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1.
Cureus ; 16(8): e66582, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39252741

RESUMEN

BACKGROUND: Chronic kidney disease (CKD) leads to a high rate of complications requiring hospital admission for advanced management. Therefore, this study aims to analyze the main causes of hospitalization following the initiation of renal replacement therapy (RRT). MATERIALS AND METHODS: This observational and descriptive study utilized a non-probabilistic quota sampling method, reviewing a total of 423 medical records from General Regional Hospital 1 of the Mexican Social Security Institute in Querétaro. The study evaluated the frequency and causality of hospitalizations during a retrospective period from 2018 to 2023. RESULTS: There were 1,162 hospitalization events involving 423 patients; 71.63% of patients started RRT with peritoneal dialysis, while 26% began with hemodialysis. The leading cause of hospitalization was electrolyte imbalance (397; 34.17%), followed by peritonitis associated with peritoneal dialysis (351; 30.21%), change to hemodialysis (270; 23.24%), Tenckhoff catheter dysfunction (209; 17.99%), and fluid overload (205; 17.64%). The group with the highest number of events was renal-related complications, followed by infectious causes. CONCLUSIONS: Hospitalizations in end-stage CKD patients often arise from the complex renal pathophysiology and complications related to acute and decompensated renal function. This condition refers to the kidneys' failure to maintain essential physiological functions despite ongoing treatment, leading to issues such as electrolyte imbalances, fluid overload, and uremic syndrome. To reduce morbidity and mortality, measures such as enhanced training in ambulatory dialysis, improved catheter care, and early infection detection are crucial. A comprehensive approach that addresses both acute issues and preventive strategies is essential for improving clinical outcomes and quality of life for these patients.

2.
Cureus ; 16(7): e65060, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39171022

RESUMEN

Lemierre's syndrome, a rare complication of oropharyngeal infections, is characterized by septic thrombophlebitis primarily affecting the internal jugular vein, which can lead to septicemia, thrombotic obstruction, and potential dissemination to distant sites. We present the case of a 54-year-old male with a history of chronic smoking and newly diagnosed laryngeal carcinoma, complicated by Lemierre's syndrome. Initial symptoms included odynophagia, dyspnea, and cervical swelling, with subsequent diagnosis confirming thrombosis of the internal jugular vein via ultrasound, CT, and MRI. Treatment included broad-spectrum antibiotics and anticoagulation, followed by oncological management for the carcinoma. This case underscores the diagnostic challenge posed by concurrent malignancy and highlights the critical role of early recognition and comprehensive treatment involving antibiotics, anticoagulation, and oncological therapy. Multidisciplinary collaboration is crucial for optimizing outcomes in complex cases like this, emphasizing the need for heightened clinical suspicion and prompt intervention involving proper imaging diagnosis, appropriate antibiotic coverage, and timely microbiological recognition for adjustment of antimicrobial therapy.

3.
BMC Ophthalmol ; 24(1): 312, 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39075390

RESUMEN

Immune checkpoint inhibitors (ICI) such as Programmed cell Death 1 (PD-1) inhibitors have improved cancer treatment by enhancing the immune system's ability to target malignant cells. Their use is associated with immune-related adverse events (irAEs), including uveitis. The profile of pro-inflammatory cytokines underlying Anti-PD-1-induced uveitis shares significant overlap with that of non-infectious uveitis. Current corticosteroid treatments for uveitis while effective are fraught with vision threatening side effects. The cytokine profile in ICI-related uveitis has a large overlap with that of noninfectious uveitis, this overlap strongly supports the potential for therapy that activates the PD-1 axis in the eye to treat uveitis. Indeed, ICI related uveitis often resolves with cessation of the ICI, restoring the endogenous PD-1 axis. The potential benefit of targeting many pro-inflammatory cytokines via local PD-1 axis activation is mitigating ocular inflammation while minimizing adverse effects.


Asunto(s)
Citocinas , Inhibidores de Puntos de Control Inmunológico , Receptor de Muerte Celular Programada 1 , Uveítis , Humanos , Uveítis/inducido químicamente , Uveítis/tratamiento farmacológico , Uveítis/inmunología , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Citocinas/metabolismo , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores
4.
Int J Mol Sci ; 25(10)2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38791178

RESUMEN

Three-dimensional cell cultures have improved the evaluation of drugs for cancer therapy, due to their high similarity to solid tumors. In melanoma, autophagy appears to show a dual role depending on the progression of the disease. p62 protein has been proposed for the evaluation of autophagic flux since its expression is an indicator of the state of autophagy. Pentoxifylline (PTX) and Norcantharidin (NCTD) are drugs that have been shown to possess anticancer effects. In this work, we used B16F1 mouse melanoma cells in two-dimensional (2D) monolayer cultures and three-dimensional (3D) spheroids to test the effect of PTX and NCTD over the p62 expression. We analyzed the effect on p62 expression through Western blot and immunofluorescence assays. Our results indicate that PTX decreases p62 expression in both cell culture models, while Norcantharidin increases its expression in 3D cultures at 24 h. Therefore, these drugs could have a potential therapeutic use for the regulation of autophagy in melanoma, depending on the state of evolution of the disease.


Asunto(s)
Autofagia , Compuestos Bicíclicos Heterocíclicos con Puentes , Pentoxifilina , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Animales , Ratones , Pentoxifilina/farmacología , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Melanoma Experimental/metabolismo , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/patología , Técnicas de Cultivo de Célula , Proteína Sequestosoma-1/metabolismo , Proteína Sequestosoma-1/genética , Antineoplásicos/farmacología , Esferoides Celulares/efectos de los fármacos , Esferoides Celulares/metabolismo
5.
Transplant Proc ; 56(2): 297-305, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38395659

RESUMEN

BACKGROUND: To describe and establish the efficacy and safety of Mycophenolate Mofetil (Micoflavin) in patients with de novo renal transplantation during one-year post-transplant follow-up. As secondary objectives, the behavior of mycophenolic acid (MPA) C0 levels in this population, the relationship between MPA levels and renal function of the grafts, the incidence of acute rejection, and the incidence of adverse effects were evaluated. METHODS: A prospective cohort study was conducted on patients who received a first kidney transplant from a deceased donor between March 1, 2021, and February 28, 2022, at the Alma Mater of Antioquia Hospital of the Antioquia's University, in Medellín, Colombia. MPA C0 levels were taken from the patients on days 15, 30, 90, 180, and 360 after the kidney transplantation. RESULTS: Patients presented MPA therapeutic levels in the study. The average of the MPA levels in the population was 2.5 µg/mL, with an IQR of 2.13 to 3.32. There were 5 acute rejections (27%), but none of the patients with acute rejection presented subtherapeutic levels of mycophenolate. No significant relationship was observed between mycophenolic acid levels and rejection (P = .255). The patients who completed the study had no gastrointestinal intolerance to mycophenolate, cytomegalovirus infections, or significant hematological complications. CONCLUSIONS: MMF (Micoflavin) maintained mycophenolic acid levels C0 within the therapeutic range, was well tolerated and without the presence of significant adverse events, and maintained stable renal function throughout the follow-up period in the population studied.


Asunto(s)
Trasplante de Riñón , Ácido Micofenólico , Humanos , Ácido Micofenólico/efectos adversos , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Receptores de Trasplantes , Estudios Prospectivos , Colombia , Inmunosupresores/efectos adversos , Inhibidores Enzimáticos , Rechazo de Injerto/epidemiología
7.
Emerg Infect Dis ; 30(2): 380-383, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38270112

RESUMEN

We conducted surveillance studies in Sinaloa, Mexico, to determine the circulation of tick-borne relapsing fever spirochetes. We collected argasid ticks from a home in the village of Camayeca and isolated spirochetes. Genomic analysis indicated that Borrelia turicatae infection is a threat to those living in resource-limited settings.


Asunto(s)
Infecciones por Borrelia , Borrelia , Fiebre Recurrente , Garrapatas , Animales , México/epidemiología , Borrelia/genética , Fiebre Recurrente/epidemiología , Infecciones por Borrelia/epidemiología
8.
Echocardiography ; 41(1): e15733, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38284668

RESUMEN

The coexistence of bicuspid aortic valve disease and coronary artery disease is well-established, but the identification of cardiac amyloidosis in this population has surged with advancing imaging techniques, introducing complexities in patient management. This case report emphasizes the pivotal role of multimodality imaging in accurately diagnosing three concurrent pathologies.


Asunto(s)
Neuropatías Amiloides Familiares , Estenosis de la Válvula Aórtica , Infarto del Miocardio , Humanos , Estenosis de la Válvula Aórtica/diagnóstico , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Neuropatías Amiloides Familiares/complicaciones , Neuropatías Amiloides Familiares/diagnóstico por imagen , Neuropatías Amiloides Familiares/patología , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/patología , Infarto del Miocardio/complicaciones
9.
Stem Cell Res Ther ; 14(1): 312, 2023 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-37904232

RESUMEN

BACKGROUND: Thymic epithelial cells (TECs) are responsible for shaping the repertoires of T cells, where their postnatal regeneration depends on a subset of clonogenic TECs. Despite the implications for regenerative medicine, their cultivation and expansion remain challenging. Primary explant cell culture is a technique that allows the seeding and expansion of difficult-to-culture cells. Here, we report a reliable and simple culture system to obtain functional TECs and thymic interstitial cells (TICs). METHODS: To establish primary thymic explants, we harvested 1 mm cleaned fragments of thymus from 5-week-old C57/BL6 mice. Tissue fragments of a complete thymic lobe were placed in the center of a Petri dish with 1 mL of DMEM/F-12 medium supplemented with 20% fetal bovine serum (FBS) and 1% penicillin‒streptomycin. To compare, thymic explants were also cultivated by using serum-free DMEM/F-12 medium supplemented with 10% KnockOut™. RESULTS: We obtained high numbers of functional clonogenic TECs and TICs from primary thymic explants cultivated with DMEM/F-12 with 20% FBS. These cells exhibited a highly proliferative and migration profile and were able to constitute thymospheres. Furthermore, all the subtypes of medullary TECs were identified in this system. They express functional markers to shape T-cell and type 2 innate lymphoid cells repertoires, such as Aire, IL25, CCL21 and CD80. Finally, we also found that ≥ 70% of lineage negative TICs expressed high amounts of Aire and IL25. CONCLUSION: Thymic explants are an efficient method to obtain functional clonogenic TECs, all mTEC subsets and different TICs Aire+IL25+ with high regenerative capacity.


Asunto(s)
Inmunidad Innata , Linfocitos , Ratones , Animales , Timo/metabolismo , Células Epiteliales/metabolismo , Linfocitos T , Diferenciación Celular
10.
Exp Appl Acarol ; 91(1): 99-110, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37584844

RESUMEN

Soft ticks from the Ornithodoros genus are vectors of relapsing fever (RF) spirochetes around the world. In Mexico, they were originally described in the 19th century. However, few recent surveillance studies have been conducted in Mexico, and regions where RF spirochetes circulate remain vague. Here, the presence of soft ticks in populated areas was assessed in two sites from the Mexican states of Aguascalientes and Zacatecas. Argasidae ticks were collected, identified by morphology and mitochondrial 16S rDNA gene sequencing, and tested for RF borreliae. The specimens in both sites were identified as Ornithodoros turicata but no RF spirochetes were detected. These findings emphasize the need to update the distribution of these ticks in multiple regions of Mexico and to determine the circulation of RF borreliosis in humans and domestic animals.


Asunto(s)
Argasidae , Borrelia , Ornithodoros , Fiebre Recurrente , Humanos , Animales , Fiebre Recurrente/epidemiología , Borrelia/genética , Animales Domésticos
11.
Dermatol Online J ; 29(5)2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-38478642

RESUMEN

Human monkeypox is a viral zoonosis that has recently emerged worldwide. Clinical cutaneous features include papules, vesicles, and pustules. However, atypical manifestations mimicking other infectious diseases are being reported more frequently. We present a 41-year-old man patient with untreated HIV with generalized rupioid crusted ulcerated plaques with perineal ulceration that were found to represent monkeypox and cytomegalovirus infections.


Asunto(s)
Coinfección , Infecciones por VIH , Mpox , Sífilis , Masculino , Humanos , Adulto , Sífilis/patología , Citomegalovirus , Coinfección/diagnóstico , Coinfección/patología , Piel/patología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico
12.
Inorg Chem ; 61(37): 14553-14559, 2022 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-36074140

RESUMEN

Tubular boron clusters represent a class of extremely unusual geometries that can be regarded as a key indicator for the 2D-to-3D boron structural evolution as well as the embryos for boron nanotubes. While a good number of pure boron or metal-doped boron tubular clusters have been reported so far, most of them are two-ring tubular structures, and their higher-ring analogues are very scarce. We report herein the first example of a four-ring tubular boron motif in the cagelike global minimum of Be2B24+. Global-minimum searches of MB24q and M2B24q (M = alkali/alkaline-earth metals; q = 1+, 0, 1-) reveal that the most stable structure of Be2B24+ is a C2v-symmetric cage having a four-ring tubular boron moiety, whereas it is a high-lying isomer for those having a two/three-ring tubular boron motif for all other systems. The B24 framework in Be2B24+ can be viewed as consisting of two two-ring B12 tubular structures linked together at one side of the B6 rings along the high-symmetry axis and two offside B6 rings capped by two Be atoms. The Be2-B24 bonding is best described as Be22+ in an excited triplet state, forming two highly polarized covalent bonds with B24- in a quartet spin state. The unique ability of beryllium to make strong covalent and electrostatic interactions makes the Be2B24+ cluster stable in such an unusual geometry.

13.
ACS Omega ; 7(35): 31059-31068, 2022 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-36092557

RESUMEN

The purpose of this paper is to study the effect of polypyrrole (PPy) on cellulose acetate (CA) membranes prepared by the electrospinning technique (controlled variables) in the recovery of gold complexes of aqueous solutions that are environmentally ecofriendly. CA-PPy membranes were characterized by SEM, EDS, FTIR spectroscopy, contact angle measurements, electrical conductivity, and mechanical tests. They were submerged in two aqueous solutions using two gold complexes, AuI2 - and AuBr4 -, at room temperature. The recovery percentage was evaluated for several hours using the atomic adsorption technique for both complexes. The main findings indicate that the percentage of recovery in the first hours of the test was very high (>80%). The adsorption efficiency maxima were similar for both complexes (91%). The Langmuir model suggests the formation of a monolayer on the surface. The electrical conductivity did not change over time, and the mechanical properties indicate reuse in several experiments. Furthermore, the theoretical analysis showed that the system is helpful at acidic pH, funding its minimum energy. It is shown in this study that the used CA-PPy membranes show adsorption, absorption, and reusable properties with the effective recovery of the complexes in the first hours. These membranes could substitute for materials that are not environmentally ecofriendly.

14.
Arch Gynecol Obstet ; 306(6): 2035-2045, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35997971

RESUMEN

PURPOSE: This study aimed to determine the efficacy of non-hormonal therapy with citalopram vs fluoxetine for treating vasomotor syndrome (VMS) and urogenital syndrome of menopause (GSM) in Mexican women. METHODS: A parallel prospective randomized clinical trial was conducted in 91 postmenopausal women with a total score on the Menopause Rating Scale (MRS) ≥ 17 and with the clinical diagnosis of VSM and GSM. Patients were randomly assigned to receive citalopram (n = 49) or fluoxetine (n = 42). Follow-up was carried out at 3 and 6 months. RESULTS: The citalopram group experienced a significant improvement compared to the fluoxetine group in the MRS total score (p < 0.01), as well as in the psychological (p < 0.001) and somatic (p < 0.0001) domains at 3 and 6 months of follow-up. After 6 months of follow-up, the group that received citalopram decreased the relative risk (RR) to present VMS symptoms (RR = 0.30, CI 0.19-0.5, p = 0.0001), depressed mood (RR = 0.31, CI 0.15-0.6, p = 0.0002), irritability (RR = 0.40, CI 0.22-0.73, p = 0.002), anxiety (RR = 0.30, CI 0.13-0.69, p = 0.003), physical and mental exhaustion (RR = 0.35, CI 0.18-0.67, p = 0.001), sexual problems (RR = 0.18, CI 0.06-0.48, p = 0.0001), vaginal dryness (RR = 0.34, CI 0.14-0.80, p = 0.01), and urinary problems (RR = 0.36, CI 0.14-0.92, p = 0.043). CONCLUSION: We conclude that citalopram tends to improve VSM and GSM symptoms in postmenopausal Mexican women. Thus, we recommend the daily use of citalopram 20 mg. However, further studies will be required to support the results of the present work. These should include a larger number of patients and a placebo group. CLINICAL TRIAL REGISTRATION: This clinical trial was retrospectively registered by the United States National Library of Medicine in the www. CLINICALTRIALS: gov database on 04/20/2022. The given test Registration Number is NCT05346445.


Asunto(s)
Citalopram , Fluoxetina , Humanos , Femenino , Citalopram/uso terapéutico , Estudios Prospectivos , Posmenopausia/psicología , Menopausia/psicología , Síndrome
15.
Rev. med. hered ; 33(3)jul. 2022.
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1424202

RESUMEN

Objetivo : Analizar el desarrollo de políticas de recursos humanos en salud en Perú. Material y métodos : Estudio transversal de análisis de Políticas de recursos humanos en Salud. Se identificaron lineamientos de política, se analizó grado de cumplimiento considerando tres herramientas de implementación: regulación, persuasión e incentivos. El análisis histórico consideró: acción política, respuesta sociedad civil y adaptación estatal. Resultados : Entre 1980 y 2020 se identificaron 11 lineamientos de política sectorial (cinco con un lineamiento en recursos humanos) y dos lineamentos de política específicos de recursos humanos; no necesariamente coincidentes. Los instrumentos de implementación de políticas más utilizadas fueron control, incentivo y mixtas. Los incentivos incluyeron, mayores salarios y puntajes al postular a especialidad. Hubo distorsiones tipo boomerang. Conclusiones : No se identificó Política de Estado en recursos humanos en salud. Los limitados efectos de las políticas sectoriales se basaron en la escasa participación de actores sociales, la alta rotación de funcionarios, el limitado control y el uso incompleto de incentivos. La eficacia y sostenibilidad de una política requiere apropiación, liderazgo, financiamiento y armonización de las herramientas de implementación.


SUMMARY Objective : To evaluate the human resources policy in the health care sector in Peru. Methods : A cross-sectional study was performed; policy guidelines, degree of tracing evaluating implementation, regulation, persuasion, and incentives. Results : We identified 11 policy guidelines between 1908 and 2020 (5 with at least one human resource guidelines) and specific human resource guidelines. The implementation policy tools most commonly used were control, incentives and mixt tools. Incentives used were higher salaries and scores for postulants to specialties. Boomerang distortions were found. Conclusions : No state policies in human resources were found. Limited effects of sectorial policies were based on low social participation, high rotation of managers, and limited control and use of incentives. Efficacy and sustainability of a policy requires leadership, financing and harmonization of implementation tools.

16.
SLAS Discov ; 27(6): 349-357, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35580766

RESUMEN

Small-molecule high-throughput screening (HTS) campaigns have frequently been used to identify lead molecules that can alter expression of disease-relevant proteins in cell-based assays. However, most cell-based HTS assays require short compound exposure periods to avoid toxicity and ensure that compounds are stable in media for the duration of the exposure. This limits the ability of HTS assays to detect inhibitors of the synthesis of target proteins with long half-lives, which can often exceed the exposure times utilized in most HTS campaigns. One such target is alpha-synuclein (α-syn)-a protein well-known for its pathological aggregation in Parkinson's Disease (PD) and other forms of neurodegeneration known collectively as synucleinopathies. Here, we report the development of an HTS assay using a CRISPR-engineered neuroblastoma cell line expressing a destabilized luciferase reporter inserted at the end of the coding region of the SNCA locus. The resultant destabilized fusion protein exhibited a significant reduction in half-life compared to the endogenous, unmodified α-syn protein, and accurately reported reductions in α-syn levels due to known protein translation inhibitors and specific α-syn siRNAs. The robustness and utility of this approach was shown by using the resulting cell line (dsLuc-Syn) to screen a focused library of 3,192 compounds for reduction of α-syn. These data demonstrate the general utility of converting endogenous loci into destabilized reporter genes capable of identifying inhibitors of gene expression of highly stable proteins even in short-term assays.


Asunto(s)
Enfermedad de Parkinson , alfa-Sinucleína , Línea Celular , Expresión Génica , Ensayos Analíticos de Alto Rendimiento/métodos , Humanos , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo
17.
Cureus ; 14(4): e24553, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35509730

RESUMEN

Left ventricular diverticulum is a rare cardiac congenital anomaly. It is believed to be caused by the impaired development of the endocardial tube during the fourth week of embryologic development. It contains endocardium, myocardium, and pericardium and displays normal contraction. We hereby report a case of a patient with a left ventricular apical diverticulum who presented with unstable angina and was initially misdiagnosed as a ventricular septal defect. Since there were no complications or symptoms associated with the anomaly, the management was conservative. This manuscript also highlights the importance of using multiple diagnostic imaging modalities to exclude differential diagnoses.

18.
PLoS Comput Biol ; 18(1): e1009778, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-35041647

RESUMEN

The clinical outcome of SARS-CoV-2 infection varies widely between individuals. Machine learning models can support decision making in healthcare by assessing fatality risk in patients that do not yet show severe signs of COVID-19. Most predictive models rely on static demographic features and clinical values obtained upon hospitalization. However, time-dependent biomarkers associated with COVID-19 severity, such as antibody titers, can substantially contribute to the development of more accurate outcome models. Here we show that models trained on immune biomarkers, longitudinally monitored throughout hospitalization, predicted mortality and were more accurate than models based on demographic and clinical data upon hospital admission. Our best-performing predictive models were based on the temporal analysis of anti-SARS-CoV-2 Spike IgG titers, white blood cell (WBC), neutrophil and lymphocyte counts. These biomarkers, together with C-reactive protein and blood urea nitrogen levels, were found to correlate with severity of disease and mortality in a time-dependent manner. Shapley additive explanations of our model revealed the higher predictive value of day post-symptom onset (PSO) as hospitalization progresses and showed how immune biomarkers contribute to predict mortality. In sum, we demonstrate that the kinetics of immune biomarkers can inform clinical models to serve as a powerful monitoring tool for predicting fatality risk in hospitalized COVID-19 patients, underscoring the importance of contextualizing clinical parameters according to their time post-symptom onset.


Asunto(s)
Anticuerpos Antivirales/sangre , COVID-19 , SARS-CoV-2/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/inmunología , COVID-19/terapia , Biología Computacional , Diagnóstico por Computador , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Glicoproteína de la Espiga del Coronavirus/inmunología , Adulto Joven
19.
Materials (Basel) ; 14(23)2021 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-34885434

RESUMEN

The present research work shows the effect on the carbonation of Portland cement-based mortars (PC) with the addition of green materials, specifically residues from two groups: agricultural and industrial wastes, and minerals and fibres. These materials have the purpose of helping with the waste disposal, recycling, and improving the durability of concrete structures. The specimens used for the research were elaborated with CPC 30R RS, according to the Mexican standard NMX-C-414, which is equivalent to the international ASTM C150. The aggregates were taken from the rivers Lerma and Huajumbaro, in the State of Michoacan, Mexico, and the water/cement relation was 1:1 in weight. The carbonation analyses were performed with cylinder specimens in an accelerated carbonation test chamber with conditions of 65 +/- 5% of humidity and 25 +/- 2 °C temperature. The results showed that depending on the PC substitutions, the carbonation front advance of the specimens can increase or decrease. It is highlighted that the charcoal ashes, blast-furnace slags, and natural perlite helped to reduce the carbonation advance compared to the control samples, consequently, they contributed to the durability of concrete structures. Conversely, the sugarcane bagasse ash, brick manufacturing ash, bottom ash, coal, expanded perlite, metakaolin, and opuntia ficus-indica dehydrated fibres additions increased the velocity of carbonation front, helping with the sequestration of greenhouse gases, such as CO2, and reducing environmental pollution.

20.
mBio ; 12(5): e0247321, 2021 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-34607456

RESUMEN

Most known SARS-CoV-2 neutralizing antibodies (nAbs), including those approved by the FDA for emergency use, inhibit viral infection by targeting the receptor-binding domain (RBD) of the spike (S) protein. Variants of concern (VOC) carrying mutations in the RBD or other regions of S reduce the effectiveness of many nAbs and vaccines by evading neutralization. Therefore, therapies that are less susceptible to resistance are urgently needed. Here, we characterized the memory B-cell repertoire of COVID-19 convalescent donors and analyzed their RBD and non-RBD nAbs. We found that many of the non-RBD-targeting nAbs were specific to the N-terminal domain (NTD). Using neutralization assays with authentic SARS-CoV-2 and a recombinant vesicular stomatitis virus carrying SARS-CoV-2 S protein (rVSV-SARS2), we defined a panel of potent RBD and NTD nAbs. Next, we used a combination of neutralization-escape rVSV-SARS2 mutants and a yeast display library of RBD mutants to map their epitopes. The most potent RBD nAb competed with hACE2 binding and targeted an epitope that includes residue F490. The most potent NTD nAb epitope included Y145, K150, and W152. As seen with some of the natural VOC, the neutralization potencies of COVID-19 convalescent-phase sera were reduced by 4- to 16-fold against rVSV-SARS2 bearing Y145D, K150E, or W152R spike mutations. Moreover, we found that combining RBD and NTD nAbs did not enhance their neutralization potential. Notably, the same combination of RBD and NTD nAbs limited the development of neutralization-escape mutants in vitro, suggesting such a strategy may have higher efficacy and utility for mitigating the emergence of VOC. IMPORTANCE The U.S. FDA has issued emergency use authorizations (EUAs) for multiple investigational monoclonal antibody (MAb) therapies for the treatment of mild to moderate COVID-19. These MAb therapeutics are solely targeting the receptor-binding domain of the SARS-CoV-2 spike protein. However, the N-terminal domain of the spike protein also carries crucial neutralizing epitopes. Here, we show that key mutations in the N-terminal domain can reduce the neutralizing capacity of convalescent-phase COVID-19 sera. We report that a combination of two neutralizing antibodies targeting the receptor-binding and N-terminal domains may be beneficial to combat the emergence of virus variants.


Asunto(s)
Anticuerpos Neutralizantes/inmunología , COVID-19/genética , COVID-19/inmunología , Mutación/inmunología , Motivos de Unión al ARN/inmunología , SARS-CoV-2/genética , SARS-CoV-2/inmunología , Humanos , Pruebas de Neutralización
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