ATPergic signaling disruption in human sepsis as a potential source of biomarkers for clinical use.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated inflammatory response to infection. To date, there is no specific treatment established for sepsis. In the extracellular compartment, purines such as adenosine triphosphate (ATP) and adenosine play essential roles in the immune/inflammatory responses during sepsis and septic shock. The balance of extracellular levels among ATP and adenosine is intimately involved in the signals related to immune stimulation/immunosuppression balance. Specialized enzymes, including CD39, CD73, and adenosine deaminase (ADA), are responsible to metabolize ATP to adenosine which will further sensitize the P2 and P1 purinoceptors, respectively. Disruption of the purinergic pathway had been described in the sepsis pathophysiology. Although purinergic signaling has been suggested as a potential target for sepsis treatment, the majority of data available were obtained using pre-clinical approaches. We hypothesized that, as a reflection of deregulation on purinergic signaling, septic patients exhibit differential measurements of serum, neutrophils and monocytes purinergic pathway markers when compared to two types of controls (healthy and ward). It was observed that ATP and ADP serum levels were increased in septic patients, as well as the A2a mRNA expression in neutrophils and monocytes. Both ATPase/ADPase activities were increased during sepsis. Serum ATP and ADP levels, and both ATPase and ADPase activities were associated with the diagnosis of sepsis, representing potential biomarkers candidates. In conclusion, our results advance the translation of purinergic signaling from pre-clinical models into the clinical setting opening opportunities for so much needed new strategies for sepsis and septic shock diagnostics and treatment.

Sex-dependent GOAL screening performance in adults at risk for obstructive sleep apnea.

OBJECTIVE: To evaluate possible sex-related differences in the performance of the GOAL, a 4-item obstructive sleep apnea (OSA) screening instrument in adults. METHODS: Between July 2019 and June 2021, this cross-sectional study included consecutively recruited patients from one Brazilian sleep laboratory undergoing overnight polysomnography. Individuals with GOAL scores ≥ 2 of a maximum of 4 points are classified at high risk for OSA diagnosis. Actual OSA severity was based on the apnea-hypopnea index: ≥ 5.0/h as any OSA, ≥ 15.0/h as moderate-to-severe OSA, and ≥ 30.0/h as severe OSA. Performance of the GOAL instrument in women and men was assessed by the discriminatory ability (obtained from area under the curve [AUC]-Receiver Operating Characteristic curves) and 2×2 contingency tables. RESULTS: A total of 2,978 subjects (55.3% males) were evaluated. The frequency of GOAL-defined OSA high-risk was statistically higher in men when compared to women (p < 0.001). The GOAL predictive parameters for screening all severity OSA levels were as follows: in females, sensitivity ranging from 58.2% to 78.3% and specificity ranging from 60.0% to 77.6%, while in males, sensitivity ranging from 90.5% to 96.9% and specificity from 20.7% to 46.8%. The GOAL questionnaire had similar discriminatory properties, assessed by AUC, in women and in men: i) any OSA: 0.741 vs. 0.771 (p = 0.204), ii) moderate-to-severe OSA: 0.727 vs. 0.737 (p = 0.595), and iii) severe OSA: 0.728 vs. 0.703 (p = 0.240); respectively. CONCLUSIONS: The GOAL instrument emerges as a useful tool for screening adult individuals and displays similar performance in both women and men.

Population structure of Annona crassiflora: an endemic plant species of the Brazilian Cerrado.

Habitat fragmentation has numerous consequences, particularly to endemic species, and has a negative impact on the genetic diversity of neglected species, leading to genetic drift. Annona crassiflora Mart. is a species that is endemic to Brazil, and its incidence in the Cerrado biome has decreased. The identification and characterization of its remaining diversity is necessary for its conservation. Our aim was to study the population structure of A. crassiflora populations from different Cerrado regions in Minas Gerais State, Brazil (Corinto, Curvelo, Carmo da Mata, Boa Esperança, and Paraguaçu) using inter-simple sequence repeat (ISSR) markers and DNA content. Nuclear DNA content was estimated by flow cytometry using 10 individuals from each population. ISSR markers were used for genotyping accessions in order to study their genetic diversity and population structures. We found considerable genetic variation among populations, with the highest variability observed in the Curvelo population. There was a significant positive correlation between DNA content and latitude (r = 0.46, P = 0. 0003). A Bayesian-based cluster analysis grouped the populations into three clusters, which followed their geographical origins. There was some level of genetic diversity and differentiation among the populations, suggesting the need for a conservation plan for this species. The ISSR markers and DNA content analysis were effective in studying the genetic diversity and population structure of A. crassiflora.

Diagnostic approaches in unsuspected oral lesions of syphilis.

Awareness of the increased prevalence of syphilis is essential for early diagnosis and treatment, and to prevent the spread of the disease. Although serological studies are the primary tool used to confirm the diagnosis of secondary syphilis, biopsy of unsuspected oral lesions is not uncommon in the routine oral pathology laboratory. In these cases, histopathological characteristics are likely to indicate the possibility of syphilis, and an immunohistochemical reaction can confirm it. The aim of the present study was to highlight the histological features and test the efficacy of immunohistochemistry in the detection of Treponema pallidum in oral lesions biopsied with the assumption of a non-syphilitic disease. Thirty-nine tissue samples from patients for whom the possibility of syphilis was suggested on the basis of histopathological findings, were retrieved from the surgical oral pathology service files and submitted to immunohistochemical staining for T. pallidum. The study was approved by the institutional ethics committee. Eighteen of the tissue samples were positive for T. pallidum. Following this, the contributing clinicians were contacted to check whether they had asked for serological examinations when the diagnostic report was received; for all 18 positive cases, the clinicians confirmed that the patients had tested positive at that time. This study shows the importance of clinical-pathological correlation and the value of immunohistochemistry in the diagnosis of unsuspected syphilis.

Candida albicans: Frequency and characterization in oral cancer (Stage I) from smokers and drinkers.

The frequency and the biotype of Candida albicans, from patients with epidermoid carcinoma of the oral mucosa (stage I) were evaluated. The patients chosen were habitual drinkers and smokers, aged 34 to 81 years who had not submitted previously to any treatment. They exhibited ulcero-vegetative lesions, mainly on the floor of the mouth, palate and tongue and were classified as stage TNM 100 - TNM 200. Samples from the buccal mucosa were collected for mycological study including: identification of yeasts, serotyping, determination of exo-enzymes as proteinase and phospholipase as well as "killer" assay for biotype characterization. Positive cultives for yeasts were observed in 51.5% of the patients(17/33), being 21.2% represented by C. albicans, all serotype A. The "killer" test demonstrated two different biotypes of C. albicans, namely 211(71.4%) and 611(28.6%), with high levels of proteinase (Prz < 0.30), while phospholipase presented intermediary levels (Pz > 0.29 and =/< 0.69). These data suggested a potentiality to virulence of C. albicans, although did not show an association of a particular biotype with the carcinogenic factors present or with the development of oral epidermoid carcinoma in this initial stage.