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OBJECTIVE: Patients with nonmelanoma skin cancer (NMSC)-ie, basal cell carcinoma (BCC) or squamous cell carcinoma (SCC)-have an increased risk of developing a second skin cancer. The aim of this study was to describe the frequency, incidence per 1000 person-years, and predictors of a second skin cancer in a cohort of patients with NMSC treated with Mohs micrographic surgery (MMS). MATERIAL AND METHODS: Prospective study of a national cohort of patients with NMSC who underwent MMS at 22 Spanish hospitals between July 2013 and February 2020; case data were recorded in the REGESMOHS registry. The study variables included demographic characteristics, frequency and incidence per 1000 person-years of second skin cancers diagnosed during the study period, and risk factors identified using mixed-effects logistic regression. RESULTS: We analyzed data for 4768 patients who underwent MMS; 4397 (92%) had BCC and 371 (8%) had SCC. Mean follow-up was 2.4 years. Overall, 1201 patients (25%) developed a second skin cancer during follow-up; 1013 of the tumors were BCCs (21%), 154 were SCCs (3%), and 20 were melanomas (0.4%). The incidence was 107 per 1000 person-years (95% CI, 101-113) for any cancer, 90 per 1000 person-years (95% CI, 85-96) for BCC, 14 (95% CI, 12-16) per 1000 person-years for SCC, and 2 (95% CI, 1-3) per 1000 person-years for melanoma. More men than women developed a subsequent skin cancer (738 [61%] vs 463 [39%]). The main risk factors were a history of multiple tumors before diagnosis (relative risk [RR], 4.6; 95% CI, 2.9-7.1), immunosuppression (RR, 2.1; 95% CI, 1.4-3.1), and male sex (RR, 1.6; 95% CI, 1.4-1.9). CONCLUSION: Patients have an increased risk of developing a second tumor after MMS treatment of NMSC. Risk factors are a history of multiple tumors at diagnosis, immunosuppression, and male sex.
Assuntos
Carcinoma Basocelular , Carcinoma de Células Escamosas , Melanoma , Neoplasia de Células Basais , Neoplasias Cutâneas , Carcinoma Basocelular/epidemiologia , Carcinoma Basocelular/patologia , Carcinoma Basocelular/cirurgia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Estudos de Coortes , Feminino , Humanos , Masculino , Melanoma/complicações , Cirurgia de Mohs , Estudos Prospectivos , Fatores de Risco , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/cirurgiaRESUMO
BACKGROUND: The elderly population is increasing and more patients in this group undergo Mohs micrographic surgery (MMS). The few publications investigating MMS in elderly people conclude that it is a safe procedure; however, these are single-centre studies without a comparison group. OBJECTIVE: To compare the characteristics of patients, tumours, MMS and 1-year follow-up in patients younger than 80 years, with patients older than 80 years at the time of surgery. METHODS: Data was analysed from REGESMOHS, a prospective cohort study of patients treated with MMS. The participating centres were 19 Spanish hospitals where at least one MMS is performed per week. Data on characteristics of the patient, tumour and surgery were recorded. Follow-up data were collected from two visits; the first within 1 month postsurgery and the second within the first year. RESULTS: From July 2013 to October 2016, 2575 patients that underwent MMS were included in the registry. Of them, 1942 (75.4%) were aged <80 years and 633 (24.6%) were ≥80 years old. In the elderly, the tumour size was significantly higher with a higher proportion of squamous cell carcinoma. Regarding surgery, elderly more commonly had tumours with deeper invasion and required a higher number of Mohs surgery stages, leaving larger defects and requiring more time in the operating room. Despite this, the incidence of postoperative complications was the same in both groups (7%) and there were no significant differences in proportion of relapses in the first-year follow-up. CONCLUSION: The risk of short-term complications and relapses were similar in elderly and younger groups. MMS is a safe procedure in the elderly.
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Cirurgia de Mohs , Recidiva Local de Neoplasia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Cirurgia de Mohs/efeitos adversos , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Sistema de Registros , Carga TumoralRESUMO
INTRODUCTION: The Spanish Mohs Surgery Registry is used to collect data on the use and outcomes of Mohs micrographic surgery (MMS) in Spain. The aim of this study was to describe perioperative and intraoperative data recorded for MMS procedures performed between July 2013 (when the registry started) and January 2016. MATERIAL AND METHODS: Prospective cohort study of data from 18 hospitals. The data collected included type of anesthesia, surgical technique, hospital admission, number of Mohs stages, management of preoperative risk factors, additional treatments, previous treatments, type of tumor, operating time, and complications. RESULTS: Data were available for 1796 operations. The most common tumor treated by MMS was basal cell carcinoma (85.96%), followed by squamous cell carcinoma (6.18%), lentigo maligna (2.81%), and dermatofibrosarcoma protuberans (1.97%). Primary tumors accounted for 66.9% of all tumors operated on; 19.2% of tumors were recurrent and 13.9% were persistent. The most common previous treatment was surgical. MMS was mostly performed under local anesthesia (86.7% of cases) and as an outpatient procedure (71.8%). The frozen section technique was used in 89.5% of cases. One stage was needed to achieve tumor-free margins in 56.45% of patients; 2 stages were required in 32.1% of patients, 3 in 7.1%%, 4 in 2.7%, and 5 or more in 1.8%. The defect was reconstructed by the dermatologist in 98% of patients and the most common technique was flap closure (47.2%). Intraoperative complications were recorded for just 1.62% of patients and the median (interquartile range) duration of surgery was 75 (60-100) minutes. CONCLUSION: The characteristics of the patients and tumors treated by MMS are similar to those reported for similar studies in other geographic areas. Lentigo maligna and dermatofibrosarcoma protuberans accounted for a higher proportion of cases in our series, and repair of the surgical defect by a dermatologist was also more common. Operating times in MMS are not much longer than those reported for other procedures and the rate of intraoperative complications is very low.
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Cirurgia de Mohs/estatística & dados numéricos , Neoplasias Cutâneas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Anestesia/métodos , Anestesia/estatística & dados numéricos , Terapia Combinada , Feminino , Humanos , Complicações Intraoperatórias/epidemiologia , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Cirurgia de Mohs/métodos , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Procedimentos de Cirurgia Plástica/estatística & dados numéricos , Sistema de Registros , Gestão de Riscos , Neoplasias Cutâneas/terapia , Espanha , Retalhos CirúrgicosRESUMO
INTRODUCTION: The Spanish registry of Mohs micrographic surgery started collecting data in July 2013. The aim of the registry is to report on the use of this technique in Spain and the outcomes achieved. In the present article, we describe the characteristics of patients and the tumors treated. MATERIAL AND METHODS: This is a prospective cohort study of patients treated with Mohs micrographic surgery. The participating centers are hospitals where at least one intervention of this type is performed each week. All patients considered for Mohs micrographic surgery in participating centers are included in the registry except those who have been declared legally incompetent. RESULTS: Between July 2013 and October 2014, data from 655 patients were included in the registry. The most common tumor involved was basal cell carcinoma, and the most common histological subtype was infiltrative basal cell carcinoma. Most of the tumors treated were located on the face or scalp, and the most common site was the nose. Almost 40% of the tumors treated were recurrent or persistent, and preoperative tumor size was similar to that reported in other European studies and in Australia. In total, 45.5% of patients had received previous surgical treatment. CONCLUSION: The findings are similar to those reported in other studies, and the data collected are useful for assessing whether the results of studies carried out elsewhere are applicable in Spain.
Assuntos
Carcinoma Basocelular/cirurgia , Cirurgia de Mohs/estatística & dados numéricos , Sistema de Registros , Neoplasias Cutâneas/cirurgia , Carcinoma/epidemiologia , Carcinoma/cirurgia , Carcinoma Basocelular/epidemiologia , Terapia Combinada , Bases de Dados Factuais , Dermatofibrossarcoma/epidemiologia , Dermatofibrossarcoma/cirurgia , Neoplasias Faciais/epidemiologia , Neoplasias Faciais/cirurgia , Humanos , Hospedeiro Imunocomprometido , Melanoma/epidemiologia , Melanoma/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Estudos Prospectivos , Fatores de Risco , Terapia de Salvação , Neoplasias Cutâneas/epidemiologia , Espanha/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: Dematiaceous, or dark-pigmented, fungi are known to cause infections such as phaeohyphomycosis, chromoblastomycosis, and mycetoma. These fungi are becoming increasingly important opportunistic pathogens in solid organ transplant recipients (SOTR). We present a retrospective chart review of 27 SOTR who developed phaeohyphomycosis infections post transplant from 1988 to 2009. METHODS: Cases were reviewed for fungal species isolated, date and source of culture, immunosuppressive and fungal therapy used, and outcome. The majority of isolates obtained were from the skin and soft tissue, with 3 pulmonary and brain abscesses. RESULTS: The time from transplantation to onset of infection ranged from 2 months to 11 years. The species isolated were Exophiala (11), Ochroconis (3), Alternaria (2), Phoma (2), Wangiella (1), Cladosporium (1), Aureobasidium (1), Chaetomium (1), Coniothyrium (1), and non-sporulating fungi (2). An additional 4 patients had infections confirmed by pathology, but no cultures were done. Most of the affected skin lesions were surgically debrided and treated with itraconazole; 2 patients were treated with voriconazole and 2 with amphotericin D. Death from fungal disease occurred only in patients with pulmonary and brain abscesses. CONCLUSIONS: As the number of SOTR increases, so does the incidence of fungal infections in that population. Surgery, along with antifungal therapy and a reduction in immunosuppression, are the cornerstones of treatment.
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Abscesso Encefálico/microbiologia , Terapia de Imunossupressão/efeitos adversos , Abscesso Pulmonar/microbiologia , Infecções Oportunistas/microbiologia , Feoifomicose/microbiologia , Feoifomicose/terapia , Adulto , Idoso , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Abscesso Encefálico/tratamento farmacológico , Desbridamento , Feminino , Humanos , Itraconazol/uso terapêutico , Abscesso Pulmonar/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/terapia , Transplante de Órgãos/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Voriconazol/uso terapêutico , Adulto JovemRESUMO
The conformational and ionization properties of linear poly(ethylenimine) are studied by combining the site binding model (SB) with the rotational isomeric state (RIS) model, developed by Flory to calculate the conformational properties of neutral linear molecules. The resulting approach (the SBRIS model) is used to rationalise the experimental poly(ethylenimine) titration curves. By fitting the experimental macroconstants, conformational and binding parameters are obtained. The obtained values are consistent with previous binding and structural information. The emergence of triplet interaction between protonated sites is explained as a natural consequence of the coupling between binding and conformational equilibria. When only nearest neighbour interactions are considered, transfer matrix techniques are used in the calculations. In order to account for excluded volume and long-range electrostatic interactions, Monte Carlo simulations are performed. The results indicate that at high ionic strengths, long-range interactions have a very limited impact on the titration curves. However, for long chains, they have a significant influence on the radius of gyration.
RESUMO
BACKGROUND: Mohs micrographic surgery (MMS) is a specialized procedure usually limited to specific indications (e.g. high-risk basal cell carcinomas [BCCs]). OBJECTIVE: To determine the recurrence rate of MMS for BCC at a tertiary referral centre in Barcelona, Spain. METHODS: Review of medical records of patients undergoing 534 consecutive MMS interventions for confirmed BCCs. The main outcome measure was biopsy-proven recurrence of BCC at the same anatomical location after MMS. RESULTS: A total of 489 patients underwent MMS for 534 BCCs from April 1999 to December 2011. The patients' mean age was 66 years. The most frequent location was the nasal/perinasal region (38.4%, n = 205). The surgical interventions of 47.9% (n = 256) were for primary BCCs and 52.1% (n = 278) procedures were for recurrent or residual BCCs. The mean follow-up was 30.5 months (range 1145 months). Thirty-two recurrences were identified in total. The raw recurrence rate following MMS for primary BCCs was 1.2% (3/256) compared to 10.4% (32/278) for recurrent BCC. On multivariate analysis (Cox proportional hazard model) only prior treatment (P = 0.018, hazard ratio [HR] 4.68 with 95% confidence intervals [CI] 1.3016.79), multiple prior treatments (P = 0.013, HR 2.72 [95%CI 1.245.96]), and healing by secondary intention (P = 0.041, HR 2.88 [95%CI 1.047.97]) were independent prognostic factors of recurrence after MMS. LIMITATIONS: The limitations of our study are those of a retrospective study. CONCLUSION: Mohs micrographic surgery for primary high-risk BCCs has a high success rate but the cumulative probability of recurrence increases significantly when tumours with recurrences are referred for MMS.
Assuntos
Carcinoma Basocelular/cirurgia , Cirurgia de Mohs/métodos , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Cutâneas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Basocelular/mortalidade , Carcinoma Basocelular/patologia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Estudos Retrospectivos , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Espanha/epidemiologia , Taxa de Sobrevida/tendências , Resultado do Tratamento , Adulto JovemRESUMO
In January 2012, vismodegib (Erivedge, manufactured by Genentech) became the first selective inhibitor of the Hedgehog signaling pathway to be approved by the US Food and Drug Administration for the treatment of locally advanced and metastatic basal cell carcinoma. The drug selectively binds to Smoothened, a 7-helix transmembrane receptor, thereby inhibiting activation of transcription factors of the glioma-associated oncogene family and suppressing tumor proliferation and growth. Studies published to date have assessed the efficacy of vismodegib according to clinical and radiologic outcomes but little information is available on the molecular mechanisms underpinning the proven clinical efficacy of the drug. This review will cover recent data on the Hedgehog signaling pathway and data from clinical trials with vismodegib in the treatment of basal cell carcinoma, and will consider its use in other types of tumor.
Assuntos
Anilidas/uso terapêutico , Carcinoma Basocelular/tratamento farmacológico , Piridinas/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Anilidas/farmacologia , Ensaios Clínicos como Assunto , Proteínas Hedgehog/efeitos dos fármacos , Proteínas Hedgehog/fisiologia , Humanos , Piridinas/farmacologia , Transdução de Sinais/efeitos dos fármacosRESUMO
Bone wax is an inert, malleable material used as a hemostatic agent in treating surgical defects. Healing by secondary intention is an appropriate approach for certain situations in dermatologic surgery. When surgical wounds are deep enough for such tissues as bone or cartilage to be exposed, dressings may adhere to granulation tissue, making removal and subsequent wound care difficult and painful. In such cases bone wax can be molded around deep tissues to create an ideal occlusive, hemostatic microenvironment that facilitates second-intention wound healing.
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Procedimentos Cirúrgicos Dermatológicos , Hemostáticos , Palmitatos , Ceras , Cicatrização , HumanosRESUMO
Wegener's granulomatosis is an autoimmune disease where autoantibodies target human autoantigen PR3, a serine protease locates on the neutrophil membrane. This disease affects blood small vessels and could be deadly. The origin of these autoantibodies is unknown, but infections have been implicated with autoimmune disease. In this study, we explored potential molecular mimicry between human PR3 and homologous pathogens through in silico analysis. Thirteen serine proteases from human pathogens (Klebsiella pneumoniae, Acinetobacter baumannii, Salmonella sp., Streptococcus suis, Vibrio parahaemolyticus, Bacteroides fragilis, Enterobacter ludwigii, Vibrio alginolyticus, Staphylococcus haemolyticus, Enterobacter cloacae, Escherichia coli and Pseudomonas aeruginosa) shared structural homology and amino acid sequence identity with human PR3. Epitope prediction found an only conserved epitope IVGG, located between residues 59-74. However, multiple alignments showed conserved regions that could be involved in cross-reactivity between human and pathogens serine proteases (90-98, 101-108, 162-169, 267 and 262 residues positions). In conclusion, this is the first report providing in silico evidence about the existence of molecular mimicry between human and pathogens serine proteases, that could explain the origins of autoantibodies found in patients suffering from Wegener's granulomatosis.
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Calciofilaxia/diagnóstico , Transplante de Rim , Transplante de Fígado , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Rapid and safe diagnosis of bacteremia is a continuous challenge in clinical microbiology. In this work, we evaluated a multiple PCR system that identifies 23 common pathogens as well as the production of 3 resistance mechanisms potentially present in them. METHODS: During a period of 2 months the positive blood cultures were processed in the usual way for identification and determination of their antimicrobial sensitivity. At the same time were incorporated into FilmArray panels. RESULTS: The agreement between two methods for bacterial identification was 100%. The time of obtaining the results by the molecular technique did not exceed 1 hour 15 minutes and in 7 cases of the 21 studied (33%) a modification of the empirical therapy was carried out. CONCLUSIONS: The implementation of rapid techniques such as multiple PCR offers a fast, reliable and easy to perform diagnosis in the therapeutic management of sepsis.
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Bacteriemia/diagnóstico , Reação em Cadeia da Polimerase/métodos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Farmacorresistência Bacteriana/genética , Humanos , Testes de Sensibilidade Microbiana , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Regesmohs registry is a nationwide registry including patients evaluated for Mohs surgery in 17 Spanish centres since July 2013. Given that Mohs surgery is the therapy with best results for high risk basal cell carcinoma (BCC) and other skin tumours, we wanted to describe the reasons that lead to some patients being excluded from this therapy and the alternative treatments that they received. These data may be useful to avoid excluding patients for Mohs surgery use, to estimate the healthcare demand of these patients and the demand for Hedgehog inhibitors therapy in this group. OBJECTIVE: To describe patients excluded for Mohs surgery after pre-surgical assessment, and the treatments that they received. METHODS: Regesmohs includes all consecutive patients assessed for Mohs surgery in the participating centres, collecting data on patient characteristics, intervention, and short and long-term results. Patients excluded for Mohs surgery after pre-surgical evaluation were described. RESULTS: 3011 patients were included in Regesmohs from July 2013 to October 2016. In 85, Mohs surgery was not performed as they were considered inadequate candidates. 67 had BCC. Reasons for exclusion were: medical contraindication (27.1%, n=23) low-risk tumour in (18.8%, n=16) and giant tumour and bone invasion (15.3%, n=13). Only 1 patient (1.2%) showed lymph node involvement and no patients had visceral metastases. Of the 85 excluded patients, 29 (34.1%) were treated with conventional surgery, 24 (28.3%) with radiotherapy, 4 (4.7%) with inhibitors of the Hedgehog pathway (only indicated for BCC), and 2 (2.4%) received palliative care. We had no follow-up data on 14 patients (16.5%). CONCLUSION: Medical comorbidities were the most common reason for withholding Mohs surgery. Withholding therapy on the basis of distant extension is uncommon. Most excluded patients received simpler therapies: conventional surgery or radiotherapy, with hedgehog inhibitors being a new option.
Assuntos
Cirurgia de Mohs , Seleção de Pacientes , Neoplasias Cutâneas/cirurgia , Suspensão de Tratamento , Idoso , Idoso de 80 Anos ou mais , Carcinoma Basocelular/tratamento farmacológico , Carcinoma Basocelular/radioterapia , Carcinoma Basocelular/cirurgia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Comorbidade , Contraindicações de Procedimentos , Feminino , Proteínas Hedgehog/antagonistas & inibidores , Humanos , Masculino , Proteínas de Neoplasias/antagonistas & inibidores , Cuidados Paliativos , Estudos Prospectivos , Sistema de Registros , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/radioterapia , EspanhaRESUMO
Here, we investigated for the first time the frequency and number of circulating tumor plasma cells (CTPC) in peripheral blood (PB) of newly diagnosed patients with localized and systemic plasma cell neoplasms (PCN) using next-generation flow cytometry (NGF) and correlated our findings with the distinct diagnostic and prognostic categories of the disease. Overall, 508 samples from 264 newly diagnosed PCN patients, were studied. CTPC were detected in PB of all active multiple myeloma (MM; 100%), and smoldering MM (SMM) patients (100%), and in more than half (59%) monoclonal gammopathy of undetermined significance (MGUS) cases (p <0.0001); in contrast, CTPC were present in a small fraction of solitary plasmacytoma patients (18%). Higher numbers of CTPC in PB were associated with higher levels of BM infiltration and more adverse prognostic features, together with shorter time to progression from MGUS to MM (p <0.0001) and a shorter survival in MM patients with active disease requiring treatment (p ≤ 0.03). In summary, the presence of CTPC in PB as assessed by NGF at diagnosis, emerges as a hallmark of disseminated PCN, higher numbers of PB CTPC being strongly associated with a malignant disease behavior and a poorer outcome of both MGUS and MM.
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Citometria de Fluxo , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Mieloma Múltiplo/diagnóstico , Células Neoplásicas Circulantes/metabolismo , Plasmócitos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Diagnóstico Diferencial , Feminino , Citometria de Fluxo/métodos , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/metabolismo , Mieloma Múltiplo/metabolismo , Estadiamento de Neoplasias , Células Neoplásicas Circulantes/patologia , Plasmócitos/patologia , Prognóstico , Sensibilidade e EspecificidadeRESUMO
Targeting of the minus-end directed microtubule motor cytoplasmic dynein to a wide array of intracellular substrates appears to be mediated by an accessory factor known as dynactin [1-4]. Dynactin is a multi-subunit complex that contains a short actin-related protein 1 (Arp 1) filament with capZ at the barbed end and p62 at the pointed end [5]. The location of the p62 subunit and the proposed role for dynactin as a multifunctional targeting complex raise the possibility of a dual role for p62 in dynein targeting and in Arp1 pointed-end capping. In order to gain further insight into the role of p62 in dynactin function, we have cloned cDNAs that encode two full-length isoforms of the protein from rat brain. We found that p62 is homologous to the nuclear migration protein Ropy-2 from Neurospora [6]; both proteins contain a zinc-binding motif that resembles the LIM domain of several other cytoskeletal proteins [7]. Overexpression of p62 in cultured mammalian cells revealed colocalization with cortical actin, stress fibers, and focal adhesion sites, sites of potential interaction between microtubules and the cell cortex [8,9]. The p62 protein also colocalized with polymers of overexpressed wild-type or barbed-end-mutant Arp1, but not with a pointed-end mutant. Deletion of the LIM domain abolished targeting of p62 to focal-adhesion sites but did not interfere with binding of p62 to actin or Arp1. These data implicate p62 in Arp1 pointed-end binding and suggest additional roles in linking dynein and dynactin to the cortical cytoskeleton.
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Actinas/metabolismo , Citoesqueleto/metabolismo , Proteínas dos Microfilamentos , Proteínas Associadas aos Microtúbulos/química , Proteínas Associadas aos Microtúbulos/metabolismo , Domínios de Homologia de src , Sequência de Aminoácidos , Animais , Sítios de Ligação , Células COS , Clonagem Molecular , DNA Complementar/genética , Complexo Dinactina , Proteínas Associadas aos Microtúbulos/genética , Modelos Moleculares , Mutação , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Estrutura Quaternária de Proteína , Ratos , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Deleção de Sequência , Dedos de Zinco/genéticaRESUMO
The objective of this study was to evaluate the activity of ertapenem and other antimicrobials against extended-spectrum beta-lactamase (ESBL)-producing enterobacteria isolated from patients' urine samples at 4 community healthcare centers in the Madrid (Spain) area and to determine the prevalence of ESBL-producing enterobacteria in community-acquired urinary tract infections. The antibiotic susceptibility results were compared by patient age and sex. A total of 293 strains were studied. The minimum inhibitory concentration (MIC) for each antibiotic was determined using the agar dilution method. The tested carbapenems were the antibiotics with the greatest activity (ertapenem MIC(90)=0.06 mg/l; imipenem MIC(90)=0.5 mg/l), with no intermediate or resistant strains being observed. High rates of resistance to ciprofloxacin (80.9%) and cotrimoxazole were observed (62.1%). The global prevalence of ESBL-producing enterobacteria was 3.6% (293/8,139). Prevalence according to areas was 5.3% in Getafe, 3.45% in Arguelles, 3.02% in Alcala de Henares and 3.56% in Mostoles. The global prevalence of ESBL-producing Escherichia coli was 4.15% (279/6,721). The analysis of resistance according to patient sex (males versus females) showed no significant differences. The analysis of resistance according to patient age (<50 years versus > or = 50 years) showed statistically significant differences (more resistance among subjects > or = 50 years old) for cotrimoxazole (OR=0.43, 95%CI: 0.20-0.93, p=0.018) and ciprofloxacin (OR=0.32, 95%CI: 0.14-0.74, p=0.0027). In view of the good activity shown by ertapenem, and the continuous increase in the prevalence of ESBL strains, this antibiotic and some of the others could be a good choice for the treatment of community-acquired urinary tract infections produced by such bacteria in Spain.
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Antibacterianos/farmacologia , Bacteriúria/microbiologia , Escherichia coli/efeitos dos fármacos , Urina/microbiologia , Resistência beta-Lactâmica , beta-Lactamas/farmacologia , Adulto , Bacteriúria/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Farmacorresistência Bacteriana Múltipla , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/enzimologia , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/microbiologia , Ertapenem , Escherichia coli/enzimologia , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/epidemiologia , Proteínas de Escherichia coli/análise , Feminino , Humanos , Masculino , Proteínas de Membrana/análise , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Ambulatório Hospitalar/estatística & dados numéricos , Espanha/epidemiologia , beta-Lactamases/análiseRESUMO
Resumen La presente investigación tuvo como objetivo identificar y describir los niveles de desarrollo de la noción de "mitad" en un grupo de niños de dos comunidades indígenas pertenecientes al pueblo shipibo-konibo de la región Ucayali, en la Amazonía del Perú. Se trabajó con 14 estudiantes de edades entre 7 y 13 años, seis de ellos pertenecientes a la comunidad de Bethel y ocho a la comunidad de Bena Jema. Todos fueron evaluados utilizando el método clínico-crítico de Jean Piaget. Los estudiantes de la comunidad de Bethel fueron evaluados con una tarea centrada en cantidades discretas y los de la comunidad de Bena Jema, con la misma tarea y con otra centrada en cantidades continuas. Los desempeños de los participantes evidenciaron cuatro niveles de desarrollo en cada una de las tareas. Sus respuestas fueron consistentes con otras investigaciones que evaluaron la misma noción en contextos occidentales. Los resultados apoyan la universalidad en la construcción de la noción de "mitad", pero evidencian un retraso en la adquisición de los niveles por parte de los niños evaluados, si se toma como referencia los currículos nacionales. Se discuten los hallazgos resaltando la universalidad de las estructuras lógico-matemáticas y la necesidad de repensar el momento y la forma en que la noción de "mitad" aparece en el currículo.
Abstract This research aims to identify and describe developmental levels of the notion of "half" in a group of children from two Shipibo-Konibo native communities of the Ucayali region, in the Peruvian Amazon rainforest. Fourteen students aged between 7 and 16 participated, six from Bethel community and eight from Bena Jema community. The community of Bethel is located approximately 6 hours by river from the city of Pucallpa, while Bena Jema is located within Pucallpa's boundaries, in the Yarinacocha district. All participants were assessed using Jean Piaget's clinical-critical method, with two tasks. In the first task, focusing on discrete quantities: different sets of cards with the picture of a fish were presented sequentially, some with an even number of units and some with an odd number. Participants were asked to choose and present back half of each set. In the second task, focusing on continuous quantities: participants were asked to choose and present half of a single raw spaghetti, which they needed to break with their hands. If the resulting pieces were unequal, they were asked to break them again and redistribute the results. Students from Bena Jema community were assessed with both tasks, while students from Bethel community were assessed only with the discrete quantities task. The results showed four developmental levels in the discrete quantities task. In the first level, participants took any one of two parts of the set to be "half", without checking if they were equal or whether putting them back together reconstituted the original whole. In the second level, participants took any one of two equal parts to be "half", but were inconsistent and accepted the possibility of the parts being unequal. In the third level, participants only took any one of two equal parts to be "half" but had difficulties splitting odd-numbered sets, including sets with fewer elements than the even-numbered ones they had previously split correctly. In the fourth level, the task was solved successfully with both even-numbered and odd-numbered sets. For the continuous quantities task, three levels were found. In the first level, any one of two raw spaghetti pieces was taken to be "half", without checking their evenness. In the second level, participants took any two equal pieces of the raw spaghetti to be "half", but without checking whether putting them back together reconstituted the original whole, with no extra parts remaining. In the third level, participants took any one of two equal pieces to be "half", checking whether putting them back together reconstituted the original whole. These results are consistent with reports from previous research assessing the notion of "half" in Western contexts. Results support universality in the development of the notion of "half", but show a delay in the participants' level of acquisition, taking Peru's national curriculum as reference. This study is a contribution to the understanding of the development of the notion of "half" in indigenous children living in Amazonian native communities, and shows the relevance of the Piagetian clinical-critical interview in these sociocultural contexts. The implications of these findings are discussed in relation to the universality of logical-mathematical knowledge, as well as the need to rethink the timing and manner in which the notion of "half" appears in the curriculum.