Optofluidic Sensor Based on Polymer Optical Microresonators for the Specific, Sensitive and Fast Detection of Chemical and Biochemical Species.

The accurate, rapid, and specific detection of DNA strands in solution is becoming increasingly important, especially in biomedical applications such as the trace detection of COVID-19 or cancer diagnosis. In this work we present the design, elaboration and characterization of an optofluidic sensor based on a polymer-based microresonator which shows a quick response time, a low detection limit and good sensitivity. The device is composed of a micro-racetrack waveguide vertically coupled to a bus waveguide and embedded within a microfluidic circuit. The spectral response of the microresonator, in air or immersed in deionised water, shows quality factors up to 72,900 and contrasts up to 0.9. The concentration of DNA strands in water is related to the spectral shift of the microresonator transmission function, as measured at the inflection points of resonance peaks in order to optimize the signal-over-noise ratio. After functionalization by a DNA probe strand on the surface of the microresonator, a specific and real time measurement of the complementary DNA strands in the solution is realized. Additionally, we have inferred the dissociation constant value of the binding equilibrium of the two complementary DNA strands and evidenced a sensitivity of 16.0 pm/µM and a detection limit of 121 nM.

Predictive Factors of Mortality in Patients with Severe COVID-19 Treated in the Intensive Care Unit: A Single-Center Study in Vietnam.

INTRODUCTION: The fourth outbreak of COVID-19 with the delta variant in Vietnam was very fierce due to the limited availability of vaccines and the lack of healthcare resources. During that period, the high mortality of patients with severe and critical COVID-19 caused many concerns for the health system, especially the intensive care units. This study aimed to analyze the predictive factors of death and survival in patients with severe and critical COVID-19. METHODS: We conducted a cross-sectional and descriptive study on 151 patients with severe and critical COVID-19 hospitalized in the Intensive Care Unit of Binh Duong General Hospital. RESULTS: Common clinical symptoms of severe and critical COVID-19 included shortness of breath (97.4%), fatigue (89.4%), cough (76.8%), chest pain (47.7%), loss of smell (48.3%), loss of taste (39.1%), and headache (21.2%). The abnormal biochemical features were leukopenia (2.1%), anemia, thrombocytopenia (18%), hypoxia with low PaO2 (34.6%), hypocapnia with reduced PaCO2 (29.6%), and blood acidosis (18.4%). Common complications during hospitalization were septic shock (15.2%), cardiogenic shock (5.3%), and embolism (2.6%). The predictive factors of death were being female, age > 65 years, cardiovascular comorbidity, thrombocytopenia (< 137.109/l), and hypoxia at inclusion or after the first week or blood acidosis (pH < 7.28). The use of a high dose of corticosteroids reduced the mortality during the first 3 weeks of hospitalization but significantly increased risk of death after 3 and 4 weeks. CONCLUSIONS: Common clinical symptoms, laboratory features, and death-related complications of critical and severe COVID-19 patients were found in Vietnamese patients during the fourth wave of the COVID-19 pandemic. The results of this study provide new insight into the predictive factors of mortality for patients with severe and critical COVID-19.

Prevalence of Thalassemia in the Vietnamese Population and Building a Clinical Decision Support System for Prenatal Screening for Thalassemia.

Introduction: The prevalence of thalassemia among the Vietnamese population was studied, and clinical decision support systems for prenatal screening of thalassemia were created. The aim of this report was to investigate the prevalence of thalassemia in the Vietnamese population, building a clinical decision support system for prenatal screening for thalassemia. Methods: A cross-sectional study was conducted on pregnant women and their husbands visiting the Vietnam National Hospital of Obstetrics and Gynecology from October 2020 to December 2021. A total of 10112 medical records of first-time pregnant women and their husbands were collected. Results: A clinical decision support system was built, including 2 different types of systems for prenatal screening for thalassemia (an expert system and 4 AI-based CDSS). One thousand nine hundred ninety-two cases were used to train and test machine learning models, while 1555 cases were used for specialized expert system evaluation. There were ten key variables for AI-based CDSS for machine learning. The four most important features in thalassemia screening were identified. The accuracy of the expert system and AI-based CDSS was compared. The rate of patients with Alpha thalassemia is 10.73% (1085 patients), the rate of patients with beta-thalassemia is 2.24% (227 patients), and 0.29% (29 patients) of patients carry both alpha-thalassemia and beta-thalassemia gene mutations. The expert system showed an accuracy of 98.45%. Among the AI-based CDSS developed, the multilayer perceptron (MLP) model was the most stable regardless of the training database (accuracy of 98,5% using all features and 97% using only the four most important features). Conclusions: When comparing the expert system with the AI-based CDSS, the accuracy of the expert system and AI-based models was comparable. The developed expert system for prenatal thalassemia screening showed high accuracy. AI-based CDSS showed satisfactory results. Further development of such systems is promising with a view to their introduction into clinical practice.

Guillain-Barré Syndrome in Patient With SARS-CoV-2 PCR Positivity Treated Successfully With Therapeutic Exchange Plasma: A First Case Report From Vietnam.

Since the first case of Guillain-Barré syndrome (GBS)-associated SARS-CoV-2 (COVID-19) infection reported in 2020, a series of cases have been published in some countries. In this case report, we present a young patient with GBS, whose clinical and laboratory data were appropriate for the diagnosis of GBS due to COVID-19 infection. Neurological examination revealed the muscular weakness of lower limbs with Medical Research Council (MRC) scale of 2/5 associated with diminished reflexes. Laboratory studies showed the positive nasal swab RT-PCR test for COVID-19, leukopenia, increased ferritin and LDH levels, normal electrolyte and liver and kidney function, and normal chest X-ray. The result of cerebrospinal fluid showed the albuminocytologic dissociation. The patient was treated with remdesivir, dexamethasone, anticoagulation, and therapeutic plasma exchange (TPE). Patient's muscle weakness was significantly improved after 1 week of admission. He was discharged at 23rd days of hospitalization and followed-up in the out-patients department.

Acute Respiratory Distress Syndrome Associated with Multisystem Inflammatory Syndrome in a Child with Covid-19 and Diabetic Ketoacidosis: A Case Report.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (Covid-19), has uncontrollable effects on many organs. A great number of previously published scientific reports have revealed that patients with diabetes mellitus face a more severe form of Covid-19 with a higher death rate. Here we present the case of a 13-year-old unvaccinated boy who was admitted to an intensive care unit (ICU) with a history of fever, cough, dyspnea, throat pain, nausea, and confusion that progressed to lethargy after 24 h. On clinical examination, he was in a coma with Kussmaul's breathing, and was anuric. His blood biochemical analysis demonstrated hyperglycemia, severe metabolic acidosis, kidney failure, electrolyte disturbances, and inflammation. Chest x-ray showed pneumonia and a pleural effusion. The results of the SARS-CoV-2 real-time polymerase chain reaction were positive. The patient was diagnosed with Covid-19-induced acute respiratory distress syndrome associated with multisystem inflammatory syndrome in children secondary to his acute respiratory failure, acute kidney injury, and new-onset type 1 diabetes mellitus with diabetic ketoacidosis. He was intubated for invasive mechanical ventilation and received a normal saline infusion and continuous insulin infusion (0.1 IU/kg/h) for the treatment of his diabetic ketoacidosis. He was also treated with methylprednisolone, aspirin, and heparin, and underwent continuous renal replacement therapy for acute renal failure for 9 days. The patient was discharged from ICU on day 16 and was followed up regularly as an outpatient with daily treatment, including subcutaneous insulin injection (30 IU/day) and a calcium channel blocker for hypertension (nifedipine 20 mg/day).

The Use of Therapeutic Plasma Exchange in the Treatment of a Pregnant Woman with COVID-19 Induced Acute Respiratory Distress Syndrome.

A 27-year-old woman at 17 weeks gestation was admitted to the intensive care unit (ICU) with a history of fever, dyspnea, and dry cough for 3 days. She was diagnosed with coronavirus disease 2019 (COVID-19) based on her nasopharyngeal swab polymerase chain reaction (PCR) that was positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the ICU, the patient developed acute respiratory distress syndrome (ARDS) and increased levels of inflammatory markers. She was then intubated for mechanical ventilation and had a treatment for critical COVID-19 illness during pregnancy. She also received three cycles on alternating days of therapeutic plasma exchange (TPE) since she was failing to respond to conventional medical treatment. During hospitalization, the patient's fetus was closely monitored by repetitive ultrasound. After 27 days of hospitalization and 10 days of mechanical ventilation weaning, the patient's respiratory condition improved and her inflammatory biomarkers normalized. She was discharged from the hospital with an apparently healthy 20th week fetus. This case report highlights the role of TPE for treatment of ARDS due to cytokine storm in pregnant women with severe COVID-19 infection. This case emphasizes that careful evaluation of clinical and biological progression of the patient's status is very important and when conventional therapies are failing, alternative therapies such as TPE should be considered.

Bradycardia unresponded to atropin testing was successfully treated with therapeutic plasma exchange in a patient with severe COVID-19 complicated by Guillain-Barré syndrome: A case report.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been an alarming situation worldwide for the past 2 years. The symptoms of coronavirus disease 2019 (COVID-19) are not only confined to the respiratory system but also affect a multitude of organ systems. Bradycardia associated with Guillain-Barré syndrome (GBS) is a rare autonomic and peripheral neurological complication of COVID-19. In this case report, we present the case of a 26-year-old man diagnosed with bradycardia associated with GBS after contracting COVID-19. Initially, this patient had the classical symptoms of COVID-19 and was hospitalized in the intensive care unit (ICU) for acute respiratory distress syndrome (ARDS). Then, he developed weakness in the lower extremities, diminished tendon reflexes, a loss of sensation without sphincter muscle disorders, and bradycardia. His bradycardia did not respond to atropine. The patient was treated concurrently with a high-flow nasal cannula, systemic corticosteroids, anticoagulation, and therapeutic plasma exchange (TPE) for COVID-19-induced ARDS, bradycardia, and GBS. His ARDS and bradycardia improved after the first cycle of TPE and medical treatment. After three cycles of TPE, the patient progressively recovered his muscle strength in the lower limbs and regained peripheral sensation. He was discharged from the hospital in stable condition after 4 weeks of hospitalization and was followed up after 6 months for cardiorespiratory and neurological complications. This case report elucidates the potential difficulties and challenges that physicians may encounter in diagnosing and treating COVID-19-induced bradycardia and GBS during the pandemic outbreak. However, the patient outcomes with the treatment combining the conventional treatment with therapeutic plasma exchange seem to be optimistic.

Direct Synthesis of Gold Nanoparticles in Polymer Matrix.

We report an original method for directly fabricating gold nanoparticles (Au NPs) in a polymer matrix using a thermal treatment technique and theoretically and experimentally investigate their plasmonic properties. The polymeric-metallic nanocomposite samples were first prepared by simply mixing SU-8 resist and Au salt with different concentrations. The Au NPs growth was triggered inside the polymer through a thermal process on a hot plate and in air environment. The Au NPs creation was confirmed by the color of the nanocomposite thin films and by absorption spectra measurements. The Au NPs sizes and distributions were confirmed by transmission electron microscope measurements. It was found that the concentrations of Au salt and the annealing temperatures and durations are all crucial for tuning the Au NPs sizes and distributions, and, thus, their optical properties. We also propose a simulation model for calculations of Au NPs plasmonic properties inside a polymer medium. We realized that Au NPs having large sizes (50 to 100 nm) play an important role in absorption spectra measurements, as compared to the contribution of small NPs (<20 nm), even if the relative amount of big Au NPs is small. This simple, low-cost, and highly reproducible technique allows us to obtain plasmonic NPs within polymer thin films on a large scale, which can be potentially applied to many fields.

A Study on the Fabrication of an Effective Natural Substance Based on Schisandra chinensis Extracted Fermentation.

PURPOSE: In this study, a high-efficiency Schisandra chinensis extract (SCE) produced by the fermentation of effective microorganisms (EM) was used as an antioxidant material in preparing cosmetic products. SUBJECTS AND METHODS: We conducted the study by extracting S. chinensis via EM fermentation to increase the efficiency. Tyrosinase inhibitory factor analysis, pH, and thermal stability were measured to verify the properties of the prepared products. RESULTS: The efficacy and whitening effects of the prepared substances were verified using tyrosinase inhibitory factor analysis. As a result, it was found that both the SCE and SCE fermentation (SCEF) exhibited high, naturally originating, antioxidation ability. In addition, the pH and thermal stability of the substances were evaluated to optimize the cosmetic fabrication conditions. In this context, as the concentration of the added extract increased, the pH value decreased. The evaluation of safety and stability indicated that the substances contained effective chemical components having antioxidant activity, suppressing skin aging, and whitening effects in a weak acid range consistent with a pH of 6.25-2.98. Furthermore, there were no safety problems with the use of the obtained products even after they had been stored for 60 days. CONCLUSION: The SCE substance is demonstrated as a possible material for cosmetic application.

Direct fabrication and characterization of gold nanohole arrays.

We demonstrate a one-step fabrication method to realize desired gold (Au) nanoholes arrays by using a one-photon absorption based direct laser writing technique. Thanks to the optically induced thermal effect of Au material at 532 nm excitation wavelength, the local temperature at the laser focus area can reach as high as 600°C, which induces an evaporation of the Au thin film resulting in a metallic nanohole. By controlling the laser spot movement and exposure time, different two-dimensional Au nanoholes structures with periodicity as small as 500 nm have been demonstrated. This allows obtaining plasmonic nanostructures in a single step without needing the preparation of polymeric template and lift-off process. By this direct fabrication technique, the nanoholes do not have circular shape as the laser focusing spot, due to the non-uniform heat transfer in a no-perfect flat Au film. However, the FDTD simulation results and the experimental measurement of the transmission spectra show that the properties of fabricated plasmonic nanoholes arrays are very close to those of ideal plasmonic nanostructures. Actually, the plasmonic resonance depends strongly on the periodicity of the metallic structures while the heterogeneous form of the holes simply enlarges the resonant peak. Furthermore, it is theoretically demonstrated that the non-perfect circular shape of the Au hole allows amplifying the electromagnetic field of the resonant peak by several times as compared to the case of perfect circular shape. This could be an advantage for application of this fabricated structure in laser and nonlinear optics domains.

Overcoming Wnt-ß-catenin dependent anticancer therapy resistance in leukaemia stem cells.

Leukaemia stem cells (LSCs) underlie cancer therapy resistance but targeting these cells remains difficult. The Wnt-ß-catenin and PI3K-Akt pathways cooperate to promote tumorigenesis and resistance to therapy. In a mouse model in which both pathways are activated in stem and progenitor cells, LSCs expanded under chemotherapy-induced stress. Since Akt can activate ß-catenin, inhibiting this interaction might target therapy-resistant LSCs. High-throughput screening identified doxorubicin (DXR) as an inhibitor of the Akt-ß-catenin interaction at low doses. Here we repurposed DXR as a targeted inhibitor rather than a broadly cytotoxic chemotherapy. Targeted DXR reduced Akt-activated ß-catenin levels in chemoresistant LSCs and reduced LSC tumorigenic activity. Mechanistically, ß-catenin binds multiple immune-checkpoint gene loci, and targeted DXR treatment inhibited expression of multiple immune checkpoints specifically in LSCs, including PD-L1, TIM3 and CD24. Overall, LSCs exhibit distinct properties of immune resistance that are reduced by inhibiting Akt-activated ß-catenin. These findings suggest a strategy for overcoming cancer therapy resistance and immune escape.

Effect of the Optimize Heart Failure Care Program on clinical and patient outcomes - The pilot implementation in Vietnam.

BACKGROUND: The Ho-Chi-Minh-city Heart Institute in Vietnam took part in the Optimize Heart Failure (OHF) Care Program, designed to improve outcomes following heart failure (HF) hospitalization by increasing patient awareness and optimizing HF treatment. METHODS: HF patients hospitalized with left ventricular ejection-fraction (LVEF) <50% were included. Patients received guideline-recommended HF treatment and education. Clinical signs, treatments and outcomes were assessed at admission, discharge, 2 and 6 months (M2, M6). Patients' knowledge and practice were assessed at M6 by telephone survey. RESULTS: 257 patients were included. Between admission and M2 and M6, heart rate decreased significantly, and clinical symptoms improved significantly. LVEF increased significantly from admission to M6. 85% to 99% of patients received education. At M6, 45% to 78% of patients acquired knowledge and adhered to practice regarding diet, exercise, weight control, and detection of worsening symptoms. High use of renin-angiotensin-aldosterone-system inhibitors (91%), mineralocorticoid-receptor-antagonists (77%) and diuretics (85%) was noted at discharge. Beta-blocker and ivabradine use was less frequent at discharge but increased significantly at M6 (from 33% to 51% and from 9% to 20%, respectively, p < 0.001). There were no in-hospital deaths. Readmission rates at 30 and 60 days after discharge were 8.3% and 12.5%, respectively. Mortality rates at 30 days, 60 days and 6 months were 1.2%, 2.5% and 6.4%, respectively. CONCLUSIONS: The OHF Care Program could be implemented in Vietnam without difficulty and was associated with high usage of guideline-recommended drug therapy. Although education was delivered, patient knowledge and practice could be further improved at M6 after discharge.

Redox-sensitive nanoparticles from amphiphilic cholesterol-based block copolymers for enhanced tumor intracellular release of doxorubicin.

A novel amphiphilic cholesterol-based block copolymer comprised of a polymethacrylate bearing cholesterol block and a polyethylene glycol block with reducible disulfide bonds (PC5MA-SS-PEO) was synthesized and evaluated as a redox-sensitive nanoparticulate delivery system. The self-assembled PC5MA-SS-PEO nanoparticles (SS-NPs) encapsulated the anticancer drug doxorubicin (DOX) with high drug loading (18.2% w/w) and high encapsulation efficiency (94.9%). DOX-encapsulated PC5MA-SS-PEO self-assembled nanoparticles (DOX-encapsulated SS-NPs) showed excellent stability and exhibited a rapid DOX release in response to dithiothreitol reductive condition. Importantly, following internalization by lung cancer cells, the reducible DOX-encapsulated SS-NPs achieved higher cytotoxicity than the non-reducible thioester NPs whereas blank nanoparticles were non-cytotoxic. Furthermore, in vivo imaging studies in tumor-bearing severe combined immunodeficiency (SCID) mice showed that the nanoparticles preferentially accumulated in tumor tissue with remarkably reduced accumulation in the healthy non-target organs. The results indicated that the SS-NPs may be a promising platform for cancer-cell specific delivery of hydrophobic anticancer drugs. FROM THE CLINICAL EDITOR: The use of nanocarriers for drug delivery against tumors has been under intense research. One problem of using carrier system is the drug release kinetics at tumor site. In this article, the authors continued their previous study in the development of an amphiphilic cholesterol-based block copolymer with redox-sensitive modification, so that the payload drug could be released in response to the microenvironment. The interesting results should provide a new direction for designing future novel nanocarrier systems.

Nanocomposite hydrogels based on liquid crystalline brush-like block copolymer-Au nanorods and their application in H2O2 detection.

New nanocomposite hydrogels from liquid crystalline brush-like block copolymers (LCBBCs) and gold nanorods (AuNRs) were synthesized and characterized. The hydrogels protected and stabilized AuNRs, which presented peroxidase-like activity and catalysed the oxidation of a substrate in the presence of H2O2 and elicited a sensitive chromogenic response. This reusable, table-top stable, free-standing nanocomposite hydrogel platform can be used to develop a simple and reproducible method to detect H2O2.

Long circulating self-assembled nanoparticles from cholesterol-containing brush-like block copolymers for improved drug delivery to tumors.

Amphiphilic brush-like block copolymers composed of polynorbonene-cholesterol/poly(ethylene glycol) (P(NBCh9-b-NBPEG)) self-assembled to form a long circulating nanostructure capable of encapsulating the anticancer drug doxorubicin (DOX) with high drug loading (22.1% w/w). The release of DOX from the DOX-loaded P(NBCh9-b-NBPEG) nanoparticles (DOX-NPs) was steady at less than 2% per day in PBS. DOX-NPs were effectively internalized by human cervical cancer cells (HeLa) and showed dose-dependent cytotoxicity, whereas blank nanoparticles were noncytotoxic. The DOX-NPs demonstrated a superior in vivo circulation time relative to that of free DOX. Tissue distribution and in vivo imaging studies showed that DOX-NPs preferentially accumulated in tumor tissue with markedly reduced accumulation in the heart and other vital organs. The DOX-NPs greatly improved survival and significantly inhibited tumor growth in tumor-bearing SCID mice compared to that for the untreated and free DOX-treated groups. The results indicated that self-assembled P(NBCh9-b-NBPEG) may be a useful carrier for improving tumor delivery of hydrophobic anticancer drugs.

Microfluidic approach for highly efficient synthesis of heparin-based bioconjugates for drug delivery.

This paper demonstrates the highly efficient synthesis of amphiphilic heparin-folic acid-retinoic acid (HFR) bioconjugates with a high drug coupling ratio by a microfluidic approach. The microfluidic synthesis enabled the conjugation of 17 molecules of retinoic acid to each heparin chain with 21 possible groups for attachment after reacting for several minutes. In contrast, about 11 molecules of the drug were covalently conjugated to one heparin chain after 4 days in the bulk reaction. The microfluidic based-HFR bioconjugates readily self-assembled in aqueous media to form uniform nanoparticles, while the product from the bulk reaction formed non-uniform nanoparticles with broad size distribution. The HFR nanoparticles with high drug content effectively delivered the drug to folate receptor-positive cancer cells with superior cellular uptake and selective cytotoxicity in vitro compared to HFR nanoparticles synthesized in bulk reaction. With the ability to achieve high drug content in heparin carrier within a short reaction time, the microfluidic technique offers new alternatives for the efficient synthesis of polymer-based conjugates for drug delivery.

An inorganic-organic diblock copolymer photoresist for direct mesoporous SiCN ceramic patterns via photolithography.

A high resolution negative-tone-type of inorganic-organic diblock copolymer photoresist was synthesized as a novel precursor for simple and direct fabrication of SiCN ceramic mesoporous patterns with ordered nanoscale pores by using a "top-down" photolithographic technique and the subsequent sacrificial processes of a "bottom-up" self-assembled nanostructure.

Droplet synthesis of well-defined block copolymers using solvent-resistant microfluidic device.

Well-defined diblock copolymers were synthesized via an exothermic RAFT route by a droplet microfluidic process using a solvent-resistant and thermally stable fluoropolymer microreactor fabricated by a non-lithographic embedded template method. The resulting polymers were compared to products obtained from continuous flow capillary reactor and conventional bulk synthesis. The droplet based microreactor demonstrated superior molecular weight distribution control by synthesizing a higher molecular weight product with higher conversion and narrow polydispersity in a much shorter reaction time. The high quality of the as-synthesized block copolymer PMMA-b-PS led to a generation of micelles with a narrow size distribution that could be used as a template for well-ordered mesoporous silica with regular frameworks and high surface areas.