Parkinson’s disease (PD) has become the second most common neurodegenerative condition following Alzheimer’s disease (AD), exhibiting high prevalence and incident rates. Current care strategies for PD patients include brief appointments, which are sparsely allocated, at outpatient clinics, where, in the best case scenario, expert neurologists evaluate disease progression using established rating scales and patient-reported questionnaires, which have interpretability issues and are subject to recall bias. In this context, artificial-intelligence-driven telehealth solutions, such as wearable devices, have the potential to improve patient care and support physicians to manage PD more effectively by monitoring patients in their familiar environment in an objective manner. In this study, we evaluate the validity of in-office clinical assessment using the MDS-UPDRS rating scale compared to home monitoring. Elaborating the results for 20 patients with Parkinson’s disease, we observed moderate to strong correlations for most symptoms (bradykinesia, rest tremor, gait impairment, and freezing of gait), as well as for fluctuating conditions (dyskinesia and OFF). In addition, we identified for the first time the existence of an index capable of remotely measuring patients’ quality of life. In summary, an in-office examination is only partially representative of most PD symptoms and cannot accurately capture daytime fluctuations and patients’ quality of life.

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder, yet its underlying causes remain elusive. The conventional perspective on disease pathogenesis attributes alterations in neuronal excitability to molecular changes resulting in synaptic dysfunction. Early hyperexcitability is succeeded by a progressive cessation of electrical activity in neurons, with amyloid beta (Aβ) oligomers and tau protein hyperphosphorylation identified as the initial events leading to hyperactivity. In addition to these key proteins, voltage-gated sodium and potassium channels play a decisive role in the altered electrical properties of neurons in AD. Impaired synaptic function and reduced neuronal plasticity contribute to a vicious cycle, resulting in a reduction in the number of synapses and synaptic proteins, impacting their transportation inside the neuron. An understanding of these neurophysiological alterations, combined with abnormalities in the morphology of brain cells, emerges as a crucial avenue for new treatment investigations. This review aims to delve into the detailed exploration of electrical neuronal alterations observed in different AD models affecting single neurons and neuronal networks.

The orexin system is related to food behavior, energy balance, wakefulness and the reward system. It consists of the neuropeptides orexin A and B, and their receptors, orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R). OX1R has selective affinity for orexin A, and is implicated in multiple functions, such as reward, emotions, and autonomic regulation. This study provides information about the OX1R distribution in human hypothalamus. The human hypothalamus, despite its small size, demonstrates a remarkable complexity in terms of cell populations and cellular morphology. Numerous studies have focused on various neurotransmitters and neuropeptides in the hypothalamus, both in animals and humans, however, there is limited experimental data on the morphological characteristics of neurons. The immunohistochemical analysis of the human hypothalamus revealed that OX1R is mainly found in the lateral hypothalamic area, the lateral preoptic nucleus, the supraoptic nucleus, the dorsomedial nucleus, the ventromedial nucleus, and the paraventricular nucleus. The rest of the hypothalamic nuclei do not express the receptor, except for a very low number of neurons in the mammillary bodies. After identifying the nuclei and neuronal groups that were immunopositive for OX1R, a morphological and morphometric analysis of those neurons was conducted using the Golgi method. The analysis revealed that the neurons in the lateral hypothalamic area were uniform in terms of their morphological characteristics, often forming small groups of three to four neurons. A high proportion of neurons in this area (over 80%) expressed the OX1R, with particularly high expression in the lateral tuberal nucleus (over 95% of neurons). These results were analyzed, and shown to represent, at the cellular level, the distribution of OX1R, and we discuss the regulatory role of orexin A in the intra-hypothalamic areas, such as its special role in the plasticity of neurons, as well as in neuronal networks of the human hypothalamus.

Although spatial memory has been widely studied in rodents, developmental studies involving humans are limited in number and sample size. We designed and studied the validity of two simple experimental setups for the evaluation of spatial memory and navigation development. The dataset of this study was composed of 496 schoolchildren, from 4 to 15 years old. Participants were tested blindfolded on their ability to navigate in a square area between three stool stations while performing an item-collecting task, having observed the experimental space and procedure (Test 1) or having, in addition, executed the task open-eyed (Test 2). The performance times were analyzed to identify age-specific differences. Parametric methods, including the one-way ANOVA and independent samples t-test, were employed. Statistically significant differences were observed in the mean performance time among age groups, as well as within the same age groups when comparing Test 1 and Test 2. Our results revealed a performance improvement with aging for both functions and showed that spatial memory and spatial navigation develop throughout childhood and puberty and interact during development. When children integrate visual stimuli with other sensory inputs, they can form stronger spatial memories, thereby enhancing their navigation skills. The proposed experimental setup is considered feasible and can be used for behavioral studies of navigation-related memory in children and beyond with appropriate adaptations, allowing for large-scale assessment.

Introduction: We evaluated the expression of a panel of apoptosis-associated microRNAs (miRNAs) in leukemic blasts isolated from AML patients and investigated their predicted targets. Patients and Methods: We used bone marrow or peripheral blood that were donated by nine AML patients (5 male, 4 female) at diagnosis. Mononuclear cells were isolated by Ficoll-Histopaque (Sigma Aldrich) density gradient centrifugation and were cryopreserved in liquid nitrogen at the Cancer Biobank Center of the University of Ioannina. MicroBeads technology (Miltenyl Biotec) was used for magnetic cell sorting of CD34+ cells of patients' samples, while mononuclear blood cells from healthy individuals were used as controls. Small RNA (< 200 b) was isolated using the NucleoSpin® miRNA kit (Macherey Nagel). Simultaneous quantification of 84 apoptosis- associated miRNAs was performed by using the miScript miRNA PCR Array Human Apoptosis (MIHS-114ZF, Qiagen) in a LightCycler® 480 instrument (Roche AG, Rotkreuz, Switzerland), and relative quantitation of expression was determined by the comparative CT method. For miRNA target prediction we used the RNA22 tool: https://cm.jefferson.edu/rna22 Results: We found 34 downregulated and 20 upregulated miRNAs compared to control. Among the downregulated miRNAs was the miR-29 family and among the upregulated was the miR-181 family, both of which have been previously implicated in AML. The top 10 downregulated miRNAs were miR-31-5p, miR-451a, miR-29b-3p, miR-409-3p, miR-144-3p, miR-9-5p, miR-192-5p, miR-542-3p, miR-134-5p, miR-29c-3p, whereas the top 10 upregulated miRNAs were miR-34a-5p, miR-181a-5p, miR-181c-5p, miR-181d-5p, miR-181b-5p, miR-222-3p, miR-125b-5p, miR-221-3p, Let-7c-5p, miR-186-3p. We used RNA22 to identify genes that are predicted to be simultaneously targeted by all of the 10 top downregulated miRNAs and also the genes that are predicted to be simultaneously targeted by all of the 10 top upregulated miRNAs. The predicted targets for all top 10 downregulated miRNAs include NSD1, MYST4 and SACS. NSD1 is an histone methyltransferase, whereas MYST4 is an histone acetyltransferase. The predicted targets of all top 10 upregulated miRNAs include 35 genes among which are zinc finger transcription factors with proapoptotic activity (ZNF704, ZNF268) and Solute Carrier (SLC) membrane transporters (SLC24A2, SLC24A4, SLC35E3) of undefined functions. When we compared miRNA expression in patients with abnormal karyotype versus patients with normal karyotype we found miR-125a-5p to be overexpressed in patients with abnormal karyotype. Overexpression of miR-125b has been previously reported in patients with myelodysplastic syndromes and APL and plays important roles in mitochondrial apoptosis. Conclusions: A variety of microRNAs are dysregylated in patients with AML. We confirm that the miR-29 family and the miR-181 family have altered expression in AML. We found miR-125a-5p to be overexpressed in patients with abnormal karyotype. Among predicted targets of the upregulated miRNAs are genes encoding proapoptotic zinc finger proteins and Solute Carrier membrane transporters, whereas among the predicted targets of the downregulated miRNAs are genes involved in chromatin remodeling, suggesting that altered function of epigenetic modifiers in AML may be due to dysregylation of miRNAs.