589 research outputs found

    Structure and dimension of global branches of solutions to multiparameter nonlinear equations

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    A general study of the dimension and connectivity properties of branches of solutions of equations depending on n-parameters are studied using the homotopy properties of 0-epi maps

    Pharmacological rescue of adult hippocampal neurogenesis in a mouse model of X-linked intellectual disability

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    Oligophrenin-1 (OPHN1) is a Rho GTPase activating protein whose mutations cause X-linked intellectual disability (XLID). How loss of function of Ophnl affects neuronal development is only partly understood. Here we have exploited adult hippocampal neurogenesis to dissect the steps of neuronal differentiation that are affected by Ophn1 deletion. We found that mice lacking Ophnl display a reduction in the number of newborn neurons in the dentate gyrus. A significant fraction of the Ophn1-deficient newly generated neurons failed to extend an axon towards CM, and showed an altered density of dendritic protrusions. Since Ophnl-deficient mice display overactivation of Rho-associated protein kinase (ROCK) and protein kinase A (PICA) signaling, we administered a clinically approved ROCK/PICA inhibitor (fasudil) to correct the neurogenesis defects. While administration of fasudil was not effective in rescuing axon formation, the same treatment completely restored spine density to control levels, and enhanced the long-term survival of adult-born neurons in mice lacking Ophn1. These results identify specific neurodevelopmental steps that are impacted by Ophn1 deletion, and indicate that they may be at least partially corrected by pharmacological treatment. (C) 2017 The Authors. Published by Elsevier Inc

    Development of a Self-Sufficient LoRaWAN Sensor Node with Flexible and Glass Dye-Sensitized Solar Cell Modules Harvesting Energy from Diffuse Low-Intensity Solar Radiation

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    This paper aims to demonstrate the viability of energy harvesting for wide area wireless sensing systems based on dye-sensitized solar cells (DSSCs) under diffuse sunlight conditions, proving the feasibility of deploying autonomous sensor nodes even under unfavorable outdoor scenarios, such as during cloudy days, in the proximity of tall buildings, among the trees in a forest and during winter days in general. A flexible thin-film module and a glass thin-film module, both featuring an area smaller than an A4 sheet of paper, were initially characterized in diffuse solar light. Afterward, the protype sensor nodes were tested in a laboratory in two different working conditions, emulating outdoor sunlight in unfavorable lighting and weather to reconstruct a worst-case scenario. A Li-Po battery was employed as a power reserve for a long-range wide area network (LoRaWAN)-based sensor node that transmitted data every 8 h and every hour. To this end, an RFM95x LoRa module was used, while the node energy management was attained by exploiting a nano-power boost charger buck converter integrated circuit conceived for the nano-power harvesting from the light source and the managing of the battery charge and protection. A positive charge balance was demonstrated by monitoring the battery trend along two series of 6 and 9 days, thus allowing us to affirm that the system’s permanent energy self-sufficiency was guaranteed even in the worst-case lighting and weather scenario

    Gut microbiota profile in CDKL5 deficiency disorder patients

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    : CDKL5 deficiency disorder (CDD) is a neurodevelopmental condition characterized by global developmental delay, early-onset seizures, intellectual disability, visual and motor impairments. Unlike Rett Syndrome (RTT), CDD lacks a clear regression period. Patients with CDD frequently encounter gastrointestinal (GI) disturbances and exhibit signs of subclinical immune dysregulation. However, the underlying causes of these conditions remain elusive. Emerging studies indicate a potential connection between neurological disorders and gut microbiota, an area completely unexplored in CDD. We conducted a pioneering study, analyzing fecal microbiota composition in individuals with CDD (n = 17) and their healthy relatives (n = 17). Notably, differences in intestinal bacterial diversity and composition were identified in CDD patients. In particular, at genus level, CDD microbial communities were characterized by an increase in the relative abundance of Clostridium_AQ, Eggerthella, Streptococcus, and Erysipelatoclostridium, and by a decrease in Eubacterium, Dorea, Odoribacter, Intestinomonas, and Gemmiger, pointing toward a dysbiotic profile. We further investigated microbiota changes based on the severity of GI issues, seizure frequency, sleep disorders, food intake type, impairment in neuro-behavioral features and ambulation capacity. Enrichment in Lachnoclostridium and Enterobacteriaceae was observed in the microbiota of patients with more severe GI symptoms, while Clostridiaceae, Peptostreptococcaceae, Coriobacteriaceae, Erysipelotrichaceae, Christensenellaceae, and Ruminococcaceae were enriched in patients experiencing daily epileptic seizures. Our findings suggest a potential connection between CDD, microbiota and symptom severity. This study marks the first exploration of the gut-microbiota-brain axis in subjects with CDD. It adds to the growing body of research emphasizing the role of the gut microbiota in neurodevelopmental disorders and opens doors to potential interventions that target intestinal microbes with the aim of improving the lives of patients with CDD

    EVALUATION OF LIVER PARENCHYMA AND PERFUSION USING DYNAMIC CONTRAST-ENHANCED COMPUTED TOMOGRAPHY AND CONTRAST-ENHANCED ULTRASONOGRAPHY IN CAPTIVE GREEN IGUANAS (IGUANA IGUANA) UNDER GENERAL ANESTHESIA

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    Background: Contrast-enhanced diagnostic imaging techniques are considered useful in veterinary and human medicine to evaluate liver perfusion and focal hepatic lesions. Although hepatic diseases are a common occurrence in reptile medicine, there is no reference to the use of contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CECT) to evaluate the liver in lizards. Therefore, the aim of this study was to evaluate the pattern of change in echogenicity and attenuation of the liver in green iguanas (Iguana iguana) after administration of specific contrast media. Results: An increase in liver echogenicity and density was evident during CEUS and CECT, respectively. In CEUS, the mean \ub1 SD (median; range) peak enhancement was 19.9% \ub1 7.5 (18.3; 11.7-34.6). Time to peak enhancement was 134.0 \ub1 125.1 (68.4; 59.6-364.5) seconds. During CECT, first visualization of the contrast medium was at 3.6 \ub1 0.5 (4; 3-4) seconds in the aorta, 10.7 \ub1 2.2 (10.5; 7-14) seconds in the hepatic arteries, and 15 \ub1 4.5 (14.5; 10-24) seconds in the liver parenchyma. Time to peak was 14.1 \ub1 3.4 (13; 11-21) and 31 \ub1 9.6 (29; 23-45) seconds in the aorta and the liver parenchyma, respectively. Conclusion: CEUS and dynamic CECT are practical means to determine liver hemodynamics in green iguanas. Distribution of contrast medium in iguana differed from mammals. Specific reference ranges of hepatic perfusion for diagnostic evaluation of the liver in iguanas are necessary since the use of mammalian references may lead the clinician to formulate incorrect diagnostic suspicions

    Evaluation of the Iatrogenic Sciatic Nerve Injury following Double Pelvic Osteotomy Performed with Piezoelectric Cutting Tool in Dogs

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    (1) Background: The double pelvic osteotomy (DPO) is a prophylactic surgical procedure associated with 0.4% incidence of sciatic nerve injury. The piezoelectric cutting tool is a surgical device able to involve only mineralized tissue avoiding neurovascular tissue and other soft tissue. This study aimed to evaluate the sciatic nerve injury observed in dogs underwent iliac osteotomy performed using the piezoelectric cutting tool. (2) Methods: Dogs underwent DPO performed with piezoelectric cutting tool were included. Neurological assessment was performed 6 and 24 h after surgery and then repeated 12 days, 4 and 8 weeks after surgery. Temporary and or permanent sciatic nerve injury were recorded. (3) Results: 84 DPOs performed in fifty dogs were included. No temporary/permanent neurological disease associated with iatrogenic damage of the sciatic nerve were observed. (4) Conclusions: The iliac osteotomy performed with piezoelectric cutting tool was not associated to iatrogenic sciatic nerve injury

    Metabolomics Fingerprint Predicts Risk of Death in Dilated Cardiomyopathy and Heart Failure

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    BACKGROUND: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Metabolomics may help refine risk assessment and potentially guide HF management, but dedicated studies are few. This study aims at stratifying the long-term risk of death in a cohort of patients affected by HF due to dilated cardiomyopathy (DCM) using serum metabolomics via nuclear magnetic resonance (NMR) spectroscopy. METHODS: A cohort of 106 patients with HF due to DCM, diagnosed and monitored between 1982 and 2011, were consecutively enrolled between 2010 and 2012, and a serum sample was collected from each participant. Each patient underwent half-yearly clinical assessments, and survival status at the last follow-up visit in 2019 was recorded. The NMR serum metabolomic profiles were retrospectively analyzed to evaluate the patient's risk of death. Overall, 26 patients died during the 8-years of the study. RESULTS: The metabolomic fingerprint at enrollment was powerful in discriminating patients who died (HR 5.71, p = 0.00002), even when adjusted for potential covariates. The outcome prediction of metabolomics surpassed that of N-terminal pro b-type natriuretic peptide (NT-proBNP) (HR 2.97, p = 0.005). Metabolomic fingerprinting was able to sub-stratify the risk of death in patients with both preserved/mid-range and reduced ejection fraction [hazard ratio (HR) 3.46, p = 0.03; HR 6.01, p = 0.004, respectively]. Metabolomics and left ventricular ejection fraction (LVEF), combined in a score, proved to be synergistic in predicting survival (HR 8.09, p = 0.0000004). CONCLUSIONS: Metabolomic analysis via NMR enables fast and reproducible characterization of the serum metabolic fingerprint associated with poor prognosis in the HF setting. Our data suggest the importance of integrating several risk parameters to early identify HF patients at high-risk of poor outcomes

    Use of Transversus Abdominis Plane and Intercostal Blocks in Bitches Undergoing Laparoscopic Ovariectomy: A Randomized Controlled Trial

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    In humans and dogs, loco-regional anesthesia is associated with lower peri-operative opioid consumption and less related side effects. The combination of transversus abdominis plane (TAP) and intercostal blocks can be used to desensitize the entire abdominal wall in dogs. The aim of this study was to evaluate the effectiveness of TAP and intercostal blocks in bitches undergoing laparoscopic ovariectomy. Twenty client-owned bitches were enrolled in this double-blinded randomized controlled trial. After premedication with dexmedetomidine, methadone and ketamine, the animals were randomized into two groups. Dogs in the TAP group received intercostal blocks from T8 to T10 and a TAP block with ropivacaine. Dogs in the FEN group received a fentanyl bolus and a constant rate infusion for the entire duration of the procedure. Intra-operative cardiovascular stability, post-operative pain scores, rescue opioid requirement, dysphoria during recovery, time to attain sternal recumbency and interest in food at 6 h post-extubation were compared. Bitches in the TAP group received a statistically significant lower amount of rescue fentanyl intra-operatively and methadone post-operatively. Pain scores were lower in the TAP group until 6 h post-extubation. No difference was found for dysphoric recoveries, time to attain sternal recumbency and appetite at 6 h post-extubation. No adverse event was recorded for any of the dogs. The combination of TAP and intercostal blocks can be part of an effective multi-modal analgesic strategy in bitches undergoing laparoscopic ovariectomy

    Lymphatic drainage mapping with indirect lymphography for canine mammary tumors

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    Mammary gland tumors are the most common canine neoplasms. They account for 25– 50% of all tumors diagnosed in bitches. Metastases and recurrences develop in about 35–70% of bitches following excision. The presence of regional lymph node metastases is a relevant factor affecting prognosis and treatment in cases of mammary gland tumors. The sentinel lymph node (SLN) is the first lymph node (or nodes) in the regional lymphatic basin that receives lymphatic flow from the primary neoplasm. The aim of this study is to investigate the SLN with indirect lymphography for a mammary tumor in dogs. The knowledge of the precise drainage pattern and SLN of the neoplastic mammary glands would provide clinically relevant information to the surgeon and to the oncologist, and it would be of high importance for the surgeon not only for performing the most adequate surgical excision but also for determining an accurate post-surgical prognosis
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