Accuracy of acute hyperglycemia as a biomarker of severe brain damage in children with traumatic brain injury.

PURPOSE: Biomarkers are substances measured at the systemic level to evaluate organic responses in certain situations, establishing diagnoses, disease staging, and prognosis. Blood glucose is a biomarker recognized as a predictor of prognosis in children victims of traumatic brain injury (TBI). The scope of this study was to identify the accuracy of blood glucose as a biomarker of severe brain injury. METHODS: A retrospective analytical study was conducted through the consecutive review of medical records of children and teenage victims of TBI who underwent neurological surgery between 2016 and 2023 in a level 1 trauma center. Two groups were compared: children with Glasgow Coma Scale (GCS) score ≤ 8 and children with GCS > 8. We calculated the predictive values to define the accuracy of blood glucose as a biomarker of brain injury. RESULTS: Ninety-two medical records were included for analysis. Hyperglycemia predominated in cases with GCS ≤ 8 (48% vs 3%; p < 0.0001; OR, 30; 95% CI, 5.9902-150.2448). The glycemic measurement considering the cutoff point of 200 mg/dL or 11.1 mmol/L showed a specificity of 97%, a positive predictive value of 86%, an accuracy of 84%, and a likelihood ratio for a positive test of 16. CONCLUSION: Victims with GCS ≤ 8 are 16 times more likely to develop acute hyperglycemia after TBI when compared to those with GCS > 8. Blood glucose is a biomarker with an accuracy of 84% to predict severe brain injury, considering the cutoff point of 200 mg/dL or 11.1 mmol/L.

Unveiling ecological/evolutionary insights in HIV viral load dynamics: Allowing random slopes to observe correlational changes to CpG-contents and other molecular and clinical predictors.

In the context of infectious diseases, the dynamic interplay between ever-changing host populations and viral biology demands a more flexible modeling approach than common fixed correlations. Embracing random-effects regression models allows for a nuanced understanding of the intricate ecological and evolutionary dynamics underlying complex phenomena, offering valuable insights into disease progression and transmission patterns. In this article, we employed a random-effects regression to model an observed decreasing median plasma viral load (pVL) among individuals with HIV in Mexico City during 2019-2021. We identified how these functional slope changes (i.e. random slopes by year) improved predictions of the observed pVL median changes between 2019 and 2021, leading us to hypothesize underlying ecological and evolutionary factors. Our analysis involved a dataset of pVL values from 7325 ART-naïve individuals living with HIV, accompanied by their associated clinical and viral molecular predictors. A conventional fixed-effects linear model revealed significant correlations between pVL and predictors that evolved over time. However, this fixed-effects model could not fully explain the reduction in median pVL; thus, prompting us to adopt random-effects models. After applying a random effects regression model-with random slopes and intercepts by year-, we observed potential "functional changes" within the local HIV viral population, highlighting the importance of ecological and evolutionary considerations in HIV dynamics: A notably stronger negative correlation emerged between HIV pVL and the CpG content in the pol gene, suggesting a changing immune landscape influenced by CpG-induced innate immune responses that could impact viral load dynamics. Our study underscores the significance of random effects models in capturing dynamic correlations and the crucial role of molecular characteristics like CpG content. By enriching our understanding of changing host-virus interactions and HIV progression, our findings contribute to the broader relevance of such models in infectious disease research. They shed light on the changing interplay between host and pathogen, driving us closer to more effective strategies for managing infectious diseases. SIGNIFICANCE OF THE STUDY: This study highlights a decreasing trend in median plasma viral loads among ART-naïve individuals living with HIV in Mexico City between 2019 and 2021. It uncovers various predictors significantly correlated with pVL, shedding light on the complex interplay between host-virus interactions and disease progression. By employing a random-slopes model, the researchers move beyond traditional fixed-effects models to better capture dynamic correlations and evolutionary changes in HIV dynamics. The discovery of a stronger negative correlation between pVL and CpG content in HIV-pol sequences suggests potential changes in the immune landscape and innate immune responses, opening avenues for further research into adaptive changes and responses to environmental shifts in the context of HIV infection. The study's emphasis on molecular characteristics as predictors of pVL adds valuable insights to epidemiological and evolutionary studies of viruses, providing new avenues for understanding and managing HIV infection at the population level.

Vigilancia activa en cáncer de próstata en un grupo de pacientes asistidos en el Centro Docente Asociado de Oncología Médica Rivera: Cooperativa Médica de Rivera (COMERI) / Active surveillance in prostate cancer in a group of patients assisted at the Rivera Associated Teaching Center for Medical Oncology: Rivera Medical Cooperative (COMERI) / Vigilância ativa do câncer de próstata em um grupo de pacientes atendidos no Rivera Associated Teaching Center for Medical Oncology: Rivera Medical Cooperative (COMERI)

Introducción: En Uruguay el cáncer de próstata ocupa el primer lugar en incidencia y el tercer lugar en mortalidad en el hombre. La mayoría de estos cánceres se diagnostican en estadios precoces. Hoy en día, para pacientes con adenocarcinoma de muy bajo riesgo, bajo riesgo o riesgo intermedio favorable, la vigilancia activa es una opción adecuada. Objetivos: Describir una población de pacientes con cáncer de próstata de muy bajo riesgo, bajo riesgo o riesgo intermedio favorable, en vigilancia activa en COMERI. Material y métodos: Estudio descriptivo, observacional, retrospectivo. Se incluyeron pacientes con cáncer de próstata de muy bajo riesgo, bajo riesgo o riesgo intermedio favorable, tratados entre 2010 y 2018 en COMERI. Se recopilaron datos en el sistema de registro clínico electrónico. Resultados: Se incluyeron 33 pacientes, la mediana de edad al diagnóstico fue de 74 años. Todos los pacientes fueron sometidos a controles clínicos y determinación de PSA cada 3 meses. El tacto rectal se realizó en forma anual. El tiempo mediano de vigilancia activa fue de 33 meses. Durante el seguimiento, se observaron pocas variaciones en los valores de PSA. El 21% de los pacientes fue sometido a una nueva biopsia durante el seguimiento activo, y en todos los casos, el Gleason se mantuvo incambiado. Ningún paciente abandonó la modalidad de vigilancia activa. Conclusión: En nuestro entorno, la vigilancia activa se considera una opción terapéutica válida para pacientes altamente seleccionados con cáncer de próstata de muy bajo riesgo, bajo riesgo o riesgo intermedio favorable, y es bien aceptada por ellos.

Introduction: In Uruguay, prostate cancer ranks first in incidence and third in mortality among men. The majority of these cancers are diagnosed at early stages. Nowadays, active surveillance is an appropriate option for patients with adenocarcinoma of very low risk, low risk, or favorable intermediate risk. Objectives: To describe a population of patients with prostate cancer of very low risk, low risk, or favorable intermediate risk under active surveillance at COMERI. Materials and Methods: Descriptive, observational, retrospective study. Patients with prostate cancer of very low risk, low risk, or favorable intermediate risk treated between 2010 and 2018 at COMERI were included. Data were collected from the electronic clinical registry system. Results: Thirty-three patients were included, with a median age at diagnosis of 74 years. All patients underwent clinical monitoring and PSA determination every 3 months. Digital rectal examination was performed annually. The median time of active surveillance was 33 months. During follow-up, there were few variations in PSA values. 21% of patients underwent a repeat biopsy during active surveillance, and in all cases, the Gleason score remained unchanged. No patient discontinued active surveillance. Conclusion: In our setting, active surveillance is considered a valid therapeutic option for highly selected patients with prostate cancer of very low risk, low risk, or favorable intermediate risk, and it is well accepted by them.

Introdução: No Uruguai, o câncer de próstata ocupa o primeiro lugar em incidência e o terceiro lugar em mortalidade entre os homens. A maioria desses cânceres é diagnosticada em estágios precoces. Atualmente, para pacientes com adenocarcinoma de risco muito baixo, baixo risco ou risco intermediário favorável, a vigilância ativa é uma opção adequada. Objetivos: Descrever uma população de pacientes com câncer de próstata de risco muito baixo, baixo risco ou risco intermediário favorável sob vigilância ativa em COMERI. Material e métodos: Estudo descritivo, observacional, retrospectivo. Foram incluídos pacientes com câncer de próstata de risco muito baixo, baixo risco ou risco intermediário favorável, tratados entre 2010 e 2018 em COMERI. Os dados foram coletados no sistema de registro clínico eletrônico. Resultados: Foram incluídos 33 pacientes, com mediana de idade no diagnóstico de 74 anos. Todos os pacientes foram submetidos a controles clínicos e determinação de PSA a cada 3 meses. O toque retal foi realizado anualmente. O tempo médio de vigilância ativa foi de 33 meses. Durante o acompanhamento, houve poucas variações nos valores de PSA. 21% dos pacientes foram submetidos a uma nova biópsia durante a vigilância ativa, e em todos os casos, o Gleason permaneceu inalterado. Nenhum paciente abandonou a modalidade de vigilância ativa. Conclusão: Em nosso ambiente, a vigilância ativa é considerada uma opção terapêutica válida para pacientes altamente selecionados com câncer de próstata de risco muito baixo, baixo risco ou risco intermediário favorável, e é bem aceita por eles.

Identifying metabolic parameters related to severity and extent of periodontitis in down syndrome patients.

BACKGROUND AND OBJECTIVE: Systemic metabolic status and periodontitis can be related in patients with Down syndrome (DS). The objective of this study was to identify metabolic indicators (anthropometric measurements, blood pressure, and serum markers) related to severity and extent of periodontitis in DS patients. METHODS: A cross-sectional study was conducted with 49 patients with DS. Periodontal evaluation included the periodontal probing depth (PPD), clinical attachment level (CAL), gingival bleeding index (GBI), and visible plaque index (VPI). Periodontitis severity was classified by the stages system. The extent of periodontitis was assessed as the percentage of sites with CAL ≥3 mm, CAL ≥4 mm, PPD ≥4 mm, and PPD ≥5 mm. The metabolic condition of the participants was determined by analyzing anthropometric parameters, blood pressure, and serum markers. Data were analyzed using the Mann-Whitney test, Spearman's correlation coefficient, and multivariate regression analysis. RESULTS: Periodontitis stage 3/4 was detected in 32.7% of patients, with high values of VPI (54.6 ± 35.8) and GBI (42.4 ± 33.3). The severity of periodontitis was related to higher mean corpuscular hemoglobin (ß = .291, p = .028) and mean corpuscular volume values (ß = .293, p = .046). Arm circumference measurements were inversely related to CAL ≥3 mm (ß = -.408, p = .023), PPD ≥4 mm (ß = -.475, p = .006), and PPD ≥5 mm (ß = -.443, p = .010). CONCLUSIONS: The findings suggest that the severity and extent of periodontitis may be related to some metabolic parameters in DS patients.

Experimental infectious challenge in pigs leads to elevated fecal calprotectin levels following colitis, but not enteritis.

BACKGROUND: Fecal calprotectin is largely applied as a non-invasive intestinal inflammation biomarker in human medicine. Previous studies in pigs investigated the levels of fecal calprotectin in healthy animals only. Thus, there is a knowledge gap regarding its application during infectious diarrhea. This study investigated the usefulness of fecal calprotectin as a biomarker of intestinal inflammation in Brachyspira hyodysenteriae and Salmonella Typhimurium infected pigs. RESULTS: Fecal samples from pigs with colitis (n = 18) were collected from animals experimentally inoculated with B. hyodysenteriae (n = 8) or from sham-inoculated controls (n = 3). Fecal samples from pigs with enteritis (n = 14) were collected from animals inoculated with Salmonella enterica serovar Typhimurium (n = 8) or from sham-inoculated controls (n = 4). For both groups, fecal samples were scored as: 0 = normal; 1 = soft, wet cement; 2 = watery feces; 3 = mucoid diarrhea; and 4 = bloody diarrhea. Fecal calprotectin levels were assayed using a sandwich ELISA, a turbidimetric immunoassay and a point-of-care dipstick test. Fecal calprotectin levels were greater in colitis samples scoring 4 versus ≤ 4 using ELISA, and in feces scoring 3 and 4 versus ≤ 1 using immunoturbidimetry (P < 0.05). No differences were found in calprotectin concentration among fecal scores for enteritis samples, regardless of the assay used. All samples were found below detection limits using the dipstick method. CONCLUSIONS: Fecal calprotectin levels are increased following the development of colitis, but do not significantly change due to enteritis. While practical, the use of commercially available human kits present sensitivity limitations. Further studies are needed to validate the field application of calprotectin as a marker of intestinal inflammation.

Nonsurgical periodontal therapy decreases the severity of rheumatoid arthritis and the plasmatic and salivary levels of RANKL and Survivin: a short-term clinical study.

AIM: To investigate the influence of nonsurgical periodontal treatment (NSPT) on clinical periodontal status, rheumatoid arthritis (RA) activity, and plasmatic and salivary levels of biomarkers through a controlled clinical trial on individuals with RA and periodontitis (PE). METHODS: Sixty-six individuals from a convenience sample were considered eligible and consecutively allocated in 3 groups: (1) individuals without PE and RA (-PE-RA, n = 19); (2) individuals without PE and with RA (-PE+RA, n = 23), and (3) individuals with PE and RA (+PE+RA, n = 24). Full-mouth periodontal clinical examinations, Disease Activity Score (DAS-28) evaluations, and analysis in plasma and saliva of RANKL, OPG, RANKL/OPG, and Survivin were performed at baseline (T1) and 45 days after NSPT (T2). RESULTS: NSPT in the +PE+RA group was very effective to improve periodontal condition. At T2, significant reductions in DAS-28 were observed in +PE+RA (p = 0.011). Significantly higher levels of Survivin and RANKL were observed in saliva and plasma from RA individuals (with and without PE) compared to controls. Additionally, Survivin e RANKL demonstrated positive correlations with DAS-28 and an expressively significant reduction in +PE+RA at T2 (p < 0.001). CONCLUSIONS: NSPT was effective on improving both the periodontal and the RA clinical status and reducing the concentration of Survivin and RANKL in saliva and plasma. PRACTICAL IMPLICATIONS: Nonsurgical periodontal treatment was effective on reducing the concentration of Survivin and RANKL and on improving both the periodontal and the RA clinical status of affected individuals. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials (ReBEC) protocol #RBR-8g2bc8 ( http://www.ensaiosclinicos.gov.br/rg/RBR-8g2bc8/ ).

Plasma interleukin-6 levels correlate with survival in patients with bacterial sepsis and septic shock.

In this study, IL-6 levels were assessed as inflammatory biomarker of bacterial sepsis in patients hospitalized at the ICU of the hospital of Colombia. Materials and methods: Prospective study on 62 patients diagnosed with sepsis and septic shock. An ELISA assay was used to test serum levels of IL-6 at admission and 48 h after admission. Variables were analyzed by χ2 test (alfa <0.05). Multivariable Cox regression was used to determine the survival with the statistical program SPSS v23.00. Results: Patient's median age was 53 years old and 59.7% were male. Lung was the most common primary site of infection (43.5%), and hypertension comorbidity with higher prevalence (40%). Infection by Gram negative bacteria were significantly more frequent among patients than Gram positive (P = 0.037). Overall, survival analysis showed that 10 (16.1%) patients died with a survival median of 7.00 +4.874 (2-3) days. In patients with sepsis we detected a significant decline in the average of IL-6 serum levels after 48 h of admission [7.50 (SD: 7.00-68.00) pg/mL vs. 68.00 [SD: 7.00-300.00] pg/mL (P = 0.000). Only 25% of patients with septic shock who presented high levels of IL-6 at the time of admission and at 48 h had a survival up to 15 days (P = 0.005). Conclusion: We found significant differences between the plasma levels of IL-6 during the first 48 h after admission to the ICU among patients with sepsis and septic shock. Patients with sepsis had a significant decline in IL-6 levels, whereas in patients who developed septic shock, levels of this cytokine remained high and have a lower survival compared to those who maintained low levels of IL-6.

Biomarcadores na bexiga hiperativa: artigo de revisão / Biomarkers in overactive bladder: review article

A bexiga hiperativa caracteriza-se pela urgência miccional, geralmente acompa- nhada de noctúria e aumento da frequência urinária. Trata-se de afecção preva- lente, com enorme comprometimento da qualidade de vida, em todos os seus as- pectos. Diversos biomarcadores vêm sendo estudados para melhor caracterização dos diferentes fenótipos da afecção, entre eles as neurotrofinas urinárias, o ATP, a genômica e a microbiota urinária. Acredita-se que tal caracterização poderá ter implicações para prevenção, fisiopatologia e individualização do tratamento.(AU)

The overactive bladder is characterized by urinary urgency, usually accompanied by nocturia and increased urinary frequency. It is a prevalent condition, with enormous impairment of quality of life, in all its aspects. Several biomarkers have been studied to better characterize the different phenotypes of the condition, including urinary neurotrophins, ATP, genomics and urinary microbiota. It is believed that such charac- terization may have implications for prevention, pathophysiology and individualiza- tion of treatment.(AU)

Evaluation of monocyte to HDL cholesterol ratio and other inflammatory markers in patients with psoriasis

Abstract Background Psoriasis is a chronic systemic inflammatory disease frequently associated with serious comorbidities. Objectives To investigate the systemic inflammatory burden in psoriasis and to assess the correlation between traditional and novel inflammatory markers and the severity of the disease. Methods This cross-sectional study was conducted on 60 patients with psoriasis vulgaris and 50 healthy volunteers. Data including demographics, Psoriasis Area and Severity Index scores, and laboratory results were analyzed and compared. Results Compared with the control group, the psoriatic patients had significantly higher high sensitive C-reactive protein, serum amyloid A, erythrocyte sedimentation rate, leukocyte, neutrophil, neutrophil-to-lymphocyte ratio, monocyte to high density lipoprotein (HDL) cholesterol ratio, and aspartate aminotransferase levels, and significantly lower HDL cholesterol levels (p < 0.05). No significant difference was found in procalcitonin, lymphocyte, monocyte, hemoglobin, red blood cell distribution width, platelet, mean platelet volume, platelet distribution width, lymphocyte-to-monocyte ratio, anti-cyclic citrullinated peptide, glucose, alanine aminotransaminase, blood urea nitrogen, creatinine, triglyceride, total cholesterol, and LDL cholesterol levels between the two groups (p > 0.05). The Psoriasis Area and Severity Index score was positively correlated with high-sensitivity C-reactive protein, serum amyloid A, and monocyte to HDL cholesterol ratio, and negatively correlated with lymphocyte-to-monocyte ratio (p < 0.05). Study limitations This was a single-center study with relatively limited numbers of patients and controls. Conclusions The data show that high sensitivity C-reactive protein, serum amyloid A, erythrocyte sedimentation rate, neutrophil-to-lymphocyte ratio, and monocyte to HDL cholesterol ratio can be used as markers of systemic inflammation in patients with psoriasis. Moreover, high sensitivity C-reactive protein, serum amyloid A, monocyte to HDL cholesterol ratio and lymphocyte-to-monocyte ratio are closely related to the Psoriasis Area and Severity Index score, and they may be regarded as objective indicators in determining the disease severity.

Childhood trauma, psychiatric disorders, and criminality in women: Associations with serum levels of brain-derived neurotrophic factor.

Psychiatric disorders and childhood trauma are highly prevalent in female inmates. Brain-derived neurotrophic factor (BDNF) plays a number of roles in neuronal survival, structure, and function. Data in the literature suggest that it is a neurobiological substrate that moderates the impact of childhood adversities on the late expression of psychiatric disorders. The aim of this study was to determine whether five childhood trauma subtypes-physical abuse, sexual abuse, emotional abuse, physical neglect, and emotional neglect-are associated with adult psychiatric disorders, BDNF levels, and criminality among incarcerated women. This was a cross-sectional study involving a consecutive sample of 110 women, divided into three groups of women (forensic - mentally ill who committed crimes, clinical psychiatric inpatients and healthy controls). The Childhood Trauma Questionnaire and the Mini-International Neuropsychiatric Interview-Plus were applied in the whole sample, and BDNF levels were measured in a sub-sample of 54 women. The rates of mental illness and childhood trauma were high in the forensic group. Emotional abuse was higher in the clinical and forensic groups than in the healthy control group. Lower BDNF levels were associated with emotional abuse in the forensic group as well as with sexual abuse in the healthy control group. After multinomial logistic regression, lower levels of BDNF, higher levels of emotional abuse and the presence of familial offense were considered factors related to clinical psychiatric group. The results of this study underscore the idea that BDNF may be an important factor related to the development of diseases and criminality in women who are victims of childhood trauma, becoming a possible biological marker.

Evaluation of monocyte to HDL cholesterol ratio and other inflammatory markers in patients with psoriasis.

BACKGROUND: Psoriasis is a chronic systemic inflammatory disease frequently associated with serious comorbidities. OBJECTIVES: To investigate the systemic inflammatory burden in psoriasis and to assess the correlation between traditional and novel inflammatory markers and the severity of the disease. METHODS: This cross-sectional study was conducted on 60 patients with psoriasis vulgaris and 50 healthy volunteers. Data including demographics, Psoriasis Area and Severity Index scores, and laboratory results were analyzed and compared. RESULTS: Compared with the control group, the psoriatic patients had significantly higher high sensitive C-reactive protein, serum amyloid A, erythrocyte sedimentation rate, leukocyte, neutrophil, neutrophil-to-lymphocyte ratio, monocyte to high density lipoprotein (HDL) cholesterol ratio, and aspartate aminotransferase levels, and significantly lower HDL cholesterol levels (p < 0.05). No significant difference was found in procalcitonin, lymphocyte, monocyte, hemoglobin, red blood cell distribution width, platelet, mean platelet volume, platelet distribution width, lymphocyte-to-monocyte ratio, anti-cyclic citrullinated peptide, glucose, alanine aminotransaminase, blood urea nitrogen, creatinine, triglyceride, total cholesterol, and LDL cholesterol levels between the two groups (p > 0.05). The Psoriasis Area and Severity Index score was positively correlated with high-sensitivity C-reactive protein, serum amyloid A, and monocyte to HDL cholesterol ratio, and negatively correlated with lymphocyte-to-monocyte ratio (p < 0.05). STUDY LIMITATIONS: This was a single-center study with relatively limited numbers of patients and controls. CONCLUSIONS: The data show that high sensitivity C-reactive protein, serum amyloid A, erythrocyte sedimentation rate, neutrophil-to-lymphocyte ratio, and monocyte to HDL cholesterol ratio can be used as markers of systemic inflammation in patients with psoriasis. Moreover, high sensitivity C-reactive protein, serum amyloid A, monocyte to HDL cholesterol ratio and lymphocyte-to-monocyte ratio are closely related to the Psoriasis Area and Severity Index score, and they may be regarded as objective indicators in determining the disease severity.

Development of New Serum Biomarkers for Early Lymphedema Detection.

Background: Early lymphedema detection may reduce the symptoms and improve clinical outcomes. However, the lack of reliable serum biomarkers capable of predicting lymphedema development is a current medical problem. In this study, we investigated if serum levels of hyaluronic acid (HA) and leukotriene B4 (LTB4), two molecules involved in lymphedema development, may work as predictors of this condition. Methods and Results: A mouse model of acquired lymphedema was generated through ablation of tail dermal lymphatic network. Tail diameter was measured daily, and HA and LTB4 serum levels were analyzed before and during the development of lymphedema. We found increased serum levels of HA and reduced levels of LTB4 at early days before the appearance of lymphedema signs. Similar results were observed in the lymphedema tissue. Increased local and systemic inflammation was also detected at early time points. Moreover, the ratio LTB4/HA arises as the strongest predictor for lymphedema development. In fact, we found an inverse correlation in our model, where reduced LTB4/HA levels showed increased lymphedema signs. Conclusions: These findings suggest that serum ratio of LTB4/HA may be a useful biomarker to predict acquired lymphedema development, with potential to be used in clinical conditions such as breast cancer patients.

Efeito do tratamento periodontal não cirúrgico em indivíduos com artrite reumatóide e periodontite: aspectos epidemiológicos, clínicos, microbiológicos e biomarcadores / Effect of non-surgical periodontal treatment in individuals with rheumatoid arthritis and periodontitis: epidemiological, clinical, microbiological and biomarkers aspects

Objetivos: Evidências atuais reconhece que a periodontite (PE) e a artrite reumatóide (AR) compartilham comuns fatores de risco e alguns caminhos fisiopatológicos semelhantes, como inflamação crônica induzida por citocinas pró-inflamatórias e destruição de tecidos conjuntivos e ósseos. Assim, esta tese apresenta quatro estudos da possível associação entre PE e AR com os seguintes objetivos: avaliar a condição periodontal, gravidade e extensão da periodontite e aspectos clínicos e epidemiológicos da sua associação com a AR. Investigar a influência do tratamento periodontal não cirúrgico (TPNS) sobre os parâmetros clínicos periodontais, níveis bacterianos de A. actinomycetemcomitans, P. gingivalis, T. forsythia, T dentícola e a atividade da AR (DAS28). Adicionalmente quantificar níveis sanguíneos e salivares dos biomarcadores RANKL, OPG, RANKL / OPG, Survivina, e anticorpos antipeptídeos citrulinados cíclicos (ACPAs) e anti-carbamiladas (Anti-CarP). Métodos: A amostra do estudo foi composta por um total de 471 indivíduos divididos aleatoriamente em grupos, de acordo com o objetivo de cada estudo. O ensaio clínico realizou as seguintes avaliações no início do estudo (T1) e 45 dias (T2) após TPNC: exames periodontais de boca completa, análise microbiológica por meio de qPCR em tempo real, avaliações do Disease Activity Score (DAS-28). Em adição, a quantificação de biomarcadores e anticorpos Anti-Carp e ACPAs realizada por meio de ELISA no soro/saliva. Resultados: O presente estudo reportou uma alta prevalência de PE em indivíduos com AR e uma importante associação entre ocorrência, gravidade e extensão da PE associadas à AR e ao tabagismo. O tratamento periodontal não cirúrgico foi eficaz em melhorar a condição cliníca periodontal, reduziu a presença dos patógenos periodontais avaliados e melhorou o quadro clínico da AR (redução dos escores de DAS-28). Adicionalmente, reduziu os níveis de survivina, RANKL e concentração de ACPAs e Anti-CarP. Conclusão: Nossos achados corroboram a robustez das evidências científicas da associação entre periodontite e AR. Assim, o controle da infecção periodontal em pacientes com AR e PE pode ser uma importante ferramenta terapêutica no controle da AR.

Objectives: Current evidence recognizes that periodontitis (PE) and rheumatoid arthritis (RA) share common risk factors and some similar pathophysiological pathways, such as chronic inflammation induced by pro-inflammatory cytokines and destruction of connective and bone tissues. Thus, this thesis presents four studies of the possible association between PE and RA with the following objectives: to assess the periodontal condition, severity and extent of periodontitis and the clinical and epidemiological aspects of its association with RA. To investigate the influence of non-surgical periodontal treatment (TPNS) on the periodontal clinical parameters, bacterial levels of A. actinomycetemcomitans, P. gingivalis, T. forsythia, T dentic and the activity of RA (DAS28). In addition to quantify blood and salivary levels of the biomarkers RANKL, OPG, RANKL / OPG, Survivina, and cyclic citrullinated anti-peptide antibodies (ACPAs) and anti-carbamylates (Anti-CarP). Methods: The study sample consisted of a total of 471 individuals randomly divided into groups, according to the objective of each study. The clinical trial performed the following assessments at baseline (T1) and 45 days (T2) after TPNC: periodontal examinations of full mouth, microbiological analysis using real-time qPCR, assessments of the Disease Activity Score (DAS-28). In addition, the quantification of biomarkers and Anti-Carp antibodies and ACPAs performed by ELISA in serum / saliva. Results: The present study reported a high prevalence of PE in individuals with RA and an important association between the occurrence, severity and extent of PE associated with RA and smoking. The non-surgical periodontal treatment was effective in improving the clinical periodontal condition, reduced the presence of the periodontal pathogens evaluated and improved the clinical picture of RA (reduced DAS-28 scores). Additionally, it reduced the levels of survivin, RANKL and concentration of ACPAs and Anti-CarP. Conclusion: Our findings corroborate the robustness of the scientific evidence on the association between periodontitis and RA. Thus, the control of periodontal infection in patients with RA and PE can be an important therapeutic tool in the control of RA.

Vitamin D Receptor Gene Polymorphisms Are Associated With Leprosy in Southern Brazil.

Vitamin D, together with its nuclear receptor (VDR), plays an important role in modulating the immune response, decreasing the inflammatory process. Some polymorphisms of the VDR gene, such as BsmI (G>A rs1544410), ApaI (G>T rs7975232), and TaqI (T>C rs731236) could affect its stability and mRNA transcription activity, while FokI T>C (rs2228570) gives a truncated protein with three fewer amino acids and more efficiency in binding vitamin D. This study evaluated these four polymorphisms in the immunopathogenesis of leprosy in 404 patients and 432 control individuals without chronic or infectious disease in southern Brazil. When analyzing differences in the allele and genotype frequency of polymorphisms between patients (leprosy per se, multibacillary, and paucibacillary clinical forms) and controls, we found no statistically significant association. Regarding haplotype analysis, the bAt haplotype was associated with protection from leprosy per se (P = 0.004, OR = 0.34, CI = 0.16-0.71) and from the multibacillary clinical form (P = 0.005, OR = 0.30, CI = 0.13-0.70). In individuals aged 40 or more years, this haplotype has also showed protection against leprosy per se and multibacillary (OR = 0.26, CI = 0.09-0.76; OR = 0.26, CI = 0.07-0.78, respectively), while the BAt haplotype was a risk factor for leprosy per se in the same age group (OR = 1.34, CI = 1.04-1.73). In conclusion, despite having found no associations between the VDR gene polymorphisms with the development of leprosy, the haplotypes formed by the BsmI, ApaI, and TaqI polymorphisms were associated with leprosy per se and the multibacillary clinical form.

A Clinical Staging Model for Obsessive-Compulsive Disorder: Is It Ready for Prime Time?

Recent changes to the diagnostic classification of obsessive-compulsive disorder (OCD), including its removal from the anxiety/neurotic, stress-related and somatoform disorders chapters of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and International Classification of Diseases 11th Revision (ICD-11), are based on growing evidence of unique pathogenic signatures and linked diagnostic and treatment approaches. In this review, we build on these recent developments and propose a 'clinical staging model' of OCD that integrates the severity of symptoms and phase of illness for personalised case management. A clinical staging model is especially relevant for the early identification and management of subthreshold OCD - a substantial and largely neglected portion of the population who, despite having milder symptoms, experience harms that may impact personal relationships, work-related functioning and productivity. Research on the pathogenesis, classification and management of such cases is needed, including the development of new outcomes measures that prove sensitive to changes in future clinical trials. Early intervention strategies in OCD are likely to yield better long-term outcomes.

Schizophrenia TreAtment with electRic Transcranial Stimulation (STARTS): design, rationale and objectives of a randomized, double-blinded, sham-controlled trial / Tratamento da esquizofrenia com estimulação transcraniana por corrente contínua (ETCC): fundamentação teórica e objetivos de um ensaio clínico randomizado, duplo-cego, controlado por simulação

Abstract Introduction Schizophrenia is a severe mental disorder. While some antipsychotic medications have demonstrated efficacy in treating positive symptoms, there is no widely recognized treatment for negative symptoms, which can cause significant distress and impairment for patients with schizophrenia. Here we describe the rationale and design of the STARTS study (Schizophrenia TreAtment with electRic Transcranial Stimulation), a clinical trial aimed to test the efficacy of a non-pharmacological treatment known as transcranial direct current stimulation (tDCS) for treating the negative symptoms of schizophrenia Methods The STARTS study is designed as a randomized, sham-controlled, double-blinded trial evaluating tDCS for the treatment of the negative symptoms of schizophrenia. One-hundred patients will be enrolled and submitted to 10 tDCS sessions over the left dorsolateral prefrontal cortex (anodal stimulation) and left temporoparietal junction (cathodal stimulation) over 5 consecutive days. Participants will be assessed using clinical and neuropsychological tests before and after the intervention. The primary outcome is change in the Positive and Negative Syndrome Scale (PANSS) negative subscale score over time and across groups. Biological markers, including blood neurotrophins and interleukins, genetic polymorphisms, and motor cortical excitability, will also be assessed. Results The clinical results will provide insights about tDCS as a treatment for the negative symptoms of schizophrenia, and the biomarker investigation will contribute towards an improved understanding of the tDCS mechanisms of action. Conclusion Our results could introduce a novel therapeutic technique for the negative symptoms of schizophrenia. Clinical trial registration: ClinicalTrials.gov, NCT02535676 .

Resumo Introdução A esquizofrenia é um transtorno mental grave. Embora alguns medicamentos antipsicóticos tenham demonstrado eficácia no tratamento de sintomas positivos, não há tratamento amplamente reconhecido para sintomas negativos, o que pode causar sofrimento e prejuízo significativos para pacientes com esquizofrenia. Aqui descrevemos a fundamentação teórica e o design do estudo STARTS (Schizophrenia TreAtment with electRic Transcranial Stimulation), um ensaio clínico destinado a testar a eficácia de um tratamento não farmacológico conhecido como estimulação transcraniana por corrente contínua (ETCC) para tratar os sintomas negativos da esquizofrenia. Métodos O estudo STARTS foi concebido como um ensaio clínico randomizado, controlado por simulação, duplo-cego, avaliando a ETCC para o tratamento dos sintomas negativos da esquizofrenia. Cem pacientes serão incluídos e submetidos a 10 sessões de ETCC sobre o córtex pré-frontal dorsolateral esquerdo (estimulação anódica) e a junção temporoparietal esquerda (estimulação catodal) durante 5 dias consecutivos. Os participantes serão avaliados através de testes clínicos e neuropsicológicos antes e após a intervenção. O desfecho primário é a mudança na pontuação da subescala negativa da Escala da Síndrome Positiva e Negativa (Positive and Negative Syndrome Scale [PANSS]) ao longo do tempo e entre os grupos. Marcadores biológicos, incluindo neurotrofinas e interleucinas do sangue, polimorfismos genéticos e excitabilidade cortical motora, também serão avaliados. Resultados Os resultados clínicos fornecerão informações sobre a ETCC como um tratamento para os sintomas negativos da esquizofrenia, e a investigação dos biomarcadores contribuirá para uma melhor compreensão dos mecanismos de ação da ETCC. Conclusão Nossos resultados podem trazer uma nova técnica terapêutica para o tratamento dos sintomas negativos da esquizofrenia. Registro do ensaio clínico: ClinicalTrials.gov, NCT02535676.

The first postoperative-stimulated serum thyroglobulin is a prognostic factor for thyroid microcarcinomas / A primeira dosagem sérica de tireoglobulina estimulada pós-operatória é um fator prognóstico para os microcarcinomas da tireoide

Abstract Introduction: Endogenous thyroid-stimulating hormone-stimulated thyroglobulin collected after total thyroidectomy is a useful predictor of better prognosis in patients with differentiated thyroid carcinomas in general, but studies with microcarcinomas are scarce. Objective: To assess whether the first postoperative stimulated thyroglobulin measurement is a prognostic factor in patients with microcarcinoma. Methods: The medical data of 150 differentiated thyroid carcinoma patients were studied retrospectively, and 54 (36%) cases with microcarcinoma were selected. The first postoperative stimulated thyroglobulin (1st stimulated thyroglobulin), measured after thyroidectomy, initial presentation data, and microcarcinomas treatment were assessed regarding outcome. Worse prognosis was defined as neoplasm persistence/recurrence. Results: Persistence/recurrence occurred in 27.8% of the cases. These patients were identified according to the following parameters: receiving more than one 131iodine dose (100% vs. 0%; p < 0.0001); accumulated 131iodine dose (232.14 ± 99.09 vs. 144 ± 33.61 mCi; p < 0.0001); presented active disease in the last assessment (53.3% vs. 0%; p < 0.0001); follow-up time (103.07 ± 61.27 vs. 66.85 ± 70.14 months; p = 0.019); and 1st stimulated thyroglobulin (19.01 ± 44.18 vs. 2.19 ± 2.54 ng/dL; p < 0.0001). After multivariate logistic regression, only the 1stSTg [odds ratio = 1.242; 95% confidence interval: 1.022-1.509; p = 0.029] and follow-up time (odds ratio = 1.027; 95% confidence interval: 1.007-1.048; p = 0.007) were independent predictors of risk of persistence/recurrence. The cutoff point of 1.6 ng/dL for the 1st stimulated thyroglobulin was significantly associated with disease persistence/recurrence [area under the curve = 0.713 (p = 0.019)]. Conclusion: The first stimulated thyroglobulin predicted disease persistence/recurrence in patients with microcarcinoma.

Resumo Introdução: A tireoglobulina estimulada pelo hormônio tireoestimulante endógeno coletada após tireoidectomia total é um preditor útil de melhor prognóstico em pacientes com carcinomas diferenciados de tireoide em geral, mas os estudos com microcarcinomas são escassos. Objetivo: Avaliar se a primeira medida pós-operatória de tireoglobulina estimulada é um fator prognóstico em pacientes com microcarcinoma. Método: Os dados clínicos de 150 pacientes com carcinoma diferenciado de tireoide foram estudados retrospectivamente e 54 (36%) casos com microcarcinoma foram selecionados. A primeira dosagem de tireoglobulina estimulada (1a TgE) pós-operatória, medida após a tireoidectomia, os dados da apresentação inicial e tratamento do microcarcinoma foram avaliados quanto ao resultado. O pior prognóstico foi definido como a persistência/recorrência da neoplasia. Resultados: A persistência/recorrência ocorreu em 27,8% dos casos. Esses pacientes foram identificados de acordo com os seguintes parâmetros: receberam mais de uma dose de iodo131 (100% vs. 0%; p < 0,0001); dose acumulada de iodo131 (232,14 ± 99,09 vs. 144 ± 33,61 mCi; p < 0,0001); apresentou doença ativa na última avaliação (53,3% vs. 0%; p < 0,0001); tempo de seguimento (103,07 ± 61,27 vs. 66,85 ± 70,14 meses; p = 0,019); e 1ªTgE (19,01 ± 44,18 vs. 2,19 ± 2,54 ng/dL; p < 0,0001). Após a regressão logística multivariada, apenas a 1ª TgE [odds ratio = 1.242; intervalo de confiança de 95%: 1,022-1,509; p = 0,029] e tempo de seguimento (odds ratio = 1,027; intervalo de confiança de 95%: 1,007-1,048; p = 0,007) foram preditores independentes de risco de persistência/recorrência. O ponto de corte de 1,6 ng/dL para a 1a TgE foi significativamente associado à persistência/recidiva da doença [área abaixo da curva = 0,713 (p = 0,019)]. Conclusão: A 1ª dosagem sérica de tireoglobulina estimulada previu a persistência/recorrência da doença em pacientes com microcarcinoma.

The impact of implant abutment surface treatment with TiO2 on peri-implant levels of angiogenesis and bone-related markers: a randomized clinical trial.

The goal of this randomized, blinded, split-mouth controlled clinical trial was to assess the influence of abutment surface treatment on tissue healing. Fifteen patients received two implants distributed randomly to two groups: test (TiO2 abutment surface), control (standard abutment surface). Levels of epidermal growth factor (EGF), bone morphogenetic protein 9 (BMP-9), endothelin 1 (ET-1), fibroblast growth factor (FGF), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) were quantified in the peri-implant fluid after 3, 14, 30, and 60 days. Inter-group comparisons indicated higher levels of EGF, BMP-9, ET-1, FGF, and PlGF in the test group after 30days (P<0.05). PlGF levels were also higher in the test group after 60 days. In the test group, intra-group analysis revealed different levels of ET-1 and FGF between days 3 and 30, and days 3 and 60 (P<0.05); furthermore, VEGF levels were significantly higher on day 60 than on day 3 (P <0.05). In the control group, intra-group analysis demonstrated significantly different levels of ET-1, FGF, and PlGF between days 3 and 60 and of PlGF between days 14 and 60 (P<0.05). In conclusion, abutment surfaces treated with TiO2 influenced the levels of angiogenesis and bone-related markers.

The first postoperative-stimulated serum thyroglobulin is a prognostic factor for thyroid microcarcinomas.

INTRODUCTION: Endogenous thyroid-stimulating hormone-stimulated thyroglobulin collected after total thyroidectomy is a useful predictor of better prognosis in patients with differentiated thyroid carcinomas in general, but studies with microcarcinomas are scarce. OBJECTIVE: To assess whether the first postoperative stimulated thyroglobulin measurement is a prognostic factor in patients with microcarcinoma. METHODS: The medical data of 150 differentiated thyroid carcinoma patients were studied retrospectively, and 54 (36%) cases with microcarcinoma were selected. The first postoperative stimulated thyroglobulin (1st stimulated thyroglobulin), measured after thyroidectomy, initial presentation data, and microcarcinomas treatment were assessed regarding outcome. Worse prognosis was defined as neoplasm persistence/recurrence. RESULTS: Persistence/recurrence occurred in 27.8% of the cases. These patients were identified according to the following parameters: receiving more than one 131iodine dose (100% vs. 0%; p<0.0001); accumulated 131iodine dose (232.14±99.09 vs. 144±33.61mCi; p<0.0001); presented active disease in the last assessment (53.3% vs. 0%; p<0.0001); follow-up time (103.07±61.27 vs. 66.85±70.14 months; p=0.019); and 1st stimulated thyroglobulin (19.01±44.18 vs. 2.19±2.54ng/dL; p<0.0001). After multivariate logistic regression, only the 1stSTg [odds ratio=1.242; 95% confidence interval: 1.022-1.509; p=0.029] and follow-up time (odds ratio=1.027; 95% confidence interval: 1.007-1.048; p=0.007) were independent predictors of risk of persistence/recurrence. The cutoff point of 1.6ng/dL for the 1st stimulated thyroglobulin was significantly associated with disease persistence/recurrence [area under the curve=0.713 (p=0.019)]. CONCLUSION: The first stimulated thyroglobulin predicted disease persistence/recurrence in patients with microcarcinoma.

Clinical attachment loss and molecular profile of inflamed sites before treatment

Abstract Objective: To monitor early periodontal disease progression and to investigate clinical and molecular profile of inflamed sites by means of crevicular fluid and gingival biopsy analysis. Methodology: Eighty-one samples of twenty-seven periodontitis subjects and periodontally healthy individuals were collected for the study. Measurements of clinical parameters were recorded at day −15, baseline and 2 months after basic periodontal treatment aiming at monitoring early variations ofthe clinical attachment level. Saliva, crevicular fluid and gingival biopsies were harvested from clinically inflamed and non-inflamed sites from periodontal patients and from control sites of healthy patients for the assessment of IL-10, MMP-8, VEGF, RANKL, OPG and TGF-β1 protein and gene expression levels. Results: Baseline IL-10 protein levels from inflamed sites were higher in comparison to both non-inflamed and control sites (p<0.05). Higher expression of mRNA for IL-10, RANK-L, OPG, e TGF-β1 were also observed in inflamed sites at day −15 prior treatment (p<0.05). After the periodontal treatment and the resolution of inflammation, seventeen percent of evaluated sites still showed clinically detectable attachment loss without significant differences in the molecular profile. Conclusions: Clinical attachment loss is a negative event that may occur even after successful basic periodontal therapy, but it is small and limited to a small percentage of sites. Elevated inflammation markers of inflamed sites from disease patients reduced to the mean levels of those observed in healthy subjects after successful basic periodontal therapy. Significantly elevated both gene and protein levels of IL-10 in inflamed sites prior treatment confirms its modulatory role in the disease status.