Continued dysregulation of the B cell lineage promotes multiple sclerosis activity despite disease modifying therapies.

A clear understanding of the origin and role of the different subtypes of the B cell lineage involved in the activity or remission of multiple sclerosis (MS) is important for the treatment and follow-up of patients living with this disease. B cells, however, are dynamic and can play an anti-inflammatory or pro-inflammatory role, depending on their milieu. Depletion of B cells has been effective in controlling the progression of MS, but it can have adverse side effects. A better understanding of the role of the B cell subtypes, through the use of surface biomarkers of cellular activity with special attention to the function of memory and other regulatory B cells (Bregs), will be necessary in order to offer specific treatments without inducing undesirable effects.

Efectividad de las intervenciones estructurales para la promoción del uso del preservativo en adolescentes y jóvenes: revisión sistemática / Effectiveness of structural interventions to promote condom use in adolescents and young people: Systematic Review

RESUMEN Objetivo Evaluar la efectividad de las intervenciones de tipo estructural o multicomponente dirigidas al incremento del uso del preservativo en adolescentes y jóvenes, identificar las estrategias que conforman las intervenciones evaluadas y reconocer los modelos teóricos que sustentan dichas intervenciones. Metodología Diseño: revisión sistemática de la literatura. Fuente de datos: se consultaron las bases de datos MEDLINE vía OVID, Embase y CENTRAL para buscar estudios sobre intervenciones dirigidas al incremento del uso del preservativo en adolescentes y jóvenes. Selección de estudios: se seleccionaron un total de 7 investigaciones primarias donde se evaluaba el efecto de una intervención estructural o multicomponente para incrementar el uso del preservativo en adolescentes y jóvenes. La calidad de los estudios fue evaluada usando la herramienta para valoración de riesgo de sesgos de Cochrane. Resultados Cinco investigaciones mostraron cambios en los porcentajes del uso del preservativo con valores entre 53 % y el 68 %. Las intervenciones planteadas orientaban sus acciones más a nivel individual con estrategias como: educación sobre salud sexual, consejería en salud reproductiva, conocimientos acerca del preservativo, conocimientos acerca de las ITS/VIH. A nivel organizacional y del entorno iban dirigidas a la provisión de preservativos. Los modelos teóricos planteados en los estudios están centrados en la conducta humana, comportamiento del individuo y el aprendizaje social. Discusión Las intervenciones de tipo estructural que tienen como fin el incremento del uso del preservativo en adolescentes y jóvenes parecen mostrar cambios significativos a nivel individual, pero se desconocen los posibles cambios generados a nivel de la organización y del entorno.(AU)

ABSTRACT Objective Evaluate the effectiveness of structural or multicomponent interventions aimed at increasing the use of condoms in adolescents and young adults, identifying the strategies that form the interventions evaluated, and recognizing the theoretical models that support these interventions. Methodology Design: Systematic review of literature. Data source: MEDLINE databases were consulted via OVID, Embase, and CENTRAL in order to search for studies on interventions aimed at increasing the use of condoms in adolescents and young adults. Selection of studies: A total of 7 primary investigations were selected, in which the effect of a structured or multicomponent intervention to increase the use of condoms in adolescents and young adults was evaluated. The quality of the studies was evaluated using the Cochrane bias risk assessment. Results Five investigations show changes in the percentages of condom use with values between 53% and 68%. The interventions targeted guided their actions more at individual level with strategies such as sexual health education, reproductive health counseling, knowledge about the condom, knowledge about STIs / HIV, than at organizational and environ-mental levels, which were aimed at the provision of condoms. The theoretical models proposed in the studies are focused on human behavior, individual behavior, and social learning. Conclusion Structural interventions that aim to increase the use of condoms in adolescents and young adults seem to show significant changes at individual level, but possible changes generated at both organization and environment levels are unknown.(AU)

[Effectiveness of structural interventions to promote condom use in adolescents and young people: Systematic Review]. / Efectividad de las intervenciones estructurales para la promoción del uso del preservativo en adolescentes y jóvenes: revisión sistemática.

OBJECTIVE: Evaluate the effectiveness of structural or multicomponent interventions aimed at increasing the use of condoms in adolescents and young adults, identifying the strategies that form the interventions evaluated, and recognizing the theoretical models that support these interventions. METHODOLOGY: Design: Systematic review of literature. Data source: MEDLINE databases were consulted via OVID, Embase, and CENTRAL in order to search for studies on interventions aimed at increasing the use of condoms in adolescents and young adults. Selection of studies: A total of 7 primary investigations were selected, in which the effect of a structured or multicomponent intervention to increase the use of condoms in adolescents and young adults was evaluated. The quality of the studies was evaluated using the Cochrane bias risk assessment. RESULTS: Five investigations show changes in the percentages of condom use with values between 53% and 68%. The interventions targeted guided their actions more at individual level with strategies such as sexual health education, reproductive health counseling, knowledge about the condom, knowledge about STIs / HIV, than at organizational and environ-mental levels, which were aimed at the provision of condoms. The theoretical models proposed in the studies are focused on human behavior, individual behavior, and social learning. CONCLUSION: Structural interventions that aim to increase the use of condoms in adolescents and young adults seem to show significant changes at individual level, but possible changes generated at both organization and environment levels are unknown.

OBJETIVO: Evaluar la efectividad de las intervenciones de tipo estructural o multicomponente dirigidas al incremento del uso del preservativo en adolescentes y jóvenes, identificar las estrategias que conforman las intervenciones evaluadas y reconocer los modelos teóricos que sustentan dichas intervenciones. METODOLOGÍA: Diseño: revisión sistemática de la literatura. Fuente de datos: se consultaron las bases de datos MEDLINE vía OVID, Embase y CENTRAL para buscar estudios sobre intervenciones dirigidas al incremento del uso del preservativo en adolescentes y jóvenes. Selección de estudios: se seleccionaron un total de 7 investigaciones primarias donde se evaluaba el efecto de una intervención estructural o multicomponente para incrementar el uso del preservativo en adolescentes y jóvenes. La calidad de los estudios fue evaluada usando la herramienta para valoración de riesgo de sesgos de Cochrane. RESULTADOS: Cinco investigaciones mostraron cambios en los porcentajes del uso del preservativo con valores entre 53 % y el 68 %. Las intervenciones planteadas orientaban sus acciones más a nivel individual con estrategias como: educación sobre salud sexual, consejería en salud reproductiva, conocimientos acerca del preservativo, conocimientos acerca de las ITS/VIH. A nivel organizacional y del entorno iban dirigidas a la provisión de preservativos. Los modelos teóricos planteados en los estudios están centrados en la conducta humana, comportamiento del individuo y el aprendizaje social. DISCUSIÓN: Las intervenciones de tipo estructural que tienen como fin el incremento del uso del preservativo en adolescentes y jóvenes parecen mostrar cambios significativos a nivel individual, pero se desconocen los posibles cambios generados a nivel de la organización y del entorno.

Role of CXCL13 in the formation of the meningeal tertiary lymphoid organ in multiple sclerosis.

Immunomodulatory therapies available for the treatment of patients with multiple sclerosis (MS) accomplish control and neutralization of peripheral immune cells involved in the activity of the disease cascade but their spectrum of action in the intrathecal space and brain tissue is limited, taking into consideration the persistence of oligoclonal bands and the variation of clones of lymphoid cells throughout the disease span. In animal models of experimental autoimmune encephalomyelitis (EAE), the presence of CXCL13 has been associated with disease activity and the blockade of this chemokine could work as a potential complementary therapeutic strategy in patients with MS in order to postpone disease progression. The development of therapeutic alternatives with ability to modify the intrathecal inflammatory activity of the meningeal tertiary lymphoid organ to ameliorate neurodegeneration is mandatory.

Factores asociados con la adherencia a la actividad física en pacientes con enfermedades crónicas no transmisibles / Factors associated with adherence to physical activity in patients with chronic non-communicable diseases

RESUMEN Objetivo Determinar los factores asociados a la adherencia a la actividad física en pacientes con enfermedades crónicas no transmisibles ECNT en la red de salud Ladera del municipio de Santiago de Cali. Métodos Se realizó un estudio de casos y controles con 268 adultos con diagnóstico de Diabetes o Hipertensión u obesidad, 134 casos y 134 controles de la red de salud E.S.E Ladera. Para el análisis univariado se realiza análisis de frecuencias y estadística descriptiva. En el análisis bivariado se aplican pruebas de Chi-cuadrado y t de Student, ambas con un IC del 95%, para el análisis Multivariado se realizó regresión logística binaria y se estimó la razón de probabilidad a través del Odds Ratio (OR). Resultados Factores con OR<1: la autopercepción del estado de salud, espacios adecuados para la actividad física, autocuidado de la salud, periodicidad de actividad, demostraron ser facilitadores para la adherencia a la actividad física. Los factores con OR>1: estar solo durante el día, haber dejado de realizar ejercicio físico, considerar el ejercicio físico poco importante, espacios inseguros, falta de prescripción del ejercicio, fueron barreras para la adherencia a la actividad física. Conclusiones Percibirse con buena calidad de vida, tener la actividad física programada por el sistema de salud y ambientes adecuados y seguros, facilitan la adherencia, mientras no pertenecer a un grupo familiar, no considerar la prescripción a la actividad física importante y estar en zonas inseguras, limitan la adherencia.(AU)

ABSTRACT Objective To determine the factors associated with adherence to physical activity in patients with chronic non-communicable diseases (CND) in the Ladera health network of the municipality of Santiago de Cali. Methods A case-control study was conducted with 268 adults diagnosed with diabetes, high blood pressure or obesity, 134 cases and 134 controls, treated at the Empresa Social del Estado (E.S.E) Ladera healthcare network. Univariate analysis included frequency analysis and descriptive statistics. Chi-square and t Student tests were applied for bivariate analysis, both with a 95% CI; binary logistic regression was performed for the multivariate analysis and probability was estimated using the Odds Ratio (OR). Results Factors with OR<1 -self-perception of physical condition, appropriate spaces for physical activity, self-care, and frequency of activity- promote adherence to physical activity. Factors with OR>1 -being alone during the day, having stopped doing physical exercise, considering physical exercise as unimportant, unsafe spaces, and lack of indication of exercise- were barriers to adherence to physical activity. Conclusions Perceiving oneself with good quality of life and having a physical activity prescription by the healthcare system, as well as adequate and safe environments, promote adherence. On the other hand, not belonging to a family group, considering physical activity prescription as unimportant and being in unsafe areas, hinder adherence.(AU)

[Factors associated with adherence to physical activity in patients with chronic non-communicable diseases]. / Factores asociados con la adherencia a la actividad física en pacientes con enfermedades crónicas no transmisibles.

OBJECTIVE: To determine the factors associated with adherence to physical activity in patients with chronic non-communicable diseases (CND) in the Ladera health network of the municipality of Santiago de Cali. METHODS: A case-control study was conducted with 268 adults diagnosed with diabetes, high blood pressure or obesity, 134 cases and 134 controls, treated at the Empresa Social del Estado (E.S.E) Ladera healthcare network. Univariate analysis included frequency analysis and descriptive statistics. Chi-square and t Student tests were applied for bivariate analysis, both with a 95% CI; binary logistic regression was performed for the multivariate analysis and probability was estimated using the Odds Ratio (OR). RESULTS: Factors with OR<1 -self-perception of physical condition, appropriate spaces for physical activity, self-care, and frequency of activity- promote adherence to physical activity. Factors with OR>1 -being alone during the day, having stopped doing physical exercise, considering physical exercise as unimportant, unsafe spaces, and lack of indication of exercise- were barriers to adherence to physical activity. CONCLUSIONS: Perceiving oneself with good quality of life and having a physical activity prescription by the healthcare system, as well as adequate and safe environments, promote adherence. On the other hand, not belonging to a family group, considering physical activity prescription as unimportant and being in unsafe areas, hinder adherence.

OBJETIVO: Determinar los factores asociados a la adherencia a la actividad física en pacientes con enfermedades crónicas no transmisibles ECNT en la red de salud Ladera del municipio de Santiago de Cali. MÉTODOS: Se realizó un estudio de casos y controles con 268 adultos con diagnóstico de Diabetes o Hipertensión u obesidad, 134 casos y 134 controles de la red de salud E.S.E Ladera. Para el análisis univariado se realiza análisis de frecuencias y estadística descriptiva. En el análisis bivariado se aplican pruebas de Chi-cuadrado y t de Student, ambas con un IC del 95%, para el análisis Multivariado se realizó regresión logística binaria y se estimó la razón de probabilidad a través del Odds Ratio (OR). RESULTADOS: Factores con OR<1: la autopercepción del estado de salud, espacios adecuados para la actividad física, autocuidado de la salud, periodicidad de actividad, demostraron ser facilitadores para la adherencia a la actividad física. Los factores con OR>1: estar solo durante el día, haber dejado de realizar ejercicio físico, considerar el ejercicio físico poco importante, espacios inseguros, falta de prescripción del ejercicio, fueron barreras para la adherencia a la actividad física. CONCLUSIONES: Percibirse con buena calidad de vida, tener la actividad física programada por el sistema de salud y ambientes adecuados y seguros, facilitan la adherencia, mientras no pertenecer a un grupo familiar, no considerar la prescripción a la actividad física importante y estar en zonas inseguras, limitan la adherencia.

Evidence of disease control: a realistic concept beyond NEDA in the treatment of multiple sclerosis.

Although no evidence of disease activity (NEDA) permits evaluation of response to treatment in the systematic follow-up of patients with multiple sclerosis (MS), its ability to accomplish detection of surreptitious activity of disease is limited, thus being unable to prevent patients from falling into a non-reversible progressive phase of disease. A protocol of evaluation based on the use of validated biomarkers that is conducted at an early stage of disease would permit the capture of abnormal neuroimmunological phenomena and lead towards intervention with modifying therapy before tissue damage has been reached.

Autologous Bone Marrow Transplantation in Multiple Sclerosis: Biomarker Relevance for Patient Recruitment and Follow up.

BACKGROUND: Despite the current availability of disease modifying therapies for the treatment of multiple sclerosis, there are still patients who suffer from severe neurological dysfunction in the relapsing-remitting or early progressive forms of the disease. For these patients autologous hematopoietic stem cell transplant offers an important therapeutic solution to prevent progression to irreversible disability. In spite of multiple studies in the last two decades, patient inclusion criteria, protocols for peripheral blood stem cell mobilization and bone marrow cell conditioning and methodology of follow up for autologous hematopoietic stem cell transplant in multiple sclerosis have not been strictly unified. METHODS: We reviewed five recent clinical studies that confirmed the positive outcome of transplant in spite of disclosing significant differences in methodology of enrollment including patient disease subtypes, disease duration range, disability, regimens of peripheral blood stem cell mobilization and bone marrow cell conditioning, scheduling of imaging studies after transplant, and absence of laboratory biomarkers consistently applied to these studies. RESULTS: Therapy with autologous hematopoietic stem cell transplant has shown best results among young individuals with severe relapsing-remitting or early progressive disease through its ability to maintain no evidence of disease activity status in a significantly higher proportion of patients after transplant in comparison to patients treated with disease modifying therapies. Important cross-sectional differences in the reviewed studies were found. CONCLUSION: A specific and careful selection of biomarkers, based on the current physiopathological mechanisms known to result in multiple sclerosis, will contribute to a better and earlier patient selection for autologous hematopoietic stem cell transplant and follow up process. An objective and measurable response could be obtained with the determination of biomarkers at the onset of treatment and after follow-up on reconstitution of the immune response. The application of such parameters could also help further our understanding of pathogenesis of the disease.

Identification of novel membrane structures in Plasmodium falciparum infected erythrocytes

Little is known about the molecular mechanisms underlying the release of merozoites from malaria infected erythrocytes. In this study membranous structures present in the culture medium at the time of merozoite release have been characterized. Biochemical and ultrastructural evidence indicate that membranous structures consist of the infected erythrocytes membrane, the parasitophorous vacuolar membrane and the residual body containing electron dense material. These are subcellular compartments expected in a structure that arises as a consequence of merozoite release from the infected cell. Ultrastrutural studies show that a novel structure extends from the former parasite compartment to the membrane. Since these membrane modifications are detected only after merozoites have been released from the infected erythrocyte, it is proposed that they might play a role in the release of merozoites from the host cell.

Anterior horn cell degeneration in polymyositis associated with human T lymphotropic virus Type-1 in patients from Barbados

Anterior horn cell degeneration has only ocassionally been noted in patients with tropical spastic paraparesis associated with human T lymphotropic virus type-1 (HTLV-1) infection. We report on three adult patients with HTLV-1-associated polymyositis who had clinical evidence of anterior horn cell degeneration. One patient had moderate proximal weakness and muscle wasting in all four limbs, while two had mild upper limb weakness with more profound proximal weakness and wasting in the lower limbs. In all three patients, elctromyographic findings were compatible with motor unit loss and muscle biopsies showed mononuclear inflammatory cell infiltration; muscle cell biopsies in two patients showed features of denervation. Immunoglobulin G (IgG) antibodies to HTLV-1 were detected by enzyme-linked immunosorbent assay (ELISA) and confirmed by Western immunoblot in serum and cerobrospinal fluid in all three patients. In two, cell cultures were established from peripheral blood lymphocytes and HTLV-1 antigen was identified by immunofluorescence and the ELISA antigen-capture technique using an anti-p19 HTLV-1 mouse monoclonal antibody. The three cases illustrate the variety of neuromuscular disease, other than spastic paraparesis, that may occur in HTLV-1 infection. In some cases of HTLV-1-associated polymyositis, anterior horn cell degeneration may make a significant contribution to the muscle atrophy observed. (AU)

Identification of human T-cell leukemia/lymphoma virus type I antibodies, DNA, and protein in patients with polymyositis

OBJECTIVE: To investigate a possible association between human T cell leukemia/lymphoma virus type I (HTLV-I) and polymyositis (PM). METHODS: Sera and muscle biopsy samples from 9 Jamaican PM patients were compared with specimens from American HTLV-I positive PM patients and normal controls. Sera were evaluated for HTLV antibodies by enzyme-linked immunosorbent assay and Western blot. The biopsy samples were analyzed for HTLV-I/II DNA by polymerase chain reaction and were also immunohistochemically stained for HTLV gp46 envelope protein. RESULTS: Seven of the 8 Jamaican PM patients from whom sera were available were HTLV-I seropositive. The muscle biopsies of all 9 Jamaican patients demonstrated severe lymphocytic infiltration, cellular degeneration, myofiber atrophy, and fibrosis. Each muscle biopsy specimen contained HTLV-I DNA. Two of 6 samples demonstrated intense staining for HTLV-I gp46 in many of the invading mononuclear cells and weak staining for HTLV-I gp46 in many of the other specimens were weakly positive for gp46 in rare mononuclear cells. All controls specimens were negative for the presence of HTLV-I DNA and protein. CONClUSION: HTLV-I is associated with an inflammatory muscle disease characterized by direct invasion of the affected muscle by HTLV-I-infected mononuclear cells.(AU)

Anterior horn cell degeneration in HTLV-1 associated polymyositis in patients from Barbados - abstract

Anterior horn cell degeneration has only been noted occasionally in patients with tropical spastic paraparesis associated with human T-lymphotropic virus type I infection (HTLV-I). We report on three adult patients with HTLV-I associated polymyositis who had evidence of anterior horn cell degeneration. One patient had moderate proximal weakness in all 4 limbs, while 2 had mild upper limb weakness and profound proximal weakness in the lower limbs. Electromyographic findings indicated motor unit loss. Muscle biopsies in 2 patients showed features of denervation, as well as mono-nuclear inflammatory cell infiltration. HTLV-1 IgG antibodies were detected by enzyme-linked immunosorbent assay, and confirmed by Western-immunoblot, in serum and cerebrospinal fluid in all 3 patients. In two, cell cultures were established from peripheral blood lymphocytes and HTLV-1 antigen was identified by immunofluorescence and the ELISA antigen capture technique, using an anti-p 19 HTLV-1 mouse monoclonal antibody. These 3 cases illustrate the variety of neuromuscular disease, other than spastic paraparesis, that may occur in HTLV-1 infection. Anterior horn cell degeneration may coexist with HTLV-1 associated polymyositis and may make a significant contribution to the muscle atrophy observed in these cases (AU)

HTLV-I and polymyositis in Jamaica

1gG antibodies to human T-cell ilymphotropic virus (HTLV-1) were found in 11 of 13 (85 percent) Jamaican patients with idiopathic adult patients with polymyositis. The association was first observed in 7 patients with polymyositis who were included in a control group of 100 patiants with neurological and neuromusclar diseasee in a serological investigation of the prevalence of HTLV-1 antibody in patients with tropical spastic paraparesis. All 7 patients with polymyositis were positive for the antibody by an enzyme-linked immunosorbent assay, confirmed by western blot. Because of this striking association a further 6 patients with polymyositis were identified and tested, 4 of whom were also seropositive for HTLV-1 antibody. (AU)

Isolation and characterization of HTLV-I from symptomatic family members with tropical spastic paraparesis (HTLV-I encephalomyeloneuropathy)

Human T lymphotropic virus type I (HTLV-I) was isolated from peripheral blood- and cerebrospinal fluid-derived mononuclear cells of a 13-y-old boy and from the peripheral blood lymphocytes of both his parents. All three had IgG antibodies to HTLV-I and varying degrees of the clinical features of tropical spastic paraparesis (TSP). The son also had IgG antibodies specific for HTLV-I in his serum. Isolations were successfully made from peripheral blood lymphocytes and cerebrospinal fluid lymphocytes stimulated with interleukin-2 or cocultivated with umbilical cord blood mononuclear cells. Established cell lines contained HTLV-I antigen by immunfluorescence and cell-associated virus by electron microscopy; cells became transformed in vitro as determined by their continuous growth in the absence of exogenous interleukin-2. This boy is the youngest TSP patient known to be reported, and the isolation of HTLV-I from all three family members suggests the causative role of this virus in TSP. (AU)

Comparison of a human T-cell lymphotropic virus type I strain from cerebrospinal fluid of a Jamaican patient with tropical spastic paraparesis with a prototype human T-cell lymphotropic virus type I

The isolation and characterization of a human T-cell lymphotrophic virus type I (HTLV-I) from cerebrospinal fluid of a Jamaican patient with tropical spastic paraparesis is described. The virus isolate is a typical type C retrovirus as seen by electron microscopy and is related to prototype HTLV-I isolated from patients with adult T-cell leukemia but is not identical to this prototype HTLV-I as seen by restriction enzyme mapping.(AU)

Pathological and immunological observations on tropical spastic paraparesis in patients from Jamaica

The neuropathological examination of the spinal cord of 2 Jamaican patients with classical tropical spastic paraparesis disclosed an intense chronic meningomyelitis with demyelination. In the 1 case in which serum and cerebrospnal fluid were available, antibodies to the human T-lymphotropic virus type 1 were found. (AU)