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1.
Arch Sex Behav ; 53(6): 2159-2172, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38514492

RESUMEN

Individuals with paraphilic interests in sexual violence or children may be more likely to sexually offend if they possess offense-supportive cognitions. These cognitions may develop in response to childhood adversity. However, this idea is largely based on research in men convicted of sexual offenses and may not generalize to non-incarcerated adults with paraphilic interests. In a sample of 178 adults screened for paraphilic interests in violence or children (from the general Czech population), we hypothesized that childhood sexual abuse and emotional neglect would be associated with offense-supportive cognitions about rape and child molestation. Participants came from a nationally representative sample of Czech adults and were selected if they self-reported high levels of sexual interest in violence and/or children. Participants completed an online survey with self-report measures of sexual orientation, offense-supportive cognitions (Bumby RAPE and MOLEST scales), and childhood sexual abuse and emotional neglect (Childhood Trauma Questionnaire). Controlling for gender, age, and sexual orientation, we found that both rape-supportive cognitions and child molestation-supportive cognitions were significantly associated with higher levels of childhood sexual abuse, but not emotional neglect. These findings indicate that childhood sexual abuse may lead to offense-supportive cognitions among men and women with paraphilia.


Asunto(s)
Cognición , Humanos , Masculino , Femenino , República Checa , Adulto , Persona de Mediana Edad , Niño , Experiencias Adversas de la Infancia/psicología , Experiencias Adversas de la Infancia/estadística & datos numéricos , Abuso Sexual Infantil/psicología , Abuso Sexual Infantil/estadística & datos numéricos , Violación/psicología , Trastornos Parafílicos/psicología , Delitos Sexuales/psicología , Delitos Sexuales/estadística & datos numéricos , Conducta Sexual/psicología , Adultos Sobrevivientes del Maltrato a los Niños/psicología , Adultos Sobrevivientes del Maltrato a los Niños/estadística & datos numéricos , Adulto Joven , Encuestas y Cuestionarios , Adolescente
2.
Proc Natl Acad Sci U S A ; 117(23): 12952-12960, 2020 06 09.
Artículo en Inglés | MEDLINE | ID: mdl-32457139

RESUMEN

Effective biomarkers for multiple sclerosis diagnosis, assessment of prognosis, and treatment responses, in particular those measurable in blood, are largely lacking. We have investigated a broad set of protein biomarkers in cerebrospinal fluid (CSF) and plasma using a highly sensitive proteomic immunoassay. Cases from two independent cohorts were compared with healthy controls and patients with other neurological diseases. We identified and replicated 10 cerebrospinal fluid proteins including IL-12B, CD5, MIP-1a, and CXCL9 which had a combined diagnostic efficacy similar to immunoglobulin G (IgG) index and neurofilament light chain (area under the curve [AUC] = 0.95). Two plasma proteins, OSM and HGF, were also associated with multiple sclerosis in comparison to healthy controls. Sensitivity and specificity of combined CSF and plasma markers for multiple sclerosis were 85.7% and 73.5%, respectively. In the discovery cohort, eotaxin-1 (CCL11) was associated with disease duration particularly in patients who had secondary progressive disease (PCSF < 4 × 10-5, Pplasma < 4 × 10-5), and plasma CCL20 was associated with disease severity (P = 4 × 10-5), although both require further validation. Treatment with natalizumab and fingolimod showed different compartmental changes in protein levels of CSF and peripheral blood, respectively, including many disease-associated markers (e.g., IL12B, CD5) showing potential application for both diagnosing disease and monitoring treatment efficacy. We report a number of multiple sclerosis biomarkers in CSF and plasma for early disease detection and potential indicators for disease activity. Of particular importance is the set of markers discovered in blood, where validated biomarkers are lacking.


Asunto(s)
Quimiocina CCL11/análisis , Quimiocina CCL20/sangre , Inflamación/inmunología , Esclerosis Múltiple/diagnóstico , Adulto , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Estudios de Casos y Controles , Quimiocina CCL11/inmunología , Quimiocina CCL20/inmunología , Estudios de Cohortes , Femenino , Humanos , Inflamación/sangre , Inflamación/líquido cefalorraquídeo , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/sangre , Esclerosis Múltiple/líquido cefalorraquídeo , Esclerosis Múltiple/inmunología , Pronóstico , Proteómica , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Adulto Joven
3.
Mult Scler ; 28(6): 872-884, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34392718

RESUMEN

BACKGROUND: Neurofilament light (NFL) has been increasingly recognized for prognostic and therapeutic decisions. OBJECTIVE: To validate the utility of cerebrospinal fluid NFL (cNFL) as a biomarker in clinical practice of relapsing-remitting multiple sclerosis (RRMS). METHODS: RRMS patients (n = 757) who had cNFL analyzed as part of the diagnostic work-up in a single academic multiple sclerosis (MS) center, 2001-2018, were retrospectively identified. cNFL concentrations were determined with two different immunoassays and the ratio of means between them was used for normalization. RESULTS: RRMS with relapse had 4.4 times higher median cNFL concentration (1134 [interquartile range (IQR) 499-2744] ng/L) than those without relapse (264 [125-537] ng/L, p < 0.001) and patients with gadolinium-enhancing lesions had 3.3 times higher median NFL (1414 [606.8-3210] ng/L) than those without (426 [IQR 221-851] ng/L, p < 0.001). The sensitivity and specificity of cNFL to detect disease activity was 75% and 98.5%, respectively. High cNFL at MS onset predicted progression to Expanded Disability Status Scale (EDSS) ⩾ 3 (p < 0.001, hazard ratios (HR) = 1.89, 95% CI = 1.44-2.65) and conversion to secondary progressive MS (SPMS, p = 0.001, HR = 2.5, 95% CI = 1.4-4.2). CONCLUSIONS: cNFL is a robust and reliable biomarker of disease activity, treatment response, and prediction of disability and conversion from RRMS to SPMS. Our data suggest that cNFL should be included in the assessment of patients at MS-onset.


Asunto(s)
Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Biomarcadores/líquido cefalorraquídeo , Progresión de la Enfermedad , Humanos , Filamentos Intermedios/patología , Esclerosis Múltiple/líquido cefalorraquídeo , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple Recurrente-Remitente/patología , Proteínas de Neurofilamentos/líquido cefalorraquídeo , Recurrencia , Sistema de Registros , Estudios Retrospectivos
4.
J Neurochem ; 159(3): 618-628, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34478561

RESUMEN

Kappa free light chain (KFLC) index, a measure for intrathecal production of free kappa chains, has been increasingly recognized for its diagnostic potential in multiple sclerosis (MS) as a quantitative alternative to IgG oligoclonal bands (OCBs). Our objective was to investigate the sensitivity, specificity, and overall diagnostic accuracy of KFLC index in MS. KFLC index was prospectively determined as part of the diagnostic workup in patients with suspected MS (n = 327) between May 2013 and February 2020. Patients with clinically isolated syndrome (CIS), radiologically isolated syndrome (RIS), and MS had markedly higher KFLC index (44.6, IQR 16-128) compared with subjects with other neuro-inflammatory disorders (ONID) and symptomatic controls (SC) (2.19, IQR 1.68-2.98, p < 0.001). KFLC index had a sensitivity of 0.93 (95% CI 0.88-0.95) and specificity of 0.87 (95% CI 0.8-0.92) to discriminate CIS/RIS/MS from ONID and SC (AUC 0.94, 95% CI 0.91-0.97, p < 0.001). KFLC index and intrathecal fraction (IF) KFLC had similar accuracies to detect MS. Treatment with disease-modifying therapy (DMT) did not influence the level of KFLC index and it was not affected by demographic factors or associated with degenerative or inflammatory biomarkers in cerebrospinal fluid (CSF). KFLC index in MS diagnostics has methodological advantages compared to OCB and is independent to subjective interpretation. Moreover, it is an attractive diagnostic tool since the diagnostic specificity and sensitivity of KFLC index are similar with that of OCBs and KFLCIF and better than for IgG index. We show that KFLC index was influenced neither by DMT nor by demographic factors or other inflammatory or degenerative processes in MS as determined by biomarkers in CSF.


Asunto(s)
Cadenas Ligeras de Inmunoglobulina/análisis , Esclerosis Múltiple/diagnóstico , Adulto , Biomarcadores , Enfermedades Desmielinizantes/diagnóstico , Diagnóstico Diferencial , Progresión de la Enfermedad , Femenino , Humanos , Inmunoglobulina G/análisis , Inflamación/diagnóstico , Imagen por Resonancia Magnética , Masculino , Esclerosis Múltiple/diagnóstico por imagen , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Médula Espinal/química , Médula Espinal/metabolismo
5.
J Neurol Neurosurg Psychiatry ; 92(2): 189-194, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33106366

RESUMEN

OBJECTIVE: To compare outcomes after treatment with autologous haematopoietic stem cell transplantation (AHSCT) and alemtuzumab (ALZ) in patients with relapsing-remitting multiple sclerosis. METHODS: Patients treated with AHSCT (n=69) received a conditioning regimen of cyclophosphamide (200 mg/kg) and rabbit anti-thymocyte globulinerG (6.0 mg/kg). Patients treated with ALZ (n=75) received a dose of 60 mg over 5 days, a repeated dose of 36 mg over 3 days after 1 year and then as needed. Follow-up visits with assessment of the expanded disability status scale score, adverse events and MR investigations were made at least yearly. RESULTS: The Kaplan-Meier estimates of the primary outcome measure 'no evidence of disease activity' was 88% for AHSCT and 37% for ALZ at 3 years, p<0.0001. The secondary endpoint of annualised relapse rate was 0.04 for AHSCT and 0.1 for ALZ, p=0.03. At last follow-up, the proportions of patients who improved, were stable or worsened were 57%/41%/1% (AHSCT) and 45%/43%/12% (ALZ), p=0.06 Adverse events grade three or higher were present in 48/69 patients treated with AHSCT and 0/75 treated with ALZ in the first 100 days after treatment initiation. The most common long-term adverse event was thyroid disease with Kaplan-Meier estimates at 3 years of 21% for AHSCT and 46% for ALZ, p=0.005. CONCLUSIONS: In this observational cohort study, treatment with AHSCT was associated with a higher likelihood of maintaining 'no evidence of disease activity'. Adverse events were more frequent with AHSCT in the first 100 days, but thereafter more common in patients treated with ALZ.


Asunto(s)
Alemtuzumab/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Esclerosis Múltiple Recurrente-Remitente/terapia , Fármacos Neuroprotectores/uso terapéutico , Adulto , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Estimación de Kaplan-Meier , Masculino , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Resultado del Tratamiento
6.
Int J Mol Sci ; 22(10)2021 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-34068231

RESUMEN

Stress granules (SGs) are membrane-less assemblies arising upon various stresses in eukaryotic cells. They sequester mRNAs and proteins from stressful conditions and modulate gene expression to enable cells to resume translation and growth after stress relief. SGs containing the translation initiation factor eIF3a/Rpg1 arise in yeast cells upon robust heat shock (HS) at 46 °C only. We demonstrate that the destabilization of Rpg1 within the PCI domain in the Rpg1-3 variant leads to SGs assembly already at moderate HS at 42 °C. These are bona fide SGs arising upon translation arrest containing mRNAs, which are components of the translation machinery, and associating with P-bodies. HS SGs associate with endoplasmatic reticulum and mitochondria and their contact sites ERMES. Although Rpg1-3-labeled SGs arise at a lower temperature, their disassembly is delayed after HS at 46 °C. Remarkably, the delayed disassembly of HS SGs after the robust HS is reversed by TDP-43, which is a human protein connected with amyotrophic lateral sclerosis. TDP-43 colocalizes with HS SGs in yeast cells and facilitates cell regrowth after the stress relief. Based on our results, we propose yeast HS SGs labeled by Rpg1 and its variants as a novel model system to study functions of TDP-43 in stress granules disassembly.


Asunto(s)
Gránulos Citoplasmáticos/fisiología , Proteínas de Unión al ADN/metabolismo , Factor 3 de Iniciación Eucariótica/química , Respuesta al Choque Térmico , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Unión al ADN/genética , Retículo Endoplásmico/metabolismo , Factor 3 de Iniciación Eucariótica/genética , Factor 3 de Iniciación Eucariótica/metabolismo , Humanos , Mitocondrias/metabolismo , Estabilidad Proteica , ARN Mensajero/genética , ARN Mensajero/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crecimiento & desarrollo , Proteínas de Saccharomyces cerevisiae/genética
7.
Acta Neurol Scand ; 139(5): 422-427, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30657162

RESUMEN

BACKGROUND: Little is known about what leads to recovery between relapses in multiple sclerosis (MS), particularly following treatment. In the past, it has been demonstrated that soluble neural cell adhesion molecule (sNCAM), a putative biomarker of neuroplasticity, increased following steroid treatment in the Cerebrospinal fluid (CSF) of MS subjects undergoing acute relapses. Taking this a step further, we have evaluated the effect of disease-modifying treatment (DMTs) on CSF sNCAM levels in various subtypes of MS. METHODS: We measured CSF sNCAM levels at baseline and after 12-24 months of DMT in 69 patients, 49 relapsing-remitting MS (RRMS), 20 progressive MS(PMS), and 24 healthy controls (HC) using an in-house ELISA. Of this, 31 patients had received natalizumab, 17 mitoxantrone, and 21 fingolimod. Changes in disability were measured using EDSS and disease severity by MSSS. In conjunction, CSF NfL levels were also measured. RESULTS: At baseline, the mean sNCAM level was 268.7 ng/mL (SD: 109 ng/mL) in MS patients compared with 340.6 ng/ml (SD: 139 ng/mL) in HC, and PMS had significantly lower sNCAM (239.2 ng/mL, SD: 123.0, P = 0.019) compared to RRMS (269.4, SD: 127.4, P = 0.043). After natalizumab and mitoxantrone treatments, we observed an increase in mean sNCAM. However, in the fingolimod-treated group, mean sNCAM decreased. There was no correlation found with EDSS or MSSS, or NfL levels as a whole. CONCLUSIONS: Cerebrospinal fluid sNCAM levels were found to be lower in MS than in HC and the lowest sNCAM levels were found in PMS. Following natalizumab and mitoxantrone treatments, we observed an elevation in sNCAM levels, an effect that was not observed following fingolimod treatment. These changes, however, did not appear to correlate with disability in the short-term or NfL levels.


Asunto(s)
Biomarcadores/líquido cefalorraquídeo , Antígeno CD56/líquido cefalorraquídeo , Factores Inmunológicos/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/líquido cefalorraquídeo , Esclerosis Múltiple Recurrente-Remitente/dietoterapia , Adulto , Ensayo de Inmunoadsorción Enzimática , Femenino , Clorhidrato de Fingolimod/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Mitoxantrona/uso terapéutico , Esclerosis Múltiple/líquido cefalorraquídeo , Natalizumab/uso terapéutico
8.
Acta Neurol Scand ; 140(3): 177-183, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31087810

RESUMEN

BACKGROUND: Elevated levels of the cerebrospinal fluid (CSF) neuronal injury markers (neurofilament light chain [NF-L] and total tau protein [t-tau]) and of the astroglial marker glial fibrillary acidic protein (GFAP) are found in etiologically different neurological disorders affecting the peripheral and the central nervous system. AIMS: To explore the role of CSF biomarkers in the clinical management of patients admitted for alarming neurological symptoms, but in whom neurological disorders could be excluded. METHODS: Study participants were patients seeking medical attention for neurological symptoms primarily considered to be caused by a neurological diagnosis and investigated according to clinical routine. Demographic, clinical, and CSF data were extracted retrospectively from medical records. Patients with a final neurological diagnosis were excluded. RESULTS: Out of 990 patients, 900 with a neurological diagnosis were excluded leaving 90 patients without a final neurological diagnosis. Sixty-eight (75.6%) were females. Median (range) age at lumbar puncture was 34.7 (16.9-65.1) years. Age-adjusted CSF-NF-L, CSF-t-tau, and CSF-GFAP concentrations were normal in 89 (98.9%), 86 (95.6%), and 87 (96.7%) patients, respectively. CONCLUSION: In patients with significant neurological symptoms but in whom a neurological diagnosis could not be made, the CSF markers NF-L, t-tau, and GFAP did not indicate signs of neuronal or astroglial cell damage close to symptom onset. Consequently, increased levels of CSF markers are not expected in this patient group and, if present, should raise suspicion of underlying neurological disorders and motivate further investigations.


Asunto(s)
Proteína Ácida Fibrilar de la Glía/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso/líquido cefalorraquídeo , Proteínas de Neurofilamentos/líquido cefalorraquídeo , Proteínas tau/líquido cefalorraquídeo , Adulto , Anciano , Biomarcadores/líquido cefalorraquídeo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/patología
9.
J Neurochem ; 146(3): 322-332, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29676479

RESUMEN

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Several biomarkers including proteins and lipids have been reported in MS cerebrospinal fluid (CSF), reflecting different aspects of the pathophysiology particularly of relapsing-remitting MS (RRMS). Sulfatide, abundant in the myelin sheath and a proposed target for autoimmune attack in MS, has been reported altered in MS CSF. Here, we investigated the potential of CSF sulfatide and its isoforms as biomarkers in MS. A highly sensitive and quantitative mass spectrometry method was employed to determine levels of sulfatide isoforms in CSF from RRMS and progressive MS (PMS) patients, and healthy donors (HD). We demonstrate that levels of total CSF sulfatide and C24:1, C26:1, and C26:1-OH isoforms were significantly increased in PMS compared with RRMS patients and HD, while C23:0-OH was significantly decreased in CSF from PMS patients compared to the other two groups. Multivariate discriminant analysis showed that CSF sulfatide isoform pattern in PMS patients was distinct and non-overlapping with that of RRMS patients and HD. Sulfatide levels did not correlate with tested biomarkers or clinical parameters. The results suggest that CSF sulfatide isoform levels may be used to discriminate the phenotype of MS and might play a role in the progression of the disease.


Asunto(s)
Esclerosis Múltiple Recurrente-Remitente/líquido cefalorraquídeo , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Esclerosis Múltiple/líquido cefalorraquídeo , Esclerosis Múltiple/diagnóstico , Sulfoglicoesfingolípidos/líquido cefalorraquídeo , Adulto , Estudios de Casos y Controles , Citocinas/líquido cefalorraquídeo , Progresión de la Enfermedad , Femenino , Proteína Ácida Fibrilar de la Glía/líquido cefalorraquídeo , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Proteínas de Neurofilamentos/líquido cefalorraquídeo , Análisis de Componente Principal , Isoformas de Proteínas/líquido cefalorraquídeo , Curva ROC , Sulfoglicoesfingolípidos/química , Linfocitos T/metabolismo , Adulto Joven
10.
J Pediatr ; 198: 265-272.e3, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29730147

RESUMEN

OBJECTIVE: To assess olfactory function in children and to create and validate an odor identification test to diagnose olfactory dysfunction in children, which we called the Universal Sniff (U-Sniff) test. STUDY DESIGN: This is a multicenter study involving 19 countries. The U-Sniff test was developed in 3 phases including 1760 children age 5-7 years. Phase 1: identification of potentially recognizable odors; phase 2: selection of odorants for the odor identification test; and phase 3: evaluation of the test and acquisition of normative data. Test-retest reliability was evaluated in a subgroup of children (n = 27), and the test was validated using children with congenital anosmia (n = 14). RESULTS: Twelve odors were familiar to children and, therefore, included in the U-Sniff test. Children scored a mean ± SD of 9.88 ± 1.80 points out of 12. Normative data was obtained and reported for each country. The U-Sniff test demonstrated a high test-retest reliability (r27 = 0.83, P < .001) and enabled discrimination between normosmia and children with congenital anosmia with a sensitivity of 100% and specificity of 86%. CONCLUSIONS: The U-Sniff is a valid and reliable method of testing olfaction in children and can be used internationally.


Asunto(s)
Odorantes , Trastornos del Olfato/congénito , Trastornos del Olfato/diagnóstico , Olfato/fisiología , Niño , Preescolar , Femenino , Humanos , Internacionalidad , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
11.
J Neurochem ; 141(2): 296-304, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-27787906

RESUMEN

Cerebrospinal fluid (CSF) biomarkers can reflect different aspects of the pathophysiology of relapsing-remitting multiple sclerosis (RRMS). Understanding the impact of different disease modifying therapies on the CSF biomarker profile may increase their implementation in clinical practice and their appropriateness for monitoring treatment efficacy. This study investigated the influence of first-line (interferon beta) and second-line (natalizumab) therapies on seven CSF biomarkers in RRMS and their correlation with clinical and radiological outcomes. We included 59 RRMS patients and 39 healthy controls. The concentrations of C-X-C motif chemokine 13 (CXCL13), C-C motif chemokine ligand 2 (CCL2), chitinase-3-like protein 1 (CHI3L1), glial fibrillary acidic protein, neurofilament light protein (NFL), and neurogranin were determined by ELISA, and chitotriosidase (CHIT1) was analyzed by spectrofluorometry. RRMS patients had higher levels of NFL, CXCL13, CHI3L1, and CHIT1 than controls (p < 0.001). Subgroup analysis revealed higher NFL, CXCL13 and CHIT1 levels in patients treated with first-line therapy compared to second-line therapy (p = 0.008, p = 0.001 and p = 0.026, respectively). NFL and CHIT1 levels correlated with relapse status, and NFL and CXCL13 levels correlated with the formation of new magnetic resonance imaging lesions. Furthermore, we found an association between inflammatory and degenerative biomarkers. The results indicate that CSF levels of NFL, CXCL13, CHI3L1, and CHIT1 correlate with the clinical and/or radiological disease activity, providing additional dimensions in the assessment of treatment efficacy.


Asunto(s)
Progresión de la Enfermedad , Esclerosis Múltiple Recurrente-Remitente/líquido cefalorraquídeo , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Natalizumab/uso terapéutico , Adolescente , Adulto , Biomarcadores/líquido cefalorraquídeo , Quimiocina CXCL13/líquido cefalorraquídeo , Femenino , Proteína Ácida Fibrilar de la Glía/líquido cefalorraquídeo , Humanos , Factores Inmunológicos/uso terapéutico , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Proteínas de Neurofilamentos/líquido cefalorraquídeo , Resultado del Tratamiento , Adulto Joven
12.
Ann Neurol ; 79(6): 950-8, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27038238

RESUMEN

OBJECTIVE: Many JC virus antibody-positive relapsing-remitting multiple sclerosis (RRMS) patients who are stable on natalizumab switch to other therapies to avoid progressive multifocal leukoencephalopathy. METHODS: We compared outcomes for all RRMS patients switching from natalizumab due to JC virus antibody positivity at 3 Swedish multiple sclerosis centers with different preferential use of rituximab and fingolimod (Stockholm, n = 156, fingolimod 51%; Gothenburg, n = 64, fingolimod 88%; Umeå, n = 36, fingolimod 19%), yielding a total cohort of N = 256 (fingolimod 55%). RESULTS: Within 1.5 years of cessation of natalizumab, 1.8% (rituximab) and 17.6% (fingolimod) of patients experienced a clinical relapse (hazard ratio for rituximab = 0.10, 95% confidence interval [CI] = 0.02-0.43). The hazard ratio (favoring rituximab) for adverse events (5.3% vs 21.1%) and treatment discontinuation (1.8% vs 28.2%) were 0.25 (95% CI = 0.10-0.59) and 0.07 (95% CI = 0.02-0.30), respectively. Furthermore, contrast-enhancing lesions were found in 1.4% (rituximab) versus 24.2% (fingolimod) of magnetic resonance imaging examinations (odds ratio = 0.05, 95% CI = 0.00-0.22). Differences remained when adjusting for possible confounders (age, sex, disability status, time on natalizumab, washout time, follow-up time, and study center). INTERPRETATION: Our findings suggest an improved effectiveness and tolerability of rituximab compared with fingolimod in stable RRMS patients who switch from natalizumab due to JC virus antibody positivity. Although residual confounding factors cannot be ruled out, the shared reason for switching from natalizumab and the preferential use of either rituximab or fingolimod in 2 of the centers mitigates these concerns. Ann Neurol 2016;79:950-958.


Asunto(s)
Clorhidrato de Fingolimod/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Natalizumab/uso terapéutico , Sistema de Registros , Rituximab/uso terapéutico , Adulto , Anticuerpos/sangre , Femenino , Clorhidrato de Fingolimod/efectos adversos , Humanos , Virus JC/inmunología , Masculino , Persona de Mediana Edad , Recurrencia , Rituximab/efectos adversos , Resultado del Tratamiento , Adulto Joven
13.
Mult Scler ; 23(1): 62-71, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27003946

RESUMEN

BACKGROUND: The disease-modifying therapies (DMTs) in relapsing-remitting multiple sclerosis (RRMS) vary in their mode of action and when therapies are changed, the consequences on inflammatory and degenerative processes are largely unknown. OBJECTIVE: We investigated the effect of switching from other DMTs to fingolimod on cerebrospinal fluid (CSF) biomarkers. METHODS: 43 RRMS patients were followed up after 4-12 months of fingolimod treatment. Concentrations of C-X-C motif chemokine 13 (CXCL13), chemokine (C-C motif) ligand 2 (CCL2), chitinase-3-like protein 1 (CHI3L1), glial fibrillary acidic protein (GFAP), neurofilament light protein (NFL), and neurogranin (NGRN) were analyzed by enzyme-linked immunosorbent assay (ELISA), while chitotriosidase (CHIT1) was analyzed by spectrofluorometry. RESULTS: The levels of NFL, CXCL13, and CHI3L1 decreased ( p < 0.05) after fingolimod treatment. Subgroup analysis revealed a reduction in NFL ( p < 0.001), CXCL13 ( p = 0.001), CHI3L1 ( p < 0.001), and CHIT1 ( p = 0.002) in patients previously treated with first-line therapies. In contrast, the levels of all analyzed biomarkers were essentially unchanged in patients switching from natalizumab. CONCLUSION: We found reduced inflammatory activity (CXCL13, CHI3L1, and CHIT1) and reduced axonal damage (NFL) in patients switching from first-line DMTs to fingolimod. Biomarker levels in patients switching from natalizumab indicate similar effects on inflammatory and degenerative processes. The CSF biomarkers provide an additional measure of treatment efficacy.


Asunto(s)
Clorhidrato de Fingolimod/líquido cefalorraquídeo , Esclerosis Múltiple/líquido cefalorraquídeo , Adulto , Biomarcadores/líquido cefalorraquídeo , Quimiocina CXCL13/líquido cefalorraquídeo , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Clorhidrato de Fingolimod/uso terapéutico , Proteína Ácida Fibrilar de la Glía/líquido cefalorraquídeo , Humanos , Inflamación/líquido cefalorraquídeo , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/tratamiento farmacológico , Proteínas de Neurofilamentos/líquido cefalorraquídeo , Resultado del Tratamiento , Adulto Joven
14.
Arch Sex Behav ; 46(5): 1349-1359, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28155009

RESUMEN

The main aims of this research were to test the similarity of masculinity-femininity in long-term male same-sex couples from the Czech Republic and to examine whether this similarity predicts higher relationship quality. In Study 1, participants (N = 30) and their partners completed the Dyadic Adjustment Scale (DAS) and the Childhood Gender Nonconformity Scale (CGN). In Study 2, participants (N = 40) and their partners completed DAS and the Gender Diagnosticity Scale (GD). Results showed that the partners were no more alike than individuals paired at random in their CGN or GD, but greater similarity in CGN between partners increased Dyadic Cohesion (r = -.41 [-.71, -.02]) and Affectional Expression (r = -.38 [-.60, -.13]). Our results add to previous evidence showing that similarity in same-sex couples increased relationship quality. Although, on average, gay men were not coupled on the basis of homogamy in gender roles, their relationship quality is linked to the gender egalitarian model rather than to the gender stratified one. Thus, a widespread stereotype suggesting that same-sex partners are divided by different gender roles seems to be, at least in our sample from a Western society, rather incorrect.


Asunto(s)
Feminidad , Homosexualidad Masculina/psicología , Masculinidad , Parejas Sexuales/psicología , Adulto , Conducta de Elección , República Checa , Composición Familiar , Femenino , Humanos , Masculino , Satisfacción Personal , Personalidad , Minorías Sexuales y de Género
15.
Perception ; 46(3-4): 484-497, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28056656

RESUMEN

As previously suggested, preferences for kin body odor might undergo an adaptive change over the course of puberty in order to avoid potential inbreeding, resulting in aversion to body odor of the opposite-gender kin as individuals mature sexually. However, studies based on mutual body odor aversion are rather inconclusive. We therefore investigated whether children's reports of individuals smelling good or bad differed as a function of age and pubertal status. We asked 219 children (94 male) aged 10 to 15 years to assess their pubertal development using a standardized measure and to name individuals they thought smelled good or bad. Results of the present study show that the older the girls were, the more likely they were to name males than females among nice-smelling people. Further, in both girls and boys alike, children with higher puberty scores were more likely to name children than adults. Neither in girls nor in boys did we observe any concurrent effect of age or pubertal status on children's reports of persons thought to smell bad. Irrespective of whether these changes are driven by age itself or age-related phenomena, these results suggest a shift toward a more general positive attitude to peers rather than active kin avoidance.


Asunto(s)
Envejecimiento/psicología , Odorantes , Percepción Olfatoria , Maduración Sexual , Adolescente , Constitución Corporal , Niño , Femenino , Humanos , Masculino
16.
Mult Scler ; 22(12): 1587-1595, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-26754805

RESUMEN

BACKGROUND: Microglia-mediated proteolysis of the triggering receptor expressed on myeloid cells-2 (TREM-2) produces soluble TREM-2 (sTREM-2) that can be measured in cerebrospinal fluid (CSF) samples. Loss-of-function mutations in TREM2 or in the gene encoding its adaptor protein cause the rare Nasu-Hakola disease (NHD). Multiple sclerosis (MS) is an autoimmune disease that in common with NHD is characterized by demyelination and microglial activation. OBJECTIVE: To investigate the potential utility of sTREM-2 as a biomarker for MS and to follow treatment effects. METHODS: sTREM-2 was analyzed in CSF samples from subjects with MS (N = 59); relapsing-remitting MS (RRMS) (N = 36), secondary progressive MS (SPMS) (N = 20) and primary progressive MS (PPMS) (N = 3), and controls (N = 27). CSF levels of sTREM-2 were also assessed before and after treatment of patients with natalizumab or mitoxantrone. RESULTS: CSF levels of sTREM-2 were significantly increased in patients with RRMS, SPMS, and PPMS compared with controls. After natalizumab treatment, the levels of sTREM-2 were normalized to control levels. The levels of sTREM-2 were also reduced after mitoxantrone treatment. CONCLUSION: Increased CSF levels of sTREM-2, a new marker of microglial activation, in MS and normalization upon treatment with either natalizumab or mitoxantrone support a role for microglial activation in active MS.


Asunto(s)
Factores Inmunológicos/farmacología , Glicoproteínas de Membrana/líquido cefalorraquídeo , Glicoproteínas de Membrana/efectos de los fármacos , Mitoxantrona/farmacología , Esclerosis Múltiple Crónica Progresiva/líquido cefalorraquídeo , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/líquido cefalorraquídeo , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Natalizumab/farmacología , Receptores Inmunológicos/efectos de los fármacos , Inhibidores de Topoisomerasa II/farmacología , Adulto , Biomarcadores/líquido cefalorraquídeo , Femenino , Estudios de Seguimiento , Humanos , Factores Inmunológicos/administración & dosificación , Masculino , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Natalizumab/administración & dosificación , Inhibidores de Topoisomerasa II/administración & dosificación
17.
Parasitology ; 143(9): 1193-203, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27350331

RESUMEN

Sex of the fetus is genetically determined such that an equal number of sons and daughters are born in large populations. However, the ratio of female to male births across human populations varies significantly. Many factors have been implicated in this. The theory that natural selection should favour female offspring under suboptimal environmental conditions implies that pathogens may affect secondary sex ratio (ratio of male to female births). Using regression models containing 13 potential confounding factors, we have found that variation of the secondary sex ratio can be predicted by seroprevalence of Toxoplasma across 94 populations distributed across African, American, Asian and European continents. Toxoplasma seroprevalence was the third strongest predictor of secondary sex ratio, ß = -0·097, P < 0·01, after son preference, ß = 0·261, P < 0·05, and fertility, ß = -0·145, P < 0·001. Our preliminary results suggest that Toxoplasma gondii infection could be one of the most important environmental factors influencing the global variation of offspring sex ratio in humans. The effect of latent toxoplasmosis on public health could be much more serious than it is usually supposed to be.


Asunto(s)
Razón de Masculinidad , Toxoplasmosis/epidemiología , Clima , Factores de Confusión Epidemiológicos , Ingestión de Energía , Femenino , Fertilidad , Salud Global , Estado de Salud , Humanos , Renta , Masculino , Matrimonio/estadística & datos numéricos , Prevalencia , Análisis de Regresión , Factores Socioeconómicos , Toxoplasmosis/fisiopatología , Adulto Joven
18.
Aging Clin Exp Res ; 28(2): 239-47, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26231091

RESUMEN

BACKGROUND: The aim of this study was to describe an instrumental activities of daily living (IADL) measure: Functional Activities Questionnaire (FAQ), which is often used in clinical settings as a self- or informant-based measure of IADL. However, the FAQ's relationship with age or education in healthy aging has not been investigated. METHODS: FAQ and a neuropsychological battery were administered to old and very old Czech adults (n = 540). Participants met strict inclusion criteria for the absence of any active or past neurodegenerative disorders. RESULTS: FAQ is significantly dependent on age and education, but not gender. Younger subjects and those with higher education have the lowest scores in the FAQ and show a higher degree of functional independence. FAQ moderately correlates with speed of processing, visual-perceptual and executive functions measures (Trail Making Tests, Stroop Test) and depressive symptoms, but not with episodic memory (WMS-III logical memory). We present normative percentile values for different age groups from 60 to 96 years of age. CONCLUSIONS: The present study shows conclusively that IADL measures, such as FAQ, should not be used without appropriate normative data, especially in very old adults. Thus, it has the ability to differentiate functional dependence due to age-related decline from neurodegenerative disease.


Asunto(s)
Envejecimiento , Función Ejecutiva , Destreza Motora , Desempeño Psicomotor , Percepción Visual , Actividades Cotidianas , Factores de Edad , Anciano , Anciano de 80 o más Años , Envejecimiento/fisiología , Envejecimiento/psicología , República Checa , Depresión , Escolaridad , Femenino , Humanos , Masculino , Memoria Episódica , Persona de Mediana Edad , Pruebas Neuropsicológicas , Valores de Referencia , Encuestas y Cuestionarios
20.
Sci Rep ; 14(1): 10369, 2024 05 06.
Artículo en Inglés | MEDLINE | ID: mdl-38710748

RESUMEN

Emotions experienced within sleep mentation (dreaming) affect mental functioning in waking life. There have been attempts at enhancing dream emotions using olfactory stimulation. Odors readily acquire affective value, but to profoundly influence emotional processing, they should bear personal significance for the perceiver rather than be generally pleasant. The main objective of the present sleep laboratory study was to examine whether prolonged nocturnal exposure to self-selected, preferred ambient room odor while asleep influences emotional aspects of sleep mentation and valence of post-sleep core affect. We asked twenty healthy participants (12 males, mean age 25 ± 4 years) to pick a commercially available scented room diffuser cartridge that most readily evoked positively valenced mental associations. In weekly intervals, the participants attended three sessions. After the adaptation visit, they were administered the odor exposure and odorless control condition in a balanced order. Participants were awakened five minutes into the first rapid eye movement (REM) stage that took place after 2:30 a.m. and, if they had been dreaming, they were asked to rate their mental sleep experience for pleasantness, emotional charge, and magnitude of positive and negative emotions and also to evaluate their post-sleep core affect valence. With rs < 0.20, no practically or statistically significant differences existed between exposure and control in any outcome measures. We conclude that in young, healthy participants, the practical value of olfactory stimulation with self-selected preferred scents for enhancement of dream emotions and post-sleep core affect valence is very limited.


Asunto(s)
Sueños , Emociones , Odorantes , Humanos , Masculino , Adulto , Femenino , Sueños/fisiología , Sueños/psicología , Adulto Joven , Emociones/fisiología , Sueño/fisiología , Olfato/fisiología , Sueño REM/fisiología , Vigilia/fisiología
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