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BACKGROUND: Continuous automatic optimisation of cardiac resynchronisation therapy (CRT), stimulating only the left ventricle to fuse with intrinsic right bundle conduction (synchronised left ventricular stimulation), might offer better outcomes than conventional CRT in patients with heart failure, left bundle branch block, and normal atrioventricular conduction. This study aimed to compare clinical outcomes of adaptive CRT versus conventional CRT in patients with heart failure with intact atrioventricular conduction and left bundle branch block. METHODS: This global, prospective, randomised controlled trial was done in 227 hospitals in 27 countries across Asia, Australia, Europe, and North America. Eligible patients were aged 18 years or older with class 2-4 heart failure, an ejection fraction of 35% or less, left bundle branch block with QRS duration of 140 ms or more (male patients) or 130 ms or more (female patients), and a baseline PR interval 200 ms or less. Patients were randomly assigned (1:1) via block permutation to adaptive CRT (an algorithm providing synchronised left ventricular stimulation) or conventional biventricular CRT using a device programmer. All patients received device programming but were masked until procedures were completed. Site staff were not masked to group assignment. The primary outcome was a composite of all-cause death or intervention for heart failure decompensation and was assessed in the intention-to-treat population. Safety events were collected and reported in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02205359, and is closed to accrual. FINDINGS: Between Aug 5, 2014, and Jan 31, 2019, of 3797 patients enrolled, 3617 (95·3%) were randomly assigned (1810 to adaptive CRT and 1807 to conventional CRT). The futility boundary was crossed at the third interim analysis on June 23, 2022, when the decision was made to stop the trial early. 1568 (43·4%) of 3617 patients were female and 2049 (56·6%) were male. Median follow-up was 59·0 months (IQR 45-72). A primary outcome event occurred in 430 of 1810 patients (Kaplan-Meier occurrence rate 23·5% [95% CI 21·3-25·5] at 60 months) in the adaptive CRT group and in 470 of 1807 patients (25·7% [23·5-27·8] at 60 months) in the conventional CRT group (hazard ratio 0·89, 95% CI 0·78-1·01; p=0·077). System-related adverse events were reported in 452 (25·0%) of 1810 patients in the adaptive CRT group and 440 (24·3%) of 1807 patients in the conventional CRT group. INTERPRETATION: Compared with conventional CRT, adaptive CRT did not significantly reduce the incidence of all-cause death or intervention for heart failure decompensation in the included population of patients with heart failure, left bundle branch block, and intact AV conduction. Death and heart failure decompensation rates were low with both CRT therapies, suggesting a greater response to CRT occurred in this population than in patients in previous trials. FUNDING: Medtronic.
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Terapia de Resincronización Cardíaca , Insuficiencia Cardíaca , Humanos , Masculino , Femenino , Bloqueo de Rama/etiología , Bloqueo de Rama/terapia , Estudios Prospectivos , Resultado del Tratamiento , Terapia de Resincronización Cardíaca/efectos adversos , Terapia de Resincronización Cardíaca/métodos , Volumen Sistólico , ElectrocardiografíaRESUMEN
Access to better health care anticipates that more medical devices can be found alongside skeletal remains. Those employed in oral rehabilitation, with available brands or batch/series, can prove useful in the identification process. A previous study in the Colecção de Esqueletos Identificados Século XXI described macroscopically the dental prostheses. An unusual case of a dental device with chromatic alterations demonstrated to require a more detailed analysis. The individual, a 53-year-old male, exhibited, at both arches, a fixed tooth-supported rehabilitation, with gold colouring classified initially as a gold-palladium alloy. Simultaneously, a green pigmentation deposit was observable in bone and prosthesis. This investigation aimed to verify the elemental composition of the dental prosthesis alloy. Elemental analysis was performed by X-ray fluorescence in two regions (labial surface of the prosthetic crown and the root surface of the lower right lateral incisor). Both the spectra and the qualitative results found higher levels of copper and aluminium, followed by nickel, iron, zinc, and manganese. No gold or palladium was detected. The most probable assumption is that a copper-aluminium alloy was used, as its elemental concentration corresponds to those measured in similar devices. Dental prostheses of copper-aluminium alloys have been made popular since the 1980s, particularly in the USA, Japan, and Eastern Europe. Apart from the biographical information, it was also known that the individual's place of birth was an Eastern European country, which highlighted the usefulness of this type of information when dealing with missing people cases.
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Prótesis Dental , Paladio , Masculino , Humanos , Persona de Mediana Edad , Rayos X , Portugal , Paladio/análisis , Cobre/análisis , Aluminio/análisis , Fluorescencia , Incisivo , Aleaciones de Oro/análisisRESUMEN
Intensive Care to facilitate Organ Donation (ICOD) consists of the initiation or continuation of intensive care measures in patients with a devastating brain injury (DBI) in whom curative treatment is deemed futile and death by neurological criteria (DNC) is foreseen, to incorporate organ donation into their end-of-life plans. In this study we evaluate the outcomes of patients subject to ICOD and identify radiological and clinical factors associated with progression to DNC. In this first prospective multicenter study we tested by multivariate regression the association of clinical and radiological severity features with progression to DNC. Of the 194 patients, 144 (74.2%) patients fulfilled DNC after a median of 25 h (95% IQR: 17-44) from ICOD onset. Two patients (1%) shifted from ICOD to curative treatment, both were alive at discharge. Factors associated with progression to DNC included: age below 70 years, clinical score consistent with severe brain injury, instability, intracranial hemorrhage, midline shift ≥5 mm and certain types of brain herniation. Overall 151 (77.8%) patients progressed to organ donation. Based on these results, we conclude that ICOD is a beneficial and efficient practice that can contribute to the pool of deceased donors.
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Cuidados Críticos , Obtención de Tejidos y Órganos , Humanos , Estudios Prospectivos , Masculino , Femenino , Obtención de Tejidos y Órganos/métodos , Persona de Mediana Edad , Anciano , España , Adulto , Lesiones Encefálicas , Muerte Encefálica , Unidades de Cuidados IntensivosRESUMEN
Haemorrhoidal disease and anal fissure are the two most frequent entities within benign anal pathology, both of which have a negative impact on patients' quality of life. To date, there is no specific questionnaire in Spanish to assess the impact on quality of life in patients suffering from these conditions. The aim of our study is to validate in Spanish a questionnaire for this purpose, adapting it to our daily clinical practice. The HEMO-FISS-CdV is the Spanish version of the original HEMO-FISS-QoL by Abramowitz. The questionnaire consists of 23 items organised in 4 dimensions (physical, psychological, defecation and sexuality). The reliability of the new tool was assessed by determining internal consistency using Cronbach's alpha and Guttman's coefficient. It was also correlated with the quality of life questionnaire SF12 version 2. The Cronbach's alpha obtained for our questionnaire (HEMO-FISS-CdV) was 0.951 (ICC 95% +-0.016), with a range between 0.935 and 0.967. The Guttman two-half coefficient had a value of 0.910. Patients with internal haemorrhoids, anal fissure or both had higher values on the HEMO-FISS-CdV questionnaire than patients without internal haemorrhoids and these differences were significant (p<0.05). Both diseases have a negative impact on patients' quality of life. The HEMO-FISS-CdV questionnaire provides a tool in Spanish that easily and specifically assesses the impact of haemorrhoidal disease and anal fissure on quality of life.
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BACKGROUND AND AIMS: Minor nonspecific gastrointestinal subepithelial lesions (usually defined by the term 'tumor') are usually associated with a malignant illness and cancer. The aim of this study was to assess anxiety-distress and carcinophobia in patients referred to specialized monographic outpatient clinics for evaluation and treatment of this type of lesion. METHODS: Prospective, multicenter, cohort study. Specific self-reported questionnaires were used to report threatening life-experiences and to assess levels of distress (The Hospital Anxiety and Depression Scale) and cancer-related worries (The Cancer Worry Scale). RESULTS: Forty participants were included and analyzed at baseline. Pathologic and borderline anxiety were detected in 13% (5/40, 95%CI: 4-27%) and 35% (14/40, 95%CI: 21-52%) of participants, respectively, whereas, cancer-related worries (moderate to very high) were observed in 48% (19/40, 95%CI: 32-64%) of participants. Pathologic global distress was identified in 25% (10/40, 95%CI: 13-42%) of subjects. Higher educational level (university studies), a lack of lifetime psychiatric comorbidity and a lack of family history of cancer were associated with less anxiety, global distress and carcinophobia. CONCLUSIONS: Almost half of the patients diagnosed with a minor nonspecific gastrointestinal subepithelial lesion presented anxiety-distress and/or carcinophobia. Specific associations with anxiety-distress reaction and fears were detected.
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Ansiedad , Neoplasias , Humanos , Estudios de Cohortes , Estudios Prospectivos , Ansiedad/complicaciones , Comorbilidad , Depresión/epidemiología , Depresión/complicacionesRESUMEN
BACKGROUND: The Public Health Services at the Metropolitan Region (MR) of Chile have nine acute psychiatric beds per 100,000 inhabitants, under international recommendations. AIM: The present study will evaluate the resolution capacity of the main MR Psychiatric Emergency Room (PER), which may help assess the impact of the availability of acute beds in the MR. MATERIAL AND METHODS: A retrospective observational study of electronic patient records for all adult patients attending PER of the Psychiatric Institute "Dr. José Horwitz B." between 2017 and 2020 was analyzed. Crude and adjusted Incidence Rate Ratios were obtained for the indication of hospitalization, admissions, and those rejected due to lack of acute psychiatric beds. RESULTS: 90,464 attendances were evaluated on 41,541 patients, and hospitalization was indicated for 12.5% of them. Admissions were carried out in 59.5%, and 35.9% did not occur due to a lack of acute psychiatric beds. When comparing the adjusted Incidence Rates, only a higher hospitalization rate was observed for users from regions (IRR = 1,267; 95% CI: 1,11-1,44; p-value < 0.001) and during the first half of 2020 (IRR = 1.49; CI95%: 1.35-1.65; p-value < 0.001). CONCLUSIONS: The demand for psychiatric hospitalizations and the low availability of acute psychiatric beds in the MR probably have unsuspected consequences. The solution requires multilevel planning among all the actors involved.
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Capacidad de Camas en Hospitales , Hospitalización , Humanos , Chile/epidemiología , Estudios Retrospectivos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Hospitalización/estadística & datos numéricos , Capacidad de Camas en Hospitales/estadística & datos numéricos , Adulto Joven , Adolescente , Necesidades y Demandas de Servicios de Salud/estadística & datos numéricos , Trastornos Mentales/epidemiología , Trastornos Mentales/terapia , AncianoRESUMEN
Most of the research on titanium-based dental implants (Ti-discs) is focused on how they are able to stimulate the formation of new tissue and/or cytotoxic studies, with very scarce data on their effects on functional responses by immunocompetent cells. In particular, the link between the rewiring of innate immune responses and surface biomaterials properties is poorly understood. To address this, we characterize the functional response of macrophage cultures to four different dental titanium surfaces (MA: mechanical abrasion; SB + AE: sandblasting plus etching; SB: sandblasting; AE: acid etching). We use different Toll-like receptor (TLR) ligands towards cell surface receptors (bacterial lipopolysaccharide LPS for TLR4; imiquimod for TLR7; synthetic bacterial triacylated lipoprotein for TLR2/TLR1) and endosomal membrane receptor (poly I:C for TLR3) to simulate bacterial (cell wall bacterial components) or viral infections (dsRNA and ssRNA). The extracellular and total LDH levels indicate that exposure to the different Ti-surfaces is not cytotoxic for macrophages under resting or TLR-stimulated conditions, although there is a tendency towards an impairment in macrophage proliferation, viability or adhesion under TLR4, TLR3 and TLR2/1 stimulations in SB discs cultures. The secreted IL-6 and IL-10 levels are not modified upon resting macrophage exposure to the Ti-surfaces studied as well as steady state levels of iNos or ArgI mRNA. However, macrophage exposure to MA Ti-surface do display an enhanced immune response to TLR4, TLR7 or TLR2/1 compared to other Ti-surfaces in terms of soluble immune mediators secreted and M1/M2 gene expression profiling. This change of characteristics in cellular phenotype might be related to changes in cellular morphology. Remarkably, the gene expression of Tlr3 is the only TLR that is differentially affected by distinct Ti-surface exposure. These results highlight the relevance of patterned substrates in dental implants to achieve a smart manipulation of the immune responses in the context of personalized medicine, cell-based therapies, preferential lineage commitment of precursor cells or control of tissue architecture in oral biology.
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Implantes Dentales , Titanio , Células Cultivadas , Lipopolisacáridos/metabolismo , Lipopolisacáridos/farmacología , Macrófagos/metabolismo , Titanio/metabolismo , Titanio/farmacología , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 3/metabolismo , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 7/metabolismo , Receptor Toll-Like 9/metabolismo , Receptores Toll-Like/metabolismoRESUMEN
BACKGROUND: Chronic spontaneous urticaria (CSU) may occasionally exhibit long-lasting lesions with bruising, usually considered a hallmark of urticarial vasculitis (UV). Histopathology of these chronic urticarial lesions has not been extensively studied. METHODS: Skin biopsies from patients with anti-H1 resistant CSU were evaluated for several parameters (edema, location, intensity, and cell composition of the inflammatory infiltrate, and abnormalities in the blood vessels). RESULTS: We studied 45 patients (37 female/8 male, mean age 49.3 years) with CSU, 60% of whom with occasional bruising lesions and 3 patients with hypocomplementemic UV. Histopathology in CSU showed mainly perivascular and interstitial inflammatory infiltrate (91.1%), including eosinophils (80%), neutrophils (77.8%), and lymphocytes (71.1%), vasodilatation (88.9%), intravascular neutrophils (95.6%), dermal edema (51.1%), swelling of endothelial cells (51.1%), and minor and rare fibrinoid necrosis and karyorrhexis (6.7%). Significant karyorrhexis and frank fibrinoid necrosis were observed, respectively, in two and three cases of UV. In patients with occasional bruising, mast cells occurred in fewer cases whereas eosinophils were more frequent, but no statistically significant difference was found for other parameters. CONCLUSIONS: Histopathological findings were not significantly different between CSU with or without bruising lesions. Bruising may be associated with more severe forms of CSU with no histopathological signature, although UV cannot be completely excluded based on histopathology.
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Urticaria Crónica/patología , Contusiones/patología , Piel/patología , Urticaria/patología , Vasculitis Leucocitoclástica Cutánea/patología , Adulto , Anciano , Biopsia , Estudios de Casos y Controles , Proteínas del Sistema Complemento/inmunología , Células Endoteliales/patología , Eosinófilos/patología , Femenino , Humanos , Linfocitos/patología , Masculino , Mastocitos/patología , Persona de Mediana Edad , Neutrófilos/patología , Urticaria/diagnóstico , Vasculitis Leucocitoclástica Cutánea/inmunologíaRESUMEN
Focal epilepsy can be conceptualized as a network disorder, and the functional epileptic network can be described as a complex system of multiple brain areas that interact dynamically to generate epileptic activity. However, we still do not fully understand the functional architecture of epileptic networks. We studied a cohort of 21 patients with extratemporal focal epilepsy. We used independent component analysis of functional magnetic resonance imaging (fMRI) data. In order to identify the epilepsy-related components, we examined the general linear model-derived electroencephalography-fMRI (EEG-fMRI) time courses associated with interictal epileptic activity as intrinsic hemodynamic epileptic biomarkers. Independent component analysis revealed components related to the epileptic time courses in all 21 patients. Each epilepsy-related component described a network of spatially distributed brain areas that corresponded to the specific epileptic network in each patient. We also provided evidence for the interaction between the epileptic activity generated at the epileptic network and the physiological resting state networks. Our findings suggest that independent component analysis, guided by EEG-fMRI epileptic time courses, have the potential to define the functional architecture of the epileptic network in a noninvasive way. These data could be useful in planning invasive EEG electrode placement, guiding surgical resections, and more effective therapeutic interventions.
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Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/fisiopatología , Epilepsias Parciales/diagnóstico por imagen , Epilepsias Parciales/fisiopatología , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiopatología , Adolescente , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Electroencefalografía/métodos , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Análisis de Componente Principal/métodos , Estudios Prospectivos , Adulto JovenRESUMEN
Endocrine-disrupting chemicals include natural and synthetic estrogens, such as 17α-ethynilestradiol (EE2), which can affect reproduction, growth and immunity. Estrogen signalling is mediated by nuclear or membrane estrogen receptors, such as the new G-protein-coupled estrogen receptor 1 (GPER1). The present work studies the effect of EE2 and G1 (an agonist of GPER1) on body and muscle parameters and growth-related genes of 54 two-year-old seabreams. The fish were fed a diet containing EE2 (EE2 group) and G1 (G1 group) for 45 days and then a diet without EE2 or G1 for 122 days. An untreated control group was also studied. At 45 days, the shortest body length was observed in the G1 group, while 79 and 122 days after the cessation of treatments, the shortest body growth was observed in the EE2 group. Hypertrophy of white fibers was higher in the EE2 and G1 groups than it was in the control group, whereas the opposite was the case with respect to hyperplasia. Textural hardness showed a negative correlation with the size of white fibers. At the end of the experiment, all fish analyzed in the EE2 group showed a predominance of the gonadal ovarian area. In addition, the highest expression of the mafbx gene (upregulated in catabolic signals) and mstn2 (myogenesis negative regulator) was found in EE2-exposed fish.
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Etinilestradiol/farmacología , Proteínas de Peces/genética , Músculo Esquelético/efectos de los fármacos , Dorada/fisiología , Animales , Acuicultura , Proteínas de Peces/agonistas , Expresión Génica/efectos de los fármacos , Masculino , Músculo Esquelético/fisiología , Receptores de Estrógenos/genética , Receptores Acoplados a Proteínas G/genética , Dorada/genética , Dorada/crecimiento & desarrollo , Testículo/efectos de los fármacosRESUMEN
OBJECTIVE: To compare Individual Meaning-Centered Psychotherapy-Palliative Care (IMCP-PC) to counselling-based psychotherapy in patients receiving home palliative care (PC). METHODS: Fifty-one patients with advanced-stage cancer receiving home PC were recruited for this. Two-arm (individual meaning-centered psychotherapy-palliative-IMCP-PC-care vs. counselling) randomized feasibility trial. Anxiety, depression, demoralization, and emotional distress were evaluated before and after three psychotherapy sessions. Patient perceptions of the treatment were assessed after completion of therapy. RESULTS: Thirty-two patients (16 in each group) completed all three sessions as well as the pre- and post-therapy questionnaires and were therefore included in the final analysis. All patients in the IMCP-PC group showed a significant decrease in levels of demoralization (despair), anxiety, depression, and emotional distress. By contrast, the only variable that significantly improved in the counselling group was demoralization. The post-treatment questionnaire revealed no significant between-group differences regarding patient perception of the structure, focus, or length of treatment. However, the IMCP-PC group rated the treatment more highly with regard to its value in helping them to find meaning in life. CONCLUSIONS: IMCP-PC is a specific psychotherapy tailored to the needs of patients with advanced cancer. The results of the present study indicate that this treatment is suitable for patients at end of life that are not able to attend outpatient sessions. Although more research is needed, the findings of this feasibility trial suggest that the IMCP-PC merits consideration for patients receiving home palliative care (PC).
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Neoplasias/psicología , Neoplasias/terapia , Cuidados Paliativos/métodos , Psicoterapia/métodos , Anciano , Ansiedad/etiología , Ansiedad/psicología , Ansiedad/terapia , Trastornos de Ansiedad/etiología , Trastornos de Ansiedad/psicología , Trastornos de Ansiedad/terapia , Estudios de Factibilidad , Femenino , Enfermería de Cuidados Paliativos al Final de la Vida , Humanos , Masculino , Estadificación de Neoplasias , Neoplasias/patología , Proyectos Piloto , Medicina de Precisión/métodos , Distrés Psicológico , Encuestas y CuestionariosRESUMEN
Composite spectrum (CS) is a data-fusion technique that reduces the number of spectra to be analyzed, simplifying the analysis process for machine monitoring and fault detection. In this work, vibration signals from five components of a combine harvester (thresher, chopper, straw walkers, sieve box, and engine) are obtained by placing four accelerometers along the combine-harvester chassis in non-optimal locations. Four individual spectra (one from each accelerometer) and three CS (non-coherent, coherent and poly-coherent spectra) from 18 cases are analyzed. The different cases result from the combination of three working conditions of the components-deactivated (off), balanced (healthy), and unbalanced (faulty)-and two speeds-idle and maximum revolutions per minute (RPM). The results showed that (i) the peaks can be identified in the four individual spectra that correspond to the rotational speeds of the five components in the analysis; (ii) the three formulations of the CS retain the relevant information from the individual spectra, thereby reducing the number of spectra required for monitoring and detecting rotating unbalances within a combine harvester; and, (iii) data noise reduction is observed in coherent and poly-coherent CS with respect to the non-coherent CS and the individual spectra. This study demonstrates that the rotating unbalances of various components within agricultural machines, can be detected with a reduced number of accelerometers located in non-optimal positions, and that it is feasible to simplify the monitoring with CS. Overall, the coherent CS may be the best composite spectra formulation in order to monitor and detect rotating unbalances in agricultural machines.
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SAPHO syndrome is a rare entity, composed of dermatologic and osteoarticular manifestations. There are no validated diagnostic criteria and treatment is empirical, with a recent focus on biologics. Herein, we present a 50-year-old woman who developed palmoplantar pustulosis and sternoclavicular osteitis, with typical findings on bone scintigraphy. Treatment with bisphosphonate, low-dose systemic corticosteroid, and cyclosporine allowed complete resolution of the articular and dermatologic manifestations with no side effects.
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Síndrome de Hiperostosis Adquirido/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , Conservadores de la Densidad Ósea/uso terapéutico , Inmunosupresores/uso terapéutico , Huesos/diagnóstico por imagen , Ciclosporina/uso terapéutico , Quimioterapia Combinada , Femenino , Humanos , Ácido Ibandrónico/uso terapéutico , Persona de Mediana Edad , Prednisolona/uso terapéutico , CintigrafíaRESUMEN
BACKGROUND: There is little information about the early clinical features of cardioembolic stroke before complementary examinations. OBJECTIVE: The aim of this study was to identify risk factors, clinical features, and early outcomes of cardioembolic stroke. METHODS: Retrospective study based on prospectively collected data available from a university medical center hospitalbased stroke registry. Consecutive patients diagnosed with cardioembolic infarction were selected and compared to those diagnosed with an atherothrombotic stroke. Predictors of cardioembolic infarction were assessed by multivariate analysis. RESULTS: From a cohort of 4597 consecutive patients, we studied 956 patients diagnosed with cardioembolic infarction (80 years [standard deviation (SD) 9.14]; 63% women) and 945 with atherothrombotic infarction (77.01 years [SD 9.75]; 49.8% women). The univariate comparative analysis reported that advanced age (≥ 85 years), female gender, atrial fibrillation (AF), ischemic heart disease, and congestive heart failure were significantly more frequent in the cardioembolic group, whereas hypertension, diabetes, peripheral vascular disease, heavy smoking, hyperlipidemia, and previous transient ischemic attack were significant in the atherothrombotic group. In the logistic regression model, AF (odds ratio [OR] 15.75, 95% confidence interval [CI]: 12.14-20.42), ischemic heart disease (OR 3.12, 95% CI: 2.16-4.5), female gender (OR 1.56, 95% CI: 1.22-2.00), and sudden-onset (OR 1.97, 95% CI: 1.54-2.51), were independent significant predictors of cardioembolic stroke. CONCLUSIONS: Potential cardioembolic stroke requires a comprehensive evaluation, since early classification and identification through predictors would improve effective management.
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Accidente Cerebrovascular Embólico/diagnóstico , Accidente Cerebrovascular Trombótico/diagnóstico , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Estudios Retrospectivos , Factores de RiesgoRESUMEN
To provide a bibliometric and contents analyses of the Spanish research in the field of gender dysphoria based on a literature review.
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Bibliometría , Disforia de Género , Edición/estadística & datos numéricos , Humanos , Lenguaje , EspañaRESUMEN
Melatonin has been shown to enhance tear secretion associated with dinucleotide diadenosine tetraphosphate. This study investigated the isolated action of melatonin and its analogs, agomelatine, N-butanoyl-2-(2-methoxy-6H-isoindolo[2,1-a]indol-11-yl) ethanamine (IIK7), and 5-methoxycarbonylamino-N-cetyltryptamine (5-MCA-NAT) (10 µl at 100 µM), on tear secretion when applied topically in the rabbit cornea and its relationship with the melatonin MT1, MT2, and MT3/quinone reductase QR2 receptors. The results showed a significant increase in tear secretion, with a maximal effect at 60 minutes for the agonists (138.9% ± 6.5%, 128.9% ± 6.4%, and 120.0% ± 5.2%, respectively; P < 0.05; 100% control) but not for melatonin (101.6% ± 7.9%; P > 0.05). Agonist action was tested combined with the antagonists DH97 (MT2 selective), prazosin (MT3/QR2 inhibitor), and luzindole (nonselective MT membrane receptor) (10 µl at 100 µM). DH97 reversed the effect of agomelatine, IIK7, and 5-MCA-NAT up to 30.85% ± 7.6%,108% ± 7.2%, and 87.01% ± 7.6%, respectively (P < 0.05; 100% control). Luzindole antagonized agomelatine and 5-MCA-NAT up to 67.35% ± 7.6% and 92.12% ± 8%, respectively (P < 0.05). Prazosin only reversed 5-MCA-NAT action up to 84.2% ± 7.7% (P < 0.05). These results suggest different pathways for the agonists to act through MT membrane receptors. Therefore, agomelatine, IIK7, and 5-MCA-NAT act through MT membrane receptors as secretagogues of tear secretion, and these analogs could be considered excellent therapeutic candidates for dry eye treatment. SIGNIFICANCE STATEMENT: Currently, dry eye with aqueous deficit is treated by adding artificial tears palliatively. This study shows that topical installation of three melatonin analogs (agomelatine, IIK7, and 5-MCA-NAT), but not melatonin, in therapeutic doses in the rabbit cornea significantly increases tear production, acting through different melatonin membrane receptor subtypes. Therefore, this study suggests that melatoninergic compounds could be considered excellent therapeutic candidates for dry eye treatment and ocular surface diseases occurring with a reduction in tear production.
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Aparato Lagrimal/efectos de los fármacos , Melatonina/farmacología , Lágrimas/fisiología , Acetamidas/farmacología , Animales , Córnea/efectos de los fármacos , Isoindoles/farmacología , Aparato Lagrimal/fisiología , Masculino , Melatonina/análogos & derivados , Prazosina/farmacología , Conejos , Triptaminas/farmacologíaRESUMEN
OBJECTIVE: To describe an adult patient with Rasmussen's disease with focal dystonia as the most disabling symptom and the good response to unilateral globus pallidus internus (GPi) deep brain stimulation (DBS). METHODS: Retrospective review of clinical records and diagnostic tests. RESULTS: The patient had displayedmild focal seizures with sensory and motor symptoms on the left arm and hemiface since the age of 22. Ten years later she experienced abrupt onset of focal left dystonia involving mainly the leg. Brain MRI showed progressive right hemisphere atrophy, and 18 fluorodeoxyglucose-positron emission tomography (18FDG-PET) showed right hypometabolism mainly over the frontal and insular regions. Brain biopsy confirmed chronic encephalitis. The dystonia became very severe and made walking extremely difficult. Different treatments including dopaminergic, anticholinergic, immunomodulatory drugs and botulinum toxin were ineffective. Finally the patient was treated with unilateral GPi DBS. Shortly after the onset of the stimulation, the dystonia started to improve. Parameters have been adjusted, and 18 months after surgery the patient is able to walk and run unaided, although a mild left leg dystonia persists. CONCLUSION: Rasmussen's disease may be difficult to diagnose in adult patients. Associated movement disorders may be more disabling than seizures. Focal dystonia may be treated successfully with DBS.
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Estimulación Encefálica Profunda/métodos , Distonía/terapia , Encefalitis/fisiopatología , Globo Pálido , Adulto , Anticonvulsivantes/uso terapéutico , Biopsia , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/fisiopatología , Enfermedad Crónica , Distonía/etiología , Distonía/fisiopatología , Electroencefalografía , Electromiografía , Encefalitis/complicaciones , Femenino , Humanos , Pierna , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Convulsiones/tratamiento farmacológico , Convulsiones/etiología , Convulsiones/fisiopatología , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
INTRODUCTION: Cow's milk allergy (CMA) is a common diagnosis in infants, requiring the exclusion of cow's milk until tolerance is recovered. In the present study, we aim to determine which factors are associated with the development of tolerance. METHODS: Retrospective, observational study of subjects who underwent the same clinical follow-up methodology. We studied 245 cases of CMA (125 IgE-mediated and 120 non-IgE-mediated). The following variables were analysed: age at diagnosis, gender, type of delivery, type of feeding received, feeding during the first months of life, clinical features, and type of feed received as treatment: casein hydrolysates or casein hydrolysates with Lactobacillus rhamnosus GG (LGG). RESULTS: Factors associated with earlier tolerance were non-IgE-mediated CMA (HR = 2.92; 95% CI: 2.20-3.88) and patients receiving casein hydrolysate with LGG (HR = 1.79; 95% CI: 1.33-2.42). Later tolerance was associated with caesarean delivery (HR = 0.78; 95% CI: 0.58-1.05) and breastfeeding for a period of at least 3 days (HR = 0.64; 95% CI: 0.44-0.93). The multivariate study shows that the type of formula (HR = 1.61; 95% CI: 1.19-2.18) and the type of CMA (HR = 2.82; 95% CI: 2.12-3.85) have an effect on the recovery time. Casein hydrolysates with LGG reduces the recovery time in IgE-mediated (HR = 1.88; 95% CI: 1.17-3.01) and non-IgE-mediated CMA (HR = 1.46; 95% CI: 0.98-2.17). CONCLUSIONS: Tolerance acquisition is faster in non-IgE-mediated CMA subjects and in those who received casein hydrolysate with LGG.
Asunto(s)
Tolerancia Inmunológica , Hipersensibilidad a la Leche/epidemiología , Alérgenos/inmunología , Animales , Caseínas/uso terapéutico , Bovinos , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Inmunoglobulina E/metabolismo , Masculino , Hipersensibilidad a la Leche/dietoterapia , Hipersensibilidad a la Leche/inmunología , Proteínas de la Leche/inmunología , Estudios Retrospectivos , Factores de Riesgo , España/epidemiologíaRESUMEN
BACKGROUND: In this research, using computed tomography (CT) and magnetic resonance imaging (MRI), we provide a thorough description of the standard appearance of a right tarsal joint in a Bengal tiger (Panthera tigris). CT scans were performed using a bone and soft tissue window setting, and three-dimensional surface reconstructed CT images were obtained. The MRI protocol was based on the use of Spin-echo (SE) T1-weighted and Gradient-echo (GE) STIR T2-weighted pulse sequences. Magnetic resonance (MR) images were taken in the transverse, sagittal and dorsal planes. We also performed anatomical dissections to facilitate the interpretation of the different structures of the tarsus joint and allow comparisons with CT and MRI images. RESULTS: The CT images allowed us to observe differences between the bones and soft tissues of the tarsal joint. When applying the bone window setting, the obtained footage showed the anatomy between the medulla and cortex. Additionally, the trabecular bone was delineated. By contrast, the soft tissue window allowed the main soft tissue structures of the tarsal joint, including ligaments, muscles and tendons, to be differentiated. Footage of the main anatomical structures of the standard tiger tarsus was obtained through MRI. The SE T1-weighted images showed the best evaluation of the cortical, subchondral and trabecular bone of the tibia, fibula, tarsus and metatarsus bones. Nonetheless, the GE STIR T2-weighted images allowed us to better visualize the articular cartilage and synovial fluid. In both MRI pulse sequences, the ligaments and tendons appeared with low signal intensity compared with muscles that were visible with intermediate signal intensity. CONCLUSIONS: The results of this CT and MRI study of the Bengal tiger tarsal joint provide some valuable anatomical information and may be useful for diagnosing disorders in this large non-domestic cat.
Asunto(s)
Imagen por Resonancia Magnética/veterinaria , Tarso Animal/anatomía & histología , Tigres , Tomografía Computarizada por Rayos X/veterinaria , Animales , Cadáver , FemeninoRESUMEN
BACKGROUND: Previous studies analyzed a series of representative anatomical regions in the human body; however, there is a wide structural and cellular variability in the constitution of the skin. Our objective was to perform a comprehensive assessment of human skin hydration throughout the largest possible area. MATERIALS AND METHODS: Hydration was registered by Corneometer® CM825 probe in 23 anatomical regions of five healthy men. Each zone was analyzed by 2-cm segments in the supine, prone, and lateral positions. A total of 7863 measurements were registered. RESULTS: Differences in the degree of hydration among the prone, supine, and lateral regions were observed. The chest and back showed a pattern of increased hydration toward the neck area. Higher levels of hydration were evidenced in the proximal areas and in the regions near the elbow and knee. The regions of greater mechanical wear and with greater exposure to the sun exhibited a lower degree of hydration. CONCLUSION: The human skin exhibited hydration patterns influenced by anatomical function and the degree of sun exposure. Detailed information of the hydration patterns could serve as reference for the design of topical products, as an indicator of their effectiveness, and for the monitoring of skin pathologies.