RESUMO
Important sex-related differences have been observed in the onset, prevalence, and clinical phenotype of depression, based on several epidemiological studies. Social, behavioural, and educational factors have a great role in underlying this bias; however, also several biological factors are extensively involved. Indeed, sexually dimorphic biological systems might represent the underlying ground for these disparities, including cerebral structures and neural correlates, reproductive hormones, stress response pathways, the immune system and inflammatory reaction, metabolism, and fat distribution. Furthermore, in this perspective, it is also important to consider and focus the attention on specific ages and life stages of individuals: indeed, women experience during their life specific periods of reproductive transitional phases, which are not found in men, that represent windows of particular psychological vulnerability. In addition to these, other biologically related risk factors, including the occurrence of sleep disturbances and the exposure to childhood trauma, which are found to differentially affect men and women, are also putative underlying mechanisms of the clinical bias of depression. Overall, by taking into account major differences which characterize men and women it might be possible to improve the diagnostic process, as well as treat more efficiently depressed individuals, based on a more personalized medicine and research.
Assuntos
Depressão , Hormônios , Masculino , Humanos , Feminino , Depressão/etiologia , Fatores de Risco , Caracteres Sexuais , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Hipófise-Suprarrenal , Fatores SexuaisRESUMO
Narrowband Internet of Things (NB-IoT) has quickly become a leading technology in the deployment of IoT systems and services, owing to its appealing features in terms of coverage and energy efficiency, as well as compatibility with existing mobile networks. Increasingly, IoT services and applications require location information to be paired with data collected by devices; NB-IoT still lacks, however, reliable positioning methods. Time-based techniques inherited from long-term evolution (LTE) are not yet widely available in existing networks and are expected to perform poorly on NB-IoT signals due to their narrow bandwidth. This investigation proposes a set of strategies for NB-IoT positioning based on fingerprinting that use coverage and radio information from multiple cells. The proposed strategies were evaluated on two large-scale datasets made available under an open-source license that include experimental data from multiple NB-IoT operators in two large cities: Oslo, Norway, and Rome, Italy. Results showed that the proposed strategies, using a combination of coverage and radio information from multiple cells, outperform current state-of-the-art approaches based on single cell fingerprinting, with a minimum average positioning error of about 20 m when using data for a single operator that was consistent across the two datasets vs. about 70 m for the current state-of-the-art approaches. The combination of data from multiple operators and data smoothing further improved positioning accuracy, leading to a minimum average positioning error below 15 m in both urban environments.
RESUMO
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can exert antidepressant, anti-inflammatory and neuroprotective properties, but the exact molecular mechanism underlying their effects is still not fully understood. We conducted both in vitro and clinical investigations to test which EPA or DHA metabolites are involved in these anti-inflammatory, neuroprotective and antidepressant effects. In vitro, we used the human hippocampal progenitor cell line HPC0A07/03C, and pre-treated cells with either EPA or DHA, followed by interleukin 1beta (IL1ß), IL6 and interferon-alpha (IFN-α). Both EPA and DHA prevented the reduction in neurogenesis and the increase in apoptosis induced by these cytokines; moreover, these effects were mediated by the lipoxygenase (LOX) and cytochrome P450 (CYP450) EPA/DHA metabolites, 5-hydroxyeicosapentaenoic acid (HEPE), 4-hydroxydocosahexaenoic acid (HDHA), 18-HEPE, 20-HDHA, 17(18)-epoxyeicosatetraenoic acid (EpETE) and 19(20)-epoxydocosapentaenoic acid (EpDPA), detected here for the first time in human hippocampal neurones using mass spectrometry lipidomics of the supernatant. In fact, like EPA/DHA, co-treatment with these metabolites prevented cytokines-induced reduction in neurogenesis and apoptosis. Moreover, co-treatment with 17(18)-EpETE and 19(20)-EpDPA and the soluble epoxide hydroxylase (sEH) inhibitor, TPPU (which prevents their conversion into dihydroxyeicosatetraenoic acid (DiHETE)/ dihydroxydocosapentaenoic acid (DiHDPA) metabolites) further enhanced their neurogenic and anti-apoptotic effects. Interestingly, these findings were replicated in a sample of n = 22 patients with a DSM-IV Major Depressive Disorder, randomly assigned to treatment with either EPA (3.0 g/day) or DHA (1.4 g/day) for 12 weeks, with exactly the same LOX and CYP450 lipid metabolites increased in the plasma of these patients following treatment with their precursor, EPA or DHA, and some evidence that higher levels of these metabolites were correlated with less severe depressive symptoms. Overall, our study provides the first evidence for the relevance of LOX- and CYP450-derived EPA/DHA bioactive lipid metabolites as neuroprotective molecular targets for human hippocampal neurogenesis and depression, and highlights the importance of sEH inhibitors as potential therapeutic strategy for patients suffering from depressive symptoms.
Assuntos
Transtorno Depressivo Maior , Ácidos Graxos Ômega-3 , Sistema Enzimático do Citocromo P-450/metabolismo , Sistema Enzimático do Citocromo P-450/farmacologia , Sistema Enzimático do Citocromo P-450/uso terapêutico , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Ácido Eicosapentaenoico/uso terapêutico , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Hipocampo/metabolismo , Humanos , Inflamação/metabolismo , Lipoxigenase/metabolismo , Lipoxigenase/farmacologia , Lipoxigenase/uso terapêutico , NeurogêneseRESUMO
The endocannabinoid (eCB) system is considered relevant in the pathophysiology of affective disorders, and a potential therapeutic target, as its hypoactivity is considered an important risk factor of depression. However, the biological mechanisms whereby the eCB system affects mood remain elusive. Through a systematic review, thirty-seven articles were obtained from the PubMed/Medline, Web of Science, Embase, PsychInfo, and CINAHL databases, investigating the role of the eCB system on the immune system and neurogenesis, as well as resulting behavioural effects in rodent models of affective disorders. Overall, activation of the eCB system appears to decrease depressive-like behaviour and to be anti-inflammatory, while promoting neuro- and synaptogenesis in various models. Activation of cannabinoid receptors (CBRs) is shown to be crucial in improving depressive-like and anxiety-like behaviour, although cannabidiol administration suggests a role of additional mechanisms. CB1R signalling, as well as fatty acid amide hydrolase (FAAH) inhibition, are associated with decreased pro-inflammatory cytokines. Moreover, activation of CBRs is required for neurogenesis, which is also upregulated by FAAH inhibitors. This review is the first to assess the association between the eCB system, immune system and neurogenesis, alongside behavioural outcomes, across rodent models of affective disorders. We confirm the therapeutic potential of eCB system activation in depression and anxiety, highlighting immunoregulation as an important mechanism whereby dysfunctional behaviour and neurogenesis can be improved.
Assuntos
Endocanabinoides , Neurogênese , Animais , Ansiedade , Inflamação , Transtornos do Humor/tratamento farmacológicoRESUMO
Two types of consonant gemination characterize Italian: lexical and syntactic. Italian lexical gemination is contrastive, so that two words may differ by only one geminated consonant. In contrast, syntactic gemination occurs across word boundaries and affects the initial consonant of a word in specific contexts, such as the presence of a monosyllabic morpheme before the word. This study investigates the acoustic correlates of Italian lexical and syntactic gemination, asking if the correlates for the two types are similar in the case of stop consonants. Results confirmed previous studies showing that duration is a prominent gemination cue, with a lengthened consonant closure and a shortened pre-consonant vowel for both types. Results also revealed the presence, in about 10%-12% of instances, of a double stop-release burst, providing strong support for the biphonematic nature of Italian geminated stop consonants. Moreover, the timing of these bursts suggests a different planning process for lexical vs syntactic geminates. The second burst, when present, is accommodated within the closure interval in syntactic geminates, while lexical geminates are lengthened by the extra burst. This suggests that syntactic gemination occurs during a post-lexical phase of production planning, after timing has already been established.
Assuntos
Fonética , Percepção da Fala , Acústica , ItáliaRESUMO
BACKGROUND: Although the pro-inflammatory cytokine, interleukin (IL)6, has been generally regarded as "depressogenic", recent research has started to question this assumption, in light of the fact that this cytokine can also have anti-inflammatory properties. This bimodal action seems to be dependent on its concentration levels, and on the concomitant presence of other pro-inflammatory cytokines. METHODS: We exposed a human hippocampal progenitor cell line HPC0A07/03C to cytokine levels described in depressed patients (IL6 5pg/ml with IL1ß 10pg/ml or Macrophage Migration Inhibitory Factor (MIF) 300pg/ml), in healthy subjects (IL6 with IL1ß, 1pg/ml or MIF 10pg/ml), as well as to the potentially anti-inflammatory, much higher concentrations of IL6 (50000pg/ml). RESULTS: Treatment with high concentrations of IL6 with IL1ß or MIF (resembling depressed patients) decreases neurogenesis when compared with low concentrations of the same cytokines (healthy subjects), and that this is mediated via production of, respectively, IL8 and IL1ß in cell supernatant. Instead, treatment with the very high, anti-inflammatory concentration of IL6 (50000pg/ml) together with high IL1ß or MIF prevents the decrease in neurogenesis and reduces both IL8 and IL1ß. When the high concentrations of both IL1ß and MIF were used in co-treatment, as a model of treatment resistant depression, we also demonstrate a reduction in neurogenesis, and that this is mediated via a decrease in IL4; moreover, co-treatment with high IL1ß and MIF and the very high concentration of IL6 prevents the reduction in neurogenesis, and increases IL4. CONCLUSIONS: Our results demonstrate that IL6 can exert both pro- and anti-inflammatory (potentially antidepressant) properties, depending on its concentrations and combinations with other inflammatory cytokines.
RESUMO
Perinatal psychopathologies affect more than 25% of women during and after their gestational period. These psychiatric disorders can potentially determine important biological variations in their organisms, affecting many different physiological and metabolic pathways. Of relevance, any of these changes occurring in the mother can alter the normal composition of breast milk, particularly the concentration of nutritional and inflammatory components, which play a role in child brain functioning and development. Indeed, there is evidence showing that changes in milk composition can contribute to cognitive impairments and alterations in mental abilities in children. This review aims to shed light on the unique intergenerational role played by breast milk composition, from maternal psychopathologies to child development.
Assuntos
Desenvolvimento Infantil , Leite Humano , Animais , Criança , Feminino , Humanos , Fatores Imunológicos , Mães , Gravidez , PsicopatologiaRESUMO
The weighted k-nearest neighbors (WkNN) algorithm is by far the most popular choice in the design of fingerprinting indoor positioning systems based on WiFi received signal strength (RSS). WkNN estimates the position of a target device by selecting k reference points (RPs) based on the similarity of their fingerprints with the measured RSS values. The position of the target device is then obtained as a weighted sum of the positions of the k RPs. Two-step WkNN positioning algorithms were recently proposed, in which RPs are divided into clusters using the affinity propagation clustering algorithm, and one representative for each cluster is selected. Only cluster representatives are then considered during the position estimation, leading to a significant computational complexity reduction compared to traditional, flat WkNN. Flat and two-step WkNN share the issue of properly selecting the similarity metric so as to guarantee good positioning accuracy: in two-step WkNN, in particular, the metric impacts three different steps in the position estimation, that is cluster formation, cluster selection and RP selection and weighting. So far, however, the only similarity metric considered in the literature was the one proposed in the original formulation of the affinity propagation algorithm. This paper fills this gap by comparing different metrics and, based on this comparison, proposes a novel mixed approach in which different metrics are adopted in the different steps of the position estimation procedure. The analysis is supported by an extensive experimental campaign carried out in a multi-floor 3D indoor positioning testbed. The impact of similarity metrics and their combinations on the structure and size of the resulting clusters, 3D positioning accuracy and computational complexity are investigated. Results show that the adoption of metrics different from the one proposed in the original affinity propagation algorithm and, in particular, the combination of different metrics can significantly improve the positioning accuracy while preserving the efficiency in computational complexity typical of two-step algorithms.
RESUMO
The automatic identification of foreign accents can play a crucial role in various speech systems, including speaker identification, e-learning, telephone banking, and more. Additionally, it can greatly enhance the robustness of Automatic Speech Recognition (ASR) systems. Non-native accents in speech signals are characterized by distinct pronunciations, prosody, and voice characteristics of the speaker. However, automatically identifying foreign accents poses significant challenges, particularly in the context of multi-class modeling. Multi-classification models face difficulties in achieving high performance and dealing with computational challenges when confronted with multi-dimensional and unbalanced datasets, such as those with more than two accents. Furthermore, the choice of features remains a bottleneck problem for Foreign Accent Identification (FAID), further hindering performance in these tasks. Consequently, the accuracy of current systems is typically low. To address these challenges, this paper proposes a framework based on the Multi-Kernel Extreme Learning Machine (MKELM) model for the multi-classification of FAID. The MKELM model utilizes a novel weighted scheme to classify various non-native English accents, including Arabic, Chinese, Korean, French, and Spanish. The model first combines Mel-frequency cepstral coefficients (MFCCs) and prosodic features as input, trains pairwise binary classifiers independently, and subsequently employs a weighting scheme to distinguish between classes and identify accents. Through experiments, the proposed model achieves an accuracy rate of 84.72% using a paired weighting scheme. In contrast, the accuracy rate drops to 66.5% when employing the traditional non-weighted multi-classification scheme. A comparison with other models demonstrates the significant advantages of the proposed model in FAID multi-class classification, showcasing improved accuracy, reduced computational complexity (requiring fewer computations, faster learning rates, and shorter training time), and enhanced stability compared to state-of-the-art classification methods.
RESUMO
Exposure to early-life stress (ELS) has been related to an increased susceptibility to psychiatric disorders later in life. Although the molecular mechanisms underlying this association are still under investigation, glucocorticoid signaling has been proposed to be a key mediator. Here, we used two preclinical models, the prenatal stress (PNS) animal model and an in vitro model of hippocampal progenitor cells, to assess the long-term effect of ELS on FKBP5, NR3C1, NR3C2, and FoxO1, four stress-responsive genes involved in the effects of glucocorticoids. In the hippocampus of male PNS rats sacrificed at different time points during neurodevelopment (PND 21, 40, 62), we found a statistically significant up-regulation of FKBP5 at PND 40 and PND 62 and a significant increase in FoxO1 at PND 62. Interestingly, all four genes were significantly up-regulated in differentiated cells treated with cortisol during cell proliferation. As FKBP5 was consistently modulated by PNS at adolescence (PND 40) and adulthood (PND 62) and by cortisol treatment after cell differentiation, we measured a panel of miRNAs targeting FKBP5 in the same samples where FKBP5 expression levels were available. Interestingly, both miR-20b-5p and miR-29c-3p were significantly reduced in PNS-exposed animals (both at PND40 and 62) and also in the in vitro model after cortisol exposure. Our results highlight the key role of miR-20b-5p and miR-29c-3p in sustaining the long-term effects of ELS on the stress response system, representing a mechanistic link possibly contributing to the enhanced stress-related vulnerability to mental disorders.
Assuntos
Hidrocortisona , MicroRNAs , Adolescente , Animais , Feminino , Humanos , Masculino , Gravidez , Ratos , Glucocorticoides , MicroRNAs/genética , MicroRNAs/metabolismo , Transdução de SinaisRESUMO
Objective: An emerging marker of depression in the perinatal period is represented by a reduction in the autonomic nervous system (ANS) activity, reflected by heart rate variability (HRV). This scoping review aims to map the association between HRV and depression during the perinatal period and to understand its potential clinical implications. Introduction: Previous evidence associated ANS dysfunction and depressive symptomatology in the general population. Few observational and intervention studies investigated how HRV could be related to both pre- and post-partum depressive symptoms. However, high heterogeneity in the study designs and methods has been reported. Therefore, this scoping review plans to combine all these findings to build a starting point for future research. Inclusion criteria: This scoping review will consider articles focusing on the association between HRV and depression in the peripartum and - when available - on the impact of interventions on HRV and how this correlates with changes in depressive symptoms. Studies will be included with no restrictions on participants' age, peripartum time points for the assessment, and HRV parameters collected. Methods: We will perform a systematic search using the Medline (PubMed), PsychInfo, and Web of Science (WoS) databases. Two authors will independently screen titles, abstracts, and then full-text articles that meet the inclusion criteria. The review will include only journal articles published in English, with no time limitations. Data will be extracted and presented in tables and/or graphical representations to summarise and describe the results. Extracted data will be reported in a comprehensive summary.
RESUMO
BAG3, a member of the BAG family of heat shock protein (HSP) 70 cochaperones, is expressed in response to stressful stimuli in a number of normal cell types and constitutively in a variety of tumors, including pancreas carcinomas, lymphocytic and myeloblastic leukemias, and thyroid carcinomas. Down-regulation of BAG3 results in cell death, but the underlying molecular mechanisms are still elusive. Here, we investigated the molecular mechanism of BAG3-dependent survival in human osteosarcoma (SAOS-2) and melanoma (M14) cells. We show that bag3 overexpression in tumors promotes survival through the NF-kappaB pathway. Indeed, we demonstrate that BAG3 alters the interaction between HSP70 and IKKgamma, increasing availability of IKKgamma and protecting it from proteasome-dependent degradation; this, in turn, results in increased NF-kappaB activity and survival. These results identify bag3 as a potential target for anticancer therapies in those tumors in which this gene is constitutively expressed. As a proof of principle, we show that treatment of a mouse xenograft tumor model with bag3siRNA-adenovirus that down-regulates bag3 results in reduced tumor growth and increased animal survival.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Regulação Neoplásica da Expressão Gênica , Quinase I-kappa B/metabolismo , Animais , Antineoplásicos/farmacologia , Apoptose , Proteínas Reguladoras de Apoptose , Linhagem Celular Tumoral , Feminino , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Modelos Biológicos , NF-kappa B/metabolismo , RNA Interferente Pequeno/metabolismoRESUMO
Accumulating evidence suggests that chronic stress can be a cofactor for the initiation and progression of cancer. Here we evaluated the role of endothelial nitric oxide synthase (eNOS) in stress-promoted tumour growth of murine B16F10 melanoma cell line in C57BL/6 mice. Animals subjected to restraint stress showed increased levels adrenocorticotropic hormone, enlarged adrenal glands, reduced thymus weight and a 3.61-fold increase in tumour growth in respect to no-stressed animals. Tumour growth was significantly reduced in mice treated with the ß-antagonist propranolol. Tumour samples obtained from stressed mice displayed high levels of vascular endothelial growth factor (VEGF) protein in immunohistochemistry. Because VEGF can induce eNOS increase, and nitric oxide is a relevant factor in angiogenesis, we assessed the levels of eNOS protein by Western blot analysis. We found a significant increase in eNOS levels in tumour samples from stressed mice, indicating an involvement of this enzyme in stress-induced tumour growth. Accordingly, chronic stress did not promote tumour growth in eNOS(-/-) mice. These results disclose for the first time a pivotal role for eNOS in chronic stress-induced initiation and promotion of tumour growth.
Assuntos
Melanoma Experimental/patologia , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Fisiológico , Animais , Doença Crônica , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Masculino , Melanoma Experimental/enzimologia , Melanoma Experimental/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Receptores Adrenérgicos beta/metabolismo , Transdução de SinaisRESUMO
The GEMMA database consists of recordings of disyllabic words: vowel-consonant-vowel (VCV) for nongeminate cases and vowel-consonant-consonant-vowel (VCCV) for geminate cases. The consonants in the words are stops /b/, /d/, /g/, /p/, /t/, /k/, affricates /ts/, /dz/, /ʧ/, /ʤ/, fricatives /f/, /v/, /s/, /z/ (singleton only) and /Ê/ (geminate only), nasals /m/, /n/ and /ɲ/ (geminate only), and liquids /l/, /r/ and / λ / (geminate only). The database also includes recordings for glides (/j/, /w/). The vowels in the words are /a, i, u/; words are symmetric with respect to vowel. Six native adult speakers of Standard Italian, raised and living in Rome, Italy, three female and three male, uttered the speech materials in three different recording sessions; three repetitions for each word per speaker were therefore collected. The dataset also includes the durations of vowel and consonant segments for all cases where the consonant can be singleton vs. geminate (see [1] and [2]).
RESUMO
BACKGROUND: Exposure to traumatic experience represents one of the key environmental factors influencing the risk for several psychiatric disorders, in particular when suffered during childhood, a critical period for brain development, characterized by a high level of neuroplasticity. Abnormalities affecting neurotrophic factors might play a fundamental role in the link between childhood trauma (CT) and early life stress (ELS) and psychiatric disorders. METHODS: A systematic review was conducted, considering genetic, biochemical and expression studies along with cognitive and brain structure imaging investigations, based on PubMed and Web of Science databases (available up until November 2021), to identify potential neuroplasticity related biomarkers associated both with CT/ELS and psychiatric disorders. The search was followed by data abstraction and study quality assessment (Newcastle-Ottawa Scale). RESULTS: 103 studies met our eligibility criteria. Among them, 65 were available for genetic, 30 for biochemical and 3 for mRNA data; 45 findings were linked to specific symptomatology/pathologies, 16 with various cognitive functions, 19 with different brain areas, 6 on methylation and 36 performed on control subjects for the Brain Derived Neurotrophic Factor (BDNF); whereas 4 expression/biochemical studies covered Neurotrophin 4 (NT-4), Vascular Endothelium Growth Factor (VEGF), Epidermal Growth Factor (EGF), Fibroblast Growth Factor (FGF), and Transforming Growth Factor ß1 (TGF-ß1). LIMITATIONS: Heterogeneity of assessments (biological, psychological, of symptomatology, and CT/ELS), age range and ethnicity of samples for BDNF studies; limited studies for other neurotrophins. CONCLUSIONS: Results support the key role of BDNF (in form of Met allele) as biomarker, both at genetic and biochemical level, in mediating the effect of CT/ELS in psychiatric disorders, passing through specific cognitive functions and specific brain region architecture.
Assuntos
Experiências Adversas da Infância , Transtornos Mentais , Biomarcadores/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Cognição , Humanos , Transtornos Mentais/genética , Biologia MolecularRESUMO
The LaMIT database consists in recordings of 100 Italian sentences. The sentences in the database were designed so to include all phonemes of the Italian language, and also take into account the typical frequency of each phoneme in written Italian. Four native adult speakers of Standard Italian, raised and living in Rome, Italy, two female and two male, pronounced the sentences in two different recording sessions; two repetitions for each sentence per speaker were therefore collected, for a total of 800 recordings. The database was specifically created for application in the LaMIT project, that focuses on the application to the Italian language of the Lexical Access model proposed by Ken Stevens for American English. The model relies on the detection of specific acoustic discontinuities called landmarks and other acoustic cues to features that characterize each phoneme. Each recording was thus processed to generate a set of labeling files that identify both predicted landmarks and other cues, and actual landmarks/cues. The labeling files, compiled according to the labeling syntax used in the Praat speech processing software, are also made available as part of the LAMIT database.
RESUMO
Despite the progressive increase of early diagnosis, a subset of prostate cancers show a metastasizing and lethal course, not always predictable upon the traditional prognostic parameters. The object of this study was to investigate the role of the survival co-chaperone protein BAG3 as a new prognostic marker for prostate cancer. BAG3 was detected by immunohistochemistry in 55 specimens of surgically removed prostate carcinomas and in 15 surgical specimens of non-neoplastic prostate tissues. Results were compared with clinic-pathological data and outcome of patients and statistically evaluated. BAG3 resulted expressed in all the cases: Non-neoplastic prostate tissue showed a cytoplasmatic staining with apical reinforcement, a finding which appears consistent with the reported connection of the protein with the membrane focal cell-adhesion complexes. In prostate carcinomas, BAG3 showed a progressive decrease of the expression level from well- to low-differentiated carcinoma, coupled with the loss of polarisation of the signal in metastasizing cases. These results indicate that BAG3 intra-cytoplasmic delocalisation is a specific feature of cancer versus non-neoplastic prostate and a candidate new marker for prediction of prostate cancer invasiveness and behaviour.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenocarcinoma/metabolismo , Biomarcadores Tumorais/análise , Neoplasias da Próstata/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Proteínas Reguladoras de Apoptose , Intervalo Livre de Doença , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologiaRESUMO
BACKGROUND: Cutaneous melanoma (CM) is the most lethal form of skin malignancy, which registers a constant increase in incidence worldwide. The identification of molecular alteration(s) involved in its biological aggressiveness represents a major challenge for researchers, considering that existing therapies are ineffective to treat metastasizing cases. The epigenetic control of chromatin dynamics during DNA synthesis, replication, and repair is fundamental for the orderly progression of cell proliferation. The Chromatin Assembly Factor 1 (CAF-1) complex acts as a major regulator of this process; its intermediate (p60) subunit has been recently proposed as a novel proliferation and prognostic marker for several tumors. We aimed to establish if the evaluation of the expression of CAF-1/p60 in primary CM may help define the prevision of outcome of patients. METHODS: Immunohistochemistry with anti-CAF-1/p60 was performed on paraffin-embedded tissue sections of 130 cases of primary CM retrieved from the archive files of the Department of Biomorphological and Functional Sciences, Section of Pathology, University "Federico II" of Naples, Italy. Results were compared with histopathological and follow-up data of patients. RESULTS: CAF-1/p60 was expressed in all CM. A significant statistical association between the overexpression of the protein and the occurrence of skin, node and/or distant metastases (P < 0.05) emerged, independently from histopathological prognostic factors. CONCLUSIONS: CAF-1/p60 looks promising as a new prognostic marker for CM and sheds new light on the molecular events associated with photocancerogenesis and melanoma biology.The screening for CAF-1/p60 might contribute to the molecular sub-classification of CM, with improved translational outcomes.
Assuntos
Fator 1 de Modelagem da Cromatina/biossíntese , Regulação Neoplásica da Expressão Gênica , Melanoma/patologia , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Resultado do TratamentoRESUMO
BACKGROUND: The hairdressing trade may potentially expose its practitioners and their customers to blood-borne infections. METHODS: Knowledge, attitudes and behaviours towards occupational risk of HIV, HBV and HCV infections were evaluated in a cross-sectional survey, conducted during spring 2008, in 105 out of 112 randomly selected hairdressers of Palermo. Participants were queried by answering to an anonymous questionnaire. RESULTS: Most of hairdressers (93.3%) knew that HIV and hepatitis are transmitted through parenteral route and could also be transmitted by razors. The availability of gloves was inadequate, up to 30% of the participants never used them and up to 50% usually reused them. In total, 90 respondents stated to perform a sterilization process of the cutting instruments by ultraviolet light, but only 70 sterilized the articles between two customers and only 34.3% executed a daily disinfection of the hair brushes. Statistical analysis showed that younger age and post-primary school instruction were significantly associated with knowledge and procedures that could prevent transmission of blood-borne virus (P = 0.01 and P < 0.01, respectively). Moreover, only 32 hairdressers agreed to participate to a free specific course on occupational risk offered by the University of Palermo. CONCLUSION: Although the level of awareness among hairdressers about HIV, hepatitis and risk of transmission was good, there were some unsafe practices that may lead to infections due to blood-borne viruses. The present article highlights the need to improve specific health messages in media campaigns carried out to general population, diffusing more appropriate educational materials for salons and organizing obligatory refresher courses for the hairdressing sector.
Assuntos
Comércio , Contaminação de Equipamentos/prevenção & controle , Infecções por HIV/transmissão , Conhecimentos, Atitudes e Prática em Saúde , Hepatite B/transmissão , Hepatite C/transmissão , Desinfecção , Cabelo , Humanos , ItáliaRESUMO
AIMS: Prostatic cancer may remain organ-confined indefinitely; in a number of patients, however it gives rise to clinical symptoms and death. The biological behaviour of this tumour mostly remains difficult to predict. A promising tool for diagnosis and prognosis of some human tumours is the chromatin assembly factor-1 (CAF-1), involved in the control of higher order chromatin organization. The aim was to explore the role of CAF-1/p60 protein as a new prognostic marker for prostatic cancer. METHODS AND RESULTS: The expression of CAF-1/p60 was evaluated by immunohistochemistry and Western blotting in a selected series of prostatic cancers and in prostatic cancer cell lines. Results were compared with clinicopathological data and outcome of patients. CAF-1/p60 was expressed in all cases, with a linear increase from low-grade tumours (Gleason score <7) to high-grade prostatic cancers (Gleason score >7). By comparing results with follow-up data, a significant association between overexpression of CAF-1/p60 and unfavourable behaviour of prostatic cancer emerged, and its predictive value was independent of classical prognostic factors. CONCLUSIONS: In our series of cases, overexpression of CAF-1/p60 characterized prostatic cancers with a worse prognosis. CAF-1/p60 has a potential role as a new reliable prognostic biomarker for prostatic cancer.