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1.
Ann Surg Oncol ; 30(9): 5733-5742, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37270440

RESUMEN

BACKGROUND: This study evaluated the efficacy of pressurized intraperitoneal aerosol chemotherapy (PIPAC) with systemic chemotherapy as a bidirectional approach for gastric cancer (GC) patients with synchronous peritoneal metastases (SPM). METHODS: A retrospective analysis of a prospective PIPAC database was queried for patients who underwent a bidirectional approach between October 2019 and April 2022 at two high-volume GC surgery units in Italy (Verona and Siena). Surgical and oncological outcomes were analyzed. RESULTS: Between October 2019 and April 2022, 74 PIPAC procedures in 42 consecutive patients with Eastern Cooperative Oncology Group performance status ≤2 were performed-32 patients treated in Verona and 10 in Siena. Twenty-seven patients (64%) were female and median age at first PIPAC was 60.5 years (I-III quartiles: 49-68 years). Median Peritoneal Cancer Index (PCI) was 16 (I-III quartiles: 8-26) and 25 patients (59%) had at least two PIPAC procedures. Major complications according to the Common Terminology Criteria for Adverse Events (CTCAE; 3 and 4) occurred in three (4%) procedures, and, according to the Clavien-Dindo classification (>3a), one (1%) severe complication occurred. There were no reoperations or deaths within 30 days. Median overall survival (mOS) from diagnosis was 19.6 months (range 14-24), and mOS from first PIPAC was 10.5 months (range 7-13). Excluding cases with very heavy metastatic peritoneal burden, with PCI from 2 to 26, treated with more than one PIPAC, mOS from diagnosis was 22 months (range 14-39). Eleven patients (26%) underwent curative-intent surgery after a bidirectional approach. R0 was achieved in nine (82%) patients and complete pathological response was obtained in three (27%) cases. CONCLUSIONS: Patient selection is associated with bidirectional approach efficacy and feasibility for SPM GC treatment, which may allow potentially curative surgical radicalization in highly selected cases.


Asunto(s)
Neoplasias Peritoneales , Neoplasias Gástricas , Humanos , Femenino , Persona de Mediana Edad , Masculino , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Cisplatino/uso terapéutico , Neoplasias Peritoneales/secundario , Doxorrubicina , Estudios Retrospectivos , Estudios Prospectivos , Aerosoles
2.
Scand J Caring Sci ; 35(2): 457-467, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32311779

RESUMEN

AIMS: Assessing pain in children with autism spectrum disorders (ASDs) can be extremely challenging, since many cannot self-report pain. This study aims to test the validity of the Non-Communicating Children's Pain Checklist - Revised (NCCPC-R) in identifying pain in children and adolescents affected by ASDs. MATERIALS AND METHODS: A two-phase validation study based on (a) the translation and cultural adaptation of the NCCPC-R to Italian and to ASD-specific needs and context; and (b) the validation of a modified, 32-item version of the NCCPC-R. In all, 141 carers of children aged 6-16 years with ASDs were asked to recall an in-pain episode and a not-in-pain episode of their child and to rate on a 3-point scale (0 = not at all, 3 = very often) each behaviour included in the tool. Internal consistency (Cronbach's α), explorative and confirmative factorial structure, as well as concurrent and discriminant validity, were all assessed. RESULTS: Confirmatory factor analysis established the revised version of the NCCPC-R for children with ASDs (named = NCCPC-RASD ), formed from 10 of the original 30 items categorised into three factors ('Changing in mood', 'Increasing in tension' and 'Alerting reaction') to have an acceptable level of reliability. The tool was internally consistent (α = 0.741 during in-pain episodes, α = 0.790 during not-in-pain episodes) and was able to discriminate between in-pain episodes (13.36 out of 40; CI 95% 12.34-14.39) and not-in-pain episodes (7.84 out of 40; CI 95% 6.86-8.82, p < 0.001). CONCLUSIONS: These results provide preliminary evidence that the 10-item version of the NCCPC-RASD is a reliable and valid tool for assessing pain in children with ASD.


Asunto(s)
Trastorno del Espectro Autista , Adolescente , Trastorno del Espectro Autista/complicaciones , Niño , Análisis Factorial , Humanos , Dolor/diagnóstico , Dimensión del Dolor , Psicometría , Reproducibilidad de los Resultados , Encuestas y Cuestionarios
4.
Biochim Biophys Acta ; 1842(2): 269-74, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24326104

RESUMEN

Inherited thrombocytopenias are heterogeneous diseases caused by at least 20 genes playing different role in the processes of megakaryopoiesis and platelet production. Some forms, such as thrombocytopenia 4 (THC4), are very rare and not well characterized. THC4 is an autosomal dominant mild thrombocytopenia described in only one large family from New Zealand and due to a mutation (G41S) of the somatic isoform of the cytochrome c (CYCS) gene. We report a novel CYCS mutation (Y48H) in patients from an Italian family. Similar to individuals carrying G41S, they have platelets of normal size and morphology, which are only partially reduced in number, but no prolonged bleeding episodes. In order to determine the pathogenetic consequences of Y48H, we studied the effects of the two CYCS mutations in yeast and mouse cellular models. In both cases, we found reduction of respiratory level and increased apoptotic rate, supporting the pathogenetic role of CYCS in thrombocytopenia.


Asunto(s)
Apoptosis/genética , Citocromos c/genética , Metabolismo Energético/genética , Mutación Missense , Trombocitopenia/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Células Cultivadas , Preescolar , Análisis Mutacional de ADN , Embrión de Mamíferos/citología , Salud de la Familia , Femenino , Fibroblastos/citología , Fibroblastos/metabolismo , Humanos , Pulmón/citología , Masculino , Ratones , Datos de Secuencia Molecular , Consumo de Oxígeno/genética , Linaje , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crecimiento & desarrollo , Saccharomyces cerevisiae/metabolismo , Homología de Secuencia de Aminoácido , Trombocitopenia/patología
5.
Nephrol Dial Transplant ; 30(7): 1193-202, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26047633

RESUMEN

BACKGROUND: Pregnancy on dialysis is increasingly being reported. This study evaluates the behavioural profile of the children of mothers on dialysis and the parental stress their mothers undergo when compared with a group of mothers affected by a different chronic disease (microcythaemia) and a group of healthy control mothers. METHODS: Between 2000 and 2012, 23 on-dialysis mothers gave birth to 24 live-born children in Italy (23 pregnancies, 1 twin pregnancy, one of the twins deceased soon after delivery); of these, 16 mothers and 1 father (whose wife died before the inquiry) were included in the study (1 mother had died and the father was unavailable; 2 were not asked to participate because their children had died and 3 were unavailable; children: median age: 8.5, min-max: 2-13 years). Twenty-three mothers affected by transfusion-dependent microcythaemia or drepanocitosis (31 pregnancies, 32 children) and 35 healthy mothers (35 pregnancies, 35 children; median age of the children: 7, min-max: 1-13 years) were recruited as controls. All filled in the validated questionnaires: 'Child Behaviour Checklist' (CBCL) and the 'Parental Stress Index-Short Form' (PSI-SF). RESULTS: The results of the CBCL questionnaire were similar for mothers on dialysis and healthy controls except for pervasive developmental problems, which were significantly higher in the dialysis group, while microcythaemia mothers reported higher emotional and behavioural problems in their children in 8 CBCL sub-scales. Two/16 children in the dialysis and 3/32 in the microcythaemia group had pathological profiles, as assessed by T-scores (p: ns). PSI-SF indicated a normal degree of parental stress in microcythaemia subjects and healthy controls, while mothers on dialysis declared significantly lower stress, suggesting a defensive response in order to minimize problems, stress or negativity in their relationship with their child. CONCLUSIONS: According to the present analysis, the emotional and behavioural outcome is normal in most of the children from on-dialysis mothers. A 'positive defence' in the dialysis mothers should be kept in mind when tailoring psychological support for this medical miracle.


Asunto(s)
Conducta Infantil/psicología , Fallo Renal Crónico/terapia , Trastornos Mentales/diagnóstico , Madres/psicología , Diálisis Renal/efectos adversos , Estrés Psicológico/diagnóstico , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Preescolar , Consejo , Femenino , Humanos , Lactante , Italia , Fallo Renal Crónico/psicología , Masculino , Trastornos Mentales/etiología , Embarazo , Estrés Psicológico/etiología , Encuestas y Cuestionarios
6.
Heliyon ; 10(9): e29936, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38707401

RESUMEN

Intact (whole) cell MALDI TOF mass spectrometry is a commonly used tool in clinical microbiology for several decades. Recently it was introduced to analysis of eukaryotic cells, including cancer and stem cells. Besides targeted metabolomic and proteomic applications, the intact cell MALDI TOF mass spectrometry provides a sufficient sensitivity and specificity to discriminate cell types, isogenous cell lines or even the metabolic states. This makes the intact cell MALDI TOF mass spectrometry a promising tool for quality control in advanced cell cultures with a potential to reveal batch-to-batch variation, aberrant clones, or unwanted shifts in cell phenotype. However, cellular alterations induced by change in expression of a single gene has not been addressed by intact cell mass spectrometry yet. In this work we used a well-characterized human ovarian cancer cell line SKOV3 with silenced expression of a tumor suppressor candidate 3 gene (TUSC3). TUSC3 is involved in co-translational N-glycosylation of proteins with well-known global impact on cell phenotype. Altogether, this experimental design represents a highly suitable model for optimization of intact cell mass spectrometry and analysis of spectral data. Here we investigated five machine learning algorithms (k-nearest neighbors, decision tree, random forest, partial least squares discrimination, and artificial neural network) and optimized their performance either in pure populations or in two-component mixtures composed of cells with normal or silenced expression of TUSC3. All five algorithms reached accuracy over 90 % and were able to reveal even subtle changes in mass spectra corresponding to alterations of TUSC3 expression. In summary, we demonstrate that spectral fingerprints generated by intact cell MALDI-TOF mass spectrometry coupled to a machine learning classifier can reveal minute changes induced by alteration of a single gene, and therefore contribute to the portfolio of quality control applications in routine cell and tissue cultures.

7.
J Biol Chem ; 287(36): 30358-67, 2012 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-22807446

RESUMEN

Nascent HLA-class I molecules are stabilized by proteasome-derived peptides in the ER and the new complexes proceed to the cell surface through the post-ER vesicles. It has been shown, however, that less stable complexes can exchange peptides in the Trans Golgi Network (TGN). HLA-B27 are the most studied HLA-class I molecules due to their association with Ankylosing Spondylitis (AS). Chimeric proteins driven by TAT of HIV have been exploited by us to deliver viral epitopes, whose cross-presentation by the HLA-B27 molecules was proteasome and TAP-independent and not restricted to Antigen-Presenting Cells (APC). Here, using these chimeric proteins as epitope suppliers, we compared with each other and with the HLA-A2 molecules, the two HLA-B*2705 and B*2709 alleles differing at residue 116 (D116H) and differentially associated with AS. We found that the antigen presentation by the two HLA-B27 molecules was proteasome-, TAP-, and APC-independent whereas the presentation by the HLA-A2 molecules required proteasome, TAP and professional APC. Assuming that such difference could be due to the unpaired, highly reactive Cys-67 distinguishing the HLA-B27 molecules, C67S mutants in HLA-B*2705 and B*2709 and V67C mutant in HLA-A*0201 were also analyzed. The results showed that this mutation did not influence the HLA-A2-restricted antigen presentation while it drastically affected the HLA-B27-restricted presentation with, however, remarkable differences between B*2705 and B*2709. The data, together with the occurrence on the cell surface of unfolded molecules in the case of C67S-B*2705 mutant but not in that of C67S-B*2709 mutant, indicates that Cys-67 has a more critical role in stabilizing the B*2705 rather than the B*2709 complexes.


Asunto(s)
Presentación de Antígeno/fisiología , Células Presentadoras de Antígenos/inmunología , Epítopos/inmunología , Antígeno HLA-B27/inmunología , Complejo de la Endopetidasa Proteasomal/inmunología , Células Presentadoras de Antígenos/metabolismo , Epítopos/genética , Epítopos/metabolismo , Antígeno HLA-A2/genética , Antígeno HLA-A2/inmunología , Antígeno HLA-A2/metabolismo , Antígeno HLA-B27/genética , Antígeno HLA-B27/metabolismo , Células HeLa , Humanos , Complejo de la Endopetidasa Proteasomal/metabolismo , Pliegue de Proteína
8.
J Med Genet ; 49(9): 569-77, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22972948

RESUMEN

BACKGROUND: Isolated complex II deficiency is a rare form of mitochondrial disease, accounting for approximately 2% of all respiratory chain deficiency diagnoses. The succinate dehydrogenase (SDH) genes (SDHA, SDHB, SDHC and SDHD) are autosomally-encoded and transcribe the conjugated heterotetramers of complex II via the action of two known assembly factors (SDHAF1 and SDHAF2). Only a handful of reports describe inherited SDH gene defects as a cause of paediatric mitochondrial disease, involving either SDHA (Leigh syndrome, cardiomyopathy) or SDHAF1 (infantile leukoencephalopathy). However, all four SDH genes, together with SDHAF2, have known tumour suppressor functions, with numerous germline and somatic mutations reported in association with hereditary cancer syndromes, including paraganglioma and pheochromocytoma. METHODS AND RESULTS: Here, we report the clinical and molecular investigations of two patients with histochemical and biochemical evidence of a severe, isolated complex II deficiency due to novel SDH gene mutations; the first patient presented with cardiomyopathy and leukodystrophy due to compound heterozygous p.Thr508Ile and p.Ser509Leu SDHA mutations, while the second patient presented with hypotonia and leukodystrophy with elevated brain succinate demonstrated by MR spectroscopy due to a novel, homozygous p.Asp48Val SDHB mutation. Western blotting and BN-PAGE studies confirmed decreased steady-state levels of the relevant SDH subunits and impairment of complex II assembly. Evidence from yeast complementation studies provided additional support for pathogenicity of the SDHB mutation. CONCLUSIONS: Our report represents the first example of SDHB mutation as a cause of inherited mitochondrial respiratory chain disease and extends the SDHA mutation spectrum in patients with isolated complex II deficiency.


Asunto(s)
Complejo II de Transporte de Electrones/deficiencia , Genes Recesivos/genética , Mutación de Línea Germinal/genética , Leucoencefalopatías/genética , Errores Innatos del Metabolismo/genética , Enfermedades Mitocondriales/genética , Succinato Deshidrogenasa/genética , Secuencia de Aminoácidos , Secuencia de Bases , Western Blotting , Encéfalo/patología , Preescolar , Transporte de Electrón , Complejo II de Transporte de Electrones/química , Complejo II de Transporte de Electrones/genética , Femenino , Prueba de Complementación Genética , Humanos , Lactante , Recién Nacido , Leucoencefalopatías/complicaciones , Imagen por Resonancia Magnética , Masculino , Errores Innatos del Metabolismo/complicaciones , Errores Innatos del Metabolismo/enzimología , Enfermedades Mitocondriales/complicaciones , Enfermedades Mitocondriales/enzimología , Datos de Secuencia Molecular , Músculo Esquelético/patología , Mutación/genética , Saccharomyces cerevisiae/metabolismo , Succinato Deshidrogenasa/química
9.
Paediatr Child Health ; 18(9): 465-9, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24426806

RESUMEN

INTRODUCTION: Access to health care for medically uninsured immigrant and refugee children is a public health concern due to the consequences of delayed or substandard care for child development and health. OBJECTIVE: To explore possible differences in help-seeking and service delivery across migratory statuses, institutions and provinces. METHODS: A review was undertaken of 2035 emergency files of immigrant, refugee and undocumented children without provincial health care coverage who sought care at three major paediatric hospitals in Montreal (Quebec) and Toronto (Ontario) during 2008 and 2009. RESULTS: Refugee claimant children with Interim Federal Health Program benefits consulted for less urgent problems than the overall hospital population, except in one hospital that had a multicultural paediatric ambulatory clinic. Undocumented children and new permanent resident immigrant children within the three-month waiting period for provincial health care coverage were over-represented in the very urgent triage category and presented more often for injuries, trauma and mental health problems than did refugee claimant children. DISCUSSION/CONCLUSIONS: Wide interhospital differences suggest that the predicament of limited access to health care of these groups of vulnerable medically uninsured children needs to be addressed through further research to inform policies and develop training.


INTRODUCTION: L'accès aux soins de santé pour les enfants immigrants et réfugiés qui n'ont pas d'assurance est un problème de santé publique, en raison des conséquences du retard des soins ou des soins de second ordre sur leur développement et leur santé. OBJECTIF: Explorer les différences possibles de recherche d'aide et de prestation des soins selon les statuts migratoires, les établissements et les provinces. MÉTHODOLOGIE: Les chercheurs ont entrepris une analyse de 2 035 dossiers urgents d'enfants immigrants, réfugiés et sans papiers, sans assurance-maladie provinciale, qui ont consulté dans trois grands hôpitaux pédiatriques de Montréal, au Québec, et de Toronto, en Ontario, en 2008 et en 2009. RÉSULTATS: Les enfants demandeurs du statut de réfugié profitant des prestations du Programme fédéral de santé intérimaire consultaient pour des problèmes moins urgents que l'ensemble de la population hospitalière, sauf dans un hôpital doté d'une clinique ambulatoire pédiatrique multiculturelle. Les enfants sans papiers et les enfants immigrants qui étaient de nouveaux résidents permanents assujettis à la période d'attente de trois mois avant d'avoir droit à l'assurance-maladie provinciale étaient surreprésentés dans la catégorie de triage très urgent et présentaient plus souvent des blessures, des traumatismes et des problèmes de santé mentale que les enfants demandeurs du statut de réfugié. EXPOSÉ ET CONCLUSIONS: D'après les vastes différences interhos-pitalières, il faudrait poursuivre les recherches sur la situation difficile causée par l'accès limité aux soins de santé de ces groupes d'enfants non assurés vulnérables pour étayer les politiques et élaborer les formations.

10.
J Inorg Biochem ; 246: 112301, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37392615

RESUMEN

A new heteroleptic copper(II) compound named C0-UDCA was prepared by reaction of [Cu(phen)2(OH2)](ClO4)2 (C0) with the bile ursodeoxycholic acid (UDCA). The resulting compound is able to inhibit the lipoxygenase enzyme showing more efficacy than the precursors C0 and UDCA. Molecular docking simulations clarified the interactions with the enzyme as due to allosteric modulation. The new complex shows antitumoral effect on ovarian (SKOV-3) and pancreatic (PANC-1) cancer cells at the Endoplasmic Reticulum (ER) level by activating the Unfolded Protein Response. In particular, the chaperone BiP, the pro-apoptotic protein CHOP and the transcription factor ATF6 are upregulated in the presence of C0-UDCA. The combination of Intact Cell MALDI-MS and statistical analysis have allowed us to discriminate between untreated and treated cells based on their mass spectrometry fingerprints.


Asunto(s)
Inhibidores de la Lipooxigenasa , Neoplasias , Inhibidores de la Lipooxigenasa/farmacología , Ácido Ursodesoxicólico/farmacología , Fenantrolinas/química , Cobre/farmacología , Cobre/química , Simulación del Acoplamiento Molecular , Estrés del Retículo Endoplásmico , Línea Celular , Inhibidores Enzimáticos/farmacología , Apoptosis , Neoplasias Pancreáticas
11.
Blood ; 115(2): 265-73, 2010 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-19965651

RESUMEN

Activation of the T cell-mediated immune response has been associated with changes in the expression of specific microRNAs (miRNAs). However, the role of miRNAs in the development of an effective immune response is just beginning to be explored. This study focuses on the functional role of miR-146a in T lymphocyte-mediated immune response and provides interesting clues on the transcriptional regulation of miR-146a during T-cell activation. We show that miR-146a is low in human naive T cells and is abundantly expressed in human memory T cells; consistently, miR-146a is induced in human primary T lymphocytes upon T-cell receptor (TCR) stimulation. Moreover, we identified NF-kB and c-ETS binding sites as required for the induction of miR-146a transcription upon TCR engagement. Our results demonstrate that several signaling pathways, other than inflammation, are influenced by miR-146a. In particular, we provide experimental evidence that miR-146a modulates activation-induced cell death (AICD), acting as an antiapoptotic factor, and that Fas-associated death domain (FADD) is a target of miR-146a. Furthermore, miR-146a enforced expression impairs both activator protein 1 (AP-1) activity and interleukin-2 (IL-2) production induced by TCR engagement, thus suggesting a role of this miRNA in the modulation of adaptive immunity.


Asunto(s)
Inmunidad Adaptativa/fisiología , Regulación de la Expresión Génica/fisiología , Interleucina-2/biosíntesis , Activación de Linfocitos/fisiología , MicroARNs/metabolismo , Linfocitos T/metabolismo , Muerte Celular/fisiología , Proteína de Dominio de Muerte Asociada a Fas/inmunología , Proteína de Dominio de Muerte Asociada a Fas/metabolismo , Humanos , Interleucina-2/inmunología , Células Jurkat , MicroARNs/inmunología , Proteínas Proto-Oncogénicas c-ets/inmunología , Proteínas Proto-Oncogénicas c-ets/metabolismo , Receptores de Antígenos de Linfocitos T/inmunología , Receptores de Antígenos de Linfocitos T/metabolismo , Elementos de Respuesta/fisiología , Transducción de Señal/fisiología , Linfocitos T/citología , Linfocitos T/inmunología , Factor de Transcripción AP-1/inmunología , Factor de Transcripción AP-1/metabolismo , Transcripción Genética/fisiología
12.
RSC Adv ; 12(39): 25342-25353, 2022 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-36199318

RESUMEN

The main goal of the presented study was to design a biosensor-based system for epinephrine (EP) detection using a poly-thiophene derivative and tyrosinase as a biorecognition element. We compared two different electroanalytical techniques to select the most prominent technique for analyzing the neurotransmitter. The prepared biosensor system exhibited good parameters; the differential pulse (DPV) technique presented a wide linear range (1-20 µM and 30-200 µM), with a low detection limit (0.18 nM and 1.03 nM). In the case of chronoamperometry (CA), a high signal-to-noise ratio and lower reproducibility were observed, causing a less broad linear range (10-200 µM) and a higher detection limit (125 nM). Therefore, the DPV technique was used for the calculation of sensitivity (0.0011 µA mM-1 cm-2), stability (49 days), and total surface coverage (4.18 × 10-12 mol cm-2). The biosensor also showed very high selectivity in the presence of common interfering species (i.e. ascorbic acid, uric acid, norepinephrine, dopamine) and was successfully applied for EP determination in a pharmaceutical sample.

13.
ACS Omega ; 7(38): 33749-33768, 2022 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-36188279

RESUMEN

The study of neurotransmitters and stress hormones allows the determination of indicators of the current stress load in the body. These species also create a proper strategy of stress protection. Nowadays, stress is a general factor that affects the population, and it may cause a wide range of serious disorders. Abnormalities in the level of neurohormones, caused by chronic psychological stress, can occur in, for instance, corporate employees, health care workers, shift workers, policemen, or firefighters. Here we present a new nanomaterials-based sensors technology development for the determination of neurohormones. We focus on fluorescent sensors/biosensors that utilize nanomaterials, such as quantum dots or carbon nanomaterials. Nanomaterials, owing to their diversity in size and shape, have been attracting increasing attention in sensing or bioimaging. They possess unique properties, such as fluorescent, electronic, or photoluminescent features. In this Review, we summarize new trends in adopting nanomaterials for applications in fluorescent sensors for neurohormone monitoring.

14.
Artículo en Inglés | MEDLINE | ID: mdl-34639523

RESUMEN

Benzodiazepines have proven to be highly effective for treating insomnia and anxiety. Although considered safe when taken for a short period of time, a major risk-benefit dilemma arises in the context of long-term use, relating to addiction, withdrawal symptoms, and potential side effects. For these reasons, benzodiazepines are not recommended for treating chronic sleep disorders, anxiety disorders, nor for people over the age of 65, and withdrawal among long-term users is a public health issue. Indeed, only 5% of patients manage to discontinue using these drugs on their own. Even with the help of a general practitioner, this rate does not exceed 25 to 30% of patients, of which approximately 7% manage to remain drug-free in the long term. Cognitive Behavioral Therapies (CBT) offer a crucial solution to this problem, having been shown to increase abstinence success to 70-80%. This article examines traditional and novel CBT techniques in this regard, such as Acceptance and Commitment Therapy, which address both the underlying condition (insomnia/anxiety) and the substance-related disorder. The theoretical framework and evidence supporting the use of these approaches are reviewed. Finally, current research gaps are discussed, and key research perspectives are proposed.


Asunto(s)
Terapia de Aceptación y Compromiso , Terapia Cognitivo-Conductual , Trastornos del Inicio y del Mantenimiento del Sueño , Síndrome de Abstinencia a Sustancias , Trastornos de Ansiedad/tratamiento farmacológico , Benzodiazepinas/uso terapéutico , Humanos , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico
15.
J Hepatol ; 52(5): 644-51, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20338659

RESUMEN

BACKGROUNDS & AIMS: The hepatitis C virus NS3 protein is taken up by myeloid cells in a TLR2-independent manner and activates myeloid cells via TLR2. This study aimed to identify the endocytic receptor(s) involved in the uptake of NS3 by myeloid cells and its relation with TLR2. METHODS: Inhibitors and transfected cells were used to identify the nature of the NS3-binding receptors expressed by myeloid cells. The cooperation between scavenger receptors (SRs) and TLR2 in the NS3-mediated activation of myeloid cells was evaluated using inhibitors, cells from TLR2(-/-) mice, and confocal microscopy. The involvement of SRs in NS3 cross-presentation was evaluated in vitro using an NS3-specific human T-cell clone. RESULTS: We observed that SRs are the main binding structures for NS3 on myeloid cells and identified the SRs SRA-1 and SREC-I as endocytic receptors for NS3. Moreover, both SRs and TLR2 cooperate in NS3-induced myeloid cell activation. CONCLUSION: This study highlights a central role for SRs in NS3 uptake and cross-presentation, and demonstrates a tightly orchestrated cooperation between signalling and endocytic innate receptors in NS3 recognition.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/fisiología , Células Dendríticas/inmunología , Hepacivirus/inmunología , Receptores Depuradores/inmunología , Receptores Depuradores de Clase F/fisiología , Receptor Toll-Like 2/fisiología , Proteínas no Estructurales Virales/inmunología , Animales , Células de la Médula Ósea/citología , Células de la Médula Ósea/inmunología , Células CHO , Diferenciación Celular , Cricetinae , Cricetulus , Células Dendríticas/citología , Células Dendríticas/virología , Endocitosis , Humanos , Receptores de Lipopolisacáridos/inmunología , Ratones , Monocitos/citología , Monocitos/fisiología , Células Mieloides/fisiología , Receptores Depuradores/metabolismo , Proteínas Recombinantes/inmunología , Transfección , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/metabolismo
16.
Mol Genet Metab ; 100(4): 345-8, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20472482

RESUMEN

Mutations of the BCS1L gene are a recognised cause of isolated respiratory chain complex III deficiency and underlie several fatal, neonatal mitochondrial diseases. Here we describe a 20-year-old Kenyan woman who initially presented as a floppy infant but whose condition progressed during childhood and adolescence with increasing muscle weakness, focal motor seizures and optic atrophy. Muscle biopsy demonstrated complex III deficiency and the pathogenicity of a novel, homozygous BCS1L mutation was confirmed by yeast complementation studies. Our data indicate that BCS1L mutations can cause a variable, neurological course which is not always fatal in childhood.


Asunto(s)
Complejo III de Transporte de Electrones/deficiencia , Complejo III de Transporte de Electrones/genética , Mitocondrias/enzimología , Mitocondrias/genética , Mutación/genética , ATPasas Asociadas con Actividades Celulares Diversas , Secuencia de Aminoácidos , Secuencia de Bases , Niño , Análisis Mutacional de ADN , Complejo III de Transporte de Electrones/química , Femenino , Prueba de Complementación Genética , Humanos , Lactante , Recién Nacido , Datos de Secuencia Molecular , Músculo Esquelético/enzimología , Músculo Esquelético/patología , Embarazo , Saccharomyces cerevisiae , Fracciones Subcelulares/enzimología , Análisis de Supervivencia , Factores de Tiempo , Adulto Joven
17.
Stem Cells ; 26(5): 1275-87, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18292209

RESUMEN

Human mesenchymal stem cells (MSC) are immunosuppressive and poorly immunogenic but may act as antigen-presenting cells (APC) for CD4(+) T-cell responses; here we have investigated their ability to serve as APC for in vitro CD8(+) T-cell responses. MSC pulsed with peptides from viral antigens evoked interferon (IFN)-gamma and Granzyme B secretion in specific cytotoxic T lymphocytes (CTL) and were lysed, although with low efficiency. MSC transfected with tumor mRNA or infected with a viral vector carrying the Hepatitis C virus NS3Ag gene induced cytokine release but were not killed by specific CTL, even following pretreatment with IFN-gamma. To investigate the mechanisms involved in MSC resistance to CTL-mediated lysis, we analyzed expression of human leukocyte antigen (HLA) class I-related antigen-processing machinery (APM) components and of immunosuppressive HLA-G molecules in MSC. The LMP7, LMP10, and ERp57 components were not expressed and the MB-1 and zeta molecules were downregulated in MSC either unmanipulated or pretreated with IFN-gamma. Surface HLA-G was constitutively expressed on MSC but was not involved in their protection from CTL-mediated lysis. MSC supernatants containing soluble HLA-G (sHLA-G) inhibited CTL-mediated lysis, whereas those lacking sHLA-G did not. The role of sHLA-G in such inhibition was unambiguously demonstrated by partial restoration of lysis following sHLA-G depletion from MSC supernatants. In conclusion, human MSC can process and present HLA class I-restricted viral or tumor antigens to specific CTL with a limited efficiency, likely because of some defects in APM components. However, they are protected from CTL-mediated lysis through a mechanism that is partly sHLA-G-dependent.


Asunto(s)
Antígenos de Neoplasias/inmunología , Antígenos Virales/inmunología , Antígenos de Histocompatibilidad Clase I/inmunología , Células Madre Mesenquimatosas/inmunología , Linfocitos T/inmunología , Presentación de Antígeno/efectos de los fármacos , Presentación de Antígeno/inmunología , Células Presentadoras de Antígenos/citología , Células Presentadoras de Antígenos/efectos de los fármacos , Células Presentadoras de Antígenos/inmunología , Línea Celular , Citotoxicidad Inmunológica/efectos de los fármacos , Granzimas/antagonistas & inhibidores , Antígenos HLA/inmunología , Antígenos HLA-G , Hepacivirus/efectos de los fármacos , Hepacivirus/inmunología , Humanos , Tolerancia Inmunológica/efectos de los fármacos , Inmunofenotipificación , Interferón gamma/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/enzimología , Péptidos/inmunología , Serpinas/metabolismo , Solubilidad/efectos de los fármacos , Linfocitos T/efectos de los fármacos , Linfocitos T Citotóxicos
18.
Clin Immunol ; 129(2): 286-94, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18753013

RESUMEN

Evidence suggests that T-cell response to myelin basic protein (MBP) plays an important role in multiple sclerosis (MS). However, the mechanism of generation for MBP immunogenic epitopes is unclear. A series of specific CD4(+) T-cell lines was obtained by stimulating peripheral blood mononuclear cells from MS patients with synthetic peptides spanning the entire MBP sequence. T-cell lines recognizing MBP(8-27), MBP(13-32), and MBP(23-42) peptides, whose sequences are identical for humans and rats, specifically proliferated and produced large amounts of interferon-gamma in response to autologous dendritic cells (DCs) loaded in vitro with apoptotic rat oligodendrocytes. Results suggest that MBP epitopes generated from enzymatic processing of apoptotic glial cells by DCs might be relevant to MS pathogenesis.


Asunto(s)
Apoptosis , Células Dendríticas/inmunología , Epítopos de Linfocito T , Esclerosis Múltiple/etiología , Proteína Básica de Mielina/inmunología , Oligodendroglía/inmunología , Adulto , Secuencia de Aminoácidos , Animales , Células Cultivadas , Citocinas/biosíntesis , Femenino , Antígenos HLA-DR/genética , Antígenos de Histocompatibilidad Clase II/metabolismo , Humanos , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Proteína Básica de Mielina/química , Ratas
19.
Psychiatry Res ; 225(3): 522-30, 2015 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-25534756

RESUMEN

The goal of the study was to estimate the prevalence of current and lifetime mental disorders in a consecutive sample (n=300) of detainees and prison inmates held in an Italian prison and compare it with the prevalence observed in a sample randomized from the community (n=300) within the same age interval (18-55 years) and sex proportion of prisoners, and with a similar socio-economic status. Psychiatric disorders were identified with the Mini International Neuropsychiatric Interview (MINI). Current psychiatric disorders were present in 58.7% of prisoners and 8.7% of the comparison group. Lifetime psychiatric disorders were present in 88.7% of prisoners and 15.7% of the comparison group. Current anxiety disorders and current stress-related disorders were related to prisoners serving their first-ever prison sentence. A variable fraction of prisoners with an ongoing psychopathology is not diagnosed or does not receive proper treatment. The provision of effective treatment to prisoners with psychiatric disorders might have potentially substantial public health benefits.


Asunto(s)
Trastornos Mentales/epidemiología , Trastornos Mentales/psicología , Prisioneros/psicología , Prisioneros/estadística & datos numéricos , Adolescente , Adulto , Trastorno de Personalidad Antisocial/epidemiología , Trastorno de Personalidad Antisocial/psicología , Trastornos de Ansiedad/epidemiología , Trastornos de Ansiedad/psicología , Estudios Transversales , Femenino , Necesidades y Demandas de Servicios de Salud/estadística & datos numéricos , Humanos , Italia , Masculino , Persona de Mediana Edad , Adulto Joven
20.
Soc Sci Med ; 93: 78-85, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23906124

RESUMEN

The Canadian government's recent cuts to healthcare coverage for refugee claimants has rekindled the debate in Canada about what medical services should be provided to individuals with precarious immigration status, and who should pay for these services. This article further explores this debate, focussing on the perceptions of healthcare workers in Montreal, a large multiethnic Canadian city. In April-June 2010, an online survey was conducted to assess how clinicians, administrators, and support staff in Montreal contend with the ethical and professional dilemmas raised by the issue of access to healthcare services for pregnant women and children who are partially or completely uninsured. Drawing on qualitative analysis of answers (n = 237) to three open-ended survey questions, we identify the discursive frameworks that our respondents mobilized when arguing for, or against, universal access to healthcare for uninsured patients. In doing so, we highlight how their positions relate to their self-evaluations of Canada's socioeconomic situation, as well as their ideological representations of, and sense of social connection to, precarious status immigrants. Interestingly, while abstract values lead some healthcare workers to perceive uninsured immigrants as "deserving" of universal access to healthcare, negative perceptions of these migrants, coupled with pragmatic considerations, pushed most workers to view the uninsured as "underserving" of free care. For a majority of our respondents, the right to healthcare of precarious status immigrants has become a "privilege", that as taxpayers, they are increasingly less willing to contribute to. We conclude by arguing for a reconsideration of access to healthcare as a right, and offer recommendations to move in this direction.


Asunto(s)
Actitud del Personal de Salud , Servicios de Salud del Niño , Emigración e Inmigración/legislación & jurisprudencia , Personal de Salud/psicología , Accesibilidad a los Servicios de Salud , Servicios de Salud Materna , Adulto , Canadá , Niño , Determinación de la Elegibilidad , Femenino , Personal de Salud/estadística & datos numéricos , Derechos Humanos , Humanos , Masculino , Persona de Mediana Edad , Embarazo , Investigación Cualitativa , Encuestas y Cuestionarios , Cobertura Universal del Seguro de Salud
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