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1.
Cell Mol Life Sci ; 81(1): 219, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38758230

RESUMO

HMGA1 is a structural epigenetic chromatin factor that has been associated with tumor progression and drug resistance. Here, we reported the prognostic/predictive value of HMGA1 for trabectedin in advanced soft-tissue sarcoma (STS) and the effect of inhibiting HMGA1 or the mTOR downstream pathway in trabectedin activity. The prognostic/predictive value of HMGA1 expression was assessed in a cohort of 301 STS patients at mRNA (n = 133) and protein level (n = 272), by HTG EdgeSeq transcriptomics and immunohistochemistry, respectively. The effect of HMGA1 silencing on trabectedin activity and gene expression profiling was measured in leiomyosarcoma cells. The effect of combining mTOR inhibitors with trabectedin was assessed on cell viability in vitro studies, whereas in vivo studies tested the activity of this combination. HMGA1 mRNA and protein expression were significantly associated with worse progression-free survival of trabectedin and worse overall survival in STS. HMGA1 silencing sensitized leiomyosarcoma cells for trabectedin treatment, reducing the spheroid area and increasing cell death. The downregulation of HGMA1 significantly decreased the enrichment of some specific gene sets, including the PI3K/AKT/mTOR pathway. The inhibition of mTOR, sensitized leiomyosarcoma cultures for trabectedin treatment, increasing cell death. In in vivo studies, the combination of rapamycin with trabectedin downregulated HMGA1 expression and stabilized tumor growth of 3-methylcholantrene-induced sarcoma-like models. HMGA1 is an adverse prognostic factor for trabectedin treatment in advanced STS. HMGA1 silencing increases trabectedin efficacy, in part by modulating the mTOR signaling pathway. Trabectedin plus mTOR inhibitors are active in preclinical models of sarcoma, downregulating HMGA1 expression levels and stabilizing tumor growth.


Assuntos
Proteína HMGA1a , Sarcoma , Trabectedina , Trabectedina/farmacologia , Humanos , Sarcoma/tratamento farmacológico , Sarcoma/patologia , Sarcoma/genética , Sarcoma/metabolismo , Proteína HMGA1a/metabolismo , Proteína HMGA1a/genética , Animais , Linhagem Celular Tumoral , Camundongos , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Prognóstico , Feminino , Leiomiossarcoma/tratamento farmacológico , Leiomiossarcoma/patologia , Leiomiossarcoma/genética , Leiomiossarcoma/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Artif Organs ; 48(7): 753-762, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38404240

RESUMO

BACKGROUND: New versions of the polyester polymer alloy (PEPA) membrane have appeared over the years, with increases in both the pore size and the amount of polyvinylpyrrolidone (PVP) to optimize hydrophilicity performance. This study aimed to assess the efficacy of the most recently developed PEPA dialyzer, the FDY series, in hemodialysis (HD) modality in terms of uremic toxin removal and albumin loss and to compare it with that of several high-flux dialyzers currently used in HD and post-dilution hemodiafiltration (HDF) treatments. METHODS: A prospective study was carried out in 21 patients. All patients underwent six dialysis sessions with the same routine dialysis parameters; only the dialyzer and/or the dialysis modality varied: FX80 in HD, FDY 180 in HD, Clearum HS17 in HDF, Elisio 19H in HDF, Vitapes 180 in HDF, and FX80 in post-dilution HDF. The reduction ratios (RR) of urea, creatinine, ß2-microglobulin, myoglobin, κFLC, prolactin, α1-microglobulin, α1-acid glycoprotein, λFLC, and albumin were compared intraindividually. Dialysate albumin loss was also measured. RESULTS: Both membranes FDY and FX80 are high-flux dialyzers and are applied here in high-flux HD. The average RR of ß2-microglobulin was slightly lower in the two HD treatments than in the HDF treatments. Comparison of dialysis treatments revealed that the PEPA FDY dialyzer in the HD modality was more effective than the FX80 dialyzer in high-flux HD and was as effective as post-dilution HDF, especially in terms of myoglobin, κFLC, prolactin, α1-microglobulin, and λFLC RRs. The FDY treatments obtained similar albumin RR in blood and slightly higher dialysate albumin loss, although the values were clinically acceptable. CONCLUSIONS: The most recently developed PEPA dialyzers in the HD modality were as effective as all treatments in the HDF modality and were clearly superior to high-flux helixone HD treatment. These results confirm that this dialyzer should be categorized within the medium cut-off (MCO) membrane classification.


Assuntos
Membranas Artificiais , Poliésteres , Diálise Renal , Humanos , Masculino , Diálise Renal/instrumentação , Diálise Renal/métodos , Pessoa de Meia-Idade , Feminino , Idoso , Estudos Prospectivos , Poliésteres/química , Ligas/química , Idoso de 80 Anos ou mais , Hemodiafiltração/instrumentação , Hemodiafiltração/métodos , Adulto , Polímeros/química
3.
Med ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39013460

RESUMO

Exceptional elite controllers represent an extremely rare group of people with HIV-1 (PWH) who exhibit spontaneous, high-level control of viral replication below the limits of detection in sensitive clinical monitoring assays and without disease progression in the absence of antiretroviral therapy for prolonged periods, frequently exceeding 25 years. Here, we discuss the different cases that have been reported in the scientific literature, their unique genetic, virological, and immunological characteristics, and their relevance as the best model for the functional cure of HIV-1.

4.
Arthroplast Today ; 28: 101457, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39100421

RESUMO

Background: Leg length discrepancy following hip arthroplasty causes dissatisfaction to the patient; thus, preoperative planning and implant selection is critical. The purpose of this study was to measure the articular-trochanteric distance (ATD) and femoral neck length (FNL) in our population and compare them to those of 3 of the most used uncemented stems. Methods: In this cross-sectional study, 401 hip radiographs of healthy adults were collected between January and July 2022. The vertical ATD and FNL were measured. A linear regression model was used to identify the relationship between these measurements and age, sex, and height. A logistic regression model was used to assess the matching of native hips with the neck length of the stem. Results: Mean age was 60 years, and 74.56% were women. In 94.3% of hips, the ATD was negative, 3.73% neutral, and 2% positive. In our population, 0.25% of FNL were shorter than POLARSTEM (Smith & Nephew, UK), 10.72% shorter than MetaFix stem (Corin, UK), and 11.97% shorter than Corail stem (DePuy Synthes, USA). In the logistic regression analysis, matching for the POLARSTEM was associated with age but not with sex or height. Conversely, for MetaFix and Corail, stem matching was associated with sex and height. Conclusions: Anthropometric hip measurements vary among individuals, and variables such as age, sex, and height must be considered during preoperative planning and implant selection to avoid leg length discrepancy. Additional studies, including different implants, are required to guide surgeons in selecting a femoral stem that best matches the patient's native hip.

5.
Nefrologia (Engl Ed) ; 44(3): 354-361, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38679516

RESUMO

INTRODUCTION: New generation helixone dialyzers has recently been developed as part of the ongoing effort to improve dialyzer hemocompatibility and avoid adverse reactions to synthetic dialyzers. This study aimed to assess the performance and albumin loss of this new dialyzer series in hemodiafiltration and compare it with the previous generation helixone series. MATERIAL AND METHODS: A prospective study was conducted in 19 patients. Each patient underwent eight dialysis sessions with the same routine dialysis parameters; only the dialyzer varied: FX60 CorDiax, FX CorAL 60, FX600 CorDiax, FX CorAL 600, FX80 CorDiax, FX CorAL 80, FX800 CorDiax, and FX CorAL 800. The reduction ratios (RR) of urea, creatinine, ß2-microglobulin, myoglobin, kappa-free immunoglobulin light chains (κFLC), prolactin, α1-microglobulin, α1-acid glycoprotein, lambda immunoglobulin light chains (λFLC), and albumin were compared intra-individually. Dialysate albumin loss was also measured. RESULTS: All treatments were well tolerated. The mean amount of replacement fluid ranged from 31 to 34 L. Comparison of dialysis treatments showed no differences between small molecules and even up to those the size of ß2-microglobulins. Little differences were found between myoglobin, κFLC, prolactin, α1-microglobulin, and λFLC RRs, and only FX80 CorDiax was slightly superior to the others. Mean dialysate albumin losses were similar, with less than 2.5 g lost in each dialyzer. The FX80 CorDiax showed slightly higher global removal scores than the other dialyzers evaluated, except for FX CorAL 800. CONCLUSION: The new generation helixone dialyzers series has been updated to minimise the risk of adverse reactions, while maintaining the effectiveness and albumin loss achieved by the previous most advanced helixone generation.


Assuntos
Hemodiafiltração , Humanos , Estudos Prospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Hemodiafiltração/instrumentação , Hemodiafiltração/métodos , Desenho de Equipamento , Adulto , Resultado do Tratamento , Albumina Sérica/análise , Idoso de 80 Anos ou mais
6.
Int J Cardiol ; 408: 132117, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38710232

RESUMO

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is believed to have low overall mortality rate, that could be influenced by gender, particularly among probands. We aimed to evaluate the survival rates and possible gender differences in a homogeneous cohort of HCM proband patients, referred for genetic testing, from the same geographical area, without differences in medical care access nor clinical referral pathways. METHODS: we compared the mortality rates of a cohort of consecutive HCM probands referred for genetic testing (2000-2022), from a Spanish region (xxx1) with a centralized genetic testing pathway, with its control reference population by Ederer II method. Gender differences were analyzed. RESULTS: Among the 649 HCM probands included in this study, there were significantly more men than women (61.3% vs 38.7, p < 0.05), with an earlier diagnosis (53.5 vs 61.1 years old, p < 0.05). Clinical evolution or arrhythmogenic HCM profile did no show no significant gender differences. Mean follow up was 9,8 years ±6,6 SD (9,9 ± 7 vs 9,6 ± 6,1, p = 0.59). No statistically significant differences in observed mortality, expected survival and excess mortality were found in the general HCM proband cohort. However, we found a significant excess mortality in female probands with HCM. No additional differences in analysis by genetic status were identified. CONCLUSION: Expected survival in our HCM probands did not differ from its reference population. However, despite no gender differences in phenotype severity were identified, proband HCM women did present a diagnosis delay and worse mortality outcomes.


Assuntos
Cardiomiopatia Hipertrófica , Testes Genéticos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/mortalidade , Cardiomiopatia Hipertrófica/diagnóstico , Testes Genéticos/métodos , Adulto , Idoso , Análise de Sobrevida , Estudos de Coortes , Seguimentos , Taxa de Sobrevida/tendências , Encaminhamento e Consulta , Espanha/epidemiologia , Fatores Sexuais , Caracteres Sexuais
7.
bioRxiv ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38328248

RESUMO

Fast-spiking parvalbumin (PV)-positive cells are key players in orchestrating pyramidal neuron activity, and their dysfunction is consistently observed in myriad brain diseases. To understand how immune complement dysregulation - a prevalent locus of brain disease etiology - in PV cells may drive disease pathogenesis, we have developed a transgenic mouse line that permits cell-type specific overexpression of the schizophrenia-associated complement component 4 (C4) gene. We found that overexpression of mouse C4 (mC4) in PV cells causes sex-specific behavioral alterations and concomitant deficits in synaptic connectivity and excitability of PV cells of the prefrontal cortex. Using a computational network, we demonstrated that these microcircuit deficits led to hyperactivity and disrupted neural communication. Finally, pan-neuronal overexpression of mC4 failed to evoke the same deficits in behavior as PV-specific mC4 overexpression, suggesting that C4 perturbations in fast-spiking neurons are more harmful to brain function than pan-neuronal alterations. Together, these results provide a causative link between C4 and the vulnerability of PV cells in brain disease.

8.
Eur Stroke J ; 9(2): 486-493, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38189284

RESUMO

INTRODUCTION: Reperfusion therapies represent promising treatments for patients with Central Retinal Artery Occlusion (CRAO), but access is limited due to low incidence and lack of protocols. We aimed to describe the benefit of implementing a Retinal Stroke-Code protocol regarding access to reperfusion, visual acuity and aetiological assessment. PATIENTS AND METHODS: Prospective cohort study performed at a Comprehensive Stroke Centre. Criteria for activation were sudden monocular, painless vision loss within 6 h from onset. Eligible patients received IAT when immediately available and IVT otherwise. All patients were followed by ophthalmologists to assess best-corrected visual acuity (BCVA) and visual complications, and by neurologists for aetiological workup. Visual amelioration was defined as improvement of at least one Early Treatment Diabetic Retinopathy Study (ETDRS) letter from baseline to 1 week. RESULTS: Of 49 patients with CRAO, 15 (30.6%) received reperfusion therapies (12 IVT, 3 IAT). Presentation beyond 6 h was the main contraindication. Patients receiving reperfusion therapies had better rates of visual improvement (33.3% vs 5.9%, p = 0.022). There were no complications related to reperfusion therapies. Rates of neovascular glaucoma were non-significantly lower in patients receiving reperfusion therapies (13.3% vs 20.6%, p = 0.701). Similar rates of atherosclerotic, cardioembolic and undetermined aetiologies were observed, leading to 10 new diagnosed atrial fibrillation and five carotid revascularizations. CONCLUSION: A comprehensive acute management of CRAO is feasible despite low incidence. In our study, reperfusion therapies were safe and associated with higher rates of visual recovery. A similar etiological workup than ischemic stroke led to of high proportion of underlying aetiologies.


Assuntos
Reperfusão , Oclusão da Artéria Retiniana , Acuidade Visual , Humanos , Feminino , Masculino , Idoso , Oclusão da Artéria Retiniana/terapia , Estudos Prospectivos , Pessoa de Meia-Idade , Reperfusão/métodos , Recuperação de Função Fisiológica , Idoso de 80 Anos ou mais , Acidente Vascular Cerebral/terapia , Resultado do Tratamento
9.
Clin Transl Oncol ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38662171

RESUMO

The 2021 World Health Organization (WHO) classification has updated the definition of grade 2 gliomas and the presence of isocitrate dehydrogenase (IDH) mutation has been deemed the cornerstone of diagnosis. Though slow-growing and having a low proliferative index, grade 2 gliomas are incurable by surgery and complementary treatments are vital to improving prognosis. This guideline provides recommendations on the multidisciplinary treatment of grade 2 astrocytomas and oligodendrogliomas based on the best evidence available.

10.
Mult Scler Relat Disord ; 87: 105678, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38728960

RESUMO

BACKGROUND: We aimed to investigate the characteristics of cognitive impairment in older people with multiple sclerosis (MS). METHODS: Cross-sectional study that included participants that were examined with a common and comprehensive neuropsychological protocol. The subjects were matched by sociodemographic variables and the following groups were generated for comparisons: young MS versus healthy controls (HC) (n = 246), old MS versus HC (n = 198), young MS vs old MS (n = 226), MS vs Alzheimer's disease (AD)(n = 70), and MS vs Parkinson's disease (PD) (n = 62). The ICCoDiMS criteria were used to define cognitive impairment in MS. RESULTS: Cognitive impairment was more frequent in young than old patients (70.8 % vs 52.2 %). Attention and speed processing is the most frequent cognitive domain impaired in MS (54.9 % of young MS vs 32.7 % of old MS). The frequency of impairment in attention/processing speed (54.9 % vs 32.7 %) and episodic memory (27.9 % vs 14.3) was higher in the young group than in the old group. There were no statistically significant differences in the distribution of impairment in executive function (46.0 % vs 35.3 %), visuospatial (17.9 % vs 9.5 %), and language (12.4 % vs 17.7 %). In those patients meeting the criteria for cognitive impairment, young MS patients showed lower performance in attention/processing speed tests. Conversely, old MS patients showed lower performance in episodic memory, verbal fluency, and planning. There were no differences in the correlations between SDMT and other neuropsychological tests in young and old patients, which suggests similar cognitive processes underlying SDMT performance in both groups. There were differences between old MS and prodromal AD, especially in episodic memory, while the cognitive profile of old MS was largely shared with PD. CONCLUSIONS: Our study found that the cognitive profile of MS is defined by a characteristic impairment in attention and processing speed, which is present during the lifespan. The impairment in processing speed is less prominent in old age, whereas the impairment of other cognitive functions becomes more relevant. These findings suggest potential differences in the pathophysiological processes associated with cognitive impairment between young and old ages that warrant further investigation.


Assuntos
Envelhecimento , Disfunção Cognitiva , Esclerose Múltipla , Humanos , Masculino , Feminino , Estudos Transversais , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Esclerose Múltipla/complicações , Esclerose Múltipla/fisiopatologia , Pessoa de Meia-Idade , Adulto , Envelhecimento/fisiologia , Idoso , Atenção/fisiologia , Testes Neuropsicológicos , Adulto Jovem , Função Executiva/fisiologia , Doença de Parkinson/complicações , Doença de Parkinson/fisiopatologia
11.
Adv Rheumatol ; 64(1): 52, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987832

RESUMO

BACKGROUND: Systemic sclerosis (SSc) is a rare chronic autoimmune disease with heterogeneous manifestations. In the last decade, several clinical trials have been conducted to evaluate new treatment options for SSc. The purpose of this work is to update the recommendations of the Brazilian Society of Rheumatology in light of the new evidence available for the pharmacological management of SSc. METHODS: A systematic review including randomized clinical trials (RCTs) for predefined questions that were elaborated according to the Patient/Population, Intervention, Comparison, and Outcomes (PICO) strategy was conducted. The rating of the available evidence was performed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. To become a recommendation, at least 75% agreement of the voting panel was needed. RESULTS: Six recommendations were elaborated regarding the pharmacological treatment of Raynaud's phenomenon, the treatment (healing) and prevention of digital ulcers, skin involvement, interstitial lung disease (ILD) and gastrointestinal involvement in SSc patients based on results available from RCTs. New drugs, such as rituximab, were included as therapeutic options for skin involvement, and rituximab, tocilizumab and nintedanib were included as therapeutic options for ILD. Recommendations for the pharmacological treatment of scleroderma renal crisis and musculoskeletal involvement were elaborated based on the expert opinion of the voting panel, as no placebo-controlled RCTs were found. CONCLUSION: These guidelines updated and incorporated new treatment options for the management of SSc based on evidence from the literature and expert opinion regarding SSc, providing support for decision-making in clinical practice.


Assuntos
Doença de Raynaud , Reumatologia , Escleroderma Sistêmico , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológico , Humanos , Brasil , Reumatologia/normas , Doença de Raynaud/tratamento farmacológico , Sociedades Médicas , Doenças Pulmonares Intersticiais/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Rituximab/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Úlcera Cutânea/etiologia , Antirreumáticos/uso terapêutico
12.
Lancet HIV ; 11(6): e389-e405, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38816141

RESUMO

BACKGROUND: Allogeneic haematopoietic stem-cell transplantation (allo-HSCT) markedly reduces HIV reservoirs, but the mechanisms by which this occurs are only partly understood. In this study, we aimed to describe the dynamics of virological and immunological markers of HIV persistence after allo-HSCT. METHODS: In this prospective observational cohort study, we analysed the viral reservoir and serological dynamics in IciStem cohort participants with HIV who had undergone allo-HSCT and were receiving antiretroviral therapy, ten of whom had received cells from donors with the CCR5Δ32 mutation. Participants from Belgium, Canada, Germany, Italy, the Netherlands, Spain, Switzerland, and the UK were included in the cohort both prospectively and retrospectively between June 1, 2014 and April 30, 2019. In the first 6 months after allo-HSCT, participants had monthly assessments, with annual assessments thereafter, with the protocol tailored to accommodate for the individual health status of each participant. HIV reservoirs were measured in blood and tissues and HIV-specific antibodies were measured in plasma. We used the Wilcoxon signed-rank test to compare data collected before and after allo-HSCT in participants for whom longitudinal data were available. When the paired test was not possible, we used the Mann-Whitney U test. We developed a mathematical model to study the factors influencing HIV reservoir reduction in people with HIV after allo-HSCT. FINDINGS: We included 30 people with HIV with haematological malignancies who received a transplant between Sept 1, 2009 and April 30, 2019 and were enrolled within the IciStem cohort and included in this analysis. HIV reservoirs in peripheral blood were reduced immediately after full donor chimerism was achieved, generally accompanied by undetectable HIV-DNA in bone marrow, ileum, lymph nodes, and cerebrospinal fluid, regardless of donor CCR5 genotype. HIV-specific antibody levels and functionality values declined more slowly than direct HIV reservoir values, decaying significantly only months after full donor chimerism. Mathematical modelling suggests that allogeneic immunity mediated by donor cells is the main viral reservoir depletion mechanism after massive reservoir reduction during conditioning chemotherapy before allo-HSCT (half-life of latently infected replication-competent cells decreased from 44 months to 1·5 months). INTERPRETATION: Our work provides, for the first time, data on the effects of allo-HSCT in the context of HIV infection. Additionally, we raise the question of which marker can serve as the last reporter of the residual viraemia, postulating that the absence of T-cell immune responses might be a more reliable marker than antibody decline after allo-HSCT. FUNDING: amfAR (American Foundation for AIDS Research; ARCHE Program), National Institutes of Health, National Institute of Allergy and Infectious Diseases, and Dutch Aidsfonds.


Assuntos
Infecções por HIV , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por HIV/imunologia , Infecções por HIV/virologia , Masculino , Estudos Prospectivos , Feminino , Adulto , Pessoa de Meia-Idade , HIV-1/imunologia , Transplante Homólogo , Biomarcadores/sangue , Carga Viral , Anticorpos Anti-HIV/sangue
13.
Front Psychol ; 15: 1373541, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38988382

RESUMO

Introduction: Timely and accurate diagnosis of the earliest manifestations of Alzheimer's disease (AD) is critically important. Cognitive challenge tests such as the Loewenstein Acevedo Scales for Semantic Interference and Learning (LASSI-L) have shown favorable diagnostic properties in a number of previous investigations using amyloid or FDG PET. However, no studies have examined LASSI-L performance against cerebrospinal fluid biomarkers of AD, which can be affected before the distribution of fibrillar amyloid and other changes that can be observed in brain neuroimaging. Therefore, we aimed to evaluate the relationship between LASSI-L scores and CSF biomarkers and the capacity of the cognitive challenge test to detect the presence of amyloid and tau deposition in patients with subjective cognitive decline and amnestic mild cognitive impairment (MCI). Methods: One hundred and seventy-nine patients consulting for memory loss without functional impairment were enrolled. Patients were examined using comprehensive neuropsychological assessment, the LASSI-L, and cerebrospinal fluid (CSF) biomarkers (Aß1-42/Aß1-40 and ptau181). Means comparisons, correlations, effect sizes, and ROC curves were calculated. Results: LASSI-L scores were significantly associated with CSF biomarkers Aß1-42/Aß1-40 in patients diagnosed with MCI and subjective cognitive decline, especially those scores evaluating the capacity to recover from proactive semantic interference effects and delayed recall. A logistic regression model for the entire sample including LASSI-L and age showed an accuracy of 0.749 and an area under the curve of 0.785 to detect abnormal amyloid deposition. Conclusion: Our study supports the biological validity of the LASSI-L and its semantic interference paradigm in the context of the early stages of AD. These findings emphasize the utility and the convenience of including sensitive cognitive challenge tests in the assessment of patients with suspicion of early stages of AD.

14.
Rev. colomb. cir ; 38(4): 759-763, 20230906. fig
Artigo em Espanhol | LILACS | ID: biblio-1511136

RESUMO

Introducción. La intususcepción del apéndice corresponde a su invaginación en el ciego. Existen varias causas, pero la endometriosis ha sido informada pocas veces. Aunque el diagnóstico se debe sospechar clínicamente, por lo general su causa solo se determina en el intraoperatorio, donde se deben tener en cuenta causas oncológicas que requieran una resección amplia. Caso clínico. Mujer de 21 años que consultó por dolor abdominal agudo generalizado. Se practicó una tomografía computarizada de abdomen, observando una intususcepción del apéndice en el ciego, estriación de la grasa pericecal y adenomegalias. Se realizó laparoscopia diagnóstica encontrando intususcepción casi completa del apéndice cecal, de aspecto neoplásico. Se convirtió a laparotomía para proceder a hemicolectomía derecha, con vaciamiento ganglionar y anastomosis del íleon al colon transverso. Discusión. La sospecha clínica de intususcepción debe corroborarse mediante ecografía, tomografía o estudios baritados. El tratamiento siempre es quirúrgico, como en el caso de nuestra paciente, quien evolucionó de forma adecuada y continuó asintomática después de un año de seguimiento. Conclusión. El diagnóstico temprano de la intususcepción permite realizar tratamientos quirúrgicos menos agresivos y disminuye el riesgo de filtración de la anastomosis. Se debe tener en cuenta el diagnóstico de endometriosis como posible causa. Se debe realizar el manejo complementario por parte de ginecología.


Introduction. The intussusception of the appendix corresponds to its invagination in the cecum. There are several causes, endometriosis being rarely reported. Although the diagnosis must be suspected clinically, its cause is generally only determined intraoperatively, where oncological causes that require extensive resection must be taken into account. Clinical case. A 21-year-old woman who consulted due to acute generalized abdominal pain, an abdominal tomography was performed, finding an intussusception of the appendix in the cecum, striation of pericecal fat, and lymph nodes. A diagnostic laparoscopy was performed, finding almost complete intussusception of the appendix, with a neoplastic appearance. She was converted to laparotomy to perform a right hemicolectomy, with lymph node dissection and ileal to transverse anastomosis. Discussion. Clinical suspicion of intussusception should be confirmed by ultrasound, abdominal tomography, or barium studies. Treatment is always surgical, as in the case of our patient, who evolved adequately and remained asymptomatic after one year of follow-up. Conclusion. Early diagnosis of intussusception allows for less aggressive surgical treatment and decreases the risk of anastomosis leakage. The diagnosis of endometriosis should be taken into account as a possible cause. Complementary management by gynecologists should be performed.


Assuntos
Humanos , Apendicite , Endometriose , Neoplasias do Apêndice , Colectomia , Intussuscepção
15.
Rev. Asoc. Méd. Argent ; 136(1): 14-18, mar. 2023. tab
Artigo em Espanhol | LILACS | ID: biblio-1553747

RESUMO

El objetivo de este artículo es comparar las propiedades químicas y farmacológicas del telmisartán y el losartán, y su metabolito activo EXP3174, con el fin de entender por qué el telmisartán es efectivo en pacientes hospitalizados con Covid-19 mientras que el losartán no lo es. Se llevó a cabo una revisión bibliográfica exhaustiva de las propiedades químicas, farmacocinéticas y farmacodinámicas de ambos fármacos y se destacaron las diferencias más importantes que podrían estar relacionadas con su efectividad en pacientes con Covid-19. Se concluyó que las propiedades farmacológicas del telmisartán, como su mayor afinidad por el receptor AT1, su duración de acción prolongada y su capacidad para modular la inflamación podrían explicar su efectividad en pacientes con Covid-19. Por otro lado, las propiedades farmacológicas del losartán, como su menor afinidad por el receptor AT1 y su rápido metabolismo, pueden limitar su efectividad en pacientes con Covid-19. Estos resultados resaltan la importancia de comprender las propiedades químicas y farmacológicas de los medicamentos para identificar posibles candidatos terapéuticos efectivos en el tratamiento de Covid-19. (AU)


The objective of this article is to compare the chemical and pharmacological properties of telmisartan and losartan and their active metabolite EXP3174 to understand why telmisartan is effective in hospitalized patients with COVID-19 while losartan is not. A comprehensive literature review of the chemical, pharmacokinetic and pharmacodynamic properties of both drugs was done to highlight the most important differences that may be related to their efficacy in patients with COVID-19. It was concluded that the pharmacological properties of telmisartan, such as its higher affinity for the AT1 receptor, its long duration of action and its ability to modulate inflammation, could explain its efficacy in patients with COVID-19. On the other hand, the pharmacological properties of losartan, such as its lower affinity for the AT1 receptor and its rapid metabolism, may limit its efficacy in patients with COVID-19. These results highlight the importance of understanding the chemical and pharmacological properties of drugs to identify potential effective therapeutic candidates for the treatment of COVID-19. (AU)


Assuntos
Losartan/farmacologia , Telmisartan/farmacologia , Tratamento Farmacológico da COVID-19 , Ensaios Clínicos Controlados como Assunto , Losartan/química , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Telmisartan/química , Hospitalização
16.
CienciaUAT ; 16(2): 114-125, ene.-jun. 2022. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1374904

RESUMO

Resumen Las organizaciones del sector público tienen como reto dar respuesta y solucionar las necesidades de la sociedad. Ante ese desafío, su gestión debe indagar la eficiencia de sus tareas. En esta vertiente, la reflexividad es una pieza clave, fundamental para el desempeño de los equipos de trabajo y útil para evaluar, buscar soluciones y tomar decisiones. El objetivo del presente estudio fue establecer, en una dependencia del gobierno mexicano, si la integración, el involucramiento y la retroalimentación, influyen en la reflexividad. El diseño fue cuantitativo, no experimental, transversal y causal. Se encuestó a 108 empleados. Los datos se recolectaron con un cuestionario auto administrado y como técnica de análisis se usó un modelo de ecuaciones estructurales con mínimos cuadrados parciales (PLS). Los resultados revelan que la integración, el involucramiento y la retroalimentación en esa dependencia tienen un efecto favorable y significativo en la reflexividad, reflejado en mayor medida en la búsqueda de acuerdos para alcanzar las metas laborales y la ejecución competente del trabajo; siendo la retroalimentación la variable de mayor influencia.


Abstract The challenge of public sector organizations is to respond and solve the needs of society. Faced with this hurdle, management must seek to improve task efficiency. In this regard, reflexivity is a key variable for team performance and useful for evaluating, seeking solutions, and making decisions. The aim of the present research is to determine if integration, involvement, and feed-back variables have an influence on reflexivity, within the context of a government department. A quantitative, non-experimental, cross-sectional and causal design was employed. A sample of 108 employees was surveyed. Data were collected through a self-administered questionnaire and a model of structural equations with partial least squares (PLS) was used as an analysis technique. Results reveal that integration, involvement and feedback have a favorable and significant effect on reflexivity. In this context reflexivity is reflected to a greater extent in the search for agreements to achieve work goals and competent job execution. Overall, the variable exerting the greatest influence is feedback.

17.
Evid. actual. práct. ambul ; 24(3): e002133, 2021.
Artigo em Espanhol | LILACS, UNISALUD, BINACIS | ID: biblio-1291041

RESUMO

La hidatidosis o equinococosis quística es una infección endémica en varias regiones de Argentina. Su forma más frecuente, la hidatidosis hepática, suele ser asintomática por largos periodos de tiempo y, de presentar síntomas, los mismos suelen ser solapados, inespecíficos y crónicos. Por este motivo, los métodos complementarios de diagnóstico resultan indispensables en la valoración de estos pacientes. Entre ellos, la ecografía continúa siendo el método de elección con el que iniciar la evaluación ante la sospecha de hidatidosis hepática; otros métodos, como la serología, la tomografía computada o la resonancia magnética, pueden resultar de utilidad en casos específicos y siempre contextualizados por la clínica, epidemiología, y los hallazgos ecográficos. (AU)


Hydatidosis or cystic echinococcosis is an endemic infection in several regions of Argentina. Its most frequent form, hepatic hydatidosis, is usually asymptomatic for long periods of time and, if symptoms occur, they are usually overlapping, non-specific and chronic. For this reason, complementary diagnostic methods are essential in the evaluation of these patients. Among them, ultrasound remains the method of choice to initiate the evaluation of suspected hepatic hydatidosis; other methods, such as serology, computed tomography or magnetic resonance imaging, may be useful in specific cases and always contextualised by the clinical, epidemiology and ultrasound findings. (AU)


Assuntos
Humanos , Masculino , Adulto , Ultrassonografia , Equinococose Hepática/diagnóstico por imagem , Argentina , Saúde da População Rural , Doenças Endêmicas , Equinococose Hepática/epidemiologia
18.
Rev. colomb. obstet. ginecol ; 72(1): 12-23, Jan.-Mar. 2021. tab
Artigo em Espanhol | LILACS | ID: biblio-1251609

RESUMO

RESUMEN Objetivo: evaluar la prevalencia de yodo deficiencia y de bocio en mujeres indígenas gestantes de cinco áreas no metropolitanas en Colombia. Materiales y métodos: estudio de corte transversal descriptivo. Se incluyeron mujeres embarazadas de cualquier edad gestacional sin condiciones patológicas del embarazo, atendidas en los centros de salud comunitarios o en sus residencias. Se excluyeron aquellas con comorbilidades presentes al momento del embarazo y también a quienes recibían suplementos con yodo. Muestreo aleatorio simple. Se midieron las características sociodemográficas y obstétricas, la concentración de yodo en orina y la presencia de bocio de acuerdo a la metodología de la Organización Mundial de la Salud. Se realizó un análisis descriptivo. Resultados: 189 gestantes indígenas fueron candidatas a ingresar al estudio, de las cuales 2 no aceptaron participar y 62 tenían criterios de exclusión, finalmente se analizaron 125. La concentración urinaria de yodo tuvo una mediana de 184,4 µg/L (min-max: 12,0-390,0). Un total de 42 gestantes (33,6%) tenían yodo deficiencia (< 100 µg/L) y se evidenció bocio (grado 1-2) en 43 (34,4%). No se identificó bocio grados 3 o 4. Conclusiones: embarazadas indígenas residentes en áreas no metropolitanas evidenciaron alta prevalencia de bocio y yodo deficiencia. Se requiere evaluar los efectos materno-perinatales e implementar intervenciones nutricionales.


ABSTRACT Objective: To assess the prevalence of goiter and iodine deficiency in indigenous pregnant women coming from five non-metropolitan areas in Colombia. Materials and methods: Descriptive cross-sectional cohort study that included pregnant women of any gestational age with no pregnancy-related conditions, seen in community health centers or in their homes. Patients with comorbidities at the time of pregnancy and those who were receiving iodine supplementation were excluded. Simple random sampling was used. The sociodemographic and obstetric characteristics, urinary iodine concentration and the presence of goiter were measured in accordance with the World Health Organization methodology. A descriptive analysis was performed. Results: Of 189 indigenous pregnant women who were candidates to enter the study, 2 declined participation, and 62 had exclusion criteria, and 125 were included in the final analysis. The mean urinary iodine concentration was 184.4 µg/L (min-max: 12.0-390.0). A total of 42 women (33.6%) had iodine deficiency (< 100 µg/L), and goiter (grade 1-2) was found in 43 (34.4%). No grade 3 or 4 goiter was identified. Conclusions: A high prevalence of goiter and iodine deficiency was found in indigenous pregnant women living in non-metropolitan areas. There is a need to assess maternal and perinatal effects and to implement nutritional interventions.


Assuntos
Humanos , Feminino , Gravidez , Deficiência de Iodo , Prevalência , Gestantes , Bócio , Povos Indígenas
19.
Rev. colomb. ciencias quim. farm ; 49(1): 137-158, Jan.-Apr. 2020. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1144343

RESUMO

RESUMEN Son conocidos los efectos de los anticoagulantes como tratamiento o profilaxis de eventos trombóticos, esto permitió establecer una terapia individualizada según sus necesidades. Se realizó un estudio descriptivo, transversal, no aleatorizado, en 138 pacientes hospitalizados mayores de edad en una institución de cuarto nivel de atención con tratamiento anticoagulante terapéutico y profiláctico, se abordó el tipo de fármaco indicado, periodicidad, efectos adversos, controles de laboratorio, interacciones farmacológicas y causalidad de las reacciones adversas. Se encontró que el anticoagulante con mayor frecuencia de uso fue enoxaparina (68%), el control más utilizado fue el tiempo de protrombina (60,39%), interacciones farmacológicas se identificaron en 47,1%, las más frecuentes con ácido acetil salicílico (29,7% del total de interacciones), las reacciones adversas más frecuentes fueron de índole hematológico (58,3%); y la evaluación de causalidad de reacciones adversas fue 4,2% probable. El estudio mostró que el anticoagulante más utilizado fue enoxaparina. Las interacciones farmacológicas de los anticoagulantes fueron muy frecuentes, especialmente con warfarina. Las reacciones adversas de mayor ocurrencia fueron las de tipo hemorrágico ; y la evaluación de causalidad fue de categoría posible para la mayoría de estas reacciones adversas.


SUMMARY The effects of anticoagulants are known as treatment or prophylaxis of thrombotic events, allowing to establish an individualized therapy according to their needs. A descriptive cross-sectional, non-randomized study was carried out in 138 hospitalized patients of legal age in a fourth-level care institution with therapeutic and prophylactic anticoagulant treatment, addressing the type of drug indicated, periodicity, side effects, laboratory controls, pharmacological interactions and causality of adverse reactions. It was found that the anticoagulant with the highest frequency of use was enoxaparin (68%), the most used control was the prothrombin time (60.39%), pharmacological interactions were identified in 47.1%, being the most frequent with acetylsalicylic acid (29.7% of the total number of interactions), the most frequent adverse reactions were of a hematological nature (58.3%); and the causality assessment of adverse reactions was 4.2% probable. The study showed that the most used anticoagulant was enoxaparin. The pharmacological interactions of anticoagulants were very frequent, especially with warfarin. The most frequent adverse reactions were those of hemorrhagic type; and the causality assessment was of possible category for most of these adverse reactions.

20.
Med. UIS ; 31(3): 21-25, sep.-dic. 2018. tab
Artigo em Espanhol | LILACS | ID: biblio-1002516

RESUMO

Resumen Introducción: el hipotiroidismo se ha asociado con deterioro cognitivo, así como con reducción en la calidad de vida; sin embargo, existe controversia al respecto porque la evidencia es contradictoria. El hipotiroidismo parece provocar alteraciones en el estado cognitivo y en el estado de ánimo en adultos mayores, por lo que se requieren estudios para establecer dicha asociación y de esta manera evaluar el tratamiento sustitutivo hormonal. Objetivo: determinar la prevalencia de hipotiroidismo subclínico, deterioro cognitivo en el adulto mayor y su posible asociación en pacientes adultos mayores. Material y métodos: estudio transversal, descriptivo, y analítico, realizado en el módulo de gerontología en la Clínica Medicina Familiar "Dr. Ignacio Chávez", Ciudad De México, de junio a noviembre de 2016. Se realizó muestreo no probabilístico por conveniencia. Se aplicó el examen Mini mental para deterioro cognitivo. Se enviaron las muestras de sangre al laboratorio para la realización de pruebas de función tiroidea. El análisis estadístico se realizó con la prueba de chi cuadrado de independencia con nivel de significancia de 0,05. Se utilizó el programa estadístico Statistical Package for the Social Sciences, versión 22. Resultados: se estudiaron 120 adultos mayores con un promedio de edad de 78,2 años. El 35,8% de los pacientes presentaron hipotiroidismo subclínico, y el 63% presentó algún grado de deterioro cognitivo. Al asociar estas variables, no se obtuvo significancia estadística (p=0,556). Conclusiones: este estudio demuestra una alta prevalencia de hipotiroidismo subclínico y de deterioro cognitivo en la población de estudio, sin que se haya presentado asociación entre ambas variables. MÉD.UIS. 2018;31(3):21-25.


Abstract Introduction: hypothyroidism has been related to cognitive impairment, as well as a reduction in life quality, however, controversy exists in this matter because evidence is contradictory. Hypothyroidism seems to cause changes in elderly's cognitive and emotional state. Studies are required to establish such relationship, and to evaluate substitute hormonal treatment. Objective: to determine the prevalence of subclinical hypothyroidism and cognitive impairment in older adults and its possible association in elderly patients. Material and Methods: cross-sectional, analytic, descriptive study, carried out in a Gerontology Module from Family Medicine Clinic "Dr. Ignacio Chávez" in Mexico City, from June to November 2016. Non probabilistic convenience sampling was done. Mini Mental Status Exam was applied for cognitive impairment. Blood Samples were sent to laboratory to make thyroid function tests. Statistical Analysis including independence Chi-Square with significance level 0,05. Statistical Package for the Social Science version 22 was used. Results: 120 older adults were studied, the average age was 78,2. 35.8% of the patients presented subclinical hypothyroidism, and 63% presented some degree of cognitive impairment. While relating this variables, no statistical significance was obtained (p=0,556). Conclusions: The present study demonstrated a high prevalence of subclinical hypothyroidism and cognitive impairment in the study population. The relationship between the two variables was not demonstrated. MÉD.UIS. 2018;31(3):21-25.


Assuntos
Humanos , Masculino , Idoso , Idoso de 80 Anos ou mais , Hipotireoidismo , Qualidade de Vida , Idoso , Saúde Mental , Disfunção Cognitiva
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