RESUMEN
BACKGROUND: There is little evidence on KRAS mutational profiles in colorectal cancer (CRC) peritoneal metastases (PM). This study aims to determine the prevalence of specific KRAS mutations and their prognostic value in a homogeneous cohort of patients with isolated CRC PM treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. MATERIALS AND METHODS: Data were collected from 13 Italian centers, gathered in a collaborative group of the Italian Society of Surgical Oncology. KRAS mutation subtypes have been correlated with clinical and pathological characteristics and survival [overall survival (OS), local (peritoneal) disease-free survival (LDFS) and disease-free survival (DFS)]. RESULTS: KRAS mutations occurred in 172 patients (47.5%) out of the 362 analyzed. Two different prognostic groups of KRAS mutation subtypes were identified: KRASMUT1 (G12R, G13A, G13C, G13V, Q61H, K117N, A146V), median OS > 120 months and KRASMUT2 (G12A, G12C, G12D, G12S, G12V, G13D, A59E, A59V, A146T), OS: 31.2 months. KRASMUT2 mutations mainly occurred in the P-loop region (P < 0.001) with decreased guanosine triphosphate (GTP) hydrolysis activity (P < 0.001) and were more frequently related to size (P < 0.001) and polarity change (P < 0.001) of the substituted amino acid (AA). When KRASMUT1 and KRASMUT2 were combined with other known prognostic factors (peritoneal cancer index, completeness of cytoreduction score, grading, signet ring cell, N status) in multivariate analysis, KRASMUT1 showed a similar survival rate to KRASWT patients, whereas KRASMUT2 was independently associated with poorer prognosis (hazard ratios: OS 2.1, P < 0.001; DFS 1.9, P < 0.001; LDFS 2.5, P < 0.0001). CONCLUSIONS: In patients with CRC PM, different KRAS mutation subgroups can be determined according to specific codon substitution, with some mutations (KRASMUT1) that could have a similar prognosis to wild-type patients. These findings should be further investigated in larger series.
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Neoplasias Colorrectales , Mutación , Neoplasias Peritoneales , Proteínas Proto-Oncogénicas p21(ras) , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/mortalidad , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/genética , Masculino , Femenino , Proteínas Proto-Oncogénicas p21(ras)/genética , Persona de Mediana Edad , Pronóstico , Anciano , Adulto , Quimioterapia Intraperitoneal Hipertérmica , Supervivencia sin Enfermedad , Estudios Retrospectivos , Procedimientos Quirúrgicos de Citorreducción , Anciano de 80 o más AñosRESUMEN
α-catenin is a crucial protein at cell junctions that provides connection between the actin cytoskeleton and the cell membrane. At adherens junctions (AJs), α-catenin forms heterodimers with ß-catenin that are believed to resist force on F-actin. Outside AJs, α-catenin forms homodimers that regulates F-actin organization and directly connect the cell membrane to the actin cytoskeleton, but their mechanosensitive properties are inherently unknown. By using ultra-fast laser tweezers we found that a single α-ß-catenin heterodimer does not resist force but instead slips along F-actin in the direction of force. Conversely, the action of 5 to 10 α-ß-catenin heterodimers together with force applied toward F-actin pointed end engaged a molecular switch in α-catenin, which unfolded and strongly bound F-actin as a cooperative catch bond. Similarly, an α-catenin homodimer formed an asymmetric catch bond with F-actin triggered by protein unfolding under force. Our data suggest that α-catenin clustering together with intracellular tension engage a fluid-to-solid phase transition at the membrane-cytoskeleton interface.
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Actinas , beta Catenina , Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Uniones Adherentes/metabolismo , Cadherinas/metabolismo , alfa Catenina/metabolismo , beta Catenina/metabolismoRESUMEN
OBJECTIVES: Planned treatment interruption (PTI) of antiretroviral therapy (ART) in adults is associated with adverse outcomes. The PENTA 11 trial randomized HIV-infected children to continuous ART (CT) vs. CD4-driven PTIs. We report 5 years' follow-up after the end of main trial. METHODS: Post-trial, all children resumed ART. Clinical, immunological, virological and treatment data were collected annually. A sub-study investigated more detailed immunophenotype. CT and PTI arms were compared using intention-to-treat. Laboratory parameters were compared using linear regression, adjusting for baseline values; mixed models were used to include all data over time. RESULTS: In all, 101 children (51 CT, 50 PTI) contributed a median of 7.6 years, including 5.1 years of post-trial follow-up. Post-trial, there were no deaths, one pulmonary tuberculosis and no other CDC stage B/C events. At 5 years post-trial, 90% of children in the CT vs. 82% in the PTI arm had HIV RNA < 50 copies/mL (P = 0.26). A persistent increase in CD8 cells was observed in the PTI arm. The sub-study (54 children) suggested that both naïve and memory populations contributed to higher CD8 cells following PTI. Mean CD4/CD8 ratios at 5 years post-trial were 1.22 and 1.08 in CT and PTI arms, respectively [difference (CT - PTI) = -0.15; 95% CI: -0.34-0.05), P = 0.14]. The sub-study also suggested that during the trial and at early timepoints after the end of the trial, reduction in CD4 in the PTI arm was mainly from loss of CD4 memory cells. CONCLUSIONS: Children tolerated PTI with few long-term clinical, virological or immunological consequences.
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Infecciones por VIH , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Niño , Infecciones por VIH/tratamiento farmacológico , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Carga ViralRESUMEN
BACKGROUND: Colonic J pouch reconstruction has been found to be associated with a lower incidence of anastomotic leakage than straight anastomosis. However, studies on this topic are underpowered and retrospective. This randomized trial evaluated whether the incidence of anastomotic leakage was reduced after colonic J pouch reconstruction compared with straight colorectal anastomosis following anterior resection for rectal cancer. METHODS: This multicentre RCT included patients with rectal carcinoma who underwent low anterior resection followed by colorectal anastomosis. Patients were assigned randomly to receive a colonic J pouch or straight colorectal anastomosis. The main outcome measure was the occurrence of major anastomotic leakage. The incidence of global (major plus minor) anastomotic leakage and general complications were secondary outcomes. Risk factors for anastomotic leakage were identified by regression analysis. RESULTS: Of 457 patients enrolled, 379 were evaluable (colonic J pouch arm 190, straight colorectal arm 189). The incidence of major and global anastomotic leakage, and general complications was 14·2, 19·5 and 34·2 per cent respectively in the colonic J pouch group, and 12·2, 19·0 and 27·0 per cent in the straight colorectal anastomosis group. No statistically significant differences were observed between the two arms. In multivariable logistic regression analysis, male sex (odds ratio 1·79, 95 per cent c.i. 1·02 to 3·15; P = 0·042) and high ASA fitness grade (odds ratio 2·06, 1·15 to 3·71; P = 0·015) were independently associated with the occurrence of anastomotic leakage. CONCLUSION: Colonic J pouch reconstruction does not reduce the incidence of anastomotic leakage and postoperative complications compared with conventional straight colorectal anastomosis. Registration number NCT01110798 (http://www.clinicaltrials.gov).
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Colon/cirugía , Reservorios Cólicos , Procedimientos de Cirugía Plástica , Neoplasias del Recto/cirugía , Recto/cirugía , Grapado Quirúrgico , Anciano , Anastomosis Quirúrgica/efectos adversos , Anastomosis Quirúrgica/métodos , Fuga Anastomótica/epidemiología , Fuga Anastomótica/etiología , Reservorios Cólicos/efectos adversos , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Procedimientos de Cirugía Plástica/efectos adversos , Procedimientos de Cirugía Plástica/métodos , Grapado Quirúrgico/métodosRESUMEN
Background: Tumor immune microenvironment (TME) plays a key role in malignant pleural mesothelioma (MPM) pathogenesis and treatment outcome, supporting a role of immune checkpoint inhibitors as anticancer approach. This study retrospectively investigated TME and programmed death ligand 1 (PD-L1) expression in naïve MPM cases and their change under chemotherapy. Patients and methods: Diagnostic biopsies of MPM patients were collected from four Italian and one Slovenian cancer centers. Pathological assessment of necrosis, inflammation, grading, and mitosis was carried out. Ki-67, PD-L1 expression, and tumor infiltrating lymphocytes were detected by immunohistochemistry. When available, the same paired sample after chemotherapy was analyzed. Pathological features and clinical characteristics were correlated to overall survival. Results: TME and PD-L1 expression were assessed in 93 and 65 chemonaive MPM samples, respectively. Twenty-eight samples have not sufficient tumor tissue for PD-L1 expression. Sarcomatoid/biphasic samples were characterized by higher CD8+ T lymphocytes and PD-L1 expression on tumor cells, while epithelioid showed higher peritumoral CD4+ T and CD20+ B lymphocytes. Higher CD8+ T lymphocytes, CD68+ macrophages, and PD-L1 expression were associated with pathological features of aggressiveness (necrosis, grading, Ki-67). MPM cases characterized by higher CD8+ T-infiltrate showed lower response to chemotherapy and worse survival at univariate analysis. Patients stratification according to a combined score including CD8+ T lymphocytes, necrosis, mitosis, and proliferation index showed median overall survival of 11.3 months compared with 16.4 months in cases with high versus low combined score (P < 0.003). Subgroup exploratory analysis of 15 paired samples before and after chemotherapy showed a significant increase in cytotoxic T lymphocytes in MPM samples and PD-L1 expression in immune cells. Conclusions: TME enriched with cytotoxic T lymphocytes is associated with higher levels of macrophages and PD-L1 expression on tumor cells and with aggressive histopathological features, lower response to chemotherapy and shorter survival. The role of chemotherapy as a tumor immunogenicity inducer should be confirmed in a larger validation set.
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Antineoplásicos Inmunológicos/uso terapéutico , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias Pulmonares/patología , Mesotelioma/patología , Neoplasias Pleurales/patología , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Inmunológicos/farmacología , Antígeno B7-H1/inmunología , Biomarcadores de Tumor/inmunología , Biopsia , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/mortalidad , Linfocitos Infiltrantes de Tumor/inmunología , Macrófagos/inmunología , Masculino , Mesotelioma/tratamiento farmacológico , Mesotelioma/inmunología , Mesotelioma/mortalidad , Mesotelioma Maligno , Persona de Mediana Edad , Índice Mitótico , Pleura/citología , Pleura/inmunología , Pleura/patología , Neoplasias Pleurales/tratamiento farmacológico , Neoplasias Pleurales/inmunología , Neoplasias Pleurales/mortalidad , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Linfocitos T Citotóxicos/inmunología , Resultado del Tratamiento , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/genética , Microambiente Tumoral/inmunologíaRESUMEN
Bois noir (BN) is the most widespread disease of the grapevine yellows complex in the Euro-Mediterranean area. BN is caused by 'Candidatus Phytoplasma solani' (BNp), transmitted from herbaceous plants to grapevine by polyphagous insect vectors. In this study, genetic diversity among BNp strains and their prevalence and possible association with grapevine symptom severity were investigated in a Sangiovese clone organic vineyard in the Chianti Classico area (Tuscany). Field surveys over 2 years revealed a range of symptom severity on grapevine and an increase of BN incidence. A TaqMan allelic discrimination assay detected only tufB type b among BNp strains, suggesting the prevalence of the bindweed-related ecology. Nucleotide sequence analyses of vmp1 and stamp genes identified 12 vmp1 and 16 stamp sequence variants, showing an overall positive selection for such genes. The prevalent genotype was Vm43/St10, reported for the first time in this study and closely related to strains identified only in the French Eastern Pyrenees. BNp strains identified in the examined vineyard and mostly grouped in separate bindweed-related phylogenetic clusters showed statistically significant differences in their distribution in grapevines exhibiting distinct symptom severity. These results suggest the possible occurrence of a range of virulence within BNp strain populations in the Chianti Classico area.
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Phytoplasma/clasificación , Enfermedades de las Plantas/microbiología , Vitis/microbiología , ADN Bacteriano/genética , ADN Bacteriano/metabolismo , Italia , Tipificación Molecular , Filogenia , Phytoplasma/genéticaRESUMEN
BACKGROUND: Rectum-sparing approaches appear to be appropriate in rectal cancer patients with a major (mCR) or complete clinical response (cCR) after neoadjuvant therapy. The aim of the present study is to evaluate the effectiveness of rectum-sparing approaches at 2 years after the completion of neoadjuvant treatment. STUDY DESIGN: Patients with rectal adenocarcinoma eligible to receive neoadjuvant therapy will be prospectively enrolled. Patients will be restaged 7-8 weeks after the completion of neoadjuvant therapy and those with mCR (defined as absence of mass, small mucosal irregularity no more than 2 cm in diameter at endoscopy and no metastatic nodes at MRI) or cCR will be enrolled in the trial. Patients with mCR will undergo local excision, while patients with cCR will either undergo local excision or watch and wait policy. The main end point of the study is to determine the percentage of rectum preservation at 2 years in the enrolled patients. CONCLUSION: This protocol is the first prospective trial that investigates the role of both local excision and watch and wait approaches in patients treated with neoadjuvant therapy for rectal cancer. The trial is registered at clinicaltrials.gov (NCT02710812).
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Adenocarcinoma/terapia , Neoplasias del Recto/terapia , Espera Vigilante , Adenocarcinoma/cirugía , Quimioradioterapia Adyuvante , Quimioterapia Adyuvante , Humanos , Terapia Neoadyuvante , Tratamientos Conservadores del Órgano , Periodo Preoperatorio , Radioterapia Adyuvante , Neoplasias del Recto/cirugía , Recto , Proyectos de InvestigaciónRESUMEN
BACKGROUND: Semantic memory may be impaired in clinically recognized states of cognitive impairment. We investigated the relationship between semantic memory and depressive symptoms (DS) in patients with cognitive impairment. METHODS: 323 cognitively healthy controls and 848 patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia were included. Semantic knowledge for famous faces, world capitals, and word vocabulary was investigated. RESULTS: Compared to healthy controls, we found a statistically significant difference of semantic knowledge in the MCI groups and the AD group, respectively. Results of the SCD group were mixed. However, two of the three semantic memory measures (world capitals and word vocabulary) showed a significant association with DS. CONCLUSIONS: We found a difference in semantic memory performance in MCI and AD as well as an association with DS. Results suggest that the difference in semantic memory is due to a storage loss rather than to a retrieval problem.
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Enfermedad de Alzheimer/psicología , Disfunción Cognitiva/psicología , Depresión/psicología , Memoria , Semántica , Anciano , Austria , Estudios de Casos y Controles , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Estudios ProspectivosRESUMEN
BACKGROUND: Local excision for rectal cancer is expected to offer a better functional outcome than conventional surgery. The aim of the present study was to compare quality of life and bowel function in patients with rectal cancer who underwent either local excision or conventional surgery after chemoradiotherapy. METHODS: This was a retrospective multicentre study. Patients who underwent local excision were compared with those who had mesorectal excision. Quality of life and bowel function were investigated using validated questionnaires (European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-CR29 and Memorial Sloan-Kettering Cancer Center Bowel Function Instrument) at a median follow-up of 49 (range 13-95) months. Further analysis was undertaken of data from patients who underwent local excision alone compared with those requiring subsequent radical surgery. Statistical significance was set at P < 0·010. RESULTS: The mean constipation score was significantly better in the local excision group than in the mesorectal excision group (3·8 (95 per cent c.i. 0·3 to 7·2) versus 19·8 (12·1 to 27·4); P < 0·001). Compared with patients who underwent mesorectal excision, those who had local excision had less sensation of incomplete emptying (mean score 3·7 (3·4 to 4·0) versus 2·8 (2·5 to 3·1); P < 0·001) and second bowel movements within 15 min (mean score 3·6 (3·3 to 3·9) versus 3·0 (2·7 to 3·3); P = 0·006). Patients who underwent local excision alone scored better than those who had mesorectal excision, particularly for bowel function, who, in turn, scored better than patients requiring subsequent radical surgery following local excision. CONCLUSION: Patients who underwent local excision had a better quality of life and bowel function than those who underwent mesorectal excision.
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Quimioradioterapia Adyuvante , Terapia Neoadyuvante , Calidad de Vida , Neoplasias del Recto/terapia , Adenocarcinoma/terapia , Adulto , Anciano , Anciano de 80 o más Años , Estreñimiento/complicaciones , Defecación , Incontinencia Fecal/complicaciones , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
Bovine adrenal gland tumours are considered relatively common, although scarce data are available about their real incidence, pathological characterization, classification criteria and immunohistochemical profile. This study describes the morphological and immunophenotypical characteristics of 35 dairy cattle adrenal gland tumors from Northern Italy and compare them with human pathology. Macroscopical, histological, histochemical and immunohistochemical investigations were performed. Microscopically proliferative lesions were classified as focal hyperplasia (8/35), primary cortical tumors (15/35) , primary medullary tumors (12/35). The cortical tumors showed a highly heterogeneous spectrum of morphological aspects not matching the two major diagnostic categories of adenoma and carcinoma in either cattle or humans. The medullary tumors (7 neuroblastomas and 5 pheochromocytomas) showed morphological and immunophenotypical features largely overlapping with human counterparts. Although limited by the small number of neoplasms and the lack of evidence of metastases precluding a clear distinction between benign and malignant lesions, this study represents the first attempt to compare the bovine and the human pathology. The present data support the concept that adrenal tumors in cattle have distinctive features that deserve a species- specific classification.
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Neoplasias de las Glándulas Suprarrenales/veterinaria , Corteza Suprarrenal/patología , Neoplasias de las Glándulas Suprarrenales/epidemiología , Neoplasias de las Glándulas Suprarrenales/patología , Animales , Bovinos , Femenino , Humanos , Italia/epidemiologíaRESUMEN
BACKGROUND: Health-related quality of life (HRQOL) is an important issue in the context of dementia care. The purpose of this study was to investigate the association between HRQOL and depressive symptoms in patients with subjective cognitive decline (SCD) and subtypes of mild cognitive impairment (MCI) and Alzheimer´s disease (AD). METHODS: In this cross-sectional, observational study, a control group and four experimental groups (SCD, non-amnestic MCI, amnesticMCI, AD) were compared. Neuropsychological measurers (NTBV) and psychological questionnaires were used for data collection. RESULTS: The control group scored higher than patients with SCD, naMCI, aMCI, or AD for the Mental Health Component Score (MHCS) of the Short Form of the Health Survey (SF-36). The Physical Health Component Score (PHCS) of the SF-36 differed only between some groups. Furthermore, cognitive variables were more strongly associated with the physical aspects of HRQOL, whereas depressive symptoms were more strongly related with the mental aspects of HRQOL. CONCLUSIONS: HRQOL and depressive symptoms are closely related in patients with cognitive impairments. Therefore, it is of great importance to assess patients with subjective impairment carefully in terms of depressive symptoms.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Depresión , Calidad de Vida , Anciano , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/fisiopatología , Enfermedad de Alzheimer/psicología , Austria/epidemiología , Cognición , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/psicología , Depresión/diagnóstico , Depresión/psicología , Autoevaluación Diagnóstica , Femenino , Estado de Salud , Humanos , Entrevista Psicológica/métodos , Masculino , Pruebas de Estado Mental y DemenciaRESUMEN
Regulation of genomic activity occurs through the manipulation of DNA by competent mechanoenzymes. Force-clamp optical tweezers that allow the structural dynamics of the DNA molecule to be measured were used here to investigate the kinetics of mechanically-driven strand reannealing. When the force on the torsionally unconstrained λ-phage DNA is decreased stepwise from above to below the overstretching transition, reannealing occurs via discrete shortening steps separated by exponentially distributed time intervals. Kinetic analysis reveals a transition barrier 0.58 nm along the reaction coordinate and an average reannealing-step size of â¼750 bp, consistent with the average bp interval separating segments of more than 10 consecutive AT bases. In an AT-rich DNA construct, in which the distance between segments of more than 10 consecutive AT is reduced to â¼210 bps, the reannealing step reduces accordingly without changes in the position of the transition barrier. Thus, the transition barrier for reannealing is determined by the presence of segments of more than 10 consecutive AT bps independent of changes in sequence composition, while the length of the reannealing strand changes according to the distance between poly-AT segments at least 10 bps long.
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Secuencia Rica en At/genética , ADN Viral/metabolismo , Desnaturalización de Ácido Nucleico , Bacteriófago lambda , Secuencia de Bases , Fenómenos Biomecánicos , Cinética , Concentración OsmolarRESUMEN
BACKGROUND: Several pieces of evidence indicate that a complex relationship exists between constitutional telomere length (TL) and the risk of cutaneous melanoma. Although the general perception is that longer telomeres increase melanoma risk, some studies do not support this association. We hypothesize that discordant data are due to the characteristics of the studied populations. OBJECTIVES: To evaluate the association of TL with familial and sporadic melanoma. MATERIALS AND METHODS: TL was measured by multiplex quantitative polymerase chain reaction in leukocytes from 310 patients with melanoma according to familial/sporadic and single/multiple cancers and 216 age-matched controls. RESULTS: Patients with sporadic melanoma were found to have shorter telomeres compared with those with familial melanoma. In addition, shorter telomeres, while tending to reduce the risk of familial melanoma regardless of single or multiple tumours, nearly trebled the risk of single sporadic melanoma. CONCLUSIONS: This is the first time that TL has been correlated to opposite effects on melanoma risk according to the presence or absence of familial predisposition. Individual susceptibility to melanoma should be taken into account when assessing the role of TL as a risk factor.
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Melanoma/patología , Neoplasias Cutáneas/patología , Telómero/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Inhibidor p18 de las Quinasas Dependientes de la Ciclina/genética , Femenino , Predisposición Genética a la Enfermedad/genética , Humanos , Masculino , Melanoma/genética , Persona de Mediana Edad , Factores de Riesgo , Neoplasias Cutáneas/genética , Adulto JovenRESUMEN
Peripheral nerve function is significantly affected by ageing. During ageing process, multiple changes occur on tissue cells and extracellular matrix. The aim of this work was to study the ageing-associated changes of peripheral nerves in adult and old regularly slaughtered cattle compared with young calves, and correlate them to the features reported in humans and laboratory animals. Samples of axial dorsal metacarpal nerves from 44 cows were collected immediately after slaughtering. Each nerve was dissected and divided into two fragments: one used for morphological evaluation (n = 43) and the other one for biochemical analysis (n = 31). Axonal degeneration, demyelination, thickness of perineurium and endoneurium and increase of mast cells were the most important features detected. The mean amount of glycosaminoglycan quantitative content recorded in the samples increased with the age. Axonal degeneration, demyelination and thickness of endoneurium were positively and significantly correlated with biochemistry. The presence of changes affecting the different elements of the peripheral nerves, similar to that reported in humans and in laboratory species, the easy availability of the nerve tissue in this species, the considerable size of the samples and the life conditions more similar to humans than to laboratory animals, allows the authors to consider cattle as a potential good model for the comparative study of spontaneous ageing nerve lesions.
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Envejecimiento/fisiología , Bovinos/anatomía & histología , Nervios Periféricos/anatomía & histología , Nervios Periféricos/fisiología , Envejecimiento/patología , Análisis de Varianza , Animales , Axones/patología , Bovinos/fisiología , Enfermedades Desmielinizantes/patología , Enfermedades Desmielinizantes/veterinaria , Femenino , Glicosaminoglicanos/análisis , Mastocitos/patología , Metacarpo/inervación , Vaina de Mielina/patología , Vaina de Mielina/ultraestructuraRESUMEN
BACKGROUND: Deficits in facial emotion recognition (FER) have been shown to substantially impair several aspects in everyday life of affected individuals (e.g. social functioning). Presently, we aim at assessing differences in emotion recognition performance in three patient groups suffering from mild forms of cognitive impairment compared to healthy controls. METHODS: Performance on a concise emotion recognition test battery (VERT-K) of 68 patients with subjective cognitive decline (SCD), 44 non-amnestic (non-aMCI), and 25 amnestic patients (aMCI) with mild cognitive impairment (MCI) was compared with an age-equivalent sample of 138 healthy controls all of which were recruited within the framework of the Vienna Conversion to Dementia Study. Additionally, patients and controls underwent individual assessment using a comprehensive neuropsychological test battery examining attention, executive functioning, language, and memory (NTBV), the Beck Depression Inventory (BDI), and a measure of premorbid IQ (WST). RESULTS: Type of diagnosis showed a significant effect on emotion recognition performance, indicating progressively deteriorating results as severity of diagnosis increased. Between-groups effect sizes were substantial, showing non-trivial effects in all comparisons (Cohen's ds from -0.30 to -0.83) except for SCD versus controls. Moreover, emotion recognition performance was higher in women and positively associated with premorbid IQ. CONCLUSIONS: Our findings indicate substantial effects of progressive neurological damage on emotion recognition in patients. Importantly, emotion recognition deficits were observable in non-amnestic patients as well, thus conceivably suggesting associations between decreased recognition performance and global cognitive decline. Premorbid IQ appears to act as protective factor yielding lesser deficits in patients showing higher IQs.
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Amnesia/psicología , Disfunción Cognitiva/diagnóstico , Emociones , Expresión Facial , Reconocimiento Facial , Prosopagnosia/etiología , Anciano , Amnesia/etiología , Austria , Estudios de Casos y Controles , Cognición , Disfunción Cognitiva/fisiopatología , Demencia/complicaciones , Función Ejecutiva , Femenino , Humanos , Memoria , Persona de Mediana Edad , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , Reconocimiento en Psicología , Índice de Severidad de la EnfermedadRESUMEN
AIM: The study evaluated, in a proof of concept, the usefulness of a prosthesis (plug) in addition to video assisted ablation of pilonidal sinus (VAAPS) for treatment of recurrent pilonidal sinus. METHOD: This is a case series of recurrent complex pilonidal sinus treated by VAAPS plus plug positioning. RESULTS: Four patients were analysed. All were successfully treated by this new approach. No difficulties in inserting the plug were identified. Complete healing was achieved in all cases. No infection or recurrence was reported during a limited follow-up. CONCLUSION: This new technique allows a minimally invasive scarless approach to recurrent pilonidal sinus.
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Técnicas de Ablación/métodos , Seno Pilonidal/cirugía , Cirugía Asistida por Video/métodos , Técnicas de Ablación/instrumentación , Adulto , Estudios de Seguimiento , Humanos , Masculino , Estudios Prospectivos , Recurrencia , Tampones Quirúrgicos , Resultado del Tratamiento , Cirugía Asistida por Video/instrumentación , Adulto JovenRESUMEN
Eight polymorphic microsatellite loci were developed for the brook lamprey Lampetra planeri through 454 sequencing and their usefulness was tested in 45 individuals of both L. planeri and the river lamprey Lampetra fluviatilis. The number of alleles per loci ranged between two and five; the Italian and Irish populations had a mean expected heterozygosity of 0·388 and 0·424 and a mean observed heterozygosity of 0·418 and 0·411, respectively.
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Genética de Población , Lampreas/genética , Repeticiones de Microsatélite , Animales , Heterocigoto , Irlanda , Italia , Análisis de Secuencia de ADNRESUMEN
The overstretching transition in torsionally unconstrained DNA is studied by means of atomistic molecular dynamics simulations. The free-energy profile as a function of the length of the molecule is determined through the umbrella sampling technique providing both a thermodynamic and a structural characterization of the transition pathway. The zero-force free-energy profile is monotonic but, in accordance with recent experimental evidence, becomes two-state at high forces. A number of experimental results are satisfactorily predicted: (i) the entropic and enthalpic contributions to the free-energy difference between the basic (B) state and the extended (S) state; (ii) the longitudinal extension of the transition state and (iii) the enthalpic contribution to the transition barrier. A structural explanation of the experimental finding that overstretching is a cooperative reaction characterized by elementary units of approximately 22 base pairs is found in the average distance between adenine/thymine-rich regions along the molecule. The overstretched DNA adopts a highly dynamical and structurally disordered double-stranded conformation which is characterized by residual base pairing, formation of non-native intra-strand hydrogen bonds and effective hydrophobic screening of apolar regions.
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Modelos Químicos , Modelos Moleculares , Simulación de Dinámica Molecular , Módulo de Elasticidad , Conformación de Ácido Nucleico , Desnaturalización de Ácido Nucleico , Transición de Fase , Estrés Mecánico , Resistencia a la TracciónRESUMEN
INTRODUCTION: Although intragastric balloons have been in use for several years to achieve weight reduction in obese patients, acute renal failure after gastric balloon positioning is reported in few studies CASE REPORT: A 32-year-old white infertile woman undergone Bioenterics Intragastric Balloon (BIB) positioning in an attempt to weight loss and improve her fertility status. After only six days of persisting vomiting acute renal failure was found. A complete recovery of renal function was obtained after 14 days. CONCLUSION: Acute renal failure was due to persistent vomiting leading to dehydration. Physicians involved in BIB patients management must consider the possibility of major complications in all hyperemetic subjects. BIB removal, with a concomitant intravenous fluid replacement and minerals or vitamins supplementation has to be taken into account as an emergency procedure.