Upper limb motor pre-clinical assessment in Parkinson's disease using machine learning

Abstract Introduction Parkinson's disease (PD) is a common neurodegenerative disorder characterized by disabling motor and non-motor symptoms. For example, idiopathic hyposmia (IH), which is a reduced olfactory sensitivity, is typical in >95% of PD patients and is a preclinical marker for the pathology. Methods In this work, a wearable inertial device, named SensHand V1, was used to acquire motion data from the upper limbs during the performance of six tasks selected by MDS-UPDRS III. Three groups of people were enrolled, including 30 healthy subjects, 30 IH people, and 30 PD patients. Forty-eight parameters per side were computed by spatiotemporal and frequency data analysis. A feature array was selected as the most significant to discriminate among the different classes both in two-group and three-group classification. Multiple analyses were performed comparing three supervised learning algorithms, Support Vector Machine (SVM), Random Forest (RF), and Naive Bayes, on three different datasets. Results Excellent results were obtained for healthy vs. patients classification (F-Measure 0.95 for RF and 0.97 for SVM), and good results were achieved by including subjects with hyposmia as a separate group (0.79 accuracy, 0.80 precision with RF) within a three-group classification. Overall, RF classifiers were the best approach for this application. Conclusion The system is suitable to support an objective PD diagnosis. Further, combining motion analysis with a validated olfactory screening test, a two-step non-invasive, low-cost procedure can be defined to appropriately analyze people at risk for PD development, helping clinicians to identify also subtle changes in motor performance that characterize PD onset

Monitoring the Prevalence of Antimicrobial Resistance in Companion Animals: Results from Clinical Isolates in an Italian University Veterinary Hospital

The role of companion animals in the spread of antimicrobial resistance (AMR) is still not well known. As part of a wider surveillance system, this study aimed to provide data about AMR in bacterial isolates from infections in companion animals referred to an Italian University Veterinary Hospital (VUH) from November 2020 to September 2022. A total of 940 isolates were identified with MALDI-TOF MS and subsequently the antimicrobial susceptibility test (AST) for 12 antimicrobials was performed. Urine was the most commonly submitted specimen (54.92%) and Escherichia coli was the most common bacterial species isolated (36.06%). Out of the 940 isolates, 747 (79.47%) were nonsusceptible to at least one drug (AMR), while 420 (44.68%) were considered multidrug resistant (MDR). The highest nonsusceptibility percentages were recorded for clindamycin (59.65 %), erythromycin (58.96 %), ampicillin (52.85%), and enrofloxacin (48.19%). Alarming percentages were recorded also for ceftiofur (25.51%), amoxicillin–clavulanate (22.99%), and piperacillin–tazobactam (15.85%). In multivariable risk factors analysis, previous use of invasive devices ( in both cases) and previous use of antimicrobials ( in both cases) were statistically related with higher AMR and MDR percentages. Apart from a general evaluation, the study focused on specific bacterial species (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) and specimens (blood cultures, urine from suspected healthcare-associated urinary tract infections, and surgical site infections), showing in both cases higher AMR and MDR percentages compared to average. These data highlight the urgency to further investigate AMR spread in pets and how passive surveillance systems can be effective tools to monitor AMR and to optimize antimicrobial use

Biomechanical parameter assessment for classification of Parkinson's disease on clinical scale

The primary goal of this study was to investigate computerized assessment methods to classify motor dysfunctioning of patients with Parkinsonâ\u80\u99s disease on the clinical scale. In this proposed system, machine learningâ\u80\u93based computerized assessment methods were introduced to assess the motor performance of patients with Parkinsonâ\u80\u99s disease. Biomechanical parameters were acquired from six exercises through wearable inertial sensors: SensFoot V2 and SensHand V1. All patients were evaluated via neurologist by means of the clinical scale. The average rating was calculated from all exercise ratings given by clinicians to estimate overall rating for each patient. Patients were divided in two groups: slightâ\u80\u93mild patients with Parkinsonâ\u80\u99s disease and moderateâ\u80\u93severe patients with Parkinsonâ\u80\u99s disease according to average rating (â\u80\u9c0: slight and mildâ\u80\u9d and â\u80\u9c1: moderate and severeâ\u80\u9d). Feature selection methods were used for the selection of significant features. Selected features were trained in support vector machine, logistic regression, and neural network to classify the two groups of patients. The highest classification accuracy obtained by support vector machine classifier was 79.66%, with 0.8790 area under the curve. A 76.2% classification accuracy was obtained with 0.7832 area under the curve through logistic regression. A 83.10% classification accuracy was obtained by neural network classifier, with 0.889 area under the curve. Strong distinguishability of the models between the two groups directs the high possibility of motor impairment classification through biomechanical parameters in patients with Parkinsonâ\u80\u99s disease based on the clinical scale

Synthesis of thia-Michael-Type Adducts between Naphthoquinones and N-Acetyl-L-Cysteine and Their Biological Activity

A series of naphthoquinones, namely, 1,4-naphthoquinone, menadione, plumbagin, juglone, naphthazarin, and lawsone, were reacted with N-acetyl-L-cysteine, and except for lawsone, which did not react, the related adducts were obtained. After the tuning of the solvent and reaction conditions, the reaction products were isolated as almost pure from the complex reaction mixture via simple filtration and were fully characterized. Therefore, the aim of this work was to evaluate whether the antitumor activity of new compounds of 1,4-naphthoquinone derivatives leads to an increase in ROS in tumor cell lines of cervical carcinoma (HeLa), neuroblastoma (SH-SY5Y), and osteosarcoma (SaOS2, U2OS) and in normal dermal fibroblast (HDFa). The MTT assay was used to assay cell viability, the DCF-DA fluorescent probe to evaluate ROS induction, and cell-cycle analysis to measure the antiproliferative effect. Compounds 8, 9, and 12 showed a certain degree of cytotoxicity towards all the malignant cell lines tested, while compound 11 showed biological activity at higher IC50 values. Compounds 8 and 11 induced increases in ROS generation after 1 h of exposure, while after 48 h of treatment, only 8 induced an increase in ROS formation in HeLa cells. Cell-cycle analysis showed that compound 8 caused an increase in the number of G0/G1-phase cells in the HeLa experiment, while for the U2OS and SH-SY5Y cell lines, it led to an accumulation of S-phase cells. Therefore, these novel 1,4-naphthoquinone derivatives may be useful as antitumoral agents in the treatment of different cancers

Dimerization of GPCRs:Novel insight into the role of FLNA and SSAs regulating SST₂ and SST₅ homo- and hetero-dimer formation

The process of GPCR dimerization can have profound effects on GPCR activation, signaling, and intracellular trafficking. Somatostatin receptors (SSTs) are class A GPCRs abundantly expressed in pituitary tumors where they represent the main pharmacological targets of somatostatin analogs (SSAs), thanks to their antisecretory and antiproliferative actions. The cytoskeletal protein filamin A (FLNA) directly interacts with both somatostatin receptor type 2 (SST2) and 5 (SST5) and regulates their expression and signaling in pituitary tumoral cells. So far, the existence and physiological relevance of SSTs homo- and hetero-dimerization in the pituitary have not been explored. Moreover, whether octreotide or pasireotide may play modulatory effects and whether FLNA may participate to this level of receptor organization have remained elusive. Here, we used a proximity ligation assay (PLA)-based approach for the in situ visualization and quantification of SST2/SST5 dimerization in rat GH3 as well as in human melanoma cells either expressing (A7) or lacking (M2) FLNA. First, we observed the formation of endogenous SST5 homo-dimers in GH3, A7, and M2 cells. Using the PLA approach combined with epitope tagging, we detected homo-dimers of human SST2 in GH3, A7, and M2 cells transiently co-expressing HA- and SNAP-tagged SST2. SST2 and SST5 can also form endogenous hetero-dimers in these cells. Interestingly, FLNA absence reduced the basal number of hetero-dimers (-36.8 ± 6.3% reduction of PLA events in M2, P &lt; 0.05 vs. A7), and octreotide but not pasireotide promoted hetero-dimerization in both A7 and M2 (+20.0 ± 11.8% and +44.1 ± 16.3% increase of PLA events in A7 and M2, respectively, P &lt; 0.05 vs. basal). Finally, immunofluorescence data showed that SST2 and SST5 recruitment at the plasma membrane and internalization are similarly induced by octreotide and pasireotide in GH3 and A7 cells. On the contrary, in M2 cells, octreotide failed to internalize both receptors whereas pasireotide promoted robust receptor internalization at shorter times than in A7 cells. In conclusion, we demonstrated that in GH3 cells SST2 and SST5 can form both homo- and hetero-dimers and that FLNA plays a role in the formation of SST2/SST5 hetero-dimers. Moreover, we showed that FLNA regulatesSST2 and SST5 intracellular trafficking induced by octreotide and pasireotide. </p

Oxygen Sensing in Neurodegenerative Diseases: Current Mechanisms, Implication of Transcriptional Response, and Pharmacological Modulation

: Significance: Oxygen (O2) sensing is the fundamental process through which organisms respond to changes in O2 levels. Complex networks exist allowing the maintenance of O2 levels through the perception, capture, binding, transport, and delivery of molecular O2. The brain extreme sensitivity to O2 balance makes the dysregulation of related processes crucial players in the pathogenesis of neurodegenerative diseases (NDs). In this study, we wish to review the most relevant advances in O2 sensing in relation to Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Recent Advances: Over the years, it has been clarified that most NDs share common pathways, a great number of which are in relation to O2 imbalance. These include hypoxia, hyperoxia, reactive oxygen species production, metabolism of metals, protein misfolding, and neuroinflammation. Critical Issues: There is still a gap in knowledge concerning how O2 sensing plays a role in the above indicated neurodegenerations. Specifically, O2 concentrations are perceived in body sites that are not limited to the brain, but primarily reside in other organs. Moreover, the mechanisms of O2 sensing, gene expression, and signal transduction seem to correlate with neurodegeneration, but many aspects are mechanistically still unexplained. Future Directions: Future studies should focus on the precise characterization of O2 level disruption and O2 sensing mechanisms in NDs. Moreover, advances need to be made also concerning the techniques used to assess O2 sensing dysfunctions in these diseases. There is also the need to develop innovative therapies targeting this precise mechanism rather than its secondary effects, as early intervention is necessary. Antioxid. Redox Signal. 38, 160-182

Identification of a novel pathway in sporadic Amyotrophic Lateral Sclerosis mediated by the long non-coding RNA ZEB1-AS1

Background: Deregulation of transcription in the pathogenesis of sporadic Amyotrophic Lateral Sclerosis (sALS) is taking central stage with RNA-sequencing analyses from sALS patients tissues highlighting numerous deregulated long non-coding RNAs (lncRNAs). The oncogenic lncRNA ZEB1-AS1 is strongly downregulated in peripheral blood mononuclear cells of sALS patients. In addition, in cancer-derived cell lines, ZEB1-AS1 belongs to a negative feedback loop regulation with hsa-miR-200c, acting as a molecular sponge for this miRNA. The role of the lncRNA ZEB1-AS1 in sALS pathogenesis has not been characterized yet, and its study could help identifying a possible disease-modifying target. Methods: the implication of the ZEB1-AS1/ZEB1/hsa-miR-200c/BMI1 pathway was investigated in multiple patients-derived cellular models (patients-derived peripheral blood mononuclear cells and induced pluripotent stem cells-derived neural stem cells) and in the neuroblastoma cell line SH-SY5Y, where its function was inhibited via RNA interference. Molecular techniques such as Real Time PCR, Western Blot and Immunofluorescence were used to assess the pathway dysregulation. Results: Our results show a dysregulation of a signaling pathway involving ZEB1-AS1/hsa-miR-200c/β-Catenin in peripheral blood mononuclear cells and in induced pluripotent stem cells-derived neural stem cells from sALS patients. These results were validated in vitro on the cell line SH-SY5Y with silenced expression of ZEB1-AS1. Moreover, we found an increase for ZEB1-AS1 during neural differentiation with an aberrant expression of β-Catenin, highlighting also its aggregation and possible impact on neurite length. Conclusions: Our results support and describe the role of ZEB1-AS1 pathway in sALS and specifically in neuronal differentiation, suggesting that an impairment of β-Catenin signaling and an alteration of the neuronal phenotype are taking place

Predicting suicide attempts in depressed adolescents: Clarifying the role of disinhibition and childhood sexual abuse

Background Suicide is the second leading cause of death among adolescents, and depressed youth are six times more likely to make suicide attempts as compared to non-depressed adolescents. The present study examined the unique and interactive effects of two well-established correlates of suicidality – childhood sexual abuse (CSA) and disinhibition – in predicting suicide attempts among depressed adolescents. Method Participants were 163 adolescents (125 females) aged 13 to 18 (M = 15.60, SD = 1.27) diagnosed with Major Depressive Disorder (n = 95, 58.3%) and/or Dysthymia (n = 69, 42.3%) recruited from an acute residential treatment service. Participants completed interviews assessing psychopathology and suicidality, self-report measures of depressive symptoms and CSA, and a computerized disinhibition task. Results Consistent with hypotheses, CSA moderated the association between disinhibition and adolescents' report of their past year and lifetime suicide attempts. Specifically, higher disinhibition was associated with a greater likelihood of having made a suicide attempt among adolescents with a history of CSA, but not among those without. The same pattern of results held in analyses of suicide attempt frequency. Limitations Primary findings were based on observational, cross-sectional data, and therefore, causal relationships cannot be inferred. The gender imbalance in the sample precluded stratifying our analyses by gender. CSA was ascertained by self-report; replication of the results with more objective measures is warranted. Conclusions Our findings indicate that CSA and disinhibition may work together to predict elevated suicide risk, and these results have implications for early identification efforts in youth at high risk for suicide.Psycholog

Cystatin C as a nmarker of renal function Immediately after liver transplantation

To verify whether cystatin C may be of some use as a renal function marker immediately after orthotopic liver transplantation (OLT), we compared serum cystatin C (S(Cyst)), serum creatinine (S(cr)), and creatinine clearance (C(cr)) levels with the glomerular filtration rate (GFR). On postoperative days 1, 3, 5, and 7, S(Cyst) and S(cr) was measured in simultaneously drawn blood samples, whereas C(cr) was calculated using a complete 24-hour urine collection. The GFR was determined on the same days by means of iohexol plasma clearance (I-GFR). The correlation between 1/S(Cyst) and I-GFR was stronger than that of 1/S(cr) or C(cr) (P< 0.01). In the case of moderate reductions in I-GFR (80-60 mL/minute/1.73 m), S(cr) remained within the normal range, whereas the increase in S(cyst) was beyond its upper limit; for I-GFR reductions to lower levels (59-40 mL/minute/1.73 m), S(cr) increased slightly, whereas S(cyst) was twice its upper normal limit. When we isolated all of the I-GFR values on days 3, 5, and 7 that were > or = 30% lower than that recorded on the first postoperative day, S(Cyst)(P< 0.0001) and S(cr) (P< 0.01) levels were increased, whereas C(cr) remained unchanged (P = 0.09). Receiver operating characteristic (ROC) area-under-the-curve analysis showed that the diagnostic accuracy of S(cyst) was better than that of S(cr) and C(cr). S(cyst) levels of 1.4, 1.7, and 2.2 mg/L respectively predicted I-GFR levels of 80, 60, and 40 mL/minute/1.73 m. In conclusion, cystatin C is a reliable marker of renal function during the immediate post-OLT period, especially when the goal is to identify moderate changes in GFR

The Vehicle, Spring 2002

Table of Contents Black Lace Under White OxfordAmee Bohrerpage 4 We Have ForgottenAubrey Bonannopage 4 The Grand Old Drink of the SouthNatalie Espositopage 5 SymphonyChristie Jean Hallpage 6 Sol from the CityJeremy Hartzellpage 7-10 Yellow TimeErika Larsonpage 10 Death of a Salesman\u27s WifeErika Larsonpage 11-12 This SideErika Larsonpage 12 JuiceTimothy Lockmanpage 13 Chess GameMike Scalespage 13 Facing HimTimothy Lockmanpage 14 ShameRon Lybargerpage 15 Sunlit HydrantMike Scalespage 15 11-22-63Reginald Mansfieldpage 16 four cornersDave Moutraypage 17 regretting PamDave Moutraypage 18-19 Chicago SummertimeLisa Sarmpage 19 Hands of TimeJessica Shekletonpage 20 An AppointmentJosh Sopiarzpage 21 Our Fates and Old Men\u27s GlassesJosh Sopiarzpage 22 An Apple Orchard PicnicJosh Sopiarzpage 23 November GraysJoe Webbpage 24 The AxJanet Windeguthpage 25-31 The Old Porch SwingJoe Webbpage 32 Green MachineQynn McCrory, H.S. Writing Contest Winnerpage 33 My Little PonyJ. Benjamin Blount, H.S. Writing Contest Winnerpage 34 Biographiespage 35-36https://thekeep.eiu.edu/vehicle/1077/thumbnail.jp