RESUMEN
Substance use disorder prevention programs are most effective when matched appropriately to the baseline risk of the population. Individuals who misuse opioids often have unique risk profiles different from those who use other substances such as alcohol or cannabis. However, most substance use prevention programs are geared toward universal audiences, neglecting key inflection points along the continuum of care. The HEAL Prevention Cooperative (HPC) is a unique cohort of research projects that represents a continuum of care, from community-level universal prevention to indicated prevention among older adolescents and young adults who are currently misusing opioids or other substances. This paper describes the theoretical basis for addressing opioid misuse and opioid use disorder across the prevention continuum, using examples from research projects in the HPC.
Asunto(s)
Cannabis , Trastornos Relacionados con Opioides , Mal Uso de Medicamentos de Venta con Receta , Adolescente , Adulto Joven , Humanos , Trastornos Relacionados con Opioides/prevención & control , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/epidemiología , Analgésicos Opioides/uso terapéutico , Continuidad de la Atención al PacienteRESUMEN
Huntington's disease (HD) has traditionally been described as a disorder purely of the brain; however, evidence indicates that peripheral abnormalities are also commonly seen. Among others, severe unintended body weight loss represents a prevalent and often debilitating feature of HD pathology, with no therapies available. It correlates with disease progression and significantly affects the quality of life of HD patients. Curcumin, a naturally occurring polyphenol with multiple therapeutic properties, has been validated to exert important beneficial effects under health conditions as well as in different pathological settings, including neurodegenerative and gastrointestinal (GI) disorders. Here, we investigated the potential therapeutic action that curcumin-supplemented diet may exert on central and peripheral dysfunctions in R6/2 mice, a well-characterized HD animal model which recapitulates some features of human pathology. Maintenance of normal motor function, protection from neuropathology and from GI dysfunction and preservation of GI emptying and conserved intestinal contractility, proved the beneficial role of life-long dietary curcumin in HD and corroborated the potential of the compound to be exploited to alleviate very debilitating symptoms associated with the disease.
Asunto(s)
Conducta Animal/efectos de los fármacos , Curcumina/administración & dosificación , Enfermedad de Huntington/dietoterapia , Pérdida de Peso/efectos de los fármacos , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Curcumina/farmacología , Suplementos Dietéticos , Modelos Animales de Enfermedad , Femenino , Enfermedad de Huntington/fisiopatología , Masculino , Ratones , Ratones Transgénicos , Actividad Motora/efectos de los fármacos , FenotipoRESUMEN
Emerging evidence indicates that Huntington's disease (HD) may be described as multi-organ pathology. In this context, we and others have contributed to demonstrate that the disease is characterized by an impairment of the homeostasis of gastro-intestinal (GI) tract. Sphingolipids represent a class of molecules involved in the regulation and maintenance of different tissues and organs including GI system. In this study, we investigated whether the alteration of Sphingosine-1-phosphate (S1P) metabolism, previously described in human HD brains and animal models, is also detectable peripherally in R6/2 HD mice. Our findings indicate, for the first time, that sphingolipid metabolism is perturbed early in the disease in the intestinal tract of HD mice and, its modulation by K6PC-5, a selective activator of S1P synthesis, preserved intestinal integrity and homeostasis. These results further support the evidence that modulation of sphingolipid pathways may represent a potential therapeutic option in HD and suggest that it has also the potential to counteract the peripheral disturbances which may usually complicate the management of the disease and affect patient's quality of life.
Asunto(s)
Amidas/farmacología , Enfermedad de Huntington/metabolismo , Intestinos/efectos de los fármacos , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Animales , Modelos Animales de Enfermedad , Homeostasis/efectos de los fármacos , Lisofosfolípidos/metabolismo , Ratones , Fosfotransferasas (Aceptor de Grupo Alcohol)/efectos de los fármacos , Esfingolípidos/metabolismo , Esfingosina/análogos & derivados , Esfingosina/metabolismoRESUMEN
INTRODUCTION: Multiple sclerosis (MS) refers to chronic inflammation of the central nervous system including the brain and spinal cord. Dysphagia is a symptom that represents challenges in clinical practice. The aim of the present study was to evaluate the prevalence of dysphagia in an Italian cohort of subjects with MS using the Dysphagia Outcome Severity Score (DOSS), based on fibre-optic endoscopy, and determine factors that correlate with the presence of swallowing problems. MATHERIALS AND METHODS: Data were collected in a multicentre study from a consecutive sample of MS patients, irrespective of self-reported dysphagia. The study included 215 subjects. Possible scores for DOSS range from 7 to 1, with 7 indicating normal swallowing. RESULTS: One hundred twenty-four (57.7%) subjects demonstrated abnormal swallowing and 57 (26.5%) of these had swallowing problems that required nutrition/diet modifications when evaluated objectively with fibre-optic endoscopy. Subjects with dysphagia were more severely disabled and more often had a progressive form of MS, compared to MS subjects with normal swallowing. In subjects with EDSS, < 4, 8 (13.3%), had a DOSS < 4. Seventy-five percent of subjects older than 60 years of age had dysphagia. CONCLUSION: In this sample of MS patients, more nearly 60% showed swallowing problems.
Asunto(s)
Trastornos de Deglución/diagnóstico , Trastornos de Deglución/epidemiología , Esclerosis Múltiple/epidemiología , Estudios de Cohortes , Trastornos de Deglución/complicaciones , Endoscopía/métodos , Femenino , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/complicaciones , Fibras Ópticas , Prevalencia , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND AND PURPOSE: Late-onset multiple sclerosis (MS) has a prevalence of about 10-20% in natural history MS studies. Few data have been published about the long-term disease trajectory in the cohort of late-onset relapsing-remitting MS (LORRMS). The aim of this study was to identify the risk factors for reaching an Expanded Disability Status Scale (EDSS) score of 6.0 in LORRMS (onset at >40 years of age) and young-onset relapsing-remitting MS (YORRMS) (onset between 18 and 40 years of age). METHODS: Clinical and radiological [magnetic resonance imaging (MRI) of the brain] follow-up data were collected. Disability was assessed by EDSS score. A Cox proportional hazards model was used to evaluate the demographic and clinical predictors of reaching an EDSS score of 6.0 in the two cohorts. RESULTS: A total of 671 patients with relapsing-remitting MS were enrolled, 143 (21.3%) with LORRMS and 528 (78.7%) with YORRMS. In LORRMS, age at onset was 47.8 ± 5.3 (mean ± SD) years and duration of follow-up was 120.7 ± 52.7 months. In YORRMS, age at onset was 27 ± 2.7 years and duration of follow-up was 149.9 ± 92.7 months. The survival curve analyses showed a higher probability of reaching an EDSS score of 6.0 for LORRMS in a shorter time (months) than for YORRMS (94.2 vs. 103.2 months; log-rank 8.8; P < 0.05). On MRI, YORRMS showed more brain inflammatory features than LORRMS. In the multivariate Cox model, age at onset [Exp(B) value, 6.5; 95% confidence interval, 1.9-22.6; P < 0.001] and male gender [Exp(B) value, 1.7; 95% confidence interval, 1.0-2.8; P < 0.05] were the strongest predictors of reaching an EDSS score of 6.0. CONCLUSIONS: The male population with LORRMS reached severe disability faster than those with YORRMS, even when YORRMS showed more brain inflammatory features on MRI.
Asunto(s)
Encéfalo/diagnóstico por imagen , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Adolescente , Adulto , Edad de Inicio , Evaluación de la Discapacidad , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
PATIENTS AND METHODS: A longitudinal study was carried out in 255 children from 10 centres in nine developing countries over 5 years to assess the musculoskeletal outcome of children on episodic factor replacement. Outcome was documented by assessment of the annual joint bleeding rate (AJBR), WFH clinical and Pettersson radiological joint scores as well as the FISH score for activities. Of the 203 patients for whom data was available at the end of 5 years, 164 who had received only episodic treatment are included in this report. RESULTS: The median age at the beginning of the study was 10 years (IQR 7-12). The median clotting factor concentrate (CFC) usage was 662 IU kg-1 year-1 (IQ range: 280-1437). The median AJBR was 10 (IQ range: 5-17). The median AJBR was higher in the older children with the median being 5 for the 5 year old child, while it was 9 for the 10 year old and 11 for children older than 15. Given the episodic nature of the replacement therapy, those with a higher AJBR used significantly greater annual CFC doses (P < 0.001); The median change in WFH clinical score and Pettersson radiological score over the 5 years was 0.4/year for each, while the FISH deteriorated at a rate of 0.2/year with poor correlation of these changes with CFC dose. WFH and FISH scores were significantly worse in those with an AJBR of >3 per year (P = 0.001). The change in the Pettersson score was significantly more in those with an AJBR of >5 per year (P = 0.020). Significant changes in FISH scores were only noted after 10 years of age. CONCLUSION: Episodic CFC replacement over a large range of doses does not alter the natural course of bleeding in haemophilia or the musculoskeletal deterioration and should not be recommended as a long term option for treatment. Prophylaxis is the only way to preserve musculoskeletal function in haemophilia.
Asunto(s)
Factores de Coagulación Sanguínea/farmacología , Hemorragia/prevención & control , Sistema Musculoesquelético/efectos de los fármacos , Adolescente , Niño , Femenino , Humanos , Estudios Longitudinales , Masculino , Sistema Musculoesquelético/patología , Adulto JovenRESUMEN
Dynamical models implemented on the large scale architecture of the human brain may shed light on how a function arises from the underlying structure. This is the case notably for simple abstract models, such as the Ising model. We compare the spin correlations of the Ising model and the empirical functional brain correlations, both at the single link level and at the modular level, and show that their match increases at the modular level in anesthesia, in line with recent results and theories. Moreover, we show that at the peak of the specific heat (the critical state), the spin correlations are minimally shaped by the underlying structural network, explaining how the best match between the structure and function is obtained at the onset of criticality, as previously observed. These findings confirm that brain dynamics under anesthesia shows a departure from criticality and could open the way to novel perspectives when the conserved magnetization is interpreted in terms of a homeostatic principle imposed to neural activity.
Asunto(s)
Anestesia , Conectoma , Modelos Neurológicos , Vigilia/fisiología , Encéfalo/fisiología , HumanosRESUMEN
Floodplain delineation may inform protection of wetland systems under local, state, or federal laws. Nationally available Federal Emergency Management Agency Flood Insurance Rate Maps (FIRMs, "100-year floodplain" maps) focus on urban areas and higher-order river systems, limiting utility at large scales. Few other national-scale floodplain data are available. We acquired FIRMs for a large watershed and compared FIRMs to floodplain and integrated wetland area mapping methods based on (1) geospatial distance, (2) geomorphic setting, and (3) soil characteristics. We used observed flooding events (OFEs) with recurrence intervals of 25-50 to >100 years to assess floodplain estimate accuracy. FIRMs accurately reflected floodplain areas based on OFEs and covered 32% of river length, whereas soil-based mapping was not as accurate as FIRMs but characterized floodplain areas over approximately 65% of stream length. Geomorphic approaches included more areas than indicated by OFE, whereas geospatial approaches tended to cover less area. Overall, soil-based methods have the highest utility in determining floodplains and their integrated wetland areas at large scales due to the use of nationally available data and flexibility for regional application. These findings will improve floodplain and integrated wetland system extent assessment for better management at local, state, and national scales.
RESUMEN
A vast body of literature exists showing functional and structural dysfunction within the brains of patients with disorders of consciousness. However, the function (fluorodeoxyglucose FDG-PET metabolism)-structure (MRI-diffusion-weighted images; DWI) relationship and how it is affected in severely brain injured patients remains ill-defined. FDG-PET and MRI-DWI in 25 severely brain injured patients (19 Disorders of Consciousness of which 7 unresponsive wakefulness syndrome, 12 minimally conscious; 6 emergence from minimally conscious state) and 25 healthy control subjects were acquired here. Default mode network (DMN) function-structure connectivity was assessed by fractional anisotropy (FA) and metabolic standardized uptake value (SUV). As expected, a profound decline in regional metabolism and white matter integrity was found in patients as compared with healthy subjects. Furthermore, a function-structure relationship was present in brain-damaged patients between functional metabolism of inferior-parietal, precuneus, and frontal regions and structural integrity of the frontal-inferiorparietal, precuneus-inferiorparietal, thalamo-inferioparietal, and thalamofrontal tracts. When focusing on patients, a stronger relationship between structural integrity of thalamo-inferiorparietal tracts and thalamic metabolism in patients who have emerged from the minimally conscious state as compared with patients with disorders of consciousness was found. The latter finding was in line with the mesocircuit hypothesis for the emergence of consciousness. The findings showed a positive function-structure relationship within most regions of the DMN. Hum Brain Mapp 37:3707-3720, 2016. © 2016 Wiley Periodicals, Inc.
Asunto(s)
Lesión Encefálica Crónica/diagnóstico por imagen , Lesión Encefálica Crónica/fisiopatología , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Imagen de Difusión por Resonancia Magnética , Tomografía de Emisión de Positrones , Adulto , Lesión Encefálica Crónica/complicaciones , Trastornos de la Conciencia/diagnóstico por imagen , Trastornos de la Conciencia/etiología , Trastornos de la Conciencia/fisiopatología , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Persona de Mediana Edad , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Radiofármacos , Análisis de Regresión , Adulto JovenRESUMEN
BACKGROUND: Cyclophosphamide (Cyc) can induce ovarian failure and can have teratogenic effect. Few case reports of successful pregnancies after Cyc treatment in women with autoimmune diseases and malignancies have been described. To date, there are no data about Cyc effect on pregnancy outcomes in MS patients. AIM OF THE STUDY: To describe pregnancy outcomes in multiple sclerosis (MS) patients treated with Cyc before conception. METHODS: We reviewed retrospectively the medical records of all MS patients who received Cyc from 1st of January 1997 to 31st of March 2012, referring to the MS centre of the University of Catania. All pregnancies, occurred during the follow-up period after Cyc treatment, were recorded according to a computerized and standardized protocol (iMED). RESULTS: We found a total of 105 MS women of childbearing age; eleven patients experienced a pregnancy (10.4%); 10 of them had a successful delivery; and one experienced a voluntary abortion. Five women had a preterm delivery. One child was small for gestational age. CONCLUSIONS: Although the favourable pregnancy outcomes, Cyc should be avoided in young women planning a pregnancy. However, Cyc might be considered as a possible alternative to licensed therapies in few selected cases of very aggressive MS, including women of childbearing age.
Asunto(s)
Ciclofosfamida/efectos adversos , Inmunosupresores/efectos adversos , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Complicaciones del Embarazo , Resultado del Embarazo , Adulto , Femenino , Humanos , Recién Nacido , Embarazo , Estudios Retrospectivos , Adulto JovenRESUMEN
INTRODUCTION: Cladribine is an oral immune reconstitution therapy for relapsing multiple sclerosis (RMS). Hormonal and immune changes are responsible for the decline of disease activity in the third trimester of pregnancy and disease reactivation in the early post-partum period.We investigate the impact of pregnancy on disease activity in women with MS who conceived after cladribine treatment. METHODS: We recruited women of childbearing age with relapsing-remitting MS (RRMS) who became pregnant or not after being treated with cladribine. For both groups, demographic, clinical and radiological data were collected 1 year before and after treatment during a mean follow-up of 3.53 years. We compared disease activity over time between groups using variance analysis for repeated measures. RESULTS: 48 childbearing women were included. 25 women had a pregnancy after a mean of 1.75 years from the first treatment cycle. Women with or without pregnancy did not differ in demographics or pre-cladribine disease activity. No significant differences in disease activity or EDSS worsening were found between women with or without pregnancy. DISCUSSION: Our findings suggest that pregnancy does not appear to influence disease activity and disability in women previously treated with cladribine; further studies with larger numbers and longer follow-up are needed to confirm this finding.
Asunto(s)
Cladribina , Inmunosupresores , Esclerosis Múltiple Recurrente-Remitente , Humanos , Femenino , Cladribina/farmacología , Cladribina/administración & dosificación , Embarazo , Adulto , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Complicaciones del Embarazo/tratamiento farmacológico , Estudios de Seguimiento , Adulto Joven , Evaluación de la DiscapacidadRESUMEN
Health-related quality of life (HRQoL) is an important outcome from the perspective of boys with haemophilia and their parents. Few studies have captured the HRQoL of boys with haemophilia in developing countries. This article reports on the cross-cultural adaptation of the Canadian Haemophilia Outcomes - Kids Life Assessment Tool (CHO-KLAT) for use in São Paulo, Brazil. The CHO-KLAT(2.0) was translated into Portuguese, and then translated back into English. The original English and back-translation versions were compared by a group of three clinicians, whose first language was Portuguese. The resulting Portuguese version was assessed through a series of cognitive debriefing interviews with children and their parents. This process identified concepts that were not clear and revised items to ensure appropriate understanding through an iterative process. The initial back-translation was not discrepant from the original English version. We made changes to 66% of the CHO-KLAT(2.0) items based on clinical expert review and 26% of the items based on cognitive debriefings. In addition, two new items were added to the final Portuguese version to reflect the local cultural context. The final result had good face validity. This process was found to be extremely valuable in ensuring the items were accurately interpreted by the boys/parents in São Paulo Brazil. The results suggest that professional translators, clinical experts and cognitive debriefing are all required to achieve a culturally appropriate instrument. The Portuguese CHO-KLAT(2.0) is well understood by Sao Paulo boys/parents. The next step will be to test its validity and reliability locally.
Asunto(s)
Hemofilia A/psicología , Hemofilia B/psicología , Calidad de Vida , Adolescente , Brasil , Niño , Humanos , Entrevistas como Asunto , Masculino , Apoyo Social , Encuestas y Cuestionarios , TraducciónRESUMEN
Psychosocial outcomes are important in the perspective of boys with haemophilia. However, health-related quality of life (HRQoL) is based on self-report, and assumes adequate literacy. Yet, literacy is rarely assessed prior to data collection. This study sought to identify criteria that might indicate the level of literacy of children being recruited for clinical trials and to develop a simple method to prescreen those whose literacy was uncertain. We developed a brief screening tool in the form of two stories, at a grade 3 reading level, followed by comprehension questions. We applied the screening test to a sample of haemophilic boys between the ages of 7 and 13 years to assess their literacy. The data were analysed to determine the best criteria to use in identifying the ability to independently self-report for HRQoL studies. Twenty-four Brazilian boys (7.9-12.8) completed the testing. The results showed that 17 (70.8%) were literate (were able to both read and comprehend), and could complete a questionnaire without assistance. All boys over 11.0 years of age were sufficiently literate. Grade level was not found to be a helpful criterion. We recommend that all children under the age of 11.0 years be prescreened before providing self-reported HRQoL data. Those with limited literacy should be provided assistance to ensure comprehension of the questions. This is important to ensure high-quality data on HRQoL for future clinical trials.
Asunto(s)
Hemofilia A/psicología , Hemofilia B/psicología , Calidad de Vida , Adolescente , Brasil , Niño , Escolaridad , Estado de Salud , Humanos , Masculino , Encuestas y CuestionariosRESUMEN
BACKGROUND: Although multiple sclerosis (MS) Intimacy and Sexuality Questionnaire-19 (MSISQ-19) is a widely applied tool, no unique definition of sexual dysfunction (SD) based on its score exists. OBJECTIVE: To explore the impact of different MSISQ-19 cut-offs on SD prevalence and associated risk factors, providing relevant information for its application in research and clinical settings. METHODS: After defining SD according to two different MSISQ-19 cut-offs in 1155 people with MS (pwMS), we evaluated SD prevalence and association with sociodemographic and clinical features, mood status and disability via logistic regression. RESULTS: Depending on the chosen cut-off, 45% to 54% of pwMS reported SD. SD defined as MSISQ-19 score >30 was predicted by age (OR=1.01, p=0.047), cognition (OR=0.96, p=0.004) and anxiety (OR=1.03, p=0.019). SD defined as a score >3 on any MSISQ-19 item was predicted by motor disability (OR=1.12, p=0.003) and cognition (OR= 0.96, p=0.002). CONCLUSION: Applying different MSISQ-19 cut-offs influences both the estimated prevalence and the identification of risk factors for SD, a finding that should be considered during study planning and data interpretation. Preserved cognition exerts a protective effect towards SD regardless from the specific study setting, representing a key point for the implementation of preventive and therapeutic strategies.
RESUMEN
BACKGROUND: The relationship between multiple sclerosis (MS) and headache (HA) is not well known. It was reported that interferon-beta (IFNß) could induce or worsen HA. OBJECTIVE: To evaluate the impact of IFNß treatment on HA and the relationship between HA and the various commercial preparations of IFNß in mildly disabled patients with MS. METHODS: A specific questionnaire was administered to 357 relapsing-remitting MS patients. Characteristics of HAs were considered, including the temporal relationships with IFNß administration. RESULTS: One hundred and seventeen patients were treated with weekly intramuscular injections of interferon IFNß-1a (Avonex(®)), 84 with subcutaneous injections of IFNß-1b (Betaferon(®)) every other day, 48 and 108 with three times weekly subcutaneous injections of IFNß-1a (Rebif(®)) 22 mcg or IFNß-1a (Rebif(®)) 44 mcg, respectively. Three hundred and fourteen patients were affected by HA, and among them, 219 patients suffered of pre-existing HA. In this latter group, 121 subjects (55%) noted a worsening of their HA after starting IFNß therapy; this was more frequently reported by patients treated with Avonex(®) and Rebif(®) 44. Ninety-five patients experienced new HA. CONCLUSION: IFNß treatment could worsen HA in patients with pre-existing HA or cause the appearance of new HA. Among different IFNß preparations, Rebif(®) 44 and Avonex(®) seemed to be more cephalalgic than the other drugs.
Asunto(s)
Cefalea/etiología , Interferón beta/efectos adversos , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Adulto , Femenino , Cefalea/complicaciones , Cefalea/epidemiología , Humanos , Interferón beta/uso terapéutico , Masculino , Persona de Mediana Edad , Trastornos Migrañosos/complicaciones , Esclerosis Múltiple Recurrente-Remitente/complicaciones , Cefalea de Tipo Tensional/complicacionesRESUMEN
Resting state fMRI has been employed to identify alterations in functional connectivity within or between brain regions following acute and chronic exposure to Δ9-tetrahydrocannabinol (THC), the psychoactive component in cannabis. Most studies focused a priori on a limited number of local brain areas or circuits, without considering the impact of cannabis on whole-brain network organization. The present study attempted to identify changes in the whole-brain human functional connectome as assessed with ultra-high field (7T) resting state scans of cannabis users (N = 26) during placebo and following vaporization of cannabis. Two distinct data-driven methodologies, i.e. network-based statistics (NBS) and connICA, were used to identify changes in functional connectomes associated with acute cannabis intoxication and history of cannabis use. Both methodologies revealed a broad state of hyperconnectivity within the entire range of major brain networks in chronic cannabis users compared to occasional cannabis users, which might be reflective of an adaptive network reorganization following prolonged cannabis exposure. The connICA methodology also extracted a distinct spatial connectivity pattern of hypoconnectivity involving the dorsal attention, limbic, subcortical and cerebellum networks and of hyperconnectivity between the default mode and ventral attention network, that was associated with the feeling of subjective high during THC intoxication. Whole-brain network approaches identified spatial patterns in functional brain connectomes that distinguished acute from chronic cannabis use, and offer an important utility for probing the interplay between short and long-term alterations in functional brain dynamics when progressing from occasional to chronic use of cannabis.
Asunto(s)
Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Cannabis/química , Conectoma/métodos , Dronabinol/administración & dosificación , Fumar Marihuana/fisiopatología , Fumar Marihuana/psicología , Extractos Vegetales/administración & dosificación , Psicotrópicos/administración & dosificación , Adulto , Atención/efectos de los fármacos , Cognición/efectos de los fármacos , Estudios Cruzados , Método Doble Ciego , Emociones/efectos de los fármacos , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Adulto JovenRESUMEN
BACKGROUND: The identification of biomarkers able to improve the differential diagnosis between multiple sclerosis (MS) and neuromyelitis optica (NMO) is challenging because of a different prognosis and response to treatment. Growing evidence indicates that brain and CSF N-acetyl aspartate (NAA) concentration is a useful marker for characterising different phases of axonal pathology in demyelinating diseases, and preliminary studies suggest that increased serum NAA levels may be a telltale sign of acute neuronal damage or defective NAA metabolism in oligodendrocytes. OBJECTIVE: To evaluate whether serum and CSF NAA concentration differs in patients with MS and NMO. DESIGN: Observational, multicentre, prospective, cross sectional study. METHODS: Serum samples were collected from 48 relapsing-remitting MS, 32 NMO and 76 age matched healthy controls. Coeval CSF samples were available for all MS and for 8/32 NMO patients. NAA was measured in serum and CSF by liquid chromatography-mass spectrometry. RESULTS: MS patients showed higher serum and CSF NAA levels than NMO patients, and higher serum NAA levels than healthy controls (p<0.001). High serum NAA values, exceeding the 95th percentile of serum NAA values in healthy controls, were found in 100% of patients with MS and in no patient with NMO. No differences in serum NAA levels were found between NMO and healthy controls. In MS, serum and CSF NAA levels correlated with disability score. CONCLUSIONS: Determination of serum and CSF NAA levels may represent a suitable tool in the diagnostic laboratory workup to differentiate MS and NMO.
Asunto(s)
Ácido Aspártico/análogos & derivados , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Neuromielitis Óptica/diagnóstico , Adolescente , Adulto , Anciano , Ácido Aspártico/sangre , Ácido Aspártico/líquido cefalorraquídeo , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Estudios de Casos y Controles , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/sangre , Esclerosis Múltiple Recurrente-Remitente/líquido cefalorraquídeo , Neuromielitis Óptica/sangre , Neuromielitis Óptica/líquido cefalorraquídeoRESUMEN
OBJECTIVE: To evaluate thromboelastographic parameters and fibrinogen levels in women treated with transdermal 17beta estradiol. METHODS: 29 menopausal women with a history of venous thromboembolic disease were included. Nine patients composed the treatment (HT) group and 20 the control group. Coagulation was assessed by thromboelastography in samples of whole blood and platelet-poor plasma (PPP). The following thromboelastographic variables were measured: time for initial coagulation (R), blood clotting speed (K and the alpha angle), clot tensile strength (MA and G), global index of coagulation (CI) and fibrinolysis (LY30) and fibrinogen levels. RESULTS: There were no differences in the other parameters comparing both groups. Fibrinogen levels showed a 13.77 +/- 19.94% reduction in the HT group and a 5.51 +/- 8.09% increase in the control group after 6 months. CONCLUSIONS: Our data suggested that transdermal estrogen may not increase blood coagulability, but that it reduces fibrinogen levels in HT women.
Asunto(s)
Estradiol/administración & dosificación , Terapia de Reemplazo de Estrógeno , Estrógenos/administración & dosificación , Fibrinógeno/análisis , Tromboembolia Venosa/sangre , Administración Cutánea , Adulto , Análisis de Varianza , Femenino , Humanos , Persona de Mediana Edad , Proyectos Piloto , TromboelastografíaRESUMEN
AIMS: To isolate thiodiglycol (TDG)-degrading bacteria, the mustard gas hydrolysis product, and to characterize the metabolites formed and the enzymes involved in the degradation. METHODS AND RESULTS: Two strains, identified as Achromobacter xylosoxydans G5 and Paracoccus denitrificans E4, isolated from a petroleum-contaminated soil, utilized TDG as sole carbon and sulfur source. During the degradation of TDG by strain E4 [(2-hydroxyethyl)thio] acetic acid (HETA), thiodiglycolic acid (TDGA) and bis-(2-hydroxyethyl)disulfide (BHEDS) were identified by gas chromatography-mass spectrometry analysis, while HETA and TDGA were identified for strain G5. Two-dimensional isoelectric focussing-gel electrophoresis (2-D IEF/SDS-PAGE) maps of protein extracts of P. denitrificans E4 grown on TDG showed a spot identified as a methanol dehydrogenase. Increased expression of a putative iscS gene, involved in sulfur assimilation, was observed in TDG-grown cells of A. xylosoxydans G5. CONCLUSIONS: TDG degradation by P. denitrificans E4 occurred through two pathways: one involved cleavage of the C-S bond of HETA, yielding BHEDS and the other, oxidation of the alcoholic groups of TDG, yielding TDGA. The cleavage of the C-S bond of TDGA gave mercaptoacetic acid, further oxidized to acetate and sulfate. SIGNIFICANCE AND IMPACT OF THE STUDY: Increased knowledge of TDG-degrading bacteria and the possibility of using them in a tailored-two-stage mustard gas destruction process.
Asunto(s)
Achromobacter/metabolismo , Gas Mostaza/metabolismo , Paracoccus denitrificans/metabolismo , Microbiología del Suelo , Contaminantes del Suelo/metabolismo , Compuestos de Sulfhidrilo/metabolismo , Achromobacter/genética , Achromobacter/aislamiento & purificación , Biodegradación Ambiental , Disulfuros/metabolismo , Electroforesis en Gel de Poliacrilamida/métodos , Cromatografía de Gases y Espectrometría de Masas/métodos , Hidrólisis , Gas Mostaza/química , Paracoccus denitrificans/genética , Paracoccus denitrificans/aislamiento & purificación , Petróleo , ARN Ribosómico 16S/genética , Compuestos de Sulfhidrilo/química , Tioglicolatos/metabolismoRESUMEN
OBJECTIVE: The purpose of this study is to evaluate the haemodynamic and respiratory effects of dexmedetomidine vs. propofol in patients with OSAHS during the drug-induced sleep endoscopy (DISE), and analyze simultaneously the electromyography of genioglossus muscle. PATIENTS AND METHODS: We conducted a study on 50 patients with OSAHS; patients were subjected to DISE with simultaneous polygraphic cardiorespiratory measurement and electromyography of genioglossus muscle. Patients undergoing DISE were divided in two groups: in Group A (19 M; 8 W) was administered propofol TCI and in Group B (16 M; 7 W) was administered dexmedetomidine TCI. RESULTS: In Group A, a mean minimal SpO2 decreasing of 3.7% (p=0.000) and a mean SpO2 decreasing of 1.6% (p 0.001) was noticed, while there was an increase in BP20 of 14.8% (p=0.000) and HR20 of 11.1% (p=0.000). In Group B, it was showed a decreasing of mean minimal SpO2 and mean SpO2 values, about 1.8% (p=0.000) and 1.1% (p 0.009) respectively, while there was an increase of BP20 and HR20, about 8.7% (p=0.000) and 8% (p 0.002), respectively. Despite EMG activity comparing spontaneous sleep with propofol-DISE, there is a statistically significative change for the amplitude (p=0.040) and an increase of 7.01% for the area under the curve (AUC). Comparing spontaneous sleep with dexmedetomidine-DISE induced one, there is only an increase of 25.87% in the AUC. CONCLUSIONS: A greater worsening of the cardio-respiratory basal values was noted after sleep induction with Propofol and same results were obtained confronting EMG of genioglossus muscle data.