Fluctuating asymmetry (FA) is an indicator of developmental instability referred to random deviations from mean asymmetry. That average asymmetry is the directional asymmetry (DA), which, in the ...particular case of adolescent idiopathic scoliosis (AIS), corresponds to a right thoracic and left lumbar curves. Investigating the presence of FA and DA in AIS has never been done, and it is a key element of the pathophysiology of the scoliotic condition. Thirty‐six X‐rays of patients with AIS were digitized and analysed using Geometric Morphometric analyses to test for both statistical effects. The individual FA score for each patient was calculated using Procrustes ANOVA and a methodology based on the components of shape was used to estimate the individual DA score. DA is a stronger effect than FA (2.12 to 1), as it has been found in other clinical conditions. The individual DA score, with an effect size of 0.58, is a better predictor of the Cobb angle than FA score. The methodology presented in this paper to estimate DA score is a valid approach in the study of asymmetries in AIS. FA should be correlated in future studies with environmental covariates to serve as a variable in the medical prognosis, while DA will serve as a good predictor of the Cobb angle during the course of the condition, avoiding the abuse of X‐rays. This potential use of DA should be tested on 3D shape due to the three‐dimensional clinical presentation of AIS.
A new methodology has been developed that measures directional and fluctuating asymmetry, and these individual scores make it possible to predict the Cobb angle (from the DA score) and measure developmental instability (from the FA score) in patients with adolescent idiopathic scoliosis.
Objective
Adolescent idiopathic scoliosis is the most prevalent type of scoliosis, and its consequences on the human torso have not been deeply studied. In spite of being a 3D condition, clinical ...management is circumscribed to 2D images among health-care professionals. GMM is a well-recognized tool in the study of 3D shape and symmetry.
Methods
Twenty-four subjects with AIS and 24 controls were subjected to surface scan. Digitization and shape data were extracted and submitted to GMM analysis. 3D shape and asymmetry were correlated with Cobb angle in subjects with X-ray availability. Comparisons of mean shapes were done between each group and its symmetric average shape and between each group at two states: initial and 6 months after.
Results
AIS and controls show similar areas of asymmetry, being significantly higher in quantity in AIS (PD = 0.045; PD 0.037;
p
< 0.001). Significant correlation was observed between Cobb angle and Procrustes asymmetry (
r
= 0.38;
p
= 0.01) as happened with 3D shape (
r
= 0.11;
p
< 0.001). No significant changes were observed in the 3D shape of both groups 6 months after (AIS,
p
= 0.51; control,
p
= 0.304).
Conclusion
The greater asymmetry observed in AIS was expectable, but the similarity of areas of asymmetry in both groups made us suspect of directional asymmetry in the human torso that could explain the high prevalence of right scoliosis observed in nature. The shape of the torso and the asymmetry should be considered as variables to study in AIS due to its correlation with Cobb angle. Progression of the deformities was not observed in our study, maybe due to short-term follow-up.
Despite the extraordinary advances achieved to beat COVID-19 disease, many questions remain unsolved, including the mechanisms of action of SARS-CoV-2 and which factors determine why individuals ...respond so differently to the viral infection. Herein, we performed an in silico analysis to identify host microRNA targeting ACE2, TMPRSS2, and/or RAB14, all genes known to participate in viral entry and replication. Next, the levels of six microRNA candidates previously linked to viral and respiratory-related pathologies were measured in the serum of COVID-19-negative controls (n = 16), IgG-positive COVID-19 asymptomatic individuals (n = 16), and critical COVID-19 patients (n = 17). Four of the peripheral microRNAs analyzed (hsa-miR-32-5p, hsa-miR-98-3p, hsa-miR-423-3p, and hsa-miR-1246) were upregulated in COVID-19 critical patients compared with COVID-19-negative controls. Moreover, hsa-miR-32-5p and hsa-miR-1246 levels were also altered in critical versus asymptomatic individuals. Furthermore, these microRNA target genes were related to viral infection, inflammatory response, and coagulation-related processes. In conclusion, SARS-CoV-2 promotes the alteration of microRNAs targeting the expression of key proteins for viral entry and replication, and these changes are associated with disease severity. The microRNAs identified could be taken as potential biomarkers of COVID-19 progression as well as candidates for future therapeutic approaches against this disease.
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Herein, we have identified a panel of four miRNA targeting ACE2 and RAB14 genes significantly upregulated in the serum of COVID-19 critical patients compared with asymptomatic or negative individuals. These miRNAs might be taken as prognostic markers of SARS-CoV-2 infection, as well as potential therapeutic targets against COVID-19.
Identification of the emerging multidrug-resistant yeast
Candida auris
is challenging. Here, we describe the role of the Mexico national reference laboratory Instituto de Diagnóstico y Referencia ...Epidemiológicos Dr. Manuel Martínez Báez (InDRE) and the Mexican national laboratory network in the identification of
C. auris
. Reference identification of six suspected isolates was done based on phenotypic and molecular laboratory methods, including growth in special media, evaluation of isolate micromorphology, and species-specific PCR and pan-fungal PCR and sequencing. The four
C. auris
isolates identified were able to grow on modified Sabouraud agar with 10% NaCl incubated at 42 °C. With one exception, isolates of
C. auris
were spherical to ovoid yeast-like cells and blastoconidia, with no hyphae or pseudohyphae on cornmeal agar.
C. auris
isolates were resistant to fluconazole. Species-specific and pan-fungal PCR confirmed isolates as
C. auris
. Sequence analysis revealed the presence of two different
C. auris
clades in Mexico, clade I (South Asia) and clade IV (South America).
Patients with cardiovascular (CV) disease have an increased circulating angiotensin-converting enzyme 2 (ACE2) activity, but there is little information about changes in ACE2 in chronic kidney ...disease (CKD) patients without history of CV disease. We examined circulating ACE2 activity in CKD patients at stages 3-5 (CKD3-5) and in dialysis (CKD5D) without any history of CV disease.
Circulating ACE2 activity was measured in human ethylenediamine-tetraacetic acid (EDTA)-plasma samples from the NEFRONA study (n = 2572): control group (CONT) (n = 568), CKD3-5 (n = 1458) and CKD5D (n = 546). Different clinical and analytical variables such as gender; age; history of diabetes mellitus (DM), dyslipidemia and hypertension; glycaemic, renal, lipid and anaemia profiles; vitamin D analogues treatment and antihypertensive treatments (angiotensin-converting enzyme inhibitor and angiotensin receptor blockade) were analysed. Circulating ACE2 and ACE activities were measured using modified fluorimetric assay for EDTA-plasma samples, where zinc chloride was added to recover enzymatic activity.
In CKD3-5 and CKD5D, significant decrease in circulating ACE2 activity was observed when compared with CONT, but no differences were found between CKD3-5 and CKD5 when performing paired case-control studies. By multivariate linear regression analysis, male gender and advanced age were identified as independent predictors of ACE2 activity in all groups. Diabetes was identified as independent predictor of ACE2 activity in CKD3-5. Significant increase in the activity of circulating ACE was found in CKD3-5 and CKD5D when compared with CONT and in CKD5D when compared with CKD3-5. By multiple regression analysis, female gender and younger age were identified as independent predictors of ACE activity in CONT and CKD3-5. Diabetes was also identified as an independent predictor of ACE activity in CKD3-5 patients.
Circulating ACE2 and ACE activities can be measured in human EDTA-plasma samples with zinc added to recover enzymatic activity. In a CKD population without previous history of CV disease, ACE2 activity from human EDTA-plasma samples directly correlated with the classical CV risk factors namely older age, diabetes and male gender. Our data suggest that circulating ACE2 is altered in CKD patients at risk for CV event.
•Metal complexes (Co, Fe, Mn) bearing ONO ligands are highly active catalysts in CO2/epoxide coupling reaction.•Synthetized catalysts were tested successfully in catalytic coupling of CO2 with ...propylene oxide using PPNCl as co-catalyst.•The catalytic conditions for the Mn complex were optimized and reach the TOF of 1600 h−1.
The use of carbon dioxide as feedstock in copolymerization reaction with epoxides has been ideally proposed as an alternative route to produce chemicals without the use of phosgene. One of the most appealing strategies is to use metal complexes as catalysts to form cyclic organic carbonates. These organic compounds are very interesting in industry due to their enormous scope of applications. In this paper, the use of catalytic systems based on sustainable, non-toxic and cheap metal complexes (Mn, Fe, Co) containing Schiff-base tridentate ONO ligands in the synthesis of propylene carbonate (PC) from carbon dioxide and propylene oxide (PO), are discussed. All complexes were tested successfully, affording cyclic carbonate in high productivities (3800 mol PC/mol cat) using a co-catalyst. Synthetized iron and manganese complexes have shown significantly higher activities compared with the activity showed by the new cobalt complexes. The catalytic conditions using the manganese (II) complex 2 were optimized and a TOF of 1600 h−1 was reached.
This study aimed to: 1) analyze the inflammatory profile of Rheumatoid Arthritis (RA) patients, identifying clinical phenotypes associated with cardiovascular (CV) risk; 2) evaluate biologic and ...targeted-synthetic disease-modifying antirheumatic drugs (b-DMARDs and ts-DMARDs’: TNFi, IL6Ri, JAKinibs) effects; and 3) characterize molecular mechanisms in immune-cell activation and endothelial dysfunction.
A total of 387 RA patients and 45 healthy donors were recruited, forming three cohorts: i) 208 RA patients with established disease but without previous CV events; ii) RA-CVD: 96 RA patients with CV events, and iii) 83 RA patients treated with b-DMARDs/ts-DMARDs for 6 months. Serum inflammatory profiles (cytokines/chemokines/growth factors) and NETosis/oxidative stress-linked biomolecules were evaluated. Mechanistic in vitro studies were performed on monocytes, neutrophils and endothelial cells (EC).
In the first RA-cohort, unsupervised clustering unveiled three distinct groups: cluster 3 (C3) displayed the highest inflammatory profile, significant CV-risk score, and greater atheroma plaques prevalence. In contrast, cluster 1 (C1) exhibited the lowest inflammatory profile and CV risk score, while cluster 2 (C2) displayed an intermediate phenotype. Notably, 2nd cohort RA-CVD patients mirrored C3's inflammation.
Treatment with b-DMARDs or ts-DMARDs effectively reduced disease-activity scores (DAS28) and restored normal biomolecules levels, controlling CV risk. In vitro, serum from C3-RA or RA-CVD patients increased neutrophils activity and CV-related protein levels in cultured monocytes and EC, which were partially prevented by pre-incubation with TNFi, IL6Ri, and JAKinibs.
Overall, analyzing circulating molecular profiles in RA patients holds potential for personalized clinical management, addressing CV risk and assisting healthcare professionals in tailoring treatment, ultimately improving outcomes.
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•Unsupervised clustering of RA profiles revealed 3 groups with diverse inflammatory, oxidative, and netotic profiles.•RA patients without CV events but highest CV-risk showed inflammatory profiles akin to those with prior CV events.•TNFi, IL6Ri, and JAKi treatment for six months restores normal inflammatory biomolecule levels, cutting-RA-related CV-risk.•High CV risk RA serum activates neutrophils, modulates monocytes, and disrupts endothelial cells, reversed by b/ts-DMARDS.•Analyzing RA patients' molecular profiles enhances personalized management, addressing their cardiovascular risk.
This study describes the antimicrobial and anti-inflammatory effects from extracts obtained from the leaves of Salvia lavanduloides. The plant material was macerated with three solvents of ascending ...polarity (n-hexane (Sl-Hex), ethyl acetate (Sl-AcOEt), and dichloromethane (Sl-D)). The extracts, fractions (SlD-2 and SlD-3), and isolated compounds (15,16-epoxy-10-β-hydroxy-neo-cleroda-3,7,13(16),14-tetraene-17,12R:18,19-diolide (1), salviandulin A (2), and eupatorin (3)) were evaluated as antimicrobials against Gram-negative, Gram-positive bacteria and the fungus Candida albicans (Ca) using the minimum inhibitory concentration (MIC) and the anti-inflammatory activity induced by 13-acetate of 12-O-tetradecanoylforbol (TPA). Sl-D and Sl-AcOEt extracts, SlD-2 and SlD-3 fractions showed the highest antimicrobial activity. The isolated compounds showed good activity against Pseudomonas aeruginosa with a MIC < 2 μg/mL, while the anti-inflammatory activity, the Sl-Hex, Sl-D extracts, and SlD-3 fraction presented an inhibition of 62, 45 and 61%, respectively, while (2) 70% and (3) 72%.
A series of novel ONO ligands bearing an ionic pendant-armed (hereinafter indicated as ONONu, where Nu corresponds to an anionic nucleophile) were synthesized, characterized, and successfully ...coordinated to cobalt and manganese precursors. New air-stable cobalt (III) complexes (1–6) and manganese (II) complexes (7 and 8) were obtained and characterized. Single crystal X-ray diffraction analysis of the Co(III) compound 5 confirmed the presence of two quaternized ligands coordinated to the metal and iodide as counterion. These novel complexes were revealed to be active catalysts in the coupling reaction of carbon dioxide and propylene oxide (PO) in different degrees of success. Among these, the manganese complex 8 afforded the best results towards the formation of propylene carbonate (PC) with a productivity of 256 kg PC/(kg cat·h), achieving a TON of 4860.
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