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1.
Respiration ; 100(1): 1-10, 2021.
Artigo em Alemão | MEDLINE | ID: mdl-33341817

RESUMO

BACKGROUND: Although patients with chronic obstructive pulmonary disease (COPD) receive poor-quality palliative care, information about the use of palliative sedation (PS) in the last days of life is very scarce. OBJECTIVES: To compare the use of PS in hospitalized patients who died from COPD or lung cancer and identify factors correlating with PS application. METHODS: In a retrospective observational cohort study, from 1,675 patients died at a teaching hospital between 2013 and 2015, 109 patients who died from COPD and 85 from lung cancer were compared. Sociodemographic data, clinical characteristics, health care resource utilization, application of PS and prescribed drugs were recorded. RESULTS: In the last 6 months of life, patients who died from COPD had more hospital admissions due to respiratory causes and less frequent support by a palliative home care team (PHCT). Meanwhile, during their last hospitalization, patients who died from COPD had fewer do-not-resuscitate orders and were subjected to more intensive care unit admissions and cardiopulmonary resuscitation maneuvers. PS was applied less frequently in patients who died from COPD than in those who died from lung cancer (31 vs. 53%, p = 0.002). Overall, previous use of opioid drugs, support by a PHCT, and a diagnosis of COPD (adjusted odds ratio 0.48, 95% CI: 0.26-0.89, p = 0.020) were retained as factors independently related to PS. In COPD patients, only previous use of opioid drugs was identified as a PS-related factor. CONCLUSION: During their last days of life, hospitalized COPD patients receive PS less frequently than patients with lung cancer.

2.
Science ; 371(6529)2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33335017

RESUMO

The RNA binding protein TDP-43 forms intranuclear or cytoplasmic aggregates in age-related neurodegenerative diseases. In this study, we found that RNA binding-deficient TDP-43 (produced by neurodegeneration-causing mutations or posttranslational acetylation in its RNA recognition motifs) drove TDP-43 demixing into intranuclear liquid spherical shells with liquid cores. These droplets, which we named "anisosomes", have shells that exhibit birefringence, thus indicating liquid crystal formation. Guided by mathematical modeling, we identified the primary components of the liquid core to be HSP70 family chaperones, whose adenosine triphosphate (ATP)-dependent activity maintained the liquidity of shells and cores. In vivo proteasome inhibition within neurons, to mimic aging-related reduction of proteasome activity, induced TDP-43-containing anisosomes. These structures converted to aggregates when ATP levels were reduced. Thus, acetylation, HSP70, and proteasome activities regulate TDP-43 phase separation and conversion into a gel or solid phase.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Agregados Proteicos , Proteínas de Ligação a RNA/metabolismo , Envelhecimento/metabolismo , Animais , Anisotropia , Microscopia Crioeletrônica , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Células HEK293 , Histona Desacetilases/metabolismo , Humanos , Cristais Líquidos/química , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/metabolismo , Neurônios/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Inibidores de Proteassoma/farmacologia , Domínios Proteicos , Proteínas de Ligação a RNA/genética , Ratos , Ratos Sprague-Dawley
3.
Maturitas ; 144: 4-10, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33358207

RESUMO

OBJECTIVE: To assess the impact of confinement due to the coronavirus (Covid-19) pandemic on health-related quality of life (HRQoL) and resilience in peri- and postmenopausal women. MATERIAL AND METHODS: We used an online questionnaire which was sent between April 30th and May 13th, 2020 to women aged 40-70 years who were peri- or postmenopausal according to STRAW criteria. We used the 16-item Cervantes short-form scale (Cervantes-SF) to measure HRQoL, and the 14-item Wagnild and Young Resilience Scale (RS-14) to measure resilience. High scores on the Cervantes-SF indicate low HRQoL and high scores on the RS-14 indicate high levels of resilience. Covid-19 status, sociodemographic descriptors, and lifestyle variables were also evaluated. RESULTS: We included 2430 peri- and postmenopausal women with valid questionnaires. All items of the Cervantes-SF were completed in 2151 cases, whilst the RS-14 was completed in 2413 cases. There was a negative correlation between scores on the Cervantes-SF and RS-14 scales (Rho -0.350; p < 0.0001). Multiple linear regression analysis revealed a statistically significant association between Cervantes-SF scores and living with others (ß-coefficient -10.2; p < 0.001), use of antidepressants (ß 9.3; p < 0.001), physical activity (ß -8.6; p < 0.001) and sexual activity (ß -2.7; p < 0.001). Resilience was associated with the use of antidepressants (ß -5.9; p < 0.001), physical activity (ß 3.2; p < 0.001) and sexual activity (ß 1.7; p = 0.005). According to the multivariate analysis, there were no associations between either Covid-19 or menopausal status and HRQoL or resilience scores. CONCLUSIONS: During the period of mandatory Covid-19 confinement, peri- and postmenopausal women who engaged in physical and sexual activity had higher HRQoL and higher levels of resilience, whilst women who were using antidepressants had lower HRQoL and lower levels of resilience. HRQoL was greater in women who lived with others.


Assuntos
Perimenopausa/psicologia , Pós-Menopausa/psicologia , Qualidade de Vida/psicologia , Quarentena/psicologia , Resiliência Psicológica , Adulto , Idoso , Estudos Transversais , Exercício Físico/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários
4.
Sci Rep ; 10(1): 18239, 2020 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-33106523

RESUMO

Sorting nexin 4 (SNX4) is an evolutionary conserved protein that mediates recycling from endosomes back to the plasma membrane in yeast and mammalian cells. SNX4 is expressed in the brain. Altered protein levels are associated with Alzheimer's disease, but the neuronal localization and function of SNX4 have not been addressed. Using a new antibody, endogenous neuronal SNX4 co-localized with both early and recycling endosome markers, similar to the reported localization of SNX4 in non-neuronal cells. Neuronal SNX4 accumulated specifically in synaptic areas, with a predominant localization to presynaptic terminals. Acute depletion of neuronal SNX4 using independent short hairpin RNAs did not affect the levels of the transferrin receptor, a canonical SNX4 cargo. Quantitative mass spectrometry revealed that upon SNX4 knockdown the class of proteins involved in neurotransmission was the most dysregulated. This included integral membrane proteins at both the presynaptic and postsynaptic side of the synapse that participate in diverse synaptic processes such as synapse assembly, neurotransmission and the synaptic vesicle cycle. These data suggest that SNX4 is implicated in a variety of synaptic processes.

6.
J Clin Rheumatol ; 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32732523

RESUMO

OBJECTIVE: Giant cell arteritis (GCA) can cause ischemic stroke (IS) due to the involvement of the internal carotid and vertebral arteries. The aim of our study is to describe the pattern of stroke recurrence in patients with GCA-related IS and the role of vascular imaging in the follow-up of these patients. METHODS: We conducted an observational study of 2417 consecutive patients diagnosed with IS and admitted to our hospital from January 2012 to December 2018. We reviewed patients with GCA-related IS and the relationship of erythrocyte sedimentation rate, C-reactive protein, vascular status, and clinical course. RESULTS: We found 4 patients with GCA-related IS among 2417 IS patients: 1 woman (25%); median age, 77.3 years (67-85 years). Mean follow-up was 3.6 years. Initial vascular workup showed vertebral artery stenosis in all of them and internal carotid artery stenosis in 2 patients. All patients were started on treatment with full-dose prednisone, associated with methotrexate in 2 cases. Follow-up color-coded duplex sonography disclosed progression of arterial stenoses in 3 patients who suffered a recurrent IS (days after index stroke; mean, 27.67 [SD, 10.97]) despite normal C-reactive protein and erythrocyte sedimentation rate values. CONCLUSIONS: Vascular imaging, especially with color-coded duplex sonography, could play a role in the follow-up of patients with GCA-related IS and identify those patients with higher risk of recurrent stroke.

7.
Artigo em Espanhol, Inglês | LILACS-Express | LILACS | ID: biblio-1116689

RESUMO

Objetivo. Comprender los factores asociados a la salud bucal y la atención odontológica en el periodo perinatal en las mujeres y sus bebés. Métodos. Soportados en la teoría crítica y la salud colectiva, se realizó un estudio con abordaje cualitativo y cuantitativo. El cualitativo, sustentado en el interaccionismo simbólico, se hicieron entrevistas en profundidad sobre18 mujeres en postparto. En el cuantitativo mediante un estudio observacional de corte-transversal sobre 40 mujeres. Las variables explicativas y de salida se relacionaron mediante test de Chi2 para variables cualitativas y prueba t de Student para las cuantitativas. Resultados. En el cualitativo las mujeres dan importancia estética a la salud bucal, sin relacionarla con su salud general y del bebé; la atención odontológica es difícil durante el postparto y no la consideran importante para sus bebés. En el cuantitativo, 15% de las mujeres no asistieron a la consulta odontológica durante el embarazo, asociándose con el número de días de nacido del bebé. El 82,5% de las mujeres no asistieron durante el postparto, asociándose con régimen de afiliación en salud. El 72,5% de las mamás no percibía la necesidad de atención en sus bebés, asociándose a carecer de dinero para el transporte. Conclusiones. Los resultados indican la necesidad de promover mejores construcciones sobre salud bucal y atención odontológica en las mujeres evaluadas. Variables sociodemográficas, posición social, salud bucal de las mujeres se asociaron con inasistencia a la consulta odontológica durante el embarazo, el periodo postparto y la percepción de la madre de la necesidad de tratamiento del bebé.


Objective. To understand the factors associated with oral health and dental care in the perinatal period in women and their babies. Methods. Supported in the critical theory and collective health, a qualitative and quantitative study was carried out. In the qualitative one, supported by symbolic interactionism, interviews were conducted on 18 postpartum women. The quantitative one was an observational cross-sectional study on 40 women. The explanatory and output variables for qualitative study were analyzed using Chi2 test and the quantitative using Student's T-test. Results. In the qualitative approach, women give aesthetic importance to oral health, without relating it to their general health and that of the baby; dental care is difficult in postpartum period and they do not consider it important for their babies. In quantitative terms, 15% of women did not attend the dental care during pregnancy, associated with the baby's born days number. 82.5% of the women did not attend it during the postpartum period, being associated it with the health affiliation regime. 72.5% of moms did not perceive the need of attention for their babies, being associated it with a money lack for transportation. Conclusions. The results indicate the need to promote better constructions on oral health and dental care for the evaluated mothers. Sociodemographic variables, social position, and women's oral health were associated with non-attendance of the dental attention during pregnancy, the postpartum period and the mother perception of the baby's need for treatment.

8.
Mar Environ Res ; 159: 105021, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32662445

RESUMO

Variability in body condition and energy storage has important implications for fish recruitment and ecosystem structure. Understanding strategies for energy allocation to maintenance, reproduction and growth is essential to evaluate the state of the fish stocks. In this study, we address the energetics dynamics of the annual cycle of anchovies (Engraulis encrasicolus) and sardines (Sardina pilchardus) in the north-western Mediterranean Sea using indirect and direct condition indices. We assessed and validated the use of morphometric, biochemical and energetic indices for both species. Annual patterns of the relative condition index (Kn), gonadosomatic index (GSI), lipid content (% lipids) and energy density (ED) were linked to the energy allocation strategy. Our results highlight that anchovy mainly rely on income energy to reproduce, while sardine accumulate the energy during the resting period to be used in the reproduction period. Consequently, variability in the lipid content and ED between seasons was lower in anchovy than in sardine. In both species, we observed an early decline in energy reserves in late summer-early fall, which may be related to unfavourable environmental conditions during spring and summer. Regarding the use of different condition indices, both direct indices, lipid content and ED, were highly correlated with Kn for sardine. ED was better correlated with Kn than lipid content for anchovy. For the first time, a relationship between ED of gonads and GSI for sardine and anchovy was provided, highlighting the importance of the energy invested in reproduction. This work provides new insights into the energy dynamics of sardine and anchovy. We also demonstrate which are the most suitable indices to measure changes in the physiological condition of both species, providing tools for the future monitoring of the populations of these two commercially and ecologically important fish species.


Assuntos
Ecossistema , Peixes , Animais , Metabolismo Energético , Peixes/metabolismo , Mar Mediterrâneo , Alimentos Marinhos , Estações do Ano
9.
Maturitas ; 137: 57-62, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32498938

RESUMO

COVID-19 is associated with a systemic inflammatory response with activation of coagulation in symptomatic patients. The possibility of coagulopathies in peri- and postmenopausal women taking estrogen therapies makes it necessary to consider antithrombotic strategies, such as the use of low molecular weight heparins (LMWH) at specific prophylactic or treatment doses for each individual case, depending on the risk factors that each woman presents. For such reasons, a panel of experts from various Spanish scientific societies has met to develop usage recommendations for managing menopausal women taking menopausal hormone therapy (MHT) or combined hormonal contraception (CHC) during the COVID-19 pandemic.


Assuntos
Infecções por Coronavirus , Terapia de Reposição de Estrogênios , Terapia de Reposição Hormonal , Menopausa , Pandemias , Pneumonia Viral , Tromboembolia , Anticoagulantes/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Contracepção Hormonal , Humanos , Pessoa de Meia-Idade , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Fatores de Risco , Tromboembolia/etiologia , Tromboembolia/prevenção & controle
11.
Rev. cir. (Impr.) ; 72(3): 203-208, jun. 2020. tab
Artigo em Espanhol | LILACS | ID: biblio-1115543

RESUMO

Resumen Introducción: La pancreatitis aguda es una enfermedad frecuente en el país, con una tasa de mortalidad de 10%-30%. La administración profiláctica de antibióticos ha sido parte del tratamiento de pancreatitis aguda grave (PAG), por la teórica prevención de complicaciones infecciosas y reducción de mortalidad. Sin embargo, la evidencia científica disponible es controversial. Objetivo: Demostrar que los antibióticos profilácticos no disminuyen las complicaciones locales y/o sistémicas, requerimiento de Unidad de Paciente Crítico (UPC), ni mortalidad en PAG. Definimos PAG como APACHE II ≥ 8 o PCR ≥ 150 o falla multiorgánica. Material y Método: Ensayo clínico aleatorizado, con aleatorización simple mediante tabla electrónica (uso o no uso de antibióticos profilácticos) de pacientes con PAG. En el grupo que usó antibióticos profilácticos se utilizó ciprofloxacino y metronidazol por 7 días. El resto del manejo no tuvo variación. Resultados: n = 71, dos grupos aleatorizados; Grupo 1 (n = 35), sin uso de antibióticos profilácticos, y grupo 2 (n = 36) con uso de profilaxis antibiótica. 12 pacientes (16%) requirieron UPC; 6 pacientes del grupo 1, y 6 del grupo 2 (p = 0,957). Siete pacientes (9,8%) tuvieron algún tipo de complicación, 3 en el grupo 1 y 4 en el grupo 2 (p = 0,516). El promedio de estancia hospitalaria fue 18,2 ± 9,5 días en el grupo 1, y 22,6 ± 29.2 días en el grupo 2 (p = 0,495). Mortalidad: 1 paciente (1,41%) en el grupo 2 (p = 0,493). Conclusión: En este reporte preliminar, el uso de antibióticos profilácticos en PAG no mostró reducir las complicaciones, necesidad de cama en UPC, ni la mortalidad.


Introduction: Acute pancreatitis is a common disease in the country, with a mortality rate of 10%-30%. The prophylactic administration of antibiotics has been part of the treatment of severe acute pancreatitis (SAP), due to the theoretical prevention of infectious complications and mortality reduction. However, the available scientific evidence is controversial. Objective: To demonstrate that prophylactic antibiotics do not reduce local and/or systemic complications, critical patient unit (CPU) requirement, or mortality in SAP. We define SAP as APACHE II ≥ 8 or PCR ≥ 150° or multiorgan failure. Material and Method: Randomized clinical trial, with simple randomization by electronic table (use or non-use of prophylactic antibiotics) of patients with SAP. In the group that used prophylactic antibiotics, ciprofloxacin and metronidazole were used for 7 days. Results: n = 71, two randomized groups; Group 1 (n = 35), without the use of prophylactic antibiotics, and group 2 (n = 36) with the use of antibiotic prophylaxis. 12 patients (16%) required CPU; 6 patients from group 1, and 6 from group 2 (p = 0.957). Seven patients (9.8%) had some type of complication, 3 in group 1 and 4 in group 2 (p = 0.516). The average hospital stay was 18.2 ± 9.5 days in group 1, and 22.6 ± 29.2 days in group 2 (p = 0.495). Mortality: 1 patient (1.41%) in group 2 (p = 0.493). Conclusion: In this preliminary report, the use of prophylactic antibiotics in SAP was not shown to reduce complications, need for bed in CPU, or mortality.


Assuntos
Humanos , Masculino , Feminino , Pancreatite/complicações , Pancreatite/tratamento farmacológico , Antibioticoprofilaxia , Pancreatite/mortalidade , Antibacterianos/uso terapêutico
12.
High Alt Med Biol ; 21(3): 292-296, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32412860

RESUMO

Álvarez-Herms, Jesús, Sonia Julià-Sánchez, Hannes Gatterer, Francisco Corbi, Gines Viscor, and Martin Burtscher. Effects of a single power strength training session on heart rate variability when performed at different simulated altitudes. High Alt Med Biol. 21:292-296, 2020. Background: This study assessed heart rate variability (HRV) after a single power strength training session performed at different hypoxic levels. Materials and Methods: Eight physically active subjects (31.1 ± 4.3 years; 177.6 ± 3.0 cm; 70.1 ± 5.2 kg) performed 6 bouts of 15-second continuous maximal jump exercises interspersed by 3 minutes of rest at different altitude levels (total volume of each session: 20 minutes). The normoxic hypoxia levels were FiO2 low altitude: 20.9%; moderate altitude: 16.5%; and high altitude: 13.5%. Results: Average power output during the jumps was similar for all conditions (≅3150 W). Twenty-four hours before (PRE) and 24 hours after (POST) each training session, HRV parameters (R-R, square root of the mean of the sum of differences between intervals [RMSSD], pNN50, and very low frequency, low frequency, and high frequency) were determined without resulting in significant statistical differences, neither from PRE to POST nor between conditions (p > 0.05). Conclusions: This study showed a negligible perturbation of HRV parameters 24 hours after a single power strength session up to a hypoxic level equivalent to 4000 m. Further studies are needed to determine the hypoxia-dependent threshold and intensities of training loads affecting HRV.

13.
Hear Res ; 390: 107951, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32244147

RESUMO

The retinoblastoma family of pocket proteins (pRBs), composed of Rb1, p107, and p130 are negative regulators of cell-cycle progression. The deletion of any individual pRB in the auditory system triggers hair cells' (HCs) and supporting cells' (SCs) proliferation to different extents. Nevertheless, accessing their combined role in the inner ear through conditional or complete knockout methods is limited by the early mortality of the triple knockout. In quiescent cells, hyperphosphorylation and inactivation of the pRBs are maintained through the activity of the Cyclin-D1-cdk4/6 complex. Cyclin D1 (CycD1) is expressed in the embryonic and neonatal inner ear. In the mature organ of Corti (OC), CycD1 expression is significantly downregulated, paralleling the OC mitotic quiescence. Earlier studies showed that CycD1 overexpression leads to cell-cycle reactivation in cultures of inner ear explants. Here, we characterize a Cre-activated, Doxycycline (Dox)-controlled, conditional CycD1 overexpression model, which when bred to a tetracycline-controlled transcriptional activator and the Atoh1-cre mouse lines, allow for transient CycD1 overexpression and pRBs' downregulation in the inner ear in a reversible fashion. Analyses of postnatal mice's inner ears at various time points revealed the presence of supernumerary cells throughout the length of the cochlea and in the vestibular end-organs. Notably, most supernumerary cells were observed in the inner hair cells' (IHCs) region, expressed myosin VIIa (M7a), and showed no signs of apoptosis at any of the time points analyzed. Auditory and vestibular phenotypes were similar between the different genotypes and treatment groups. The fact that no significant differences were observed in auditory and vestibular function supports the notion that the supernumerary cells detected in the adult mice cochlea and macular end-organs may not impair auditory functions.

14.
J Neurointerv Surg ; 12(10): 1008-1013, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31959631

RESUMO

BACKGROUND: The Advanced Thrombectomy System (ANCD) provides a new funnel component designed to reduce clot fragmentation and facilitate retrieval in patients with stroke by locally restricting flow, allowing distal aspiration in combination with a stent retriever (SR). OBJECTIVE: To evaluate the preclinical efficacy and safety of the ANCD in a swine clot model. METHODS: Soft and firm clots were implanted in the lingual and cervical arteries of 11 swine to obtain Thrombolysis in Cerebral Infarction (TICI) 0 blood flow. Mechanical thrombectomy was performed with either a balloon guide catheter+Solitaire 2 stent retriever (BGC+SR, n=13) or ANCD+SR (n=13). TICI flow was evaluated and successful revascularization was defined as TICI 3 (normal perfusion). To characterize safety, a total of 3 passes were performed in each vessel independent of recanalization. Tissues were explanted for histopathological analysis after 3 and 30 days, respectively. RESULTS: First pass reperfusion rates were ANCD+SR: 69% and BGC+SR: 46%. Reperfusion increased after the third pass in both groups (ANCD+SR: 100%, vs BGC+SR: 77%). Recanalization was achieved after an average of 1.4 and 1.9 passes in ANCD+SR and BGC+SR (p=0.095), respectively. Vessel injury was comparable in both groups; endothelial loss at 3 days was the most common injury seen (ANCD+SR: 1.78±1.22; BGC+SR: 2.03±1.20; p=0.73), while other histopathological markers were absent or minimal. Tissues downstream from targeted vessels also showed absence or minimal lesions across both groups. CONCLUSIONS: Results in a swine clot model support the high efficacy of the ANCD+SR without causing clinically significant vessel injury potentially related to the new funnel component.

15.
Int J Cancer ; 147(4): 1163-1179, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31943158

RESUMO

Around 40% of newly diagnosed lung cancer patients are Stage IV, where the improvement of survival and reduction of disease-related adverse events is the main goal for oncologists. In this scenario, we present preclinical evidence supporting the use of ABTL0812 in combination with chemotherapy for treating advanced and metastatic Nonsmall cell lung adenocarcinomas (NSCLC) and squamous carcinomas. ABTL0812 is a new chemical entity, currently in Phase 1b/2a clinical trial for advanced squamous NSCLC in combination with paclitaxel and carboplatin (P/C), after successfully completing the first-in-human trial where it showed an excellent safety profile and signs of efficacy. We show here that ABTL0812 inhibits Akt/mTOR axis by inducing the overexpression of TRIB3 and activating autophagy in lung squamous carcinoma cell lines. Furthermore, treatment with ABTL0812 also induces AMPK activation and ROS accumulation. Moreover, combination of ABTL0812 with chemotherapy markedly increases the therapeutic effect of chemotherapy without increasing toxicity. We further show that combination of ABTL0812 and chemotherapy induces nonapoptotic cell death mediated by TRIB3 activation and autophagy induction. We also present preliminary clinical data indicating that TRIB3 could serve as a potential novel pharmacodynamic biomarker to monitor ABTL0812 activity administered alone or in combination with chemotherapy in squamous NSCLC patients. The safety profile of ABTL0812 and its good synergy with chemotherapy potentiate the therapeutic potential of current lines of treatment based on chemotherapy regimens, arising as a promising option for improving these patients therapeutic expectancy.

16.
Sci Rep ; 10(1): 1066, 2020 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-31974431

RESUMO

Invasive candidiasis (IC) is the most common nosocomial infection and a leading cause of mycoses-related deaths. High-systemic toxicity and emergence of antifungal-resistant species warrant the development of newer preventive approaches against IC. Here, we have adopted an immunotherapeutic peptide vaccine-based approach, to enhance the body's immune response against invasive candida infections. Using computational tools, we screened the entire candida proteome (6030 proteins) and identified the most immunodominant HLA class I, HLA class II and B- cell epitopes. By further immunoinformatic analyses for enhanced vaccine efficacy, we selected the 18- most promising epitopes, which were joined together using molecular linkers to create a multivalent recombinant protein against Candida albicans (mvPC). To increase mvPC's immunogenicity, we added a synthetic adjuvant (RS09) to the mvPC design. The selected mvPC epitopes are homologous against all currently available annotated reference sequences of 22 C. albicans strains, thus offering a higher coverage and greater protective response. A major advantage of the current vaccine approach is mvPC's multivalent nature (recognizing multiple-epitopes), which is likely to provide enhanced protection against complex candida antigens. Here, we describe the computational analyses leading to mvPC design.


Assuntos
Candida albicans/imunologia , Candidíase/prevenção & controle , Vacinas Fúngicas/imunologia , Candida albicans/genética , Candidíase/genética , Candidíase/imunologia , Candidíase/microbiologia , Biologia Computacional , Simulação por Computador , Desenho de Fármacos , Epitopos de Linfócito B/genética , Epitopos de Linfócito B/imunologia , Vacinas Fúngicas/administração & dosagem , Vacinas Fúngicas/genética , Humanos , Vacinas de Subunidades
17.
J Hum Hypertens ; 34(5): 404-410, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31435006

RESUMO

We aimed to evaluate brachial and central blood pressure (BP) estimates and biomarker levels in lacunar ischemic stroke (IS) and other IS subtypes (nonlacunar stroke). We studied 70 functionally independent subjects consecutively admitted to our institution after a first episode of IS. Subjects with previous heart failure were excluded. BP was measured at admission and during the subacute phase of stroke (5-7 days after stroke onset). Aortic pulse wave velocity (aPWV), augmentation index (AIx), and 24 h brachial and central BP (24h-ABPM) were measured by means of a Mobil-O-Graph device during the subacute phase of stroke. Determination of N-terminal prohormone of brain natriuretic peptide (NT-proBNP), urinary albumin excretion, and echocardiography were performed in all subjects. After adjusting for age and clinical severity, lacunar IS had significantly higher levels of BP at admission (systolic BP 173 ± 37 vs 153 ± 28 mmHg, p = 0.006; diastolic BP: 97 ± 21 vs 86 ± 16 mmHg, p = 0.035) and during the subacute phase of stroke (systolic BP 152 ± 23 vs 134 ± 19 mmHg, p = 0.001; diastolic BP: 84 ± 14 and 77 ± 10 mmHg, respectively; p = 0.038) but lower NT-proBNP levels (median: 36,277 vs 274 pg/mL, p = 0.009) than nonlacunar IS. Central BP, aPWV, and AIx were not different between lacunar and nonlacunar IS, neither the rate of target organ damage. In conclusion, patients with a first episode of lacunar IS have higher BP values at admission and during the subacute phase of stroke and lower levels of NT-proBNP, suggesting a closer relationship with hypertension of this IS subtype.

18.
J Neurointerv Surg ; 12(1): 77-81, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31197024

RESUMO

INTRODUCTION: Endovascular treatment of stroke, although highly effective, may fail to reach complete recanalization in around 20% of cases. The Advanced Thrombectomy System (ANCD) is a novel stroke thrombectomy device designed to reduce clot fragmentation and facilitate retrieval by inducing local flow arrest and allowing distal aspiration in combination with a stent retriever. We aimed to assess the preclinical efficacy of ANCD. METHODS: Soft red blood cell (RBC)-rich (n=20/group) and sticky fibrin-rich (n=30/group) clots were used to create middle cerebral artery (MCA) occlusions in two vascular phantoms. Three different treatment strategies were tested: (1) balloon guide catheter + Solitaire (BGC+SR); (2) distal access catheter + SR (DAC+SR); and (3) ANCD+SR, until complete recanalization was achieved or to a maximum of three passes. The recanalization rate was determined after each pass. RESULTS: After one pass, ANCD+SR resulted in an increased recanalization rate (94%) for all clots together compared with BGC+SR (66%; p<0.01) or DAC+SR (80%; p=0.04). After the final pass the recanalization rate increased in all three groups but remained higher with ANCD+SR (100%) than with BGC+SR (74%; p<0.01) or DAC+SR (90%; p=0.02). The mean number of passes was lower with ANCD+SR (1.06) than with BGC+SR (1.46) or DAC+SR (1.25) (p=0.01). A logistic regression model adjusted for treatment arm, clot type, and model used showed that both RBC-rich clots (OR 8.1, 95% CI 1.6 to 13.5) and ANCD+SR (OR 3.9, 95% CI 1.01 to 15.8) were independent predictors of first-pass recanalization. CONCLUSION: In in vitro three-dimensional models replicating MCA-M1 occlusion, ANCD+SR showed significantly better recanalization rates in fewer passes than other commonly used combinations of devices.


Assuntos
Modelos Cardiovasculares , Stents , Trombectomia/instrumentação , Trombectomia/métodos , Fibrina , Humanos , Infarto da Artéria Cerebral Média/cirurgia , Acidente Vascular Cerebral/cirurgia , Instrumentos Cirúrgicos , Trombose/cirurgia , Resultado do Tratamento
19.
J Crit Care ; 55: 79-85, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31715535

RESUMO

PURPOSE: Frailty is a common condition among critically ill patients. Usually evaluated in a mixed population of medical, cardiac and surgical patients, we aimed to assess the impact of frailty on short- and long-term mortality exclusively in critically ill older medical patients. MATERIALS AND METHODS: We included 285 patients aged≥70 years admitted to ICU (2009-2017). Comorbidities, severity scores, treatment intensity and complications were recorded. Pre-hospital frailty, measured by Clinical Frailty Scale (CFS), was defined as a score ≥ 5 according to this scale. RESULTS: Prevalence of frailty (CFS ≥ 5) of 18.6%. Frail patients were more likely to be female (64.2% vs. 35.6%, p < .001) or suffer from heart failure (17% vs. 6%,p = .021). Apache II score was higher in frail than in non-frail patients (27.4 ±â€¯7.1 vs. 24.8 ±â€¯8.6,p = .041). Age, comorbidities, treatment intensity, complications, and ICU and hospital length of stay were similar between frail and non-frail patients. Life-sustaining treatment limitation was more frequent in frail patients (47.2% vs. 20.7%,p < .001). Except for ICU mortality, frailty was an independent predictor of short- and long-term mortality after adjustment for sociodemographic, comorbidities, severity scores, treatment intensity and complications. CONCLUSIONS: Frailty (CFS ≥ 5) was independently associated with short- and long-term mortality in older patients admitted to ICU exclusively due to a medical reason.

20.
Anal Bioanal Chem ; 411(28): 7461-7472, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31616968

RESUMO

Five commercial ionic liquid (IL) columns have been evaluated for the first time for the gas chromatography-mass spectrometry (GC-MS) analysis of low molecular weight carbohydrate (LMWC) standards (mono-, di-, and trisaccharides, inositols, and iminosugars). A previous derivatization step was necessary to convert the LMWCs into their volatile and stable derivatives. Compared with conventional GC stationary phases, such as HP-1 and Supelcowax® 10, IL columns have shown a different selectivity in the separation of target compounds. Among the IL columns, only SLB™-IL82 allowed the elution of all the LMWCs studied. Its performance in terms of peak width and asymmetry, evaluated under different oven temperature conditions, was shown to be dependent on the carbohydrate class considered. As an example of application, a SLB™-IL82 column was successfully used to separate the complex mixtures of LMWCs in hyacinth and mulberry extracts. This column is an interesting alternative to the conventional stationary phases used in the GC analysis of LMWCs in real-world samples. Graphical abstract.


Assuntos
Carboidratos/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Líquidos Iônicos/química , Extratos Vegetais/química , Temperatura
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