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1.
Neurol Sci ; 42(1): 333-336, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32651857

RESUMEN

In its typical presentation, chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) occurs more often in old males as a progressive/recurrent motor and sensory nerve dysfunction with tendon areflexia. However, CIDP has also atypical clinical presentations, including pure sensory neuropathies, among which chronic immune sensory polyradiculopathy (CISP) accounts for only 0.5% of all CIDP, with no juvenile cases reported as yet. A 17-year-old girl presented for a progressive sensory ataxia and hands clumsiness. Diffuse tendon areflexia and hypokinaesthesia were observed. Motor and sensory nerve conduction studies were normal. F-waves were normal in median nerves and elongated in tibial nerves. H-reflex and somatosensory evoked potentials (SSEP) were absent. CSF normal cellularity with hyperproteinorrachia was found. Paraneoplastic, metabolic, and paraproteinemic neuropathies were excluded. A diagnosis of CISP has been made based on the presence of pure sensory symptoms in a polyneuropathic distribution, normal peripheral nerve conduction studies, and two supportive criteria (SSEP and CSF). Our paper describes the first CISP case in the pediatric age. We confirm SSEP and CSF as useful complementary tests for this diagnosis also at this age and suggest that clinicians should consider CISP in the spectrum of sporadic sensory ataxias of the pediatric age. We also suggest that in the presence of normal F-wave and peripheral motor nerve conduction, an absent H-reflex can further substantiate SSEPs in the diagnosis of CISP. Intravenous immunoglobulins were rapidly effective and safe.


Asunto(s)
Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante , Polirradiculopatía , Adolescente , Niño , Potenciales Evocados Somatosensoriales , Femenino , Humanos , Inmunoglobulinas Intravenosas , Masculino , Conducción Nerviosa , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/diagnóstico
2.
Neurobiol Dis ; 74: 295-304, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25486547

RESUMEN

Long-term administration of l-3,4-dihydroxyphenylalanine (levodopa), the mainstay treatment for Parkinson's disease (PD), is accompanied by fluctuations in its duration of action and motor complications (dyskinesia) that dramatically affect the quality of life of patients. Levodopa-induced dyskinesias (LID) can be modeled in rats with unilateral 6-OHDA lesions via chronic administration of levodopa, which causes increasingly severe axial, limb, and orofacial abnormal involuntary movements (AIMs) over time. In previous studies, we showed that the direct activation of CB1 cannabinoid receptors alleviated rat AIMs. Interestingly, elevation of the endocannabinoid anandamide by URB597 (URB), an inhibitor of endocannabinoid catabolism, produced an anti-dyskinetic response that was only partially mediated via CB1 receptors and required the concomitant blockade of transient receptor potential vanilloid type-1 (TRPV1) channels by capsazepine (CPZ) (Morgese et al., 2007). In this study, we showed that the stimulation of peroxisome proliferator-activated receptors (PPAR), a family of transcription factors activated by anandamide, contributes to the anti-dyskinetic effects of URB+CPZ, and that the direct activation of the PPARγ subtype by rosiglitazone (RGZ) alleviates levodopa-induced AIMs in 6-OHDA rats. AIM reduction was associated with an attenuation of levodopa-induced increase of dynorphin, zif-268, and of ERK phosphorylation in the denervated striatum. RGZ treatment did not decrease striatal levodopa and dopamine bioavailability, nor did it affect levodopa anti-parkinsonian activity. Collectively, these data indicate that PPARγ may represent a new pharmacological target for the treatment of LID.


Asunto(s)
Antidiscinéticos/farmacología , Discinesia Inducida por Medicamentos/tratamiento farmacológico , Levodopa/toxicidad , PPAR gamma/agonistas , Trastornos Parkinsonianos/metabolismo , Tiazolidinedionas/farmacología , Animales , Antidiscinéticos/farmacocinética , Antidiscinéticos/toxicidad , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Dinorfinas/metabolismo , Discinesia Inducida por Medicamentos/metabolismo , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Levodopa/farmacocinética , Levodopa/farmacología , Masculino , Oxidopamina , PPAR gamma/metabolismo , Trastornos Parkinsonianos/tratamiento farmacológico , Fosforilación/efectos de los fármacos , Ratas Sprague-Dawley , Ratas Wistar , Rosiglitazona
4.
Anim Genet ; 45(2): 256-66, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24303943

RESUMEN

Italy counts several sheep breeds, arisen over centuries as a consequence of ancient and recent genetic and demographic events. To finely reconstruct genetic structure and relationships between Italian sheep, 496 subjects from 19 breeds were typed at 50K single nucleotide polymorphism loci. A subset of foreign breeds from the Sheep HapMap dataset was also included in the analyses. Genetic distances (as visualized either in a network or in a multidimensional scaling analysis of identical by state distances) closely reflected geographic proximity between breeds, with a clear north-south gradient, likely because of high levels of past gene flow and admixture all along the peninsula. Sardinian breeds diverged more from other breeds, a probable consequence of the combined effect of ancient sporadic introgression of feral mouflon and long-lasting genetic isolation from continental sheep populations. The study allowed the detection of previously undocumented episodes of recent introgression (Delle Langhe into the endangered Altamurana breed) as well as signatures of known, or claimed, historical introgression (Merino into Sopravissana and Gentile di Puglia; Bergamasca into Fabrianese, Appenninica and, to a lesser extent, Leccese). Arguments that would question, from a genomic point of view, the current breed classification of Bergamasca and Biellese into two separate breeds are presented. Finally, a role for traditional transhumance practices in shaping the genetic makeup of Alpine sheep breeds is proposed. The study represents the first exhaustive analysis of Italian sheep diversity in an European context, and it bridges the gap in the previous HapMap panel between Western Mediterranean and Swiss breeds.


Asunto(s)
Variación Genética , Genoma , Filogeografía , Ovinos/genética , Animales , Cruzamiento , Genotipo , Italia , Polimorfismo de Nucleótido Simple
5.
Eur J Gynaecol Oncol ; 35(6): 731-3, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25556283

RESUMEN

PURPOSE OF INVESTIGATION: An endometrioid carcinoma coexisting with choriocarcinomatous differentiation is an uncommon event with an aggressive clinical course and a poor prognosis. MATERIALS AND METHODS: The authors describe an endometrioid carcinoma of the endometrium provided with a focus of choriocarcinoma-like cells in a 50-year-old menstruated woman with a history of abnormal uterine bleeding. A total bilateral hystero-annessectomy was performed. RESULTS: Histopathologic study showed endometrioid adenocarcinoma limited to the endometrium with a single microinvasive (< one mm) choriocarcinomatous focus. Immunohistochemistry established intense reactivity of tumor cells for CK 7 and AE1/AE3, for beta-human chorionic gonadotropin (beta-hCG), and for HER2 confirming the diagnosis. During the clinical course and follow-up, serum levels of beta-hCG were always negative. Up to date the patient is still alive with no evidence of disease. CONCLUSION: Even if endometrioid carcinoma with choriocarcinomatous differentiation is considered highly malignant, occasionally it may have a good prognosis, especially when a non-invasive behaviour is detected together with negative serum beta-hCG levels.


Asunto(s)
Carcinoma Endometrioide/patología , Coriocarcinoma/patología , Neoplasias Endometriales/patología , Carcinoma Endometrioide/sangre , Diferenciación Celular , Gonadotropina Coriónica Humana de Subunidad beta/sangre , Neoplasias Endometriales/sangre , Femenino , Humanos , Persona de Mediana Edad
6.
Eur J Gynaecol Oncol ; 35(6): 662-5, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25556271

RESUMEN

According to the National Health and Social Life Survey, sexual dysfunction affects about 43% of perimenopausal women. A diagnosis of cancer has a profound physical, emotional, and social impact, influencing the relationship with the body, the perception of illness and death, family, social and professional relationships, and the relationship with the partner and, consequently, sexuality. Loss of desire, dyspareunia, orgasmic disorder, difficulties in emotional and physical closeness to the partner, feelings of shame, and inadequacy commonly occur after treatment for uterine cancer; however, if these problems are associated with surgery or with radiotherapy, still remains unclear. According to this study, the authors may conclude that the experience of cancer could lead patients to a rediscovery of. their own sexuality and to an improvement in the relationship with their partner, showing that, sometimes, the relational and psychological factors assume greater importance than physical effects on sexuality, and they can somewhere compensate the morphofunctional failure.


Asunto(s)
Sexualidad , Neoplasias Uterinas/psicología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Satisfacción Personal , Neoplasias Uterinas/radioterapia , Neoplasias Uterinas/cirugía
7.
ESMO Open ; 9(9): 103680, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39214048

RESUMEN

BACKGROUND: Mesenchymal-epithelial transition (MET) exon 14 (METex14) skipping mutation is a rare alteration in non-small-cell lung cancer (NSCLC), occurring in about 3%-4% of cases. Here we report disease and patient characteristics, and efficacy and tolerability of MET inhibitors among advanced METex14 NSCLC patients from the Italian real-world registry ATLAS. MATERIALS AND METHODS: Clinical-pathological and molecular data, and treatment efficacy/tolerability outcomes were retrospectively collected from the ATLAS registry. RESULTS: From July 2020 to July 2023 a total of 146 METex14 advanced NSCLC patients were included across 27 Italian centers. Median age was 74 years, and most patients were male (52%), with an Eastern Cooperative Oncology Group performance status < 2 (72%) and adenocarcinoma subtype (83%). One hundred and twenty-five out of 146 (86%) patients received at least one line of systemic anticancer therapy. Fifty-six (38%) were treated with capmatinib and 34 (23%) with tepotinib. 29% and 52% of them received targeted treatment in the first and second line, respectively. In the cohort of patients treated with MET inhibitors, the response rate (RR) was 37% (33% in previously treated patients and 46% in treatment-naïve) with a disease control rate of 62%. With a median follow-up of 10.8 months, progression-free survival was 6.6 months [95% confidence interval (CI) 4.3-8.3 months] and overall survival was 10.7 months (95% CI 7.2-19.3 months). In patients with measurable brain metastases (17 cases), the intracranial RR was 41%. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 12% of patients with grade 3 peripheral edema in 7% of cases. A fatal adverse reaction occurred in one patient due to pneumonitis. TRAEs-related dose reduction and discontinuation were reported in 6% and 8% of cases, respectively. CONCLUSION: Capmatinib and tepotinib represent an effective treatment option in NSCLC patients with METex14. Real-world efficacy outcomes are worse than those reported in prospective clinical trials. Their activity is more pronounced in the treatment-naïve population, suggesting that this is the right setting in the management of patients with METex14.

8.
ESMO Open ; 9(6): 103592, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38878323

RESUMEN

BACKGROUND: Osimertinib represents the standard of care for the treatment of advanced non-small-cell lung cancer (NSCLC) harboring classical epidermal growth factor receptor (EGFR) mutations, constituting 80%-90% of all EGFR alterations. In the remaining cases, an assorted group of uncommon alterations of EGFR (uEGFR) can be detected, which confer variable sensitivity to previous generations of EGFR inhibitors, overall with lower therapeutic activity. Data on osimertinib in this setting are limited and strongly warranted. PATIENTS AND METHODS: The ARTICUNO study retrospectively evaluated data on osimertinib activity from patients with advanced NSCLC harboring uEGFR treated in 21 clinical centers between August 2017 and March 2023. Data analysis was carried out with a descriptive aim. Investigators collected response data according to RECIST version 1.1 criteria. The median duration of response, progression-free survival (mPFS), and overall survival were estimated by the Kaplan-Meier method. RESULTS: Eighty-six patients harboring uEGFR and treated with osimertinib were identified. Patients with 'major' uEGFR, that is, G719X, L861X, and S768I mutations (n = 51), had an overall response rate (ORR) and mPFS of 50% and 9 months, respectively. Variable outcomes were registered in cases with rarer 'minor' mutations (n = 27), with ORR and mPFS of 31% and 4 months, respectively. Among seven patients with exon 20 insertions, ORR was 14%, while the best outcome was registered among patients with compound mutations including at least one classical EGFR mutation (n = 13). Thirty patients presented brain metastases (BMs) and intracranial ORR and mPFS were 58% and 9 months, respectively. Amplification of EGFR or MET, TP53 mutations, and EGFR E709K emerged after osimertinib failure in a dataset of 18 patients with available rebiopsy. CONCLUSION: The ARTICUNO study confirms the activity of osimertinib in patients with uEGFR, especially in those with compound uncommon-common mutations, or major uEGFR, even in the presence of BMs. Alterations at the E709 residue of EGFR are associated with resistance to osimertinib.


Asunto(s)
Acrilamidas , Compuestos de Anilina , Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Neoplasias Pulmonares , Mutación , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Estudios Retrospectivos , Acrilamidas/uso terapéutico , Acrilamidas/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Receptores ErbB/genética , Compuestos de Anilina/uso terapéutico , Compuestos de Anilina/farmacología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Indoles , Pirimidinas
9.
Clin Exp Obstet Gynecol ; 40(4): 607-8, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24597270

RESUMEN

Posterior reversible encephalopathy syndrome (PRES), is an acute, neurotoxic state. It is a very rare clinico-neuroradiological entity, and it is a complication of multiple clinical conditions. The association of PRES with toxemia in pregnancy is established. In this article, the authors discuss the case of a 22-year-old woman, gravida 1, 36-week pregnant, with extensive, bilateral white matter hypodensity, predominantly involving the parieto-occipital lobes region. These changes were highly suggestive of posterior reversible encephalopathy. This case report demonstrates that early treatment with control of blood pressure seizures can reverse this condition and also prevent progression to an irreversible damage, thus emphasizing the need for early diagnosis and treatment.


Asunto(s)
Síndrome de Leucoencefalopatía Posterior/diagnóstico , Complicaciones del Embarazo/diagnóstico , Cesárea , Femenino , Edad Gestacional , Humanos , Hipertensión/complicaciones , Hipertensión/terapia , Síndrome de Leucoencefalopatía Posterior/patología , Síndrome de Leucoencefalopatía Posterior/terapia , Embarazo , Resultado del Embarazo , Tomografía Computarizada por Rayos X , Adulto Joven
10.
Clin Exp Obstet Gynecol ; 40(4): 596-8, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24597266

RESUMEN

Placenta accreta refers to any abnormally invasive placental implantation. Diagnosis is suspected postpartum with failed delivery of a retained placenta. Massive obstetrical hemorrhage is a known complication, often requiring peripartum hysterectomy. The authors report a case of placenta accreta in a primiparous patient with multinodular leiofibromyomatosis of the uterus following failed manual removals of a retained placenta. They describe a conservative management in a stable patient desiring future fertility with a unilateral prophylactic uterine artery embolization, a multidose regimen of methotrexate, and a subsequent abdominal myomectomy.


Asunto(s)
Preservación de la Fertilidad/métodos , Placenta Accreta/terapia , Embolización Terapéutica , Femenino , Humanos , Histerectomía , Metotrexato/administración & dosificación , Paridad , Embarazo , Arteria Uterina , Miomectomía Uterina
11.
Clin Exp Obstet Gynecol ; 40(4): 524-30, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24597248

RESUMEN

Endometriosis is a chronic disorder, clinically associated with chronic pelvic pain, dyspareunia, dysmenorrhea, and infertility. Its socio-economic impact is extensive, given the large number of affected women in reproductive age, its symptomatology (that interferes with normal social life and the patient's ability to work), and its frequent association with infertility. Nonetheless, the diagnosis of endometriosis is still difficult and late in the evolution of the disorder. The authors have used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) criteria to make a systematic review of the literature of the last 28 years, seeking to identify potential biomarkers useful for a non-invasive diagnosis of endometriosis. The authors have highlighted more than 50 biomarkers in the studies included in the present report, but they have not succeeded in identifying a clinically useful non-invasive diagnostic biomarker or panel of biomarkers. More studies are needed before biomarkers can be introduced in clinical practice.


Asunto(s)
Biomarcadores/análisis , Endometriosis/diagnóstico , Antígenos de Carbohidratos Asociados a Tumores/análisis , Líquido Ascítico/química , Autoanticuerpos/análisis , Biomarcadores/sangre , Biomarcadores/orina , Antígeno Ca-125 , Citocinas/análisis , Endometrio/química , Femenino , Hormonas/análisis , Humanos , Recuento de Linfocitos
12.
Plant Biol (Stuttg) ; 25(6): 973-980, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37429743

RESUMEN

Plant trait-based functional spectra are crucial to assess ecosystem functions and services. Whilst most research has focused on aboveground vegetative traits (leaf economic spectrum, LES), contrasting evidence on any coordination between the LES and root economic spectrum (RES) has been reported. Studying spectra variation along environmental gradients and accounting for species' phylogenetic relatedness may help to elucidate the strength of coordination between above- and belowground trait variation. We focused on leaf and root traits of 39 species sampled in three distinct habitats (front, back and slack) along a shoreline-inland gradient on coastal dunes. We tested, within a phylogenetic comparative framework, for the presence of the LES and RES, for any coordination between these spectra, and explored their relation to variation in ecological strategies along this gradient. In each habitat, three-quarters of trait variation is captured in two-dimensional spectra, with species' phylogenetic relatedness moderately influencing coordination and trade-off between traits. Along the shoreline-inland gradient, aboveground traits support the LES in all habitats. Belowground traits are consistent with the RES in the back-habitat only, where the environmental constraints are weaker, and a coordination between leaf and root traits was also found, supporting the whole-plant spectrum (PES). This study confirms the complexity when seeking any correlation between the LES and RES in ecosystems characterized by multiple environmental pressures, such as those investigated here. Changes in traits adopted to resist environmental constraints are similar among species, independent of their evolutionary relatedness, thus explaining the low phylogenetic contribution in support of our results.


Asunto(s)
Evolución Biológica , Ecosistema , Filogenia , Plantas , Hojas de la Planta
13.
Eur J Gynaecol Oncol ; 33(6): 656-7, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23327066

RESUMEN

OBJECTIVES: The aim of this study was to illustrate the importance of hysteroscopy in the evolution of mitotically active leiomyoma to leiomyosarcoma (LMS). Uterine sarcomas are rare tumors. The three microscopic criteria are: 1) the presence of coagulative tumor necrosis, 2) high mitotic index (exceeding 15 x 10 catabolite gene activator (CGA) and 3) occurrence of moderate to severe cytologic atypia. The authors report a case of a 52-year-old nulliparous woman with a LMS detected two months after a hysteroscopic resection of a mitotically active leiomyoma. After the first hysteroscopic resection the diagnosis was atypical leiomyoma with a mitotic index of two per ten high-power field (hpf) in the absence of coagulation necrosis. After two months, a new myoma was detected and another hysteroscopic resection was performed: the microscopic diagnosis was LMS and a total abdominal hysterectomy with bilateral salpingo-oophorectomy (BSO) was performed. CONCLUSION: The patient must undergo close clinical and instrumental follow-up procedures. Hysteroscopy plays an important role in the evaluation and evolution of both recurrent and de novo disease.


Asunto(s)
Histeroscopía/métodos , Leiomioma/cirugía , Leiomiosarcoma/patología , Miomectomía Uterina , Neoplasias Uterinas/cirugía , Femenino , Humanos , Leiomioma/patología , Leiomiosarcoma/cirugía , Persona de Mediana Edad , Neoplasias Uterinas/patología
14.
Clin Exp Obstet Gynecol ; 39(4): 519-21, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23444758

RESUMEN

Optical trocars have been introduced as an alternative technique for obtaining access to the peritoneal cavity. The advantage is that each layer of the abdominal wall can be identified avoiding inadvertent injuries due to a lack of vision. From March 2010 to March 2011, 138 women underwent laparoscopy for benign diseases. They were submitted to gynecological laparoscopy for direct optical access. There was no evidence of vascular injuries. This study confirms that the optical trocar is a safe, rapid, and effective method, that offers a real perception of the safety of the entrance into the abdomen.


Asunto(s)
Procedimientos Quirúrgicos Ginecológicos/instrumentación , Adulto , Diseño de Equipo , Femenino , Procedimientos Quirúrgicos Ginecológicos/métodos , Humanos , Laparoscopía , Persona de Mediana Edad , Neumoperitoneo Artificial , Resultado del Tratamiento , Adulto Joven
15.
Eur Rev Med Pharmacol Sci ; 26(1): 225-231, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35048999

RESUMEN

OBJECTIVE: Corpus callosum (CC) is commonly affected in multiple sclerosis (MS), with known association between CC atrophy and MS clinical activity. In this study, we assessed the association of callosal atrophy, lesions volume and residual CC volume with the clinical disability of early MS patients. SUBJECTS AND METHODS: Thirteen MS subjects (9 female, mean age 36.9 years), studied with magnetic resonance imaging (MRI) were selected. MRI scans were performed at baseline (T0), at 6 (T1), 12 (T2), and 24 months (T3) from baseline. CC was segmented into three sections (genu, body, and splenium); callosal boundaries were outlined and all CC lesions were manually traced. Normal CC and CC lesion volumes were measured using a semiautomatic software. RESULTS: From January 2014 to December 2016, all selected patients had confluent lesions on MRI at T3 with a significant increase in the size of confluent lesions compared to baseline (p=0.0007). At T1, a significant increase in the size of confluent (p=0.02) and single lesions located in the callosal body (p=0.04) was detected in patients with EDSS ≥1.5. Also, CC residual volume (CCR) rather than the whole CC volume (CCV) significantly correlated (p=0.03) with the clinical progression of MS in the whole cohort. CONCLUSIONS: In early MS patients with higher EDSS at baseline, a significant increase in confluent CC lesions size is evident, particularly in the callosal body. Also, median CCR is significantly associated with MS progression in the whole MS group, regardless of initial EDSS. Given their significant association with disability, we encourage measuring CC body lesions and residual CC size for therapeutic decisions and prognostic planning in early MS.


Asunto(s)
Cuerpo Calloso , Esclerosis Múltiple , Adulto , Atrofia/patología , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/patología , Progresión de la Enfermedad , Femenino , Humanos , Imagen por Resonancia Magnética , Esclerosis Múltiple/patología
16.
J Neurosci Methods ; 338: 108685, 2020 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-32173400

RESUMEN

Aggregates of alpha-synuclein (αSyn) have been described in Parkinson's disease (PD) patients, and recent evidence has suggested that the most toxic αSyn species in PD are small soluble aggregates including oligomers, prefibrils, protofibrils. The physiological function of αSyn is still highly debated, with a possible role in synaptic vesicle trafficking and release at the presynaptic compartment, and in the regulation of gene expression in the nucleus. Emerging evidence indicate that most of αSyn functions are related with the crucial ability to bind biological membranes, which is associated with structural conversion from a disordered monomer to an α-helical enriched structure. Conformational properties of αSyn can be modulated by a number of factors including post-translational modifications, gene duplication and triplication-driven overexpression, single point mutations, environmental changes, which affect membrane binding and the protein propensity to aggregate in toxic species. The recognized toxic role of αSyn in PD has laid the rational for purposing of αSyn-based, neuropathologically relevant preclinical models of PD. Different approaches have led to the establishment of transgenic models, viral vector-based models, and more recently models based on the intracerebral inoculation of exogenous αSyn preformed fibrils/oligomers. Here, we overview and compare viral vector-based models of αSyn overexpression and models obtained by direct intracerebral infusion of in vitro preformed αSyn species. The advantages and pitfalls associated with these different approaches are discussed.


Asunto(s)
Enfermedad de Parkinson , alfa-Sinucleína , Animales , Humanos , Enfermedad de Parkinson/genética , Roedores , Virus , alfa-Sinucleína/genética
17.
Epidemiol Psychiatr Sci ; 30: e1, 2020 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-33331255

RESUMEN

AIMS: Healthcare workers exposed to coronavirus 2019 (COVID-19) patients could be psychologically distressed. This study aims to assess the magnitude of psychological distress and associated factors among hospital staff during the COVID-19 pandemic in a large tertiary hospital located in north-east Italy. METHODS: All healthcare and administrative staff working in the Verona University Hospital (Veneto, Italy) during the COVID-19 pandemic were asked to complete a web-based survey from 21 April to 6 May 2020. Symptoms of post-traumatic distress, anxiety and depression were assessed, respectively, using the Impact of Event Scale (IES-R), the Self-rating Anxiety Scale (SAS) and the Patient Health Questionnaire (PHQ-9). Personal socio-demographic information and job characteristics were also collected, including gender, age, living condition, having pre-existing psychological problems, occupation, length of working experience, hospital unit (ICUs and sub-intensive COVID-19 units vs. non-COVID-19 units). A multivariable logistic regression analysis was performed to identify factors associated with each of the three mental health outcomes. RESULTS: A total of 2195 healthcare workers (36.9% of the overall hospital staff) participated in the study. Of the participants, 35.7% were nurses, 24.3% other healthcare staff, 16.4% residents, 13.9% physicians and 9.7% administrative staff. Nine per cent of healthcare staff worked in ICUs, 8% in sub-intensive COVID-19 units and 7.6% in other front-line services, while the remaining staff worked in hospital units not directly engaged with COVID-19 patients. Overall, 63.2% of participants reported COVID-related traumatic experiences at work and 53.8% (95% CI 51.0%-56.6%) showed symptoms of post-traumatic distress; moreover, 50.1% (95% CI 47.9%-52.3%) showed symptoms of clinically relevant anxiety and 26.6% (95% CI 24.7%-28.5%) symptoms of at least moderate depression. Multivariable logistic regressions showed that women, nurses, healthcare workers directly engaged with COVID-19 patients and those with pre-existing psychological problems were at increased risk of psychopathological consequences of the pandemic. CONCLUSIONS: The psychological impact of the COVID-19 pandemic on healthcare staff working in a highly burdened geographical of north-east Italy is relevant and to some extent greater than that reported in China. The study provides solid grounds to elaborate and implement interventions pertaining to psychology and occupational health.


Asunto(s)
COVID-19/psicología , Personal de Salud/psicología , Trastornos Mentales/epidemiología , Adulto , Femenino , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Pandemias , Factores de Riesgo , SARS-CoV-2 , Factores Sexuales , Centros de Atención Terciaria/estadística & datos numéricos
18.
Anim Genet ; 40(5): 737-42, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19466941

RESUMEN

The objective of this work was to characterize the complete coding region of the ovine acylCoA:diacylglycerol acyltransferase 1 (DGAT1) gene of three Italian sheep breeds: Sarda, Altamurana and Gentile di Puglia. Characterization was accomplished by direct sequencing of 8676 bp of the relevant DNA, including introns and partial 5' and 3' untranslated regions (UTRs). We detected five novel SNPs; one SNP (g.5553C>T) is located in intron 2, has similar frequencies in the three breeds and showed a negative association with milk fat content. More interesting is an SNP in the 5' UTR (g.127C>A), the occurrence of which is rare in the higher milk-fat breeds (Altamurana and Gentile di Puglia); it is located in the core sequence of Sp1, a putative binding site of transcription factors. This SNP showed a significant negative association with milk fat content in the Sarda sheep. Because DGAT1 plays a fundamental role in triacylglycerol synthesis, the novel detected SNP in the 5' UTR of the DGAT1 gene might explain, at least partially, the variation of fat content in the milk of Sarda sheep.


Asunto(s)
Diacilglicerol O-Acetiltransferasa/genética , Leche/química , Ovinos/genética , Animales , Secuencia de Bases , Cartilla de ADN/genética , Estudios de Asociación Genética/veterinaria , Italia , Datos de Secuencia Molecular , Polimorfismo de Nucleótido Simple/genética , Análisis de Secuencia de ADN/veterinaria
19.
Anim Genet ; 40(6): 982-5, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19706028

RESUMEN

In this study, we investigated the susceptibility to scrapie of Sarda breed sheep carrying the genotype ARQ/ARQ with additional polymorphisms at the PRNP gene. To do this, we examined 256 scrapie-affected sheep and 320 flock-mate negative controls from 24 flocks. Logistic regression analysis demonstrated that sheep carrying the ARQ/ARQ genotype with additional dimorphisms had lower risk of becoming scrapie affected when compared with those with ARQ/ARQ(wildtype) genotype. ARQ/ARQ genotypes that were detected with heterozygous or homozygous p.Asn176Lys and p.Met137Thr dimorphisms were associated with the lowest susceptibility to the disease. A significant lower risk was also associated with the p.Arg154His dimorphism, while p.Leu141Phe had a protective effect that was not statistically significant.


Asunto(s)
Predisposición Genética a la Enfermedad , Polimorfismo Genético , Priones/genética , Scrapie/genética , Animales , Ovinos
20.
J Dairy Sci ; 92(12): 5814-33, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19923587

RESUMEN

Dairy sheep have been farmed traditionally in the Mediterranean basin in southern Europe, central Europe, eastern Europe, and in Near East countries. Currently, dairy sheep farming systems vary from extensive to intensive according to the economic relevance of the production chain and the specific environment and breed. Modern breeding programs were conceived in the 1960s. The most efficient selection scheme for local dairy sheep breeds is based on pyramidal management of the population with the breeders of nucleus flocks at the top, where pedigree and official milk recording, artificial insemination, controlled natural mating, and breeding value estimation are carried out to generate genetic progress. The genetic progress is then transferred to the commercial flocks through artificial insemination or natural-mating rams. Increasing milk yield is still the most profitable breeding objective for several breeds. Almost all milk is used for cheese production and, consequently, milk content traits are very important. Moreover, other traits are gaining interest for selection: machine milking ability and udder morphology, resistance to diseases (mastitis, internal parasites, scrapie), and traits related to the nutritional value of milk (fatty acid composition). Current breeding programs based on the traditional quantitative approach have achieved appreciable genetic gains for milk yield. In many cases, further selection goals such as milk composition, udder morphology, somatic cell count, and scrapie resistance have been implemented. However, the possibility of including other traits of selective interest is limited by high recording costs. Also, the organizational effort needed to apply the traditional quantitative approach limits the diffusion of current selection programs outside the European Mediterranean area. In this context, the application of selection schemes assisted by molecular information, to improve either traditional dairy traits or traits costly to record, seems to be attractive in dairy sheep. At the moment, the most effective strategy seems to be the strengthening of research projects aimed at finding causal mutations along the genes affecting traits of economic importance. However, genome-wide selection seems to be unfeasible in most dairy sheep breeds.


Asunto(s)
Cruzamiento/métodos , Industria Lechera/métodos , Industria Lechera/tendencias , Ovinos/genética , Animales , Cruzamiento/normas , Femenino , Inmunidad Innata/genética , Lactancia/genética , Enfermedades de las Ovejas/genética
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