Determinación de Valores de Armonía del Perfil Facial en la Población Chilena / Determination of harmony values of the facial profile in the Chilean population

El realizar un tratamiento ortodóntico sólo en base a referencias de tejidos duros, puede llevar a resultados estéticos desfavorables, debido a la gran variabilidad que existe en los tejidos blandos que los recubren. Arnett et al. (1999) presentaron un análisis basado en los tejidos blandos y determinó normas que definen un rostro armónico. Sin embargo, éstas normas se obtuvieron de pacientes norteamericanos y puede que no reflejen los conceptos estéticos de nuestra población. El objetivo del presente trabajo fue determinar valores de armonía facial para la población chilena, utilizando el análisis cefalométrico de tejidos blandos presentado por Arnett et al., y compararlos con los valores previamente establecidos para la población caucásica. Se analizaron 200 fotografías y se clasificaron los perfiles en balanceados y no balanceados según el criterio de un grupo de especialistas. Posteriormente se analizaron las telerradiografías correspondientes a los perfiles clasificados, con el análisis cefalométrico de tejidos blandos. Los valores de las diferentes variables fueron analiza dos separadamente por sexo, clase esqueletal y biotipo facial, y se determinaron las diferencias entre las variables presentadas por Arnett et al. y las obtenidas en el presente estudio. Para ello se utilizaron pruebas de significancia estadística como el test t y otros no paramétricos. Sólo se encontró diferencias significativas en dos variables respecto de las normas sugeridas por Arnett et al., correspondientes a un menor espesor del labio inferior en ambos sexos, y una mayor prominencia del pómulo en mujeres chilenas, por lo que consideramos que los valores de armonía de Arnett et al., pueden ser también aplicados como parámetro estético para la población chilena.

Performing an orthodontic treatment based only on hard tissue references can lead to unfavorable aesthetic results due to the great variability that exists in soft tissues that cover them. In 1999, W.Arnett, presented an analysis based on soft tissues and determined norms that define a harmonious face. However, these standards that were obtained from North Americans and Chilean aesthetic concepts could be different. The aim of the study was to determine the values of facial harmony for the Chilean population, using the cephalometric analysis of soft tissues presented by Arnett, and compare them with the values previously established for the Caucasian population. In this study 200 photographs were analyzed, and the profiles were classified in balanced and unbalanced according to the criteria of a group of specialists. Subsequently, teleradiographs corresponding to the classified profiles were analyzed, with the cephalometric analysis of soft tissues. The values of the different variables were analyzed separately by sex, skeletal class and facial biotype, and the differences between the variables presented by Arnett et al., and those obtained in the present study. For this purpose, statistical significance tests such as the t test and other non- parametric tests were used. There were only significant differences in two variables: inferior lip variables in both sexes, and a greater prominence of the cheekbone in Chilean women, therefore we consider that the values of harmony of Arnett, can also be applied as an aesthetic parameter for the Chilean population.

Hypervascular Pseudonodular Plaque-Like Ultrasound Morphology in Angiolymphoid Hyperplasia. / Morfología ecográfica en placa pseudonodular hipervascular en hiperplasia angiolinfoide.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a benign vascular proliferation characterized by solitary or multiple angiomatous lesions. It is most common in young or middle-aged women, and the lesions typically affect the head and neck, showing a particular predilection for the periauricular region. The differential diagnosis in patients with ALHE is broad and includes both benign and malignant conditions. We report on a series of cases of periauricular ALHE in which ultrasound imaging revealed an hypervascular, pseudonodular and plaque-like morphology with clinical and histologic correlations. It also evidenced vascular communication between lesions that appeared to be separate on clinical examination. Familiarity with such ultrasound presentations could help to improve diagnostic accuracy and facilitate disease monitoring in patients with ALHE.

Juvenile, adult and late-onset systemic lupus erythematosus: a long term follow-up study from a geographic and ethnically homogeneous population.

OBJECTIVES: This paper aims to identify clinical and serological differences, damage accrual and mortality, in juvenile, adult and late-onset SLE. METHODS: We conducted our study with patients fulfilling SLE classification criteria taken from the Hospital Gregorio Marañon Autoimmune Systemic Rheumatic Diseases' Registry (1986 to 2012). Clinical characteristics, laboratory data and therapies used during the course of the disease were analysed with patients divided into 3 groups: juvenile-onset (≤ 18 years), adult-onset (19-50) and late onset (>50 years). RESULTS: Four hundred and forty-five patients were included. Renal disease and cutaneous manifestations were more frequent in the juvenile-onset group at disease onset. During follow-up, juvenile-onset group presented a higher incidence of renal disease, malar rash, Raynaud's phenomenon, cutaneous vasculitis, and neuropsychiatric manifestations than the other two groups. Arthritis and lymphopoenia were more frequent in the adult-onset group. Arterial hypertension and neoplasm were more frequent in the late-onset group. Low serum complement, anti-dsDNA, anti-U1RNP and anti-Sm antibodies were more common in the juvenile-onset group. Patients with late-onset SLE had more damage accrual. Thirty-seven patients (8.3%) died during the study. All-cause mortality was significantly higher in the late-onset group. Age at disease onset >50 years was an independent risk factor for damage accrual (OR, 2.2; 95%CI, 1.1-4.6; p=0.029) and mortality (OR, 2.6; 95%CI, 1.1-6.3; p=0.03). CONCLUSIONS: We found significant differences in clinical and serological profiles between juvenile, adult and late-onset SLE. The most significant of which was a higher prevalence of neuropsychiatric and renal complications as well as different autoantibody signatures for the juvenile-onset group.

Estimates of genetic parameters for reproductive traits in Brahman cattle breed.

This study was designed to estimate genetic parameters for the following traits of Brahman cattle in Brazil: age at first calving (AFC), calving interval (CI), rebreeding (REB), and stayability (STAY). For REB, the value 1 was assigned to heifers that rebred and calved after first calving and the value 0 was assigned to heifers that failed to rebreed after first calving. Likewise, for STAY, the value 1 was assigned to cows that calved at least 3 times by the time they reach 6 yr of age; otherwise, the value 0 was assigned. A bivariate analysis was used to estimate covariances components by using linear animal model for CI and AFC and threshold animal model for REB and STAY. The mean h(2) were 0.10, 0.02, 0.22, and 0.10 for AFC, CI, REB, and STAY, respectively. The genetic correlations were ­0.13 between AFC and CI, ­0.35 between AFC and REB, ­0.57 between AFC and STAY, and 0.32 between REB and STAY, which reveal that cows that remain productive for longer periods in the herd also start breeding younger and present greater chances to REB. The selection of Brahman cattle for reproductive traits, such as AFC, CI, REB, and STAY, will render low magnitude and long-term responses.

Estimates of genetic parameters for growth traits in Brahman cattle using random regression and multitrait models.

Random regression models (RRM) and multitrait models (MTM) were used to estimate genetic parameters for growth traits in Brazilian Brahman cattle and to compare the estimated breeding values obtained by these 2 methodologies. For RRM, 78,641 weight records taken between 60 and 550 d of age from 16,204 cattle were analyzed, and for MTM, the analysis consisted of 17,385 weight records taken at the same ages from 12,925 cattle. All models included the fixed effects of contemporary group and the additive genetic, maternal genetic, and animal permanent environmental effects and the quadratic effect of age at calving (AAC) as covariate. For RRM, the AAC was nested in the animal's age class. The best RRM considered cubic polynomials and the residual variance heterogeneity (5 levels). For MTM, the weights were adjusted for standard ages. For RRM, additive heritability estimates ranged from 0.42 to 0.75, and for MTM, the estimates ranged from 0.44 to 0.72 for both models at 60, 120, 205, 365, and 550 d of age. The maximum maternal heritability estimate (0.08) was at 140 d for RRM, but for MTM, it was highest at weaning (0.09). The magnitude of the genetic correlations was generally from moderate to high. The RRM adequately modeled changes in variance or covariance with age, and provided there was sufficient number of samples, increased accuracy in the estimation of the genetic parameters can be expected. Correlation of bull classifications were different in both methods and at all the ages evaluated, especially at high selection intensities, which could affect the response to selection.

Estimativas de parâmetros genéticos para características de crescimento em ovinos da raça Suffolk no Brasil / Estimates of genetic parameters for growth traits in Suffolk sheep in Brazil

O objetivo do trabalho foi estimar os parâmetros genéticos das características de crescimento da raça Suffolk, a fim de fornecer subsídio para a definição de estratégias de seleção para programas de melhoramento genético. Os dados analisados, coletados entre os anos de 2007 a 2009, são referentes a ovinos da raça Suffolk oriundos de uma propriedade localizada no Estado de São Paulo, Brasil, participante do programa de melhoramento genético Ovigol, conduzido pela empresa Aries Reprodução e Melhoramento Genético Ovino Ltda. em parceria com a empresa AbacusBio Limited, da Nova Zelândia. As características avaliadas foram: peso ao nascer (PN), ganho de peso pré-desmame (GPP) e peso ao desmame (PD), com número de registro de 1.039, 636 e 649 animais, respectivamente. Para análise estatística, utilizou-se o procedimento GLM do programa computacional SAS; para a consistência do pedigree e para as estimativas dos parâmetros genéticos, os programas computacionais utilizados foram Relax2: pedigree analysis program e o WOMBAT, respectivamente. O modelo linear geral incluiu sexo, grupo de contemporâneos (tipo de parto e ano de nascimento), covariável idade ao desmame (GPP e PD) com efeito quadrático, efeito genético aditivo direto, efeito de ambiente permanente materno e efeito residual. As herdabilidades para PN, GPP e PD foram 0,06, 0,42 e 0,37, respectivamente. As correlações genéticas entre PN e GPP, PN e PD e GPP e PD foram -0,10, -0,03 e 0,97, respectivamente. Na população estudada, as características GPP e PD, apresentam altas respostas à seleção, ao contrário do PN. As características PN e GPP são suficientes para compor um índice de seleção, sendo aconselhável o monitoramento do PN na fase inicial do programa.

The aim of this study was to estimate genetic parameters for growth of Suffolk, in order to provide a basis for the definition of selection strategies for breeding programs. The data analyzed are for Suffolk sheep, collected between years 2007 to 2009, from a property located in the State of São Paulo - Brazil, a participant in the Ovigol breeding program conducted by the company (Aries Reproduction and Breeding Sheep Ltd.) in partnership with (AbacusBio) New Zealand Limited. The evaluated characteristics were: birth weight (PN), weight gain pre-weaning (GPP) and weaning weight (PD), with registration number 1039, 636 and 649 respectively. For statistical analysis we used the GLM procedure of SAS software, for the consistency of pedigree and genetic parameter estimates software Relax2: pedigree analysis program and WOMBAT, respectively, were used. The general linear model included sex, contemporary group (type of birth and year of birth), covariate age at weaning (GPP and PD) with a quadratic effect, direct genetic effect, maternal permanent environmental effect and residual effect. Heritability estimates for PN, PD and GPP were 0.06, 0.42 and 0.37, respectively. Genetic correlations between PN and GPP, and PN and PD and GPP were -0.10, -0.03 and 0.97, respectively. In the study population characteristics GPP and PD have a high response to selection, unlike the PN. The GPP and PN characteristics are enough to make a selection index, it is advisable to monitor the PN in the initial phase of the program.

Genetic parameters for body weight in meat quail.

The aim of this study was to estimate genetic parameters for BW in meat quail at different ages. A total of 24,382 weight records from 3,652 quail, born between 2009 and 2011, were evaluated. Weekly BW was measured from hatch until 42 d of age. The genetic parameters were estimated by the restricted maximum likelihood method using a multivariate animal model. Heritability of BW ranged from 0.03 to 0.23. Genetic correlations were mainly high and positive. Selection for BW at 28 d of age yielded good indirect genetic progress in BW at 42 d of age.

Direct incorporation of the NKT-cell activator α-galactosylceramide into a recombinant Listeria monocytogenes improves breast cancer vaccine efficacy.

BACKGROUND: Immune suppression in the tumour microenvironment remains a major limitation to successful immunotherapy of cancer. In the current study, we analysed whether the natural killer T cell-activating glycolipid α-galactosylceramide could overcome immune suppression and improve vaccination against metastatic breast cancer. METHODS: Mice with metastatic breast cancer (4T1 model) were therapeutically treated with a Listeria monocytogenes-based vaccine expressing tumour-associated antigen Mage-b followed by α-galactosylceramide as separate agents, or as a complex of α-galactosylceramide stably incorporated into Listeria-Mage-b. Effects on metastases, tumour weight, toxicity and immune responses were determined. RESULTS: Sequential treatments of mice with established 4T1 breast carcinomas using Listeria-Mage-b followed by α-galactosylceramide as a separate agent was highly effective at reducing metastases, but was accompanied by severe liver toxicity. In contrast, combined therapy using Listeria-Mage-b modified by incorporation of α-galactosylceramide resulted in nearly complete elimination of metastases without toxicity. This was associated with a significant increase in the percentage of natural killer T cells in the spleen, and an increase in natural killer cell activity and in T cell responses to Mage-b. CONCLUSIONS: Our results suggest that direct incorporation of α-galactosylceramide into a live bacterial vaccine vector is a promising non-toxic new approach for the treatment of metastatic breast cancer.

The effects of rituximab on the lipid profile of patients with active systemic lupus erythematosus: results from a nationwide cohort in Spain (LESIMAB).

INTRODUCTION: Patients with systemic lupus erythematosus (SLE) have increased cardiovascular risk related to lipid changes induced by inflammatory activity, proteinuria and treatments. Our objective was to analyse lipid changes in a cohort of patients with SLE resistant to standard treatments who were treated with rituximab. METHODS: The study population comprised a retrospective multicentre, national cohort of patients with SLE resistant to standard treatments who were treated with rituximab. The basic lipid profile, concomitant treatment and disease activity were analysed at the start of the treatment, 24 weeks later, and at the end of the follow-up period. The effects of the main lupus variables and therapy on the lipid changes were analysed. RESULTS: Seventy-nine patients with active lupus treated with rituximab were assessed during 149.3 patient-years. Prior to the treatment, 69% had dyslipidaemia. The most frequent abnormalities were a low-density lipoprotein (LDL) level of ≥100 mg/dl (34%) and a high-density lipoprotein (HDL) level of <50 mg/dl (27%). Baseline total cholesterol (TC) and LDL levels correlated with the degree of proteinuria, while the concentration of triglycerides (TGs) correlated with the SLE Disease Activity Index (SLEDAI). TGs were reduced at short- and long-term follow-up after rituximab treatment. A multiple linear regression analysis identified that the reduction of the lupus inflammatory activity, particularly changes in proteinuria, was the only independent variable that was positively associated with the reduction in TGs after 24 weeks (p=0.001) and with TC (p=0.005) and TGs (p<0.001) at the end of the follow-up period. CONCLUSION: Our results suggest that rituximab may improve the long-term lipid profile of patients with SLE refractory to standard treatment, mainly by reducing inflammatory activity.

Understanding respiratory syncytial virus infection to improve treatment and immunity.

Despite significant research since it was discovered more than 50 years ago, respiratory syncytial virus (RSV) continues to be the leading agent causing infant hospitalization and respiratory distress worldwide. Although RSV normally does not cause mortality, this virus is recognized as a major public health and economic burden around the globe. RSV can modulate host immunity leading to an inflammatory response that produces lung damage and virus dissemination in the host airways. Remarkably, infection with the virus elicits poor immunity that in most cases fails to protect against subsequent exposures. Here, we review advances made on the understanding of the lifecycle of the virus, some of the molecular mechanisms it has evolved to cause pathology and ineffective immunity during infection. Hopefully, ongoing research will contribute to developing new drugs and candidate vaccines that will decrease the health burden caused by this virus.

Multicenter longitudinal study of B-lymphocyte depletion in refractory systemic lupus erythematosus: the LESIMAB study.

OBJECTIVE: This study aimed to investigate the effectiveness and safety of single and repeated courses of rituximab in patients with refractory lupus. METHODS: LESIMAB is a multicenter, retrospective, longitudinal study of lupus patients who have not responded to standard therapy and have been treated with rituximab. Response rates at six months and at follow-up were defined as efficacy outcomes. Complete response was defined as a SELENA-SLEDAI score ≤ two and a SELENA-SLEDAI Flare Index of zero. Partial response was defined as a reduction in the SELENA-SLEDAI score of ≥four points with no new or worsening of symptoms. Adverse events were collected. RESULTS: Seventy-three (62.9%) of 116 patients achieved a response at six months (complete in 22 and partial in 51). Ninety-seven (77.6%) of 128 patients achieved a response after a mean follow-up of 20.0 ± 15.2 months (complete in 50 and partial in 47). High baseline SLEDAI score, previous treatment with ≥100 mg/day prednisone, and no history of severe hematologic flare were associated with response after the first treatment course. The median time to response was 6.5 months (95% CI, 5.0-8.0). Thirty-seven patients (38.1%) relapsed after the first infusion. The flare was severe in seven cases and mild to moderate in 29 cases. Serious infection rate was 12.6/100 patient-years. A schedule of four weekly doses was associated with more serious infections. Six patients died: two of infection and four of lupus complications. CONCLUSION: Rituximab can be an effective treatment option for patients who have refractory lupus with severe or life-threatening disease with an acceptable tolerance profile.

Virulence mechanisms displayed by Salmonella to impair dendritic cell function.

Dendritic cells (DCs) link innate and adaptive immunity by directly recognizing pathogen-associated molecular patterns (PAMPs) on bacteria. DCs can capture and degrade bacteria and present their antigens on MHC molecules to T cells. PAMP recognition promotes DC maturation, a phenotypic change that empowers them to prime naïve T cells. As a result, an adaptive immune response that specifically targets bacteria-derived antigens is initiated. Consequently, any impairment of DC function might contribute to bacterial survival and dissemination in the host. Therefore, the characterization of DC-bacteria interactions is required to understand the mechanisms used by virulent bacteria to avoid adaptive immunity. An example of a bacterial pathogen capable of interfering with DC function is Salmonella enterica serovar Typhimurium (S. Typhimurium), which causes a typhoid-like disease in mice. Virulent strains of S. Typhimurium are able to differentially modulate the entrance to DCs and avoid lysosomal degradation, to prevent antigen presentation on MHC molecules. These features of virulent S. Typhimurium are controlled by virulence factors encoded by Salmonella Pathogenicity Islands 1 and 2. Modulation of DC functions by the activity of these gene products is supported by several recent studies, which have shown that pathogenesis might depend on this attribute of virulent S. Typhimurium. Here we discuss recent data showing that several virulence factors from Salmonella are required to differentially modulate DC function and adaptive immunity in the host.

Pericardial tamponade in a patient with polymyalgia rheumatica.

We report a patient who developed pericarditis and pericardial tamponade coinciding with polymyalgia rheumatica onset. Our patient did not show any clinical sign of vasculitis; temporal artery biopsies were negative for giant cell arteritis. Pericardial biopsy in our case shows inflammatory perivascular lymphocytary infiltrates thus we believe pericardial effusion has an inflammatory-immunologic origin. Cardiac manifestations are exceptional in polymyalgia rheumatica, though it should be considered in the differential diagnosis in patients with pericarditis over 50 years. The recognition of this uncommon manifestation is very important due to the good response to corticosteroid treatment.

Cognitive dysfunction in systemic lupus erythematosus: prevalence and correlates.

Little is known about the mechanisms and relevance of cognitive dysfunction in systemic lupus erythematosus (SLE) patients who never displayed major neuropsychiatric manifestations (nSLE). Thirty-one nSLE female patients and 31 cognitively healthy control women were recruited. Sociodemographic, clinical, neuropsychological and SLE-related markers were collected including cerebral perfusion by single-photon emission computed tomography. Prevalences of cognitive complaints were 22.6% in nSLE versus 6.5% in the control group (p = 0.147); respective prevalences of cognitive dysfunction were 32.3 versus 6.5% (p = 0.01). Within the nSLE group, all cognitive domains appeared similarly affected, and correlations were found between cognitive dysfunction and less skilled occupation (r = -0.41, p = 0.02) and between cognitive complaints and depressive symptoms (r = 0.35, p = 0.05). Cognitive dysfunction is rather frequent in nSLE and seems to negatively impinge on social functioning.

Genetic variation in the nuclear factor kappaB pathway in relation to susceptibility to rheumatoid arthritis.

OBJECTIVE: To examine genetic association between rheumatoid arthritis (RA) and known polymorphisms in core genes of the nuclear factor (NF)kappaB pathway, the major intracellular pathway in RA pathogenesis. METHODS: Discovery and replication sample sets of Spanish patients with RA and controls were studied. A total of 181 single nucleotide polymorphisms (SNPs) uniformly spaced along the genomic sequences of 17 core genes of the NFkappaB pathway (REL, RELA, RELB, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, IKBKA, IKBKB, IKBKE, IKBKAP, KBRAS1, KBRAS2, MAP3K1, MAP3K14, TAX1BP1) were studied by mass spectrometry analysis complemented with 5'-nuclease fluorescence assays in the discovery set, 458 patients with RA and 657 controls. SNPs showing nominal significant differences were further investigated in the replication set of 1189 patients with RA and 1092 controls. RESULTS: No clear reproducible association was found, although 12 SNPs in IKBKB, IKBKE and REL genes showed significant association in the discovery set. Interestingly, two of the SNPs in the IKBKE gene, weakly associated in the discovery phase, showed a trend to significant association in the replication phase. Pooling both sample sets together, the association with these two SNPs was significant. CONCLUSION: We did not find any major effect among the explored members of the NFkappaB pathway in RA susceptibility. However, it is possible that variation in the IKBKE gene could have a small effect that requires replication in additional studies.

Combined therapy with rituximab plus cyclophosphamide/vincristine/prednisone for Sjogren's syndrome-associated B-cell non-Hodgkin's lymphoma.

Sjogren's syndrome (SS) is characterized by an increased risk of developing non-Hodgkin's lymphoma (NHL). Optimal treatment for NHL-complicating SS is not clearly established. NHL, which expresses the CD20 antigen on tumor cell surfaces, is a disease entity candidate to treatment with anti-CD20 monoclonal antibodies. We report clinical and immunological data of a patient with SS and NHL who was treated with a regimen consisting of cyclophosphamide/vincristine/prednisone (CVP) plus rituximab. A 68-year-old women had a 26-year history of SS and autoimmune thyroiditis. The clinical course of SS was complicated with severe splenomegaly. An increased percentage of CD19+ B cells (up to 30%) was detected in peripheral blood during follow-up. Clonal rearrangement of immunoglobulin heavy chain was detected. Low-grade B marginal zone lymphoma was diagnosed (peripheral blood immunophenotype: CD19+CD20+CD23+sIg+Kappa; bone marrow immunophenotype: 25% lymphocytes; CD19+CD20+CD79A/BCL2+). She received a total of six cycles of CVP plus rituximab (375 mg/m2). Therapy was well tolerated, and B lymphocytes were depleted from the peripheral blood. Splenomegaly normalized. No evidence of neoplastic infiltration was detected in bone marrow after completion of therapy, while certain symptoms of SS (sicca and arthralgia) improved with treatment. CVP plus rituximab proved effective in a patient with SS with NHL.

A double-blind placebo controlled trial of etanercept in patients with giant cell arteritis and corticosteroid side effects.

OBJECTIVE: Open label studies have suggested that tumour necrosis factor (TNF) antagonists led to sustained improvement and corticosteroid sparing effect in patients with giant cell arteritis (GCA). To confirm these observations, we conducted a randomised, double-blind, placebo controlled trial with etanercept in patients with biopsy-proven GCA with side effects secondary to corticosteroids. METHODS: We randomly assigned patients with GCA to receive etanercept (n = 8) or placebo (n = 9) over 1 year together with corticosteroids that were reduced according to a predefined schedule. The primary outcome was the ability to withdraw the corticosteroid therapy and control the disease activity at 12 months. RESULTS: Baseline characteristics were similar in the two groups, although patients in the etanercept group showed higher levels of basal glycaemia (p = 0.02) and a higher erythrocyte sedimentation rate (ESR) (p = 0.01). After 12 months, 50% of the patients in the etanercept group and 22.2% in the placebo group were able to control the disease without corticosteroid therapy (p value not significant). Patients in the etanercept group had a significant lower dose of accumulated prednisone during the first year of treatment (p = 0.03). There were no differences in the number and type of adverse events. CONCLUSION: The limited number of patients included in this study does not allow us to draw definitive conclusions. Etanercept therapy was well tolerated in this aged population. The therapeutic role of etanercept in patients with GCA should be evaluated in studies with a larger number of patients.