Imbalance of SARS-CoV-2-specific CCR6+ and CXCR3+ CD4+ T cells and IFN-γ + CD8+ T cells in patients with Long-COVID.

Long-COVID (LC) is characterised by persistent symptoms for at least 3 months after acute infection. A dysregulation of the immune system and a persistent hyperinflammatory state may cause LC. LC patients present differences in activation and exhaustion states of innate and adaptive compartments. Different T CD4+ cell subsets can be identified by differential expression of chemokine receptors (CCR). However, changes in T cells with expression of CCRs such as CCR6 and CXCR3 and their relationship with CD8+ T cells remains unexplored in LC. Here, we performed unsupervised analysis and found CCR6+ CD4+ subpopulations enriched in COVID-19 convalescent individuals upon activation with SARS-CoV-2 peptides. SARS-CoV-2 specific CCR6+ CD4+ are decreased in LC patients, whereas CXCR3+ CCR6- and CCR4+ CCR6- CD4+ T cells are increased. LC patients showed lower IFN-γ-secreting CD8+ T cells after stimulation with SARS-CoV-2 Spike protein. This work underscores the role of CCR6 in the pathophysiology of LC.

Hypersensitivity reaction to Abiraterone, successful desensitization protocol in prostate cancer patient.

INTRODUCTION: In prostate cancer, androgens are key in the growth of both normal prostate and cancer cells. Abiraterone acetate inhibits CYP17, an important target in prostate cancer given its central role in the production of adrenal and tumor-derived androgens. Although abiraterone is generally well tolerated, common adverse effects such as hypertension, hypokalemia, and hepatotoxicity have been reported. CLINICAL CASE: We present the case of an 83-year-old Mexican man with high-volume EC IV prostate cancer resistant to castration, orchiectomy, and bone, liver, and lung metastases. First-line treatment with the CHAARTED scheme was indicated, by patient decision refuse chemotherapy treatment. On the fourth day of starting treatment, he developed pruritic erythematous macular skin lesions and urticaria on the posterior chest that resolved spontaneously. A generalized erythematous and pruritic maculopapular rash appeared 12 days after starting abiraterone, for which she was referred to allergies. MANAGEMENT AND RESULTS: An oral provocation test was performed for two days, presenting localized macular lesions eight hours after the administration of abiraterone. An oral desensitization protocol was carried out for ten days in which no hypersensitivity reactions were observed, thus achieving the successful administration of abiraterone.

Valvulitis: a new echocardiographic criterion for the diagnosis of bioprosthetic aortic valve infective endocarditis.

INTRODUCTION AND OBJECTIVES: Diffuse homogeneous hypoechoic leaflet thickening, with a wavy leaflet motion documented by transesophageal echocardiography (TEE), has been described in some cases of prosthetic valve endocarditis (PVE) involving aortic bioprosthesis (AoBio-PVE). This echocardiographic finding has been termed valvulitis. We aimed to estimate the prevalence of valvulitis, precisely describe its echocardiographic characteristics, and determine their clinical significance in patients with AoBio-PVE. METHODS: From 2011 to 2022, 388 consecutive patients with infective endocarditis (IE) admitted to a tertiary care hospital were prospectively included in a multipurpose database. For this study, all patients with AoBio-PVE (n=86) were selected, and their TEE images were thoroughly evaluated by 3 independent cardiologists to identify all cases of valvulitis. RESULTS: The prevalence of isolated valvulitis was 12.8%, and 20.9% of patients had valvulitis accompanied by other classic echocardiographic findings of IE. A total of 9 out of 11 patients with isolated valvulitis had significant valve stenosis, whereas significant aortic valve regurgitation was documented in only 1 patient. Compared with the other patients with AoBio-PVE, cardiac surgery was less frequently performed in patients with isolated valvulitis (27.3% vs 62.7%, P=.017). In 4 out of 5 patients with valve stenosis who did not undergo surgery but underwent follow-up TEE, valve gradients significantly improved with appropriate antibiotic therapy. CONCLUSIONS: Valvulitis can be the only echocardiographic finding in infected AoBio and needs to be identified by imaging specialists for early diagnosis. However, this entity is a diagnostic challenge and additional imaging techniques might be required to confirm the diagnosis. Larger series are needed.

The Delfos Platform: A Conceptual Model-Based Solution for the Enhancement of Precision Medicine.

The use in the clinical practice of the vast amount of genomic data generated by current sequencing technologies constitutes a bottleneck for the progress of Precision Medicine (PM). Various problems inherent to the genomics domain (i.e., dispersion, heterogeneity, discrepancies, lack of standardization, and data quality issues) remain unsolved. In this paper, we present the Delfos platform, a conceptual model-based solution developed following a rigorous methodological and ontological background, whose main aim is to minimize the impact of these problems when transferring the research results to clinical practice. This paper presents the SILE method that provides methodological support for the Delfos platform, the Conceptual Schema of the Genome that provides a shared understanding of the domain, and the technological architecture behind the implementation of the platform. This paper also exemplifies the use of the Delfos platform through two use cases that involve the study of the DNA variants associated with the risk of developing Dilated Cardiomyopathies and Neuroblastoma.

Design, synthesis and validation of a new Crimped Head-Piece for DNA-Encoded libraries generation.

Codification of DNA Encoded Libraries (DELs) is critical for successful ligand identification of molecules that bind a protein of interest (POI). There are different encoding strategies that permit, for instance, the customization of a DEL for testing single or dual pharmacophores (single strand DNA) or for producing and screening large diversity libraries of small molecules (double strand DNA). Both approaches challenges, either from the synthetic and encoding point of view, or from the selection methodology to be utilized for the screening. The Head-Piece contains the DNA sequence that is attached to a chemical compound, allowing the encoding of each molecule with a unique DNA tag. Designing the Head-Piece for a DNA-encoded library involves careful consideration of several key aspects including DNA barcode identity, sequence length and attachment chemistry. Here we describe a double stranded DNA versatile Head-Piece that can be used for the generation of single or dual pharmacophore libraries, but also shows other advanced DEL functionalities, stability and enlarged encoding capacity.

Colonic Anastomoses Reinforced With Ethyl-2-Cyanoacrylate Compared With Polydioxanone Sutures Alone in Fecal Peritonitis: An Experimental Study in Wistar Rats.

INTRODUCTION: The use of tissue adhesives has been proposed as an anastomosis reinforcement; however, their efficacy has not been evaluated in a contaminated environment. The objective of this study was to determine if the use of sutures reinforced with ethyl-2-cyanoacrylate for colonic anastomoses in the presence of fecal peritonitis, in a murine animal model, decreases the frequency of dehiscence. METHODS: Wistar rats were used. Fecal peritonitis was established until reaching 18 hours of evolution. Then, resection and anastomosis of the colon were performed with only polydioxanone (PDS) sutures in the control group and reinforcement with ethyl-2-cyanoacrylate in the experimental group. The dehiscence frequency and burst pressure were evaluated six days after the anastomosis was performed. RESULTS: We included 30 Wistar rats, all males, with a median age of five months and an average weight of 350.43 g. Anastomotic dehiscence was observed in 53.33% of the control group, in contrast with 13.33% of the experimental group (p = 0.020). There was no significant difference in burst pressure between the two groups. CONCLUSION: The use of ethyl-2-cyanoacrylate, in an experimental murine animal model, as reinforcement in colonic anastomoses in the presence of fecal peritonitis decreases the frequency of anastomotic dehiscence, although it does not increase resistance to burst pressure.

Development of a novel cryostructured composite coating of xanthan-bovine collagen-oregano essential oil spraying applied for the preservation of commercial biscuits marketed in Mexico.

Cryostructured gels, better known as cryogels, are a very important emerging class of biomaterials that have diverse applications in food preservation. This work shows a novel alternative to prepare a cryostructured composite coating made from a blend of xanthan, bovine collagen, and oregano essential oil. The composite coating was suitably applied onto the surface of preservative-free biscuits which were stored for 15 days at 25 ± 2°C and 52% ± 1% relative humidity. The evaluation focused mainly on the changes in the physicochemical, textural, and microbiological characteristics of the biscuits. It was found that the coated samples significantly (p < 0.05) decreased moisture absorption, water activity, and fungal growth. However, the composite coating minimally impacted the quality of biscuits in terms of color, texture profile, and surface microstructure. Overall, the cryostructured composite coating constitutes an advance in technological strategies aimed at the preservation of baked products. This will allow, in the future, the development of novel coatings on bakery products to generate new trends in the conservation of their properties and extension of shelf life. This could be achieved through the implementation of new technologies in the food industry, with the aim of making them more environmentally friendly and contributing to the generation of less plastic waste. PRACTICAL APPLICATION: The study and application of cryogels, as innovative systems in the food industry, allow to expand and diversify the materials that can function as coatings to maintain some quality characteristics, in this case in bakery products, so it is important to analyze their effects and consider them to improve conservation processes.

Comparative study of conventional frying and air frying on the quality of potatoes (Solanum tuberosum L.).

The human being has historically consumed fried foods for centuries; however, conventional frying has a disadvantage, immersion in vegetable and/or animal oils, which leads to the search for different options. This is why air frying is a good alternative, which still has a wide field of study. In this work, frozen French fries of a brand marketed in Mexico that were subjected to frying in canola oil and air frying were compared. They were evaluated through the change in the removed moisture content, water activity, color profile, hardness, fracturability, and surface damage by SEM, thermal analysis by MDSC, and chemical by FTIR-ATR spectroscopy. Air-fried French fries were found to contain about 48% less moisture, fewer perceptible color changes, and less surface damage translated into better crunchiness compared with conventionally fried. It was also found that the changes at the chemical level are smaller, mainly attributed to the absence of canola oil and that the thermal transitions are more stable in terms of temperatures and enthalpies, which makes it possible to emphasize that air frying is a good alternative for developing new fried products that allow expanding the variety of these in the market without sacrificing some quality attributes.

Occurrence of SARS-CoV-2 viremia is associated with genetic variants of genes related to COVID-19 pathogenesis.

Introduction: SARS-CoV-2 viral load has been related to COVID-19 severity. The main aim of this study was to evaluate the relationship between SARS-CoV-2 viremia and SNPs in genes previously studied by our group as predictors of COVID-19 severity. Materials and methods: Retrospective observational study including 340 patients hospitalized for COVID-19 in the University Hospital La Princesa between March 2020 and December 2021, with at least one viremia determination. Positive viremia was considered when viral load was above the quantifiable threshold (20 copies/ml). A total of 38 SNPs were genotyped. To study their association with viremia a multivariate logistic regression was performed. Results: The mean age of the studied population was 64.5 years (SD 16.6), 60.9% patients were male and 79.4% white non-Hispanic. Only 126 patients (37.1%) had at least one positive viremia. After adjustment by confounders, the presence of the minor alleles of rs2071746 (HMOX1; T/T genotype OR 9.9 p < 0.0001), rs78958998 (probably associated with SERPING1 expression; A/T genotype OR 2.3, p = 0.04 and T/T genotype OR 12.9, p < 0.0001), and rs713400 (eQTL for TMPRSS2; C/T + T/T genotype OR 1.86, p = 0.10) were associated with higher risk of viremia, whereas the minor alleles of rs11052877 (CD69; A/G genotype OR 0.5, p = 0.04 and G/G genotype OR 0.3, p = 0.01), rs2660 (OAS1; A/G genotype OR 0.6, p = 0.08), rs896 (VIPR1; T/T genotype OR 0.4, p = 0.02) and rs33980500 (TRAF3IP2; C/T + T/T genotype OR 0.3, p = 0.01) were associated with lower risk of viremia. Conclusion: Genetic variants in HMOX1 (rs2071746), SERPING1 (rs78958998), TMPRSS2 (rs713400), CD69 (rs11052877), TRAF3IP2 (rs33980500), OAS1 (rs2660) and VIPR1 (rs896) could explain heterogeneity in SARS-CoV-2 viremia in our population.

Diagnostic Assessment of Respiratory and Hemodynamic Changes Related to Prone Position in COVID-19 Patients.

OBJECTIVE: To study the respiratory patterns and the hemodynamic variations related to postural changes in inpatients with coronavirus disease (COVID-19). METHODS: This report is a prospective study in a cohort of inpatients admitted with COVID-19. We recruited 10 patients admitted to the hospital with moderate or severe COVID-19 who showed improvement in oxygen saturation with prone positioning. We performed cardiorespiratory polygraphy and hemodynamic evaluations by thoracic electrical bioimpedance. RESULTS: We observed a median minimum oxygen saturation of 85.00% (IQR: 7.00) in the supine position versus 91.00% (IQR: 8.00) (P = 0.173) in the prone position. The airflow restriction in the supine position was 2.70% (IQR: 6.55) versus 1.55% (IQR: 2.80) (P = 0.383) in the prone position. A total of 36.4% of patients were classified as having a normo-hemodynamic state in the supine position, whereas 54.5% were classified in this group in the prone position (P = 0.668). A decrease in vascular resistance was observed in the prone position (18.2% of vasoconstriction) compared to the supine position (36.4% of vasoconstriction) (P = 0.871). CONCLUSION: This brief report describes the effects of prone positioning on respiratory and hemodynamic variables in 10 patients with moderate or severe COVID-19.

Assessment of atmospheric emissivity models for clear-sky conditions with reanalysis data.

Atmospheric longwave downward radiation (Ld) is one of the significant components of net radiation (Rn), and it drives several essential ecosystem processes. Ld can be estimated with simple empirical methods using atmospheric emissivity (εa) submodels. In this study, eight global models for εa were evaluated, and the best-performing model was calibrated on a global scale using a parametric instability analysis approach. The climatic data were obtained from a dynamically consistent scale resolution of basic atmospheric quantities and computed parameters known as NCEP/NCAR reanalysis (NNR) data. The performance model was evaluated with monthly average values from the NNR data. The Brutsaert equation demonstrated the best performance, and then it was calibrated. The seasonal global trend of the Brutsaert equation calibrated coefficient ranged between 1.2 and 1.4, and the K-means analysis identified five homogeneous zones (clusters) with similar behavior. Finally, the calibrated Brutsaert equation improved the Rn estimation, with an error reduction, at the worldwide scale, of 64%. Meanwhile, the error reduction for each cluster ranged from 18 to 77%. Hence, Brutsaert's equation coefficient should not be considered a constant value for use in εa estimation, nor in time or location.

Psychometric properties of the self-efficacy scale for chronic disease management (SEMCD-S) in older Colombian adults.

BACKGROUND: Self-efficacy alludes to personal competence in an individual's effectiveness when facing stressful situations. This construct has been related to different domains of the health field, finding that high levels of self-efficacy benefit human functioning and enhance well-being. METHODS: The present study aimed to determine the psychometric properties of the self-efficacy scale for managing chronic diseases (SEMCD-S) by assessing factorial, convergent and divergent validity, reliability, and measurement invariance. Likewise, the comparison of self-efficacy according to socio-demographic characteristics was proposed by contrasting latent factors. An instrumental, transactional, descriptive, and non-experimental design study was carried out with the participation of 325 Colombian senior citizens. RESULTS: The findings suggest that the scale has appropriate psychometric properties. The one-factor structure exhibited a satisfactory fit, the mean-variance extracted reported acceptable figures and the correlation analysis with other constructs supported this instrument's convergent and discriminant validity. Likewise, it was invariant to the different socio-demographic aspects examined, while the internal consistency figures were high. Differences in the means of the latent factors were only detected in the academic grade. In this case, older adults with a primary school level attained higher self-efficacy values than those who had completed high school or university studies. CONCLUSIONS: It is concluded that the self-efficacy scale for chronic disease management is a valid and reliable instrument that can be used in the Colombian context to measure and compare this construct.

3D Virtual modelling, 3D printing and extended reality for planning of implant procedure of short-term and long-term mechanical circulatory support devices and heart transplantation.

Introduction: The use of three-dimensional (3D) reconstruction and printing technology, together with extended reality applied to advanced heart failure adult patients with complex anatomy, is rapidly spreading in clinical practice. We report practical experience with application to acute and chronic heart failure: planning and performing mechanical circulatory device insertion or heart transplantation. Methods: From November 2019 until February 2022, 53 3D virtual biomodels were produced for intervention planning (using Virtual/Augmented Reality and/or 3D printing), following a specific segmentation and preprocessing workflow for biomodelling, in patients with advanced heart failure due to structural heart disease or cardiomyopathies. Four of those patients were complex cases requiring mechanical circulatory support implant procedures in our center. Results: One short-term and three long-term ventricular assist device system were successfully clinically implanted after application of this technique. In other two cases with extremely high procedural risk, visualized after application of this multimodality imaging, heart transplantation was elected. Conclusion: 3D printing based planning and virtual procedure simulation, are of great importance to select appropriate candidates for mechanical circulatory support in case of complex patient anatomy and may help to diminish periprocedural complications. Extended reality represents a perspective tool in planification of complex surgical procedures or ventricular assist device insertion in this setting.

Histiocitosis combinada de tipo Langerhans (Histiocitosis de células de Langerhans y enfermedad de Erdheim-Chester) en varón de 64 años con mutaciones en BRAF y NRAS: a propósito de un caso / Combined histiocytosis of the Langerhans group (Langerhans cell histiocytosis and Erdheim-Chester disease) in a 64-year-old man with BRAF and NRAS mutations: a case report

Paciente varón de 64 años con antecedente de enfermedad de Crohn que en el contexto de un episodio de dolor abdominal agudo es ingresado en el hospital, siendo diagnosticado, tras el estudio histológico de una biopsia cutánea y otra pulmonar, de una histiocitosis combinada encuadrada dentro de las histiocitosis del grupo L (Langerhans). En la biopsia cutánea se evidenció proliferación de células histiocitarias con positividad inmunohistoquímica para Langerina, CD1a, S100, resultando el estudio molecular de la misma positivo para la mutación BRAF p.V600E. En la biopsia pulmonar se evidenció una proliferación de células histiocitarias con positividad inmunohistoquímica para CD68 y para S100 y negatividad para Langerina y CD1a, detectándose en la misma mutaciones en NRAS c.38G>A en el exón 2 (p.G13D).(AU)

We present a case of a 64-year-old male with a history of Crohn's disease who presented with an episode of acute abdominal pain. He was being investigated for a dermatological lesion. A skin and lung biopsy both revealed histiocytosis of the “L” (Langerhans) group. The skin biopsy showed a proliferation of histiocytic cells expressing Langerin, CD1a and S100 and the molecular study was positive for the BRAF p.V600E mutation. In the lung biopsy, a proliferation of histiocytic cells was found, which were positive for CD68 and S100 and negative for Langerin and CD1a; mutations in NRAS c.38G>A in exon 2 (p.G13D) were also detected.(AU)

[Combined histiocytosis of the Langerhans group (Langerhans cell histiocytosis and Erdheim-Chester disease) in a 64-year-old man with BRAF and NRAS mutations: a case report]. / Histiocitosis combinada de tipo Langerhans (Histiocitosis de células de Langerhans y enfermedad de Erdheim-Chester) en varón de 64 años con mutaciones en BRAF y NRAS: a propósito de un caso.

We present a case of a 64-year-old male with a history of Crohn's disease who presented with an episode of acute abdominal pain. He was being investigated for a dermatological lesion. A skin and lung biopsy both revealed histiocytosis of the "L" (Langerhans) group. The skin biopsy showed a proliferation of histiocytic cells expressing Langerin, CD1a and S100 and the molecular study was positive for the BRAF p.V600E mutation. In the lung biopsy, a proliferation of histiocytic cells was found, which were positive for CD68 and S100 and negative for Langerin and CD1a; mutations in NRAS c.38G>A in exon 2 (p.G13D) were also detected.

N-aryltetrahydroisoquinoline derivatives as HA-CD44 interaction inhibitors: Design, synthesis, computational studies, and antitumor effect.

Hyaluronic acid (HA) plays a crucial role in tumor growth and invasion through its interaction with cluster of differentiation 44 (CD44), a non-kinase transmembrane glycoprotein, among other hyaladherins. CD44 expression is elevated in many solid tumors, and its interaction with HA is associated with cancer and angiogenesis. Despite efforts to inhibit HA-CD44 interaction, there has been limited progress in the development of small molecule inhibitors. As a contribution to this endeavour, we designed and synthesized a series of N-aryltetrahydroisoquinoline derivatives based on existing crystallographic data available for CD44 and HA. Hit 2e was identified within these structures for its antiproliferative effect against two CD44+ cancer cell lines, and two new analogs (5 and 6) were then synthesized and evaluated as CD44-HA inhibitors by applying computational and cell-based CD44 binding studies. Compound 2-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinolin-5-ol (5) has an EC50 value of 0.59 µM against MDA-MB-231 cells and is effective to disrupt the integrity of cancer spheroids and reduce the viability of MDA-MB-231 cells in a dose-dependent manner. These results suggest lead 5 as a promising candidate for further investigation in cancer treatment.