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1.
Breast Cancer Res Treat ; 205(3): 579-587, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38453783

RESUMO

PURPOSE: There have been significant advances in the treatment of metastatic breast cancer (BC) over the past years, and long-term outcomes after a diagnosis of brain metastases are lacking. We aimed to identify predictors of brain metastases at initial breast cancer diagnosis, describe overall survival (OS) in the past decade, and identify factors associated with OS after brain metastases diagnosis. METHODS: We evaluated patients with de novo stage IV BC using the Surveillance, Epidemiology and End Results database from 2010 to 2019. Multivariate logistic regression was conducted to assess predictors of brain metastases at initial breast cancer diagnosis. OS was estimated using the Kaplan-Meier method and log rank test was used to compare differences between groups. Cox regression was used to assess associations between several variables and OS. RESULTS: 1,939 patients with brain metastases at initial breast cancer diagnosis were included. Factors associated with this presentation were grade III/IV tumors, ductal histology, hormone receptor (HR)-negative/human epidermal growth factor receptor 2 (HER2)-positive subtype, and extracranial metastases. Patients with HR-positive/HER2-positive disease had the longest OS (median 18 months) and 12.2% were alive at 8 years. Factors associated with shorter OS included older age, lower income, triple-negative subtype, higher grade, and visceral metastases. CONCLUSION: Over the last decade, the median OS of patients with brain metastases at initial breast cancer diagnosis remained poor; however, a substantial minority survive 5 or more years, with rates higher in patients with HER2-positive tumors. In addition to tumor subtype, OS varied according to age, extracranial metastases, and sociodemographic factors.


Assuntos
Neoplasias Encefálicas , Neoplasias da Mama , Programa de SEER , Humanos , Feminino , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/epidemiologia , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Neoplasias da Mama/epidemiologia , Pessoa de Meia-Idade , Idoso , Adulto , Receptor ErbB-2/metabolismo , Prognóstico , Análise de Sobrevida , Estadiamento de Neoplasias , Estimativa de Kaplan-Meier
2.
Breast Cancer Res Treat ; 201(3): 489-498, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37418032

RESUMO

PURPOSE: Male breast cancer accounts for approximately 1% of all breast cancer diagnoses. Unfortunately, a lack of information exists regarding late effects of breast cancer treatment in men. METHODS: An online survey directed towards male breast cancer patients was distributed via social medial and emails from June to July 2022. Participants were asked about their disease characteristics, treatments and side effects from the disease or treatment. Patients and treatment variables were reported via descriptive statistics. Univariate logistic regression was performed to evaluate associations between different treatment variables and outcomes expressed by odds ratio. RESULTS: A total of 127 responses were analyzed. Median age of the participants was 64 years (range 56-71 years). A total of 91 participants (71.7%) revealed they experienced late effects secondary to their cancer or cancer treatment. The most concerning physical and psychological symptoms reported were fatigue and fear of recurrence respectively. Axillary lymph node dissection was associated with swollen arm and with difficulty in arm or shoulder movement. Systemic chemotherapy was related to bothersome hair loss and changes on interest in sex; and endocrine therapy was associated with feeling less masculine. CONCLUSION: Our study showed that men suffer several late effects from treatments for breast cancer. Lymphedema, difficulty with arm and shoulder movement, sexual dysfunction and hair loss should be discussed with males as it can be distressing for some patients and decrease their quality of life.


Assuntos
Neoplasias da Mama Masculina , Neoplasias da Mama , Linfedema , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Neoplasias da Mama/complicações , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Neoplasias da Mama Masculina/epidemiologia , Neoplasias da Mama Masculina/terapia , Neoplasias da Mama Masculina/etiologia , Qualidade de Vida , Axila/patologia , Excisão de Linfonodo/efeitos adversos , Linfedema/cirurgia
3.
Sensors (Basel) ; 22(22)2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36433290

RESUMO

Eddy current (EC) testing has become one of the most common techniques for measuring metallic planar structures in various industrial scenarios such as infrastructures, automotive, manufacturing, and chemical engineering. There has been significant progress in measuring the geometry, electromagnetic properties, and defects of metallic planar structures based on electromagnetic principles. In this review, we summarize recent developments in EC computational models, systems, algorithms, and measurement approaches for planar structures. First, the computational models including analytical models, numerical methods, and plate property estimation algorithms are introduced. Subsequently, the impedance measurement system and probes are presented. In plate measurements, sensor signals are sensitive to probe lift-off, and various algorithms for reducing the lift-off effect are reviewed. These approaches can be used for measureing thickness and electromagnetic properties. Furthermore, defect detection for metallic plates is also discussed.

4.
Int J Mol Sci ; 23(20)2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36293379

RESUMO

Central nervous system (CNS) metastases are common in breast cancer (BC) patients and are particularly relevant as new treatments for BC are prolonging survival. Here, we review advances in the treatment of CNS metastases from BC, including radiotherapy, systemic therapies, and the evolving role of immunotherapy. The use of radiotherapy and chemotherapy is the cornerstone of treatment for CNS metastases. However, new targeted therapies have recently been developed, including anti-HER2 agents and antibody-drug conjugates that have presented promising results for the treatment of these patients.


Assuntos
Neoplasias Encefálicas , Neoplasias da Mama , Neoplasias do Sistema Nervoso Central , Imunoconjugados , Segunda Neoplasia Primária , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias do Sistema Nervoso Central/terapia , Imunoconjugados/uso terapêutico , Sistema Nervoso Central/patologia , Receptor ErbB-2 , Neoplasias Encefálicas/tratamento farmacológico
5.
J Mol Cell Cardiol ; 111: 114-122, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28780067

RESUMO

RATIONALE: Quantifying cellular proteins in ventricular myocytes (MCs) is challenging due to tissue heterogeneity and the variety of cell sizes in the heart. In post-weaning cardiac ontogeny, rod-shaped MCs make up the majority of the cardiac mass while remaining a minority of cardiac cells in number. Current biochemical analyses of cardiac proteins do not correlate well the content of MC-specific proteins to cell type or size in normally developing tissue. OBJECTIVE: To develop a new large-particle fluorescent-activated cell sorting (LP-FACS) strategy for the purification of adult rod-shaped MCs. This approach is developed to enable growth-scaled measurements per-cell of the MC proteome and sarcomeric proteins (i.e. myosin heavy chain (MyHC) and alpha-actin (α-actin)) content. METHODS AND RESULTS: Individual cardiac cells were isolated from 21 to 94days old mice. An LP-FACS jet-in-air system with a 200-µm nozzle was defined for the first time to purify adult MCs. Cell-type specific immunophenotyping and sorting yielded ≥95% purity of adult MCs independently of cell morphology and size. This approach excluded other cell types and tissue contaminants from further analysis. MC proteome, MyHC and α-actin proteins were measured in linear biochemical assays normalized to cell numbers. Using the allometric coefficient α, we scaled the MC-specific rate of protein accumulation to growth post-weaning. MC-specific volumes (α=1.02) and global protein accumulation (α=0.94) were proportional (i.e. isometric) to body mass. In contrast, MyHC and α-actin accumulated at a much greater rate (i.e. hyperallometric) than body mass (α=1.79 and 2.19 respectively) and MC volumes (α=1.76 and 1.45 respectively). CONCLUSION: Changes in MC proteome and cell volumes measured in LP-FACS purified MCs are proportional to body mass post-weaning. Oppositely, MyHC and α-actin are concentrated more rapidly than what would be expected from MC proteome accumulation, cell enlargement, or animal growth alone. LP-FACS provides a new standard for adult MC purification and an approach to scale the biochemical content of specific proteins or group of proteins per cell in enlarging MCs.


Assuntos
Actinas/metabolismo , Envelhecimento/metabolismo , Separação Celular/métodos , Citometria de Fluxo/métodos , Miócitos Cardíacos/citologia , Miosinas/metabolismo , Proteoma/metabolismo , Desmame , Animais , Animais Recém-Nascidos , Peso Corporal , Tamanho Celular , Ventrículos do Coração/citologia , Imunofenotipagem , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Tamanho do Órgão , Tamanho da Partícula , Sarcômeros/metabolismo
6.
Hippocampus ; 27(12): 1224-1229, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28833901

RESUMO

Hippocampal dendritic spine density rapidly increases following estradiol (E2 ) treatment, but the types of spines and trafficking of synaptic markers have received little investigation. We assessed rapid effects of E2 over time on the density of four spine types (stubby, filopodial, long thin, and mushroom) and trafficking of AMPA receptor subunit GluA2 and PSD95 on tertiary, apical dendrites in CA1. Castrated male rats received 20 µg kg-1 of E2 or vehicle and were sacrificed 30 or 120 min later. Images of Golgi-Cox impregnated and PSD95/GluA2 stained dendrites were captured under the confocal microscope and quantified with IMARIS-XT. Stubby and filopodial spine densities did not change following treatment. Long-thin spines significantly decreased at 30 min while mushroom spines significantly increased at 120 min. GluA2, PSD95, and GluA2/PSD95 colocalization levels in stubby or long thin spines did not change, but filopodial spines had significantly reduced GluA2 levels at 30 min. Mushroom spines showed significantly increased levels for GluA2, PSD95 and GluA2/PSD95 colocalization at 120 min. Because GluA2 is important for memory consolidation, current results present novel data suggesting that trafficking of GluA2 to mushroom spines provides one mechanism contributing to estradiol's ability to enhance learning and memory by the PI3 signaling pathway.


Assuntos
Região CA1 Hipocampal/efeitos dos fármacos , Espinhas Dendríticas/efeitos dos fármacos , Estradiol/farmacologia , Estrogênios/farmacologia , Pseudópodes/efeitos dos fármacos , Receptores de AMPA/metabolismo , Animais , Região CA1 Hipocampal/citologia , Região CA1 Hipocampal/metabolismo , Espinhas Dendríticas/metabolismo , Proteína 4 Homóloga a Disks-Large/metabolismo , Masculino , Orquiectomia , Pseudópodes/metabolismo , Ratos Sprague-Dawley
7.
Ann Surg Oncol ; 24(11): 3300-3305, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28801882

RESUMO

BACKGROUND: The newly termed tumor 'noninvasive follicular thyroid neoplasm with papillary-like nuclear features' (NIFTP) acts in an indolent manner and can likely be safely managed with a thyroid lobectomy. Preoperative fine-needle aspiration (FNA) is the cornerstone of surgical planning, but the ability of FNA to distinguish NIFTP from other variants of papillary thyroid carcinoma (PTC) has not been well-evaluated. METHODS: A 9-year retrospective review of the preoperative cytology and surgical pathology of PTC patients who underwent a thyroidectomy at our tertiary referral center. RESULTS: Overall, 174 patients with 177 PTCs had a preoperative FNA followed by a thyroidectomy, and met our inclusion criteria. Of the 21 patients with NIFTP, the preoperative cytology was read as malignant in three (14%), suspicious for malignancy in three (14%), follicular neoplasm in ten (48%), atypia of undetermined significance in four (19%), and benign in one (5%) nodule. When comparing patients with NIFTP with other variants of PTC, patients with NIFTP were younger (p = 0.023) and less likely to have malignant cytology (p < 0.001). On multivariable regression modeling, malignant cytology was independently associated with a decreased risk of a final diagnosis of NIFTP (odds ratio 0.064, 95% confidence interval 0.018-0.233, p < 0.001). CONCLUSIONS: Patients with a final diagnosis of NIFTP are less likely to have preoperative FNA diagnosis of malignancy than those with final pathology of classical or other variants of PTC. Surgeons should take this into consideration when considering between a lobectomy and total thyroidectomy for patients with suspected PTC.


Assuntos
Adenocarcinoma Folicular/diagnóstico , Carcinoma Papilar/diagnóstico , Citodiagnóstico/métodos , Neoplasias da Glândula Tireoide/diagnóstico , Adenocarcinoma Folicular/cirurgia , Carcinoma Papilar/cirurgia , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Cuidados Pré-Operatórios , Prognóstico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia
8.
Inorg Chem ; 56(17): 10584-10595, 2017 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-28829579

RESUMO

A series of monoanionic Ir(III) complexes (2-4) of general formula [Ir(C^N)2(b-trz)](TBA) are presented, where C^N indicates three different cyclometallating ligands (Hppy = 2-phenylpyridine; Hdfppy = 2-(2,4-difluoro-phenyl)pyridine; Hpqu = 2-methyl-3-phenylquinoxaline), b-trz is a bis-tetrazolate anionic N^N chelator (H2b-trz = di(1H-tetrazol-5-yl)methane), and TBA = tetrabutylammonium. 2-4 are prepared in good yields by means of the reaction of the suitable b-trz bidentate ligand with the desired iridium(III) precursor. The chelating nature of the ancillary ligand, thanks to an optimized structure and geometry, improves the stability of the complexes, which have been fully characterized by NMR spectroscopy and high-resolution MS, while X-ray structure determination confirmed the binding mode of the b-trz ligand. Density functional theory calculations show that the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) are mainly localized on the metal center and the cyclometalating ligands, while the bis-tetrazolate unit does not contribute to the frontier orbitals. By comparison with selected classes of previously published cationic and anionic complexes with high ligand field and even identical cyclometallating moieties, it is shown that the HOMO-LUMO gap is similar, but the absolute energy of the frontier orbitals is remarkably higher for anionic vs cationic compounds, due to electrostatic effects. 2-4 exhibit reversible oxidation and reduction processes, which make them interesting candidates as active materials for light emitting electrochemical cells, along with red, green, and blue emission, thanks to the design of the C^N ligands. Photoluminescence quantum yields range from 28% (4, C^N = pqu, red emitter) to 83% (3, C^N = dfppy, blue emitter) in acetonitrile, with the latter compound reaching 95% in poly(methyl methacrylate) (PMMA) matrix. In thin films, the photoluminescence quantum yield decreases substantially probably due to the small intersite distance between the complexes and the presence of quenching sites. In spite of this, surprisingly stable electroluminescence was observed for devices employing complex 2, demonstrating the robustness of the anionic compounds.

9.
Med Sci (Basel) ; 12(1)2024 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-38535156

RESUMO

Breast cancer in men represents approximately 1% of all breast cancer diagnoses. Among all patients with breast cancer, approximately 30% will develop brain metastases. Over the past decade, there have been multiple advances in the treatment of metastatic breast cancer; however, long-term outcomes of this presentation in male patients are lacking. We evaluated male patients with de novo stage IV breast cancer using the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2019. Overall survival (OS) was estimated using the Kaplan-Meier method and differences between groups were compared using log rank tests. In total, 22 male patients with brain metastases at initial breast cancer diagnosis were included. Patients with HR-positive/HER2-negative tumors had the longest OS (median 13 months). Factors associated with shorter overall survival were advanced age, unmarried marital status, lower household income, and grade III disease, among others. Brain metastases remains an unmet medical need for patients with breast cancer; the development of new drugs may provide an improvement in overall survival for male patients in the future.


Assuntos
Neoplasias Encefálicas , Neoplasias da Mama , Humanos , Masculino , Mama , Análise de Sobrevida , Bases de Dados Factuais
10.
PLoS One ; 19(2): e0297523, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38394236

RESUMO

BACKGROUND: Schizophrenia, a complex neuropsychiatric disorder, is believed to be influenced by various factors including environmental exposures. A potential environmental factor is the infection by the obligate intracellular parasitic protozoan, Toxoplasma gondii which affects neurotransmitter levels, which could potentially exacerbate, trigger symptoms of schizophrenia or make them worst. OBJECTIVE: To investigate the association between Toxoplasma gondii seropositivity and psychopathological presentation in persons with schizophrenia in Ecuador. METHODS: This study was conducted at the Neuroscience Institute of Guayaquil, Ecuador. Among 368 inpatients, 104 were selected based on specific inclusion and exclusion criteria. Descriptive statistics captured patient characteristics and mental health outcomes. Logistic regression models estimated the effect of toxoplasmosis on various mental health outcomes, controlling for demographic and health-related variables. RESULTS: 86.5% of participants were seropositive for toxoplasmosis. Toxoplasma-seropositive schizophrenic patients had a lower risk of depression but a significantly higher risk of disorientation. The most prevalent mental health outcomes were Language Impairments (70.2%) and Bizarre Behavior (76.0%). CONCLUSION: Our findings suggest that Toxoplasma gondii seropositivity may have specific effects on mental functions in schizophrenic patients, particularly reducing the risk of depression but increasing the risk of disorientation. Further studies are required to clarify these associations and the potential underlying mechanisms.


Assuntos
Esquizofrenia , Toxoplasma , Toxoplasmose , Humanos , Equador/epidemiologia , Anticorpos Antiprotozoários , Toxoplasmose/complicações , Toxoplasmose/epidemiologia , Esquizofrenia/complicações , Esquizofrenia/epidemiologia , Esquizofrenia/parasitologia , Confusão , Fatores de Risco , Estudos Soroepidemiológicos
11.
Front Microbiol ; 15: 1360488, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38525076

RESUMO

The genus Dendroctonus is a Holarctic taxon composed of 21 nominal species; some of these species are well known in the world as disturbance agents of forest ecosystems. Under the bark of the host tree, these insects are involved in complex and dynamic associations with phoretic ectosymbiotic and endosymbiotic communities. Unlike filamentous fungi and bacteria, the ecological role of yeasts in the bark beetle holobiont is poorly understood, though yeasts were the first group to be recorded as microbial symbionts of these beetles. Our aim was characterize and compare the gut fungal assemblages associated to 14 species of Dendroctonus using the internal transcribed spacer 2 (ITS2) region. A total of 615,542 sequences were recovered yielding 248 fungal amplicon sequence variants (ASVs). The fungal diversity was represented by 4 phyla, 16 classes, 34 orders, 54 families, and 71 genera with different relative abundances among Dendroctonus species. The α-diversity consisted of 32 genera of yeasts and 39 genera of filamentous fungi. An analysis of ß-diversity indicated differences in the composition of the gut fungal assemblages among bark beetle species, with differences in species and phylogenetic diversity. A common core mycobiome was recognized at the genus level, integrated mainly by Candida present in all bark beetles, Nakazawaea, Cladosporium, Ogataea, and Yamadazyma. The bipartite networks confirmed that these fungal genera showed a strong association between beetle species and dominant fungi, which are key to maintaining the structure and stability of the fungal community. The functional variation in the trophic structure was identified among libraries and species, with pathotroph-saprotroph-symbiotroph represented at the highest frequency, followed by saprotroph-symbiotroph, and saprotroph only. The overall network suggested that yeast and fungal ASVs in the gut of these beetles showed positive and negative associations among them. This study outlines a mycobiome associated with Dendroctonus nutrition and provides a starting point for future in vitro and omics approaches addressing potential ecological functions and interactions among fungal assemblages and beetle hosts.

12.
J Orthop Sci ; 18(4): 592-8, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23636573

RESUMO

BACKGROUND: Hip fractures are associated with high morbidity, mortality, and cost. Implants used for hip fracture fixation can fail for many reasons including lag screw cut-out. Tip-apex distance (TAD) is indicative of the position and depth of a screw in the femoral head and has been shown to be associated with cut-out failure. We conducted a systematic review of the published literature to quantify the association between TAD and cut-out failure for patients undergoing hip fracture fixation surgery. METHODS: We performed a search of the Medline, Embase, and Cochrane databases. We performed abstract and full text reviews independently and in duplicate. We used a random effects model to combine, in duplicate, the incidence of cut-out for patients who had TAD <25 mm and TAD >25 mm. We also combined mean TAD values for patients who had cut-out failure and those who did not. RESULTS: Seventeen studies were eligible for this review, four of which were included in combined analysis of dichotomous outcomes and seven in combined analysis of continuous outcomes. Patients with TAD >25 mm had a significantly greater risk of cut-out than patients with TAD <25 mm (RR = 12.71). Patients who experienced implant cut-out had significantly higher TAD scores than those who did not (mean difference = 6.54 mm). CONCLUSION: Tip-apex distance is an important concept in relation to cut-out failure of hip fracture fixation surgery. Surgeons should understand and apply the concept of TAD to improve outcomes for their patients.


Assuntos
Fixação Interna de Fraturas , Fraturas do Quadril/diagnóstico por imagem , Fraturas do Quadril/cirurgia , Parafusos Ósseos , Humanos , Radiografia
13.
Medicina (B Aires) ; 73(4): 349-62, 2013.
Artigo em Espanhol | MEDLINE | ID: mdl-23924537

RESUMO

Obstructive sleep apnoea syndrome (OSAS) is one of the most relevant chronic respiratory pathologies due to its high prevalence and impact in morbidity and mortality. In 2001, the Asociación Argentina de Medicina Respiratoria (AAMR) published the first Argentinean Consensus on Sleep-Related breathing Disorders. Since then, wide new scientific evidence has emerged, increasing significantly the knowledge about this pathology. According to this, the Sleep-Related breathing Disorders and Oxygen Therapy Section of the AAMR, decided to update its Consensus, developing this Practical Guidelines on Management of patients with OSAS. A working group was created with members belonging to the section, experts in OSAS. They extensively reviewed the literature and wrote these guidelines, orientated to practical resolution of clinical problems and giving answers to questions emerged from dealing with patients who suffer from this syndrome. The document defines OSAS and describes the diagnosis and severity criteria, as well as the risk factors, ways of presentation and epidemiology. Clinical consequences, mainly on cognition, cardiovascular system and metabolism are pointed out. Different diagnostic methods, with their indications and technical aspects for validation and interpretation are detailed. Finally, we describe therapeutic alternatives, as well as practical aspects of their implementation. The authors' aim was to generate an accessible tool for teaching and spreading the knowledge on these disorders, which have a great impact in public health.


Assuntos
Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/terapia , Argentina , Humanos , Avanço Mandibular/métodos , Oximetria , Polissonografia , Fatores de Risco , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/fisiopatologia , Sociedades Médicas
14.
Addict Neurosci ; 82023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37842014

RESUMO

Stimulant-use disorders can present with long-term cognitive and mental health deficits. Little is known about the underlying molecular mechanisms perpetuating sex differences in cognitive and behavioral deficits in preclinical models of addiction to stimulants such as methamphetamine (MA). The current study investigated the neurochemical shifts underlying sex disparities in MA-induced working memory deficits and an addictive phenotype following abstinence from chronic MA abuse. We used our previously reported mouse model of voluntary oral methamphetamine administration (VOMA) consisting of an acquisition phase (days 1-14) characterized by escalating doses of MA and a binge phase (days 14-28) characterized by static doses. Female VOMA mice exhibited sustained MA consumption during the binge phase, demonstrating sex-specific vulnerabilities to the maintenance of MA addiction. The 8-arm radial maze was used to test spatial working memory performance following abstinence from VOMA. Results indicate working memory deficits correlated to higher MA consumption in females only. Hippocampal and accumbal tissue were collected and analyzed by immunoblotting. Female VOMA mice had decreased GluA1, but not GluA2, in the hippocampus, which may perpetuate synaptic destabilization and working memory deficits. Female-specific increases in GluA1 and p-GSK3ß expression in accumbal tissue suggest vulnerability toward abstinence-induced drug craving and heightened downstream neurotoxicity. Our study reveals female-specific neurochemical shifts in hippocampal and accumbal AMPA receptor signaling following abstinence from chronic MA consumption that may perpetuate female susceptibility to MA-induced cognitive deficits. These data demonstrate a novel molecular pathway that would exacerbate memory deficits and perpetuate an addictive phenotype in female populations following MA abuse.

15.
Case Rep Hematol ; 2023: 7877536, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36950529

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has affected millions of people around the world. Vaccination against COVID-19 has been approved for the following three vaccines in the United States: Pfizer-BioNTech, Moderna, and Janssen. Hematological complications of vaccination have been reported in the literature but remain as a rare phenomenon. We present the case of a patient who developed severe thrombocytopenia within twenty-four hours following the Pfizer-BioNTech vaccination. Commonly encountered differentials including heparin-induced thrombocytopenia and common viral etiologies were ruled out, and other causes such as drug reactions deemed unlikely as the etiology of this presentation after a broad workup. Nucleocapsid antibodies against COVID-19 were found to be positive which indicated that vaccination was at least the second encounter with this virus for our patient, which has been reported previously as the cause of immune thrombocytopenia (ITP), and this might be the culprit for sudden onset. He responded to the first-line ITP treatment with corticosteroids and intravenous immunoglobulin (IVIG) as evidenced by the fast recovery of platelet count and lack of recurrence of thrombocytopenia.

16.
Biosci Rep ; 43(2)2023 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-36651565

RESUMO

Protein-protein interactions (PPI) play a key role in predicting the function of a target protein and drug ability to affect an entire biological system. Prediction of PPI networks greatly contributes to determine a target protein and signal pathways related to its function. Polyadenylation of mRNA 3'-end is essential for gene expression regulation and several polyadenylation factors have been shown as valuable targets for controlling protozoan parasites that affect human health. Here, by using a computational strategy based on sequence-based prediction approaches, phylogenetic analyses, and computational prediction of PPI networks, we compared interactomes of polyadenylation factors in relevant protozoan parasites and the human host, to identify key proteins and define potential targets for pathogen control. Then, we used Entamoeba histolytica as a working model to validate our computational results. RT-qPCR assays confirmed the coordinated modulation of connected proteins in the PPI network and evidenced that silencing of the bottleneck protein EhCFIm25 affects the expression of interacting proteins. In addition, molecular dynamics simulations and docking approaches allowed to characterize the relationships between EhCFIm25 and Ehnopp34, two connected bottleneck proteins. Interestingly, the experimental identification of EhCFIm25 interactome confirmed the close relationships among proteins involved in gene expression regulation and evidenced new links with moonlight proteins in E. histolytica, suggesting a connection between RNA biology and metabolism as described in other organisms. Altogether, our results strengthened the relevance of comparative genomics and interactomics of polyadenylation factors for the prediction of new targets for the control of these human pathogens.


Assuntos
Entamoeba histolytica , Parasitos , Animais , Humanos , Fatores de Poliadenilação e Clivagem de mRNA/genética , Fatores de Poliadenilação e Clivagem de mRNA/metabolismo , Entamoeba histolytica/genética , Parasitos/metabolismo , Filogenia , Genômica , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo
17.
Am J Public Health ; 102(5): 884-92, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22420793

RESUMO

OBJECTIVES: We studied the effect of antiretroviral therapy (ART) on the quality of life (QOL) of Cubans with HIV/AIDS. METHODS: We conducted a cross-sectional study including administration of the Medical Outcomes Study-HIV Health Survey Questionnaire to a representative sample of the 1592 Cubans receiving ART in 2004. For univariate analyses, we compared mean HIV scale scores. We used logistic regression models to estimate the association between role function and year of diagnosis, between pain and sex, and between health transition and region of diagnosis, with adjustment for demographics, ART regimen, and clinical status. RESULTS: There were 354 participants (73 women, 281 men). Scores for all functional activities showed means higher than 80 out of 100. Pain interfered more in women than in men (73.2 vs 81.9; P = .01). When HIV diagnosis occurred after 2001, the probability of experiencing difficulties performing work (odds ratio [OR] = 4.42; 95% CI = 1.83, 10.73) and pain (OR = 1.70; 95% CI = 1.01, 2.88) increased compared with earlier diagnosis. People treated with indinavir showed a greater perception of general health (58.9 vs 52.4; P = .045) and greater health improvement (78.6 vs 67.8; P = .002). CONCLUSIONS: Although Cubans receiving ART are maintaining a high QOL, we observed significant differences by sex and time of diagnosis. QOL assessment can serve as a health outcome and may allow identification of QOL reductions potentially related to ART side effects.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Qualidade de Vida , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/fisiopatologia , Síndrome da Imunodeficiência Adquirida/psicologia , Atividades Cotidianas , Adulto , Estudos Transversais , Cuba/epidemiologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Nível de Saúde , Inquéritos Epidemiológicos , Humanos , Relações Interpessoais , Masculino , Saúde Mental , Pessoa de Meia-Idade , Dor/complicações , Dor/psicologia , Percepção , Características de Residência , Fatores Sexuais , Fatores de Tempo
18.
Clin Case Rep ; 10(11): e6510, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36415706

RESUMO

The two cases we present are the first to demonstrate novel manifestations of COVID-19 related interaction between the liver and the immune system in pediatric patients. Written informed consent was obtained from the parent/guardian to publish this report in accordance with the journal's patient consent policy.

19.
J Microbiol Methods ; 192: 106376, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34798175

RESUMO

The aetiology of diarrhoea in a patient in Cuba with HIV was investigated. Although molecular diagnostics are still not used in many under-resourced settings, here traditional methods were supported by use of PCR. This approach enabled detection of a dual infection (Cystoisospora belli and Enterocytozoon bieneusi), the latter of which was not identified by microscopy with Didier's trichromic staining.


Assuntos
Coccidiose/diagnóstico , Diarreia/diagnóstico , Enterocytozoon/isolamento & purificação , Microsporidiose/diagnóstico , Sarcocystidae/isolamento & purificação , Adulto , Anti-Infecciosos/uso terapêutico , Coccidiose/tratamento farmacológico , Cuba , Diarreia/microbiologia , Diarreia/parasitologia , Enterocytozoon/genética , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Hospedeiro Imunocomprometido , Masculino , Microsporidiose/tratamento farmacológico , Técnicas de Diagnóstico Molecular , Reação em Cadeia da Polimerase , Sarcocystidae/genética , Sarcoma de Kaposi/complicações , Sarcoma de Kaposi/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
20.
JAMA Netw Open ; 4(3): e210498, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33656528

RESUMO

Importance: The unaffordability of drugs has been a persistent and elusive challenge in the US health care system. Little is known about the prevalence and persistence of cost-related medication nonadherence (CRN) in a population with high-cost, high-need resource utilization. Objective: To evaluate the prevalence and persistence of CRN among Medicare beneficiaries at high risk of hospitalization as well as the characteristics associated with CRN in this population. Design, Setting, and Participants: This cohort study used survey data from Medicare patients at high risk of hospitalization and with a life expectancy greater than 12 months at an urban academic medical center from November 6, 2012, to January 30, 2018. Patients were followed up for 12 months at 3-month intervals from baseline, for a total of 5 surveys. Data were analyzed from September 1, 2020, to January 5, 2021. Main Outcomes and Measures: Self-reported CRN, using a metric of persistence and transiency. Based on the results of the 5 surveys, CRN was categorized as persistent (3 or more surveys), intermittent (2), transient (1), and any (1 or more). Multiple logistic regression analyses were used to evaluate factors associated with persistent and transient CRN. Results: Of the 1655 Medicare beneficiaries followed up during the 15-month study period, 1036 (62.6%) were women and 1452 (87.7%) were Black or African American; 769 (46.5%) were younger than 65 years, and 886 (53.5%) were 65 years or older (mean [SD] age, 62.4 [15.9] years). A total of 374 patients (22.6%) reported CRN at baseline, 810 (48.9%) reported any CRN, and 230 (13.9%) reported persistent CRN (148 [19.2%] of those younger than 65 years and 82 [9.3%] of those 65 years or older). The 230 patients who had persistent CRN accounted for 28% of those who reported CRN at least once during the 15-month study period. Younger age (eg, <50 years vs 75 years: adjusted odds ratio [AOR], 3.07; 95% CI, 1.61-5.86; P = .001), worse self-reported health (AOR, 1.59; 95% CI, 1.10-2.31; P = .01), and depression (AOR, 1.58; 95% CI, 1.11-2.24; P = .01) were associated with greater likelihood of persistent CRN. The population-adjusted prevalence of CRN was 53.6% (887 patients). Conclusions and Relevance: The findings suggest that CRN is prevalent, moderately persistent, and variable in the Medicare population at high risk of hospitalization despite coverage by insurance. Longitudinal follow-up and refined predictive modeling of CRN appear to be needed to identify and target more precisely those with persistent CRN and to develop effective interventions.


Assuntos
Custos de Medicamentos/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Adesão à Medicação/estatística & dados numéricos , Idoso , Feminino , Humanos , Masculino , Medicare , Pessoa de Meia-Idade , Medição de Risco , Estados Unidos
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