Focused ultrasound for opening blood-brain barrier and drug delivery monitored with positron emission tomography

Focused ultrasound (FUS) is a minimally-invasive technology used for treatment of many diseases, including diseases related to the colon, uterus, prostate, and brain. Although it has been mainly used for ablative procedures, the ability of FUS to open the blood-brain barrier (BBB) presents a promising new application. However, the mechanism of BBB opening by FUS remains unclear. This review focuses on the use of FUS to open the BBB for enhancing drug delivery and investigating how Positron Emission Tomography (PET) provides insight into the underlying mechanism

Investigating Voice as a Biomarker for Leucine-Rich Repeat Kinase 2-Associated Parkinson's Disease

We investigate the potential association between leucine-rich repeat kinase 2 (LRRK2) mutations and voice. Sustained phonations ('aaah' sounds) were recorded from 7 individuals with LRRK2-associated Parkinson's disease (PD), 17 participants with idiopathic PD (iPD), 20 non-manifesting LRRK2-mutation carriers, 25 related non-carriers, and 26 controls. In distinguishing LRRK2-associated PD and iPD, the mean sensitivity was 95.4% (SD 17.8%) and mean specificity was 89.6% (SD 26.5%). Voice features for non-manifesting carriers, related non-carriers, and controls were much less discriminatory. Vocal deficits in LRRK2-associated PD may be different than those in iPD. These preliminary results warrant longitudinal analyses and replication in larger cohorts

Propuesta metodológica para la toma de decisiones entre rehabilitación y clausura de sitios de disposición final

Ponència presentada al IX Simposio Iberoamericano de Ingeniería de Residuos, Panamá, del 20 al 24 de setembre de 2021En México, los residuos sólidos urbanos (RSU) generados se deposita preferentemente en rellenos sanitarios (RESA); sin embargo, en número, solo el 13% de los sitios de disposición final (SDF) son RESA y el 87% son sitios no controlados (SNC). Los SNC implican riesgos para la salud y al ambiente. La SEMARNAT ha buscado que los SDF del país cumplan con la NOM-083-SEMARNAT-2003; y para ello ha elaborado con otras instituciones, manuales y guías; sin embargo, aplicar estos documentos, representa un gran gasto para los municipios que tienen SNC. El objetivo de este trabajo fue proponer una metodología para evaluar a nivel preliminar SNC, que con menores costos y tiempo, apoye en la toma de decisión entre clausura o rehabilitación. Para ello, la propuesta comprende: ubicación de SDF y análisis histórico del área afectada mediante Mapa Digital de INEGI, Google Mapas y Google Earth Pro; análisis del cumplimiento de la NOM-083-SEMARNAT-2003 con el Sistema de Información Geográfica para el Manejo de RSU (SIGMIRSU) y la aplicación de una Tabla de Verificación a responsables del SDF; así como la elaboración de recomendaciones. Se eligieron como casos de estudio el SDF de Xalatlaco, Estado de México y el SDF de Tlalpujahua, Michoacán. La aplicación de la metodología para la evaluación a nivel preliminar, evidenció que el SDF de Xalatlaco requiere de atención urgente y debe ser revisado de cerca con la Secretaría del Medio Ambiente; y que el SDF de Tlalpujahua, tiene posibilidades de ser rehabilitado para operar conforme a la NOM-083-SEMARNAT-2003.In Mexico, the municipal solid waste (MSW) generated is preferably deposited in sanitary landfills (SL); however, in number, only 13% of the final disposal sites (FDS) are SL and 87% are uncontrolled sites (UNS). The UNS pose risks to health and the environment. SEMARNAT has sought that the country's SDF comply with NOM-083-SEMARNAT-2003; and for this it has prepared with other institutions, manuals and guides; However, applying these documents represents a great expense for municipalities that have UNS. The objective of this work was to propose a methodology to evaluate UNS at a preliminary level, which with lower costs and time, supports decision-making between closure or rehabilitation. For this, the proposal includes: FDS location and historical analysis of the affected area using INEGI's Digital Map, Google Maps and Google Earth Pro; analysis of compliance of NOM-083-SEMARNAT-2003 with the Geographic Information System for MSW Management (SIGMIRSU) and the application of a Verification Table to those responsible for the SDF; as well as that the development of recommendations. The FDS of Xalatlaco, State of Mexico and the SDF of Tlalpujahua, Michoacán were chosen as case studies. The application of the methodology for the evaluation at a preliminary level, showed that the SDF of Xalatlaco requires urgent attention and should be closely reviewed with the Ministry of the Environment; and the SDF of Tlalpujahua, has the possibility of being reactivated to operate according to NOM-083-SEMARNAT2003

BBB opening with focused ultrasound in nonhuman primates and Parkinson’s disease patients: Targeted AAV vector delivery and PET imaging

血液脳関門開放術による遺伝子治療法の開発 --身体を傷つけない脳疾患の治療を目指して--. 京都大学プレスリリース. 2023-04-20.Intracerebral vector delivery in nonhuman primates has been a major challenge. We report successful blood-brain barrier opening and focal delivery of adeno-associated virus serotype 9 vectors into brain regions involved in Parkinson’s disease using low-intensity focus ultrasound in adult macaque monkeys. Openings were well tolerated with generally no associated abnormal magnetic resonance imaging signals. Neuronal green fluorescent protein expression was observed specifically in regions with confirmed blood-brain barrier opening. Similar blood-brain barrier openings were safely demonstrated in three patients with Parkinson’s disease. In these patients and in one monkey, blood-brain barrier opening was followed by 18F-Choline uptake in the putamen and midbrain regions based on positron emission tomography. This indicates focal and cellular binding of molecules that otherwise would not enter the brain parenchyma. The less-invasive nature of this methodology could facilitate focal viral vector delivery for gene therapy and might allow early and repeated interventions to treat neurodegenerative disorders

What Do We Know about Theory of Mind Impairment in Parkinson’s Disease?

Theory of mind (ToM) is a social cognitive skill that involves the ability to attribute mental states to self and others (what they think (cognitive ToM) and feel (affective ToM)). We aim to provide an overview of previous knowledge of ToM in Parkinson’s disease (PD). In the last few years more attention has been paid to the study of this construct as a non-motor manifestation of PD. In advanced stages, both components of ToM (cognitive and affective) are commonly impaired, although in early PD results remain controversial. Executive dysfunction correlates with ToM deficits and other cognitive domains such as language and visuospatial function have also been related to ToM. Recent studies have demonstrated that PD patients with mild cognitive impairment show ToM deficits more frequently in comparison with cognitively normal PD patients. In addition to the heterogeneity of ToM tests administered in different studies, depression and dopaminergic medication may also be acting as confounding factors, but there are still insufficient data to support this. Neuroimaging studies conducted to understand the underlying networks of cognitive and affective ToM deficits in PD are lacking. The study of ToM deficit in PD continues to be important, as this may worsen quality of life and favor social stigma. Future studies should be considered, including assessment of the patients’ cognitive state, associated mood disorders, and the role of dopaminergic deficit

ACTUALIZACIÓN EN LA ENFERMEDAD DE PARKINSON

La enfermedad de Parkinson es un trastorno neurodegenerativo complejo y de presentación heterogénea. Aunque aún no se dispone de ningún fármaco que enlentezca la progresión de la enfermedad, existe un arsenal terapéutico extenso y eficaz para el control sintomático en cada una de sus fases, por lo que es importante realizar un diagnóstico preciso así como un correcto manejo de fármacos que garantice un estado óptimo en los paciente que la sufren, lo que resultará en una mejora en su calidad de vida. Además, dado que es el trastorno neurodegenerativo más frecuente tras la enfermedad de Alzheimer y que su factor de riesgo principal es la edad, la enfermedad de Parkinson supone, cada vez más, un reto de salud pública en nuestras sociedades occidentales progresivamente envejecidas. Esta revisión pretende actualizar los aspectos clínicos y diagnósticos fundamentales de la enfermedad de Parkinson así como las principales estrategias terapéuticas disponibles

Social Cognition and Mild Cognitive Impairment in Mid-Stage Parkinson’s Disease

Mild cognitive impairment (MCI) is a relevant non-motor feature in Parkinson’s disease (PD). Social cognition (SC) is a cognitive domain that refers to the ability to decode others’ intentions and to guide behavior in social contexts. We aimed to compare SC performance in mid-stage PD patients compared to a healthy population and according to their cognitive state. Fifty-two PD patients were classified as being cognitively normal (PD-CN) or having mild cognitive impairment (PD-MCI) following the Movement Disorder Society (MDS) Level II criteria. SC assessment included facial emotion recognition (FER), affective and cognitive theory of mind (ToM), and self-monitoring (RSMS test). Twenty-seven age-matched healthy controls (HC) were enrolled. PD-MCI patients scored worse than HC on affective and cognitive ToM task scores. Only cognitive ToM scores were significantly lower when compared with the PD-MCI and PD-CN groups. We found no differences in FER or self-monitoring performance. There were significant correlations between cognitive ToM and executive functions, memory, language, and attention, whereas FER and affective ToM correlated with memory. Our findings indicates that SC is normal in cognitively unimpaired and non-depressed mid-stage PD patients, whereas a decline in affective and cognitive ToM is linked to the presence of MCI