Temporal dynamics of neurovascular unit changes following blood-brain barrier opening in the putamen of non-human primates.

Low-intensity focused ultrasound (LIFU) combined with intravenously circulating microbubbles has recently emerged as a novel approach for increasing delivery through the blood-brain barrier (BBB). This technique safely and transiently enables therapeutic agents to overcome the BBB, which typically poses a significant obstacle for treatment of brain disorders. However, the full impact of LIFU on the entire neurovascular unit (NVU), as well as the mechanisms and factors involved in restoring BBB integrity still require further elucidation.

Calbindin and Girk2/Aldh1a1 define resilient vs vulnerable dopaminergic neurons in a primate Parkinson's disease model.

The differential vulnerability of dopaminergic neurons of the substantia nigra pars compacta (SNc) is a critical and unresolved question in Parkinson´s disease. Studies in mice show diverse susceptibility of subpopulations of nigral dopaminergic neurons to various toxic agents. In the primate midbrain, the molecular phenotypes of dopaminergic neurons and their differential vulnerability are poorly characterized.

The road ahead to successful BBB opening and drug-delivery with focused ultrasound.

This review delves into the innovative technology of Blood-Brain Barrier (BBB) opening with low-intensity focused ultrasound in combination with microbubbles (LIFU-MB), a promising therapeutic modality aimed at enhancing drug delivery to the central nervous system (CNS). The BBB's selective permeability, while crucial for neuroprotection, significantly hampers the efficacy of pharmacological treatments for CNS disorders. LIFU-MB emerges as a non-invasive and localized method to transiently increase BBB permeability, facilitating the delivery of therapeutic molecules.

Neurovascular and immune factors of vulnerability of substantia nigra dopaminergic neurons in non-human primates.

Dopaminergic neurons in the ventral tier of the substantia nigra pars compacta (SNc) degenerate prominently in Parkinson's disease (PD), while those in the dorsal tier and ventral tegmental area are relatively spared. The factors determining why these neurons are more vulnerable than others are still unrevealed. Neuroinflammation and immune cell infiltration have been demonstrated to be a key feature of neurodegeneration in PD.

Nigrostriatal blood-brain barrier opening in Parkinson's disease.

Background: The nigrostriatal system is especially vulnerable to neurodegeneration in Parkinson's disease (PD) and the blood-brain barrier (BBB) is a limiting factor for delivery of therapeutic agents to the brain. This pilot study aimed to demonstrate safety, feasibility and tissue penetration (by 18F-Choline-positron emission tomography (PET)) of MR-guided focused ultrasound (MRgFUS) simultaneous BBB opening (BBB-O) in the substantia nigra (SN) and putamen in PD.

Methods: Three patients underwent MRgFUS for midbrain and putamen BBB-O.

Gut microbiota produces biofilm-associated amyloids with potential for neurodegeneration.

Age-related neurodegenerative diseases involving amyloid aggregation remain one of the biggest challenges of modern medicine. Alterations in the gastrointestinal microbiome play an active role in the aetiology of neurological disorders. Here, we dissect the amyloidogenic properties of biofilm-associated proteins (BAPs) of the gut microbiota and their implications for synucleinopathies.

Comparison of green solvents for the revalorization of orange by-products: Carotenoid extraction and in vitro antioxidant activity.

Orange peels contain a considerable number of bioactive compounds such as carotenoids, that can be used as ingredients in high-value products. The aim of this study was to compare orange peel extracts obtained with different green solvents (vegetable oils, fatty acids, and deep eutectic solvents (DES)). In addition, the chemical characterization of a new hydrophobic DES formed by octanoic acid and l-proline (C8:Pro) was performed.

Dopaminergic denervation and associated MRI microstructural changes in the nigrostriatal projection in early Parkinson's disease patients.

Loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) and a profound reduction of striatal dopamine are two hallmarks of Parkinson's disease (PD). However, it's unclear whether degeneration starts at the neuronal soma or the striatal presynaptic terminals, and how microstructural degeneration is linked to dopaminergic loss is also uncertain. In this study, thirty de novo PD patients and twenty healthy subjects (HS) underwent 6-[F]-fluoro-L-dopa (FDOPA) PET and MRI studies no later than 12 months from clinical diagnosis.

Green Assessment of Phenolic Acid Composition and Antioxidant Capacity of Advanced Potato Mutant Lines through UPLC-qTOF-MS/MS Quantification.

Potatoes are one of the most consumed crops worldwide. They contain a high amount of bioactive compounds such as phenolic compounds and vitamins with important antioxidant activities, which makes this crop of high biological value for human health. The goal of this research was to biochemically evaluate polyphenol levels and antioxidant capacities in parent and control genotypes compared to advanced mutant potato lines in the MV generation.

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

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.

Green Solvents: Emerging Alternatives for Carotenoid Extraction from Fruit and Vegetable By-Products.

Carotenoids have important implications for human health and the food industry due to their antioxidant and functional properties. Their extraction is a crucial step for being able to concentrate them and potentially include them in food products. Traditionally, the extraction of carotenoids is performed using organic solvents that have toxicological effects.

Neuroinflammation, immune response and α-synuclein pathology: how animal models are helping us to connect dots.

Introduction: A key pathological event occurring in Parkinson's disease (PD) is the transneuronal spreading of alpha-synuclein (α-syn). Other hallmarks of PD include neurodegeneration, glial activation, and immune cell infiltration in susceptible brain regions. Although preclinical models can mimic most of the key characteristics of PD, it is crucial to know the biological bases of individual differences between them when choosing one over another, to ensure proper interpretation of the results and to positively influence the outcome of the experiments.

Combined Dietary Education and High-Intensity Interval Resistance Training Improve Health Outcomes in Patients with Coronary Artery Disease.

Background: Reducing cardiovascular risk through lifestyle changes that include a heart-healthy diet and regular exercise is recommended in the rehabilitation of patients with coronary artery disease (CAD). We pilot-tested the effectiveness of a dietary-education and high-intensity interval resistance training (DE-HIIRT) program on healthy food choices and associated anthropometric variables in patients with established CAD.

Methods: A total of 22 participants, aged 60.

Sustainable Development and Storage Stability of Orange By-Products Extract Using Natural Deep Eutectic Solvents.

The citrus industry produces large amounts of waste rich in bioactive compounds that have important effects on human health. Their extraction was performed using organic solvents, and a greener alternative to those solvents are natural deep eutectic solvents (NADES). The present study aimed to obtain and optimize extracts rich in polyphenols and flavonoids from orange peels using NADES and monitor polyphenol stability in the extracts for 30 days.

Impact of Service-Learning on Physiotherapy Students: Exercise Programs for Patients with Heart Transplantation and Acute Coronary Syndrome-A Randomized Clinical Trial.

Introduction: Service-learning (SL) seems to be useful for healthcare students. This study aimed at comparing an SL program versus a traditional approach (TA) on moral sensitivity, ethical competences, knowledge, teaching quality, SL participation and performance, and satisfaction in physiotherapy students.

Methods: Randomized clinical trial.

MOTS-c promotes muscle differentiation in vitro.

MOTS-c (mitochondrial open reading frame of the 12 S rRNA-c) is a newly discovered peptide that has been shown to have a protective role in whole-body metabolic homeostasis. This could be a consequence of the effect of MOTS-c on muscle tissue. Here, we investigated the role of MOTS-c in the differentiation of human (LHCN-M2) and murine (C2C12) muscle progenitor cells.

Striatal Blood-Brain Barrier Opening in Parkinson's Disease Dementia: A Pilot Exploratory Study.

Background: Parkinson's disease (PD) exhibits a high prevalence of dementia as disease severity and duration progress. Focused ultrasound (FUS) has been applied for transient blood-brain barrier (BBB) opening of cortical regions in neurodegenerative disorders. The striatum is a primary target for delivery of putative therapeutic agents in PD.

Neuron types in the primate striatum: Stereological analysis of projection neurons and interneurons in control and parkinsonian monkeys.

Aims: The striatum is mainly composed of projection neurons. It also contains interneurons, which modulate and control striatal output. The aim of the present study was to assess the percentages of projection neurons and interneuron populations in the striatum of control monkeys and of parkinsonian monkeys.

Cerebral metabolic pattern associated with progressive parkinsonism in non-human primates reveals early cortical hypometabolism.

Dopaminergic denervation in patients with Parkinson's disease is associated with changes in brain metabolism. Cerebral in-vivo mapping of glucose metabolism has been studied in severe stable parkinsonian monkeys, but data on brain metabolic changes in early stages of dopaminergic depletion of this model is lacking. Here, we report cerebral metabolic changes associated with progressive nigrostriatal lesion in the pre-symptomatic and symptomatic stages of the progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkey model of Parkinson's Disease.

Motor and non-motor circuit disturbances in early Parkinson disease: which happens first?

For the last two decades, pathogenic concepts in Parkinson disease (PD) have revolved around the toxicity and spread of α-synuclein. Thus, α-synuclein would follow caudo-rostral propagation from the periphery to the central nervous system, first producing non-motor manifestations (such as constipation, sleep disorders and hyposmia), and subsequently impinging upon the mesencephalon to account for the cardinal motor features before reaching the neocortex as the disease evolves towards dementia. This model is the prevailing theory of the principal neurobiological mechanism of disease.

Robust Data-Driven Leak Localization in Water Distribution Networks Using Pressure Measurements and Topological Information.

This article presents a new data-driven method for locating leaks in water distribution networks (WDNs). It is triggered after a leak has been detected in the WDN. The proposed approach is based on the use of inlet pressure and flow measurements, other pressure measurements available at some selected inner nodes of the WDN, and the topological information of the network.

Lack of Parkinsonian Pathology and Neurodegeneration in Mice After Long-Term Injections of a Proteasome Inhibitor in Olfactory Bulb and Amygdala.

Proteinaceous inclusions, called Lewy bodies (LBs), are used as a pathological hallmark for Parkinson's disease (PD). Recent studies suggested a prion-like spreading mechanism for α-synucleinopathy where early neuropathological deposits occur, among others, in the olfactory bulb (OB) and amygdala. LBs contain insoluble α-synuclein and many other ubiquitinated proteins, suggesting a role of protein degradation system failure in PD pathogenesis.

Dimensions of household food waste focused on family and consumers.

Food waste produced in homes represents the largest fraction of food waste generated along the food chain. Therefore, adequate prevention measures based on the quantitative and qualitative dimensions of the problem need to be put in place to reduce waste. The objective of the review was to identify areas of interest in relation to the food waste in households, considering the family unit as a whole as well as individual family members.

Oral subchronic exposure to the mycotoxin ochratoxin A induces key pathological features of Parkinson's disease in mice six months after the end of the treatment.

Some epidemiological studies with different levels of evidence have pointed to a higher risk of Parkinson's disease (PD) after exposure to environmental toxicants. A practically unexplored potential etiological factor is a group of naturally-occurring fungal secondary metabolites called mycotoxins. The mycotoxin ochratoxin A (OTA) has been reported to be neurotoxic in mice.