Susceptibility of Candida albicans Strains Isolated from Vaginal Secretion in Front of the Mycocins of Wickerhamomyces anomalus.

Mycocins are substances that have the potential to affect other sensitive yeasts or microorganisms. Wickerhamomyces anomalus is a yeast that produces mycocins that have great biotechnological potential, being highly competitive in many habitats, as it is adaptable to a wide range of environmental conditions. Thus, they are targets for studies in different areas, including the environment, industry, and medical sciences. Yeasts of the genus Candida are of great importance due to the high frequency with which they colonize and infect the human host. Yeast infections are often difficult to treat due to the acquisition of resistance against antifungals, leading to studies focusing in new treatment alternatives. This work aims to verify the inhibition of Candida albicans isolated from vaginal secretion by mycocins produced by Wickerhamomyces anomalus. Tests were carried out in solid medium and microdilution tests, where mycocins proved to be efficient in inhibiting the growth of C. albicans, hemolysis, and irritation in an organotypic model, which showed that the mycocins produced by W. anomalus are safe and non-irritating. Thus, the results of this work can provide scientific evidence for the application of mycocins in the production of new antifungal alternatives.

A Brazilian Inter-Hospital Candidemia Outbreak Caused by Fluconazole-Resistant Candida parapsilosis in the COVID-19 Era.

Horizontal transmission of fluconazole-resistant Candida parapsilosis (FRCP) through healthcare workers' hands has contributed to the occurrence of candidemia outbreaks worldwide. Since the first COVID-19 case in Brazil was detected in early 2020, hospitals have reinforced hand hygiene and disinfection practices to minimize SARS-CoV-2 contamination. However, a Brazilian cardiology center, which shares ICU patients with a cancer center under a FRCP outbreak since 2019, reported an increased FRCP candidemia incidence in May 2020. Therefore, the purpose of this study was to investigate an inter-hospital candidemia outbreak caused by FRCP isolates during the first year of the COVID-19 pandemic in Brazil. C. parapsilosis bloodstream isolates obtained from the cancer (n = 35) and cardiology (n = 30) centers in 2020 were submitted to microsatellite genotyping and fluconazole susceptibility testing. The ERG11 gene of all isolates from the cardiology center was sequenced and compared to the corresponding sequences of the FRCP genotype responsible for the cancer center outbreak in 2019. Unprecedentedly, most of the FRCP isolates from the cardiology center presented the same genetic profile and Erg11-Y132F mutation detected in the strain that has been causing the persistent outbreak in the cancer center, highlighting the uninterrupted horizontal transmission of clonal isolates in our hospitals during the COVID-19 pandemic.

Characteristics and Outcomes of Heart Transplant Recipients With Coronavirus-19 Disease in a High-volume Transplant Center.

BACKGROUND: Heart transplant (HT) recipients may be at higher risk of acquiring SARS-CoV-2 infection and developing critical illness. The aim of this study is to describe characteristics and outcomes of HT recipients infected by SARS-COV-2, from a high-volume transplant center. METHODS: We have described data of all adult HT recipients with confirmed coronavirus disease 2019 by RT-PCR in nasopharyngeal samples from April 5, 2020, to January 5, 2021. Outcomes and follow-up were recorded until February 5, 2021. RESULTS: Forty patients were included. Twenty-four patients (60%) were men; the median age was 53 (40-60) y old; median HT time was 34 mo; and median follow-up time 162 d. The majority needed hospitalization (83%). Immunosuppressive therapy was reduced/withdrawn in the majority of patients, except from steroids, which were maintained. Seventeen patients (42.5%) were classified as having severe disease according to the ordinal scale developed by the World Health Organization Committee. They tended to have lower absolute lymphocyte count (P < 0.001) during follow-up when compared with patients with mild disease. Thirty-day mortality was 12.5%. However, a longer follow-up revealed increased later mortality (27.5%), with median time to death around 35 d. Bacterial nosocomial infections were a leading cause of death. Cardiac allograft rejection (10%) and ventricular dysfunction (12.5%) were also not negligible. CONCLUSIONS: Major findings of this study corroborate other cohorts' results, but it also reports significant rate of later events, suggesting that a strict midterm surveillance is advisable to HT recipients with coronavirus disease 2019.

Hydroxychloroquine plus azithromycin early treatment of mild COVID-19 in an outpatient setting: a randomized, double-blinded, placebo-controlled clinical trial evaluating viral clearance.

BACKGROUND: Hydroxychloroquine has shown potential to block viral replication of SARS-CoV-2 in some in vitro studies. This randomised, double-blinded, placebo controlled clinical trial evaluated the efficacy of hydroxychloroquine plus azithromycin (HCQ/AZT) in reducing viral loads in patients with early and mild SARS-CoV-2 infection. METHODS: A single-centre randomised placebo-controlled clinical trial was conducted with outpatients with early and mild SARS-CoV-2 infection. Inclusion criteria were: patients aged 18-65 years with symptoms suggestive of COVID-19 for < 5 days, no significant comorbidities, and positive nasopharyngeal/oropharyngeal swab screening tests (POCT-PCR). Randomised patients received either hydroxychloroquine for 7 days plus azithromycin for 5 days or placebo. The primary endpoint was viral clearance within a 9-day period. Secondary endpoints included viral load reduction, clinical evolution, hospitalization rates, chest computed tomography evolution, and adverse effects. RESULTS: From 107 potential trial participants, 84 were enrolled following predetermined criteria. Statistical analyses were performed on an intention-to-treat (N = 84) and per-protocol (PP) basis (N = 70). On the PP analysis, the treatment (N = 36) and placebo (N = 34) groups displayed similar demographic characteristics. At 95% CI, no statistically significant between-group differences were found in viral clearance rates within 9 days following enrolment (P = 0.26). CONCLUSIONS: This randomised, double-blinded, placebo-controlled clinical trial evaluating outpatients with early and mild COVID-19 showed that viral clearance rates within a 9-day period from enrolment did not change with HCQ/AZT treatment compared with placebo, although no major cardiovascular events were observed in participants without comorbidities. Secondary outcomes were also not significantly improved with HCQ/AZT treatment compared with placebo. These findings do not support use of HCQ/AZT in this setting.

Platelet Reactivity and Coagulation Markers in Patients with COVID-19.

INTRODUTION: COVID-19 is associated with an increased risk of thrombotic events. However, the contribution of platelet reactivity (PR) to the aetiology of the increased thrombotic risk associated with COVID-19 remains unclear. Our aim was to evaluate PR in stable patients diagnosed with COVID-19 and hospitalized with respiratory symptoms (mainly dyspnoea and dry cough), in comparison with a control group comprised of non-hospitalized healthy controls. METHODS: Observational, case control study that included patients with confirmed COVID-19 (COVID-19 group, n = 60) and healthy individuals matched by age and sex (control group, n = 60). Multiplate electrode aggregometry (MEA) tests were used to assess PR with adenosine diphosphate (MEA-ADP, low PR defined as < 53 AUC), arachidonic acid (MEA-ASPI, low PR < 86 AUC) and thrombin receptor-activating peptide 6 (MEA-TRAP, low PR < 97 AUC) in both groups. RESULTS: The rates of low PR with MEA-ADP were 27.5% in the COVID-19 group and 21.7% in the control group (OR = 1.60, p = 0.20); with MEA-ASPI, the rates were, respectively, 37.5% and 22.5% (OR = 3.67, p < 0.001); and with MEA-TRAP, the incidences were 48.5% and 18.8%, respectively (OR = 9.58, p < 0.001). Levels of D-dimer, fibrinogen, and plasminogen activator inhibitor 1 (PAI-1) were higher in the COVID-19 group in comparison with the control group (all p < 0.05). Thromboelastometry was utilized in a subgroup of patients and showed a hypercoagulable state in the COVID-19 group. CONCLUSION: Patients hospitalized with non-severe COVID-19 had lower PR compared to healthy controls, despite having higher levels of D-dimer, fibrinogen, and PAI-1, and hypercoagulability by thromboelastometry. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04447131.

The "false-positive" conundrum: IgA reference level overestimates the seroprevalence of antibodies to SARS-CoV-2.

BACKGROUND: On 12 June 2020, Brazil reached the second position worldwide in the number of COVID-19 cases. Authorities increased the number of tests performed, including the identification of antibodies to SARS-CoV-2 (IgG, IgA, and IgM). There was an overflooding of the market with several tests, and the presence of possible false-positive results became a challenge. The purpose of this study was to describe the seroprevalence and immunoglobulin blood levels in a group of asymptomatic individuals using the reference levels provided by the manufacturer. METHODS: Levels of IgG and IgA antibodies to SARS-CoV-2 were determined in blood serum by the same ELISA (enzyme-linked immunoassay) test. Patients must be free of symptoms. RESULTS: From 20 to 22 May 2020, 938 individuals were tested. There were 441 (47%) men, age 53 years (interquartile range (IQR) = 39-63.2). The sample included 335 (35.7%) subjects aged ≥60 years old. Subjects with a positive test were 54 (5.8%) for IgG and 96 (10.2%) for IgA and 42 (4.5%) for both IgG and IgA. The prevalence of IgG and IgA positive test was not different in men and women and not different in individuals under 60 and over 60 years of age. Conversely, analysing only individuals with positive tests, the levels of IgG in positive subjects were significantly higher than those with an IgA positive test, 3.00 (IQR = 1.68-5.65), and 1.95 (IQR = 1.40-3.38), respectively; P = 0.017. Additionally, individuals with isolated IgA positive tests had significantly lower levels of IgA than those with both IgA and IgG positive tests: 1.95 (IQR = 1.60-2.40) and 3.15 (IQR = 2.20-3.90), respectively, P = 0.005. These latter data suggest that IgA shows a deviation of the distribution to the left in comparison to IgG distribution data. Indeed, many subjects reported as IgA positive had immunoglobulin levels slightly elevated. CONCLUSIONS: In conclusion, we strongly suggest caution in the interpretation of IgA test results. This recommendation is more important for those with positive IgA just above the reference level.

Clinical and epidemiological aspects of Candidemia in eight medical centers in the state of Parana, Brazil: Parana Candidemia Network

ABSTRACT Objectives: Candida spp. has been reported as one of the common agents of nosocomial bloodstream infections and is associated with a high mortality. Therefore, this study evaluated the clinical findings, local epidemiology, and microbiological aspects of candidemia in eight tertiary medical centers in the state of Parana, South of Brazil. Methods: In this study, we reported 100 episodes of candidemia in patients admitted to eight different hospitals in five cities of the state of Parana, Brazil, using data collected locally (2016 and 2017) and tabulated online. Results: The incidence was found to be 2.7 / 1000 patients / day and 1.2 / 1000 admissions. C. albicans was responsible for 49% of all candidemia episodes. Cancer and surgery were the two most common underlying conditions associated with candidemia. The mortality rate within 30 days was 48%, and removal of the central venous catheter (p = 0.029) as well as empirical or prophylactic exposure to antifungals were both related to improved survival (p = 0.033). Conclusions: This study highlights the high burden and mortality rates of candidemia in hospitals from Parana as well as the need to enhance antifungal stewardship program in the enrolled medical centers.

Treatment of developmental defects of enamel.

Developmental defects of enamel are encountered daily in our dental practice. The management of enamel hypomineralized lesions may be challenging, especially as esthetic concern around the young population is increasing. Resin infiltration, a new technique firstly proposed to halt caries progression in the posterior segment, showed a strong positive esthetic effect in the treatment of developmental defects with different etiologies. Future in-vivo studies are needed to evaluate the longterm color stability, in order to provide a strong clinical recommendation.

Clinical and epidemiological aspects of Candidemia in eight medical centers in the state of Parana, Brazil: Parana Candidemia Network.

OBJECTIVES: Candida spp. has been reported as one of the common agents of nosocomial bloodstream infections and is associated with a high mortality. Therefore, this study evaluated the clinical findings, local epidemiology, and microbiological aspects of candidemia in eight tertiary medical centers in the state of Parana, South of Brazil. METHODS: In this study, we reported 100 episodes of candidemia in patients admitted to eight different hospitals in five cities of the state of Parana, Brazil, using data collected locally (2016 and 2017) and tabulated online. RESULTS: The incidence was found to be 2.7 / 1000 patients / day and 1.2 / 1000 admissions. C. albicans was responsible for 49% of all candidemia episodes. Cancer and surgery were the two most common underlying conditions associated with candidemia. The mortality rate within 30 days was 48%, and removal of the central venous catheter (p = 0.029) as well as empirical or prophylactic exposure to antifungals were both related to improved survival (p = 0.033). CONCLUSIONS: This study highlights the high burden and mortality rates of candidemia in hospitals from Parana as well as the need to enhance antifungal stewardship program in the enrolled medical centers.

Late Oral Complications Caused by Head and Neck Radiotherapy: Clinical and Laboratory Study.

OBJECTIVES: The aim of presented cross-sectional and observational study was to determine the prevalence of late oral complications of patients with head and neck cancer who underwent radiotherapy, by clinical and laboratory analyses. MATERIAL AND METHODS: Fifty-five patients, 43 (78.2%) men and 12 (21.8%) women, mean age 60; range 38 to 87 years, who have completed radiotherapy for head and neck cancer for at least 6 months were enrolled. The presence of xerostomia, hyposalivation, oral candidiasis, and type of oral yeasts were correlated with post-radiotherapy period. A control group, age and gender matched, was used for comparisons. The Pearson's Chi-square or Fischer's exact test was used at a significance level of 5%. RESULTS: The mean post-radiotherapy period was 32 months. The oral complications found were xerostomia (45/55, [81.8%]), hyposalivation (44/55 [80%]) and oral candidiasis (15/55 [27.2%]). Xerostomia and hyposalivation was statistically higher in the study group when compared to the control group (P < 0.05). The presence of yeast occurred in 39 (70.9%) of the patients in the study group, and Candida albicans was the most prevalent etiological agent in 25 (64.1%) of those patients (P < 0.05). CONCLUSIONS: Xerostomia and hyposalivation were the more prevalent late oral complications related to radiotherapy. Oral candidiasis was also observed, although its prevalence was lower. The need for long-term dental follow-up of patients who underwent radiotherapy of the head and neck cancer is mandatory.

Facial Paralysis in a Babylonian Plaque.

HYPOTHESIS: A terra cotta plaque [LMU 2551] from the Neo-Babylonian period (c.629-539 BCE), housed in the museum of the Archaeology Center at Loyola Marymount University, Los Angeles, is a representation of right peripheral facial paralysis. BACKGROUND: Ancient representations of pathology are rare and often difficult to identify. This is particularly true of Assyrian-Babylonian cultures where, despite numerous surviving medical texts, artistic examples of disease are almost non-existent. METHODS: Precise caliper measurements and archaeological analysis of LMU 2551 were used to confirm the authors' hypothesis. RESULTS: The facial distortions portrayed in LMU 2551 are not accidental. Measurements show a pronounced asymmetry of the lower face where the length from the mid-philtrum to the oral commissure and from the lateral edge of the ala nasi to the mid-ipsilateral nasolabial fold are twice as long in the left than in the right side. The left eye is closed, whereas the right is widely open. CONCLUSION: The described plaque is among the oldest representations of facial paralysis on record. It correlates with contemporary Babylonian texts describing neurological disorders but its function is unknown.

Yeast Mycocins: a great potential for application in health.

Mycocins have demonstrated inhibition of fungi, bacteria, parasites and viruses, in addition to being studied as epidemiological markers and in the development of vaccines. They are defined as extracellular proteins or glycoproteins with different activities, the main mechanism of action being the inhibition of ß-glucan synthesis in the cell wall of sensitive strains. Given the resistance problems created by several microorganisms to agents commonly used in clinical practice, the discovery of new substances with this purpose becomes essential. Mycocins have potential as anti-microbials because they show minimal toxicity and do not present resistance.

Biomarkers for prediction of mortality in left-sided infective endocarditis.

BACKGROUND: Evidence regarding biomarkers for risk prediction in patients with infective endocarditis (IE) is limited. We aimed to investigate the value of a panel of biomarkers for the prediction of in-hospital mortality in patients with IE. METHODS: Between 2016 and 2018, consecutive IE patients admitted to the emergency department were prospectively included. Blood concentrations of nine biomarkers were measured at admission (D0) and on the seventh day (D7) of antibiotic therapy: C-reactive protein (CRP), sensitive troponin I (s-cTnI), procalcitonin, B-type natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL), interleukin 6 (IL6), tumor necrosis factor α (TNF-α), proadrenomedullin, alpha-1-acid glycoprotein, and galectin 3. The primary endpoint was in-hospital mortality. RESULTS: Among 97 patients, 56% underwent cardiac surgery, and in-hospital mortality was 27%. At admission, six biomarkers were independent predictors of in-hospital mortality: s-cTnI (OR 3.4; 95%CI 1.8-6.4; P<0.001), BNP (OR 2.7; 95%CI 1.4-5.1; P=0.002), IL-6 (OR 2.06; 95%CI 1.3-3.7; P=0.019), procalcitonin (OR 1.9; 95%CI 1.1-3.2; P=0.018), TNF-α (OR 1.8; 95%CI 1.1-2.9; P=0.019), and CRP (OR 1.8; 95%CI 1.0-3.3; P=0.037). At admission, S-cTnI provided the highest accuracy for predicting mortality (area under the ROC curve: s-cTnI 0.812, BNP 0.727, IL-6 0.734, procalcitonin 0.684, TNF-α 0.675, CRP 0.670). After 7 days of antibiotic therapy, BNP and inflammatory biomarkers improved their performance (s-cTnI 0.814, BNP 0.823, IL-6 0.695, procalcitonin 0.802, TNF-α 0.554, CRP 0.759). CONCLUSION: S-cTnI concentration measured at admission had the highest accuracy for mortality prediction in patients with IE.

Antibiotic Activity of Wickerhamomyces anomalus Mycocins on Multidrug-Resistant Acinetobacter baumannii.

To evaluate the susceptibility of multidrug-resistant Acinetobacter baumannii to mycocins produced by Wickerhamomyces anomalus and to verify the cytotoxicity of these compounds. Three culture supernatants of W. anomalus (WA40, WA45, and WA92), containing mycocins (WA40M1, WA45M2, and WA92M3), were tested on A. baumannii using broth microdilution methods, solid medium tests, and cytotoxicity tests in human erythrocytes and in Artemia saline Leach. W. anomalus was able to produce high antimicrobial mycocins, as even at high dilutions, they inhibited A. baumannii. In a solid medium, it was possible to observe the inhibition of A. baumannii, caused by the diffusion of mycocins between agar. Finally, the three supernatants were not cytotoxic when tested on human erythrocytes and Artemia salina. According to the evidence in this study, the mycocins of W. anomalus have been effective and could be used in the development of new antimicrobial substances.

Clinical comparison between an opaque and a clear pit and fissures sealants: a 12-month split-mouth, randomized controlled study.

TRIAL DESIGN: We design a clinical splith-mouth, randomized controlled study, in which the retention of an opaque and clear pit and fissures sealants were evaluated and their effectiveness compared at 6 and 12 months of follow up. A secondary aim was to evaluate the possibility of using a fluorescence based intra-oral camera through the clear sealant to monitor enamel demineralization. METHODS: Consecutive young adolescents with at least two molars with code 0, 1, 2 caries evidenced following the International Caries Detection and Assessment System (ICDAS II) were enrolled. A split-mouth randomized allocation was carried out. One skilled operator applied the sealant under 3.5 X magnification. A second operator evaluated clinical retention and performed the intra-oral camera assessments at 6 and 12 months follow up. RESULTS: A total of 42 patients, (20 males and 22 females, mean age 14.25) with 176 dental lesions were enrolled. Nine patients dropped out accounting for 26 teeth lost during follow up. Overall, a total of 150 sealed teeth were evaluated in the study. In 77 cases the clear sealant was used, while in 73 the opaque sealant was utilized. The opaque sealant rated 100% complete retention at 6 months, and 97.3% at 12 months, while the clear selant 91.8% and 85.9% respectively. Demineralization under clear selant was registered when sealant partial detachment occurred. CONCLUSIONS: The overall retention rate of an opaque sealant was higher than that of a clear sealant after 12 months of follow-up. This difference may partly be due to difficulty in clinical detection of clear sealants during follow-up. Fluorescence based intra-oral camera seems useful to monitor enamel demineralization in clear sealant.

[Knowledge, attitude and behavior towards oral health: gender differences between parents].

OBJECTIVES: The aim of this study is to compare the results of a survey carried out on a sample of mothers and fathers about the knowledge and personal attitudes towards their own oral health and in terms of attention to that of their children. Mutual analogy and cognitive and behavioral differences between parents have been evaluated; in particular as the early assumption of a healthy lifestyle can influence the proper development of their children. MATERIALS AND METHODS: This survey was conducted using a paper questionnaire distributed to a population of parents, men and women, in several private dental practices in Rome. The study lasted about three months. RESULTS: The results obtained from this study show that values obtained by mothers and fathers are essentially equivalent, there are no statistically significant differences (p> 0.05). CONCLUSIONS: This study has shown that there are no significant thinking and behavioral differences between parents regarding their oral hygiene and that of their children. Both parents have been shown to recognize the importance of continuous monitoring and to be aware of techniques and oral hygiene aids suitable for adults and children, although this knowledge is not always applied in daily lifestyles and oral hygiene.

Oral health sentinel-based surveillance: a pilot study on dentinal hypersensitivity pain.

Aim of the study is to assess the development of a structured sentinel system for oral health data collection at national level. Furthermore, this pilot study aims to investigate the prevalence data on dentinal sensitivity pain collected through a nationwide network of epidemiological sentinels (dental hygienists). Each sentinel was given a specific number of examinees and periodicity of data collection. Overall, 116 adults were recruited from 19 Regions, 42,24% male and 57,76% female, with a mean age of 26. DH result was consistent with literature data, being 45%. All sentinel completed the standard forms and assured a good compliance. The overall good customer satisfaction assures adhesion of the sentinels to the procedure, and the regular data collection. The pilot study proved the effectiveness of a structured nationwide network of epidemiological sentinels (dental hygienists) for oral health data collection at national level. This methodology can be an essential starting point for periodic comparative studies.

[VAP and oral hygiene.A systematic review].

Ventilator associated pneumonia (VAP) is a common nosocomial infection in intensive care units. International literature showed how the use of professional oral hygiene protocols provide an essential support in VAP prevention. The aim of this study is to provide a systematic and narrative updated review, to further demonstrate that a proper protocol of oral hygiene, in special needs patients, can reduce risk of developing VAP. In this study were analyzed 10 narrative and 3 systematic reviews. Systematic reviews were evaluated with AMSTAR checklist, INSA tool was used to analyze narrative reviews. The findings of this study suggest that the use of antimicrobials combined with tooth brushing can actively contribute to reducing the incidence of VAP.