Classification of degenerative parkinsonism subtypes by support-vector-machine analysis and striatal 123I-FP-CIT indices.

OBJECTIVES: To provide an automated classification method for degenerative parkinsonian syndromes (PS) based on semiquantitative 123I-FP-CIT SPECT striatal indices and support-vector-machine (SVM) analysis. METHODS: 123I-FP-CIT SPECT was performed at a single-center level on 370 individuals with PS, including 280 patients with Parkinson's disease (PD), 21 with multiple system atrophy-parkinsonian type (MSA-P), 41 with progressive supranuclear palsy (PSP) and 28 with corticobasal syndrome (CBS) (mean age 70.3 years, 47% female, mean disease duration at scan 1.4 year), as well as 208 age- and gender-matched control subjects. Striatal volumes-of-interest (VOIs) uptake, VOIs asymmetry indices (AIs) and caudate/putamen (C/P) ratio were used as input for SVM individual classification using fivefold cross-validation. RESULTS: Univariate analyses showed significantly lower VOIs uptake, higher striatal AI and C/P ratio for each PS in comparison to controls (all p  70% accuracy. Overall, striatal AI and C/P ratio on the more affected side had the highest weighting factors. CONCLUSION: Semiquantitative 123I-FP-CIT SPECT striatal evaluation combined with SVM represents a promising approach to disentangle PD from non-degenerative conditions and from atypical PS at the early stage

Non-neuronal TRPA1 encodes mechanical allodynia associated with neurogenic inflammation and partial nerve injury in rats

Background and purpose: The pro-algesic transient receptor potential ankyrin 1 (TRPA1) channel, expressed by a subpopulation of primary sensory neurons, has been implicated in various pain models in mice. However, evidence in rats indicates that TRPA1 conveys nociceptive signals elicited by channel activators, but not those associated with tissue inflammation or nerve injury. Here, in rats, we explored the TRPA1 role in mechanical allodynia associated with stimulation of peptidergic primary sensory neurons (neurogenic inflammation) and moderate (partial sciatic nerve ligation, pSNL) or severe (chronic constriction injury, CCI) sciatic nerve injury. Experimental approach: Acute nociception and mechanical hypersensitivity associated with neurogenic inflammation and sciatic nerve injury (pSNL and CCI) were investigated in rats with TRPA1 pharmacological antagonism or genetic silencing. TRPA1 presence and function were analysed in cultured rat Schwann cells. Key results: Hind paw mechanical allodynia (HPMA), but not acute nociception, evoked by local injection of capsaicin or allyl isothiocyanate, the TRP vanilloid 1 (TRPV1) or the TRPA1 activators was mediated by CGRP released from peripheral sensory nerve terminals. CGRP-evoked HPMA was sustained by a ROS-dependent TRPA1 activation, probably in Schwann cells. HPMA evoked by pSNL, but not that evoked by CCI, was mediated by ROS and TRPA1 without the involvement of CGRP. Conclusions and implications: As found in mice, TRPA1 mediates mechanical allodynia associated with neurogenic inflammation and moderate nerve injury in rats. The channel contribution to mechanical hypersensitivity is a common feature in rodents and might be explored in humans

Fingerprints of brain disease:connectome identifiability in Alzheimer's disease

Functional connectivity patterns in the human brain, like the friction ridges of a fingerprint, can uniquely identify individuals. Does this "brain fingerprint" remain distinct even during Alzheimer's disease (AD)? Using fMRI data from healthy and pathologically ageing subjects, we find that individual functional connectivity profiles remain unique and highly heterogeneous during mild cognitive impairment and AD. However, the patterns that make individuals identifiable change with disease progression, revealing a reconfiguration of the brain fingerprint. Notably, connectivity shifts towards functional system connections in AD and lower-order cognitive functions in early disease stages. These findings emphasize the importance of focusing on individual variability rather than group differences in AD studies. Individual functional connectomes could be instrumental in creating personalized models of AD progression, predicting disease course, and optimizing treatments, paving the way for personalized medicine in AD management.</p

The Impact of the COVID-19 Pandemic on the Mental Health of Healthcare Workers in Italy: Analyzing the Role of Individual and Workplace-Level Factors in the Reopening Phase After Lockdown

IntroductionItaly is one of the high-income countries hit hardest by Covid-19. During the first months of the pandemic, Italian healthcare workers were praised by media and the public for their efforts to face the emergency, although with limited knowledge and resources. However, healthcare workers soon had to face new challenges at a time when the national health system was working hard to recover. This study focuses on this difficult period to assess the impact of the COVID-19 pandemic on the mental health of Italian healthcare workers. Materials and MethodsHealthcare workers from all Italian regions [n = 5,502] completed an online questionnaire during the reopening phase after the first wave lockdown. We assessed a set of individual-level factors (e.g., stigma and violence against HCWs) and a set of workplace-level factors (e.g., trust in the workplace capacity to handle COVID-19) that were especially relevant in this context. The primary outcomes assessed were score &gt;= 15 on the Patient Health Questionnaire-9 and score &gt;= 4 on the General Health Questionnaire-12, indicators of clinically significant depressive symptoms and psychological distress, respectively. Logistic regression analyses were performed on depressive symptoms and psychological distress for each individual- and workplace-level factor adjusting for gender, age, and profession. ResultsClinically significant depressive symptoms were observed in 7.5% and psychological distress in 37.9% of HCWs. 30.5% of healthcare workers reported having felt stigmatized or discriminated, while 5.7% reported having experienced violence. Feeling stigmatized or discriminated and experiencing violence due to being a healthcare worker were strongly associated with clinically significant depressive symptoms [OR 2.98, 95%CI 2.36-3.77 and OR 4.72 95%CI 3.41-6.54] and psychological distress [OR 2.30, 95%CI 2.01-2.64 and OR 2.85 95%CI 2.16-3.75]. Numerous workplace-level factors, e.g., trust in the workplace capacity to handle COVID-19 [OR 2.43, 95%CI 1.92-3.07] and close contact with a co-worker who died of COVID-19 [OR 2.05, 95%CI 1.56-2.70] were also associated with clinically significant depressive symptoms. Similar results were found for psychological distress. ConclusionsOur study emphasizes the need to address discrimination and violence against healthcare professionals and improve healthcare work environments to strengthen the national health system's capacity to manage future emergencies

Low in‑hospital mortality rate in patients with COVID‑19 receiving thromboprophylaxis: data from the multicentre observational START‑COVID Register

Abstract COVID-19 infection causes respiratory pathology with severe interstitial pneumonia and extra-pulmonary complications; in particular, it may predispose to thromboembolic disease. The current guidelines recommend the use of thromboprophylaxis in patients with COVID-19, however, the optimal heparin dosage treatment is not well-established. We conducted a multicentre, Italian, retrospective, observational study on COVID-19 patients admitted to ordinary wards, to describe clinical characteristic of patients at admission, bleeding and thrombotic events occurring during hospital stay. The strategies used for thromboprophylaxis and its role on patient outcome were, also, described. 1091 patients hospitalized were included in the START-COVID-19 Register. During hospital stay, 769 (70.7%) patients were treated with antithrombotic drugs: low molecular weight heparin (the great majority enoxaparin), fondaparinux, or unfractioned heparin. These patients were more frequently affected by comorbidities, such as hypertension, atrial fibrillation, previous thromboembolism, neurological disease,and cancer with respect to patients who did not receive thromboprophylaxis. During hospital stay, 1.2% patients had a major bleeding event. All patients were treated with antithrombotic drugs; 5.4%, had venous thromboembolism [30.5% deep vein thrombosis (DVT), 66.1% pulmonary embolism (PE), and 3.4% patients had DVT + PE]. In our cohort the mortality rate was 18.3%. Heparin use was independently associated with survival in patients aged ≥ 59 years at multivariable analysis. We confirmed the high mortality rate of COVID-19 in hospitalized patients in ordinary wards. Treatment with antithrombotic drugs is significantly associated with a reduction of mortality rates especially in patients older than 59 years

Development of multi-component non-sex pheromone blends to monitor both sexes of Cydia pomonella (Lepidoptera: Tortricidae)

Nineteen host plant volatiles (HPVs) were screened for attractivity to adult codling moth Cydia pomonella (L.) as a fourth component of core blends (3K) including (E,Z)-2,4-ethyl decadienoate, (E)-4,8-dimethyl-1,3,7-nonatriene and acetic acid. Each new quaternary combination was compared with a previously reported attractive bisexual lure (4K), consisting of the 3K blend plus 6-ethenyl-2,2,6-trimethyloxan-3-ol (pyranoid linalool oxide, pyrLOX). All lure evaluations were conducted in apple, Malus domestica (Borkhausen). Several compounds were found to significantly lower total and/or female catches when added to the 3K blend, including (Z)-3-hexenol, (E)-2-hexanal and hexyl butanoate (female and total moths), and (Z)-3-hexenyl acetate and linalool (female moths). Other compounds when added to the 3K blend did not increase or decrease moth catches, including methyl salicylate, (E)-beta-ocimene, limonene, beta-caryophyllene, butyl hexanoate, farnesol, terpineol, terpinen-4-ol and alpha-pinene. A few added compounds significantly increased moth catches compared with the 3K blend, including beta-pinene (male moths), (Z)-jasmone (male and total moths), (E)-beta-farnesene and beta-myrcene (female and total moths), and (E,E)-alpha-farnesene (male, female, and total moths). In addition, each of these five compounds when added to the 3K core blend performed similarly to the 4K lure (male, females, and total moths). Further studies should expand these results through tests of these and other new blends with a range of component ratios and total loading amounts. Field trials should also be replicated within all host crops of codling moth and across major geographical production regions

Synthesis and Biological Activity of Peptide α-Ketoamide Derivatives as Proteasome Inhibitors

Proteasome activity affects cell cycle progression as well as the immune response, and it is largely recognized as an attractive pharmacological target for potential therapies against several diseases. Herein we present the synthesis of a series of pseudodi/tripeptides bearing at the C-terminal position different α-ketoamide moieties as pharmacophoric units for the interaction with the catalytic threonine residue that sustains the proteolytic action of the proteasome. Among these, we identified the 1-naphthyl derivative 13c as a potent and selective inhibitor of the β5 subunit of the 20S proteasome, exhibiting nanomolar potency in vitro (β5 IC50 = 7 nM, β1 IC50 = 60 μM, β2 IC50 &gt; 100 μM). Furthermore, it significantly inhibited proliferation and induced apoptosis of the human colorectal carcinoma cell line HCT116