alive patients at hospital discharge. Only one patient experienced an adverse event of slightly low blood pressure, which rapidly self-resolved. INTERPRETATION AND CONCLUSIONS: Combined TPE+CRRT significantly improved survival outcome, neurological status, and rapid normalisation of liver functions in dengue-associated PALF.

Half-topological state in magnetic topological insulators.

We predict a novel topological state,half-topological state, in magnetic topological insulators. The topological state is characterized by different topologies of electrons with different spin orientations, i.e., electrons with one spin orientation occupy a nontrivial topological insulating state, while electrons with opposite orientation occupy another insulating state with trivial topology. We demonstrate the occurrence of the half-topological state in magnetic topological insulators by employing a minimal model. The minimal model is a combination of the spinful Haldane and the double-exchange models. The double-exchange processes maintain a spontaneous magnetic ordering, while the next-nearest-neighbor hopping in the Haldane model gives rise to a nontrivial topological insulator. The minimal model is studied by applying the dynamical mean field theory. It is found that the long-range antiferromagnetic ordering drives the system from either topological or topologically trivial antiferromagnetic insulator to the half-topological state, and finally to topologically trivial antiferromagnetic insulator. The equations for the topological phase transitions are also explicitly derived.

Unspecified opioids among opioid overdoses in Oslo, Norway.

OBJECTIVE: Since 2017, an increasing number of opioid overdoses in Oslo, Norway, has been categorized as involving unspecified opioids, as noted in the patient records by the doctor treating the patient. In this study we compare the characteristics of overdoses involving unspecified opioids, long-acting opioids, and heroin. Data on patients presenting with opioid overdose was retrospectively collected from 1 October 2013 to 31 December 2019 at the Oslo Accident and Emergency Outpatient Clinic. RESULTS: Among 2381 included cases, 459 (19.3%) involved unspecified opioids, 134 (5.6%) long-acting opioids, and 1788 (75.1%) heroin. Overdoses involving unspecified opioids needed longer observation, median 5 h 29 min vs. 4 h 54 min (long-acting opioids) and 4 h 49 min (heroin) (p < 0.001), and had a lower Glasgow coma scale score, median 10 vs. 13 in both the other groups (p < 0.001). Naloxone was given in 23.3% of cases involving unspecified opioids, vs. 12.7% involving long-acting opioids and 30.2% involving heroin (p < 0.001). A larger proportion of patients were transferred to hospital care when unspecified or long-acting opioids were involved compared to heroin, 16.3% and 18.7% respectively vs. 10.1% (p < 0.001). Our results indicate that the category "unspecified opioids" encompasses a substantial proportion of opioids acting longer than heroin.

Diagnostic Value of Fluorescence Methods, Visual Inspection and Photographic Visual Examination in Initial Caries Lesion: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aimed to investigate the efficacy of fluorescence-based methods, visual inspections, and photographic visual examinations in initial caries detection. A literature search was undertaken in the PubMed and Cochrane databases. Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines were followed, and eligible articles published from 1 January 2009 to 30 October 2019 were included if they met the following criteria: they (1) assessed the accuracy of methods of detecting initial tooth caries lesions on occlusal, proximal, or smooth surfaces in both primary and permanent teeth (in clinical); (2) used a reference standard; (3) reported data regarding the sample size, prevalence of initial tooth caries, and accuracy of the methods. Data collection and extraction, quality assessment, and data analysis were conducted according to Cochrane standards Quality Assessment of Diagnostic Accuracy Studies-2. Statistical analyses were performed using Review Manager 5.3 and STATA 14.0. A total of 12 eligible articles were included in the meta-analysis. The results showed that the sensitivity and specificity of fluorescence-based methods were 80% and 80%, respectively; visual inspection was measured at 80% and 75%, respectively; photographic visual examination was measured at 67% and 79%, respectively. We found that the visual method and the fluorescence method were reliable for laboratory use to detect early-stage caries with equivalent accuracy.

The Combination of Adaptive Convolutional Neural Network and Bag of Visual Words in Automatic Diagnosis of Third Molar Complications on Dental X-Ray Images.

In dental diagnosis, recognizing tooth complications quickly from radiology (e.g., X-rays) takes highly experienced medical professionals. By using object detection models and algorithms, this work is much easier and needs less experienced medical practitioners to clear their doubts while diagnosing a medical case. In this paper, we propose a dental defect recognition model by the integration of Adaptive Convolution Neural Network and Bag of Visual Word (BoVW). In this model, BoVW is used to save the features extracted from images. After that, a designed Convolutional Neural Network (CNN) model is used to make quality prediction. To evaluate the proposed model, we collected a dataset of radiography images of 447 patients in Hanoi Medical Hospital, Vietnam, with third molar complications. The results of the model suggest accuracy of 84% ± 4%. This accuracy is comparable to that of experienced dentists and radiologists.