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The most common conditions with symptomatic joint hypermobility are hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD). Diagnosing these overlapping connective tissue disorders remains challenging due to the lack of established causes and reliable diagnostic tests. hEDS is diagnosed applying the 2017 diagnostic criteria, and patients with symptomatic joint hypermobility but not fulfilling these criteria are labeled as HSD, which is not officially recognized by all healthcare systems. The 2017 criteria were introduced to improve diagnostic specificity but have faced criticism for being too stringent and failing to adequately capture the multisystemic involvement of hEDS. Herein, we retrospectively evaluated 327 patients from 213 families with a prior diagnosis of hypermobility type EDS or joint hypermobility syndrome based on Villefranche and Brighton criteria, to assess the effectiveness of the 2017 criteria in distinguishing between hEDS and HSD and document the frequencies of extra-articular manifestations. Based on our findings, we propose that the 2017 criteria should be made less stringent to include a greater number of patients who are currently encompassed within the HSD category. This will lead to improved diagnostic accuracy and enhanced patient care by properly capturing the diverse range of symptoms and manifestations present within the hEDS/HSD spectrum.
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Síndrome de Ehlers-Danlos , Instabilidade Articular , Humanos , Estudos Retrospectivos , Instabilidade Articular/diagnóstico , Instabilidade Articular/epidemiologia , Estudos Transversais , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/epidemiologia , Itália/epidemiologiaRESUMO
PURPOSE: Gender stereotypes refer to consensual or cultural shared beliefs about the attributes of men and women, influencing society behaviors, interpersonal relationships, education, and workplace. The literature has shown the existence of gender stereotypes on career choices, internalization of roles, and school and social experiences and demonstrates the impact of demographic factors on stereotypes. However, all the studies conducted in Italy available in scientific literature analyzed small sample sizes within specific schools of university settings, with a limited age range. METHODS: To assess the current state of gender stereotypes in Italy, we conducted an online survey from October 2022 to January 2023 on the general population residing in Italy. The questionnaire comprised sociodemographic factors and questions about gender stereotypes, investigating six fields: games, jobs, personality traits, home and family activities, sports, and moral judgments. RESULTS: The study involved 1854 participants, mostly women (70.1%) with an undergraduate or postgraduate degree (57.5%). The statistical and descriptive analyses revealed that gender stereotypes influenced respondents' beliefs, with statistically significant effects observed in most questions when stratifying by age, gender, and degree. Principal component analysis was performed to assess latent variables in different fields, revealing significant main stereotypes in each category. No statistically significant differences between men and women were found for the fields home and family activities, games, and moral judgments, confirming that stereotypes affect both men and women in the same way. CONCLUSIONS: Our results show the persistence of gender stereotypes in any fields investigated, although our cohort is predominantly composed of high educational level women living in the North of Italy. This demonstrates that the long-standing gender stereotypes are prevalent, pernicious, and, unfortunately, internalized at times even by successful women pushbacking and sabotaging them unconsciously.
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Estereotipagem , Humanos , Itália , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem , Idoso , Identidade de Gênero , Sexismo/psicologia , Adolescente , Relações InterpessoaisRESUMO
Although Parkinson's disease (PD) key neuropathological hallmarks are well known, the underlying pathogenic mechanisms of the disease still need to be elucidated to identify innovative disease-modifying drugs and specific biomarkers. NF-κB transcription factors are involved in regulating several processes associated with neurodegeneration, such as neuroinflammation and cell death, that could be related to PD pathology. NF-κB/c-Rel deficient (c-rel-/-) mice develop a progressive PD-like phenotype. The c-rel-/- mice present both prodromal and motor symptoms as well as key neuropathological features, including nigrostriatal dopaminergic neurons degeneration, accumulation of pro-apoptotic NF-κB/RelA acetylated at the lysine 310 residue (Ac-RelA(lys310)) and progressive caudo-rostral brain deposition of alpha-synuclein. c-Rel inhibition can exacerbate MPTP-induced neurotoxicity in mice. These findings support the claim that misregulation of c-Rel protein may be implicated in PD pathophysiology. In this study, we aimed at evaluating c-Rel levels and DNA-binding activity in human brains and peripheral blood mononuclear cells (PBMCs) of sporadic PD patients. We analyzed c-Rel protein content and activity in frozen substantia nigra (SN) samples from post-mortem brains of 10 PD patients and 9 age-matched controls as well as in PBMCs from 72 PD patients and 40 age-matched controls. c-Rel DNA-binding was significantly lower and inversely correlated with Ac-RelA(lys310) content in post-mortem SN of sporadic PD cases, when compared to healthy controls. c-Rel DNA-binding activity was also reduced in PBMCs of followed-up PD subjects. The decrease of c-Rel activity in PBMCs from PD patients appeared to be independent from dopaminergic medication or disease progression, as it was evident even in early stage, drug-naïve patients. Remarkably, the levels of c-Rel protein were comparable in PD and control subjects, pointing out a putative role for post-translational modifications of the protein in c-Rel dysfunctions. These findings support that PD is characterized by the loss of NF-κB/c-Rel activity that potentially has a role in PD pathophysiology. Future studies will be aimed at addressing whether the reduction of c-Rel DNA-binding could constitute a novel biomarker for PD.
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Intoxicação por MPTP , Doença de Parkinson , Humanos , Camundongos , Animais , NF-kappa B/metabolismo , Doença de Parkinson/metabolismo , Proteínas Proto-Oncogênicas c-rel/metabolismo , Leucócitos Mononucleares/metabolismo , Substância Negra/metabolismo , Neurônios Dopaminérgicos/metabolismo , Intoxicação por MPTP/patologiaRESUMO
AIM: To investigate the prevalence and clinical manifestations of reading, writing, and mathematics disorders in children with cerebral palsy (CP). We explored how the clinical profile of these children differed from those with specific learning disorders (SLDs), taking into account several factors, particularly IQ scores, neuropsychological aspects, and the presence of a visual impairment. METHOD: A prospective cross-sectional study was conducted in 42 children with CP (mean age 9 years 8 months; SD = 2 years 2 months) and 60 children with SLDs (mean age 10 years; SD = 1 year 7 months). Clinical characteristics, neuromotor and cognitive profiles, neuropsychological aspects (speech performance, academic skills, visual attention, phonological awareness, working memory), and signs of visual impairment (visual acuity, contrast sensitivity, visual field, oculomotor functions) were assessed. A machine learning approach consisting of a random forest algorithm, where the outcome was the diagnosis and the covariates were the clinical variables collected in the sample, was used for the analyses. RESULTS: About 59% of the children with CP had reading, writing, or mathematics disorders. Children with CP with learning disorders had a low performance IQ, normal phonological awareness, and working memory difficulties, whereas children with SLDs had normal performance IQ, impaired phonological awareness, and mild working memory difficulties. There were no differences in verbal IQ between the two groups. INTERPRETATION: Learning disorders are frequently associated with CP, with different clinical characteristics, compared with SLDs. Assessment of academic skills is mandatory in these children, even if the IQ is normal. At school age, specific interventions to promote academic skills in children with CP could be a major rehabilitative goal.
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Fibrillary aggregated α-synuclein (α-syn) deposition in Lewy bodies (LB) characterizes Parkinson's disease (PD) and is believed to trigger dopaminergic synaptic failure and a retrograde terminal-to-cell body neuronal degeneration. We described that the neuronal phosphoprotein synapsin III (Syn III) cooperates with α-syn to regulate dopamine (DA) release and can be found in the insoluble α-syn fibrils composing LB. Moreover, we showed that α-syn aggregates deposition, and the associated onset of synaptic deficits and neuronal degeneration occurring following adeno-associated viral vectors-mediated overexpression of human α-syn in the nigrostriatal system are hindered in Syn III knock out mice. This supports that Syn III facilitates α-syn aggregation. Here, in an interventional experimental design, we found that by inducing the gene silencing of Syn III in human α-syn transgenic mice at PD-like stage with advanced α-syn aggregation and overt striatal synaptic failure, we could lower α-syn aggregates and striatal fibers loss. In parallel, we observed recovery from synaptic vesicles clumping, DA release failure, and motor functions impairment. This supports that Syn III consolidates α-syn aggregates, while its downregulation enables their reduction and redeems the PD-like phenotype. Strategies targeting Syn III could thus constitute a therapeutic option for PD.
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Doença de Parkinson , alfa-Sinucleína , Animais , Dopamina , Neurônios Dopaminérgicos/metabolismo , Inativação Gênica , Camundongos , Camundongos Transgênicos , Doença de Parkinson/genética , Doença de Parkinson/terapia , Fenótipo , Substância Negra/metabolismo , Sinapsinas/genética , Sinapsinas/metabolismo , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismoRESUMO
BACKGROUND: Lombardy was the most affected Italian region by the first phase of the COVID-19 pandemic and underwent urgent reorganization for the management of emergencies, including subarachnoid hemorrhage from a ruptured cerebral aneurysm (aSAH). The aim of the study was to define demographics, clinical, and therapeutic features of aSAH during the COVID-19 outbreak and compare these with a historical cohort. METHODS: In this observational multicenter cohort study, patients aged 18 years or older, who were diagnosed with aSAH at the participating centers in Lombardy from March 9 to May 10, 2020, were included (COVID-19 group). In order to minimize bias related to possible SAH seasonality, the control group was composed of patients diagnosed with aSAH from March 9 to May 10 of the three previous years, 2017-2018-2019 (pre-pandemic group). Twenty-three demographic, clinical, and therapeutic features were collected. Statistical analysis was performed. RESULTS: Seventy-two patients during the COVID-19 period and 179 in the control group were enrolled at 14 centers. Only 4 patients were positive for SARS-CoV-2. The "diagnostic delay" was significantly increased (+ 68%) in the COVID-19 group vs. pre-pandemic (1.06 vs. 0.63 days, respectively, p-value = 0.030), while "therapeutic delay" did not differ significantly between the two periods (0.89 vs. 0.74 days, p-value = 0.183). Patients with poor outcome (GOS at discharge from 1 to 3) were higher during the COVID-19 period (54.2%) compared to pre-pandemic (40.2%, p = 0.044). In logistic regression analysis, in which outcome was the dichotomized Glasgow Outcome Scale (GOS), five variables showed p-values < 0.05: age at admission, WFNS grade, treatment (none), days in ICU, and ischemia. CONCLUSIONS: We documented a significantly increased "diagnostic delay" for subarachnoid hemorrhages during the first COVID-19 outbreak in Lombardy. However, despite the dramatic situation that the healthcare system was experiencing, the Lombardy regional reorganization model, which allowed centralization of neurosurgical emergencies such as SAHs, avoided a "therapeutic delay" and led to results overall comparable to the control period.
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COVID-19 , Hemorragia Subaracnóidea , Estudos de Coortes , Humanos , Pandemias , SARS-CoV-2 , Hemorragia Subaracnóidea/epidemiologia , Resultado do TratamentoRESUMO
The use of combination anti-retroviral therapy (cART) correlates with longer and healthier life and with nearly normal life expectancy in people living with HIV. However, cART does not completely restore health. Chronic immune activation and inflammation persist in treated patients and have been described as predictors for clinical events and mortality in HIV-infected patients. Limited information is available on the impact of the various cART regimens on inflammation/immunoactivation. The aim of this work was to explore the impact of elvitegravir, dolutegravir, raltegravir (integrase strand transfer inhibitors, INSTIs) and atazanavir (protease inhibitor, PI) on several soluble markers of immune activation and inflammation during the first year of effective combination anti-retroviral therapy (cART). We conducted an observational retrospective cohort study in HIV-infected cART-naïve patients who initiated an INSTI or atazanavir regimen between March 2015 and February 2016 and a serum sample was available at baseline, 6 and 12â¯months after initiation. We compared the trend of D-Dimer, TNF- α, IL-2, IL-6, IL-7, IL-10, CCL4/MIP1-ß, CCL5/RANTES, s-CD14, s-CD163, hs-CRP levels among the 4 arms of treatment. Percentage of variation from baseline was also measured for all markers. A total of 36 patients were included. We observed heterogeneous modifications in inflammation markers among arms. In particular, we noted that EVG have significant negative effect on s-CD14, hs-CRP, IL-6 and D-Dimer in respect to other INSTIs and this different effect occurs mainly during the first 6â¯months of cART. IL-7 values increased in the three arms with INSTIs (significantly only in EGV, 159.8%, pâ¯=â¯0.0003) and decreased significantly in patients on PI (-48.96%; pâ¯=â¯0.04) over the period. In conclusion, our results provide further data on changes of inflammatory marker levels, especially for the new INSTIs. Our data show that among INSTIs, EVG seems to have a worse impact on inflammation.
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Fármacos Anti-HIV/uso terapêutico , Citocinas/sangue , Quimioterapia Combinada , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , Adulto , Sulfato de Atazanavir/uso terapêutico , Feminino , HIV-1/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Inflamação/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Oxazinas/uso terapêutico , Piperazinas/uso terapêutico , Piridonas/uso terapêutico , Quinolonas/uso terapêutico , Raltegravir Potássico/uso terapêuticoRESUMO
OBJECTIVE: The COVID-19 pandemic has forced many countries into lockdown and has led to the postponement of nonurgent neurosurgical procedures. Although stress has been investigated during this pandemic, there are no reports on anxiety in neurosurgical patients undergoing nonurgent surgical procedures. METHODS: Neurosurgical patients admitted to hospitals in eastern Lombardy for nonurgent surgery after the lockdown prospectively completed a pre- and postoperative structured questionnaire. Recorded data included demographics, pathology, time on surgical waiting list, anxiety related to COVID-19, primary pathology and surgery, safety perception during hospital admission before and after surgery, and surgical outcomes. Anxiety was measured with the State-Trait Anxiety Inventory. Descriptive statistics were computed on the different variables and data were stratified according to pathology (oncological vs nononcological). Three different models were used to investigate which variables had the greatest impact on anxiety, oncological patients, and safety perception, respectively. Because the variables (Xs) were of a different nature (qualitative and quantitative), mostly asymmetrical, and related to outcome (Y) by nonlinear relationships, a machine learning approach composed of three steps (1, random forest growing; 2, relative variable importance measure; and 3, partial dependence plots) was chosen. RESULTS: One hundred twenty-three patients from 10 different hospitals were included in the study. None of the patients developed COVID-19 after surgery. State and trait anxiety were reported by 30.3% and 18.9% of patients, respectively. Higher values of state anxiety were documented in oncological compared to nononcological patients (46.7% vs 25%; p = 0.055). Anxiety was strongly associated with worry about primary pathology, surgery, disease worsening, and with stress during waiting time, as expected. Worry about positivity to SARS-CoV-2, however, was the strongest factor associated with anxiety, even though none of the patients were infected. Neuro-oncological disease was associated with state anxiety and with worry about surgery and COVID-19. Increased bed distance and availability of hand sanitizer were associated with a feeling of safety. CONCLUSIONS: These data underline the importance of psychological support, especially for neuro-oncological patients, during a pandemic.
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Ansiedade/epidemiologia , Ansiedade/psicologia , COVID-19/epidemiologia , COVID-19/psicologia , Procedimentos Neurocirúrgicos/psicologia , Inquéritos e Questionários , Adulto , Idoso , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
The identification of ancillary biomarkers useful to improve diagnosis is a major challenge for adipocytic liposarcoma (LPS), the most common type among soft tissue sarcomas affecting adulthood. Recent findings have reported the expression of some proteins belonging to Caveolin and Cavin families as a critical hallmark distinctive of the least aggressive, well-differentiated LPS tumors. These proteins are involved in the biogenesis, morphology and function of caveolae, minute bulb-shaped domains of the plasma membrane that play a crucial role in the adipose tissue by controlling hormone-dependent uptake of nutrients and contributing to the maintenance of tissue integrity. In light of this, in this paper we covered different topics, including metabolism, hypoxia and cell mechanoprotection, to outline the rationale for considering a deeper investigation of Caveolin and Cavin protein members in LPS neoplasms as an opportunity to identify pro-differentiating mechanisms that could counteract tumor growth.
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Biomarcadores Tumorais/genética , Caveolina 1/genética , Lipossarcoma/genética , Proteínas de Ligação a RNA/genética , Tecido Adiposo/crescimento & desenvolvimento , Tecido Adiposo/patologia , Cavéolas/metabolismo , Cavéolas/patologia , Diferenciação Celular/genética , Membrana Celular/genética , Membrana Celular/patologia , Humanos , Lipossarcoma/patologiaRESUMO
Caveolae are cholesterol enriched invaginations of the plasma membrane involved in a variety of processes, including glucose and fatty acids absorption, cell transduction and mechanoprotection. The biogenesis and function of caveolae depend on the activity of Caveolin (Cav-1, -2 and -3) and Cavin (Cavin-1, -2, -3 and -4) protein families. Since the membrane Cavin-2 protein was reported to play a key role in caveolae formation of adipocytes, in this work we have used a multidisciplinary approach to investigate its expression in liposarcoma (LPS), an adipocytic soft tissue sarcoma affecting adults. Data obtained through an in silico and immunohistochemical analysis suggest that Cavin-2, along with Cavin-1, Cav-1 and Cav-2, is mostly expressed in the least aggressive LPS subtype, namely well-differentiated LPS, while is almost undetectable in the more aggressive myxoid, pleomorphic and dedifferentiated LPS tumors. Accordingly, in vitro analysis confirmed that Cavin-2 expression increases in LPS tumor cell lines during differentiation as compared to proliferation, as detected by immunoblotting and immunofluorescence analysis. Overall, these data suggest that Cavin-2 represents a useful marker for discriminating the degree of differentiation in LPS tumors.
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Biomarcadores Tumorais/metabolismo , Proteínas de Transporte/metabolismo , Lipossarcoma/metabolismo , Lipossarcoma/patologia , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Proteínas de Neoplasias/metabolismo , Proteínas de Ligação a Fosfato , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Especificidade da EspécieRESUMO
BACKGROUND: Anemia is frequent during HIV infection and is predictive of mortality. Although cART has demonstrated to reduce its prevalence, several patients still experience unresolved anemia. We aimed to characterize iron homeostasis and inflammation in HIV-infected individuals with mild anemia in relation to cART. METHODS: In this retrospective cohort study, HIV-infected patients with mild anemia, CD4+ cells > 200/mm3 at baseline, maintaining virological response for 12 months after cART starting were selected within the Standardized Management of Antiretroviral Therapy Cohort (MASTER) cohort. Several inflammation and immune activation markers and iron homeostasis indexes were measured in stored samples, obtained at cART initiation (T0) and 12 months later (T1). Patients were grouped on the basis of hemoglobin values at T1: group A (> 13 g/dl) and B (< 13 g/dl). Wilcoxon rank sum test was used to compare biomarker values. Pearson correlation coefficients were calculated for all variables. RESULTS: cART improved CD4+ and CD8+ cell counts and their ratio, but this effect was significant only in group A. Only these patients had mild iron deficiency at T0 and showed higher transferrin and lower percentage of transferrin saturation than patients of group B, but differences disappeared with cART. cART decreased inflammation in all patients, but group B had higher levels of all markers than group A, reaching statistical significance only for IL-8 values at T1 (16 vs 2.9 pg/ml; p = 0.017). Hepcidin and IL-6 levels did not show significant differences between groups. Hemoglobin levels both at T0 and T1 did not correlate with any marker. CONCLUSIONS: Baseline mild anemia in HIV-infected patients cannot always be resolved with durable efficient cART, possibly due to residual inflammation or immune activation rather than unbalanced iron homeostasis. Further research is needed on cytokine profiling to understand the mechanisms that induce anemia in HIV with suppressive cART.
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Anemia/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Biomarcadores/sangue , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Homeostase , Inflamação/patologia , Ferro/metabolismo , Adulto , Anemia/sangue , Anemia/complicações , Fármacos Anti-HIV/farmacologia , Demografia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Homeostase/efeitos dos fármacos , Humanos , Inflamação/sangue , Inflamação/complicações , Pessoa de Meia-IdadeRESUMO
Rhabdomyosarcoma (RMS) is a childhood soft tissue tumor with broad expression of markers that are typically found in skeletal muscle. Cavin-1 is a recently discovered protein actively cooperating with Caveolin-1 (Cav-1) in the morphogenesis of caveolae and whose role in cancer is drawing increasing attention. Using a combined in silico and in vitro analysis here we show that Cavin-1 is expressed in myogenic RMS tumors as well as in human and primary mouse RMS cultures, exhibiting a broad subcellular localization, ranging from nuclei and cytosol to plasma membrane. In particular, the coexpression and plasma membrane interaction between Cavin-1 and Cav-1 characterized the proliferation of human and mouse RMS cell cultures, while a downregulation of their expression levels was observed during the myogenic differentiation. Knockdown of Cavin-1 or Cav-1 in the human RD and RH30 cells led to impairment of cell proliferation and migration. Moreover, loss of Cavin-1 in RD cells impaired the anchorage-independent cell growth in soft agar. While the loss of Cavin-1 did not affect the Cav-1 protein levels in RMS cells, Cav-1 overexpression and knockdown triggered a rise or depletion of Cavin-1 protein levels in RD cells, respectively, in turn reflecting on increased or decreased cell proliferation, migration and anchorage-independent cell growth. Collectively, these data indicate that the interaction between Cavin-1 and Cav-1 underlies the cell growth and migration in myogenic tumors.
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Caveolina 1/metabolismo , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Proteínas de Membrana/metabolismo , Proteínas de Ligação a RNA/metabolismo , Rabdomiossarcoma/metabolismo , Animais , Caveolina 1/genética , Diferenciação Celular , Linhagem Celular Tumoral , Células Cultivadas , Regulação para Baixo , Técnicas de Silenciamento de Genes , Humanos , Proteínas de Membrana/genética , Camundongos , Proteínas de Ligação a RNA/genética , Células Satélites de Músculo Esquelético/metabolismoRESUMO
Objectives: This study aimed to determine the impacts of upper and lower limb (UL and LL) spasticity and impairment on spinal alignment in chronic post-stroke patients. Methods: A total of 45 consecutive chronic post-stroke patients, 18 women and 27 men, from 18 to 70 years old who presented post-stroke hemiparesis were recruited in this cross-sectional study. The clinical assessment included the Modified Ashworth Scale (UL-MAS and LL-MAS spasticity), Upper Limb Motricity Index (UL-MI), FAST-UL, and Five Times Sit-to-Stand Test (5T-STS); the Associated Reaction Rating Scale was used to measure associated reactions in the hemiparetic UL, the plumb line distance from the spinous process of C7 on the sagittal (PL-C7s) and frontal plane (Pl-C7f), the kyphosis apex (PL-AK), and the spinous process of L3 (PL-L3). Angular measures of spinal alignment were measured by a Bunnell scoliometer™ (angle of trunk rotation-ATR) and a gravity-dependent inclinometer (inclination at C7-T1 and T12-L1). Results: In chronic post-stroke patients, there was found to be an association between the 5T-STS and PL-C7f (ß = 0.41, p = 0.05) and the angle of inclination at T12-L1 (ß = 0.44, p = 0.01). The FAST-UL correlated with PL-C7f (ß = -0.41, p = 0.05), while the UL-MI correlated with this last parameter (ß = -0.36, p = 0.04) and the ATR (ß = -0.31, p = 0.05). The UL-MAS showed correlation with the ATR (ß = 0.38, p = 0.01). Conclusions: The results lead to the possibility that, in chronic post-stroke patients, spinal misalignment on the frontal and sagittal plane is associated both with strength impairment and UL spasticity. The improvement or restoration of spinopelvic parameters can take advantage of therapeutic interventions targeted at motor improvement and spasticity reduction of the hemiparetic side.
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BACKGROUND: This study evaluates the repeatability and reproducibility of fat-fraction percentage (FF%) in whole-body magnetic resonance imaging (WB-MRI) of prostate cancer patients with bone metastatic hormone naive disease. METHODS: Patients were selected from the database of a prospective phase-II trial. The treatment response was assessed using the METastasis Reporting and Data System for Prostate (MET-RADS-P). Two operators identified a Small Active Lesion (SAL, <10 mm) and a Large Active Lesion (LAL, ≥10 mm) per patient, performing manual segmentation of lesion volume and the largest cross-sectional area. Measurements were repeated by one operator after two weeks. Intra- and inter-reader agreements were assessed via Interclass Correlation Coefficient (ICC) on first-order radiomics features. RESULTS: Intra-reader ICC showed high repeatability for both SAL and LAL in a single slice (SS) and volumetric (VS) measurements with values ranging from 0.897 to 0.971. Inter-reader ICC ranged from 0.641 to 0.883, indicating moderate to good reproducibility. Spearman's rho analysis confirmed a strong correlation between SS and VS measurements for SAL (0.817) and a moderate correlation for LAL (0.649). Both intra- and inter-rater agreement exceeded 0.75 for multiple first-order features across lesion sizes. CONCLUSION: This study suggests that FF% measurements are reproducible, particularly for larger lesions in both SS and VS assessments.
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Neoplasias Ósseas , Imageamento por Ressonância Magnética , Neoplasias da Próstata , Imagem Corporal Total , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Imageamento por Ressonância Magnética/métodos , Imagem Corporal Total/métodos , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Reprodutibilidade dos Testes , Estudos Prospectivos , Idoso , Variações Dependentes do Observador , Pessoa de Meia-Idade , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/patologiaRESUMO
Non-alcoholic fatty liver disease (NAFLD) is a health emergency worldwide due to its high prevalence and the lack of specific therapies. Noninvasive biomarkers supporting NAFLD diagnosis are urgently needed. Liver mitochondrial dysfunction is a central NAFLD pathomechanism that changes throughout disease progression. Blood-cell bioenergetics reflecting mitochondrial organ dysfunction is emerging for its potential applications in diagnostics. We measured real-time mitochondrial respirometry in peripheral blood mononuclear cells (PBMCs), anthropometric parameters, routine blood analytes, and circulating cytokines from a cohort of NAFLD patients (N = 19) and non-NAFLD control subjects (N = 18). PBMC basal respiration, ATP-linked respiration, maximal respiration, and spare respiratory capacity were significantly reduced in NAFLD compared to non-NAFLD cases. Correlation plots were applied to visualize relationships between known or potential NAFLD-related biomarkers, while non-parametric methods were applied to identify which biomarkers are NAFLD predictors. Basal and ATP-linked mitochondrial respiration were negatively correlated with triglycerides and fasting insulin levels and HOMA index. Maximal and spare respiratory capacity were negatively correlated with IL-6 levels. All the mitochondrial respiratory parameters were positively correlated with HDL-cholesterol level and negatively correlated with fatty liver index. We propose including blood cell respirometry in panels of NAFLD diagnostic biomarkers to monitor disease progression and the response to current and novel therapies, including mitochondrial-targeted ones.
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BACKGROUND: Stress factors associated with migration may expose minor immigrants to mental health problems. The aim of the study was to describe acute psychiatric problems, in terms of reasons for hospitalization and diagnosis at discharge, in a sample of Italian and Migrant adolescents (both first and second generation). METHODS: We collected data on socio-demographic and clinical-diagnostic characteristics of 423 Italian and Migrant adolescents (mean age: 15 years ± 1.44; range 12-17.91), hospitalized at the Child and Adolescent Neuropsychiatry Unit of the Spedali Civili of Brescia between 2014 and 2019, period prior to the coronavirus disease 19 (COVID-19) pandemic. RESULTS: A reduction in the percentage of hospitalized Italian subjects and an increase of Migrant ones was found among years (p<0.001). Suicidal attempts and psychomotor agitation were the main reasons for hospitalization in both Italian and Migrant groups; in addition, the former presented a higher number of accesses for eating disorders, while the latter for psychotic disorders. Comparing the two groups at discharge, a higher frequency of anxiety disorders (p<0.001), eating disorders (p<0.001), somatic and conversion disorders (p=0.013), and obsessive-compulsive disorder (p=0.022) was detected in the Italian sample; conversely, there was a higher frequency of suicidal attempt (p=0.025), personality disorders (p<0.001), disruptive behavior, impulse control and conduct disorders (p=0.014), and post-traumatic stress disorder (p=0.019) in the Migrant group. CONCLUSIONS: These observations, carried out during a pre-COVID-19 period, provide a starting point for understanding the psychopathology of Migrant adolescents and underline the importance of early diagnosis to guide appropriate interventions.
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Objective: To evaluate the diagnostic performance of magnetic resonance (MR) with surface coils in assessing cartilage invasion in recurrent laryngeal carcinoma after carbon dioxide transoral laser microsurgery (CO2 TOLMS). Methods: Two expert head and neck radiologists assessed cartilage invasion (infiltrated or non-infiltrated) in submucosal recurrences of laryngeal carcinoma after CO2 TOLMS: results were compared with histopathological report after salvage laryngectomy. Results: Thirty patients met the inclusion criteria and 90 cartilages were assessed. Overall sensitivity, specificity, and positive and negative predictive values for cartilage infiltration were 76, 93, 72 and 94%, respectively; for thyroid cartilage, the values were 82, 79, 69 and 88% respectively; for cricoid cartilage, all values were 100%; and for arytenoids, the values were 33, 96, 56 and 93% respectively. Conclusions: MR with surface coils was able to detect most thyroid and cricoid infiltration in the complex setting of post-CO2 TOLMS laryngeal carcinoma recurrence. In particular, the optimal performance in assessing cricoid invasion can be valuable in choosing the most appropriate treatment among total laryngectomy, open partial horizontal laryngectomies and non-surgical strategies.
Assuntos
Carcinoma , Neoplasias Laríngeas , Terapia a Laser , Humanos , Microcirurgia/métodos , Dióxido de Carbono , Estudos Retrospectivos , Recidiva Local de Neoplasia/cirurgia , Neoplasias Laríngeas/cirurgia , Neoplasias Laríngeas/patologia , Cartilagem/patologia , Cartilagem/cirurgia , Imageamento por Ressonância Magnética , Terapia a Laser/métodos , Carcinoma/cirurgia , Lasers , Laringectomia/métodosRESUMO
Despite extensive research on COVID-19's impact on healthcare workers, few studies have targeted mental health workers (MHWs) and none have investigated previous traumatic events. We investigated psychological distress in MHWs after the first lockdown in Italy to understand which COVID-19, sociodemographic, and professional variables represented greater effects, and the role of previous trauma. The survey included sociodemographic and professional questions, COVID-19 variables, and the questionnaires Life Events Checklist for DSM-5 (LEC-5), Impact of Event Scale-Revised (IES-R), and Depression Anxiety Stress Scales 21 (DASS-21). On the 271 MHWs who completed the survey (73.1% female; mean age 45.37), we obtained significant effects for contagion fear, experience of patients' death, increased workload, and worse team relationship during the first wave. Nurses were more affected and showed more post-traumatic stress symptoms, assessed by IES-R, and more depressive, anxiety, and stress symptoms, assessed by DASS-21. The strongest risk factors for distress were greater age, professional role, increased workload, worse team relationship, and separation from family members. Previous experience of severe human suffering and unwanted sexual experiences negatively impacted IES-R and DASS-21 scores. Being a psychiatrist or psychologist/psychotherapist and good team relationships were protective factors. Recent but also previous severe stressful events might represent relevant risk factors for distress, reducing resilience skills. Identifying vulnerable factors and professional categories may help in the development of dedicated measures to prevent emotional burden and support psychological health. Highlights: Psychological distress in mental health workers in the COVID-19 pandemic is more frequent in nurses, who experience more depression, anxiety, and post-traumatic stress symptoms. Previous and recent stressful events are risk factors for distress and should guide intervention strategies.
RESUMO
In pediatric rhabdomyosarcoma (RMS), elevated Akt signaling is associated with increased malignancy. Here, we report that expression of a constitutively active, myristoylated form of Akt1 (myrAkt1) in human RMS RD cells led to hyperactivation of the mammalian target of rapamycin (mTOR)/70-kDa ribosomal protein S6 kinase (p70S6K) pathway, resulting in the loss of both MyoD and myogenic capacity, and an increase of Ki67 expression due to high cell mitosis. MyrAkt1 signaling increased migratory and invasive cell traits, as detected by wound healing, zymography, and xenograft zebrafish assays, and promoted repair of DNA damage after radiotherapy and doxorubicin treatments, as revealed by nuclear detection of phosphorylated H2A histone family member X (γH2AX) through activation of DNA-dependent protein kinase (DNA-PK). Treatment with synthetic inhibitors of phosphatidylinositol-3-kinase (PI3K) and Akt was sufficient to completely revert the aggressive cell phenotype, while the mTOR inhibitor rapamycin failed to block cell dissemination. Furthermore, we found that pronounced Akt1 signaling increased the susceptibility to cell apoptosis after treatments with 2-deoxy-D-glucose (2-DG) and lovastatin, enzymatic inhibitors of hexokinase, and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), especially in combination with radiotherapy and doxorubicin. In conclusion, these data suggest that restriction of glucose metabolism and the mevalonate pathway, in combination with standard therapy, may increase therapy success in RMS tumors characterized by a dysregulated Akt signaling.
Assuntos
Proteínas Proto-Oncogênicas c-akt , Rabdomiossarcoma Embrionário , Animais , Criança , Reparo do DNA , Proteína Quinase Ativada por DNA/genética , Desoxiglucose , Doxorrubicina/farmacologia , Glucose , Glicólise , Hexoquinase/metabolismo , Histonas/metabolismo , Humanos , Antígeno Ki-67/metabolismo , Lovastatina , Inibidores de MTOR , Ácido Mevalônico , Oxirredutases/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositóis , Proteínas Proto-Oncogênicas c-akt/metabolismo , Rabdomiossarcoma Embrionário/tratamento farmacológico , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Peixe-Zebra/genéticaRESUMO
BACKGROUND: Several risk factors have been identified to predict worse outcomes in patients affected by SARS-CoV-2 infection. Machine learning algorithms represent a novel approach to identifying a prediction model with a good discriminatory capacity to be easily used in clinical practice. The aim of this study was to obtain a risk score for in-hospital mortality in patients with coronavirus disease infection (COVID-19) based on a limited number of features collected at hospital admission. METHODS AND RESULTS: We studied an Italian cohort of consecutive adult Caucasian patients with laboratory-confirmed COVID-19 who were hospitalized in 13 cardiology units during Spring 2020. The Lasso procedure was used to select the most relevant covariates. The dataset was randomly divided into a training set containing 80% of the data, used for estimating the model, and a test set with the remaining 20%. A Random Forest modeled in-hospital mortality with the selected set of covariates: its accuracy was measured by means of the ROC curve, obtaining AUC, sensitivity, specificity and related 95% confidence interval (CI). This model was then compared with the one obtained by the Gradient Boosting Machine (GBM) and with logistic regression. Finally, to understand if each model has the same performance in the training and test set, the two AUCs were compared using the DeLong's test. Among 701 patients enrolled (mean age 67.2â±â13.2âyears, 69.5% male individuals), 165 (23.5%) died during a median hospitalization of 15 (IQR, 9-24) days. Variables selected by the Lasso procedure were: age, oxygen saturation, PaO2/FiO2, creatinine clearance and elevated troponin. Compared with those who survived, deceased patients were older, had a lower blood oxygenation, lower creatinine clearance levels and higher prevalence of elevated troponin (all Pâ<â0.001). The best performance out of the samples was provided by Random Forest with an AUC of 0.78 (95% CI: 0.68-0.88) and a sensitivity of 0.88 (95% CI: 0.58-1.00). Moreover, Random Forest was the unique model that provided similar performance in sample and out of sample (DeLong test Pâ=â0.78). CONCLUSION: In a large COVID-19 population, we showed that a customizable machine learning-based score derived from clinical variables is feasible and effective for the prediction of in-hospital mortality.