Follistatin-like 1 (FSTL1) levels as potential early biomarker of cardiovascular disease in a Mexican population.

Cardiovascular diseases (CVD) are the leading cause of death globally. In recent years, follistatin-like protein 1 (FSTL1) has been proposed as an emerging potential clinical biomarker of CVD, since its concentration is upregulated in heart failure. The aim of the present study was to evaluate the association of FSTL1 levels and classic biomarkers with the risk of CVD in Mexican population. A case-control study was carried out in patients with cardiovascular diseases (CVD), arterial hypertension, but not CVD (cardiovascular risk factor-CRF), and healthy controls (control group) from the Mexican Institute of Social Security. Lipid profile, homocysteine (Hcys), serum amyloid A (SAA), FSTL1 concentration, PON1 concentration and activities [Arylesterase (ARE), and Lactonase (LAC)] were evaluated. High levels of FSTL1 were found in the CRF group and a positive association of FSTL1 (OR = 4.55; 95% CI 1.29-16.04, p = 0.02) with the presence of arterial hypertension, as well as Hcys (OR, 3.09; 95% CI 1.23-7.76, p = 0.02) and SAA (OR, 1.03; 95% CI 1.01-1.05, p < 0.01) with the presence of CVD. LAC activity (OR, 0.26; 95% CI 0.07-0.94, p = 0.04) and PON1 concentration (OR, 0.17; 95% CI 0.05-0.62, p = 0.01) were associated with a decrease in OR belonging to the group with CVD. Our results suggest that FSTL1 may be a useful biomarker for monitoring cardiovascular risk in clinical settings. However, longitudinal studies are needed to evaluate how FSTL1 could influence the association of PON1 activity and Hcys with CVD.

Functional Connectivity Hypersynchronization in Relatives of Alzheimer's Disease Patients: An Early E/I Balance Dysfunction?

Alzheimer's disease (AD) studies on animal models, and humans showed a tendency of the brain tissue to become hyperexcitable and hypersynchronized, causing neurodegeneration. However, we know little about either the onset of this phenomenon or its early effects on functional brain networks. We studied functional connectivity (FC) on 127 participants (92 middle-age relatives of AD patients and 35 age-matched nonrelatives) using magnetoencephalography. FC was estimated in the alpha band in areas known both for early amyloid accumulation and disrupted FC in MCI converters to AD. We found a frontoparietal network (anterior cingulate cortex, dorsal frontal, and precuneus) where relatives of AD patients showed hypersynchronization in high alpha (not modulated by APOE-ε4 genotype) in comparison to age-matched nonrelatives. These results represent the first evidence of neurophysiological events causing early network disruption in humans, opening a new perspective for intervention on the excitation/inhibition unbalance.

A split influenza vaccine formulated with a combination adjuvant composed of alpha-D-glucan nanoparticles and a STING agonist elicits cross-protective immunity in pigs.

BACKGROUND: Swine influenza A viruses (SwIAVs) pose an economic and pandemic threat, and development of novel effective vaccines is of critical significance. We evaluated the performance of split swine influenza A virus (SwIAV) H1N2 antigens with a plant-derived nanoparticle adjuvant alone (Nano-11) [Nano11-SwIAV] or in combination with the synthetic stimulator of interferon genes (STING) agonist ADU-S100 (NanoS100-SwIAV). Specific pathogen free (SPF) pigs were vaccinated twice via intramuscular (IM) or intradermal (ID) routes and challenged with a virulent heterologous SwIAV H1N1-OH7 virus. RESULTS: Animals vaccinated IM or ID with NanoS100-SwIAV had significantly increased cross-reactive IgG and IgA titers in serum, nasal secretion and bronchoalveolar lavage fluid at day post challenge 6 (DPC6). Furthermore, NanoS100-SwIAV ID vaccinates, even at half the vaccine dose compared to their IM vaccinated counterparts, had significantly increased frequencies of CXCL10+ myeloid cells in the tracheobronchial lymph nodes (TBLN), and IFNγ+ effector memory T-helper/memory cells, IL-17A+ total T-helper/memory cells, central and effector memory T-helper/memory cells, IL-17A+ total cytotoxic T-lymphocytes (CTLs), and early effector CTLs in blood compared with the Nano11-SwIAV group demonstrating a potential dose-sparing effect and induction of a strong IL-17A+ T-helper/memory (Th17) response in the periphery. However, the frequencies of IFNγ+ late effector CTLs and effector memory T-helper/memory cells, IL-17A+ total CTLs, late effector CTLs, and CXCL10+ myeloid cells in blood, as well as lung CXCL10+ plasmacytoid dendritic cells were increased in NanoS100-SwIAV IM vaccinated pigs. Increased expression of IL-4 and IL-6 mRNA was observed in TBLN of Nano-11 based IM vaccinates following challenge. Furthermore, the challenge virus load in the lungs and nasal passage was undetectable in NanoS100-SwIAV IM vaccinates by DPC6 along with reduced macroscopic lung lesions and significantly higher virus neutralization titers in lungs at DPC6. However, NanoS100-SwIAV ID vaccinates exhibited significant reduction of challenge virus titers in nasal passages and a remarkable reduction of challenge virus in lungs. CONCLUSIONS: Despite vast genetic difference (77% HA gene identity) between the H1N2 and H1N1 SwIAV, the NanoS100 adjuvanted vaccine elicited cross protective cell mediated immune responses, suggesting the potential role of this combination adjuvant in inducing cross-protective immunity in pigs.

Evaluation of surface disinfection methods to inactivate the beta coronavirus Murine Hepatitis Virus.

The list of EPA-approved disinfectants for coronavirus features many products for use on hard, non-porous materials. There are significantly fewer products registered for use on porous materials. Further, many common, high-touch surfaces fall in between non-porous materials such as glass and porous materials such as soft fabrics. The objective of this study was to assess the efficacy of selected commercially available disinfectant products against coronaviruses on common, high-touch surfaces. Four disinfectants (Clorox Total 360, Bleach solution, Vital Oxide, and Peroxide Multi-Surface Cleaner) were evaluated against Murine Hepatitis Virus A59 (MHV) as a surrogate coronavirus for SARS-CoV-2. MHV in cell culture medium was inoculated onto four materials: stainless steel, latex-painted drywall tape, Styrene Butadiene rubber (rubber), and bus seat fabric. Immediately (T0) or 2-hr (T2) post-inoculation, disinfectants were applied by trigger-pull or electrostatic sprayer and either held for recommended contact times (Spray only) or immediately wiped (Spray and Wipe). Recovered infectious MHV was quantified by median tissue culture infectious dose assay. Bleach solution, Clorox Total 360, and Vital Oxide were all effective (>3-log10 reduction or complete kill of infectious virus) with both the Spray Only and Spray and Wipe methods on stainless steel, rubber, and painted drywall tape when used at recommended contact times at both T0 and T2 hr. Multi-Surface Cleaner unexpectedly showed limited efficacy against MHV on stainless steel within the recommended contact time; however, it showed increased (2.3 times greater efficacy) when used in the Spray and Wipe method compared to Spray Only. The only products to achieve a 3-log10 reduction on fabric were Vital Oxide and Clorox Total 360; however, the efficacy of Vital Oxide against MHV on fabric was reduced to below 3-log10 when applied by an electrostatic sprayer compared to a trigger-pull sprayer. This study highlights the importance of considering the material, product, and application method when developing a disinfection strategy for coronaviruses on high-touch surfaces.

[Effects of the COVID-19 pandemic on a cohort of patients with vein occlusion]. / Efectos de la pandemia por SARS-CoV-2 en una cohorte de pacientes con obstrucción venosa retiniana.

BACKGROUND AND OBJECTIVES: A new coronavirus disease in humans, COVID-19, caused by SARS-CoV-2, emerged in December 2019. It has been associated with the development of thrombotic phenomena. Retinal vein occlusion (RVO) is mainly a consequence of vascular risk factors (VRF). This study aimed to analyze cases of COVID-19 in a cohort of patients with RVO (Valdecilla cohort). PATIENTS AND METHODS: Between December 2008 and December 2020, 429 patients with RVO were attended to in our clinic. Ten patients had COVID-19, one of which did not have VRF or thrombophilia. The remaining nine patients had RVO prior to the infection and VRF, six had carotid atherosclerosis, and four had antiphospholipid syndrome. The infection did not cause thrombotic phenomena in any of them. CONCLUSIONS: RVO is a rare manifestation of COVID-19. In our cohort of patients with RVO, COVID-19 disease did not lead to thrombotic events.

Flexible Passive near Field Communication Tag for Multigas Sensing.

In this work we present a full-passive flexible multigas sensing tag for the determination of oxygen, carbon dioxide, ammonia, and relative humidity readable by a smartphone. This tag is based on near field communication (NFC) technology for energy harvesting and data transmission to a smartphone. The gas sensors show an optic response that is read through high-resolution digital color detectors. A white LED is used as the common optical excitation source for all the sensors. Only a reduced electronics with very low power consumption is required for the reading of the optical responses and data transmission to a remote user. An application for the Android operating system has been developed for the power supplying and data reception from the tag. The responses of the sensors have been calibrated and fitted to simple functions, allowing a fast prediction of the gases concentration. Cross-sensitivity has also been evaluated, finding that in most of the cases it is negligible or easily correctable using the rest of the readings. The election of the target gases has been due to their importance in the monitoring of modified atmosphere packaging. The resolutions and limits of detection measured are suitable for such kinds of applications.

The SOS Chromotest applied for screening plant antigenotoxic agents against ultraviolet radiation.

In this work, we investigated the usefulness of the SOS Chromotest for screening plant antigenotoxic agents against ultraviolet radiation (UV). Fifty Colombian plant extracts obtained by supercritical fluid (CO2) extraction, twelve plant extract constituents (apigenin, carvacrol, ß-caryophyllene, 1,8-cineole, citral, p-cymene, geraniol, naringenin, pinocembrin, quercetin, squalene, and thymol) and five standard antioxidant and/or photoprotective agents (curcumin, epigallocatechin gallate, resveratrol, α-tocopherol, and Trolox®) were evaluated for their genotoxicity and antigenotoxicity against UV using the SOS Chromotest. None of the plant extracts, constituents or agents were genotoxic in the SOS Chromotest at tested concentrations. Based on the minimal extract concentration that significantly inhibited UV-genotoxicity (CIG), five plant extracts were antigenotoxic against UV as follows: Baccharis nítida (16 µg mL-1) = Solanum crotonifolium (16 µg mL-1) > Hyptis suaveolens (31 µg mL-1) = Persea caerulea (31 µg mL-1) > Lippia origanoides (62 µg mL-1). Based on CIG values, the flavonoid compounds showed the highest antigenotoxic potential as follows: apigenin (7 µM) > pinocembrin (15 µM) > quercetin (26 µM) > naringenin (38 µM) > epigallocatechin gallate (108 µM) > resveratrol (642 µM). UV-genotoxicity inhibition with epigallocatechin gallate, naringenin and resveratrol was related to its capability for inhibiting protein synthesis. A correlation analysis between compound antigenotoxicity estimates and antioxidant activity evaluated by the oxygen radical absorbance capacity (ORAC) assay showed that these activities were not related. The usefulness of the SOS Chromotest for bioprospecting of plant antigenotoxic agents against UV was discussed.

Fibromyalgia beyond reductionism. Heart rhythm fractal analysis to assess autonomic nervous system resilience.

OBJECTIVES: The prevailing linear reductionist medical model seems unable to explain complex multisymptomatic illnesses such as fibromyalgia (FM) and similar maladies. Paradigms derived from the complexity theory may provide a coherent framework for these elusive illnesses. Along these lines is the proposal that FM represents a degradation of our main complex adaptive system (the autonomic nervous system, ANS), in a failed effort to adjust to a hostile environment. Healthy complex systems have fractal structures. Heart rate fractal-like variability reflects resilient ANS performance. Our aim was to measure the heart rate variability (HRV) fractal scaling index in FM patients and to correlate this index with clinical symptoms. METHOD: We studied 30 women with FM and 30 controls. All participants filled out questionnaires assessing the severity of FM. The HRV fractal scaling index was estimated during 24 h using detrended fluctuation analysis (DFA). RESULTS: The fractal scaling index alpha-1 was higher in FM patients than in controls (mean ± sd: 1.22 ± 0.10 vs. 1.16 ± 0.09; p = 0.031). There was a positive correlation between the fractal scaling index alpha-1 and the visual analogue scale (VAS) for depression (Spearman's ρ = 0.36, p = 0.04). CONCLUSIONS: The heart rate fractal exponent alpha-1 is altered in FM patients, suggesting a rigid ANS performance. This tangible non-linear finding supports the notion that FM may represent a degradation of our main complex adaptive system, namely the ANS.

Preserving fertility in women with endometrial cancer: two clinical cases.

Endometrial cancer is diagnosed increasingly in young women who wish to have children, and treatments intended to preserve fertility in these patients are becoming more common. The authors describe two women with endometrial cancer who were diagnosed and treated at our center and who needed assisted human reproductive technology, and review current knowledge based on similar cases.

Langerhans cell histiocytosis mimicking acute dacryocystitis.

Langerhans cell histiocytosis (LCH) is a myeloid neoplasm characterized by clonal neoplastic proliferation of Langerhans-type dendritic cells associated with an inflammatory infiltrate predominantly composed of lymphocytes and eosinophils. In this article, we present an unusual case of LCH with significant swelling in the left lacrimal sac region in a 3-year-old child, clinically mimicking acute dacryocystitis. Microscopically, it showed intense inflammatory infiltrate and histiocytes with irregular nuclei. The tumor cells were positive for S-100 protein, CD1a, and CD207 (langerin). Molecular study was positive for the V600E/E2/D mutation (EXON 15). This case emphasizes the importance of careful clinical, radiographic, and microscopic evaluation, as some neoplasms may mimic common benign lesions.

Screen printed flexible radiofrequency identification tag for oxygen monitoring.

In this work, a radiofrequency identification (RFID) tag with an optical indicator for the measurement of gaseous oxygen is described. It consists of an O2 sensing membrane of PtOEP together with a full electronic system for RFID communication, all printed on a flexible substrate. The membrane is excited by an LED at 385 nm wavelength and the intensity of the luminescence generated is registered by means of a digital color detector. The output data corresponding to the red coordinate of the RGB color space is directly related to the concentration of O2, and it is sent to a microcontroller. The RFID tag is designed and implemented by screen printing on a flexible substrate for the wireless transmission of the measurement to a remote reader. It can operate in both active and passive mode, obtaining the power supply from the electromagnetic waves of the RFID reader or from a small battery, respectively. This system has been fully characterized and calibrated including temperature drifts, showing a high-resolution performance that allows measurement of very low values of oxygen content. Therefore this system is perfectly suitable for its use in modified atmosphere packaging where the oxygen concentration is reduced below 2%. As the reading of the O2 concentration inside the envelope is carried out with an external RFID reader using wireless communication, there is no need for perforations for probes or wires, so the packaging remains completely closed. With the presented device, a limit of detection of 40 ppm and a resolution as low as 0.1 ppm of O2 can be reached with a low power consumption of 3.55 mA.

Subretinal abscess due to nocardia in an immunosuppressed patient: a case report.

Systemic nocardiosis is a rarely occurring pathology, but its hematogenous spread across the eye is even less likely to occur, with only a few recorded cases. Therefore, it is not usually taken into account when a subretinal abscess is being considered for a diagnosis. However, when confronting a case with a history of immunosupression and pulmonary disease, the examination of the ocular fundus may be a very successful approach. With such aim we introduce the case of a 45-year-old immunosupressed male, without a history of pulmonary disease, whose subretinal mass evolution is accordant with an abscess. In the end, being etiologically diagnosed by means of a vitrectomy, it was concluded that the abscess was due to an infection of nocardia cyriacigeorgica, an emergent pathogen. Thus the aforementioned case is to be considered in the present study, along others, in order to shed more light on a disease which may not be readily diagnosed on account of its infrequency.

Advanced design of a x-ray absorption spectroscopy setup for measuring transition metals speciation in molten carbonates, hydroxides and hydrogenosulfates.

Battery recycling is currently becoming a crucial issue. One possible treatment path involves the use of molten salts. A mechanistic understanding of the underlying processes requires being able to analyze in situ speciation in molten salts at various temperatures. This can be advantageously achieved using x-ray absorption spectroscopy, the use of Quick-EXAFS facilities being particularly appropriate. Consequently, this paper presents the design and development of a new setup allowing carrying out Quick-EXAFS experiments in oxidizing molten salts at high temperatures. We describe the different components of a cell and the performance of the heating device. We illustrate the capabilities of the setup by analyzing the temperature evolution of Co speciation upon dissolution of LiCoO2, a typical battery electrode material, in molten carbonates, hydroxides, and hydrogenosulphates.

Smart facemask for wireless CO2 monitoring.

The use of facemasks by the general population is recommended worldwide to prevent the spread of SARS-CoV-2. Despite the evidence in favour of facemasks to reduce community transmission, there is also agreement on the potential adverse effects of their prolonged usage, mainly caused by CO2 rebreathing. Herein we report the development of a sensing platform for gaseous CO2 real-time determination inside FFP2 facemasks. The system consists of an opto-chemical sensor combined with a flexible, battery-less, near-field-enabled tag with resolution and limit of detection of 103 and 140 ppm respectively, and sensor lifetime of 8 h, which is comparable with recommended FFP2 facemask usage times. We include a custom smartphone application for wireless powering, data processing, alert management, results displaying and sharing. Through performance tests during daily activity and exercise monitoring, we demonstrate its utility for non-invasive, wearable health assessment and its potential applicability for preclinical research and diagnostics.

Effects of the COVID-19 pandemic on a cohort of patients with vein occlusion.

BACKGROUND AND OBJECTIVES: A new coronavirus disease in humans, COVID-19, caused by SARS-CoV-2, emerged in December 2019. It has been associated with the development of thrombotic phenomena. Retinal vein occlusion (RVO) is mainly a consequence of vascular risk factors (VRF). This study aimed to analyze cases of COVID-19 in a cohort of patients with RVO (Valdecilla cohort). PATIENTS AND METHODS: Between December 2008 and December 2020, 429 patients with RVO were attended to in our clinic. Ten patients had COVID-19, one of which did not have VRF or thrombophilia. The remaining nine patients had RVO prior to the infection and VRF, six had carotid atherosclerosis, and four had antiphospholipid syndrome. The infection did not cause thrombotic phenomena in any of them. CONCLUSIONS: RVO is a rare manifestation of COVID-19. In our cohort of patients with RVO, COVID-19 disease did not lead to thrombotic events.

Point-of-care lung ultrasound in children with bronchiolitis in a pediatric emergency department.

OBJECTIVES: This study assessed the association between findings of lung ultrasound (LUS) performed in the pediatric emergency department (PED) on infants with bronchiolitis and need for respiratory support. METHODS: An observational study was carried out in the PED during the epidemic seasons in two consecutive years. Infants diagnosed with bronchiolitis who fulfilled the inclusion criteria were evaluated. A group of six pediatricians performed LUS and classified lung findings into four groups: normal pattern (A), moderate interstitial pattern (B1), severe interstitial pattern (B2), and isolated consolidation (C). The relationship between LUS findings and need for respiratory support was explored. An expert sonographer, blinded to the results, reviewed the ultrasound studies to determine the interobserver reliability. RESULTS: A total of 200 infants were included (mean age 5.7 months±4.4 SD); 65 (32.5%) obtained moderate clinical scores, while 23 (11.5%) needed respiratory support at admission and 34 (17.0%) at 48h. The ultrasound findings in the PED were the following: A=89 (44.5%), B1=55 (27.5%), B2=34 (17%), and C=22 (11%). Age less than 6 weeks and moderate bronchiolitis were correlated with abnormal LUS (P<0.005). The severity of interstitial ultrasound pattern has some correlation with an increased need for respiratory support. The interobserver concordance was high (0.95, confidence interval: 0.92-0.98). CONCLUSION: LUS is a feasible tool that may help to confirm the clinical impression and assess the need for respiratory support in children with bronchiolitis, but further multicenter studies are needed.

Behavioral choice across leech species: chacun à son goût.

At any one time, animals are simultaneously bombarded with many sensory stimuli, but they typically choose to respond to only a few of them. We used multidimensional analysis to determine the behavioral responses of six species of leeches to stimulation, as the responses are affected by species identity, diet, behavioral state and stimulus location. Our results show that each of the species tested while not feeding displayed remarkably similar behaviors in response to tactile stimulation of the surface of the body. When not feeding, stimulus location was the most reliable factor in determining behavioral response. While feeding, the three sanguivorous (bloodsucking) species tested ignored stimulation, whereas the three carnivorous leeches abandoned feeding in favor of locomotory responses, regardless of phylogenetic relationships. In the sanguivorous leeches, feeding abolished all mechanically elicited responses and mechanical stimulation in turn had no effect on feeding. We also show that the behavioral hierarchy of leeches was fixed and unchanging even in species that can consume both a carnivorous and a sanguivorous diet.

A machine learning-based model for 1-year mortality prediction in patients admitted to an Intensive Care Unit with a diagnosis of sepsis.

INTRODUCTION: Sepsis is associated to a high mortality rate, and its severity must be evaluated quickly. The severity of illness scores used are intended to be applicable to all patient populations, and generally evaluate in-hospital mortality. However, patients with sepsis continue to be at risk of death after hospital discharge. OBJECTIVE: To develop a model for predicting 1-year mortality in critical patients diagnosed with sepsis. PATIENTS: The data corresponding to 5650 admissions of patients with sepsis from the Medical Information Mart for Intensive Care (MIMIC-III) database were evaluated, randomly divided as follows: 70% for training and 30% for validation. DESIGN: A retrospective register-based cohort study was carried out. The clinical information of the first 24h after admission was used to develop a 1-year mortality prediction model based on Stochastic Gradient Boosting (SGB) methodology. Variable selection was addressed using Least Absolute Shrinkage and Selection Operator (LASSO) and SGB variable importance methodologies. The predictive power was evaluated using the area under the ROC curve (AUROC). RESULTS: An AUROC of 0.8039 (95% confidence interval (CI): [0.8033 0.8045]) was obtained in the validation subset. The model exceeded the predictive performances obtained with traditional severity of disease scores in the same subset. CONCLUSION: The use of assembly algorithms, such as SGB, for the generation of a customized model for sepsis yields more accurate 1-year mortality prediction than the traditional scoring systems such as SAPS II, SOFA or OASIS.