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Resumen: Objetivos: Estudiar la eficacia de la terapia manual en el tratamiento de la cefalea tensional (CT) valorando los estudios controlados aleatorizados (ECA) publicados desde el año 2000 hasta abril del 2013. Métodos: Se realizó la búsqueda en las bases de datos MEDLINE, EBSCO, CINAHL, SCOPUS, PEDRO y OVID. Se incluyeron ECA que analizasen a pacientes con CT tratados con terapia manual y que recogiesen como variable de resultado la intensidad, frecuencia, duración del dolor de cabeza. La calidad metodológica fue valorada por 2 revisores independientes mediante la escala Jadad. Los datos de los ECA fueron extraídos por 2 revisores. Resultados: Se seleccionaron 14 ECA. Doce de ellos se consideraron de calidad aceptable (Jadad ≥ 3) y 2 de baja (Jadad = 2). Los estudios mostraron resultados positivos obteniendo disminución de la intensidad y/o frecuencia de cefaleas, reducción del consumo de medicamentos y mejora de la calidad de vida en pacientes con CT. Conclusiones: Debido a la heterogeneidad en diseños, instrumentos de medida y tratamientos de los estudios, no es posible obtener conclusiones definitivas sobre la eficacia de la terapia manual en pacientes con CT aunque se aprecien efectos beneficiosos. No obstante, el análisis de los estudios indica que, al recibir tratamiento con terapia manual, los pacientes con CT evolucionaron de forma más favorable respecto a aquellos que recibieron tratamiento habitual o un tratamiento placebo. Se requiere un mayor número de estudios con mayor calidad metodológica, así como mayor homogeneidad de los tratamientos y de los métodos de valoración de los resultados, para determinar la eficacia de la terapia manual en la CT. Abstract: Objectives: To study the efficacy of manual therapy in the treatment of tension-type headache (TTH) by assessing the quality of randomized control trials (RCTs) published from the year 2000 to April 2013. Methods: A search was performed in the following databases: MEDLINE, EBSCO, CINAHL, SCOPUS, PEDRO and OVID. An analysis was made of RCT including patients with TTH receiving any manual therapy, and assessing outcome measures including the intensity, and frequency or duration of the headache. Two independent referees reviewed the methodological quality of RCTs using the Jadad scale. Data from the studies were extracted by two different reviewers. Results: A total of fourteen RCTs were selected. Twelve studies showed acceptable quality (Jadad scale ≥3), and the remaining 2 had low quality (Jadad = 2). The studies showed positive results, including reduction in headache intensity and/or frequency, reduction of medication consumption, and improvement in quality of life. Conclusions: The effectiveness of manual therapy for TTH cannot be completely assessed due to the heterogeneity in study design, outcome measures, and different treatments. Nevertheless, the results suggest patients with TTH receiving manual therapies showed better progress than those receiving conventional treatment or placebo. Further studies of high quality using manual therapy protocols, and also including standardized outcome measures, are now needed to clarify the efficacy of manual therapy in the management of TTH. Palabras clave: Cefalea tensional, Fisioterapia, Terapia manual, Keywords: Tension-type headache, Physical therapy, Manual therapy

Objectives: To study the efficacy of manual therapy in the treatment of tension-type headache (TTH) by assessing the quality of randomised control trials (RCTs) published from the year 2000 to April 2013. Methods: A search was performed in the following databases: MEDLINE, EBSCO, CINAHL, SCOPUS, PEDRO and OVID. An analysis was made of RCT including patients with TTH receiving any manual therapy, and assessing outcome measures including the intensity, and frequency or duration of the headache. Two independent referees reviewed the methodological quality of RCTs using the Jadad scale. Data from the studies were extracted by two different reviewers. Results: A total of fourteen RCTs were selected. Twelve studies showed acceptable quality (Jadad scale ≥3), and the remaining 2 had low quality (Jadad = 2). The studies showed positive results, including reduction in headache intensity and/or frequency, reduction of medication consumption, and improvement in quality of life. Conclusions: The effectiveness of manual therapy for TTH cannot be completely assessed due to the heterogeneity in study design, outcome measures, and different treatments. Nevertheless, the results suggest patients with TTH receiving manual therapies showed better progress than those receiving conventional treatment or placebo. Further studies of high quality using manual therapy protocols, and also including standardised outcome measures, are now needed to clarify the efficacy of manual therapy in the management of TTH. Resumen: Objetivos: Estudiar la eficacia de la terapia manual en el tratamiento de la cefalea tensional (CT) valorando los estudios controlados aleatorizados (ECA) publicados desde el año 2000 hasta abril del 2013. Métodos: Se realizó la búsqueda en las bases de datos MEDLINE, EBSCO, CINAHL, SCOPUS, PEDRO y OVID. Se incluyeron ECA que analizasen a pacientes con CT tratados con terapia manual y que recogiesen como variable de resultado la intensidad, frecuencia, duración del dolor de cabeza. La calidad metodológica fue valorada por 2 revisores independientes mediante la escala Jadad. Los datos de los ECA fueron extraídos por 2 revisores. Resultados: Se seleccionaron 14 ECA. Doce de ellos se consideraron de calidad aceptable (Jadad ≥ 3) y 2 de baja (Jadad = 2). Los estudios mostraron resultados positivos obteniendo disminución de la intensidad y/o frecuencia de cefaleas, reducción del consumo de medicamentos y mejora de la calidad de vida en pacientes con CT. Conclusiones: Debido a la heterogeneidad en diseños, instrumentos de medida y tratamientos de los estudios, no es posible obtener conclusiones definitivas sobre la eficacia de la terapia manual en pacientes con CT aunque se aprecien efectos beneficiosos. No obstante, el análisis de los estudios indica que, al recibir tratamiento con terapia manual, los pacientes con CT evolucionaron de forma más favorable respecto a aquellos que recibieron tratamiento habitual o un tratamiento placebo. Se requiere un mayor número de estudios con mayor calidad metodológica, así como mayor homogeneidad de los tratamientos y de los métodos de valoración de los resultados, para determinar la eficacia de la terapia manual en la CT. Keywords: Tension-type headache, Physical therapy, Manual therapy, Palabras clave: Cefalea tensional, Fisioterapia, Terapia manual

Objective: The main aim of this systematic review is to evaluate the effectiveness of therapeutic exercise for managing pain and disability in patients with cervicogenic headache (CEH)., Methods: A protocol for this systematic review was published in PROSPERO (CRD42019122703). PRISMA and AMSTAR2 standards were followed. Based on an extensive systematic search in five databases (EMBASE, MEDLINE, CINHAL, PsychInfo and SportDISCUS) and the CENTRAL trial register, two reviewers carefully and independently assessed, selected results, collected data, rated the risk of bias (RoB) of included studies with the Cochrane risk of bias tool, synthesized the available evidence, and rated it using GRADE methodology., Results: A total of 12 manuscripts, reporting on 11 studies were included. Most studies showed a high risk of bias (63,63%). Additionally, a great deal of heterogeneity was observed regarding interventions, comparisons, and outcomes and thus, results could not be synthesized in meta-analyses. The quality of the evidence was found to be from low to very low. Significant differences with large effect sizes were found when comparing multimodal exercise vs. control groups on headache outcomes (SMD = 0.73; 95%CI [0.31, 1.14] for headache intensity and SMD = 0.98; 95%CI [0.56, 1.41], for headache frequency)., Conclusions: Findings indicate that therapeutic exercise may be effective to achieve clinically relevant reductions in headache intensity and frequency as well as disability for patients suffering from cervicogenic headache. However, more high-quality research is needed to gain confidence in this finding and possibly determine optimal types and dosage of therapeutic exercise., Competing Interests: Declaration of competing interest No conflicts of interest have been found either., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: To study the efficacy of manual therapy in the treatment of tension-type headache (TTH) by assessing the quality of randomized control trials (RCTs) published from the year 2000 to April 2013., Methods: A search was performed in the following databases: MEDLINE, EBSCO, CINAHL, SCOPUS, PEDRO and OVID. An analysis was made of RCT including patients with TTH receiving any manual therapy, and assessing outcome measures including the intensity, and frequency or duration of the headache. Two independent referees reviewed the methodological quality of RCTs using the Jadad scale. Data from the studies were extracted by two different reviewers., Results: A total of fourteen RCTs were selected. Twelve studies showed acceptable quality (Jadad scale ≥3), and the remaining 2 had low quality (Jadad=2). The studies showed positive results, including reduction in headache intensity and/or frequency, reduction of medication consumption, and improvement in quality of life., Conclusions: The effectiveness of manual therapy for TTH cannot be completely assessed due to the heterogeneity in study design, outcome measures, and different treatments. Nevertheless, the results suggest patients with TTH receiving manual therapies showed better progress than those receiving conventional treatment or placebo. Further studies of high quality using manual therapy protocols, and also including standardized outcome measures, are now needed to clarify the efficacy of manual therapy in the management of TTH., (Copyright © 2013 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

The cancer stem cell (CSC) theory is current strategy of cancer treatment. Cancers follow pathways of cancer stem cell such as Notch, Wnt and Hedgehog can be addressed with natural products or synthetic drugs to diminish the chance of new tumours. The cancer growth can also be suppressed by aiming the tumourigenic stem cells alone, instead of targeting at reducing complete tumour dimension. The recurrence of tumours after years of disease-free survival has prompted interest in the concept that cancers may have a stem cell basis. Current assumption holds that < 5% of the tumour mass may be chemo-resistant and radio-resistant, harbouring stem-like properties that impel tumour survival, development, and metastasis. There is intense an investigation to interpret CSCs based on self-renewal and multi-lineage differentiation. Nevertheless, no successful targeted therapies have reached the clinic. The ionophore antibiotic salinomycin that selectively kills breast CSCs seems to be a promising anticancer drug. Clinical trials conducted by the NIH (National Institute of Health) on several synthetic drugs demonstrate the current importance of the issue and predict a bright future for such molecular weapons against cancer.

Background: Manual therapies are generally requested by patients with tension type headache., Objective: To compare the efficacy of multimodal manual therapy vs. pharmacological care for the management of tension type headache pain by conducting a meta-analysis of randomized controlled trials., Methods: PubMed, MEDLINE, EMBASE, AMED, CINAHL, EBSCO, Cochrane Database of Systematic Reviews, Cochrane Collaboration Trials Register, PEDro and SCOPUS were searched from their inception until June 2014. All randomized controlled trials comparing any manual therapy vs. medication care for treating tension type headache adults were included. Data were extracted and methodological quality assessed independently by two reviewers. We pooled headache frequency as the main outcome and also intensity and duration. The weighted mean difference between manual therapy and pharmacological care was used to determine effect sizes., Results: Five randomized controlled trials met our inclusion criteria and were included in the meta-analysis. Pooled analyses found that manual therapies were more effective than pharmacological care in reducing frequency (weighted mean difference -0.8036, 95% confidence interval -1.66 to -0.44; three trials), intensity (weighted mean difference -0.5974, 95% confidence interval -0.8875 to -0.3073; five trials) and duration (weighted mean difference -0.5558, 95% confidence interval -0.9124 to -0.1992; three trials) of the headache immediately after treatment. No differences were found at longer follow-up for headache intensity (weighted mean difference -0.3498, 95% confidence interval -1.106 to 0.407; three trials)., Conclusion: Manual therapies were associated with moderate effectiveness at short term, but similar effectiveness at longer follow-up for reducing headache frequency, intensity and duration in tension type headache than pharmacological medical drug care. However, due to the heterogeneity of the interventions, these results should be considered with caution at this stage., (© International Headache Society 2015.)

Imidazoles and benzimidazoles are privileged heterocyclic bioactive compounds used with success in the clinical practice of innumerous diseases. Although there are many advancements in cancer therapy, microtubules remain as one of the few macromolecular targets validated for planning active anti-cancer compounds, and the design of drugs that modulate microtubule dynamics in unknown sites of tubulin is one of the goals of the medicinal chemistry. The discussion of the role of new and commercially available imidazole and benzimidazole derivatives as tubulin modulators is scattered throughout scientific literature, and indicates that these compounds have a tubulin modulation mechanism different from that of tubulin modulators clinically available, such as paclitaxel, docetaxel, vincristine and vinblastine. In fact, recent literature indicates that these derivatives inhibit microtubule formation binding to the colchicine site, present good pharmacokinetic properties and are capable of overcoming multidrug resistance in many cell lines. The understanding of the mechanisms involved in the imidazoles/benzimidazoles modulation of microtubule dynamics is very important to develop new strategies to overcome the resistance to anti-cancer drugs and to discover new biomarkers and targets for cancer chemotherapy.