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1.
Geriatr Gerontol Aging ; 18: e0000100, Apr. 2024. tab
Artigo em Inglês | LILACS | ID: biblio-1566466

RESUMO

Objective: We aimed to determine the prevalence of self-reported swallowing difficulty (dysphagia) among older Colombians and to explore the factors associated with this condition. Methods: This study presents a secondary analysis of the SABE-Colombia survey, a crosssectional study of community-dwelling older adults. The dependent variable was self reported swallowing difficulty, assessed through the question: "How often do you have difficulty or discomfort swallowing?" Descriptive and bivariate analyses of the sample were performed, followed by multivariate analysis, adjusting for confounding variables. Results: The final sample included 19 004 older Colombians, whose mean age was 69 years (56% women). The overall prevalence of swallowing difficulty was 12.2%. In the multivariate analysis, significant associations were observed between swallowing difficulty and several factors, including male sex (OR 1.14, 95%CI 1.03 ­ 1.26), age > 80 years (OR 1.26, 95%CI 1.08 ­ 1.47), dependence in activities of daily living (OR 1.62, 95%CI 1.23 ­ 2.13), cognitive impairment (OR 1.49, 95%CI 1.30 ­ 1.70), depressive symptoms (OR 1.38, 95%CI 1.15 ­ 1.65), sarcopenia (OR 1.32, 95%CI 1.02 ­ 1.69), malnutrition (OR 1.35, 95%CI 1.23 ­ 1.49), and osteoarticular disease (OR 1.18, 95%CI 1.07 ­ 1.38). Conclusion: There was a high prevalence of swallowing difficulty among older community-dwelling Colombians. Our results showed a strong correlation between swallowing difficulty and risk factors such as cognitive impairment, depressive symptoms, osteoarticular disease, and dependence in activities of daily living, but not with malnutrition or sarcopenia. (AU)


Assuntos
Idoso , Idoso de 80 Anos ou mais , Idoso , Transtornos de Deglutição
2.
ESMO Open ; 8(6): 102051, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37951129

RESUMO

BACKGROUND: In the setting of localized colon cancer (CC), circulating tumor DNA (ctDNA) monitoring in plasma has shown potential for detecting minimal residual disease (MRD) and predicting a higher risk of recurrence. With the tumor-only sequencing approach, however, germline variants may be misidentified as somatic variations, precluding the possibility of tracking in up to 11% of patients due to a lack of known somatic mutations. In this study, we assess the potential value of adding white blood cells (WBCs) to tumor tissue sequencing to enhance the accuracy of sequencing results. PATIENTS AND METHODS: A total of 148 patients diagnosed with localized CC were prospectively recruited at the Hospital Clínico Universitario in Valencia (Spain). Employing a custom 29-gene panel, sequencing was conducted on tumor tissue, plasma and corresponding WBCs. Droplet digital PCR and amplicon-based NGS were performed on plasma samples post-surgery to track MRD. Oncogenic somatic variants were identified by annotating with COSMIC, OncoKB and an internal repository of pathogenic mutations database. A variant prioritization analysis, mainly characterized by the match of oncogenic mutations with the evidence levels defined in OncoKB, was carried out to select specific targeted therapies. RESULTS: Utilizing paired tumor and WBCs sequencing, we identified somatic mutations in all patients (100%) within our cohort, compared to 89% using only tumor tissue. Consequently, the top 10 most frequently mutated genes for plasma monitoring were altered. The sequencing of WBCs identified 9% of patients with pathogenic mutations in the germline, with APC and TP53 being the most frequently mutated genes. Additionally, mutations in genes related to clonal hematopoiesis of indeterminate potential were detected in 27% of the cohort, with TP53, KRAS, and KMT2C being the most frequently altered genes. There were no observed differences in the sensitivity of monitoring MRD using ddPCR or amplicon-based NGS (p = 1). Ultimately, 41% of the patients harbored potentially targetable alterations at diagnosis. CONCLUSION: The germline testing method not only enhanced sequencing results and raised the proportion of patients eligible for plasma monitoring, but also uncovered the existence of pathogenic germline variations, thereby aiding in the identification of patients at a higher risk of hereditary cancer syndromes.


Assuntos
DNA Tumoral Circulante , Neoplasias do Colo , Humanos , DNA Tumoral Circulante/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , DNA de Neoplasias/genética , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Células Germinativas/patologia
4.
Hematol Oncol Stem Cell Ther ; 16(4): 330-336, 2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-37363982

RESUMO

BACKGROUND AND OBJECTIVES: Allogeneic stem cell transplantation (Allo-SCT) in elderly patients is a growing practice. We aimed to determine the graft-versus-host disease (GVHD) relapse-free survival (GRFS) in patients ≥65 years who underwent Allo-SCT in two countries from Latin America. PATIENTS AND METHODS: We performed a retrospective analysis of patients ≥65 years who underwent Allo-SCT in Argentina and Brazil from 2007 to 2019. RESULTS: Ninety-eight patients were evaluated, with primary diagnoses of acute myeloid leukemia and myelodysplastic syndrome; 30% of patients had a hematopoietic cell transplant-comorbidity index (HCT-CI) score ≥3 and 49% were in complete remission. Donor types included matched sibling (n = 41), matched unrelated (n = 31), and haploidentical (HID; n = 26) donors. The conditioning regimen was myeloablative in 28 patients (14 busulfan pharmacokinetically [PK]-guided) and reduced-intensity in 70 patients. The two-year non-relapse mortality (NRM) was 29%, with a higher NRM in melphalan-based compared to other conditionings (51% vs. 33%, p = 0.02). The two-year relapse rate was 24%, with a reduction in PK-guided busulfan (0% vs. 28%, p = 0.03). The two-year overall survival (OS) and GRFS was 52% and 38%, respectively, with a significant reduction in GRFS in HCT-CI ≥3 (27% vs. others 42%, p = 0.02) and donors ≥40 years (29% vs. <40 years 55%, p = 0.02). These variables remained significantly associated with GRFS after multivariate analysis. CONCLUSION: In this cohort of elderly patients from Argentina and Brazil undergoing Allo-SCT, donor age and comorbidities significantly influenced GRFS. The role of the conditioning regimen in this population deserves further investigation.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Idoso , Bussulfano , Estudos Retrospectivos , América Latina , Recidiva , Condicionamento Pré-Transplante
5.
Ultrasound Obstet Gynecol ; 62(4): 540-551, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37204929

RESUMO

OBJECTIVE: Monochorionic (MC) triplet pregnancies are extremely rare and information on these pregnancies and their complications is limited. We aimed to investigate the risk of early and late pregnancy complications, perinatal outcome and the timing and methods of fetal intervention in these pregnancies. METHODS: This was a multicenter retrospective cohort study of MC triamniotic (TA) triplet pregnancies managed in 21 participating centers around the world from 2007 onwards. Data on maternal age, mode of conception, diagnosis of major fetal structural anomalies or aneuploidy, gestational age (GA) at diagnosis of anomalies, twin-to-twin transfusion syndrome (TTTS), twin anemia-polycythemia sequence (TAPS), twin reversed arterial perfusion (TRAP) sequence and or selective fetal growth restriction (sFGR) were retrieved from patient records. Data on antenatal interventions were collected, including data on selective fetal reduction (three to two or three to one), laser surgery and any other active fetal intervention (including amniodrainage). Data on perinatal outcome were collected, including numbers of live birth, intrauterine demise, neonatal death, perinatal death and termination of fetus or pregnancy (TOP). Neonatal data such as GA at birth, birth weight, admission to neonatal intensive care unit and neonatal morbidity were also collected. Perinatal outcomes were assessed according to whether the pregnancy was managed expectantly or underwent fetal intervention. RESULTS: Of an initial cohort of 174 MCTA triplet pregnancies, 11 underwent early TOP, three had an early miscarriage, six were lost to follow-up and one was ongoing at the time of writing. Thus, the study cohort included 153 pregnancies, of which the majority (92.8%) were managed expectantly. The incidence of pregnancy affected by one or more fetal structural abnormality was 13.7% (21/153) and that of TRAP sequence was 5.2% (8/153). The most common antenatal complication related to chorionicity was TTTS, which affected just over one quarter (27.6%; 42/152, after removing a pregnancy with TOP < 24 weeks for fetal anomalies) of the pregnancies, followed by sFGR (16.4%; 25/152), while TAPS (spontaneous or post TTTS with or without laser treatment) occurred in only 4.6% (7/152) of pregnancies. No monochorionicity-related antenatal complication was recorded in 49.3% (75/152) of pregnancies. Survival was apparently associated largely with the development of these complications: there was at least one survivor beyond the neonatal period in 85.1% (57/67) of pregnancies without antenatal complications, in 100% (25/25) of those complicated by sFGR and in 47.6% (20/42) of those complicated by TTTS. The overall rate of preterm birth prior to 28 weeks was 14.5% (18/124) and that prior to 32 weeks' gestation was 49.2% (61/124). CONCLUSION: Monochorionicity-related complications, which can impact adversely perinatal outcome, occur in almost half of MCTA triplet pregnancies, creating a challenge with regard to counseling, surveillance and management. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

6.
Cancer Lett ; 561: 216156, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37019172

RESUMO

Despite the clinical success of the programmed death ligand 1 (PD-L1) blocking therapy in cancer treatment, only a subset of patients exhibits durable responses, therefore further exploration of other immunotherapeutic alternatives are needed. This paper reported the development of the PKPD-L1Vac vaccine, a new protein vaccine candidate that uses aluminum phosphate as an adjuvant and as an antigen the extracellular domain of human PD-L1 fused to a 47 amino-terminal portion of the LpdA protein from N. meningitides (PKPD-L1). The PKPD-L1 antigen has different physical and biological characteristics than those found in the natural molecule and in others PD-L1 vaccine candidates. The quimeric protein has a reduced binding capacity to the PD-1 and CD80 receptors to decrease their pro-tumoral activity. Besides, the distinctive feature of the PKPD-L1 polypeptide to be structurally aggregated could be desirable for its immunogenic properties. PKPD-L1Vac elicited anti-PD-L1-specific IgG antibodies and T lymphocyte-mediated immunity in mice and non-human primates. The vaccine administration demonstrated antitumor activity on CT-26 and B16-F10 primary tumor models in mice. Moreover, the immunization with PKPD-L1Vac increased the tumor-infiltrating lymphocytes and decreased the proportion of CD3+CD8+PD1+high anergic T cells in CT-26 tumor tissues, suggesting that the vaccine may remodel the tumor microenvironment. In summary, the PKPD-L1Vac vaccine exhibits very promising preclinical results and deserves to move forward to a phase I clinical trial.


Assuntos
Linfócitos B , Imunoterapia , Neoplasias , Animais , Humanos , Camundongos , Antígeno B7-H1 , Linfócitos T CD8-Positivos , Tolerância Imunológica , Imunoterapia/métodos , Neoplasias/terapia , Primatas/metabolismo , Microambiente Tumoral , Vacinação , Linfócitos B/imunologia
7.
J Dent Res ; 102(8): 854-862, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36908187

RESUMO

Accelerated cellular senescence may be a crucial process for periodontitis progression because it integrates the damaging effects of major periodontitis risk factors. Cellular senescence is a manifestation of aging at the cellular level. However, recent technological advances have shown that healthy young cells continuously exposed to sublethal oxidative stress undergo accelerated senescence. Although accumulation of senescent cells is normal in aged tissues, persistent bacterial infection, chronic inflammation, diabetes, and smoking promote the early onset of senescence by causing DNA damage. As a result, the premature accumulation of senescent cells not only increases tissue destruction but also limits regeneration. Senescent cells are a source of chronic inflammation, and once they start to accumulate, a "two-source" periodontal inflammation results from both bacteria-triggered and senescence-associated inflammation. Senescent cells also transmit senescence to nearby healthy cells, generating a vicious cycle that extends the affected area over time. Since senescent cells Accumulate, Limit regeneration, Transmit senescence, Exacerbate inflammation, and Remodel tissues, the acronym ALTER is suggested to summarize key senescence-associated features implicated in tissue deterioration. Given that different homeostatic mechanisms are disrupted during the transition of gingivitis to periodontitis and that the network of senescence-associated events disrupts local homeostasis, accelerated activation of cellular senescence could be a central underlying mechanism for periodontitis progression. In this review, the emerging contribution of premature DNA damage-driven cellular senescence in periodontitis is discussed. This novel knowledge is particularly important to better understand the host contribution in periodontal destruction and will help to develop new therapeutic strategies.


Assuntos
Senescência Celular , Periodontite , Humanos , Idoso , Senescência Celular/genética , Envelhecimento/fisiologia , Estresse Oxidativo , Inflamação
8.
Rev. cir. (Impr.) ; 75(1)feb. 2023.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1441448

RESUMO

El cáncer de mama (CM) es la primera causa de muerte por cáncer en mujeres tanto a nivel mundial como en Chile. Basados en características clínicas, histológicas y moleculares, múltiples estudios han identificado cuatro subtipos básicos de CM, los cuales están asociados a estrategias de tratamiento específicas y diferenciadas. El CM HER2-positivo representa un 15%-25% de todas las neoplasias mamarias y se caracteriza por su agresividad, recurrencia temprana y mayor tendencia a presentar compromiso del sistema nervioso central. En las últimas décadas, nuevas terapias dirigidas se han posicionado como el estándar de tratamiento y han cambiado la historia natural de esta enfermedad, transformándola en una enfermedad potencialmente curable incluso en etapas avanzadas. Esta revisión busca entregar un resumen de las bases biológicas de esta enfermedad. Por otro lado, dada la aparición de un creciente número de nuevas estrategias de manejo sistémico, nos proponemos revisar sus mecanismos de acción analizando reportes de datos clínicos publicados y la experiencia de nuestro grupo.


Breast cancer (BC) is the leading cause of cancer death for women both worldwide and in Chile. Based on clinical, histological, and molecular features, studies have identified four BC subtypes that correlate with treatment sensitivity. Human Epidermal growth factor Receptor type 2-positive (HER2+) BC represents 15%-25% of newly diagnosed breast neoplasms; HER2+ BC is characterized by its aggressive behavior, early recurrence, and higher risk of brain metastasis. In recent years, HER2-targeted therapies have become the mainstay of treatment and have redefined the natural history of this subtype, reducing relapse rates for early-stage patients and increasing survival in advanced-stage patients. Herein we review novel treatment strategies and their mechanisms of action, along with clinical and real-world data. We also provide a summary of currently available treatments for this subtype and our local experience regarding the management of this disease.

9.
Artigo em Inglês | MEDLINE | ID: mdl-36403725

RESUMO

OBJECTIVES: Main objective: To compare the effectiveness for checking surgical margins between SPECT-portable and mammography of the piece (RxM). SECONDARY OBJECTIVE: To standardize a pre-operative protocol using SPECT-portable and to evaluate the time required in the use of this technique. MATERIAL AND METHODS: Prospective longitudinal study with 36 patients (39 lesions) diagnosed with breast cancer (CM) with criteria for SNOLL/ROLL. A pre-surgical study of the tumor lesion was performed, after the eco-guided administration of 99mTc-nanocolloids of albumin/99mTc-macroaggregates of albumin, in the tumor lesion. Hybrid images (optical + SPECT) and 3D navigation images with gamma probe are obtained using freehandSPECT. In the operating room, 4-5 images are obtained with freehandSPECT, (I) on skin for tumor location, (II) after exposure of surgical bed for resection guide, (III) of the surgical bed after exeresis, (IV and V) the anterior-posterior and lateral surface of the surgical specimen. The three criteria to decide to extend the margins are: (a) residual activity (cps) at the edges of the surgical bed resection; (b) visual analysis of the uptake in the specimen; (c) a minimum distance of 10 mm from the edges of the specimen to the center of greatest uptake, plus the radius of the lesion. We study the concordance of: the depth measurement between ultrasound and freehandSPECT; the surgical margins between freehandSPECT vs. mammography of the specimen (RxM), considering anatomical pathology (AP) as the gold standard technique as reference; surgical time used with freehandSPECT and RxM. RESULTS: Intraoperative localization was performed in all cases. False negative (FN: no detection margin affected) with freehandSPECT: 9 margins; with RxM: 8. True positive (TP: detection margin affected) with freehandSPECT: 5 margins, with RxM: 6. True negative (TN: consider free margin when healthy) with freehandSPECT: 213 margins; with RxM: 196. Negative predictive value (NPV: probability of negative margin on unaffected part) with freehandSPECT: 95.9%, with RxM: 96.07%. Specificity with freehandSPECT: 96.8%, with RxM: 97%. The concordance of surgical bed margins between freehandSPECT and RxM: 94.5%. Between freehandSPECT and AP: 93.1%. Between RxM and PA: 93.5%, being all statistically significant (p-value <0.000), so we can affirm that both techniques are related or dependent on the reference technique, the PA. Degree of correlation between SPECT-portable and low PA (Kappa index: 0.34, 95% CI [0.22-0.47], and between RxM and moderate PA (Kappa index: 0.42, 95% CI [0.29-0.56], p-value <0.001. Comparison of the successes and failures of both techniques (SPECT-portable and RxM) and PA: Distribution χ2: 0.023 with degree of freedom 1, with value <0.05, so we can affirm that both techniques are similar, since there are no significant statistical differences. Median total OR time: 60.25 min (30-145). Mean freehandSPECT OR time: 5 scans = 10 min. CONCLUSIONS: There are no statistically significant differences in the probability to rule out affective margins that require a second surgery between both techniques (SPECT-portable and RxM) so, the technique performed with SPECT-Portable is a useful and effective procedure, which requires specific training with an optimized and multidisciplinary protocol. The time spent with SPECT-portable is feasible for daily practice.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Margens de Excisão , Estudos Prospectivos , Estudos Longitudinais , Tomografia Computadorizada de Emissão de Fóton Único , Albuminas
10.
Int J Oral Maxillofac Surg ; 52(4): 460-467, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35909027

RESUMO

Dentoskeletal changes in minimally invasive surgically assisted rapid palatal expansion (SARPE) were evaluated using cone beam computed tomography (CBCT). This was a prospective study of 30 patients who underwent minimally invasive SARPE performed under local anaesthesia plus sedation by the same surgeon, in an ambulatory setting. Pre- and postoperative CBCT images were obtained for each patient. A statistically significant increase in the linear transverse dimensions of the maxilla occurred systematically. In the canine region, a mean increase of 5.84 mm occurred at the apex level and 7.82 mm at the crown level. These dimensions were 4.83 mm and 7.68 mm, respectively, in the molar region. The cross-sectional area of the maxilla increased by a mean 12.9 mm2 at the palate level and 23.3 mm2 at the crown level. Dental inclination to the buccal aspect was detected (mean 6.1° at the canines and 8.4° at the first molars). The alveolar process tipped buccally 10° at the molar level. Nasal width increased a mean of 3.0 mm at the canine level. Through a three-dimensional analysis, this study found that minimally invasive SARPE was effective in the correction of transverse maxillary discrepancies> 5 mm in non-growing patients. Although dental inclination to the buccal aspect occurred, significant expansion of the maxilla at the skeletal and dentoalveolar levels was confirmed.


Assuntos
Técnica de Expansão Palatina , Dente , Estudos Prospectivos , Palato , Maxila/cirurgia , Tomografia Computadorizada de Feixe Cônico/métodos
12.
Lett Appl Microbiol ; 75(3): 680-688, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35687297

RESUMO

Pseudomonas aeruginosa is one of the most worrisome infectious bacteria due to its intrinsic and acquired resistance against several antibiotics and the recalcitrance of its infections; hence, the development of novel antimicrobials effective against multidrug-resistant P. aeruginosa is mandatory. In this work, silver nanoparticles obtained by green synthesis using a leaf extract and fungi were tested against a battery of clinical strains from cystic fibrosis, pneumonia and burnt patients, some of them with multidrug resistance. Both nanoparticles showed a potent antibacterial effect, causing severe damage to the cell wall, membrane and DNA, and inducing the production of reactive oxygen species. Moreover, the nanoparticles derived from fungi showed synergistic antibacterial effects with the antibiotics meropenem and levofloxacin for some clinical strains and both kinds of nanoparticles were nontoxic for larvae of the moth Galleria mellonella, encouraging further research for their implementation in the treatment of P. aeruginosa infections.


Assuntos
Nanopartículas Metálicas , Infecções por Pseudomonas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Humanos , Levofloxacino/farmacologia , Levofloxacino/uso terapêutico , Meropeném/farmacologia , Testes de Sensibilidade Microbiana , Extratos Vegetais/farmacologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa , Espécies Reativas de Oxigênio , Prata/farmacologia
13.
Biomed Pharmacother ; 149: 112883, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35692123

RESUMO

Euphorbia lathyris seeds have been used to treat various medical conditions. We previously reported that ethanolic extract from the defatted seed of Euphorbia lathyris (EE) (variety S3201) possesses a potent in vitro antitumor activity against colon cancer (CRC) cell lines. However, the effects of EE on CRC in vivo models and its possible preventive activity have not been elucidated. The aim of this study is to develop an in vivo study to corroborate its efficacy. For this purpose, two tumor induction models have been developed. In orthotopic xenograft model, it has been shown that EE reduces tumor size without hematological toxicity. The ethanolic extract induced an intense apoptosis in tumors mediated by caspase 3. Using the Azoxymethane/Dextran Sulfate Sodium model, a reduction of dysplastic polyps has been demonstrated, showing its preventive power. Furthermore, EE promoted the presence of an eubiotic microbiotal environment in the mucosa of the colon and induced an increase in antioxidant enzyme activity. This fact was accompanied by a modulation of cytokine expression that could be related to its protective mechanism. Therefore, although further experiments will be necessary to determine its applicability in the treatment of CRC, ES could be a new prevention strategy as well as treatment for this type of tumor, being a powerful candidate for future clinical trials.


Assuntos
Neoplasias do Colo , Euphorbia , Azoximetano/toxicidade , Neoplasias do Colo/tratamento farmacológico , Sulfato de Dextrana , Etanol , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
14.
Proc Natl Acad Sci U S A ; 119(22): e2200468119, 2022 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-35613051

RESUMO

Aggregation of initially stably structured proteins is involved in more than 20 human amyloid diseases. Despite intense research, however, how this class of proteins assembles into amyloid fibrils remains poorly understood, principally because of the complex effects of amino acid substitutions on protein stability, solubility, and aggregation propensity. We address this question using ß2-microglobulin (ß2m) as a model system, focusing on D76N-ß2m that is involved in hereditary amyloidosis. This amino acid substitution causes the aggregation-resilient wild-type protein to become highly aggregation prone in vitro, although the mechanism by which this occurs remained elusive. Here, we identify the residues key to protecting ß2m from aggregation by coupling aggregation with antibiotic resistance in E. coli using a tripartite ß-lactamase assay (TPBLA). By performing saturation mutagenesis at three different sites (D53X-, D76X-, and D98X-ß2m) we show that residue 76 has a unique ability to drive ß2m aggregation in vivo and in vitro. Using a randomly mutated D76N-ß2m variant library, we show that all of the mutations found to improve protein behavior involve residues in a single aggregation-prone region (APR) (residues 60 to 66). Surprisingly, no correlation was found between protein stability and protein aggregation rate or yield, with several mutations in the APR decreasing aggregation without affecting stability. Together, the results demonstrate the power of the TPBLA to develop proteins that are resilient to aggregation and suggest a model for D76N-ß2m aggregation involving the formation of long-range couplings between the APR and Asn76 in a nonnative state.


Assuntos
Amiloidose , Agregação Patológica de Proteínas , Microglobulina beta-2 , Substituição de Aminoácidos , Proteínas Amiloidogênicas/genética , Amiloidose/genética , Ensaios Enzimáticos , Escherichia coli , Humanos , Mutação Puntual , Agregação Patológica de Proteínas/genética , Dobramento de Proteína , Microglobulina beta-2/química , Microglobulina beta-2/genética , beta-Lactamases
16.
Malays J Pathol ; 44(1): 83-92, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35484890

RESUMO

INTRODUCTION: Data on pathological changes in COVID-19 are scarce. The aim of this study was to describe the histopathological and virological findings of postmortem biopsies, and the existing clinical correlations, in people who died of COVID-19. MATERIALS AND METHODS: We performed postmortem needle core biopsies of the chest in 11 people who died of COVID-19 pneumonia. Tissue examination was done by light microscopy and real-time polymerase chain reaction (RTPCR). RESULTS: The age of the patients were between 61 to 94 years. Of the 11 postmortem chest biopsies, lung tissue was obtained in 8, myocardium tissue in 7, and liver tissue in 5. Histologically of lung, the main findings pertaining to the lung were diffuse alveolar damage in proliferative phase (n = 4, 50%), diffuse alveolar damage in exudative and proliferative phase (n = 3, 37.5%), diffuse alveolar damage in exudative (n=1; 12.5%) and acute pneumonia (n = 2, 25%). Necrotising pneumonia, acute fibrinous and organising pneumonia, and neutrophils were detected in one sample each (12.5%). Another case presented myocarditis. RT-PCR showed RNA of SARS-CoV-2 in 7 of the 8 lung samples (87.5%), 2 of the 7 myocardial tissue samples (28.6%), and 1 of the 5 liver tissue samples (20%). CONCLUSION: The postmortem examinations show diffuse alveolar damage, as well as acute or necrotising pneumonia. RT-PCR of SARS-CoV-2 was positive in most lung samples.


Assuntos
COVID-19 , Pneumonia Necrosante , Pneumonia , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Humanos , Fígado/patologia , Pulmão/patologia , Pessoa de Meia-Idade , Pneumonia/patologia , Pneumonia Necrosante/patologia , SARS-CoV-2
17.
Lett Appl Microbiol ; 75(2): 210-223, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35419861

RESUMO

We evaluated an essential oil (EO) of Tagetes lucida Cav. and the mixture of its main compounds against multi-drug resistant bacteria. We found that EO and the partially reconstituted blend of its main components have antibacterial activity and inhibit antibiotic resistance (ampicillin, chloramphenicol, nalidixic acid, vancomycin and imipenem) in strains of Staphylococcus aureus ATCC 29213 and Pseudomonas aeruginosa HIM-MR01. The T. lucida EO alone or added to the antibiotics showed antimicrobial activity against S. aureus and P. aeruginosa. The EO main bioactive compounds were methyl eugenol (relative abundance in EO: 46·15%), estragole (32·93%), linalool (2·48%) and geraniol (0·33%). The mixture (PREO) of those compounds at those proportions inhibited the growth of P. aeruginosa in 45% at 683·62 µg ml-1 and that of S. aureus in 51·7% at 39·04 µg ml-1 . The PREO had higher antibacterial and modulatory activities than the original EO. In conclusion, we overcame the unpredictability of EO activity (due to their natural variability) by determining which EO components inhibited bacteria and then producing a PREO to generate a reproducible mixture with predictable antibacterial and modulation of resistance activities. Thus, the PREO, and its components, show potential as alternatives to manage multidrug-resistant pathogens.


Assuntos
Óleos Voláteis , Tagetes , Antibacterianos/farmacologia , Bactérias , Farmacorresistência Bacteriana Múltipla , Testes de Sensibilidade Microbiana , Óleos Voláteis/farmacologia , Pseudomonas aeruginosa , Staphylococcus aureus
18.
J Matern Fetal Neonatal Med ; 35(25): 8097-8102, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34470130

RESUMO

BACKGROUND: To describe the brain Doppler changes in fetuses with isolated open spina bifida (OSB). STUDY DESIGN: Doppler ultrasound measurements including the umbilical artery (UA) pulsatility index (PI), middle cerebral artery (MCA) PI, and their combination into the cerebroplacental ratio (CPR) and umbilicocerebral ratio (UCR) were performed in a cohort of fetuses with OSB. Included patients were individually matched to a control group without structural anomalies and similar gestational ages. MCA-PI and/or CPR values below the 5th centile were considered abnormal and indicative of cerebral blood redistribution, while UCR and UA-PI above the 95th centile were considered abnormal. RESULTS: During the study period, 266 fetuses were recruited, 133 normally grown fetuses with OSB and 133 matched controls. Doppler recordings were successfully obtained in all fetuses at a median gestational age of 30.9 weeks. All cases showed UA-PI within normal ranges, but fetuses with OSB showed significantly higher frequency of cerebral blood redistribution (15.0 vs. 3.0%, p < .01), MCA-PI <5th centile (10.5% vs. 3.0%, p = .01), decreased CPR (9.8% vs. 2.3%, p = .01) and increased UCR (17.2 % vs 7.5 %, p =.02). The rate of cerebral blood redistribution was significantly higher in the OSB group with ventriculomegaly in comparison to those with OSB and normal lateral ventricle diameter (18.6% vs. 3.2%, respectively; p <.05). CONCLUSION: A proportion of fetuses with isolated open spina bifida showed cerebral blood redistribution.


Assuntos
Espinha Bífida Cística , Gravidez , Feminino , Humanos , Lactente , Espinha Bífida Cística/diagnóstico por imagem , Ultrassonografia Pré-Natal , Retardo do Crescimento Fetal , Artérias Umbilicais/diagnóstico por imagem , Ultrassonografia Doppler , Feto/diagnóstico por imagem , Feto/irrigação sanguínea , Artéria Cerebral Média/diagnóstico por imagem , Idade Gestacional , Encéfalo , Fluxo Pulsátil
19.
Rev Gastroenterol Mex (Engl Ed) ; 87(3): 297-304, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34794928

RESUMO

INTRODUCTION AND AIMS: Colonoscopy quality is measured by the degree in which the examination increases the likelihood of obtaining adequate results on health. Our aim was to develop an instrument for evaluating the quality of screening colonoscopies, taking into account the performance of endoscopists and endoscopy units. MATERIALS AND METHODS: Mixed methodology was employed. The first stage (qualitative) consisted of a Medline search, from which a group of experts developed the quality score items. The second stage (quantitative) utilized a modified Delphi technique to reach consensus (3 rounds). We evaluated the psychometric properties of the instrument (reliability and construct validity) in elective screening colonoscopies (in patients ≥ 50 years of age), performed within the January-April 2017 time frame. RESULTS: A final instrument with 8 items was produced: (1) the Boston Bowel Preparation Scale score; (2) cecal intubation rate; (3) colonoscopy withdrawal time; (4) image documentation; (5) adenoma detection rate; (6) endoscopic surveillance planning; (7) perforation rate, and (8) continuous improvement programs. The instrument was evaluated in 323 colonoscopies performed by 31 endoscopists and found to be one-dimensional and reliable (Cronbach's alpha 0.76). Performance was compared between endoscopists (center 1) and an expert endoscopist from another center (center 2): Boston Bowel Preparation Scale score 8.3 vs. 7.36 (P < .001), cecal intubation rate 93.5 vs. 96%, colonoscopy withdrawal time 14.8 vs. 8.4 min (P < .001), and adenoma detection rate 34 vs. 52.2% (P < .001), respectively. CONCLUSION: The Colonoscopy Quality Score is a reliable and valid instrument for evaluating screening colonoscopy quality. Its results could be adapted to the usual endoscopic report to adjust monitorization frequency post-colonoscopy.


Assuntos
Adenoma , Neoplasias Colorretais , Adenoma/diagnóstico , Ceco , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Humanos , Psicometria , Reprodutibilidade dos Testes
20.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34312017

RESUMO

INTRODUCTION AND AIMS: Colonoscopy quality is measured by the degree in which the examination increases the likelihood of obtaining adequate results on health. Our aim was to develop an instrument for evaluating the quality of screening colonoscopies, taking into account the performance of endoscopists and endoscopy units. MATERIALS AND METHODS: Mixed methodology was employed. The first stage (qualitative) consisted of a Medline search, from which a group of experts developed the quality score items. The second stage (quantitative) utilized a modified Delphi technique to reach consensus (3 rounds). We evaluated the psychometric properties of the instrument (reliability and construct validity) in elective screening colonoscopies (in patients≥50 years of age), performed within the January-April 2017 time frame. RESULTS: A final instrument with 8 items was produced: 1) the Boston Bowel Preparation Scale score; 2) cecal intubation rate; 3) colonoscopy withdrawal time; 4) image documentation; 5) adenoma detection rate; 6) endoscopic surveillance planning; 7) perforation rate, and 8) continuous improvement programs. The instrument was evaluated in 323 colonoscopies performed by 31 endoscopists and found to be one-dimensional and reliable (Cronbach's alpha 0.76). Performance was compared between endoscopists (center 1) and an expert endoscopist from another center (center 2): Boston Bowel Preparation Scale score 8.3 vs. 7.36 (P<.001), cecal intubation rate 93.5 vs. 96%, colonoscopy withdrawal time 14.8 vs. 8.4min (P<.001), and adenoma detection rate 34 vs. 52.2% (P<.001), respectively. CONCLUSION: The Colonoscopy Quality Score is a reliable and valid instrument for evaluating screening colonoscopy quality. Its results could be adapted to the usual endoscopic report to adjust monitorization frequency post-colonoscopy.

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