Identifying patterns of diurnal blood pressure variation among ELSA‐Brasil participants

Ambulatory blood pressure monitoring (ABPM) is the gold standard method for the diagnosis of hypertension. ABPM provides a set of repeated measurements for blood pressure (BP), usually over 24 h. Traditional approaches characterize diurnal BP variation by single ABPM parameters such as average and standard deviation, regardless of the temporal nature of the data. In this way, information about the pattern of diurnal BP variation and relationship between parameters is lost. The objective of this study was to identify and characterize daily BP patterns considering the set of repeated measures from 24‐h ABPM. A total of 859 adult participants of the Brazilian Longitudinal Study of Adult Health (ELSA‐Brasil) performed a 24‐h ABPM record. Hypertension, sex, age, race/color, education, marital status, smoking, alcohol, physical activity, and BMI were the covariables analyzed. Techniques for longitudinal clustering, multinomial models, and models with mixed effects were used. Three daily BP patterns were identified. Daily BP patterns with high BP presented higher standard deviation and morning surge and lower nocturnal dipping. They showed greater systolic BP variability and faster rise than fall in diastolic BP during sleep. Hypertensive, “pardos,” and men had greater odds to present these patterns. Daily BP patterns with high BP presented the worst profile concerning ABPM parameters associated with cardiovascular risk. The daily BP patterns identified contribute to the characterization of diurnal BP variation.     

Differential effects of single versus repeated alcohol withdrawal on the expression of endocannabinoid system-related genes in the rat amygdala

Background: Endogenous cannabinoids such as anandamide and 2‐arachidonoylglycerol (2‐AG) exert important regulatory influences on neuronal signaling, participate in short‐ and long‐term forms of neuroplasticity, and modulate stress responses and affective behavior in part through the modulation of neurotransmission in the amygdala. Alcohol consumption alters brain endocannabinoid levels, and alcohol dependence is associated with dysregulated amygdalar function, stress responsivity, and affective control. Methods: The consequence of long‐term alcohol consumption on the expression of genes related to endocannabinoid signaling was investigated using quantitative RT‐PCR analyses of amygdala tissue. Two groups of ethanol (EtOH)‐exposed rats were generated by maintenance on an EtOH liquid diet (10%): the first group received continuous access to EtOH for 15 days, whereas the second group was given intermittent access to the EtOH diet (5 d/wk for 3 weeks). Control subjects were maintained on an isocaloric EtOH‐free liquid diet. To provide an initial profile of acute withdrawal, amygdala tissue was harvested following either 6 or 24 hours of EtOH withdrawal. Results: Acute EtOH withdrawal was associated with significant changes in mRNA expression for various components of the endogenous cannabinoid system in the amygdala. Specifically, reductions in mRNA expression for the primary clearance routes for anandamide and 2‐AG (fatty acid amide hydrolase [FAAH] and monoacylglycerol lipase [MAGL], respectively) were evident, as were reductions in mRNA expression for CB₁, CB₂, and GPR55 receptors. Although similar alterations in FAAH mRNA were evident following either continuous or intermittent EtOH exposure, alterations in MAGL and cannabinoid receptor‐related mRNA (e.g., CB₁, CB₂, GPR55) were more pronounced following intermittent exposure. In general, greater withdrawal‐associated deficits in mRNA expression were evident following 24 versus 6 hours of withdrawal. No significant changes in mRNA expression for enzymes involved in 2‐AG biosynthesis (e.g., diacylglicerol lipase‐α/β) were found in any condition. Conclusions: These findings suggest that EtOH dependence and withdrawal are associated with dysregulated endocannabinoid signaling in the amygdala. These alterations may contribute to withdrawal‐related dysregulation of amygdalar neurotransmission.     

Biomimetic approach to extensive fracture of anterior teeth--a case report

The fracture of anterior teeth in children and adolescents is a common injury. When most tooth structure is compromised and the broken fragment is not recovered, its restoration can become rather complex to both dentist and dental technician. Restoration of single anterior elements is one of the most demanding challenges in fixed prosthodontics. This article describes a clinical case of a 13-year-old patient with an extensive fractured central incisor and contra lateral incisor. Endodontic treatment was performed on both teeth, and a temporary removable appliance was made for esthetics. One month later, an indirect esthetic post and core was made for each tooth, and provisionals were placed. After a 6-month period of soft tissue stabilization, two pressed all-ceramic crowns were fabricated and bonded to the preparations. The authors believe this to be a stable long-term option relative to the reminiscent tooth structure, esthetic demand, and occlusal features of the case.     

Entamoeba moshkovskii perspectives of a new agent to be considered in the diagnosis of amebiasis

During the last decade Entamoeba moshkovskii has become relevant given its capacity to infect humans, especially when considering that it is morphologically indistinguishable from E. histolytica. For a long time, E. moshkovskii was considered as a free living amoeba, but in the last decade it has been demonstrated that E. moshkovskii can infect humans and can be found more frequently in regions where amebiasis shows high prevalence values, becoming a challenge to differentiate it from the E. histolytica/E. dispar complex. Recently there have been studies that raise the possibility that E. moshkovskii could be a pathogenic species, as there are reports in different countries that associated this infection with gastrointestinal symptoms even though others have described it as a non pathogenic species. For this reasons, both clinical and epidemiological studies are required.     

Clonal competition with alternating dominance in multiple myeloma

Emerging evidence indicates that tumors can follow several evolutionary paths over a patient's disease course. With the use of serial genomic analysis of samples collected at different points during the disease course of 28 patients with multiple myeloma, we found that the genomes of standard-risk patients show few changes over time, whereas those of cytogenetically high-risk patients show significantly more changes over time. The results indicate the existence of 3 temporal tumor types, which can either be genetically stable, linearly evolving, or heterogeneous clonal mixtures with shifting predominant clones. A detailed analysis of one high-risk patient sampled at 7 time points over the entire disease course identified 2 competing subclones that alternate in a back and forth manner for dominance with therapy until one clone underwent a dramatic linear evolution. With the use of the Vk*MYC genetically engineered mouse model of myeloma we modeled this competition between subclones for predominance occurring spontaneously and with therapeutic selection.     

Analysis of EGF+61A>G polymorphism and EGF serum levels in Brazilian glioma patients treated with perillyl alcohol-based therapy

Purpose

Malignant gliomas are associated with alteration in EGF/EGFR signaling. Functional EGF+61A>G polymorphism is implicated with risk, recurrence, and progression of glioma. This study aimed to establish a putative association of EGF+61A>G with risk of glioma development, production of angiogenic growth factor EGF, and the response to perillyl alcohol administered by intranasal route.

Methods

The study included 83 patients with recurrent glioma enrolled in Phase I/II trial for intranasal perillyl alcohol therapy and subjects without cancer (n?=?196) as control group. DNA was extracted from blood samples, EGF genotype performed with PCR–RFLP assay, and EGF circulating levels by enzyme immunoassay. Adequate statistical tests were performed to verify associations between polymorphism and glioma risk, and genotype correlation with EGF circulating levels. The log-rank test was also used to evaluate differences on patient survival.

Results

Patients with primary glioblastoma had high frequency of AA genotype (p?=?0.037) and A allele (p?=?0.037). Increased EGF circulating levels were observed in glioma patients with AA (p?=?0.042), AG (p?=?0.006), and AA?+?AG (p?=?0.008) genotypes compared with GG. Patients with GG genotype showed increased but not significant (p?>?0.05) survival rate, and EGF levels lower than 250?pg/mL was consistently (p?=?0.0374) associated with increased survival.

Conclusion

Presence of EGF+61A>G polymorphism in Brazilian subjects was associated with glioma risk and increased circulating EGF levels. Better response to perillyl alcohol-based therapy was observed in a group of adult Brazilian subjects with lower EGF levels.     

Colorectal carcinoma in different age groups

Purpose  

Although colorectal cancer is typical in the older population, tumor onset before age 40 is not infrequent. However, the behavior, characteristics, and prognosis of this disease in young patients are unclear when compared to the older population. It is believed that young patients have a poor prognosis. We hypothesized that young patients have a poor prognosis because they have advanced-stage cancer with more aggressive pathologic features.