Sfrp1 inhibits lung fibroblast invasion during transition to injury-induced myofibroblasts.

BACKGROUND: Fibroblast-to-myofibroblast conversion is a major driver of tissue remodelling in organ fibrosis. Distinct lineages of fibroblasts support homeostatic tissue niche functions, yet their specific activation states and phenotypic trajectories during injury and repair have remained unclear. METHODS: We combined spatial transcriptomics, multiplexed immunostainings, longitudinal single-cell RNA-sequencing and genetic lineage tracing to study fibroblast fates during mouse lung regeneration. Our findings were validated in idiopathic pulmonary fibrosis patient tissues in situ as well as in cell differentiation and invasion assays using patient lung fibroblasts. Cell differentiation and invasion assays established a function of SFRP1 in regulating human lung fibroblast invasion in response to transforming growth factor (TGF)ß1. MEASUREMENTS AND MAIN RESULTS: We discovered a transitional fibroblast state characterised by high Sfrp1 expression, derived from both Tcf21-Cre lineage positive and negative cells. Sfrp1 + cells appeared early after injury in peribronchiolar, adventitial and alveolar locations and preceded the emergence of myofibroblasts. We identified lineage-specific paracrine signals and inferred converging transcriptional trajectories towards Sfrp1 + transitional fibroblasts and Cthrc1 + myofibroblasts. TGFß1 downregulated SFRP1 in noninvasive transitional cells and induced their switch to an invasive CTHRC1+ myofibroblast identity. Finally, using loss-of-function studies we showed that SFRP1 modulates TGFß1-induced fibroblast invasion and RHOA pathway activity. CONCLUSIONS: Our study reveals the convergence of spatially and transcriptionally distinct fibroblast lineages into transcriptionally uniform myofibroblasts and identifies SFRP1 as a modulator of TGFß1-driven fibroblast phenotypes in fibrogenesis. These findings are relevant in the context of therapeutic interventions that aim at limiting or reversing fibroblast foci formation.

Effect of Terminal Hydroxy Groups on the Structural Properties of Acyl Thioureas.

The 1-acyl thiourea family [R1C(O)NHC(S)NR2R3] exhibits the flexibility to incorporate a wide variety of substituents into their structure. The structural attributes of these compounds are intricately tied to the type and extent of substitution. In the case of 3-mono-substituted thioureas (R2=H), the conformational behavior is predominantly shaped by the presence of an intramolecular N-H ⋅ ⋅ ⋅ O=C hydrogen bond. This study delves into the structural consequences stemming from the inclusion of substituents possessing hydrogen-donor capabilities within four novel 1-acyl-3-mono-substituted thiourea derivatives. A comprehensive suite of analytical techniques, encompassing FTIR, Raman spectroscopy, multinuclear (1H and 13C) NMR spectroscopy, single-crystal X-ray diffraction, and supported by computational methods, notably NBO (Natural Bond Orbital) population analysis, Hirshfeld analysis, and QTAIM (Quantum Theory of Atoms in Molecules), was harnessed to scrutinize and characterize these compounds. In the crystalline state, these compounds exhibit an intricate interplay of intermolecular interactions, prominently featuring an expansive network of hydrogen bonds between the hydroxy (-OH) groups and the carbonyl and thiocarbonyl bonds within the 1-acyl thiourea fragment. Notably, the topological analysis underscores significant distinctions in the properties of the acyl thiourea fragment and the intramolecular >C=O ⋅ ⋅ ⋅ H-N bond when transitioning from the isolated molecule to the crystalline environment.

SARS-CoV-2's brain impact: revealing cortical and cerebellar differences via cluster analysis in COVID-19 recovered patients.

BACKGROUND: COVID-19 is a disease known for its neurological involvement. SARS-CoV-2 infection triggers neuroinflammation, which could significantly contribute to the development of long-term neurological symptoms and structural alterations in the gray matter. However, the existence of a consistent pattern of cerebral atrophy remains uncertain. OBJECTIVE: Our study aimed to identify patterns of brain involvement in recovered COVID-19 patients and explore potential relationships with clinical variables during hospitalization. METHODOLOGY: In this study, we included 39 recovered patients and 39 controls from a pre-pandemic database to ensure their non-exposure to the virus. We obtained clinical data of the patients during hospitalization, and 3 months later; in addition we obtained T1-weighted magnetic resonance images and performed standard screening cognitive tests. RESULTS: We identified two groups of recovered patients based on a cluster analysis of the significant cortical thickness differences between patients and controls. Group 1 displayed significant cortical thickness differences in specific cerebral regions, while Group 2 exhibited significant differences in the cerebellum, though neither group showed cognitive deterioration at the group level. Notably, Group 1 showed a tendency of higher D-dimer values during hospitalization compared to Group 2, prior to p-value correction. CONCLUSION: This data-driven division into two groups based on the brain structural differences, and the possible link to D-dimer values may provide insights into the underlying mechanisms of SARS-COV-2 neurological disruption and its impact on the brain during and after recovery from the disease.

Targeting genomic SARS-CoV-2 RNA with siRNAs allows efficient inhibition of viral replication and spread.

A promising approach to tackle the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) could be small interfering (si)RNAs. So far it is unclear, which viral replication steps can be efficiently inhibited with siRNAs. Here, we report that siRNAs can target genomic RNA (gRNA) of SARS-CoV-2 after cell entry, and thereby terminate replication before start of transcription and prevent virus-induced cell death. Coronaviruses replicate via negative sense RNA intermediates using a unique discontinuous transcription process. As a result, each viral RNA contains identical sequences at the 5' and 3' end. Surprisingly, siRNAs were not active against intermediate negative sense transcripts. Targeting common sequences shared by all viral transcripts allowed simultaneous suppression of gRNA and subgenomic (sg)RNAs by a single siRNA. The most effective suppression of viral replication and spread, however, was achieved by siRNAs that targeted open reading frame 1 (ORF1) which only exists in gRNA. In contrast, siRNAs that targeted the common regions of transcripts were outcompeted by the highly abundant sgRNAs leading to an impaired antiviral efficacy. Verifying the translational relevance of these findings, we show that a chemically modified siRNA that targets a highly conserved region of ORF1, inhibited SARS-CoV-2 replication ex vivo in explants of the human lung. Our work encourages the development of siRNA-based therapies for COVID-19 and suggests that early therapy start, or prophylactic application, together with specifically targeting gRNA, might be key for high antiviral efficacy.

Menarche and reproductive health in Spanish Roma women from a reproductive justice perspective: a qualitative study.

OBJECTIVES: This study aimed to explore the perceptions of Roma women about their experience of menarche and reproductive health considering the principles of reproductive justice. DESIGN: Qualitative study based on semi-structured interviews with Roma women ages 18 through 67 in different neighborhoods in the southeast of Spain. Using a thematic analysis, we analyzed experiences related to menarche and menstruation and their significance for reproductive health, the preparation for the phase of menarche and intergenerational support. RESULTS: The Roma women interviewed shared their approach to the experiences of menarche and menstruation as children in their family environments with a focus on access to information provided by other women in the family and community for reproductive health management. In their discourses we observed that the onset of menstruation supposes a rupture in the public and private spaces of girls and women. CONCLUSIONS: The results of this study suggest that women and girls do not gain access to information that contributes to their reproductive wellbeing through their experience of menarche. Access to resources and skills to manage biological changes in adolescents could contribute to reducing the impact of cultural myths, false ideas and taboos that prevent advocacy and empowerment on issues of reproductive justice.

This study shows that the public spaces surrounding Roma women do not provide the tools and resources to promote and maintain their wellbeing and reproductive health after the onset of this important time. Sexual and reproductive health is not addressed during the time of childhood nor adolescence. Roma women lack a framework with an established discourse on reproductive justice, along with the necessary institutional resources. Preparation for and follow-up of the onset of menstruation among Roma women could be a key for their health. These results coincide with qualitative studies carried out in women from different cultural origins, in which menarche and menstruation are experienced as a transcendental fact. In other contexts, similar to Roma women, this stage in women's health lacks resources and information and an adequate approach from the perspective of reproductive health, which conditions the menstrual, sexual and reproductive health of women across their lifespan. Roma women experience menarche as a significant change in the life of a woman. They describe having lived the process as an abandonment of childhood and the beginning of an adult life, one that is implicitly linked to maternity and couple relationships. The results show that they defend the continuity of childhood among the new generation. Roma women express that they experienced menarche as an event that was traumatic, embarrassing and confusing. Menarche and menstruation are attended to in private and among the family, and masculine figures do not participate. The mother is the only transmitter of information and support during the process.

Lupus enteritis: A 10-year experience in a single Latin American center.

OBJECTIVE: The objective is to compare the clinical and laboratory characteristics of systemic lupus erythematosus (SLE) patients with and without lupus enteritis (LE) and to identify the factors associated with the occurrence of LE. METHODS: We performed a retrospective, case-control study in hospitalized patients with SLE who were admitted to our tertiary hospital between January 2012 and December 2021. Sixteen LE patients (cases) were matched (1:3 ratio) for sex and birth year with 48 non-LE patients (controls). Univariable and multivariable logistic regression analyses were used to identify the variables associated with LE. RESULTS: Of 2,479 SLE patients who were admitted to our hospital as inpatients, 16 (0.65%) were diagnosed as having LE. All patients, cases and controls, were of Mestizo ethnicity. SLE was diagnosed simultaneously with the first episode of LE in 10 (62.5%) patients. The median time from SLE diagnosis to the first episode of LE was 7 (IQR 0-78) months. LE patients had a shorter median disease duration [7 (0-78) vs 34 (9.5-79) months], and a significantly longer hospital stay (28.3 ± 15.8 vs 6.5 ± 7.9 days, p < 0.001) than non-LE patients. Most LE patients (93.8%) had concomitant lupus nephritis. LE patients had higher SLEDAI-2K scores than those without LE (20.5 ± 9.4 vs 9.8 ± 10.4, p < 0.001). By multivariable analysis, a higher SLEDAI-2K score (OR 1.10, 95% CI 1.02-1.18; p = 0.015) was independently associated with LE occurrence after adjusting for cutaneous involvement, lymphocyte count, serum creatinine, and serum complement C4. Recurrence was observed in two patients (12.5%), both with a bowel wall thickening > 8 mm. The two patients with large intestine-dominant LE developed intestinal pseudo-obstruction. No patient had life-threatening complications (intestinal hemorrhage, infarction, or perforation), and there were no deaths induced directly by LE itself. CONCLUSION: In patients of Mestizo ethnicity, LE occurs during the early course of SLE, frequently is one of the presenting manifestations of SLE, and in most cases, it presents with concomitant lupus nephritis. Higher levels of disease activity at diagnosis were independently associated with LE occurrence and when recurrences occur, they do so in the context of severe wall thickness.

Drawing liquid bridges from a thin viscous film.

When a particle, such as dust, contacts a thin liquid film covering a surface it is trapped by the liquid. This effect is caused by the formation of a meniscus, resulting in a capillary force that makes the particle adhere to the surface. While capillary adhesion is well-characterised in static situations, the dynamic formation of the liquid bridge after the initial contact is highly intricate. Here, we experimentally study the evolution of a liquid bridge after a glass sphere is gently brought into contact with a thin viscous film. It is found that the contact creates a ripple on the thin film, which influences the growth of the meniscus. Initially, the ripple and the meniscus are coupled and exhibit similar dynamics. This initial regime is well accounted for by a scaling law derived from lubrication theory. At a later stage, the ripple is "detached" from the liquid bridge, leading to a second regime of bridge dynamics. As a result, capillary forces are time-dependent, highlighting the importance of dynamics on adhesion.

An impact evaluation of conservation investments targeting long-distance migratory species.

We evaluated the impact of a philanthropic program investing in the conservation of sites along the Pacific Americas Flyway, which spans >16,000 km of coastline and is used by millions of shorebirds. Using a quasi-experimental, mixed methods approach, we estimated what would have happened to shorebird populations at 17 wintering sites without the sustained and additional investment they received. We modeled shorebird populations across the entire flyway and at sites with and without investment. Combining shorebird abundance estimates with a land-cover classification model, we used the synthetic control method to create counterfactuals for shorebird trends at the treatment sites. We found no evidence of an overall effect across three outcome variables. Species- and site-level treatment effects were heterogeneous, with a few cases showing evidence of a positive effect, including a site with a high level of overall investment. Results suggest six shorebirds declined across the entire flyway, including at many Latin American sites. However, the percentage of flyway populations present at the sites remained stable, and the percentage at the treatment sites was higher (i.e., investment sites) than at control sites. Multiple mechanisms behind our results are possible, including that investments have yet to mitigate impacts and negative impacts at other sites are driving declines at the treatment sites. A limitation of our evaluation is the sole focus on shorebird abundance and the lack of data that prohibits the inclusion of other outcome variables. Monitoring infrastructure is now in place to design a more robust and a priori shorebird evaluation framework across the entire flyway. With this framework, it will prove easier to prioritize limited dollars to result in the most positive conservation outcomes.

Evaluación del impacto de la inversión para la conservación enfocada en especies migratorias de largo recorrido Resumen Evaluamos el impacto de un programa filantrópico que invierte en la conservación de sitios a lo largo de la Ruta Migratoria Pacífico-Américas, la cual abarca >16,000 km de la línea costera y millones de aves playeras la usan. Estimamos con una estrategia cuasiexperimental y de métodos mixtos lo que habría pasado con las poblaciones de estas aves en 17 sitios invernales sin la inversión adicional y continua que recibieron. Modelamos estas poblaciones en toda la ruta y en sitios con y sin inversión. Combinamos las estimaciones de aves playeras con el modelo de clasificación de la cobertura del suelo y usamos el método de control sintético para crear contrafactuales para las tendencias de las aves playeras en sitios de tratamiento. No encontramos evidencia alguna de un efecto generalizado en las tres variables de los resultados. Los efectos del tratamiento de especies y de sitio fueron heterogéneos, con unos cuantos casos que mostraron evidencia de un efecto positivo, incluido un sitio con un nivel elevado de inversión general. Los resultados sugieren que seis especies de aves playeras declinaron a lo largo de toda la ruta, incluyendo en varios sitios de América Latina. Sin embargo, el porcentaje de poblaciones de la ruta presentes en los sitios permaneció estable y el porcentaje en los sitios de tratamiento (sitios de inversión) fue más elevado que en los sitios control. Muchos mecanismos son posibles detrás de nuestros resultados, incluidas las inversiones que todavía no han mitigado impactos y los impactos negativos en otros sitios que están causando las declinaciones en los sitios de tratamiento. Una limitación en nuestra evaluación es el enfoque único en la abundancia de aves playeras y la falta de datos que impiden la inclusión de otras variables de los resultados. El monitoreo de la infraestructura ahora está en una posición en la que puede diseñar un marco de evaluación más robusto y a priori de las aves playeras a lo largo de toda la ruta. Con este marco, será más fácil priorizar los dólares limitados para que los resultados de conservación sean lo más positivos posible.

Assessing three industrially produced fungi for the bioremediation of diclofenac.

Diclofenac is an emerging pollutant: toxic, persistent, and bioaccumulative, present in several environmental niches in a concentration of parts per million. This pharmaceutical's biological removal was reported with various fungal species, showing promissory results. This work aimed at diclofenac removal by individually challenging the fungal species Pleurotus ostreatus, Aspergillus niger, and Penicillium roquefortii but triying to lower the biosorption nature of cell walls by NaCl addition. P. ostreatus removed 100% of the initial diclofenac concentration, whereas A. niger and P. roqueforti removed 74% and 32%, respectively. In all three cases, biosorption by polar interactions was negligible. We demonstrated that stressful environments, such as mineral media, force the fungus to take advantage of its metabolic tools to survive, hence showing higher removal capacity when limiting growth conditions. Bioremediation is an excellent alternative to give residual fungal biomass a secondary use.

Argentine Guidelines for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis in Postmenopausal Women and Men Aged 50 Years and Older.

OBJECTIVE: The aim of this study was to provide an evidence-based framework to guide health care professionals treating patients under glucocorticoid (GC) therapy and develop guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis (GIO) in postmenopausal women and men aged ≥50 years. METHODS: An expert panel on bone diseases designed a series of clinically meaningful questions following the PICO (Population, Intervention, Comparator, and Outcome) structure. Using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology, we made a systematic literature review, extracted and summarized the effect estimates, and graded the quality of the evidence. The expert panel voted each PICO question and made recommendations after reaching an agreement of at least 70%. RESULTS: Seventeen recommendations (9 strong and 8 conditional) and 8 general principles were developed for postmenopausal women and men aged ≥50 years under GC treatment. Bone mineral density (BMD), occurrence of fragility fractures, probability of fracture at 10 years by Fracture Risk Assessment Tool, and other screening factors for low BMD are recommended for patient evaluation and stratification according to fragility fracture risk. The treatment of patients under GC therapy should include counseling on lifestyle habits and strict control of comorbidities. The goal of GIO treatment is the nonoccurrence of new fragility fractures as well as to increase or maintain BMD in certain clinical situations. This was considered for the therapeutic approach in different clinical scenarios. CONCLUSIONS: This GIO guideline provides evidence-based guidance for health care providers treating patients.

Clinical monitored in subjects metabolically healthy and unhealthy before and during a SARS-CoV-2 infection- A cross-sectional study in Mexican population.

The COVID-19 disease has forced us to consider the physiologic role of obesity and metabolically healthy and unhealthy status in response to SARS-CoV-2 infection. Hematological, coagulation, biochemical, and immunoinflammatory changes have been informed with a disparity in morbidity and mortality. Therefore, we aimed to investigate the influence of metabolic health on clinical features in a cross-sectional study in Mexican subjects with and without SARS-CoV-2 infection in non-severe stages after a rigorous classification of obese and non-obese subjects who were metabolically healthy and unhealthy. Four groups were formed: 1) metabolically healthy with normal BMI (MHN); 2) metabolically unhealthy with normal BMI (MUN); 3) metabolically healthy obese (MHO); 4) metabolically unhealthy obese (MUO). Serum proinflammatory (TNF-α, MCP-1, IL-1ß, and IL-6) and anti-inflammatory (TGF-ß, IL-1Ra, IL-4, and IL-10) cytokines, hematological parameters, coagulation, and acute phase components were evaluated. Our results showed that MHO people live with inflammaging. Meanwhile, MUN and MUO subjects develop metaflammation. Both inflammaging and metaflammation cause imperceptible modifications on hematological parameters, mainly in leukocyte populations and platelets, as well as acute phase and coagulation components. The statistical analysis revealed that many clinical features are dependent on metabolic health. In conclusion, MHO subjects seem to be transitioning from metabolically healthy to unhealthy, which is accelerated in acute processes, such as SARS-CoV-2 infection. Meanwhile, metabolically unhealthy subjects independently of BMI have a deteriorating immunometabolic status associated with a hyperinflammatory state leading to multi-organ dysfunction, treatment complications, and severe COVID-19 disease.

Squeezing Drops: Force Measurements of the Cassie-to-Wenzel Transition.

Superhydrophobic surfaces have long been the center of attention of many researchers due to their unique liquid repellency and self-cleaning properties. However, these unique properties rely on the stability of the so-called Cassie state, which is a metastable state with air-filled microstructures. This state tends to transit to the stable Wenzel state, where the inside of the microstructures eventually wets. For potential industrial applications, it is therefore critical to maintain the Cassie state. We investigate the Cassie-to-Wenzel transition on superhydrophobic micropillar surfaces by squeezing a water drop between the surface and a transparent superhydrophobic force probe. The probe's transparency allows the use of top-view optics to monitor the area of the drop as it is squeezed against a micropillared surface. The impalement, or Cassie-to-Wenzel transition, is identified as a sharp decrease in force accompanied by an abrupt change in the drop's contact area. We compare the force measured by the sensor with the capillary pressure force calculated from the observed drop shape and find a good agreement between both quantities. We also study the force and pressure at impalement as a function of the pillar's slenderness ratio. Finally, we compare the impalement pressure with three literature predictions and find that our experimental values are consistently lower than the theoretical values. We find that a possible cause of this earlier Cassie-to-Wenzel transition may be the coalescence of the squeezed drop with microdroplets that nucleate around the base of the micropillars.

Charging of drops impacting onto superhydrophobic surfaces.

When neutral water drops impact and rebound from superhydrophobic surfaces, they acquire a positive electrical charge. To measure the charge, we analyzed the trajectory of rebounding drops in an external electric field by high-speed video imaging. Although this charging phenomenon has been observed in the past, little is known about the controlling parameters for the amount of drop charging. Here we investigate the relative importance of five of these potential variables: impact speed, drop contact area, contact line retraction speed, drop size, and type of surface. We additionally apply our previously reported model for sliding drop electrification to the case of impacting drops, suggesting that the two cases contain the same charge separation mechanism at the contact line. Both our experimental results and our theoretical model indicate that maximum contact area is the dominant control parameter for charge separation.

T cell metabolism and possible therapeutic targets in systemic lupus erythematosus: a narrative review.

In the immunopathogenesis of systemic lupus erythematosus (SLE), there is a dysregulation of specific immune cells, including T cells. The metabolic reprogramming in T cells causes different effects. Metabolic programs are critical checkpoints in immune responses and are involved in the etiology of autoimmune disease. For instance, resting lymphocytes generate energy through oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO), whereas activated lymphocytes rapidly shift to the glycolytic pathway. Specifically, mitochondrial dysfunction, oxidative stress, abnormal metabolism (including glucose, lipid, and amino acid metabolism), and mTOR signaling are hallmarks of T lymphocyte metabolic dysfunction in SLE. Herein it is summarized how metabolic defects contribute to T cell responses in SLE, and some epigenetic alterations involved in the disease. Finally, it is shown how metabolic defects could be modified therapeutically.

[Adverse reactions to drugs used for COVID-19 in five Latin American countriesReações adversas a medicamentos utilizados para a COVID-19 em cinco países da América Latina]. / Reacciones adversas a medicamentos utilizados para la COVID-19 en cinco países de América Latina.

Objective: Characterize and describe reports of suspected adverse reactions to a group of drugs used in Colombia, Costa Rica, Cuba, Chile, El Salvador, Mexico, and Peru to treat or prevent coronavirus disease (COVID-19) between 1 March and 31 August 2020. Methods: A list of the 13 drugs used to treat or prevent COVID-19 was prepared, based on official and unofficial sources. Drawing on the databases of the national pharmacovigilance programs of the participating countries, reports of suspected adverse reactions to these drugs were collected for the period from 1 March and 31 August 2020. Results: A total of 3 490 reports of suspected adverse reactions were received from the pharmacovigilance programs of Peru (n = 3 037), Cuba (n = 270), Colombia (n = 108), Chile (n = 72), and El Salvador (n = 3). The drugs with the highest number of reported adverse reactions were azithromycin, ivermectin, and hydroxychloroquine. Diarrhea was the most frequent event (15.0%). Of the total suspected adverse reactions, 11.9% were reported as serious. The most frequent was QT prolongation following use of hydroxychloroquine. Of these suspected serious adverse reactions, 54.5% occurred in people over 65 years of age. Conclusions: While it is not possible to establish a causal relationship from the evaluation of spontaneous reports, the present study confirms the presence of adverse reactions-some of them serious-involving drugs used to treat or prevent COVID-19.

Objetivo: Caracterizar e descrever as notificações de suspeitas de reações adversas a um grupo de medicamentos utilizados na Colômbia, Costa Rica, Cuba, Chile, El Salvador, México e Peru, para tratar ou prevenir a doença do coronavírus (COVID-19), entre 1º de março e 31 de agosto de 2020. Métodos: Foi elaborada uma lista dos 13 medicamentos usados para tratar ou prevenir a COVID-19, segundo fontes oficiais e não oficiais. A partir das bases de dados dos programas nacionais de farmacovigilância dos países participantes, foram coletadas notificações de suspeitas de reações adversas a esses medicamentos, recebidas no período entre 1º de março e 31 de agosto de 2020. Resultados: Foram recebidas 3.490 notificações de suspeitas de reações adversas dos programas de farmacovigilância do Peru (n = 3.037), Cuba (n = 270), Colômbia (n = 108), Chile (n = 72) e El Salvador (n = 3). Os medicamentos com maior número de notificações de reações adversas foram azitromicina, ivermectina e hidroxicloroquina. A diarreia foi o evento mais frequente (15,0%). Do total de suspeitas de reações adversas, 11,9% foram notificadas como graves. A mais frequente foi o prolongamento do intervalo QT após o uso de hidroxicloroquina. Dessas suspeitas de reações adversas graves, 54,5% ocorreram em pessoas com mais de 65 anos. Conclusão: Embora não seja possível estabelecer uma relação causal com base na avaliação de relatos espontâneos, o presente estudo confirma a presença de reações adversas ­ algumas graves ­ a medicamentos que foram usados para tratar ou prevenir a COVID-19.

Carboxymethyl-Dextran-Coated Superparamagnetic Iron Oxide Nanoparticles for Drug Delivery: Influence of the Coating Thickness on the Particle Properties.

Carboxymethyl-dextran (CMD)-coated iron oxide nanoparticles (IONs) are of great interest in nanomedicine, especially for applications in drug delivery. To develop a magnetically controlled drug delivery system, many factors must be considered, including the composition, surface properties, size and agglomeration, magnetization, cytocompatibility, and drug activity. This study reveals how the CMD coating thickness can influence these particle properties. ION@CMD are synthesized by co-precipitation. A higher quantity of CMD leads to a thicker coating and a reduced superparamagnetic core size with decreasing magnetization. Above 12.5−25.0 g L−1 of CMD, the particles are colloidally stable. All the particles show hydrodynamic diameters < 100 nm and a good cell viability in contact with smooth muscle cells, fulfilling two of the most critical characteristics of drug delivery systems. New insights into the significant impact of agglomeration on the magnetophoretic behavior are shown. Remarkable drug loadings (62%) with the antimicrobial peptide lasioglossin and an excellent efficiency (82.3%) were obtained by covalent coupling with the EDC/NHS (N-ethyl-N'-(3-(dimethylamino)propyl)carbodiimide/N-hydroxysuccinimide) method in comparison with the adsorption method (24% drug loading, 28% efficiency). The systems showed high antimicrobial activity with a minimal inhibitory concentration of 1.13 µM (adsorption) and 1.70 µM (covalent). This system successfully combines an antimicrobial peptide with a magnetically controllable drug carrier.

Perchlorate-reducing bacteria from Antarctic marine sediments.

Perchlorate is a contaminant that can persist in groundwater and soil, and is frequently detected in different ecosystems at concentrations relevant to human health. This study isolated and characterised halotolerant bacteria that can potentially perform perchlorate reduction. Bacterial microorganisms were isolated from marine sediments on Deception, Horseshoe and Half Moon Islands of Antarctica. The results of the 16S ribosomal RNA (rRNA) gene sequence analysis indicated that the isolates were phylogenetically related to Psychrobacter cryohalolentis, Psychrobacter urativorans, Idiomarina loihiensis, Psychrobacter nivimaris, Sporosarcina aquimarina and Pseudomonas lactis. The isolates grew at a sodium chloride concentration of up to 30% and a perchlorate concentration of up to 10,000 mg/L, which showed their ability to survive in saline conditions and high perchlorate concentrations. Between 21.6 and 40% of perchlorate was degraded by the isolated bacteria. P. cryohalolentis and P. urativorans degraded 30.3% and 32.6% of perchlorate, respectively. I. loihiensis degraded 40% of perchlorate, and P. nivimaris, S. aquimarina and P. lactis degraded 22%, 21.8% and 21.6% of perchlorate, respectively. I. loihiensis had the highest reduction in perchlorate, whereas P. lactis had the lowest reduction. This study is significant as it is the first finding of P. cryohalolentis and. P. lactis on the Antarctic continent. In conclusion, these bacteria isolated from marine sediments on Antarctica offer promising resources for the bioremediation of perchlorate contamination due to their ability to degrade perchlorate, showing their potential use as a biological system to reduce perchlorate in high-salinity ecosystems.

Impact cratering in sand: comparing solid and liquid intruders.

How does the impact of a deformable droplet on a granular bed differ from that caused by a solid impactor of similar size and density? Here, we experimentally study this question and focus on the effect of intruder deformability on the crater shape. For comparable impact energies, we show that the crater diameter is larger for droplets than for solid intruders but that the impact of the latter results in deeper craters. Interestingly, for initially dense beds of packing fractions larger than 0.58, we find that the resultant excavated crater volume is independent of the intruder deformability, suggesting an impactor-independent dissipation mechanism within the sand for these dense beds.

Sodium metavanadate treatment improves glycogen levels in multiple tissues in a model of metabolic syndrome caused by chronic cadmium exposure in Wistar rats.

Cadmium, one of the more hazardous environmental contaminants, has been proposed as a metabolic disruptor. Vanadium has emerged as a possible treatment for metabolic diseases. Both metals are important in public health. We aimed to investigate whether vanadium treatment is effective against metabolic disturbances caused by chronic exposure to the lowest-observable adverse effect level of cadmium. Male Wistar rats were exposed to cadmium (32.5 ppm) in drinking water for 3 months. Metabolic complications such as overweight, visceral adipose gain, hyperglycemia, impaired glucose tolerance, and dyslipidemia were detected, and low glycogen levels and steatosis were observed in the tissues. Then, the control and treated animals were subdivided and treated with a solution of 5 µM NaVO3/kg/twice a week for 2 months. The control-NaVO3 group did not show zoometric or metabolic changes. A strong interaction of NaVO3 treatment over cadmium metabolic disruption was observed. The vanadium accumulation diminished cadmium concentration in tissues. Also, vanadium interaction improved glucose homeostasis. The major effect was observed on glycogen synthesis, which was fully recovered in all tissues analyzed. Additionally, vanadium treatment prevented overweight and visceral fat accumulation, improving BMI and the percentage of fat. However, NaVO3 treatment did not have an effect on dyslipidemia or steatosis. In conclusion, this work shows that vanadium administration has a strong effect against metabolic disturbances caused by chronic cadmium exposure, observing powerful interaction on glucose homeostasis.

Impact of the use of multiplex PCR on etiological diagnosis and treatment of acute respiratory infections in a private hospital of the north of the country.

BACKGROUND AND OBJECTIVE: Diseases of the respiratory system represent one of the leading causes of medical care and antibiotic prescriptions. Currently, new technologies are used for the diagnosis of respiratory diseases of viral origin, such as the FilmArray Respiratory Panel®, approved in 2012 by the FDA. The purpose of this study was to identify the correlation between the diagnosis and treatment of respiratory tract infections and the result of the polymerase chain reaction test for respiratory viruses. MATERIAL AND METHODS: The study is of a retrospective, cross-sectional, descriptive type. One-hundred and thirty-four patients who underwent a viral panel for respiratory viruses, which was positive for one or more viruses, were included. For all cases, the positive results of said test and the treatment received by patients were analyzed. RESULTS: Of the patients who underwent nasopharyngeal aspirate during hospitalization, 58 % received antibiotic treatment at admission, 13 % received combined treatment (antibiotic + antiviral), 27 % of the patients received symptomatic treatment since admission and 2 % did it with antivirals. After receiving a positive result for respiratory viruses, 38 % continued with antibiotics, 30 % with antibiotics and antivirals, 13.8 % were managed only with antivirals and 18.2 % with symptomatic treatment. CONCLUSION: Despite the global alert regarding antimicrobial resistance, patients continue to be treated with antibiotics, due to a situation that we ignore, but that is believed to be influenced by several factors.

ANTECEDENTES Y OBJETIVO: Las enfermedades del sistema respiratorio son causa frecuente de prescripción de antibióticos. Actualmente se emplean nuevas tecnologías para su diagnóstico como el FilmArray Respiratory Panel. El objetivo de este estudio es identificar la correlación entre el diagnóstico y tratamiento de infecciones de vías respiratorias con el resultado de PCR para virus respiratorios. MATERIAL Y MÉTODOS: Estudio descriptivo, transversal, retrospectivo, se incluyeron 134 pacientes atendidos en el Hospital Christus Muguerza en Saltillo, Coahuila. Para todos los casos se analizaron los resultados del panel y el tratamiento que recibieron los pacientes. RESULTADOS: El 58 % recibió tratamiento antibiótico a su ingreso, el 13 % tratamiento combinado (antibiótico + antiviral), 27 % recibió tratamiento sintomático y el 2 % fue tratado con antiviral de primera instancia. Posterior al resultado el 38 % continuó con antibiótico, el 30 % con antibiótico y antiviral, 13.8 % se manejó con antiviral y el 18.2 % con tratamiento sintomático. CONCLUSIÓN: A pesar de la alerta mundial por la resistencia a los antimicrobianos se sigue tratando a los pacientes con antibióticos, por una situación que se cree está influenciada por varios factores.