In-person versus virtual administration of the American College of Rheumatology gold standard cognitive battery in systemic lupus erythematosus: Are they interchangeable?

OBJECTIVE: During the COVID-19 pandemic, many research studies were adapted, including our longitudinal study examining cognitive impairment (CI) in systemic lupus erythematosus (SLE). Cognitive testing was switched from in-person to virtual. This analysis aimed to determine if the administration method (in-person vs. virtual) of the ACR-neuropsychological battery (ACR-NB) affected participant cognitive performance and classification. METHODS: Data from our multi-visit, SLE CI study included demographic, clinical, and psychiatric characteristics, and the modified ACR-NB. Three analyses were undertaken for cognitive performance: (1) all visits, (2) non-CI group visits only and (3) intra-individual comparisons. A retrospective preferences questionnaire was given to participants who completed the ACR-NB both in-person and virtually. RESULTS: We analysed 328 SLE participants who had 801 visits (696 in-person and 105 virtual). Demographic, clinical, and psychiatric characteristics were comparable except for ethnicity, anxiety and disease-related damage. Across all three comparisons, six tests were consistently statistically significantly different. CI classification changed in 11/71 (15%) participants. 45% of participants preferred the virtual administration method and 33% preferred in-person. CONCLUSIONS: Of the 19 tests in the ACR-NB, we identified one or more problems with eight (42%) tests when moving from in-person to virtual administration. As the use of virtual cognitive testing will likely increase, these issues need to be addressed - potentially by validating a virtual version of the ACR-NB. Until then, caution must be taken when directly comparing virtual to in-person test results. If future studies use a mixed administration approach, this should be accounted for during analysis.

Curcuma longa-Based Optical Sensor for Hydrochloric Acid and Ammonia Vapor Detection.

In this research, we present a prototype optical system that offers significant advances in detecting hydrochloric acid (HCl) and ammonia (NH3) vapors. The system utilizes a natural pigment sensor based on Curcuma longa that is securely attached to a glass surface support. Through extensive development and testing with HCl (37% aqueous solution) and NH3 (29% aqueous solution) solutions, we have successfully demonstrated the effectiveness of our sensor. To facilitate the detection process, we have developed an injection system that exposes C. longa pigment films to the targeted vapors. The interaction between the vapors and the pigment films triggers a distinct color change, which is then analyzed by the detection system. By capturing the transmission spectra of the pigment film, our system allows a precise comparison of these spectra at different concentrations of the vapors. Our proposed sensor exhibits remarkable sensitivity, allowing the detection of HCl at a concentration of 0.009 ppm using only 100 µL (2.3 mg) of pigment film. In addition, it can detect NH3 at a concentration of 0.03 ppm with a 400 µL (9.2 mg) pigment film. Integrating C. longa as a natural pigment sensor in an optical system opens up new possibilities for detecting hazardous gases. The simplicity and efficiency of our system, combined with its sensitivity, make it an attractive tool in environmental monitoring and industrial safety applications.

Thermocavitation: a mechanism to pulse fiber lasers.

In this paper, we present a novel mechanism for the generation of laser pulses based on the phenomenon of thermocavitation. Thermocavitation bubbles were generated within a glass cuvette filled with copper nitrate dissolved in water, where the tip of an optical fiber was placed very close to the bubble generation region. Once the bubble is generated, it expands rapidly and the incoming laser light transmitted through the optical fiber is reflected at the vapor-solution interface and reflected back into the fiber, which is coupled to an erbium-doped fiber ring laser. Laser pulses were extracted from the ring cavity and detected by a fast photodetector, which corresponds to a single thermocavitation event, obtaining a pulse repetition rate from 118 Hz to 2 kHz at 1560 nm, with a pulse width ranging from 64 to 57 µs. The repetition rate can be controlled by adjusting the laser power to induce thermocavitation. To our knowledge, this novel mechanism of laser pulses has not been reported in the literature.

Theoretical and experimental study of acoustic waves generated by thermocavitation and its application in the generation of liquid jets.

Numerical simulations using the Finite-Difference Time-Domain method were used to study the propagation of an acoustic wave within a truncated ellipsoidal cavity. Based in our simulations, a fluidic device was designed and fabricated using a 3D printer in order to focus an acoustic wave more efficiently and expel a liquid jet. The device consists of an ellipsoidal shaped chamber filled with a highly absorbent solution at the operating wavelength (1064 nm) in order to create a vapor bubble using a continuous wavelength laser. The bubble rapidly expands and collapses emitting an acoustic wave that propagates inside the cavity, which was measured by using a needle hydrophone. The bubble collapse, and source of the acoustic wave, occurs in one focus of the cavity and the acoustic wave is focused on the other one, expelling a liquid jet to the exterior. The physical mechanism of the liquid jet generation is momentum transfer from the acoustic wave, which is strongly focused due to the geometry of the cavity. This mechanism is different to the methods that uses pulsed lasers for the same purpose. The maximum speed of the generated liquid microjets was approximately 20 m/s. One potential application of this fluidic device can be found for inkjet printing, coating and, maybe the most attractive, for drug delivery.

The anti-CD6 antibody itolizumab provides clinical benefit without lymphopenia in rheumatoid arthritis patients: results from a 6-month, open-label Phase I clinical trial.

Itolizumab is a humanized anti-CD6 monoclonal antibody (mAb) that has previously shown encouraging results, in terms of safety and positive clinical effects, in a 6-week monotherapy clinical trial conducted in rheumatoid arthritis (RA) patients. The current Phase I study evaluated the safety and clinical response for a longer treatment of 12 itolizumab intravenous doses in subjects with active RA despite previous disease-modifying anti-rheumatic drug (DMARD) therapy. Twenty-one subjects were enrolled into four dosage groups (0·1, 0·2, 0·4 and 0·8 mg/kg). Efficacy end-points including American College of Rheumatology (ACR)20, ACR50 and ACR70 response rates and disease activity score in 28 joints (DAS28) were monitored at baseline and at specific time-points during a 10-week follow-up period. Itolizumab was well tolerated up to the highest tested dose. No related serious adverse events were reported and most adverse events were mild. Remarkably, itolizumab treatment did not produce lymphopenia and, therefore, was not associated with infections. All patients achieved a clinical response (ACR20) at least once during the study. Eleven subjects (55%) achieved at least a 20% improvement in ACR just 1 week after the first itolizumab administration. The clinical response was observed from the beginning of the treatment and was sustained during 24 weeks. The efficacy profile of this 12-week treatment was similar to that of the previous study (6-week treatment). These results reinforce the safety profile of itolizumab and provide further evidence on the clinical benefit from the use of this anti-CD6 mAb in RA patients.

Influence on the saturable absorption of the induced losses by photodeposition of zinc nanoparticles in an optical fiber.

In this work, the influence of induced losses on the saturable absorption by zinc nanoparticles photodeposited onto the core of an optical fiber end is reported. Samples with different losses were obtained by the photodeposition technique using a continuous wave laser at 1550 nm. The nonlinear absorption of the saturable absorber was characterized by the P-scan technique using a high-gain pulsed erbium-doped fiber amplifier. The results have demonstrated that for optical fibers with variable induced losses by deposited nanoparticles, the modulation depth increases proportionally based on the nonlinear absorption coefficient. With induced losses fixed at 3 dB, it was demonstrated that the modulation depth increased as a function of the optical power used in the photodeposition process. The saturation intensity of the saturable absorber presents small shifts for higher intensities.

Controllable direction of liquid jets generated by thermocavitation within a droplet.

A high-velocity fluid stream ejected from an orifice or nozzle is a common mechanism to produce liquid jets in inkjet printers or to produce sprays among other applications. In the present research, we show the generation of liquid jets of controllable direction produced within a sessile water droplet by thermocavitation. The jets are driven by an acoustic shock wave emitted by the collapse of a hemispherical vapor bubble at the liquid-solid/substrate interface. The generated shock wave is reflected at the liquid-air interface due to acoustic impedance mismatch generating multiple reflections inside the droplet. During each reflection, a force is exerted on the interface driving the jets. Depending on the position of the generation of the bubble within the droplet, the mechanical energy of the shock wave is focused on different regions at the liquid-air interface, ejecting cylindrical liquid jets at different angles. The ejected jet angle dependence is explained by a simple ray tracing model of the propagation of the acoustic shock wave inside the droplet.

In vitro activity of anidulafungin in combination with amphotericin B or voriconazole against biofilms of five Candida species.

OBJECTIVES: To evaluate the in vitro activity of anidulafungin combined with amphotericin B or voriconazole against Candida spp. biofilms. METHODS: Four Candida albicans, four Candida tropicalis, four Candida glabrata, two Candida parapsilosis and two Candida orthopsilosis blood isolates were tested by the microdilution chequerboard method combined with the XTT metabolic assay. Biofilm MIC was defined as the lowest concentration producing 50% metabolic inhibition with respect to control (BMIC50). Concentrations in the combinations ranged from 1/8 × BMIC50 to 4 × BMIC50 found for each antifungal tested alone. RESULTS: Anidulafungin plus amphotericin B acted synergistically against C. albicans and C. glabrata biofilms [fractional inhibitory concentration index (FICI): 0.082-0.387], but showed no interaction against C. tropicalis, C. parapsilosis and C. orthopsilosis (FICI: 0.516-2.099). The combination of these antifungals failed to completely remove biofilms of C. albicans and C. glabrata, decreasing the metabolic activity of the biofilms up to 80% and 95%, respectively, which did not occur when each antifungal was used alone. Anidulafungin plus voriconazole showed no interaction against all isolates. Using a less stringent criterion previously proposed to define synergism (FICI < 1) and antagonism (FICI > 1.25), antagonistic interactions were found against some isolates. CONCLUSIONS: Anidulafungin with amphotericin B results in a synergistic effect against C. albicans and C. glabrata biofilms at serum concentrations of the drugs, but showed no interaction against C. tropicalis and C. parapsilosis complex. Anidulafungin plus voriconazole showed no interaction against the five Candida species assayed. Biofilms of C. tropicalis were found to be the most resistant towards the combinations assayed. The results presented may be of potential interest in the clinical setting.

Antiviral drug discovery: broad-spectrum drugs from nature.

Covering: up to April 2014. The development of drugs with broad-spectrum antiviral activities is a long pursued goal in drug discovery. It has been shown that blocking co-opted host-factors abrogates the replication of many viruses, yet the development of such host-targeting drugs has been met with scepticism mainly due to toxicity issues and poor translation to in vivo models. With the advent of new and more powerful screening assays and prediction tools, the idea of a drug that can efficiently treat a wide range of viral infections by blocking specific host functions has re-bloomed. Here we critically review the state-of-the-art in broad-spectrum antiviral drug discovery. We discuss putative targets and treatment strategies, with particular focus on natural products as promising starting points for antiviral lead development.

Acute Postoperative Pain Due to Dental Extraction in the Adult Population: A Systematic Review and Network Meta-analysis.

This study compares the effectiveness of pharmacological treatments to develop guidelines for the management of acute pain after tooth extraction. We searched Medline, EMBASE, CENTRAL, and US Clinical Trials registry on November 21, 2020. We included randomized clinical trials (RCTs) of participants undergoing dental extractions comparing 10 interventions, including acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and combinations to placebo. After duplicate screening and data abstraction, we conducted a frequentist network meta-analysis for each outcome at 6 h (i.e., pain relief, total pain relief [TOTPAR], summed pain intensity difference [SPID], global efficacy rating, rescue analgesia, and adverse effects). We assessed the risk of bias using a modified Cochrane RoB 2.0 tool and the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. We implemented the analyses in RStudio version 3.5.3 and classified interventions from most to least beneficial or harmful. We included 82 RCTs. Fifty-six RCTs enrolling 9,095 participants found moderate- and high-certainty evidence that ibuprofen 200 to 400 mg plus acetaminophen 500 to 1,000 mg (mean difference compared to placebo [MDp], 1.68; 95% confidence interval [CI], 1.06-2.31), acetaminophen 650 mg plus oxycodone 10 mg (MDp, 1.19; 95% CI, 0.85-1.54), ibuprofen 400 mg (MDp, 1.31; 95% CI, 1.17-1.45), and naproxen 400-440 mg (MDp, 1.44; 95% CI, 1.07-1.80) were most effective for pain relief on a 0 to 4 scale. Oxycodone 5 mg, codeine 60 mg, and tramadol 37.5 mg plus acetaminophen 325 mg were no better than placebo. The results for TOTPAR, SPID, global efficacy rating, and rescue analgesia were similar. Based on low- and very low-certainty evidence, most interventions were classified as no more harmful than placebo for most adverse effects. Based on moderate- and high-certainty evidence, NSAIDs with or without acetaminophen result in better pain-related outcomes than opioids with or without acetaminophen (except acetaminophen 650 mg plus oxycodone 10 mg) or placebo.

Voriconazole inhibits biofilm formation in different species of the genus Candida.

OBJECTIVES: To determine the ability of voriconazole to inhibit the formation of biofilms. METHODS: A total of 38 blood isolates of Candida spp. (8 Candida albicans, 10 Candida tropicalis, 10 Candida glabrata, 7 Candida parapsilosis sensu stricto and 3 Candida orthopsilosis) and C. albicans ATCC 90028 and ATCC 64548 were assessed. Biofilm formation was quantified using XTT reduction assays. The inhibition of biofilm formation was determined (i) in the presence of 0.06 and 0.25 mg/L voriconazole, and (ii) on surfaces previously coated with 0.06, 0.25, 1, 4 and 16 mg/L voriconazole. RESULTS: Voriconazole reduced biofilm formation under both conditions, the extent depending on the species, isolate and drug concentration. In the presence of 0.25 mg/L, the highest reduction was found for C. parapsilosis (79% ±â€Š8.6%), followed by C. albicans (64.5% ±â€Š6.3%), C. tropicalis (53.3% ±â€Š13.1%) and C. glabrata (23.8% ±â€Š11.2%). This reduction was significant (P < 0.05) for all isolates tested. After coating the wells with voriconazole, biofilm formation was reduced in all Candida spp. examined, C. albicans being the species with the highest reduction (68.8% with 16 mg/L) and C. parapsilosis complex and C. glabrata the lowest. CONCLUSIONS: As voriconazole reduces biofilm formation it may be a good candidate for the prevention of Candida biofilm-related infections although further studies using voriconazole-impregnated catheter tubing or prostheses are required to confirm these results.

Characterization of the antimicrobial susceptibility of fungi responsible for onychomycosis in Spain.

Due to the increase of choices relative to antifungals, there is a need to improve the standardization of in vitro methods used to determine the antifungal susceptibility of fungal pathogens. Our study evaluated the in vitro susceptibility of filamentous fungi isolated from patients with toenail onychomycosis against itraconazole, ciclopirox, eberconazole, fluconazole and terbinafine. The minimum inhibitory concentration (MIC) of these antifungal agents was determined with 100 isolates, including dermatophytes (70 strains) and non-dermatophyte molds (30 strains). The susceptibility of fungal isolates was measured by using a technique modified for dermatophytes (0.5 × 10(3)-0.5 × 10(4) conidia/ml as inocula) which followed the procedures described by the Antifungal Susceptibility Testing Subcommittee of the European Committee on Antimicrobial Susceptibility Testing (AFST-EUCAST) and the Clinical and Laboratory Standard Institute (CLSI M38-A). MIC ranges were 0.016-8.0 µg/ml for itraconazole, ciclopirox and eberconazole, 0.063-32.0 µg/ml for fluonazole, and 0.004-2.0 µg/ml for terbinafine. In vitro susceptibility tests indicated that eberconazole has a broad antimicrobial profile, including dermatophytes, as well as other filamentous fungi. Terbinafine was active (0.016-0.250 µg/ml) against dermatophytes.

Ultra scale-down stress analysis of the bioprocessing of whole human cells as a basis for cancer vaccines.

This study examines the use of a capillary shear device for the rapid characterization of human cell lines in terms of their resistance to hydrodynamic stress. An ultra scale-down (USD) approach is presented to allow the use of small quantities of cells available at the early discovery stage and to expose them to a wide range of hydrodynamic stresses. In this way an indication is gained of the relative properties of different cell lines and the challenge which may be faced during full-scale processing. A design of experiments approach allowed the interaction between a number of key processing factors such as capillary length, flow rate, and number of passes to be studied in a limited number of experiments. Out of this an USD test based on flow rate in a device of fixed geometry was proposed. Based on observations made elsewhere (Ma et al., 2002, Biotechnol Bioeng 80(4): 428-437) a detailed analysis of possible geometries was performed using a combination of USD experiments and computational fluid dynamics analysis of the capillary entry region. This allowed the properties of the cells to be characterized in terms of a critical stress below which there is no significant loss of cell integrity. The results suggested that the OnyCap23 and P4E6 cell lines, used as components of a whole cell prostate cancer vaccine, are resistant to damage below critical elongational shear stress values of 235 and 275 N/m(2), respectively. Above these stress values the loss of intact cells is predicted to be significant; such loss being due to a combination of whole cells becoming permeable to trypan blue and complete breakage of cells into debris at extreme stresses. The sensitivity of cell surface markers CD9, CD44, CD59, CD81, CD147, and MHC-1 to exposure to shear stress was considerably less than for cell membrane integrity. The surface marker levels for recovered whole cells (i.e., both with and without intact cell membranes) were either independent of shear stress or showed a slight decrease with increased shear stress, for example, as for CD9. The results were used to predict successfully a capillary design where no damage would occur at a specified high flow rate; for example, as required for cell dispensing or vialling operations. Equally, the extent of loss of cell integrity was also successfully predicted in a capillary flow system designed to yield high levels of break up as may be required in intracellular analysis without the use of chemical lysing reagents or relying on autolytic damage.

Non-Invasive Identification of Atrial Fibrillation Driver Location Using the 12-lead ECG: Pulmonary Vein Rotors vs. other Locations.

Atrial fibrillation (AF) is an irregular heart rhythm due to disorganized atrial electrical activity, often sustained by rotational drivers called rotors. In the present work, we sought to characterize and discriminate whether simulated single stable rotors are located in the pulmonary veins (PVs) or not, only by using non-invasive signals (i.e., the 12-lead ECG). Several features have been extracted from the signals, such as Hjort descriptors, recurrence quantification analysis (RQA), and principal component analysis. All the extracted features have shown significant discriminatory power, with particular emphasis to the RQA parameters. A decision tree classifier achieved 98.48% accuracy, 83.33% sensitivity, and 100% specificity on simulated data.Clinical Relevance-This study might guide ablation procedures, suggesting doctors to proceed directly in some patients with a pulmonary veins isolation, and avoiding the prior use of an invasive atrial mapping system.

Cell wall and secreted proteins of Candida albicans: identification, function, and expression.

The cell wall is essential to nearly every aspect of the biology and pathogenicity of Candida albicans. Although it was initially considered an almost inert cellular structure that protected the protoplast against osmotic offense, more recent studies have demonstrated that it is a dynamic organelle. The major components of the cell wall are glucan and chitin, which are associated with structural rigidity, and mannoproteins. The protein component, including both mannoprotein and nonmannoproteins, comprises some 40 or more moieties. Wall proteins may differ in their expression, secretion, or topological location within the wall structure. Proteins may be modified by glycosylation (primarily addition of mannose residues), phosphorylation, and ubiquitination. Among the secreted enzymes are those that are postulated to have substrates within the cell wall and those that find substrates in the extracellular environment. Cell wall proteins have been implicated in adhesion to host tissues and ligands. Fibrinogen, complement fragments, and several extracellular matrix components are among the host proteins bound by cell wall proteins. Proteins related to the hsp70 and hsp90 families of conserved stress proteins and some glycolytic enzyme proteins are also found in the cell wall, apparently as bona fide components. In addition, the expression of some proteins is associated with the morphological growth form of the fungus and may play a role in morphogenesis. Finally, surface mannoproteins are strong immunogens that trigger and modulate the host immune response during candidiasis.

Evaluation of respiratory- and postural-induced changes on the ballistocardiogram signal by time warping averaging.

OBJECTIVE: The aim of this work was to evaluate the potential changes in the ballistocardiogram (BCG) signal induced by different respiratory patterns and posture, by using the dynamic time warping (DTW) technique. APPROACH: BCG signals were recorded in a group of 20 healthy volunteers, simultaneously with an electrocardiogram (ECG). Two recordings, one in a supine (SUP) and one in a standing (ST) position, including spontaneous breathing, two 1 min apneas (at full and empty-lungs, respectively) and 30 s of Valsalva, were analyzed. A warped averaged waveform was computed for each phase, from which amplitude and temporal parameters were extracted to characterize each condition. MAIN RESULTS: Variations were found in both amplitude and duration of BCG-derived parameters among manoeuvres, especially when compared to spontaneous breathing, suggesting a complex interaction between intra-thoracic pressure changes acting on venous return, together with the autonomic nervous system modulation on heart rate. The effect of a hydrostatic pressure gradient elicited by postural conditions was also evident. SIGNIFICANCE: Posture and respiratory manoeuvres affect the BCG signal in different ways, probably as a result of changes induced in preload and afterload. This supports the need to define separate normality ranges for each posture and/or breathing conditions, as well as the importance of applying specific manoeuvres to highlight any pathological response in the computed BCG parameters.

Detection of equine herpesvirus 1 genome 1B in Argentina.

To determine the genomic variation of equine herpesviruses (EHVs) isolated in Argentina between 1979 and the first half of 2004, DNA sequences from all 69 strains isolated were analysed. Sixty strains were recovered from aborted fetuses, one from leucocyte-rich plasma from a horse with respiratory signs and eight from cases of neonatal disease. The DNA was extracted from rabbit kidney epithelial (RK13) cells infected with each strain and digested with three restriction endonucleases (BamHI, Bg/II and KpnI). Two strains could be differentiated using BamHI restriction and were assigned to the EHV-1 1B prototype group. Only one of these two strains was typed EHV-1 1B with Bg/II. DNA digestion with KpnI was ineffective. The results obtained in this study demonstrate that the EHV-1 1B genome has been present in Argentina since at least 1996. The finding of two strains with this electropherotype suggests that there is genomic heterogeneity among Argentinian isolates.