Prodromal non-motor symptoms of Parkinson’s disease

The motor symptoms of Parkinson’s disease (PD), bradykinesia, muscular rigidity, and tremor depend upon degeneration of the dopaminergic neurons in the substantia nigra pars compacta. Recent neuropathological studies show that the Lewy bodies, the intraneuronal landmark of PD, accumulate in several neuronal cell types in the brain. An ascending gradient of pathological involvement, from the medulla oblongata to neocortical areas has been reported. Thus the original view of PD as a disease characterized by selective damage of the dopaminergic neurons in the mesencephalon should be updated into the concept of a severe multisystemic neurodegenerative disorder. Additionally, the neuropathological alterations outside the substantia nigra are soundly correlated with the non-motor symptoms of PD. As a result of these findings, interest is growing in the identification of prodromal non-motor symptoms of PD. Indeed, data from the literature suggest that autonomic disturbances, olfactory dysfunctions, depression and sleep disorders (in particular REM-sleep behavior disorder) may represent prodromal non-motor symptoms of PD. Several tests are available to detect most of these symptoms. Thus, the identification of prodromal non-motor symptoms may contribute to the precocious diagnosis of PD, and might be useful in the future to test the efficacy of neuroprotective agents

AQP5 is expressed in type-B intercalated cells in the collecting duct system of the rat, mouse and human kidney.

We screened human kidney-derived multipotent CD133+/CD24+ ARPCs for the possible expression of all 13 aquaporin isoforms cloned in humans. Interestingly, we found that ARPCs expressed both AQP5 mRNA and mature protein. This novel finding prompted us to investigate the presence of AQP5 in situ in kidney. We report here the novel finding that AQP5 is expressed in human, rat and mouse kidney at the apical membrane of type-B intercalated cells. AQP5 is expressed in the renal cortex and completely absent from the medulla. Immunocytochemical analysis using segment- and cell type-specific markers unambiguously indicated that AQP5 is expressed throughout the collecting system at the apical membrane of type-B intercalated cells, where it co-localizes with pendrin. No basolateral AQPs were detected in type-B intercalated cells, suggesting that AQP5 is unlikely to be involved in the net trans-epithelial water reabsorption occurring in the distal tubule. An intriguing hypothesis is that AQP5 may serve an osmosensor for the composition of the fluid coming from the thick ascending limb. Future studies will unravel the physiological role of AQP5 in the kidney

Electrophysiological actions of zonisamide on striatal neurons: Selective neuroprotection against complex I mitochondrial dysfunction

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Reduced intracranial volume in Fabry Disease: Evidence of abnormal neurodevelopment?

Introduction: Lysosomal storage disorders (LSD) are often characterized by abnormal brain development, reflected by a reduction of intracranial volume (ICV). The aim of our study was to perform a volumetric analysis of intracranial tissues in Fabry Disease (FD), investigating possible reductions of ICV as a potential expression of abnormal brain development in this condition. Materials and Methods: Forty-two FD patients (15males,mean age 43.3±13.0 years) were enrolled along with 38 healthy controls (HC) of comparable age and sex. Volumetric MRI data were segmented using SPM12 to obtain intracranial tissue volumes, from which ICV values were derived. Results: Mean ICV of FD patients was 8.1% smaller compared to the control group (p<5·10−5). Unlike what typically happens in neurodegenerative disorders, no significant differences emerged when comparing between the two groups the fractional volumes of gray matter, white matter and CSF (i.e., normalized by ICV), consistent with a harmonious volumetric reduction of intracranial structures. Discussion: The present results suggest that in FD patients an abnormality of brain development is present, expanding the current knowledge about central nervous system involvement in FD, further emphasizing the importance of an early diagnosis

Common polymorphisms in nitric oxide synthase (NOS) genes influence quality of aging and longevity in humans

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Some Observations on the Role of Water States for Biological and Therapeutical Effects

The peculiar properties of water are recalled, among them the “memory of water”, underlining the behavior of cell water, whose “ordered” structure is probably due to the endogenous electromagnetic fields generated by organelles inside the cells, such mitochondria and microtubules. Biological and clinical implications of water dynamic changes are reported, mainly based on SEP (Skin Electric Parameters) analysis and a hypothesis that has been advanced about an “action at distance” exerted by low concentration drugs. Nowadays, regarding measures of electro-cutaneous parameters our research can resort to a device of advanced electronics, APEC 300, that, beside an Electro Acupuncture operational function, but with quantitative precise values, can detect micro variations on parameters of cell aqueous solutions, and those of the water too, when the analyzed object is solicited by an external electromagnetic weak field, as well as by a drug at a very low concentration. A draft of two possible lines of research is outlined in conclusions, one depending only on ourselves and regarding “water tests” in the context of the “memory of water” experiments. By the side of EIS experiments about conductivity and impedance spectroscopy, in this article very high-resolution measures are suggested, by means of APEC 300, of an important parameter, the potential; a kind of measurements less complex and more reliable regarding the device/object interference, to which can besides easily be associated a frequency spectrum in the extremely low frequency region. In this line of research, it is the first time, for what we know, that some measurements of the potential, with its frequency spectrum, have been carried out for water without and with stimulation (the latter represented by the action of a magnetic field). This first set of measures by APEC 300 reveals the region 0–0.5 Hz as one of special interest

Increased NK Cell Count in Multiple Sclerosis Patients Treated With Dimethyl Fumarate: A 2-Year Longitudinal Study

Background: Dimethyl fumarate (DMF) is a disease-modifying drug for relapsing-remitting multiple sclerosis. Among others, DMF impedes immune activation by shifting the balance between inflammatory and regulatory cell types and by inducing apoptosis-triggered lymphopenia. Although the decrease in lymphocyte count is an early effect of the drug in several patients, the long-term impact on lymphocyte subsets is largely unknown.Methods: We performed a 2-years observational study on total lymphocyte count and subsets thereof by flow cytometry of peripheral blood of 38 multiple sclerosis patients in treatment with DMF. Data were collected at the beginning and after 3, 6, 12, and 24 months of therapy.Results: Total lymphocyte count decreased in relation to time of exposure to DMF. Mean absolute B cell count decreased by 34.1%(p &lt; 0.001) within the first 3months of therapy and then remained stable over time. Mean absolute CD3(+) T cells count decrement reached 47.5% after 12 months of treatment ( p &lt; 0.001). NK cells count showed a heterogeneous trend, increasing by 85.9%( p &lt; 0.001) after 2 years of treatment. CD4(+) T cells and CD8(+) T cells substantially decreased, with a significant increase of CD4(+)/CD8(+) ratio during the first year of therapy.Conclusions: NK cells showed a heterogeneous behavior during DMF treatment with a significant increase over time. Since NK cells may also have a regulatory effect on immune system modulation, their increase during DMF treatment might play a role in the efficacy and safety of the drug

Outcomes of music therapy interventions in cancer patients. A review of the literature

Background: Effectiveness of music-based interventions (MI) on cancer patients\u2019 anxiety, depression, pain and quality of life (QoL) is a current research theme. MI are highly variable, making it challenging to compare studies. Objective and methods: To summarize the evidence on MI in cancer patients, 40 studies were reviewed following the PRISMA statement. Studies were included if assessing at least one outcome among anxiety, depression, QoL and pain in patients aged 65 18, with an active oncological/onco-haematological diagnosis, participating to any kind of MT, during/after surgery, chemotherapy or radiotherapy. Results: A positive effect of MI on the outcomes measured was supported. Greater reductions of anxiety and depression were observed in breast cancer patients. MI involving patients admitted to a hospital ward were less effective on QoL. Conclusion: The increasing evidence about MI effectiveness, tolerability, feasibility and appreciation, supports the need of MI implementation in Oncology, Radiotherapy and Surgery wards, and promotion of knowledge among health operators

Use of wound infusion catheters for postoperative local anaesthetic administration in cats

Objectives The present study aimed to document the use of the wound infusion catheter (WIC) following a variety of surgical procedures in cats, investigating complications and risk factors associated with catheter placement or local anaesthetic (LA) administration. Methods A retrospective, multicentric study was performed. Medical databases of eight veterinary referral hospitals from 2010 to 2021 were searched to identify records of cats where WICs were used. Information regarding signalment, type of surgery, size and type of WIC placed, and LA protocol used, as well as postoperative complications, were retrieved. Results One hundred and sixty-six cases fulfilled the inclusion criteria. Feline injection site sarcoma resection was the most common surgery. Overall complications were identified in 22/166 cats (13.2%). Thirteen cats (7.8%) experienced wound-related complications, whereas nine cats (5.4%) experienced drug-delivery complications. The only factor associated with an increased risk of complications was the amount of a single dose of LA delivered through the catheter ( P <0.001). An amount higher than 2.5 ml of LA delivered at each administration was associated with an increased risk of complications. All complications were minor and self-limiting. Conclusions and relevance WICs were used for a large variety of surgical procedures with different protocols of LA administration as part of a multimodal analgesic plan in cats. The risk of complications was relatively low and self-limiting, suggesting its safe use in cats. Further prospective studies are required to evaluate efficacy of postoperative analgesia and to determine the suitable protocol for WIC handling and maintenance