Onychomycosis: clinical,mycological and in vitro susceptibility testing of isolates of Trichophyton rubrum

BACKGROUND

Onychomycosis or nail fungal infection is the most common nail disease. Despite the wide range of studies on this condition, it remains difficult to establish the correct diagnosis and effective treatment.

OBJECTIVES

To evaluate the efficacy of classical laboratory methods for the diagnosis of onychomycosis, and the in vitro susceptibility of the its main etiological agent to antifungals used in routine.

METHODS

Nail samples of 100 patients with clinically suspected feet onychomycosis were collected to confirm the diagnosis by direct mycological examination and fungal culture. In vitro antifungal susceptibility testing was performed against strains of the main dermatophyte isolated by microdilution, according to the standardized protocol (M38-A2 - CLSI)

RESULTS

Clinical diagnosis of onychomycosis was confirmed by laboratory analysis in 59% of patients. Of these, 54.2% were positive only in direct mycological examination, 44.1% in direct mycological examination and culture, and one case (1.7%) was positive only in culture, resulting in weak agreement between these tests (Kappa = 0.385; p <0.001) High minimum inhibitory concentration values of fluconazole and itraconazole were observed in 66.7% and 25.0% of isolates of T. rubrum tested. Additionally, high MIC values of terbinafine and ciclopirox was detected in only one isolate, and this was one of the strains in which in vitro activity of itraconazole and fluconazole has not been proven.

CONCLUSIONS

Poor agreement was observed between direct mycological examination and culture for the diagnosis of onychomycosis, with direct mycological examination being significantly more sensitive. Except for fluconazole, the other three antifungals tested showed good in vitro activity against clinical isolates of T. rubrum.     

Pigmented Bowen's disease

Pigmented Bowen''s disease is rare, though more prevalent in men. It presents as a well-delineated plaque in areas unexposed to sun. There are reports of association with seborrheic keratosis, solar lentigo or exuberant pigmentation of genital and intertriginous regions. A specific dermoscopy finding is the presence of brown or gray dots in regular arrangement and coiled or dotted vessels. Thus, we aim to raise awareness of the diagnosis of pigmented Bowen''s disease in pigmented lesions.     

Partial inhibition of trypomastigote entry into cultured mammalian cells by monoclonal antibodies against a surface glycoprotein of Trypanosoma cruzi

Monoclonal antibodies were raised against the surface of trypomastigote forms of Trypanosoma cruzi. Although some of these antibodies reacted against antigens shared by trypomastigote and epimastigote or amastigote forms, the majority were trypomastigote-specific. Trypomastigote-specific monoclonal antibodies recognized all infective stages, including trypomastigotes from the bloodstream of infected mice, insect feces, tissue culture and those resulting from differentiation of epimastigotes in axenic culture media. The monoclonal antibodies H1A10 and 6A2, as well as Fab fragments from H1A10, partially prevented T. cruzi invasion of LLC-MK2 cell monolayers (inhibition of 50-70%) when present throughout the entire experiment. Both antibodies recognized an 85 kDa glycoprotein (Tc-85) of the trypomastigote surface which contains N-acetyl-D-glucosamine and/or sialic acid.     

Traumatic dental injury among 12‐year‐old South Brazilian schoolchildren: prevalence,severity, and risk indicators

Abstract – An increasing prevalence of traumatic dental injury (TDI) has been reported in the last few decades. The aim of this study was to assess the prevalence and severity of TDI and its association with socio‐demographics and physical characteristics in the anterior permanent teeth of 12‐year‐old Brazilian schoolchildren. A cross‐sectional study was carried out in a population‐based sample of 1528 subjects attending 33 public and nine private schools (response rate of 83.17%). A single calibrated examiner performed the clinical examinations at the schools and recorded the TDI index (Children’s Dental Health Survey criteria), overjet and lip coverage. Height and weight were measured to calculate the body mass index (BMI). Parents/legal guardians answered a questionnaire containing socio‐demographic questions. The relationships among TDI, socio‐demographic variables and physical characteristics were assessed by survey Poisson regression models. The prevalence of TDI was 34.79% (mild trauma = 24.37%; severe trauma = 10.43%). Male schoolchildren (RR = 1.41, 95% CI = 1.23–1.61, P = 0.002) and schoolchildren from low socioeconomic status (RR = 1.32, 95% CI = 1.07–1.64, P = 0.021) were more likely to present at least one tooth with TDI, whereas students attending 7th grade (advanced students) were less likely to experience TDI (RR = 0.59, 95% CI = 0.43–0.82, P = 0.012). Regarding the severity analysis, students of mid‐high (RR = 1.46, 95% CI = 1.09–1.94, P = 0.022), mid‐low (RR = 1.68, 95% CI = 1.01–2.77, P = 0.045) and low (RR = 1.78, 95% CI = 1.11–2.85, P = 0.027) socioeconomic status were more likely to have mild trauma when compared with schoolchildren of high socioeconomic status. No significant association between severe trauma and socioeconomic status was observed. In conclusion, this study showed a high prevalence of TDI in 12‐year‐old Brazilian schoolchildren. Socio‐demographic data and school achievement were associated with TDI.     

Effects of Estrogen Deficiency and/or Caffeine Intake on Alveolar Bone Loss,Density, and Healing: A Study in Rats

Background: The aim of this study is to evaluate the effects of caffeine and/or estrogen deficiency on ligature‐induced bone loss (BL), trabecular bone area (TBA), and postextraction bone healing (BH). Methods: Rats were assigned into one of the following groups (15 each): 1) control = non‐ingestion of caffeine/sham surgery; 2) caffeine = ingestion of caffeine/sham surgery); 3) ovariectomized (OVX) = non‐ingestion of caffeine/ovariectomy; or 4) caffeine/OVX = ingestion of caffeine/ovariectomy. The rats were under caffeine administration for 65 days and/or estrogen deficiency for 51 days. On day 21 after ovariectomy, one first mandibular molar received a ligature and the contralateral tooth was not ligated. The first maxillary molars were extracted 8 days before sacrifice. BL, TBA, the positive cells for tartrate‐resistant acid phosphatase (TRAP), receptor activator of nuclear factor‐κB ligand (RANKL), and osteoprotegerin (OPG) were analyzed in the furcation area of mandibular molars. Histometric BH and gene expression of bone morphogenetic protein (BMP)‐2, BMP‐7, osteopontin, and bone sialoprotein were evaluated in alveolar sockets. Results: The caffeine group presented the greatest BL and the OVX group the highest number of TRAP‐positive (TRAP⁺) cells around ligated teeth (P <0.05). The control group presented higher TBA and BH than the other groups (P <0.05). All test groups presented higher RANKL/OPG⁺ cells than the control group around ligated/unligated teeth. The OVX and caffeine/OVX groups presented a greater number of TRAP⁺ cells around unligated teeth than the control group (P <0.05). There were no differences among groups for gene expression (P >0.05). Conclusions: Caffeine increased BL in ligated teeth. Caffeine and/or estrogen deficiency decreased TBA in the unligated teeth and reduced BH after tooth extraction.     

Oral mucosa produces cytokines and factors influencing osteoclast activity and endothelial cell proliferation, in patients with osteonecrosis of jaw after treatment with zoledronic acid

Objectives

The intravenous injection of bisphosphonates, currently used as treatment for osteoporosis, bone Paget’s disease, multiple myeloma, or bone metastases, can cause jaw bone necrosis especially in consequence of trauma. The present research aimed to clarify the mechanisms underlying bone necrosis, exploring involvement of the oral mucosa “in vivo.”

Patients and methods

Specimens of oral mucosa were removed from bisphosphonate-treated patients with or without jaw bone necrosis. In mucosa specimens, expression was evaluated of: cytokines involved in the inflammatory process, factors involved in osteoclast activity, i.e., receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin, a factor involved in cell proliferation, namely hydroxymethylglutaryl coenzyme A reductase, and a factor involved in angiogenesis, namely vascular endothelial growth factor (VEGF).

Results

Interleukin (IL)-6 and the RANK/osteoprotegerin ratio were significantly elevated in mucosa from patients with versus without jaw necrosis, whereas hydroxymethylglutaryl coenzyme A reductase and VEGF were significantly decreased.

Conclusions

Our results suggest that mucosa, stimulated by bisphosphonate released from the bone, can contribute to the development of jaw necrosis, reducing VEGF, and producing IL-6 in consequence of hydroxymethylglutaryl coenzyme A reductase reduction. In turn, IL-6 stimulates osteoclast activity, as shown by the increased RANKL/osteoprotegerin ratio.

Clinical relevance

The results of this study suggest the importance of evaluating during bisphosphonate treatment the production of IL-6, RANKL, osteoprotegerin, and VEGF, in order to monitor the jaw osteonecrosis onset. To avoid repeated mucosa excisions, the determination of these factors could be carried out in crevicular fluid.     

Clinical Impact of Oral Anticoagulation in Patients with Atrial High-rate Episodes

Background: Atrial high-rate episodes (AHREs) are common in pacemaker patients. Our aims were to compare patients with AHREs to those without them and to assess if, in those with AHREs, the initiation of oral anticoagulation (OAC) has any clinical impact on the occurrence of ischemic and hemorrhagic events. Methods: From 2014-2017 we selected patients with pacemaker in whom AHREs were detected. AHREs were defined as episodes lasting more than 6 minutes if the electrogram was available or more than 6 hours if not. We used an age- and gender-matched population with pacemaker but no AHRE as a control group (observational study). Those with AHRE were referred to their assistant physician to decide OAC initiation, based on individual circumstances (interventional study). In interventional study, the primary outcome was a composite of systemic thromboembolism or major bleeding. Secondary outcomes were clinical relevant nonmajor bleeding, major and nonmajor bleeding, CV death, and death from all causes. Results: AHREs were detected in 86 patients: 69 patients initiated OAC and the remaining 17 patients did not. When comparing patients with and without AHRE, baseline characteristics were not different between the groups, except for indexed left atrium volume—40 mL (IQR: 34-50) in AHRE group versus 35 mL (IQR: 34-40) in control group (P?=?.014). AHREs were associated with future development of atrial fibrillation (AF) and the risk was higher if AHRE duration was superior to 6 hours. Death and cardiovascular (CV) death were not significantly different between the groups with and without AHRE. Primary outcome occurred in 4.9 per 100 person-year in OAC group versus 3.4 per 100 person-year in non-OAC group (HR 1.4, 95% CI .2-11.3, P?=?.78). Secondary outcomes were not significantly different in the groups. Conclusions: In this group of patients with pacemakers, the presence of AHREs was useful for predicting the future development of AF and the risk of AF was higher in those with a longer duration of AHRE. In the AHRE group, OAC therapy was not associated with a significant difference in the risk of thromboembolism or major bleeding.     

Factors Associated With In-Hospital Mortality in Very Elderly Patients With Ischemic Stroke: A Cohort Study

IntroductionThe highest mortality rates associated with ischemic stroke occur in patients of advanced age. However, studies of factors that establish the increase in hospital mortality are scanty in this population.Material and MethodsEpidemiologic, clinical and laboratory data, etiology and ischemic stroke subtype and complications during hospitalization were analyzed in 195 patients aged 80 years or older. In attempt to associate prognostic factor with the in-hospital mortality during first 28 days from admission, the death and survivor groups were compared.ResultsAmong the 195 patients evaluated, the age was 85.3 ± 4.6 years with a mortality of 26.1%. Following the multivariate model, the factors associated with in-hospital mortality were: age (OR = 1.07, 95% CI = 1.00-1.20), the score less than or equal to 8 on Glasgow coma scale (OR = 22.87, 95% CI = 3.55-148.76), diabetes mellitus (OR = 3.40, 95% CI = 1.30-8.87), total anterior clinical subtype (OR = 5.15, 95% CI = 1.82-14.52) and infectious complications (OR = 8.38, 95% CI = 3.28-21.43).ConclusionsThe following risk factors were associated with a higher in-hospital mortality rate in patients over 79 years of age with ischemic stroke: older age, Glasgow coma score less than or equal to 8, total anterior circulation infarction, infection, and diabetes mellitus.     

Instability of Notch1 and Delta1 mRNAs and reduced Notch activity in vertebrate neuroepithelial cells undergoing S-phase

Vertebrate neurogenesis is controlled through lateral inhibitory signals triggered by the Notch receptor and its ligand Delta. In the E4 chick embryo, the capacity of neural precursors to express the neurogenic genes Notch1 and Delta1 becomes reduced during S-phase, suggesting that their competence to trigger lateral inhibitory signals varies at different stages of the cell cycle. Here we show that the reduction of neurogenic gene expression during S-phase is extensive to later developmental stages and to other species; and it correlates with lower expression of lunatic Fringe and diminished capability to induce the expression of cHairy1/Hes1 and Hes5-1. We also show that the cell cycle-dependence of Notch1 and Delta1 expression is due to a remarkable decrease of mRNA stability during S-phase. These results provide evidence that the capacity of vertebrate neural precursors to express neurogenic genes and trigger lateral inhibitory signals is functionally coordinated with the cell cycle.