The coronavirus disease 2019 (COVID-19) pandemic emerged in Wuhan, China, in late 2109, and has rapidly spread around the world. Until May 25, 2020, there were 133,521 confirmed COVID-19 cases and ...7359 deaths in Iran. The role of opportunistic fungal infections in the morbidity and mortality of COVID-19 patients remains less defined. Based on our multicenter experiences, we categorized the risks of opportunistic fungal infections in COVID-19 patients in Iran. The COVID-19 patients at high risk included those with acute respiratory distress syndrome, in intensive care units, receiving broad-spectrum antibiotics, immunosuppressants or corticosteroid, and supported by invasive or noninvasive ventilation. The patients were most likely to develop pulmonary aspergillosis, oral candidiasis, or pneumocystis pneumonia. Most diagnoses were probable as the accurate diagnosis of opportunistic fungal infections remains challenging in resource-poor settings. We summarize the clinical signs and laboratory tests needed to confirm candidiasis, aspergillosis, or pneumocystosis in our COVID-19 patients.
The fabrication of a large-scale microfluidic mold with 3D microstructures for manufacturing of the conical microwell chip using a combined projection micro-stereolithography (PµSL) 3D printing/CNC ...micro-milling method for tumor spheroid formation is presented. The PµSL technique is known as the most promising method of manufacturing microfluidic chips due to the possibility of creating complex three-dimensional microstructures with high resolution in the range of several micrometers. The purpose of applying the proposed method is to investigate the influence of microwell depths on the formation of tumor spheroids. In the conventional methods, the construction of three-dimensional microstructures and multi-height chips is difficult, time-consuming, and is performed using a multi-step lithography process. Microwell depth is an essential parameter for microwell design since it directly affects the shear stress of the fluid flow and the diffusion of nutrients, respiratory gases, and growth factors. In this study, a chip was made with microwells of different depth varying from 100 to 500 µm. The mold of the microwell section is printed by the lab-made PµSL printer with 6 and 1 µm lateral and vertical resolutions. Other parts of the mold, such as the main chamber and micro-channels, were manufactured using the CNC micro-milling method. Finally, different parts of the master mold were assembled and used for PDMS casting. The proposed technique drastically simplifies the fabrication and rapid prototyping of large-scale microfluidic devices with high-resolution microstructures by combining 3D printing with the CNC micro-milling method.
Acute respiratory distress syndrome is a common complication of severe viral pneumonia, such as influenza and COVID‐19, that requires critical care including ventilatory support, use of ...corticosteroids and other adjunctive therapies to arrest the attendant massive airways inflammation. Although recommended for the treatment of viral pneumonia, steroid therapy appears to be a double‐edged sword, predisposing patients to secondary bacterial and invasive fungal infections (IFIs) whereby impacting morbidity and mortality. Mucormycosis is a fungal emergency with a highly aggressive tendency for contiguous spread, associated with a poor prognosis if not promptly diagnosed and managed. Classically, uncontrolled diabetes mellitus (DM) and other immunosuppressive conditions including corticosteroid therapy are known risk factors for mucormycosis. Upon the background lung pathology, immune dysfunction and corticosteroid therapy, patients with severe viral pneumonia are likely to develop IFIs like aspergillosis and mucormycosis. Notably, the combination of steroid therapy and DM can augment immunosuppression and hyperglycaemia, increasing the risk of mucormycosis in a susceptible individual. Here, we report a case of sinonasal mucormycosis in a 44‐year‐old woman with hyperglycaemia secondary to poorly controlled diabetes following dexamethasone therapy on a background of influenza pneumonia and review 15 available literatures on reported cases of influenza and COVID‐19 associated mucormycosis.
This article presents a study that aims to identify the boundary conditions of a railway bridge using system identification and artificial neural networks. Vibrations generated by three different ...train types recorded during a 24-h long measurement campaign is used to identify the modal frequencies and mode shapes of a single-span 50 m long railway bridge. Frequency Domain Decomposition and Stochastic Subspace Identification with Covariance methods were used to identify the modal properties from the recorded vibrations and the effect of the used Operational Modal Analysis on the identified modal properties was evaluated. An initial finite-element (FE) model based on the design drawings was not able to replicate the observed dynamic behavior of the bridge. Using a sensitivity analysis, the key parameters of the finite-element model that impact the vibration frequencies of the bridge was determined. 300 finite-element models were created by changing the values of these key parameters within their effective range and were used to identify the relationship between these parameters and the vibration frequencies using Artificial neural networks (ANNs). Leveraging this relationship, the values of the FE model parameters that minimizes the error between the measured and computed frequencies was determined. As a result, the mean error between the computed and the identified vibration frequencies was reduced from 27.3% for the initial model to 3.0% for the updated model. The study indicates that boundary conditions are among the most influential parameter on the dynamic behavior of bridges and can deviate significantly from the simplistic models generally used in the FE models.
The role of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) has been addressed in some studies related to the current coronavirus disease-2019 (COVID-19) ...pandemic with possible higher severity and mortality in patients with hypertension. A triple-blind randomized controlled trial was designed to evaluate the effects of these medications on the COVID-19 progression.
Patients were enrolled in this trial between April and September 2020. They were randomized in 2 groups. The former dosage of ACEis/ARBs was continued in one group while in another group, the ACEis/ARBs were replaced by amlodipine ± carvedilol according to the dose equivalents. The primary outcomes were length of stay in hospitals and intensive care units (ICUs). Other outcomes include mechanical ventilation, noninvasive ventilation, readmission, and COVID-19 symptoms after discharge.
We randomized 64 patients with COVID-19 into 2 groups. Most patients were aged 66-80 and 46-65 years-old, 33 (51.6%) and 27 (42.2%), respectively. The study groups were nearly similar in baseline vital signs and characteristics. In addition, there was no significant difference in terms of recorded systolic and diastolic blood pressure measurements between groups. Furthermore, we did not find a significant difference between the days of ICU or ward admission, the discharge rate, or readmission rates between the 2 groups.
This randomized triple-blind multicentric clinical trial did not show any deleterious effects of ACEi/ARB medications in hypertensive COVID-19 patients.
The trial acquired the ethical code, IR.TUMS.VCR.REC.1399.028 and was registered in the Iranian randomized controlled trial system (registration no. IRCT20151113025025N3), https://en.irct.ir/trial/46531.
The optical pH sensor based on smart hydrogel material was designed for use in microfluidic applications. The Chitosan-tetraethyl orthosilicate (chitosan-TEOS) interpenetrating network was ...synthesized as a pH-sensitive part of the sensor. This chitosan-TEOS layer was bonded by oxygen plasma treatment to a thin layer of polydimethylsiloxane (PDMS), which enabled easily integrating of the sensor layer into the microfluidic chips. Also, the thickness of this PDMS layer worked as an adjustable parameter to control the sensitivity of the sensor. In addition, the optical astigmatism method (the method used in CD/DVD optical pick-up unit) was utilized to measure the pH-induced variations of the sensor layer by monitoring the laser beam profile on a CCD. The experimental results showed that the fabricated sensor responded to pH changes and became stable in less than 90 seconds. It showed a sensitivity of 54 pixel/pH and 94 pixel/pH using the spin-coated PDMS thickness of 75 and 28 μm, respectively.
Hospital infections such as ventilator-associated pneumonia (VAP) due to multidrug-resistant Klebsiella pneumoniae (MDR-KP) strains have increased worldwide. In addition, biofilm production by these ...resistant isolates has confronted clinicians with higher treatment failure and infection recurrence. Given the paucity of new agents and limited data on combination therapy for MDR-KPs, the present study sought to evaluate the in vitro activity of several antibiotic combinations against planktonic and biofilm MDR-KPs isolated from patients with VAP. All 10 carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates demonstrated multidrug resistance against the tested antibiotics. At planktonic mode, combinations of colistin-meropenem and amoxicillin/clavulanate in combination with meropenem, colistin, or amikacin showed synergism against 60-70% isolates. On the other hand, in the biofilm state, colistin-based combinations exhibited synergism against 50-70% isolates and the most effective combination was colistin-amikacin with 70% synergy. The results revealed that combinations of amoxicillin/clavulanate with colistin, meropenem, or amikacin in the planktonic mode and colistin with amoxicillin/clavulanate, meropenem, or amikacin in the biofilm mode could effectively inhibit CRKP isolates, and thus could be further explored for the treatment of CRKPs.
The Acinetobacter baumannii genomic resistance islands (AbGRIs), which were characterized in the genome of the global clone 2 (GC2) A. baumannii contain resistance genes. Here, we aimed to determine ...the occurrence of AbGRIs in GC2 A. baumannii obtained from COVID-19 patients in a referral hospital in Tehran, Iran. A total of 19 carbapenem-resistant A. baumannii (CRAB) isolates belonging to GC2 and sequence type 2 (ST2), including 17 from COVID-19 patients and two from the devices used in the ICU that the COVID-19 patients were admitted, were examined in this study. Antibiotic susceptibility testing was performed by the disk diffusion method. PCR and PCR mapping, followed by sequencing, were performed to characterize the structure of AbGRI resistance islands in the isolates tested. The AbGRI3 was the most frequent resistance island (RI) detected, present in all the 19 isolates, followed by AbGRI1 (15 isolates; 78.9%) and AbGRI2 (three isolates; 15.8%). Notably, AbGRIs were identified in one of the A. baumannii strains, which was isolated from a medical device used in the ICU where COVID-19 patients were admitted. Furthermore, new structures of AbGRI1 and AbGRI3 resistance islands were found in this study, which was the first report of these structures. The present study provided evidence for the circulation of the GC2 A. baumannii strains harboring AbGRI resistance islands in a referral hospital in Tehran, Iran. It was found that resistance to several classes of antibiotics in the isolates collected from COVID-19 patients is associated with the resistance genes located within AbGRIs.
Background
Limited knowledge exists on the virulence factors of
Candida tropicalis
and the mechanisms of azole resistance that lead to an intensified pathogenicity and treatment failure. We aimed to ...evaluate the virulence factors and molecular mechanisms of azole resistance among C.
tropicalis
isolated from patients with candidemia.
Materials and Methods
Several virulence factors, including extracellular enzymatic activities, cell surface hydrophobicity (CSH), and biofilm formation, were evaluated. Antifungal susceptibility pattern and expression level of
ERG11
,
UPC2
,
MDR1
, and
CDR1
genes of eight (4 fluconazole resistance and 4 fluconazole susceptible) clinical
C. tropicalis
isolates were assessed. The correlation between the virulence factors and antifungal susceptibility patterns was analyzed.
Results
During a 4 year study, forty-five
C. tropicalis
isolates were recovered from candidemia patients. The isolates expressed different frequencies of virulence determinants as follows: coagulase 4 (8.9%), phospholipase 5 (11.1%), proteinase 31 (68.9%), esterase 43 (95.6%), hemolysin 44 (97.8%), biofilm formation 45 (100%) and CSH 45(100%). All the isolates were susceptible to amphotericin B and showed the highest resistance to voriconazole. There was a significant positive correlation between micafungin minimum inhibitory concentrations (MICs) and hemolysin production (
r
s
= 0.316). However, we found a negative correlation between fluconazole MICs and esterase production (
r
s
= −0.383). We observed the high expression of
ERG11
and
UPC2
genes in fluconazole-resistant
C. tropicalis
isolates.
Conclusion
C. tropicalis
isolated from candidemia patients extensively displayed capacities for biofilm formation, hemolysis, esterase activity, and hydrophobicity. In addition, the overexpression of
ERG11
and
UPC2
genes was considered one of the possible mechanisms of azole resistance.
•Numerical (40 simulations) and experimental analysis of eight planer micromixers.•Finding, analysis, fabrication and characterization of optimum micromixer.•The optimum micromixer has 0.89 mixing ...efficiency at the 1.18mm from the origin.•The study of the chamber and obstacle effect on the mixing efficiency and pressure drop.
Mixing laminar flows in short lengths is an important issue in chemical, biochemical and medical reactions. This work presents a numerical and experimental investigation on planar micromixers for obtaining an optimum micromixer with short mixing length. The numerical investigation of eight planar micromixers with two different chambers and four obstacle geometries is carried out by using three dimensional (3D) Navier–Stokes equations at the range of 0.1–40 of the Reynolds (Re) number. In total, 40 simulations (eight micromixers at five Re numbers) were done and the optimum micromixer was obtained by the analysis of the simulation data. The optimum micromixer has 0.89 and 0.99 mixing efficiency at Re=0.1 and 40 respectively at the short distance of 1.18mm from the origin. In addition, the effect of the chamber and obstacle geometry on mixing efficiency and pressure drop at the range of 0.1–40 of Re have been investigated. The results show that the chamber geometry manifests itself at a low Re number and obstacle geometry is significant at a high Re for mixing efficiency and pressure drop. The optimum micromixer was fabricated, tested and compared with the simulation results and both of them show a similar behavior in the mixing process.
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