Prognostic indicators associated with progresses of severe dengue

Background Dengue usually progress abnormally, especially in the critical phase. The main causes of death were shock, severe bleeding and organ failure. The aim of our study was to evaluate prognostic indicators of severe dengue according to the phases of the disease progression. Methods A cross-sectional study was conducted from July to December 2017 at the National Hospital for Tropical Diseases and the Hospital for Tropical Diseases of Ho Chi Minh City. 326 patients, aged 6 years and over, including 99/326 patients with severe dengue and 227/326 patients with non-severe dengue, hospitalized in the first 3 days of illness, confirmed Dengue virus by the RT-PCR assay have been registered for the study. Clinical manifestations were monitored daily. The hematocrit, white blood cells, platelet, serum albumin, ALT, AST, bilirubin, prothrombin time (PT%, PTs), fibrinogen, aPTT, INR and creatinine were evaluated at two times: febrile phase and critical phase. Results Independent factors associated with severe dengue were identified on multivariate logistic regression models. During the first 3 days of the disease, the prognostic indicators were platelet count ≤ 100 G/L (OR = 2.2; 95%CI: 1.2–3.9), or serum albumin < 35 g/L (OR = 3.3; 95%CI: 1.8–6.1). From day 4–6, the indicator were AST > 400 U/L (OR = 3.0; 95%CI: 1.1–7.9), ALT > 400 U/L (OR = 6.6; 95%CI: 1.7–24.6), albumin < 35 g/L (OR = 3.0; 95%CI: 1.5–5.9), and bilirubin total >17 μmol/L (OR = 4.6; 95%CI: 2.0–10.4). Conclusion To predict the risk of patients with severe dengue, prognostic laboratory indicators should be indicated consistent with the progression of the disease. During the first 3 days of illness, prognostic indicators should be platelet count, or serum albumin. From the 4th - 6th day of illness, prognostic indicators should be AST, ALT, albumin, or bilirubin total.

Understanding Mud Volcano System Using Hele-Shaw (H-S) Experiment: Seismic Confirmation at East Java Mud Volcano

Numerous researchers have carried out studies on the mud volcano system in East Java. However, there have been no experiments on the mud volcano system's mechanism, including overpressure confirmed by direct subsurface data. Therefore, this study aims to directly evaluate the mud volcano system's mechanism using the Hele-Shaw (H-S) experiment with the subsurface data confirmation. The H-S experiment utilized four primary materials: quartz sand diameter below 250 µm and 320 µm to analogize the porous layer. Gypsum flour clay is the ductile layer, while mud from the Kuwu and Kesongo Mud Volcanoes is the original material from nature. Wax represents impermeable material. The sealing layer is made of wax, and oxygen represents the natural fluids of the rock formation. The overpressured zone is created by pumping oxygen into a layer of quartz sand covered by a wax as an impermeable layer. Pressure is measured digitally, and the process is continuously recorded to produce traceable data. Each material was experimented on individually to determine the critical phase characteristics, valve fault structure geometry, and validation with seismic interpretation. The results indicate that the critical phase of the mud volcano system is characterized by the dome structure at the surface, with high intensify of gas and oil seepage. Piercement structure geometry is shown by plumbing of fluidization zone, which becomes shallower than before. Furthermore, each material's piercement structure geometry shows a consistent pattern, with differences in the density of the fault and pressure structures. Thus, the H-S experiment's validation with seismic interpretation shows a similar geometry in pressure structures and valve faults as the mud volcano system's migration paths.

Leaky Gut Syndrome Is Associated with Endotoxemia and Serum (1→3)-β-D-Glucan in Severe Dengue Infection

The hallmark of severe dengue infection is the increased vascular permeability and hemodynamic alteration that might be associated with an intestinal permeability defect. However, the mechanisms underlying the gastrointestinal-related symptoms of dengue are not well characterized. A prospective observational study was conducted on patients with dengue who were categorized according to: (i) febrile versus critical phase and (ii) hospitalized patients with versus without the warning signs to evaluate the gut barrier using lactulose-to-mannitol excretion ratio (LEMR). Serum endotoxins, (1→3)-β-D-glucan (BG), and inflammatory parameters were measured. A total of 48 and 38 patients were enrolled in febrile illness and critical phase, respectively, while 22 and 64 patients presented with or without the warning signs, respectively. At enrollment, a positive LEMR test was found in 20 patients (91%) with warning signs, regardless of phase of infection. Likewise, serum endotoxins and BG, the indirect biomarkers for leaky gut, prominently increased in patients who developed severe dengue when compared with the non-severe dengue (endotoxins, 399.1 versus 143.4 pg/mL (p < 0.0001); BG, 123 versus 73.8 pg/mL (p = 0.016)). Modest impaired intestinal permeability occurred in dengue patients, particularly those with warning signs, and were associated with endotoxemia and elevated BG. Thus, leaky gut syndrome might be associated with severity of dengue infection.

Unique characteristics of new complete blood count parameters, the Immature Platelet Fraction and the Immature Platelet Fraction Count, in dengue patients

The advanced platelet parameters Immature Platelet Fraction and Immature Platelet Fraction Count have been implemented in clinical practice as measures of thrombopoietic activity, mainly in hematologic disorders that cause thrombocytopenia. The purpose of this observational study was to examine thrombopoiesis as reflected by these 2 new CBC parameters in patients infected with dengue. The study was conducted in infectious disease referral hospital in Metro Manila, the Philippines. We enrolled hospitalized patients at admission who were diagnosed with acute dengue or community acquired bacterial infection (CABI). Immature Platelet Fraction (IPF) and Immature Platelet Fraction Count were evaluated at admission and during hospitalization. A total of 606 patients were enrolled from May 1, 2017 to June 1, 2018. The participants consisted of 152 patients with dengue infection, 180 confirmed CABI, and 274 suspected CABI patients. At admission, the percent IPF (IPF%) of the patients with dengue was significantly higher than that of the confirmed CABI patients (median 3.7% versus 1.9%; p <0.001). In a time course evaluation, there was no significant difference of IPF% between the patients with dengue infection and the confirmed CABI patients in the febrile phase (median 1.9% versus 2.4%; p = 0.488), however, the IPF% of the patients with dengue infection increased to be significantly higher than that of the confirmed CABI patients in the critical phase (median 5.2% versus 2.2%; p <0.001). Our study elucidated the unique characteristics and time-course trends of IPF percent and number (IPF#) in the patients with dengue infection. IPF% and IPF# are potentially valuable parameters in dengue and further investigation is required for the optimal use in clinical practice.

From bandit nests to Sakura orchards: colonial rule, press images, and the stating of Taiwan's Northern Mountains, 1896–1908

Addressing a question of how states in both Asia and the world have resolved the dilemma posed by ecologically recalcitrant “nonstate spaces,” this essay examines a refuge in Taiwan's Northern Mountains. Resistance to Japanese rule from 1896, sheltered in the Grass Mountain uplands, precipitated not just colonial pacification, but a platform of “modern” (Western-modeled, but Meiji Japanese and Qing Chinese influenced) transformation. This was promoted through the educational and symbolic cultivation of Zhishan Rock, a press discourse of nature for public edification, as well as policies that strengthened policing, guided resettlement, and opened the area to recreation. Such tailored “stating” processes altered the image of the region, infused a culture of ecological veneration, and established a more sustainable system of oversight. A critical phase to Grass Mountain becoming a national park, these changes presented a template for Japanese (as subsequent) authorities as they struggled to manage Taiwan's unruly highland frontiers.

All-cause mortality and disease progression in SARS-CoV-2-infected patients with or without antibiotic therapy: an analysis of the LEOSS cohort

Purpose Reported antibiotic use in coronavirus disease 2019 (COVID-19) is far higher than the actual rate of reported bacterial co- and superinfection. A better understanding of antibiotic therapy in COVID-19 is necessary. Methods 6457 SARS-CoV-2-infected cases, documented from March 18, 2020, until February 16, 2021, in the LEOSS cohort were analyzed. As primary endpoint, the correlation between any antibiotic treatment and all-cause mortality/progression to the next more advanced phase of disease was calculated for adult patients in the complicated phase of disease and procalcitonin (PCT) ≤ 0.5 ng/ml. The analysis took the confounders gender, age, and comorbidities into account. Results Three thousand, six hundred twenty-seven cases matched all inclusion criteria for analyses. For the primary endpoint, antibiotic treatment was not correlated with lower all-cause mortality or progression to the next more advanced (critical) phase (n = 996) (both p > 0.05). For the secondary endpoints, patients in the uncomplicated phase (n = 1195), regardless of PCT level, had no lower all-cause mortality and did not progress less to the next more advanced (complicated) phase when treated with antibiotics (p > 0.05). Patients in the complicated phase with PCT > 0.5 ng/ml and antibiotic treatment (n = 286) had a significantly increased all-cause mortality (p = 0.029) but no significantly different probability of progression to the critical phase (p > 0.05). Conclusion In this cohort, antibiotics in SARS-CoV-2-infected patients were not associated with positive effects on all-cause mortality or disease progression. Additional studies are needed. Advice of local antibiotic stewardship- (ABS-) teams and local educational campaigns should be sought to improve rational antibiotic use in COVID-19 patients.

Determination of the Critical Phases of the Experimental Research Using Laboratory Animals: Risk Analysis

Critical phases (stages) of preclinical studies are those procedures or types of research activities whose accurate and correct implementation is a prerequisite for obtaining valid and reliable results. Russian and foreign standards require determination of the critical phases of each individual study by quality assurance staff based on checking the study protocol (plan).The aim of the study was to identify critical phases typical for most preclinical studies, and assess the potential risks during inspections.Materials and methods: the study was carried out by analysing the types and consequences of nonconformities. Numerical parameters of risks were analysed for each critical phase of the preclinical study identified by quality officers of the Joint Stock Company “Scientific and Production Association ‘HOME OF PHARMACY’”.Results: it was discovered that incorrect implementation of a procedure constituted a potential nonconformity at all the identified critical phases, and a potential consequence was acquisition of low-quality data. A combination of incorrectly implemented procedures at two or more critical phases could pose an unacceptable risk and lead to complete loss of data or failure to process data, and, as a result, the need to repeat the study.Conclusions: the highest risk was identified for such critical phases as preparation and administration of final doses of test samples, performance of physiological tests, collection of biological material samples, and handling of biological material samples by other relevant departments. Summarising the data obtained on the risks of all the critical phases, it can be concluded that risk action should take the form of regular inspections by the quality assurance staff and the study director. By adjusting the frequency of inspections, the risk of each critical phase can be made insignificant.