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ABSTRACT: Variant Creutzfeldt-Jakob disease (vCJD) is a devastating disease caused by transmission of bovine spongiform encephalopathy to humans. Although vCJD cases are now rare, evidence from appendix surveys suggests that a small proportion of the United Kingdom population may be infected without showing signs of disease. These "silent" carriers could present a risk of iatrogenic vCJD transmission through medical procedures or blood/organ donation, and currently there are no validated tests to identify infected asymptomatic individuals using easily accessible samples. To address this issue, we evaluated the performance of 3 blood-based assays in a blinded study, using longitudinal sample series from a well-established large animal model of vCJD. The assays rely on amplification of misfolded prion protein (PrPSc; a marker of prion infection) and include real-time quaking-induced conversion (RT-QuIC), and 2 versions of protein misfolding cyclic amplification (PMCA). Although diagnostic sensitivity was higher for both PMCA assays (100%) than RT-QuIC (61%), all 3 assays detected prion infection in blood samples collected 26 months before the onset of clinical signs and gave no false-positive results. Parallel estimation of blood prion infectivity titers in a sensitive transgenic mouse line showed positive correlation of infectivity with PrPSc detection by the assays, suggesting that they are suitable for detection of asymptomatic vCJD infection in the human population. This study represents, to our knowledge, the largest comparison to date of preclinical prion detection in blood samples from a relevant animal model. The outcomes will guide efforts to improve early detection of prion disease and reduce infection risks in humans.
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Síndrome de Creutzfeldt-Jakob , Animais , Síndrome de Creutzfeldt-Jakob/sangue , Síndrome de Creutzfeldt-Jakob/diagnóstico , Ovinos , Camundongos , Estudos Longitudinais , Doenças Priônicas/sangue , Doenças Priônicas/diagnóstico , Proteínas PrPSc/sangue , Príons/sangue , Humanos , Sensibilidade e Especificidade , Camundongos TransgênicosRESUMO
BACKGROUND: Little is known about practice patterns and payments for immediate lymphatic reconstruction (ILR). This study aims to evaluate trends in ILR delivery and billing practices. METHODS: We queried the Massachusetts All-Payer Claims Database between 2016 and 2020 for patients who underwent lumpectomy or mastectomy with axillary lymph node dissection for oncologic indications. We further identified patients who underwent lymphovenous bypass on the same date as tumor resection. We used ZIP code data to analyze the geographic distribution of ILR procedures and calculated physician payments for these procedures, adjusting for inflation. We used multivariable logistic regression to identify variables, which predicted receipt of ILR. RESULTS: In total, 2862 patients underwent axillary lymph node dissection over the study period. Of these, 53 patients underwent ILR. Patients who underwent ILR were younger (55.1 vs 59.3 years, P = 0.023). There were no significant differences in obesity, diabetes, or smoking history between the two groups. A greater percentage of patients who underwent ILR had radiation (83% vs 67%, P = 0.027). In multivariable regression, patients residing in a county neighboring Boston had 3.32-fold higher odds of undergoing ILR (95% confidence interval: 1.76-6.25; P < 0.001), while obesity, radiation therapy, and taxane-based chemotherapy were not significant predictors. Payments for ILR varied widely. CONCLUSIONS: In Massachusetts, patients were more likely to undergo ILR if they resided near Boston. Thus, many patients with the highest known risk for breast cancer-related lymphedema may face barriers accessing ILR. Greater awareness about referring high-risk patients to plastic surgeons is needed.
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Neoplasias da Mama , Excisão de Linfonodo , Humanos , Pessoa de Meia-Idade , Feminino , Massachusetts , Neoplasias da Mama/cirurgia , Neoplasias da Mama/economia , Excisão de Linfonodo/economia , Mastectomia/economia , Estudos Retrospectivos , Disparidades em Assistência à Saúde/economia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Idoso , Adulto , Axila/cirurgia , Mastectomia Segmentar/economia , Padrões de Prática Médica/economia , Padrões de Prática Médica/estatística & dados numéricosRESUMO
BACKGROUND: Gut microbiota is involved in the development of liver diseases such as fibrosis. We and others identified that selected sets of gut bacterial DNA and bacteria translocate to tissues, notably the liver, to establish a non-infectious tissue microbiota composed of microbial DNA and a low frequency live bacteria. However, the precise set of bacterial DNA, and thereby the corresponding taxa associated with the early stages of fibrosis need to be identified. Furthermore, to overcome the impact of different group size and patient origins we adapted innovative statistical approaches. Liver samples with low liver fibrosis scores (F0, F1, F2), to study the early stages of the disease, were collected from Romania(n = 36), Austria(n = 10), Italy(n = 19), and Spain(n = 17). The 16S rRNA gene was sequenced. We considered the frequency, sparsity, unbalanced sample size between cohorts to identify taxonomic profiles and statistical differences. RESULTS: Multivariate analyses, including adapted spectral clustering with L1-penalty fair-discriminant strategies, and predicted metagenomics were used to identify that 50% of liver taxa associated with the early stage fibrosis were Enterobacteriaceae, Pseudomonadaceae, Xanthobacteriaceae and Burkholderiaceae. The Flavobacteriaceae and Xanthobacteriaceae discriminated between F0 and F1. Predicted metagenomics analysis identified that the preQ0 biosynthesis and the potential pathways involving glucoryranose and glycogen degradation were negatively associated with liver fibrosis F1-F2 vs F0. CONCLUSIONS: Without demonstrating causality, our results suggest first a role of bacterial translocation to the liver in the progression of fibrosis, notably at the earliest stages. Second, our statistical approach can identify microbial signatures and overcome issues regarding sample size differences, the impact of environment, and sets of analyses. TRIAL REGISTRATION: TirguMECCH ROLIVER Prospective Cohort for the Identification of Liver Microbiota, registration 4065/2014. Registered 01 01 2014.
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Cirrose Hepática , Microbiota , Humanos , DNA Bacteriano/genética , RNA Ribossômico 16S/genética , Estudos Prospectivos , FibroseRESUMO
INTRODUCTION: Periodontal diseases (gingivitis and periodontitis) are chronic non-communicable inflammatory diseases. The risk of developing gingivitis and periodontitis increases during pregnancy. Also, periodontitis increases the risk of developing adverse pregnancy outcomes such as preterm birth and preeclampsia. Early diagnosis of adverse pregnancy outcomes is essential and periodontitis could be an early sign to take into consideration. MATERIAL AND METHODS: We conducted a longitudinal observational study (PERISCOPE study: CNIL, no. 1 967 084 v 0; CER, no. 01-0416) on 121 pregnant women in the first trimester to determine their oral and periodontal health status. We explored the relations between oral and periodontal health status and sociodemographic and behavior characteristics, as well as their course and outcome of pregnancy. RESULTS: A total of 47.1% of the women had periodontitis, of which only 66.7% presented clinical manifestations associated with the disease such as gingival bleeding. These women had a poorer oral and periodontal health, and a higher body mass index, and more of them developed gestational diabetes during the course of pregnancy. The remaining 33.3% showed only discreet and isolated inflammatory signs and, unless thoroughly examined, would have gone undiagnosed for periodontitis. Interestingly these women were more often primiparous, still active professionally and had had a recent oral examination. CONCLUSIONS: The PERISCOPE study is one of the few studies that reports the oral and periodontal health status of pregnant women in the first trimester. Furthermore, the results highlight the need for early oral and periodontal assessment and treatment, even in the absence of exterior clinical signs, in order to prevent periodontal disease aggravation and also, by reducing low grade systemic inflammation, possibly adverse pregnancy outcomes.
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Gengivite , Periodontite , Nascimento Prematuro , Feminino , Gravidez , Recém-Nascido , Humanos , Primeiro Trimestre da Gravidez , Estudos Longitudinais , Periodontite/complicações , Periodontite/diagnóstico , Periodontite/epidemiologia , Gengivite/diagnóstico , Gengivite/complicações , Resultado da GravidezRESUMO
The aim of this study was to analyze the link between periodontal microbiota and obesity in humans. We conducted a cohort study including 45 subjects with periodontitis divided into two groups: normo-weighted subjects with a body mass index (BMI) between 20 and 25 kg/m2 (n = 34) and obese subjects with a BMI > 30 kg/m2 (n = 11). Our results showed that obesity was associated with significantly more severe gingival inflammation according to Periodontal Inflamed Surface Area (PISA index). Periodontal microbiota taxonomic analysis showed that the obese (OB) subjects with periodontitis were characterized by a specific signature of subgingival microbiota with an increase in Gram-positive bacteria in periodontal pockets, associated with a decrease in microbiota diversity compared to that of normo-weighted subjects with periodontitis. Finally, periodontal treatment response was less effective in OB subjects with persisting periodontal inflammation, reflecting a still unstable periodontal condition and a risk of recurrence. To our knowledge, this study is the first exploring both salivary and subgingival microbiota of OB subjects. Considering that OB subjects are at higher periodontal risk, this could lead to more personalized preventive or therapeutic strategies for obese patients regarding periodontitis through the specific management of oral microbiota of obese patients.
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Microbiota , Periodontite , Humanos , Estudos de Coortes , Bactérias , Periodontite/microbiologia , Inflamação/complicações , Obesidade/complicaçõesRESUMO
(1) Background: In developed countries, the prevalence of apical periodontitis (AP) varies from 20% to 50% for reasons that could be associated with the apical periodontitis microbiota ecology. (2) Methods: We performed a clinical study in the Odontology department of Toulouse hospital in France, to sequence the 16S rRNA gene of AP microbiota and collect clinical parameters from 94 patients. Forty-four patients were characterized with a PAI (periapical index of AP severity) score lower or equal to 3, while the others had superior scores (n = 50). (3) Results: The low diversity of granuloma microbiota is associated with the highest severity (PAI = 5) of periapical lesions (Odds Ratio 4.592, IC 95% [1.6329; 14.0728]; p = 0.001; notably, a lower relative abundance of Burkholderiaceae and a higher relative abundance of Pseudomonas and Prevotella). We also identified that high blood pressure (HBP) is associated with the increase in PAI scores. (4) Conclusions: Our data show that a low diversity of bacterial ecology of the AP is associated with severe PAI scores, suggesting a causal mechanism. Furthermore, a second risk factor was blood pressure associated with the severity of apical periodontitis.
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Hipertensão , Microbiota , Periodontite Periapical , Humanos , RNA Ribossômico 16S/genética , Bactérias/genética , Microbiota/genéticaRESUMO
Lithium is a psychotropic drug used primarily in the treatment of bipolar disorder. It is renally excreted and characteristically causes nephrogenic diabetes insipidus as an adverse drug reaction. Lithium also requires serum level monitoring as there is a narrow therapeutic window and untreated toxicity can result in neurological sequelae including drowsiness, coma, seizures, and ultimately death. We present the case of a 65-year old man admitted for pituitary surgery complicated by post-operative difficult fluid management and subsequent lithium toxicity. We highlight this rare situation and the need to be vigilant in the peri-operative period with any patients on lithium who undergo pituitary surgery.
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Muir Torre syndrome is an autosomal dominant disorder characterised by germline mutations in mismatch repair genes involved in DNA repair, leading to microsatellite instability and a propensity to tumour formation. We report a case of a 67-year-old gentleman who underwent biopsy of a smooth nodular lesion on the nasal tip, histopathologically consistent with sebaceous adenoma. Immunohistochemistry suggested a loss of MSH6. Subsequent colonoscopy identified a poorly differentiated adenocarcinoma, with loss of staining for MSH6 and a germline mutation identified on genetic analysis. These findings were consistent with a diagnosis of Muir Torre syndrome. Whilst there is controversy in the literature regarding universal screening for Muir Torre syndrome, the early detection of visceral neoplasms is crucial. The authors strongly support screening for Muir Torre syndrome (with patient consent) upon discovery of a cutaneous sebaceous neoplasm, even in the absence of a personal or family history of visceral malignancy.
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Adenoma , Síndrome de Muir-Torre/diagnóstico , Neoplasias das Glândulas Sebáceas , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenoma/genética , Adenoma/patologia , Idoso , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Proteínas de Ligação a DNA/genética , Mutação em Linhagem Germinativa , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Síndrome de Muir-Torre/genética , Neoplasias das Glândulas Sebáceas/genética , Neoplasias das Glândulas Sebáceas/patologiaRESUMO
BACKGROUND/OBJECTIVES: Keratinocyte cancer impacts health-related quality of life (HRQL). Disease progression and treatment can lead to adverse physical and psychosocial consequences. The skin cancer index (SCI) is a validated tool with higher scores reflecting greater HRQL. Our objectives were to assess and compare the impact of keratinocyte cancer using the SCI in two diverse populations. METHODS: A total of 120 patients were prospectively recruited from dermatology clinics in Sydney, Australia, and Santander, Spain, providing demographics and completing the SCI. RESULTS: About 61.1% of Australians reported ≥2 skin cancers (vs 20% P = <0.001), 44.4% resulting visible scars (vs 14.8% P = <0.001). Visible scars were associated with poorer HRQL, across total SCI (68.3 vs 81.5 P = <0.001), social (76.0 vs 86.7 P = 0.003) and emotional (54.2 vs 69.7 P = 0.003) domains. Interestingly, perceived visible scars were not associated with appearance scores. The Spanish population reported greater appearance (88.0 vs 75.6 P = 0.008) and emotional (70.7 vs 60.5 P = 0.034) HRQL. Surprisingly, incidence of cancer, recent disease, gender and education were not associated with HRQL impairment. CONCLUSIONS: Australians with keratinocyte cancer experience poorer HRQL compared to a Spanish population. Offering non-surgical means when amenable and consideration of psychosocial needs during clinical course is emphasised. While our study highlights the importance of HRQL tools, our results question the sensitivity of the SCI across populations. Further research is required to substantiate its ongoing use.
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Carcinoma Basocelular/psicologia , Carcinoma de Células Escamosas/psicologia , Cicatriz/psicologia , Qualidade de Vida , Neoplasias Cutâneas/psicologia , Fatores Etários , Idoso , Austrália/epidemiologia , Carcinoma Basocelular/epidemiologia , Carcinoma Basocelular/terapia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/terapia , Estudos Transversais , Feminino , Humanos , Masculino , Estudos Prospectivos , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/terapia , Espanha/epidemiologiaRESUMO
INTRODUCTION: Proof of professional specific academic attainment is embedded within the Joint Committee on Surgical Training 2013 general surgery curriculum, mandating that all higher general surgical trainees (HST) obtain three peer-reviewed publications to qualify for Certification of Completion of Training. Yet, Modernising Medical Careers (MMC) has been associated with a trend away from the gold standard postgraduate credentials of higher degrees by research. This study aimed to evaluate the academic achievements of a post-MMC UK Deanery HST cohort to determine what additional benefits higher degree study might confer. METHOD: The Scopus bibliographic database (Elsevier, RELX Group) was used to characterise the academic profiles of 101 consecutive HSTs and supplemented with Intercollegiate Surgical Programme Curriculum data. Primary outcome measures were numbers of publications, citations and Hirsch indices (HI). RESULTS: Thirty-seven HSTs (36.6%) had been awarded higher degrees (29 Doctor of Medicine, 8 Doctor of Philosophy). Academic profiles of HSTs with higher degrees were stronger than those of HSTs without, specifically: median (range) publication numbers 16 (2-57) vs 2 (0-11, P<0.001), citations 93 (0-1600) vs 6 (0-132, P<0.001), first author publications 6 (0-33) vs 3 (0-106, P<0.001), communications to learnt societies 30 (5-79) vs 8 (2-35, P<0.001) and HI 6 (1-26) vs 1 (0-6, P<0.001). CONCLUSION: Proof of academic reach by higher degree was associated with important enhanced professional credentials, strengthening HIs sixfold. Trainers and trainees alike should be aware of the relative magnitude of such benefits when planning educational programmes.
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Educação de Pós-Graduação em Medicina , Docentes de Medicina/normas , Cirurgia Geral/educação , Sucesso Acadêmico , Educação de Pós-Graduação em Medicina/organização & administração , Educação de Pós-Graduação em Medicina/normas , Humanos , Revisão da Pesquisa por Pares , Reino UnidoRESUMO
INTRODUCTION: Women's participation in medicine has increased dramatically during the last 50 years, yet Office for National Statistics data (2016) regarding annual pay continue to show an unequivocal 34% deficit in female doctors' remuneration compared with their male counterparts. This study aimed to identify whether there are measurable differences in the training, career vectors and profiles of higher general surgical trainees (HSTs), related to gender. METHOD: The Deanery roster supplemented with Intercollegiate Surgical Curriculum Programme and Scopus data was used to identify the profiles of 101 consecutive HSTs (38 women, 63 men, single UK deanery). Primary outcome measures were training programme attrition rate, time to completion of training and achievement of third level 4 competence (3L4C) in indicative operations. Secondary outcomes were publication number, citations and Hirsch Indices (HIs). RESULTS: Attrition rates were similar irrespective of gender (female n=3 (7.9%) vs male n=6 (9.5%), p=0.871). Training duration was on average 16 months longer in women (94 (72-134) months) than men (78 (72-112), p=0.002). Operative learning curve trajectories were similar; median operations required to achieve 3L4C was 380 (f) versus 410 (m, p=1.00). Academic profiles of men were stronger than women, specifically higher degrees; men (n=31, 83.8%), women (n=6, 16.2%, p=0.001); median (range) publication number 8 (0-57) versus 3 (0-38, p=0.003), citations 43 (0-1600) versus 9 (0-774, p=0.001), and HI 3 (0-26) versus 2 (0-12, p=0.002). CONCLUSION: A complex variable gender gap was apparent related to time in training and academic profile, but not training attrition or operative learning curve trajectory.
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Escolha da Profissão , Currículo , Cirurgia Geral/educação , Médicas/estatística & dados numéricos , Sucesso Acadêmico , Adulto , Educação de Pós-Graduação em Medicina , Feminino , Humanos , Internato e Residência , Masculino , Lealdade ao Trabalho , Salários e Benefícios/estatística & dados numéricos , Reino UnidoRESUMO
Discoveries in the defective molecular composition of the epidermal barrier, such as the epidermal protein filaggrin, in those with atopic eczema (or atopic dermatitis [AD]) have proved crucial in understanding this disease, but its aetiology remains to be fully elucidated. The epidermal barrier is just one interface between the microbial world and our immune system. Recent advances in molecular technology have demonstrated for the first time the true scale of the normal human microbiome and changes seen in disease states. In this review article we discuss the role of the human microbiome in the aetiology and maintenance of AD. The role of Staphylococcus aureus within the skin microbiome is examined, in addition to the role of other bacteria and fungi, identified using novel culture-independent methods. The significant contribution of the gut microbiome and its manipulation via probiotic use is also reviewed. We emphasise that the microbiome of separate systems, including the gut, has a significant role to play in the manifestation of this cutaneous disorder. To date, there has been a lack of studies investigating whether changes to the lung microbiome may play a role in AD. An early interaction between the microbiome and immune system via multiple routes (skin-gut-lung) could feasibly affect the risk of a subsequent development of atopic diseases. When making management decisions for AD patients, clinicians must be mindful of the role of the microbiome.
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Dermatite Atópica/microbiologia , Microbiota , Pele/microbiologia , Staphylococcus aureus , Proteínas Filagrinas , Microbioma Gastrointestinal , Humanos , Probióticos , Sistema Respiratório/microbiologia , Exacerbação dos SintomasRESUMO
BACKGROUND/OBJECTIVES: In Mohs micrographic surgery (MMS) the dermatologist serves as surgeon, pathologist and reconstructive surgeon. Analysis of the factors that play a part in determining defect size and closure type may result in better patient outcomes. The objective was to identify factors contributing to the defect size and closure method employed in MMS. METHODS: Retrospective analysis of all MMS performed for non-melanoma skin cancers (NMSC) of the head at the Skin and Cancer Foundation Australia, Westmead, between 1 January and 31 December 2007. RESULTS: Tumor size was the main factor involved in the final defect size (r2 : 0.60, P < 0.001), but the sex and age of the patient, tumour pathology, site and surgeon were also significantly associated with the final defect size. In a multivariate analysis, only sex did not remain as an independent factor. Regarding closure method, the age of the patient, defect size, site and surgeon were significantly associated, but patient's age did not remain significant in the multivariate analysis. CONCLUSION: Our study has demonstrated that the performing surgeon is a relevant factor in the determination of defect size and repair methods in MMS. The factors underlying this variability require further study as decisions on closure method should be made objectively, based on patient-related and tumour-related factors. As expected, the location and size of the defect are the other factors that determine the chosen method of repair.
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Carcinoma Basocelular/cirurgia , Carcinoma de Células Escamosas/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Cirurgia de Mohs/métodos , Neoplasias Cutâneas/cirurgia , Técnicas de Fechamento de Ferimentos , Fatores Etários , Idoso , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/patologia , Orelha , Face , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica , Couro Cabeludo , Neoplasias Cutâneas/patologia , Retalhos Cirúrgicos , Carga TumoralRESUMO
There is a family of proteins from parasitic worms which combine N-terminal EF-hand domains with C-terminal dynein light chain-like domains. Data are accumulating on the biochemistry and cell biology of these proteins. However, little is known about their functions in vivo Schistosoma mansoni expresses 13 family members (SmTAL1-SmTAL13). Three of these (SmTAL1, SmTAL2 and SmTAL3) have been subjected to biochemical analysis which demonstrated that they have different molecular properties. Although their overall folds are predicted to be similar, small changes in the EF-hand domains result in differences in their ion binding properties. Whereas SmTAL1 and SmTAL2 are able to bind calcium (and some other) ions, SmTAL3 appears to be unable to bind any divalent cations. Similar biochemical diversity has been seen in the CaBP proteins from Fasciola hepatica Four family members are known (FhCaBP1-4). All of these bind to calcium ions. However, FhCaBP4 dimerizes in the presence of calcium ions, FhCaBP3 dimerizes in the absence of calcium ions and FhCaBP2 dimerizes regardless of the prevailing calcium ion concentration. In both the SmTAL and FhCaBP families, the proteins also differ in their ability to bind calmodulin antagonists and related drugs. Interestingly, SmTAL1 interacts with praziquantel (the drug of choice for treating schistosomiasis). The pharmacological significance (if any) of this finding is unknown.
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Proteínas de Ligação ao Cálcio/metabolismo , Fasciola hepatica/metabolismo , Proteínas de Helminto/metabolismo , Família Multigênica , Schistosoma mansoni/metabolismo , Animais , Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/química , Proteínas de Ligação ao Cálcio/genética , Motivos EF Hand , Fasciola hepatica/genética , Proteínas de Helminto/química , Proteínas de Helminto/genética , Ligação Proteica , Multimerização Proteica , Schistosoma mansoni/genéticaRESUMO
FH22 has been previously identified as a calcium-binding protein from the common liver fluke, Fasciola hepatica. It is part of a family of at least four proteins in this organism which combine an EF-hand containing N-terminal domain with a C-terminal dynein light chain-like domain. Here we report further biochemical properties of FH22, which we propose should be renamed FhCaBP1 for consistency with other family members. Molecular modelling predicted that the two domains are linked by a flexible region and that the second EF-hand in the N-terminal domain is most likely the calcium ion binding site. Native gel electrophoresis demonstrated that the protein binds both calcium and manganese ions, but not cadmium, magnesium, strontium, barium, cobalt, copper(II), iron (II), nickel, zinc, lead or potassium ions. Calcium ion binding alters the conformation of the protein and increases its stability towards thermal denaturation. FhCaBP1 is a dimer in solution and calcium ions have no detectable effect on the protein's ability to dimerise. FhCaBP1 binds to the calmodulin antagonists trifluoperazine and chlorpromazine. Overall, the FhCaBP1's biochemical properties are most similar to FhCaBP2 a fact consistent with the close sequence and predicted structural similarity between the two proteins.
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Proteínas de Ligação ao Cálcio/química , Dineínas/química , Fasciola hepatica/metabolismo , Proteínas de Helminto/química , Animais , Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/isolamento & purificação , Proteínas de Ligação ao Cálcio/metabolismo , Calmodulina/antagonistas & inibidores , Clorpromazina/metabolismo , Eletroforese em Gel de Poliacrilamida , Fasciola hepatica/genética , Expressão Gênica , Proteínas de Helminto/genética , Proteínas de Helminto/isolamento & purificação , Proteínas de Helminto/metabolismo , Manganês/metabolismo , Conformação Proteica , Multimerização Proteica , Trifluoperazina/metabolismoRESUMO
The common liver fluke Fasciola hepatica causes an increasing burden on human and animal health, partly because of the spread of drug-resistant isolates. As a consequence, there is considerable interest in developing new drugs to combat liver fluke infections. A group of potential targets is a family of calcium-binding proteins which combine an N-terminal domain with two EF-hand motifs and a C-terminal domain with predicted similarity to dynein light chains (DLC-like domain). The function of these proteins is unknown, although in several species, they have been localised to the tegument, an important structure at the host-parasite interface. Here, we report the X-ray crystal structure of the DLC-like domain of F. hepatica calcium-binding protein 2 (FhCaBP2), solved using single-wavelength anomalous diffraction and refined at 2.3 Å resolution in two different crystal forms. The FhCaBP2 DLC-like domain has a structure similar to other DLC domains, with an anti-parallel ß-sheet packed against an α-helical hairpin. Like other DLC domains, it dimerises through its ß2-strand, which extends in an arch and forms the fifth strand in an extended ß-sheet of the other monomer. The structure provides molecular details of the dimerisation of FhCaBP2, the first example from this family of parasite proteins.
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Proteínas de Ligação ao Cálcio/química , Dineínas/química , Fasciola hepatica/metabolismo , Fasciolíase/parasitologia , Animais , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Cristalografia por Raios X , Dineínas/genética , Dineínas/metabolismo , Motivos EF Hand , Fasciola hepatica/genética , Proteínas de Helminto/química , Proteínas de Helminto/genética , Proteínas de Helminto/metabolismo , Humanos , Modelos Moleculares , Domínios Proteicos , Proteínas RecombinantesRESUMO
FhCaBP2 is a Fasciola hepatica protein which belongs to a family of helminth calcium-binding proteins which combine an N-terminal domain containing two EF-hand motifs and a C-terminal dynein light chain-like (DLC-like) domain. Its predicted structure showed two globular domains joined by a flexible linker. Recombinant FhCaBP2 interacted reversibly with calcium and manganese ions, but not with magnesium, barium, strontium, copper (II), colbalt (II), iron (II), nickel, lead or potassium ions. Cadmium (II) ions appeared to bind non-site-specifically and destabilize the protein. Interaction with either calcium or magnesium ions results in a conformational change in which the protein's surface becomes more hydrophobic. The EF-hand domain alone was able to interact with calcium and manganese ions; the DLC-like domain was not. Alteration of a residue (Asp-58 to Ala) in the second EF-hand motif in this domain abolished ion-binding activity. This suggests that the second EF-hand is the one responsible for ion-binding. FhCaBP2 homodimerizes and the extent of dimerization was not affected by calcium ions or by the aspartate to alanine substitution in the second EF-hand. The isolated EF-hand and DLC-like domains are both capable of homodimerization. FhCaBP2 interacted with the calmodulin antagonists trifluoperazine, chlorpromazine, thiamylal and W7. Interestingly, while chlorpromazine and thiamylal interacted with the EF-hand domain (as expected), trifluoperazine and W7 bound to the DLC-like domain. Overall, FhCaBP2 has distinct biochemical properties compared with other members of this protein family from Fasciola hepatica, a fact which supports the hypothesis that these proteins have different physiological roles.
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Proteínas de Ligação ao Cálcio/metabolismo , Cálcio/metabolismo , Fasciola hepatica/metabolismo , Proteínas de Helminto/metabolismo , Modelos Moleculares , Animais , Sequência de Bases , Proteínas de Ligação ao Cálcio/química , Proteínas de Ligação ao Cálcio/genética , Biologia Computacional , Dineínas/química , Dineínas/genética , Dineínas/metabolismo , Motivos EF Hand , Fasciola hepatica/genética , Proteínas de Helminto/química , Proteínas de Helminto/genética , Dados de Sequência Molecular , Ligação Proteica , Análise de Sequência de DNA , Especificidade da EspécieRESUMO
Malnutrition can increase the risk of surgical site infection in both elective spine surgery and total joint arthroplasty. Obesity and diabetes are common comorbid conditions in patients who are malnourished. Despite the relatively high incidence of nutritional disorders among patients undergoing elective orthopaedic surgery, the evaluation and management of malnutrition is not generally well understood by practicing orthopaedic surgeons. Serologic parameters such as total lymphocyte count, albumin level, prealbumin level, and transferrin level have all been used as markers for nutrition status. In addition, anthropometric measurements, such as calf and arm muscle circumference or triceps skinfold, and standardized scoring systems, such as the Rainey-MacDonald nutritional index, the Mini Nutritional Assessment, and institution-specific nutritional scoring tools, are useful to define malnutrition. Preoperative nutrition assessment and optimization of nutritional parameters, including tight glucose control, normalization of serum albumin, and safe weight loss, may reduce the risk of perioperative complications, including infection.
Assuntos
Artroplastia de Substituição/efeitos adversos , Desnutrição/complicações , Infecções Relacionadas à Prótese/etiologia , Infecção da Ferida Cirúrgica/etiologia , Humanos , Desnutrição/diagnóstico , Desnutrição/terapia , Coluna Vertebral/cirurgia , CicatrizaçãoRESUMO
PURPOSE: The purpose of this study is to describe the oral health status of inmates. The secondary aims were to compare recidivists with first-time offenders and also study the impact of psychoactive drugs on the oral health status. DESIGN/METHODOLOGY/APPROACH: This retrospective study included 120 male inmates from a French prison. Data from the medical and the dental questionnaires and examinations were collected and analyzed. FINDINGS: The results showed that overall, the inmates had a poor oral health despite their young age. This population was at high risk regarding caries and periodontal diseases due to sedentary behaviors, improper diet, drug, alcohol and tobacco consumption. In total, 93% of inmates had at least one decayed untreated tooth and 95% had periodontal disease. The use of psychoactive drugs seemed strongly related to oral health status degradation. However, the comparison between recidivists and first-time offenders showed few differences. PRACTICAL IMPLICATIONS: The need for periodontal and dental care is considerable in this population and increased in this environment where risk factors such as addictive behaviors and poor eating habits are common. The impact of psychoactive drugs on oral health should also be taken into consideration. SOCIAL IMPLICATIONS: Unfortunately, even though strategies for the prevention and management of oral health in prisons have been put in place for some years, the results still seem insufficient. ORIGINALITY/VALUE: There are still few studies that analyze the impact of this medication on oral health in prisons.