RESUMO
Mesial temporal lobe epilepsy (MTLE) is the most common focal epilepsy. One-third of patients have drug-refractory seizures and are left with suboptimal therapeutic options such as brain tissue-destructive surgery. Here, we report the development and characterization of a cell therapy alternative for drug-resistant MTLE, which is derived from a human embryonic stem cell line and comprises cryopreserved, post-mitotic, medial ganglionic eminence (MGE) pallial-type GABAergic interneurons. Single-dose intrahippocampal delivery of the interneurons in a mouse model of chronic MTLE resulted in consistent mesiotemporal seizure suppression, with most animals becoming seizure-free and surviving longer. The grafted interneurons dispersed locally, functionally integrated, persisted long term, and significantly reduced dentate granule cell dispersion, a pathological hallmark of MTLE. These disease-modifying effects were dose-dependent, with a broad therapeutic range. No adverse effects were observed. These findings support an ongoing phase 1/2 clinical trial (NCT05135091) for drug-resistant MTLE.
Assuntos
Epilepsia do Lobo Temporal , Hipocampo , Camundongos , Animais , Humanos , Hipocampo/patologia , Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/cirurgia , Convulsões/patologia , Convulsões/cirurgia , Interneurônios/fisiologia , Encéfalo/patologiaRESUMO
BACKGROUND: The impact of the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for diagnosis and management of hypertension on the prevalence of hypertension in India is unknown. METHODS: We analyzed data from the Cardiac Prevent 2015 survey to estimate the change in the prevalence of hypertension. The JNC8 guidelines defined hypertension as a systolic blood pressure of ≥140 âmmHg or diastolic blood pressure of ≥90 âmmHg. The 2017 ACC/AHA guidelines define hypertension as a systolic blood pressure of ≥130 âmmHg or diastolic blood pressure of ≥80 âmmHg. We standardized the prevalence as per the 2011 census population of India. We also calculated the prevalence as per the World Health Organization (WHO) World Standard Population (2000-2025). RESULTS: Among 180,335 participants (33.2% women), the mean age was 40.6 â± â14.9 years (41.1 â± â15.0 and 39.7 â± â14.7 years in men and women, respectively). Among them, 8,898 (4.9%), 99,791 (55.3%), 35,694 (11.9%), 23,084 (12.8%), 9,989 (5.5%) and 2,878 (1.6%) participants belonged to age group 18-19, 20-44, 45-54, 55-64, 65-74 and â≥ â75 years respectively. The prevalence of hypertension according to the JNC8 and 2017 ACC/AHA guidelines was 29.7% and 63.8%, respectively- an increase of 115%. With the 2011 census population of India, this suggests that currently, 486 million Indian adults have hypertension according to the 2017 ACC/AHA guidelines, an addition of 260 million as compared to the JNC8 guidelines. CONCLUSION: According to the 2017 ACC/AHA guidelines, 3 in every 5 Indian adults have hypertension.
RESUMO
OBJECTIVE: Hypertension is the most important risk factor for cardiovascular morbidity and mortality. There is limited data on hypertension prevalence in India. This study was conducted to estimate the prevalence of hypertension among Indian adults. METHODS: A national level survey was conducted with fixed one-day blood pressure measurement camps across 24 states and union territories of India. Hypertension was defined as systolic blood pressure (BP) ≥140 mmHg or a diastolic BP ≥90 mmHg or on treatment for hypertension. The prevalence was age- and gender-standardized according to the 2011 census population of India. RESULTS: Blood pressure was recorded for 180,335 participants (33.2% women; mean age 40.6 ± 14.9 years). Among them, 8,898 (4.9%), 99,791 (55.3%), 35,694 (11.9%), 23,084 (12.8%), 9,989 (5.5%), and 2,878 (1.6%) participants were of the age group 18-19, 20-44, 45-54, 55-64, 65-74, and ≥ 75 years, respectively. Overall prevalence of hypertension was 30.7% (95% confidence interval [CI]: 30.5, 30.9) and the prevalence among women was 23.7% (95% CI: 23.3, 24). Prevalence adjusted for 2011 census population and the WHO reference population was 29.7% and 32.8%, respectively. CONCLUSION: There is a high prevalence of hypertension, with almost one in every three Indian adult affected.