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1.
Cell ; 184(17): 4564-4578.e18, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34302739

RESUMO

The mesencephalic locomotor region (MLR) is a key midbrain center with roles in locomotion. Despite extensive studies and clinical trials aimed at therapy-resistant Parkinson's disease (PD), debate on its function remains. Here, we reveal the existence of functionally diverse neuronal populations with distinct roles in control of body movements. We identify two spatially intermingled glutamatergic populations separable by axonal projections, mouse genetics, neuronal activity profiles, and motor functions. Most spinally projecting MLR neurons encoded the full-body behavior rearing. Loss- and gain-of-function optogenetic perturbation experiments establish a function for these neurons in controlling body extension. In contrast, Rbp4-transgene-positive MLR neurons project in an ascending direction to basal ganglia, preferentially encode the forelimb behaviors handling and grooming, and exhibit a role in modulating movement. Thus, the MLR contains glutamatergic neuronal subpopulations stratified by projection target exhibiting roles in action control not restricted to locomotion.


Assuntos
Locomoção/fisiologia , Mesencéfalo/anatomia & histologia , Animais , Gânglios da Base/metabolismo , Comportamento Animal , Feminino , Integrases/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/metabolismo , Optogenética , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo , Medula Espinal/metabolismo , Transgenes , Proteína Vesicular 2 de Transporte de Glutamato/metabolismo
2.
Cell ; 156(3): 537-48, 2014 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-24485459

RESUMO

Accurate motor-task execution relies on continuous comparison of planned and performed actions. Motor-output pathways establish internal circuit collaterals for this purpose. Here we focus on motor collateral organization between spinal cord and upstream neurons in the brainstem. We used a newly developed mouse genetic tool intersectionally with viruses to uncover the connectivity rules of these ascending pathways by capturing the transient expression of neuronal subpopulation determinants. We reveal a widespread and diverse network of spinal dual-axon neurons, with coincident input to forelimb motor neurons and the lateral reticular nucleus (LRN) in the brainstem. Spinal information to the LRN is not segregated by motor pool or neurotransmitter identity. Instead, it is organized according to the developmental domain origin of the progenitor cells. Thus, excerpts of most spinal information destined for action are relayed to supraspinal centers through exquisitely organized ascending connectivity modules, enabling precise communication between command and execution centers of movement.


Assuntos
Tronco Encefálico/fisiologia , Técnicas Genéticas , Vias Neurais , Medula Espinal/citologia , Medula Espinal/fisiologia , Animais , Axônios/fisiologia , Camundongos , Camundongos Transgênicos , Neurônios Motores/fisiologia , Neurônios/fisiologia , Neurotransmissores/metabolismo , Sinapses
3.
Artigo em Inglês | MEDLINE | ID: mdl-38598432

RESUMO

OBJECTIVE: To evaluate the short-term effectiveness of guselkumab in patients with psoriatic arthritis (PsA) and suggestive features of axial involvement in a prospective "real-life" multicentre cohort. METHODS: Between June 2022 and June 2023, PsA patients with axial involvement were evaluated if treated at least for 4 months with guselkumab. The effectiveness was evaluated by BASDAI, ASDAS, DAPSA, and achievement of BASDAI ≤ 4, also exploiting predictive factors. In a group of patients, MRI findings on sacroiliac joints were assessed before and after guselkumab administration. RESULTS: Sixty-seven patients with PsA and suggestive features of axial involvement (age 53.4 ± 11.2 years, male sex 26.9%) were treated with guselkumab. After 4 months, a significant reduction of BASDAI, ASDAS, and DAPSA was observed. A ΔBASDAI of -2.11 ± 0.43 was estimated assessing the mean difference values before and after guselkumab administration and 52.2% of patients reached a BASDAI ≤ 4. In 27 patients, MRI findings on sacroiliac joints were assessed before and after guselkumab administration. A reduction of 0.80 or larger of the sacroiliac joint lesion score was observed in the majority of patients (70.3%) based on MRI improvements, paralleling with the clinical response.No life-threatening side effects were recorded; 17.9% of patients reported minor adverse events mainly injection site reactions. CONCLUSIONS: The short-term effectiveness of guselkumab in patients with PsA and suggestive features of axial involvement was shown. Although further studies are needed, our multicentre "real-life" study may suggest the clinical usability of guselkumab in this context.

5.
Am J Hematol ; 99(1): 68-78, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37846894

RESUMO

Contemporary risk models in primary myelofibrosis (PMF) include the mutation (MIPSS70) and mutation/karyotype enhanced (MIPSS70 plus/v2.0) international prognostic scoring systems. High molecular risk (HMR) mutations incorporated in one or both of these models include ASXL1, SRSF2, EZH2, IDH1/2, and U2AF1Q157; the current study examines additional prognostic contribution from more recently described HMR mutations, including CBL, NRAS, KRAS, RUNX1, and TP53. In a cohort of 363 informative cases (median age 58 years; 60% males), mutations included JAK2 61%, CALR 24%, MPL 6%, ASXL1 29%, SRSF2 10%, U2AF1Q157 5%, EZH2 10%, IDH1/2 4%, TP53 5%, CBL 5%, NRAS 7%, KRAS 4%, and RUNX1 4%. At a median follow-up of 4.6 years, 135 (37%) deaths and 42 (11.6%) leukemic transformations were recorded. Univariate analysis confirmed significant survival impact from the original MIPSS70/plus/v2.0 HMR mutations as well as CBL (HR 2.8; p < .001), NRAS (HR 2.4; p < .001), KRAS (HR 2.1; p = .01), and TP53 (HR 2.4; p = .004), but not RUNX1 mutations (HR 1.8; p = .08). Multivariate analysis (MVA) that included both the original and more recently described HMR mutations confirmed independent prognostic contribution from ASXL1 (HR 1.8; p = .007), SRSF2 (HR 4.3; p < .001), U2AF1Q157 (HR 2.9, p = .004), and EZH2 (HR 2.4; p < .001), but not from IDH1/2 (p = .3), TP53 (p = .2), CBL (p = .3), NRAS (p = .8) or KRAS (p = .2) mutations. The lack of additional prognostic value from CBL, NRAS, KRAS, RUNX1, and TP53 was further demonstrated in the setting of (i) MVA of mutations and karyotype, (ii) MVA of MIPSS70/plus/v2.0 composite scores and each one of the recently described HMR mutations, except TP53, and iii) modified MIPSS70/plus/plus v2.0 that included CBL, NRAS, KRAS, and TP53 as part of the HMR constituency, operationally referred to as "HMR+" category. Furthermore, "HMR+" enhancement of MIPSS70/plus/plus v2.0 did not result in improved model performance, as measured by C-statistics. We conclude that prognostic integrity of MIPSS70/plus/plus v2.0, as well as their genetic components, was sustained and their value not significantly upgraded by the inclusion of more recently described HMR mutations, including CBL, NRAS, KRAS, and RUNX1. Additional studies are needed to clarify the apparent additional prognostic value of TP53 mutation and its allelic state.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core , Mielofibrose Primária , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Prognóstico , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/genética , Mutação , Proteína Supressora de Tumor p53/genética , Proteínas de Membrana/genética , GTP Fosfo-Hidrolases/genética
6.
Clin Exp Dermatol ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38860563

RESUMO

BACKGROUND: The efficacy and safety of dupilumab in atopic dermatitis (AD) have been defined in clinical trials but limited real-world evidence on long term treatment outcomes are currently available to inform clinical decisions. OBJECTIVES: to describe long-term effectiveness and safety of dupilumab up to 48 months in patients with moderate-to-severe AD. METHODS: a multicenter, retrospective, dynamic cohort study was conducted to assess long term effectiveness and safety of dupilumab in patients with moderate to severe AD in a real-world setting. Predictors of minimal disease activity (MDA) optimal treatment target criteria (defined as the simultaneous achievement of EASI90, itch NRS score ≤1, sleep NRS score ≤1 and DLQI ≤1) were investigated. RESULTS: 2576 patients were enrolled from June 2018 to July 2022. MDA optimal treatment target criteria were achieved by 506 (21.91%), 769 (40.63%), 628 (50.36%), 330 (55.37%) and 58 (54.72%) of those that reached 4, 12, 24, 36 and 48 months of follow-up, respectively. Logistic regression revealed a negative effect on MDA achievement for conjunctivitis and food allergy at all timepoints. Adverse events (AE) were mild and were observed in 373 (15.78%), 166 (7.02%), 83 (6.43%), 27 (4.50%) and 5 (4.55%) of those that reached 4, 12, 24, 36 and 48 months of follow-up. Conjunctivitis was the most frequently reported AE during the available follow-up. AE led to treatment discontinuation in <1% of patients during the evaluated time periods. CONCLUSION: High long-term effectiveness and safety of dupilumab were confirmed in this dynamic cohort of patients with moderate to severe AD, regardless of clinical phenotype and course at baseline. Further research will be needed to investigate the effect of Th2 comorbidities and disease duration on the response to dupilumab and other newer therapeutics for AD.

7.
Hematol Oncol ; 41(5): 817-827, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37415412

RESUMO

The reliability and safety of front-line ultrasonography guided core needle biopsy (UG-CNB) performed with specific uniform approach have never been evaluated in a large series of patients with lymphadenopathies suspected of lymphoma. The aim of this study was to assess the overall accuracy of UG-CNB in the lymph node histological diagnosis, using a standard reference based on pathologist consensus, molecular biology, and/or surgery. We retrospectively checked the findings concerning the application of lymph node UG-CNB from four Italian clinical units that routinely utilized 16-gauge diameter modified Menghini needle under power-Doppler ultrasonographic guidance. A data schedule was sent to all centers to investigate the information regarding techniques, results, and complications of lymph node UG-CNB in untreated patients over a 12-year period. Overall, 1000 (superficial target, n = 750; deep-seated target, n = 250) biopsies have been evaluated in 1000 patients; other 48 biopsies (4.5%), screened in the same period, were excluded because inadequate for a confident histological diagnosis. Most patients were suffering from lymphomas (aggressive B-cell non-Hodgkin lymphoma [aBc-NHL], 309 cases; indolent B-cell [iBc]-NHL, 279 cases; Hodgkin lymphoma [HL], 212 cases; and nodal peripheral T-cell [NPTC]-NHL, 30 cases) and 100 cases from metastatic carcinoma; 70 patients had non-malignant disorders. The majority of CNB results met at least one criterion of the composite reference standard. The overall accuracy of the micro-histological sampling was 97% (95% confidence interval: 95%-98%) for the series. The sensitivity of UG-CNB for the detection of aBc-NHL was 100%, for iBc-NHL 95%, for HL 93%, and for NPTC-NHL 90%, with an overall false negative rate of 3.3%. The complication rate was low (6% for all complications); no patient suffered from biopsy-related complications of grade >2 according to the Common Terminology Criteria for Adverse Events. Lymph node UG-CNB as mini-invasive diagnostic procedure is effective with minimal risk for the patient.


Assuntos
Doença de Hodgkin , Linfadenopatia , Linfoma , Humanos , Estudos Retrospectivos , Reprodutibilidade dos Testes , Linfoma/diagnóstico por imagem , Linfoma/patologia , Linfadenopatia/diagnóstico , Ultrassonografia , Doença de Hodgkin/diagnóstico por imagem , Biópsia por Agulha/métodos , Itália , Biópsia com Agulha de Grande Calibre/métodos
8.
Ann Hematol ; 102(6): 1375-1382, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37079069

RESUMO

Here, we report real-world evidence on the safety and efficacy of nilotinib as a first-line treatment in elderly patients with chronic phase CML, treated in 18 Italian centers. Sixty patients aged > 65 years (median age 72 years (65-84)) were reported: 13 patients were older than 75 years. Comorbidities were recorded at baseline in 56/60 patients. At 3 months of treatment, all patients obtained complete hematological response (CHR), 43 (71.6%) an early molecular response (EMR), while 47 (78%) reached a complete cytogenetic response (CCyR). At last follow-up, 63.4% of patients still had a deep molecular response (MR4 or better), 21.6% reached MR3 as best response and 11.6% persisted without MR. Most patients (85%) started the treatment at the standard dose (300 mg BID), maintained at 3 months in 80% of patients and at 6 months in 89% of them. At the last median follow-up of 46.3 months, 15 patients discontinued definitively the treatment (8 due to side effects, 4 died for unrelated CML causes, 1 for failure, 2 were lost to follow-up). One patient entered in treatment-free remission. As to safety, 6 patients (10%) experienced cardiovascular events after a median time of 20.9 months from the start. Our data showed that nilotinib could be, as first-line treatment, effective and relatively safe even in elderly CML patients. In this setting, more data in the long term are needed about possible dose reduction to improve the tolerability, while maintaining the optimal molecular response.


Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Idoso , Humanos , Mesilato de Imatinib/uso terapêutico , Antineoplásicos/efeitos adversos , Pirimidinas/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Resultado do Tratamento , Inibidores de Proteínas Quinases/efeitos adversos
9.
Nature ; 551(7680): 373-377, 2017 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-29059682

RESUMO

Locomotion is a universal behaviour that provides animals with the ability to move between places. Classical experiments have used electrical microstimulation to identify brain regions that promote locomotion, but the identity of neurons that act as key intermediaries between higher motor planning centres and executive circuits in the spinal cord has remained controversial. Here we show that the mouse caudal brainstem encompasses functionally heterogeneous neuronal subpopulations that have differential effects on locomotion. These subpopulations are distinguishable by location, neurotransmitter identity and connectivity. Notably, glutamatergic neurons within the lateral paragigantocellular nucleus (LPGi), a small subregion in the caudal brainstem, are essential to support high-speed locomotion, and can positively tune locomotor speed through inputs from glutamatergic neurons of the upstream midbrain locomotor region. By contrast, glycinergic inhibitory neurons can induce different forms of behavioural arrest mapping onto distinct caudal brainstem regions. Anatomically, descending pathways of glutamatergic and glycinergic LPGi subpopulations communicate with distinct effector circuits in the spinal cord. Our results reveal that behaviourally opposing locomotor functions in the caudal brainstem were historically masked by the unexposed diversity of intermingled neuronal subpopulations. We demonstrate how specific brainstem neuron populations represent essential substrates to implement key parameters in the execution of motor programs.


Assuntos
Tronco Encefálico/citologia , Tronco Encefálico/fisiologia , Locomoção/fisiologia , Vias Neurais , Aceleração , Animais , Ácido Glutâmico/metabolismo , Glicina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Optogenética
10.
Lancet Oncol ; 23(7): e334-e347, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35772465

RESUMO

The International Initiative on Thrombosis and Cancer is an independent academic working group of experts aimed at establishing global consensus for the treatment and prophylaxis of cancer-associated thrombosis. The 2013, 2016, and 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines have been made available through a free, web-based mobile phone application. The 2022 clinical practice guidelines, which are based on a literature review up to Jan 1, 2022, include guidance for patients with cancer and with COVID-19. Key recommendations (grade 1A or 1B) include: (1) low-molecular-weight heparins (LMWHs) for the initial (first 10 days) treatment and maintenance treatment of cancer-associated thrombosis; (2) direct oral anticoagulants for the initial treatment and maintenance treatment of cancer-associated thrombosis in patients who are not at high risk of gastrointestinal or genitourinary bleeding, in the absence of strong drug-drug interactions or of gastrointestinal absorption impairment; (3) LMWHs or direct oral anticoagulants for a minimum of 6 months to treat cancer-associated thrombosis; (4) extended prophylaxis (4 weeks) with LMWHs to prevent postoperative venous thromboembolism after major abdominopelvic surgery in patients not at high risk of bleeding; and (5) primary prophylaxis of venous thromboembolism with LMWHs or direct oral anticoagulants (rivaroxaban or apixaban) in ambulatory patients with locally advanced or metastatic pancreatic cancer who are treated with anticancer therapy and have a low risk of bleeding.


Assuntos
COVID-19 , Neoplasias , Trombose , Tromboembolia Venosa , Anticoagulantes/efeitos adversos , COVID-19/complicações , Hemorragia/induzido quimicamente , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Neoplasias/induzido quimicamente , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Guias de Prática Clínica como Assunto , Trombose/induzido quimicamente , Trombose/complicações , Trombose/tratamento farmacológico , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
11.
Br J Haematol ; 198(5): 847-860, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35819919

RESUMO

We evaluated the impact of liposomal doxorubicin (NPLD) supercharge-containing therapy on interim fluorodeoxyglucose positron emission tomography (interim-FDG-PET) responses in high-risk diffuse large B-cell lymphoma (DLBCL) or classical Hodgkin lymphoma (c-HL). In this phase II study (2016-2021), 81 adult patients with advanced-stage DLBCL (n = 53) and c-HL (n = 28) received front-line treatment with R-COMP-dose-intensified (DI) and MBVD-DI. R-COMP-DI consisted of 70 mg/m2 of NPLD plus standard rituximab, cyclophosphamide, vincristine and prednisone for three cycles (followed by three cycles with NPLD de-escalated at 50 mg/m2 ); MBVD-DI consisted of 35 mg/m2 of NPLD plus standard bleomycin, vinblastine and dacarbazine for two cycles (followed by four cycles with NPLD de-escalated at 25 mg/m2 ). Patients underwent R-COMP-DI and MBVD-DI with a median dose intensity of 91% and 94% respectively. At interim-FDG-PET, 72/81 patients (one failed to undergo interim-FDG-PET due to early death) had a Deauville score of ≤3. At end of treatment, 90% of patients reached complete responses. In all, 20 patients had Grade ≥3 adverse events, and four of them required hospitalisation. At a median 21-months of follow-up, the progression-free survival of the entire population was 77.3% (95% confidence interval 68%-88%). Our data suggest that the NPLD supercharge-driven strategy in high-risk DLBCL/c-HL may be a promising option to test in phase III trials, for improving negative interim-FDG-PET cases incidence.


Assuntos
Doença de Hodgkin , Linfoma Difuso de Grandes Células B , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida , Doxorrubicina/efeitos adversos , Doxorrubicina/análogos & derivados , Etoposídeo , Fluordesoxiglucose F18/uso terapêutico , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/etiologia , Estadiamento de Neoplasias , Polietilenoglicóis , Prednisona , Rituximab , Vincristina/efeitos adversos
12.
J Clin Immunol ; 42(8): 1742-1747, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35945378

RESUMO

X-linked chronic granulomatous disease is a rare disease caused by mutations in the CYBB gene. While more extensive knowledge is available on genetics, pathogenesis, and possible therapeutic options, mitochondrial activity and its implications on patient monitoring are still not well-characterized. We have developed a novel protocol to study mitochondrial activity on whole blood of XCGD patients before and after transplantation, as well as on XCGD carriers. Here we present results of these analyses and of the restoration of mitochondrial activity in hyperinflamed X-linked Chronic Granulomatous Disease after hematopoietic stem cell transplantation. Moreover, we show a strong direct correlation between mitochondrial activity, chimerism, and DHR monitored before and after transplantation and in XCGD carriers. In conclusion, based on these findings, we suggest testing this new ready-to-use marker to better characterize patients before and after treatment and to investigate disease expression in carriers.


Assuntos
Doença Granulomatosa Crônica , Transplante de Células-Tronco Hematopoéticas , Humanos , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/genética , Doença Granulomatosa Crônica/terapia , Quimerismo , Fagócitos , Heterozigoto
13.
J Med Virol ; 94(8): 3653-3660, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35411627

RESUMO

To date the optimal antiviral treatment against severe coronavirus disease 2019 (COVID-19) has not been proven; remdesivir is a promising drug with in vitro activity against several viruses, but in COVID-19 the clinical results are currently not definitive. In this retrospective observational study, we analyzed the clinical outcomes (survival analysis, efficacy, and safety) in a group of hospitalized patients with COVID-19 treated with remdesivir in comparison with a control group of patients treated with other antiviral or supportive therapies. We included 163 patients treated with remdesivir and 403 subjects in the control group; the baseline characteristics were similar in the two groups; the mortality rate was higher in the control group (24.8% vs. 2.4%, p < 0.001), the risk of intensive care unit (ICU) admission was higher in the control group (17.8% vs. 9.8%, p = 0.008); hospitalization time was significantly lower in patients treated with remdesivir (9.5 vs. 12.5 days, p < 0.001). The safety of remdesivir was good and no significant adverse events were reported. In multivariate analysis, the remdesivir treatment was independently associated with a 34% lower mortality rate (odds ratio = 0.669; p = 0.014). In this analysis, the treatment with remdesivir was associated with lower mortality, lower rate of ICU admission, and shorter time of hospitalization. No adverse events were observed. This promising antiviral treatment should also be confirmed by other studies.


Assuntos
Tratamento Farmacológico da COVID-19 , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Alanina/uso terapêutico , Antivirais/uso terapêutico , Estudos de Casos e Controles , Humanos , SARS-CoV-2 , Resultado do Tratamento
14.
BMC Cancer ; 22(1): 30, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34980006

RESUMO

BACKGROUND: Breast cancer (BC) is the most common malignancy in women, in whom it reaches 20% of the total neoplasia incidence. Most BCs are considered sporadic and a number of factors, including familiarity, age, hormonal cycles and diet, have been reported to be BC risk factors. Also the gut microbiota plays a role in breast cancer development. In fact, its imbalance has been associated to various human diseases including cancer although a consequential cause-effect phenomenon has never been proven. METHODS: The aim of this work was to characterize the breast tissue microbiome in 34 women affected by BC using an NGS-based method, and analyzing the tumoral and the adjacent non-tumoral tissue of each patient. RESULTS: The healthy and tumor tissues differed in bacterial composition and richness: the number of Amplicon Sequence Variants (ASVs) was higher in healthy tissues than in tumor tissues (p = 0.001). Moreover, our analyses, able to investigate from phylum down to species taxa for each sample, revealed major differences in the two richest phyla, namely, Proteobacteria and Actinobacteria. Notably, the levels of Actinobacteria and Proteobacteria were, respectively, higher and lower in healthy with respect to tumor tissues. CONCLUSIONS: Our study provides information about the breast tissue microbial composition, as compared with very closely adjacent healthy tissue (paired samples within the same woman); the differences found are such to have possible diagnostic and therapeutic implications; further studies are necessary to clarify if the differences found in the breast tissue microbiome are simply an association or a concausative pathogenetic effect in BC. A comparison of different results on similar studies seems not to assess a universal microbiome signature, but single ones depending on the environmental cohorts' locations.


Assuntos
Neoplasias da Mama/microbiologia , Mama/microbiologia , Disbiose/microbiologia , Microbioma Gastrointestinal/genética , Adulto , Biodiversidade , Feminino , Humanos , Pessoa de Meia-Idade , RNA Ribossômico 16S/análise
15.
Nature ; 534(7606): 206-12, 2016 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-27279213

RESUMO

Survival in threatening situations depends on the selection and rapid execution of an appropriate active or passive defensive response, yet the underlying brain circuitry is not understood. Here we use circuit-based optogenetic, in vivo and in vitro electrophysiological, and neuroanatomical tracing methods to define midbrain periaqueductal grey circuits for specific defensive behaviours. We identify an inhibitory pathway from the central nucleus of the amygdala to the ventrolateral periaqueductal grey that produces freezing by disinhibition of ventrolateral periaqueductal grey excitatory outputs to pre-motor targets in the magnocellular nucleus of the medulla. In addition, we provide evidence for anatomical and functional interaction of this freezing pathway with long-range and local circuits mediating flight. Our data define the neuronal circuitry underlying the execution of freezing, an evolutionarily conserved defensive behaviour, which is expressed by many species including fish, rodents and primates. In humans, dysregulation of this 'survival circuit' has been implicated in anxiety-related disorders.


Assuntos
Reação de Fuga/fisiologia , Reação de Congelamento Cataléptica/fisiologia , Vias Neurais/citologia , Vias Neurais/fisiologia , Substância Cinzenta Periaquedutal/citologia , Substância Cinzenta Periaquedutal/fisiologia , Tonsila do Cerebelo/citologia , Tonsila do Cerebelo/fisiologia , Animais , Neurônios GABAérgicos/fisiologia , Ácido Glutâmico/metabolismo , Masculino , Bulbo/citologia , Bulbo/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Inibição Neural/fisiologia , Técnicas de Rastreamento Neuroanatômico , Optogenética
16.
Dermatology ; 238(5): 986-995, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35462375

RESUMO

BACKGROUND: Cutaneous melanoma accounts for the majority of skin cancer-related deaths. Readily identifiable phenotypic characteristics and total body nevus count (TBNC) >50 are among the most important risk factors for cutaneous melanoma. Implementation of nevus self-count procedures and self-assessment of phenotypic traits as part of skin self-examination could be an excellent screening tool for identifying an at-risk target population. OBJECTIVES: Objectives of the study were to assess the skills of a central Italian and eastern Spanish population sample to recognize their skin lesions via the submission of a self-assessment questionnaire and to explore which self-assessment questionnaire item combination best predicts the high-risk condition of TBNC >50. METHODS: Patients aged ≥18 years filled a self-assessment questionnaire, autonomously and prior to the dermatological visit. Subsequently, dermatologists performed total body skin examination and reported patients' skin lesions on a separate questionnaire. RESULTS: We reported fair to moderate patient-dermatologist agreement for skin lesion self-assessment. The item number of nevi on the back was the single questionnaire item most accurately predicting TBNC >50. The high-sensitivity and high-specificity classification and regression tree models for the prediction of TBNC >50 displayed different items combinations; the item nevus on the back was always the first and most important predictor in both our models. CONCLUSIONS: Patients were partially able to provide correct estimation of their whole-body nevus self-count. The item nevi on the back seems to be the first and most important predictor of TBNC >50 across our models. Delivery of high-sensitivity and high-specificity prediction models based on our questionnaire item combination may help defining a high-risk target population.


Assuntos
Melanoma , Nevo Pigmentado , Nevo , Médicos , Neoplasias Cutâneas , Humanos , Melanoma/patologia , Nevo/diagnóstico , Nevo Pigmentado/diagnóstico , Nevo Pigmentado/patologia , Fenótipo , Fatores de Risco , Autoavaliação (Psicologia) , Neoplasias Cutâneas/patologia , Inquéritos e Questionários , Melanoma Maligno Cutâneo
17.
Biol Res ; 55(1): 34, 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36371313

RESUMO

BACKGROUND: The assessment of oocyte quality is, nowadays, a major challenge in aquaculture, oocyte cryopreservation, and environmental science. Oocyte quality is a determining factor in fertilization and embryo development; however, there is still a lack of rapid and sensitive cellular markers for its assessment. Currently, its estimation is predominantly based on morphological analysis, which is subjective and does not consistently reflect the developmental competence of the oocytes. Despite several recent studies investigating molecular markers related to oocyte quality, methods currently available for their determination pose various technical challenges and limitations. In this study, we developed a novel approach based on fluorescence spectroscopy to assess different intrinsic physiological parameters that can be employed to evaluate egg quality in marine invertebrates that are widely used as animal models such as sea urchins and mussels. RESULTS: Different physiological parameters, such as viability, mitochondrial activity, intracellular ROS levels, plasma membrane lipid peroxidation, and intracellular pH, for egg quality evaluation have been successfully assessed in sea urchins and mussels by using specific fluorescent dyes and detecting the fluorescent signals in eggs through fluorescence spectroscopy. CONCLUSIONS: Based on our findings, we propose these physiological markers as useful predictors of egg quality in marine invertebrates; they can be estimated rapidly, selectively, and sensitively by employing this novel approach, which, due to the speed of analysis, the low cost, and easy use can be considered a powerful analytical tool for the egg quality assessment.


Assuntos
Desenvolvimento Embrionário , Oócitos , Animais , Espectrometria de Fluorescência , Oócitos/metabolismo , Ouriços-do-Mar , Criopreservação/métodos
18.
Eur J Cancer Care (Engl) ; 31(6): e13711, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36168857

RESUMO

OBJECTIVES: The aim of this pilot trial is evaluating the preliminary effectiveness of two in-hospital interventions in the maintenance of motor performance in children/adolescents undergoing hematopoietic stem cell transplantation (HSCT). Secondary objectives investigated the interventions' feasibility, impact on fatigue and to what degree the subjects' maintained their ankle dorsiflexion range of movement (ROM), functional mobility, muscle strength and flexibility. METHODS: This trial included 5- to 18-year-old participants, affected by oncological and non-oncological diseases during hospitalisation for autologous/allogenic HSCT. The subjects were assigned to an exercise group (EG), or a counselling group based on a cluster model based on inpatient timeframe. The EG subjects performed strengthening, stretching and aerobic exercises for 30 min/5 days a week. Both groups followed rehabilitation counselling indications (RCI), 7 days a week. RESULTS: Forty-nine participants were enrolled (median age = 12.9 years) (EG n = 36). In both groups the participants maintained their baseline motor performance and ankle ROM, and the children/adolescents and parents reduced their levels of fatigue. However, the interventions were not effective in maintaining strength. CONCLUSION: In maintaining the subjects' motor performance, the RCI results are significant because they pave the way for the application in clinical practice contexts where there are poor rehabilitation resources. Clinical Trials registration NCT03842735.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Criança , Adolescente , Humanos , Pré-Escolar , Projetos Piloto , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Força Muscular/fisiologia , Fadiga/etiologia , Transplante de Células-Tronco
19.
An Acad Bras Cienc ; 94(4): e20210763, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36449902

RESUMO

The influence of food types, reproductive behaviour, and the existence of a possible stratification to the attractiveness of Calliphoridae and Mesembrinellidae flies may contribute to the definition of collection methodologies. Thus, we assessed the effectiveness of traps with two bait types exposed at two different heights in the forests for collecting the aforementioned families. Traps were exposed in the Amazon rainforest floodplain area, where 40 traps were installed in 20 trees, in three periods of the year. On each tree, one trap was installed at 0.6 m and the other at 10 m above the ground, with either bovine lung or fermented banana. A total of 1,173 individuals were collected, including 10 species of Calliphoridae (962 individuals) and four species of Mesembrinellidae (211 individuals). Of the total in each family, Calliphoridae was most abundant in 0.6m lung bait traps (41%) and Mesembrinellidae in the 0.6 m banana bait traps (29%). Calliphoridae showed greater species richness, abundance, and differentiation in composition in low traps with lung as bait. In conclusion, only dipteran species from Calliphoridae have been affected and responded the collection methodologies employed of we, which may highlight remarkable differences in collection and subsequent data interpretation of inventories and monitoring using these insects.


Assuntos
Dípteros , Animais , Bovinos , Calliphoridae , Insetos , Florestas , Árvores
20.
Radiol Med ; 127(12): 1400-1406, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36260243

RESUMO

PURPOSE: To characterize nail and enthesis abnormalities using high frequency ultrasound (HFUS) in patients with psoriasis (PSO), psoriatic arthritis (PSA) with PSO, and PSA sine PSO. MATERIAL AND METHODS: Patients with PSO, PSA with PSO, and PSA sine PSO were evaluated and compared in a cross-sectional single centre study. Nail and enthesis abnormalities were evaluated by HFUS using high frequency probes (27 MHz). After a descriptive assessment, Brown University Nail Enthesis Scale (BUNES) and Madrid Sonography Enthesitis Index (MASEI) were used to assess nail and enthesis, respectively. RESULTS: Fifty-nine patients were enrolled (19 PSO, 22 PSA with PSO, 18 PSA sine PSO). In patients with PSO and in those with PSA and PSO, HFUS evaluation identified the following nail alterations characterised by thickened matrix, inhomogeneous echogenicity of the nail bed, and increased blood flow by power Doppler. In 38.9% patients with PSA sine PSO, a subclinical nail involvement was described. No difference was observed comparing BUNES values in three groups. In PSA patients with PSO and in those with PSA sine PSO, HFUS assessment of entheses mainly showed a hypoechoic aspect and thickness of the tendon, focal cortical erosion, and ossification. A subclinical enthesis involvement in 47.4% patients with PSO was observed. No difference was reported comparing MASEI values in three groups. CONCLUSION: Qualitative and quantitative abnormalities of nail and enthesis were demonstrated by HFUS in patients with PSO, PSA with PSO, and PSA sine PSO, suggesting a practical additional tool to be used in clinical settings. Furthermore, HFUS highlighted a subclinical nail involvement in patients with PSA sine PSO and enthesis subclinical alterations in patients with PSO.


Assuntos
Artrite Psoriásica , Entesopatia , Psoríase , Humanos , Entesopatia/diagnóstico por imagem , Estudos Transversais , Artrite Psoriásica/diagnóstico por imagem , Unhas/diagnóstico por imagem , Psoríase/diagnóstico por imagem , Ultrassonografia , Índice de Gravidade de Doença
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