PMS2: a potential prognostic protein marker in oral squamous cell carcinoma.

BACKGROUND: An increase in oral squamous cell carcinoma (OSCC) cases was observed despite the reduction in exposure to classic risk factors. Although the exact cause of this trend remains unknown, epigenetic factors could be contributing to an increased occurrence of these tumors. This study aims to assess the influence of PMS2 protein immunoexpression on the prognosis of patients with OSCC. MATERIAL AND METHODS: This study comprised 76 cases of OSCC treated between 2011 and 2016. Immunohistochemical staining for PMS2 was performed. For evaluation, 10 fields per histological section were photographed at a 400x magnification and positively-stained cells were counted with Image J. Mann-Whitney and Kruskal-Wallis tests were used to compare the immunolabeling pattern with the clinical-pathological and prognostic characteristics. Survival analysis was performed with Chi-square, Long-Rank Mantel-Cox and Cox regression tests (p<0.05). RESULTS: An overexpression of PMS2 was observed in N0/1 tumors and in oral cancers found in unusual locations. In patients ≤60 years of age, high levels of PMS2 (>60%; p=0.041) were associated with low survival (p=0.029). In multivariate analysis, surgery combined with chemotherapy (p=0.030) and high PMS2 immunoexpression (p=0.042) significantly increased the risk of death for ≤60 years old patients. CONCLUSIONS: The findings of this study indicate that PMS2 can be a potential prognostic protein marker in OSCC patients 60 years of age and younger.

Effect of nutraceuticals on acanthocephalan Neoechinorhynchus buttnerae and its toxicity to the host tambaqui Colossoma macropomum.

The production of tambaqui Colossoma macropomum has been undergoing financial losses due to parasitic infection by the acanthocephalan Neoechinorhynchus buttnerae, raising an alert for aquaculture in South America. The lack of adequate treatment and use of unlicensed chemicals encourages research for alternative solutions with minimal side effects. The objectives of this study were to evaluate the in vitro antiparasitic potential of commercial nutraceutical products (Natumix® and BioFish®) against N. buttnerae and to assess the respective in vivo toxic effects on the host tambaqui. For in vitro assays, parasitized fish were necropsied for acanthocephalans sampling. The parasites were exposed to three concentrations (0.078, 0.313 and 1.25 mg/ml) of each product, as well as controls (one without product and another with a solubilizer). For the in vivo acute toxicity test, juvenile fish (<0.1 g) were exposed to five increasing concentrations of each product. Mortality of tambaqui was recorded at 24, 48, 72 and 96 h. The estimated lethal concentration (LC) for 10, 50, 90 and 99% of fish was determined to classify the toxicity of the products on the target species. After in vitro efficacy tests, the highest concentrations (1.25 mg/ml) caused 100% mortality of the parasites in both products, but only Natumix® caused 100% mortality using the intermediate concentration (0.313 mg/ml) after 24 h. According to the acute toxicity result, the LC50 classified the nutraceutical products as slightly toxic for tambaqui. The tested products had a parasiticidal effect on N. buttnerae, and the toxicity test showed that both products have therapeutic potential when added to the diet.

Association between sense of coherence and oral health-related quality of life among toddlers.

OBJECTIVE: To assess the relationship between sense of coherence (SOC) and oral health-related quality of life (OHRQoL) among children aged one to three years. PARTICIPANTS: A cross-sectional study was conducted with 276 mother-child pairs randomly selected from the city of Diamantina, Brazil. METHOD: Information was obtained on socio-demographic factors. The short version of Antonovsky's sense of coherence scale (SOC 13) and the Early Childhood Oral Health Impact Scale (ECOHIS) were administered. The children were examined for dental caries. Statistical analysis involved descriptive statistics, the calculation of Spearman's correlation coefficients and adjusted Poisson regression models. RESULTS: SOC was significantly associated with the child's OHRQoL in the multivariate analysis. Children of mothers with high SOC (PR 0.96; 95%CI 0.93,0.98; p=0.045) had a lower prevalence of a negative impact on OHRQoL. Children with severe dental caries had a greater prevalence of a negative impact on OHRQoL (PR 2.53; 95%CI 1.77,3.62; p⟨0.001). CONCLUSIONS: Maternal SOC could be a psychosocial determinant of the OHRQoL of children aged one to three years. Severe dental caries was associated with poorer quality of life.

A new species of Astyanax (Characiformes: Characidae) from Dolina Água Milagrosa, Rio Paraguai basin, Mato Grosso, Brazil.

A new species of Astyanax is described from the upper Rio Paraguai basin, Mato Grosso State, Brazil. The new species can be distinguished from congeners by having the body intensely yellowish in life (v. silvery, reddish or lightly yellow) and by morphometric and meristics traits. Astyanax dolinae n. sp. cannot be assigned to any of the Astyanax species complex currently recognized for the genus. It is only known from the Dolina Água Milagrosa, a karstic sinkhole lake, entirely fed by groundwater, surrounded by Cerrado, the savannah-like vegetation of central South America.

Remote ischemic preconditioning delays fatigue development during handgrip exercise.

Ischemic preconditioning (IPC) of one or two limbs improves performance of exercise that recruits the same limb(s). However, it is unclear whether IPC application to another limb than that in exercise is also effective and which mechanisms are involved. We investigated the effect of remote IPC (RIPC) on muscle fatigue, time to task failure, forearm hemodynamics, and deoxygenation during handgrip exercise. Thirteen men underwent RIPC in the lower limbs or a control intervention (CON), in random order, and then performed a constant load rhythmic handgrip protocol until task failure. Rates of contraction and relaxation (ΔForce/ΔTime) were used as indices of fatigue. Brachial artery blood flow and conductance, besides forearm microvascular deoxygenation, were assessed during exercise. RIPC attenuated the slowing of contraction and relaxation throughout exercise (P < 0.05 vs CON) and increased time to task failure by 11.2% (95% confidence interval: 0.7-21.7%, P <0.05 vs CON). There was no significant difference in blood flow, conductance, and deoxygenation between conditions throughout exercise (P > 0.05). In conclusion, RIPC applied to the lower limbs delayed the development of fatigue during handgrip exercise, prolonged time to task failure, but was not accompanied by changes in forearm hemodynamics and deoxygenation.

TRANSDISCIPLINARITY IN STRATEGIC DECISIONS FOR ONCOLOGICAL TREATMENTS.

The current models for equity and access to new oncological treatments are under strain due to the economic and demographic crisis in Europe as well as the rising costs of innovative drugs. Cancer treatment needs a model of patient-centered care in which an interdisciplinary care plan, based on evidence-based practice is essential for patient wellbeing. Physicians should be focused in the doctor-patient relationship and informed consent is important, especially when new medicines are prescribed. Related with informed consent, there is therapeutic privilege. Moreover, utilitarianism and social justice have to be considered without compromising human dignity and the principle of economy cannot be ignored in the provision of public services. An interdisciplinary approach is essential for the new oncological drugs approval. Therefore, transdisciplinary decision between civil society, pharmaceuticals, healthcare professionals and policy makers is essential in order to assure quality, access to innovation and equity in oncological care.

In-a-dish: induced pluripotent stem cells as a novel model for human diseases.

Human pluripotent stem cells bring promise in regenerative medicine due to their self-renewing ability and the potential to become any cell type in the body. Moreover, pluripotent stem cells can produce specialized cell types that are affected in certain diseases, generating a new way to study cellular and molecular mechanisms involved in the disease pathology under the controlled conditions of a scientific laboratory. Thus, induced pluripotent stem cells (iPSC) are already being used to gain insights into the biological mechanisms of several human disorders. Here we review the use of iPSC as a novel tool for disease modeling in the lab.

Cross-sectional study on factors associated with flossing in Brazilian young children.

PURPOSE: This cross-sectional study aimed at evaluating the factors associated with flossing by caregivers in Brazilian young children. METHODS: Its sample consisted of 305 children aged 1-3 and their mothers from the Brazilian city of Diamantina. They were selected through the Municipal Health Department from a list of registered children who had recently used the public health services. Data collection was done by means of the mothers answering a questionnaire which addressed economic and socio-demographic factors and also the mother and child characteristics and habits. In addition, an oral clinical examination was performed in order to assess Baume arch type and caries occurrence. Descriptive statistical analysis, chi-square test and Poisson regression were performed. RESULTS: It was found that the sample presented a prevalent flossing habit in 20.3% of the subjects. The flossing habit in the children was associated with the mothers' own habit of flossing daily (PR 2.32; 95% CI 1.12-4.82) and with the frequent children's tooth brushing by the mother (PR 2.85; 95% CI 1.05-7.76). CONCLUSION: A higher prevalence of flossing by caregivers in young children is associated with the mothers' own habit of flossing daily and with the frequent children's tooth brushing by the mother.

Do antibiotics prevent infection after third molar surgery? A network meta-analysis.

The aim of this systematic review was to determine whether antibiotics, compared to placebo, can prevent infection or dry socket after third molar surgery. A systematic review and network meta-analysis (NMA) was performed following registration of the protocol (CRD42021276266). Four databases and the grey literature were searched, and papers were selected based on the PICOS question. RoB 2 and GRADE were used to evaluate the risk of bias and certainty of the evidence, respectively. The NMA was performed using Stata. Of 58 randomized clinical trials identified, 34 were included in the NMA. Patients treated with amoxicillin (relative risk (RR) 0.56, 95% confidence interval (CI) 0.38-0.84; low quality of evidence) and those treated with metronidazole (RR 0.51, 95% CI 0.31-0.84; low quality of evidence) showed a lower risk of infection and dry socket when compared to patients given a placebo. Postoperative amoxicillin (750 mg) and amoxicillin plus clavulanate (500 mg + 125 mg, or 2000 mg + 125 mg), and preoperative metronidazole (800 mg) are useful to prevent infection or dry socket when compared to placebo. The low rate of infection after third molar surgery, the correct concept of antibiotic prophylaxis, and antibiotic resistance must be taken into account when choosing to treat healthy patients undergoing third molar surgery with antibiotics.

Attenuation of the levels of pro-inflammatory cytokines prevents depressive-like behavior during ethanol withdrawal in mice.

Clinical studies indicate that alcohol-dependent patients may develop depressive symptoms during abstinence, which may increase the likelihood of relapse. It is known that both in alcohol exposure and depression, there is an increase in the levels of pro-inflammatory cytokines in the brain. However, the putative contribution of increased levels of pro-inflammatory cytokines in the development of depressive-like behavior during ethanol withdrawal has not been evaluated. In the present study, we aimed to investigate if ethanol withdrawal-induced depressive-like behavior is related to increased levels of pro-inflammatory cytokines in the brain. Male mice were treated with vehicle (saline 0.9%, v.o.) or ethanol (2 g/kg, v.o.) for 14 days. After 5 days of cessation of the ethanol treatment, mice were subjected to the forced swim test (FST), tail suspension test (TST), and open field test (OFT) and then sacrificed. Their brains were analyzed for the levels of pro-inflammatory cytokines. Ethanol withdrawal mice showed increased immobility time in the FST and TST than by the control group, indicating increased depressive-like behavior. No alterations in OFT were observed. Ethanol withdrawal increased the levels of tumor necrosis factor-alpha (TNF-α) in the hippocampus and striatum, interleukin-1 beta (IL-1ß) in the hippocampus, and IL-6 in the prefrontal cortex and hippocampus. Treatment of mice with nimesulide (5 or 10 mg/kg/day), a cyclooxygenase-2 inhibitor, during ethanol withdrawal prevented the increase in immobility time in the TST. Similar results were observed in the FST upon nimesulide treatment, although with a higher dose. Nimesulide treatment (10 mg/kg) prevented the ethanol withdrawal-induced alterations in the levels of TNF-α, IL-1ß, and IL-6 in the hippocampus, prefrontal cortex, and striatum. Treatment of mice with an atypical antidepressant drug, vilazodone (0.3 or 1 mg/kg) prevented the increase in depressive-like behavior induced by ethanol withdrawal in the TST. In the FST, the increase in immobility time was prevented only by 1 mg/kg vilazodone treatment. Vilazodone prevented the increase in the levels of TNF-α, IL-1ß, and IL-6 in the hippocampus, IL-6 in the prefrontal cortex, and TNF-α in the striatum. In conclusion, these data indicate that increased levels of pro-inflammatory cytokines may play a role in the development of depressive-like behavior during ethanol withdrawal in mice.

Short isocapnic hyperoxia affects indices of vascular remodeling and intercellular adhesion molecules in healthy men.

In preparation for tracheal intubation during induction of anesthesia, the patient may be ventilated with 100% oxygen. To investigate the impact of acute isocapnic hyperoxia on endothelial activation and vascular remodeling, ten healthy young men (24±3 years) were exposed to 5-min normoxia (21% O2) and 10-min hyperoxia trials (100% O2). During hyperoxia, intercellular adhesion molecules (ICAM-1) (hyperoxia: 4.16±0.85 vs normoxia: 3.51±0.84 ng/mL, P=0.04) and tissue inhibitor matrix metalloproteinase 1 (TIMP-1) (hyperoxia: 8.40±3.84 vs normoxia: 5.73±2.15 pg/mL, P=0.04) increased, whereas matrix metalloproteinase (MMP-9) activity (hyperoxia: 0.53±0.11 vs normoxia: 0.68±0.18 A.U., P=0.03) decreased compared to the normoxia trial. We concluded that even short exposure to 100% oxygen may affect endothelial activation and vascular remodeling.

Complications after different methods for fixation of mandibular angle fractures: network meta-analysis of randomized controlled trials.

The aim of this review was to compare mandibular angle fracture fixation methods that were evaluated through randomized clinical trials considering postoperative complications. Additionally, different treatment methods were ranked based on their performance. A systematic review was performed based on the Cochrane and PRISMA guidelines. The quality of evidence and network meta-analysis were conducted using the GRADE tool and R software, respectively. Four databases were searched, and the papers were selected based on the PICOS strategy. A total of 3584 papers were found. After screening 15 papers were included. One plate placed on lateral border (tension zone) presented lower risk than one plate placed on superior border (tension zone) for infection [risk ratio (RR): 0.48, 95% confidence interval (CI): 0.33 to 0.71] and plate removal necessity (RR: 0.44, 95% CI: 0.28 to 0.69), with moderate quality of evidence. There were no significant differences among the mandibular angle fracture treatments for malocclusion and paraesthesia outcomes. In conclusion, one plate placed on the lateral border in the tension zone is the best choice regarding postoperative infection and plate removal necessity when fixing mandibular angle fractures. None of the tested fixation methods were associated with a significant risk of malocclusion and paraesthesia events.

Comparison between Erich arch bars and intermaxillary screws in maxillofacial fractures involving the dental occlusion: a meta-analysis.

This systematic review aimed to compare the Erich arch bars (EABs) with intermaxillary fixation (IMF) screws in maxillofacial fractures involving dental occlusion on perioperative parameters. Four electronic databases were searched: MedLine (Pubmed), Web of Science, VHL, and Cochrane Library. Inclusion criteria comprised clinical trials comparing the two IMF methods, assessing at least one of the outcomes: occlusal stability, oral hygiene, quality of life, time to apply and remove IMF appliances, and complications. Risk of bias was evaluated through the Cochrane risk of bias tool. Fifteen papers were included in the qualitative analysis and 12 of those in the meta-analysis. Times for EABs application (mean difference (MD) 46.83; 95% confidence interval (CI): 30.63-63.02) and removal (MD 22.89; 95% CI 14.61-31.17) were longer compared with IMF screws. There is higher risk of glove perforation (risk ratio (RR) 3.81; 95% CI 2.41-6.04) and lower risk of iatrogenic injuries (RR 0.21; 95% CI 0.09-0.48) when placing EABs compared with IMF screws. No significant differences in plaque index were found (MD 1.07; 95% CI -0.17 to 2.31). The quality of this evidence ranged from very low to low and was mainly compromised by risk of bias assessment. Further studies are necessary to evaluate transurgical IMF stability and postoperative occlusal quality and quality of life when comparing EABs with IMF screws.

Longitudinal Association between Late-Life Depression (LLD) and Frailty: Findings from a Prospective Cohort Study (MiMiCS-FRAIL).

OBJECTIVES: The aim of the present study was to investigate whether late-life depression (LLD) is associated with incident frailty over time. DESIGN: Prospective cohort study, one-year follow-up. SETTING: Geriatric outpatient clinic, Southwestern of Brazil. PARTICIPANTS: 181 follow-up participants aged 60 years or over. MEASUREMENTS: Depressive disorders were classified as Major Depressive disorder (MDD) or Subthreshold Depression (STD) according to DSM-5 criteria. Depressive symptoms were assessed with validated versions of 15-item Geriatric Depression Scale (GDS-15) and 9-item Patient Health Questionnaire (PHQ-9). We performed binary logistic regressions to estimate the odds ratio (OR) for frailty in LLD adjusting for multiple confounders. Participants who were frail at baseline were excluded from the analyses according to measures of frailty (FRAIL questionnaire and 36-item Frailty Index, FI-36). We also estimated the risk ratio or relative risk (RR) and the risk difference (RD) for incident frailty. RESULTS: We observed a 2 to 4-fold increased risk for incident frailty among participants with LLD. The presence of a depressive disorder was significantly associated with the onset of frailty (adjusted OR for FRAIL and FI-36: 3.07 [95% CI = 1.03 - 9.17] and 3.76 [95% CI = 1.09 - 12.97], respectively. Notably, the risk for frailty due to LLD was significantly higher with the FI-36 compared to the FRAIL (RR: 3.03 versus 2.23). RD was of 17.3% and 12.7% with the FRAIL and the FI-36, respectively. CONCLUSION: Our data support the association between LLD and incident frailty over one year among geriatric outpatients, reinforcing longitudinal evidence from population-based studies.

Identification of enteropathogenic and enterohaemorrhagic Escherichia coli strains by immunoserological detection of intimin.

AIMS: To evaluate the sensitivity and specificity of polyclonal and monoclonal antibodies (Mabs) against intimin in the detection of enteropathogenic and enterohaemorrhagic Escherichia coli isolates using immunoblotting. METHODS AND RESULTS: Polyclonal and Mabs against the intimin-conserved region were raised, and their reactivities were compared in enteropathogenic E. coli (EPEC) and enterohaemorrhagic E. coli (EHEC) isolates using immunoblotting analysis. In comparison with rat antiserum, rabbit anti-intimin IgG-enriched fraction had a stronger recognition pattern to a wide spectrum of intimin types in different EPEC and EHEC serotypes. On the other hand, murine monoclonal IgG2b specific to intimin, with dissociation constant of 1.3x10(-8) mol l(-1), failed in the detection of some of these isolates. CONCLUSION: All employed antibodies showed 100% specificity, not reacting with any of the eae-negative isolates. The sensitivity range was according to the employed antisera, and 97% for rabbit anti-intimin IgG-enriched fraction, followed by 92% and 78% sensitivity with rat antisera and Mab. SIGNIFICANCE AND IMPACT OF THE STUDY: The rabbit anti-intimin IgG-enriched fraction in immunoblotting analysis is a useful tool for EPEC and EHEC diagnoses.

Prognostic utility of neutrophil-to-lymphocyte ratio in patients with metastatic colorectal cancer treated using different modalities.

Introduction: Inflammation is a critical component in carcinogenesis. The neutrophil-to-lymphocyte ratio (nlr) has been retrospectively studied as a biomarker of prognosis in metastatic colorectal cancer (mcrc). Compared with a low nlr, a high nlr is associated with worse prognosis. In the present study, we compared real-world survival for patients with mcrc based on their nlr group, and we assessed the utility of the nlr in determining first-line chemotherapy and metastasectomy benefit. Methods: In this retrospective and descriptive analysis of patients with mcrc undergoing first-line chemotherapy in a single centre, the last systemic absolute neutrophil and lymphocyte count before treatment was used for the nlr. A receiver operating characteristic curve was used to estimate the nlr cut-off value, dividing the patients into low and high nlr groups. Median overall survival (mos) was compared using Kaplan-Meier curves and the log-rank test. A multivariate analysis was performed using a Cox regression model. Results: The 102 analyzed patients had a median follow-up of 15 months. Regardless of systemic therapy, approximately 20% of patients underwent metastasectomy. The nlr cut-off was established at 2.35, placing 45 patients in the low-risk group (nlr < 2.35) and 57 in the high-risk group (nlr ≥ 2.35). The Kaplan-Meier analysis showed a mos of 39.1 months in the low-risk group and 14.4 months in the high-risk group (p < 0.001). Multivariate Cox regression on the nlr estimated a hazard ratio of 3.08 (p = 0.01). Survival analysis in each risk subgroup, considering the history of metastasectomy, was also performed. In the low-risk group, mos was longer for patients undergoing metastasectomy than for those not undergoing the procedure (95.2 months vs. 22.6 months, p = 0.05). In the high-risk group, mos was not statistically different for patients undergoing or not undergoing metastasectomy (24.3 months vs. 12.7 months, p = 0.08). Conclusions: Our real-world data analysis of nlr in patients with mcrc confirmed that this biomarker is useful in predicting survival. It also suggests that nlr is an effective tool to choose first-line treatment and to predict the benefit of metastasectomy.

Zombie-ant fungi cross continents: II. Myrmecophilous hymenostilboid species and a novel zombie lineage.

Ophiocordyceps species infecting ants are globally distributed, with diversity concentrated in the tropics and decreasing with increasing latitude. Among these myrmecophilous species, the ones exhibiting the ability to manipulate host behavior, the so-called "zombie-ant fungi" of the O. unilateralis clade, have been studied progressively over the last decade. However, we know very little about other myrmecophilous groups, such as species within the Ophiocordyceps subgenus Neocordyceps. Species within this group exhibit Hymenostilbe asexual morphs with the ascospores readily breaking into part-spores and regularly kill their hosts on the forest floor, with few records of behavioral manipulation. Here, we describe five new species of Ophiocordyceps belonging to the subgenus Neocordyceps infecting ants in the rainforests of the Brazilian Amazon and Ghana and analyze their ability to manipulate host behavior. We also propose a new status for a species previously described as a variety, providing its phylogenetic placement for the first time. The species proposed herein can readily be separated using classic taxonomic criteria, and this is further supported by ecological and molecular multiloci data.

Effect of third molars in the line of mandibular angle fractures on postoperative complications: systematic review and meta-analysis.

The aim of this systematic review was to verify whether the presence of a lower third molar in the mandibular angle fracture line is associated with postoperative complications. An electronic survey was conducted in five databases. Eligibility criteria included observational and experimental studies that evaluated the association between the presence of the lower third molar in the fracture line of mandibular angle fractures and possible postoperative complications, including infection, paresthesia, necessity of plate removal, temporomandibular joint disorders, malocclusion, dehiscence, and non-union. Thirty-four papers were included in the qualitative analysis and 26 of those in the meta-analysis. The risk of bias of observational studies was assessed by Newcastle-Ottawa scale and of the clinical trials by Cochrane Collaboration risk-of-bias tool. Absence of the third molar was associated with a lower chance of postoperative infection in angle fractures compared to presence of the tooth (odds ratio 0.55, 95% confidence interval 0.34-0.88). No statistically significant difference between the groups was found for the other outcomes evaluated. The findings of this systematic review suggest that the absence of the third molar in the mandibular angle fracture line is associated with a lower postoperative infection rate when compared to angle fractures with a third molar present.

Erratum to "Gastroenteropancreatic Neuroendocrine Neoplasia Characterization in Portugal: Results from the NETs Study Group of the Portuguese Society of Endocrinology, Diabetes and Metabolism".

[This corrects the article DOI: 10.1155/2019/4518742.].