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Here, we summarize the current knowledge on cell diversity in the cortex and other brain regions from in vivo mouse models and in vitro models based on pluripotent stem cells. We discuss the mechanisms underlying cell proliferation and temporal progression that leads to the sequential generation of neurons dedicated to different layers of the cortex. We highlight models of corticogenesis from stem cells that recapitulate specific transcriptional and connectivity patterns from different cortical areas. We overview state-of-the art of human brain organoids modeling different brain regions, and we discuss insights into human cortical evolution from stem cells. Finally, we interrogate human brain organoid models for their competence to recapitulate the essence of human brain development.Tyrosine kinase inhibitors (TKIs) have drastically changed the outcome of chronic myeloid leukemia (CML) patients. A sustained and deep molecular response achieved over time paves the way to therapy discontinuation, and is a pre-requisite to attempt treatment-free remission. Monitoring of the molecular response during treatment discontinuation is routinely carried out by RQ-PCR, but it may not be the optimal tool to monitor minimal residual disease at the time of stopping treatment and during treatment discontinuation. Different digital PCR platforms (such as droplet dPCR) are available, a method based on water-emulsion droplet technology in which the sample is partitioned into 20,000 droplets and PCR amplification of the template subsequently occurs in each individual droplet. The consequent high sensitivity and precision with a very reliable quantification without the need of a calibration curve and the exquisite reproducibility makes this procedure as an ideal alternative method for the detection of very low levels of disease. Aim of this review is to describe and discuss the recent use of dPCR/ddPCR in CML, focusing in particular on its role in TKI treatment discontinuation strategies. . To review the Mayo clinic experience of cyclophosphamide in the treatment of tumefactive Multiple Sclerosis (TMS). . Retrospective chart review was performed to identify patients with TMS who did not respond to corticosteroid and plasma exchange and were treated with cyclophosphamide. Demographic, clinical, treatment, and outcome parameters were collected. . We identified 12 patients with TMS who were treated with cyclophosphamide. Median follow-up was 17 (range 1-72) months after cyclophosphamide administration. The tumefactive attack was the first clinical symptom in 5/12 patients. The median age at index attack onset was 36 (range 22-57). The median age at the first demyelinating attack was 29.3 (range 20-55). The most common clinical presentation at the index attack was the visual disturbance, followed by motor symptoms. The index attack was accompanied by headache in 5/12 patients. Median attack related Expanded Disability Status Scale (EDSS) score was 6 (range 3-9.5), which improved to 5.25 (range 1-10) after treatment with cyclophosphamide. All patients were treated with corticosteroids and plasma exchange prior to treatment with cyclophosphamide. EDSS score improved in 8/12 patients and targeted neurological deficits improved to a moderate or marked degree in 9/12 patients after cyclophosphamide administration. The number of gadolinium enhancing lesions decreased in 10/12 and 8/12 patients had lack of disease activity (no new T2 or GAD lesions) in a median (range) time of 11 months (1-16) after the last dose of cyclophosphamide. . Cyclophosphamide could be an effective option for the treatment of TMS, refractory to corticosteroids and plasmapheresis, and is associated with improvement of clinical and radiological disease activity.. Cyclophosphamide could be an effective option for the treatment of TMS, refractory to corticosteroids and plasmapheresis, and is associated with improvement of clinical and radiological disease activity.Multiple sclerosis (MS) itself and first-line disease modifying therapies do not increase the risk of contracting COVID-19. However, home isolation is likely to result in a significant decrease in participation in leisure time physical activities and an increase in sedentary behavior. Therefore, using an online cross-sectional survey we examined the impact of the COVID-19 epidemic on physical activity (PA) behavior and fitness level in an Israeli cohort of people with multiple sclerosis (PwMS). The survey PA questionnaire included 10 questions. Specifically, participants reported on whether, and to what extent, the pandemic conditions had altered their PA behavior. One hundred and twenty PwMS filled out the online survey, 78 were females with a mean age of 43.0 (S.D.=12.9) years. PA behavior during the pandemic demonstrated that 17.5% who were engaged in PA before the COVID-19 pandemic, ceased PA, 33.3% reduced their PA, 20.0% continued their PA as before, 18.3% increased their PA during the pandemic, and 10.8% did not perform any PA in the past and did not so during the pandemic. https://www.selleckchem.com/products/favipiravir-t-705.html As for the patient's self-reported fitness level, 31.7% reported that their fitness level had decreased during the pandemic, 60.0% felt no change, and 8.3% reported an improvement. Our findings serve as a call of action for all professionals involved in MS management to address physical activity behavior in PwMS during the COVID-19 epidemic. dynamic balance (DB) is a complex ability at an early age and balance deficits are related to numerous disorders. There are several balance measures but wide variation in their use has restricted the capacity to synthesise references values. The main purpose of this study was to analyse the performance of the Balance beam test (BBT) in preschool children, according to age and sex providing BBT reference values, and also to analyse its reliability and validity. could the BBT be a reliable test for measuring dynamic balance in preschool children? 593 preschool children (3-6 years) participated in this study. The BBT was used to evaluate DB by measuring distance reached, time spent, and number of steps. Differences between sex and age groups were analysed using the Mann-Whitney U and Kruskal-Wallis tests. Test-retest reliability analysis was performed using intraclass correlation coefficients and the Bland-Altman graphic. Convergent validity was investigated with the Stork Balance stand test (SBST). no significant differences were found for sex in any components of the BBT.
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Here, we summarize the current knowledge on cell diversity in the cortex and other brain regions from in vivo mouse models and in vitro models based on pluripotent stem cells. We discuss the mechanisms underlying cell proliferation and temporal progression that leads to the sequential generation of neurons dedicated to different layers of the cortex. We highlight models of corticogenesis from stem cells that recapitulate specific transcriptional and connectivity patterns from different cortical areas. We overview state-of-the art of human brain organoids modeling different brain regions, and we discuss insights into human cortical evolution from stem cells. Finally, we interrogate human brain organoid models for their competence to recapitulate the essence of human brain development.Tyrosine kinase inhibitors (TKIs) have drastically changed the outcome of chronic myeloid leukemia (CML) patients. A sustained and deep molecular response achieved over time paves the way to therapy discontinuation, and is a pre-requisite to attempt treatment-free remission. Monitoring of the molecular response during treatment discontinuation is routinely carried out by RQ-PCR, but it may not be the optimal tool to monitor minimal residual disease at the time of stopping treatment and during treatment discontinuation. Different digital PCR platforms (such as droplet dPCR) are available, a method based on water-emulsion droplet technology in which the sample is partitioned into 20,000 droplets and PCR amplification of the template subsequently occurs in each individual droplet. The consequent high sensitivity and precision with a very reliable quantification without the need of a calibration curve and the exquisite reproducibility makes this procedure as an ideal alternative method for the detection of very low levels of disease. Aim of this review is to describe and discuss the recent use of dPCR/ddPCR in CML, focusing in particular on its role in TKI treatment discontinuation strategies. . To review the Mayo clinic experience of cyclophosphamide in the treatment of tumefactive Multiple Sclerosis (TMS). . Retrospective chart review was performed to identify patients with TMS who did not respond to corticosteroid and plasma exchange and were treated with cyclophosphamide. Demographic, clinical, treatment, and outcome parameters were collected. . We identified 12 patients with TMS who were treated with cyclophosphamide. Median follow-up was 17 (range 1-72) months after cyclophosphamide administration. The tumefactive attack was the first clinical symptom in 5/12 patients. The median age at index attack onset was 36 (range 22-57). The median age at the first demyelinating attack was 29.3 (range 20-55). The most common clinical presentation at the index attack was the visual disturbance, followed by motor symptoms. The index attack was accompanied by headache in 5/12 patients. Median attack related Expanded Disability Status Scale (EDSS) score was 6 (range 3-9.5), which improved to 5.25 (range 1-10) after treatment with cyclophosphamide. All patients were treated with corticosteroids and plasma exchange prior to treatment with cyclophosphamide. EDSS score improved in 8/12 patients and targeted neurological deficits improved to a moderate or marked degree in 9/12 patients after cyclophosphamide administration. The number of gadolinium enhancing lesions decreased in 10/12 and 8/12 patients had lack of disease activity (no new T2 or GAD lesions) in a median (range) time of 11 months (1-16) after the last dose of cyclophosphamide. . Cyclophosphamide could be an effective option for the treatment of TMS, refractory to corticosteroids and plasmapheresis, and is associated with improvement of clinical and radiological disease activity.. Cyclophosphamide could be an effective option for the treatment of TMS, refractory to corticosteroids and plasmapheresis, and is associated with improvement of clinical and radiological disease activity.Multiple sclerosis (MS) itself and first-line disease modifying therapies do not increase the risk of contracting COVID-19. However, home isolation is likely to result in a significant decrease in participation in leisure time physical activities and an increase in sedentary behavior. Therefore, using an online cross-sectional survey we examined the impact of the COVID-19 epidemic on physical activity (PA) behavior and fitness level in an Israeli cohort of people with multiple sclerosis (PwMS). The survey PA questionnaire included 10 questions. Specifically, participants reported on whether, and to what extent, the pandemic conditions had altered their PA behavior. One hundred and twenty PwMS filled out the online survey, 78 were females with a mean age of 43.0 (S.D.=12.9) years. PA behavior during the pandemic demonstrated that 17.5% who were engaged in PA before the COVID-19 pandemic, ceased PA, 33.3% reduced their PA, 20.0% continued their PA as before, 18.3% increased their PA during the pandemic, and 10.8% did not perform any PA in the past and did not so during the pandemic. https://www.selleckchem.com/products/favipiravir-t-705.html As for the patient's self-reported fitness level, 31.7% reported that their fitness level had decreased during the pandemic, 60.0% felt no change, and 8.3% reported an improvement. Our findings serve as a call of action for all professionals involved in MS management to address physical activity behavior in PwMS during the COVID-19 epidemic. dynamic balance (DB) is a complex ability at an early age and balance deficits are related to numerous disorders. There are several balance measures but wide variation in their use has restricted the capacity to synthesise references values. The main purpose of this study was to analyse the performance of the Balance beam test (BBT) in preschool children, according to age and sex providing BBT reference values, and also to analyse its reliability and validity. could the BBT be a reliable test for measuring dynamic balance in preschool children? 593 preschool children (3-6 years) participated in this study. The BBT was used to evaluate DB by measuring distance reached, time spent, and number of steps. Differences between sex and age groups were analysed using the Mann-Whitney U and Kruskal-Wallis tests. Test-retest reliability analysis was performed using intraclass correlation coefficients and the Bland-Altman graphic. Convergent validity was investigated with the Stork Balance stand test (SBST). no significant differences were found for sex in any components of the BBT.
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