Pathobiology of Lomentospora prolificans: could this species serve as a model of primary antifungal resistance?

The number of fungal isolates resistant to antifungal drugs has increased dramatically over the last few years and has become an important concern for clinicians. Among these isolates, fungi showing multidrug resistance are particularly worrying because of the difficulties associated with their treatment. These factors hamper the successful recovery of patients and drastically raise mortality rates. Antifungal resistance is multifactorial and several mechanisms in different fungi have been described. There is a need to study these mechanisms in depth; however, the study of antifungal drug resistance separately for each individual species makes progress in the field very slow and tedious. The selection of a multiresistant microorganism as a model for understanding resistance mechanisms and extrapolating the results to other species could help in the search for a solution. In this mini-review, we describe the pathobiology of Lomentospora (Scedosporium) prolificans, paying special attention to its intrinsic resistance to all currently available antifungal agents. The characteristics of L. prolificans offer several advantages: the possibility of using a single microorganism for the study of resistance to different drugs, even cases of double and triple resistance; it is biologically safe for society in general as no new genetically–modified strains are needed for the experiments; it is homologous with other fungal species, and there is repetitiveness between different strains. In conclusion, we propose L. prolificans as a candidate for consideration as a fungal model for the study of resistance mechanisms against antifungal agents.     

Shifting from Declines to Improvements: Associations between a Meaningful Walking Speed Change and Cognitive Evolution over Three Years in Older Adults

Background

Although the close relationship between mobility and cognitive declines is well-known, literature has very little questioned whether improvement in walking speed over time could be associated with improvements in cognitive functions. The objective of this study was to examine the associations between a clinically meaningful improvement in walking speed and global and specific cognitive changes in older adults. Design: Prospective cohort study.

Setting

Multidomain Alzheimer Preventive Trial (MAPT) study.

Participants

Three-hundred participants from the control group of the MAPT study (mean age 74.8 ± 4.2; 57% women).

Measurements

The 4-m usual walking speed, global cognition, memory, executive functions, and processing speed measures were collected at baseline, and at 6, 12, 24 and 36 months. Participants were categorized into three groups according to their walking speed change over the three-year study: 1/ Non-Improvers (participants not presenting an increase ≥0.05m/sec on walking speed; n=138); 2/ Improvers (increase ≥0.05m/sec; n=40); Cyclic (≥0.05m/sec improvement at some time points without maintaining it through the whole period; n=122).

Results

Adjusted mixed-effect linear regressions revealed that walking speed improvers did not significantly differ from participants who never or temporarily improved their walking speed on all of global and specific cognitive functions over three years. Nevertheless, a sensitivity analysis (excluding participants with a nonclinical walking speed improvement) indicated specific cognitive trajectories per group associated with better episodic memory scores for Improvers compared to non-improvers (β=2.41, 95% CI=.12 - 4.71; p=.039).

Conclusion

This study found that the overtime trajectories of cognitive functions did not differ as a function of clinically meaningful walking speed changes in older adults. Nevertheless, secondary analyses provided new insights on the relationship between walking speed and specific cognitive functions. The novelty of this approach (switching from declines to improvements) should be considered in future large-scale, observational longitudinal studies.

     

Endodontic therapy associated with calcium hydroxide as an intracanal dressing: microbiologic evaluation by the checkerboard DNA-DNA hybridization technique

This study evaluated the predominant microbiota of infected necrotic pulps and the effects of calcium hydroxide therapy on these microorganisms by the checkerboard DNA-DNA hybridization technique. Conventional endodontic therapy associated with calcium hydroxide as intracanal dressing was performed in 12 single-rooted teeth with pulp necrosis and periradicular bone lesion. Samples were collected from the canal at baseline and 14 days after therapy, and the presence of 44 bacterial species was determined by the checkerboard method. Significant differences in the microbiota from baseline to post-therapy were sought by the paired-samples t test. The most prevalent species included F. nucleatum ss. vincentii, C. sputigena, C. ochracea, S. constellatus, V. parvula, P. gingivalis, P. melaninogenica, and S. sanguis. Most of the microorganisms were reduced after treatment, particularly A. gerencseriae, A. israelii, A. naeslundii, C. gingivalis, C. ochracea, P. gingivalis, S. noxia, S. sanguis, and S. oralis (p < 0.05). Conversely, A. actinomycetemcomitans, C. sputigena, and E. corrodens increased in numbers after therapy. These results indicate that conventional endodontic therapy with calcium hydroxide results in the reduction of pathogenic species associated with pulp necrosis. However, its use is limited, because it did not eliminate the whole spectrum of microorganisms.     

Detection of Helicobacter pylori by polymerase chain reaction in the subgingival biofilm and saliva of non-dyspeptic periodontal patients

BACKGROUND: Helicobacter pylori has been associated with the development of peptic ulcers and gastric cancer. Although the oral cavity may be a source of transmission, it is unknown whether it acts as a permanent reservoir for this bacterium, particularly in the presence of periodontal disease. The purpose of this study was to evaluate the prevalence of H. pylori by polymerase chain reaction (PCR) in the subgingival biofilm and saliva of subjects with periodontitis. METHODS: Samples were obtained from 56 periodontally healthy subjects and 169 subjects with chronic periodontitis. DNA was extracted from the samples, and the detection of H. pylori was carried out by PCR using the JW22/23 primers. RESULTS: In general, H. pylori was detected in 24% of all samples evaluated. A significantly higher prevalence of H. pylori was observed in subgingival biofilm samples (33.3%) compared to saliva samples (20%) (P <0.05). H. pylori was detected significantly more often in the saliva and subgingival samples from subjects with periodontitis (23.5% and 50%, respectively) compared to samples from periodontally healthy subjects (7.3% and 11.4%, respectively; P <0.05). CONCLUSION: H. pylori was detected frequently in the oral microbiota of subjects with periodontitis, suggesting that periodontal pocketing and inflammation may favor the colonization by this species.     

Correlates of hepatitis B among patients with mental illness in Brazil

Objective

To assess correlates of hepatitis B among adults with mental illness under care in Brazil.

Method

Cross-sectional national multicenter study of 2206 patients with mental illnesses randomly selected from 26 public mental health services. Sociodemographic and behavioral data were obtained from face-to-face interviews and psychiatric diagnoses from medical charts. Serology testing was conducted, and prevalence rate ratios were estimated by log-binomial regression.

Results

The weighted prevalence rates of current hepatitis B virus (HBV) infection (HBsAg +) and previous HBV exposure (anti-HBc +) were 2.0% [95% confidence interval (CI): 1.5%–2.7%] and 17.1% (95% CI: 16.0%–19.0%), respectively. Correlates of HBsAg + included male gender, younger age (18–29 years), unstable place of residence, intellectual disability, main psychiatric diagnosis of dementia, presence of other medical comorbitidy, use of alcohol/drugs during sex, more than one sexual partner and use of cocaine. Correlates of anti-HBc + included male gender, older age (≥ 30 years), black skin color, lower education, unstable place of residence, currently hospitalized, intellectual disability, history of any sexually transmitted disease or syphilis, poor HIV knowledge, history of imprisonment and sexual violence.

Conclusions

Hepatitis B is an important comorbidity among psychiatric patients in Brazil. Screening for HBV, effective prevention and intervention strategies, including universal HBV immunization, should be routine practices in these mental health services.     

Waardenburg syndrome: Novel mutations in a large Brazilian sample

This paper deals with the molecular investigation of Waardenburg syndrome (WS) in a sample of 49 clinically diagnosed probands (most from southeastern Brazil), 24 of them having the type 1 (WS1) variant (10 familial and 14 isolated cases) and 25 being affected by the type 2 (WS2) variant (five familial and 20 isolated cases). Sequential Sanger sequencing of all coding exons of PAX3, MITF, EDN3, EDNRB, SOX10 and SNAI2 genes, followed by CNV detection by MLPA of PAX3, MITF and SOX10 genes in selected cases revealed many novel pathogenic variants. Molecular screening, performed in all patients, revealed 19 causative variants (19/49?=?38.8%), six of them being large whole-exon deletions detected by MLPA, seven (four missense and three nonsense substitutions) resulting from single nucleotide substitutions (SNV), and six representing small indels. A pair of dizygotic affected female twins presented the c.430delC variant in SOX10, but the mutation, imputed to gonadal mosaicism, was not found in their unaffected parents. At least 10 novel causative mutations, described in this paper, were found in this Brazilian sample. Copy-number-variation detected by MLPA identified the causative mutation in 12.2% of our cases, corresponding to 31.6% of all causative mutations. In the majority of cases, the deletions were sporadic, since they were not present in the parents of isolated cases. Our results, as a whole, reinforce the fact that the screening of copy-number-variants by MLPA is a powerful tool to identify the molecular cause in WS patients.