Factors associated to mortality in children with critical COVID-19 and multisystem inflammatory syndrome in a resource-poor setting.

SARS-CoV-2 infection in children is usually asymptomatic/mild. However, some patients may develop critical forms. We aimed to describe characteristics and evaluate the factors associated to in-hospital mortality of patients with critical COVID-19/MIS-C in the Amazonian region. This multicenter prospective cohort included critically ill children (1 mo-18 years old), with confirmed COVID-19/MIS-C admitted to 3 tertiary Pediatric Intensive Care Units (PICU) in the Brazilian Amazon, between April/2020 and May/2023. The main outcome was in-hospital mortality and were evaluated using a multivariable Cox proportional regression. We adjusted the model for pediatric risk of mortality score version IV (PRISMIV) score and age/comorbidity. 266 patients were assessed with 187 in the severe COVID-19 group, 79 included in the MIS-C group. In the severe COVID-19 group 108 (57.8%) were male, median age was 23 months, 95 (50.8%) were up to 2 years of age. Forty-two (22.5%) patients in this group died during follow-up in a median time of 11 days (IQR, 2-28). In the MIS-C group, 56 (70.9%) were male, median age was 23 months and median follow-up was 162 days (range, 3-202). Death occurred in 17 (21.5%) patients with a median death time of 7 (IQR, 4-13) days. The mortality was associated with higher levels of Vasoactive Inotropic-Score (VIS), presence of acute respiratory distress syndrome (ARDS), higher levels of Erythrocyte Sedimentation Rate, (ESR) and thrombocytopenia. Critically ill patients with severe COVID-19 and MIS-C from the Brazilian Amazon showed a high mortality rate, within 12 days of hospitalization.

Antibiofilm Activity and Biocompatibility of Temporin-SHa: A Promising Antimicrobial Peptide for Control of Fluconazole-Resistant Candida albicans.

The aim of the study was to investigate the effect of antimicrobial peptides (AMPs) Hylin-a1, KR-12-a5, and Temporin-SHa in Candida albicans as well as the biocompatibility of keratinocytes spontaneously immortalized (NOK-si) and human gingival fibroblasts (FGH) cells. Initially, the susceptible (CaS-ATCC 90028) and fluconazole-resistant (CaR-ATCC 96901) C. albicans strains were grown to evaluate the effect of each AMP in planktonic culture, biofilm, and biocompatibility on oral cells. Among the AMPs evaluated, temporin-SHa showed the most promising results. After 24 h of Temporin-SHa exposure, the survival curve results showed that CaS and CaR suspensions reduced 72% and 70% of cell viability compared to the control group. The minimum inhibitory/fungicide concentrations (MIC and MFC) showed that Temporin-SHa was able to reduce ≥50% at ≥256 µg/mL for both strains. The inhibition of biofilm formation, efficacy against biofilm formation, and total biomass assays were performed until 48 h of biofilm maturation, and Temporin-SHa was able to reduce ≥50% of CaS and CaR growth. Furthermore, Temporin-SHa (512 µg/mL) was classified as non-cytotoxic and slightly cytotoxic for NOK-si and FGH, respectively. Temporin-SHa demonstrated an anti-biofilm effect against CaS and CaR and was biocompatible with NOK-si and FGH oral cells in monolayer.

Impact of pre-operative weight loss on non-alcoholic fatty liver disease histopathology and insulin resistance in individuals undergoing bariatric surgery: a propensity matched cross-sectional comparison

ABSTRACT BACKGROUND: The effect of weight loss (WL) on histopathological aspects of non-alcoholic fatty liver disease (NAFLD) may provide further insights into the dynamics of hepatic recovery after WL. OBJECTIVE: To analyze the effects of pre-operative WL on insulin resistance- and NAFLD-related histology in individuals undergoing bariatric surgery (BS) with or without pre-operative WL. DESIGN AND SETTING: A matched cross-sectional study was conducted at a public university hospital and a private clinic in Campinas, Brazil. METHODS: An analytical, observational, cross-sectional study was conducted using prospectively collected databases of individuals who underwent BS and liver biopsy at either a public tertiary university hospital (with pre-operative WL) or a private clinic (without pre-operative WL). Random electronic matching by gender, age, and body mass index (BMI) was performed and two paired groups of 24 individuals each were selected. RESULTS: Of the 48 participants, 75% were female. The mean age was 37.4 ± 9.6. The mean BMI was 38.9 ± 2.6 kg/m2. Fibrosis was the most common histopathological abnormality (91.7%). Glucose was significantly lower in the WL group (92 ± 19.1 versus 111.8 ± 35.4 mg/dL; P = 0.02). Significantly lower frequencies of macrovesicular steatosis (58.3% versus 95.8%; P = 0.004), microvesicular steatosis (12.5% versus 87.5%; P < 0.001), and portal inflammation (50% versus 87.5%; P = 0.011) were observed in the WL group. CONCLUSION: Pre-operative WL was significantly associated with lower frequencies of macro- and mi- crovesicular steatosis, portal inflammation, and lower glycemia, indicating an association between the recent trajectory of body weight and histological aspects of NAFLD.

Photobiomodulation therapy combined with static magnetic field is better than placebo in patients with fibromyalgia: a randomized placebo-controlled trial.

BACKGROUND: Fibromyalgia is a syndrome characterized by generalized chronic pain and tenderness in specific areas. Photobiomodulation therapy (PBMT) using low-level laser therapy and/or light emitting diode therapy is an electrophysical agent that can be used alone or together with a static magnetic field (PBMT-sMF) to promote analgesia in several health conditions. Little evidence exists regarding the effects of using PBMT and PBMT-sMF in patients with fibromyalgia; this evidence is conflicting. AIM: We aimed to investigate the effects of using PBMT-sMF versus a placebo on reduction of the degree-of-pain rating, impact of fibromyalgia, pain intensity, and satisfaction with treatment in patients with fibromyalgia. DESIGN: A prospectively registered, monocentric, randomized placebo-controlled trial, with blinding of patients, therapists, and assessors, was performed. SETTING: The study was conducted at the Laboratory of Phototherapy and Innovative Technologies in Health (LaPIT) in Brazil, between March and October 2020. POPULATION: Ninety female patients with fibromyalgia were randomized to undergo either PBMT-sMF (N.=45) or placebo (N.=45) treatment. METHODS: Patients from both groups received nine treatment sessions, three times a week, for 3 weeks. Clinical outcomes were collected at baseline, the end of treatment, and at the follow-up appointment 4 weeks post-treatment. The primary outcome was the degree-of-pain rating, measured by the reduction of the tender point count. RESULTS: A decrease in the degree-of-pain rating was observed in patients allocated to the PBMT-sMF group, decreasing the number of tender points when compared to placebo group at the end of treatment (P<0.0001) and at the follow-up assessment (P<0.0001). Patients did not report any adverse events. CONCLUSIONS: PBMT-sMF is superior to placebo, supporting its use in patients with fibromyalgia. CLINICAL REHABILITATION IMPACT: PBMT-sMF might be considered an important adjuvant to the treatment regimens of patients with fibromyalgia.

The Effect of Sub-Lethal Successive Applications of Photodynamic Therapy on Candida albicans Biofilm Depends on the Photosensitizer.

This study aimed to evaluate the potential of successive applications of sub-lethal doses of the antimicrobial photodynamic therapy (aPDT) mediated by Photodithazine® (PDZ) and curcumin (CUR) associated with LED in the viability, reactive oxygen species (ROS) production, and gene expression of Candida albicans. The microbial assays were performed using planktonic cultures and biofilms. Ten successive applications (Apl#) were performed: aPDT (P+L+; C+L+), photosensitizer (P+L-; C+L-), and LED (P-L+; C-L+). Control groups were used (P-L-; C-L-). The viability of C. albicans was determined by cultivating treated cultures on agar plates with or without fluconazole (FLU). In addition, the ROS detection and expression of SOD1, CAP1, and ERG11 genes were determined. For planktonic cultures, no viable colonies were observed after Apl#3 (without FLU) and Apl#2 (with FLU) for either photosensitizer. Biofilm treated with P+L+ resulted in the absence of cell viability after Apl#7, while C+L+ showed ~1.40 log10 increase in cell viability after Apl#2, regardless of FLU. For both photosensitizers, after the last application with viable colonies, the production of ROS was higher in the biofilms than in the planktonic cultures, and SOD1 expression was the highest in P+L+. A reduction of CAP1 and ERG11 expression occurred after P+L+, regardless of FLU. C+L+ had a higher level of ROS, and the treatments were non-significant for gene expression. Sub-lethal doses of aPDT mediated by CUR could induce C. albicans resistance in biofilms, while C. albicans cells in biofilms were susceptible to aPDT mediated by PDZ.

Microvesicular Steatosis in Individuals with Obesity: a Histological Marker of Non-alcoholic Fatty Liver Disease Severity.

BACKGROUND: In non-alcoholic fatty liver disease (NAFLD), steatosis can manifest through two distinct forms: macrovesicular (macroS) and microvesicular (microS). OBJECTIVE: To investigate the prevalence of microS and its association with biochemical parameters and NAFLD-related histological findings in individuals with obesity. METHODS: This is an observational retrospective cross-sectional study, enrolling individuals who underwent bariatric surgery and liver biopsy at a university hospital. A 1:2 propensity matching was performed to pair microS with isolated macroS; this matching enrolled variables "age," "gender," "body mass index (BMI)," and "obesity-associated medical problems." Clinical, biochemical, and histopathological aspects were then analyzed and compared. RESULTS: Of 115 participants, 88.7% were female; average age was 40.5 ± 5 years and mean BMI was 37.9 ± 3.3 kg/m2. Steatosis occurred in 82.6% (67.8% isolated macroS and 14.8% microS). MicroS is significantly associated with higher levels of alanine aminotransferase (ALT) (39.8 ± 26.4 vs. 26.7 ± 17.5; p = 0.04) and glucose (103.8 ± 52.6 vs. 83.3 ± 10.8; p = 0.03) and higher frequencies of moderate to severe macroS (41.2% vs. 2.0%; p < 0.001), portal fibrosis (100% vs. 50%; p < 0.001), perisinusoidal fibrosis (100% vs. 55.9%; p < 0.001), lobular inflammation (100% vs. 41.1%; p < 0.001), and portal inflammation (100% vs. 41.1%; p < 0.001). An independently positive association was observed between intensities of microS and macroS (p < 0.001). CONCLUSION: MicroS is significantly associated with higher levels of ALT and glucose and higher frequencies of moderate to severe macroS, hepatocellular ballooning, portal fibrosis, perisinusoidal fibrosis, lobular inflammation, and portal inflammation. These findings indicate that microS could be considered a reliable histological marker of NAFLD severity.

Efficacy of Antimicrobial Photodynamic Therapy Mediated by Photosensitizers Conjugated with Inorganic Nanoparticles: Systematic Review and Meta-Analysis.

Antimicrobial photodynamic therapy (aPDT) is a method that does not seem to promote antimicrobial resistance. Photosensitizers (PS) conjugated with inorganic nanoparticles for the drug-delivery system have the purpose of enhancing the efficacy of aPDT. The present study was to perform a systematic review and meta-analysis of the efficacy of aPDT mediated by PS conjugated with inorganic nanoparticles. The PubMed, Scopus, Web of Science, Science Direct, Cochrane Library, SciELO, and Lilacs databases were searched. OHAT Rob toll was used to assess the risk of bias. A random effect model with an odds ratio (OR) and effect measure was used. Fourteen articles were able to be included in the present review. The most frequent microorganisms evaluated were Staphylococcus aureus and Escherichia coli, and metallic and silica nanoparticles were the most common drug-delivery systems associated with PS. Articles showed biases related to blinding. Significant results were found in aPDT mediated by PS conjugated with inorganic nanoparticles for overall reduction of microorganism cultured in suspension (OR = 0.19 [0.07; 0.67]/p-value = 0.0019), E. coli (OR = 0.08 [0.01; 0.52]/p-value = 0.0081), and for Gram-negative bacteria (OR = 0.12 [0.02; 0.56/p-value = 0.0071). This association approach significantly improved the efficacy in the reduction of microbial cells. However, additional blinding studies evaluating the efficacy of this therapy over microorganisms cultured in biofilm are required.

Photobiomodulation Therapy Combined with a Static Magnetic Field Applied in Different Moments Enhances Performance and Accelerates Muscle Recovery in CrossFit® Athletes: A Randomized, Triple-Blind, Placebo-Controlled Crossover Trial.

The ergogenic effects of photobiomodulation therapy combined with a static magnetic field (PBMT-sMF) on exercises with characteristics similar to those of CrossFit® are unknown. This study was aimed at investigating the effects of PBMT-sMF applied at different times on recovery and physical performance in CrossFit® athletes by analyzing functional aspects, muscle damage, inflammatory processes, and oxidative stress. This was a prospectively registered, triple-blinded, placebo-controlled, crossover trial. CrossFit® athletes were recruited and assigned to receive one of the four possible interventions. Each intervention included protocols before and after the exercise (referred to as the workout of the day (WOD)). The four possibilities of intervention were as follows: placebo before and after WOD (placebo), PBMT-sMF before and placebo after WOD (PBMT-sMF before), placebo before and PBMT-sMF after WOD (PBMT-sMF after), and PBMT-sMF before and after WOD (PBMT-sMF before and after). The order of possibilities for the interventions was randomized. The primary outcome was the functional test performance. The secondary outcomes were the subjective perception of exertion, muscle damage, inflammation, and oxidative stress. The outcomes were measured before the WOD; immediately after the intervention; and 1, 24, and 48 hours after the WOD. Statistical analysis was performed using repeated measures ANOVA followed by the Bonferroni post hoc test to examine the differences between the interventions at each time point. Twelve participants were randomized and analyzed for each sequence. PBMT-sMF enhanced the performance on functional tests (calculated as a percentage of change) when applied before or after WOD in the assessment performed immediately post-WOD and at 24 and 48 hours later (p < 0.05) compared to placebo and PBMT-sMF before and after WOD. In terms of the secondary outcomes, PBMT-sMF applied before or after WOD significantly decreased the creatine kinase, catalase, and superoxide dismutase activities and interleukin-6, thiobarbituric acid, and carbonylated protein levels (all p < 0.05) compared to the other possibilities of intervention. In addition, PBMT-sMF applied before and after WOD decreased creatine kinase activity at 24 hours and IL-6 levels at 24 and 48 hours compared to placebo (p < 0.05). None of the participants reported any adverse events. PBMT-sMF enhanced the performance of functional tests, decreased the levels of biochemical markers of muscle damage and inflammation, decreased oxidative stress, and increased antioxidant activity in CrossFit® athletes when applied before or after WOD.

Efficacy of curcumin-mediated antibacterial photodynamic therapy for oral antisepsis: A systematic review and network meta-analysis of randomized clinical trials.

BACKGROUND: The presence of oral microorganisms resistant to traditional treatment is increasing, thus a search for new therapies is needed. In this context, antimicrobial photodynamic therapy (aPDT) is an approach for the treatment of antibiotic resistant andnon resistant microorganisms. Therefore, the aim of the present study was to conduct a systematic review and meta-analysis of randomized clinical trials of aPDT for oral antisepsis against oral polymicrobial biofilms. METHODS: PubMed, Science Direct, Scopus, SciELO, Lilacs, Cochrane Library and Embase databases were searched. In total, five articles were included for qualitative analysis and four articles were used for quantitative analyses. Bias assessment of the eligible articles was made using the RoB 2 criteria. Network meta-analysis was performed using the random-effect model. Subgroup's analysis was also conducted. The groups evaluated were aPDT, exposure to light only and no treatment at all (control group). The quality of evidence was assessed by CINeMA approach. RESULTS: aPDT mediated by curcumin had significant results in the reducing bacterial load (0.31-0.49 log10 UFC/ I2=0%) when compared with the control group. The included articles were classified as low risk of bias, despite biases detected by allocation and blinding. Moreover, quantitative analysis between aPDT and control group and between light and control group were classified with low risk of confidence rating, while the results from aPDT versus light were classified as moderate risk of confidence rating. CONCLUSION: aPDT has significant efficacy for oral antisepsis, however more randomized clinical trials will be needed to validate the present results.

Use of Photodynamic Therapy Associated with Antimicrobial Peptides for Bacterial Control: A Systematic Review and Meta-Analysis.

Considering the challenges related to antimicrobial resistance, other strategies for controlling infections have been suggested, such as antimicrobial photodynamic therapy (aPDT) and antimicrobial peptides (AMP). This study aims to perform a systematic review and meta-analysis to obtain evidence on the antimicrobial effectiveness of aPDT associated with AMP and establish in vitro knowledge on this topic for further study designs. The PubMed, Scopus, Web of Science, Science Direct, Scielo, and Cochrane Library databases were searched. Two independent and calibrated researchers (Kappa = 0.88) performed all the systematic steps according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The odds ratio (OR) was used as the effect measure. The Peto method was used to perform the meta-analysis due to the sparse data. Twenty studies were included in the present review. The result was significant (OR = 0.14/p = 0.0235/I-squared = 0%), showing better outcomes of aPDT associated with peptides than those of aPDT alone for controlling the microbial load. Only 20% of the studies included evaluated this approach in a biofilm culture. Combined treatment with aPDT and AMP highly increased the ability of microbial reduction of Gram-positive and Gram-negative bacteria. However, additional blind studies are required to evaluate the efficacy of this therapy on microbial biofilms.

A cobertura da Estratégia Saúde da Família e sua relação com indicadores de saúde no Brasil: a série histórica 1999-2019 / Coverage of the Family Health Strategy and its relationship with health indicators in Brazil: the historic series 1999-2019

A Estratégia Saúde da Família (ESF) foi criada como alternativa para a mudança do modelo assistencial da Atenção Primária à Saúde. Analisar a relação de sua cobertura com indicadores de saúde permite identificar seus efeitos e os impactos das políticas públicas. O objetivo desta dissertação é analisar a associação da evolução de um conjunto de doze indicadores de saúde no Brasil e a cobertura da ESF nos municípios brasileiros de 1999 a 2019. Realizado estudo ecológico com abordagem quantitativa temporal e análise de dados secundários de abrangência nacional. As bases de dados utilizadas foram: SIAB (Sistema de Informação da Atenção Básica), SINASC (Sistema de Informação sobre Nascidos Vivos), SIPNI (Sistema de Informações do Programa Nacional de Imunizações), SIM (Sistema de Informação sobre Mortalidade), SIA (Sistema de Informações Ambulatoriais), IBGE (Instituto Brasileiro de Geografia e Estatística), SISAB (Sistema de Informação em Saúde para a Atenção Básica), SIH-SUS (Sistema de Informação Hospitalar do Sistema Único de Saúde), IPEA (Instituto de Pesquisa Econômica Aplicada), SCNES (Sistema do Cadastro Nacional de Estabelecimentos de Saúde) e ANS (Agência Nacional de Saúde Suplementar). As médias anuais dos doze indicadores municipais foram as variáveis dependentes. A variável independente principal foi a cobertura pela ESF. Foram utilizados testes paramétricos e não paramétricos para verificar a associação entre os indicadores com o ano, cobertura da ESF, Índice de Gini, Índice de Vulnerabilidade Social (IVS), porte populacional, cobertura por Agente Comunitário de Saúde e por planos privados de saúde. Para mensurar a correlação entre as variáveis numéricas, utilizou-se a correlação de Spearman. O modelo Generalized Equations Estimating foi empregado para avaliar a tendência dos indicadores e a comparação de suas médias, em relação à cobertura da ESF e demais variáveis independentes. O método Stepwise foi utilizado para a seleção das variáveis de controle e adotou-se um nível de 5% de significância para o modelo múltiplo. Com o aumento do Índice de Gini ou IVS observou-se piora de onze indicadores, principalmente para a proporção de gravidez na adolescência e taxa de mortalidade infantil (TMI). Apenas a proporção de nascidos vivos com baixo peso ao nascer demonstrou ser menor quanto maior o aumento destes índices, o que tem relação com as características maternas e da assistência à saúde. A cobertura da ESF melhorou os indicadores relacionados ao acompanhamento de pré-natal, cobertura vacinal e de números de atendimentos realizados por médicos e enfermeiros na Atenção Básica. A TMI apresentou redução, mas com leve aumento no final do período pesquisado. A mortalidade neonatal tornou-se mais significativa na composição dessa taxa no Brasil, sendo mais sensível aos cuidados prestados principalmente por serviços especializados e hospitalares fora do âmbito da ESF. O efeito da cobertura da ESF nos indicadores permaneceu significativo e aumentou, conforme o incremento da cobertura, mesmo após fixar possíveis variáveis confundidoras. Os resultados evidenciam o importante papel dos determinantes sociais da saúde, o que reforça a importância da ESF como peça central de um sistema de saúde orientado pelo princípio da equidade e comprometido com a redução das iniquidades em saúde.

The Family Health Strategy (FHS) was created as an alternative to change the assistance model of Primary Health Care. Analyzing the relationship of its coverage with health indicators makes it possible to identify its effects and the impacts of public policies. This dissertation seeks to analyze the association between the evolution of a set of twelve health indicators in Brazil and the coverage of the FHS in Brazilian municipalities, from 1999 to 2019. An ecological study was carried out with a temporal quantitative approach and analysis of secondary data of national scope. The databases used were: SIAB (Primary Care Information System), SINASC (Live Birth Information System), SIPNI (National Immunization Program Information System), SIM (Mortality Information System), SIA (Outpatient Information System), IBGE (Brazilian Institute of Geography and Statistics), SISAB (Health Information System for Primary Care), SIH-SUS (Hospital Information System of the Unified Health System), IPEA (Institute for Economic Research Applied), SCNES (National Registry of Health Establishments System) and ANS (National Supplementary Health Agency). The annual averages of twelve municipal indicators were the dependent variables and the main independent variable was the coverage by the FHS. Parametric and non-parametric tests were used to verify the association between the indicators with the year, FHS coverage, Gini index, Social Vulnerability Index (SVI), population size, coverage by Community Health Agent and by private health plans. To measure the correlation between numerical variables, Spearman's correlation was used. The Generalized Equations Estimating model was used to assess the trend of the indicators and the comparison of their averages in relation to the coverage of the FHS and other independent variables. The Stepwise method was used to select the control variables and a 5% significance level was adopted for the multiple model. With the increase in the Gini Index or SVI, eleven indicators worsened, mainly for the proportion of teenage pregnancy and infant mortality rate (IMR). Only the proportion of live births with low birth weight proved to be lower the greater the increase in these indices, which is related to maternal and health care characteristics. FHS coverage improved indicators related to prenatal care, vaccination coverage and the number of visits performed by doctors and nurses in Primary Care. The IMR showed a reduction, but with a slight increase at the end of the observed period. Neonatal mortality has become more significant in the composition of this rate in Brazil, being more sensitive to care provided mainly by specialized and hospital services outside the scope of the FHS. The effect of FHS coverage on the indicators remained significant and increased as coverage increased, even after controlling for confounding variables. Social determinants were shown to have an important impact on the health indicators included in this study, which reinforces the importance of the FHS as a fundamental strategy to guarantee equitable and universal access.

Immediate effects of photobiomodulation therapy combined with a static magnetic field on the subsequent performance: a preliminary randomized crossover triple-blinded placebo-controlled trial.

There is evidence about the effects of photobiomodulation therapy (PBMT) alone and combined with a static magnetic field (PBMT-sMF) on skeletal muscle fatigue, physical performance and post-exercise recovery in different types of exercise protocols and sports activity. However, the effects of PBMT-sMF to improve the subsequent performance after a first set of exercises are unknown. Therefore, the aim of this study was to investigate the effects of PBMT-sMF, applied between two sets of exercises, on the subsequent physical performance. A randomized, crossover, triple-blinded (assessors, therapist, and volunteers), placebo-controlled trial was carried out. Healthy non-athlete male volunteers were randomized and treated with a single application of PBMT-sMF and placebo between two sets of an exercise protocol performed on isokinetic dynamometer. The order of interventions was randomized. The primary outcome was fatigue index and the secondary outcomes were total work, peak work, and blood lactate levels. Twelve volunteers were randomized and analyzed to each sequence. PBMT-sMF decreased the fatigue index compared to the placebo PBMT-sMF at second set of the exercise protocol (MD = -6.08, 95% CI -10.49 to -1.68). In addition, PBMT-sMF decreased the blood lactate levels post-intervention, and after the second set of the exercise protocol compared to placebo (p<0.05). There was no difference between PBMT-sMF and placebo in the remaining outcomes tested. Volunteers did not report adverse events. Our results suggest that PBMT-sMF is able to decrease skeletal muscle fatigue, accelerating post-exercise recovery and, consequently, increasing subsequent physical performance when applied between two sets of exercises.

Lactobacillus casei reduces the extracellular matrix components of fluconazole-susceptible Candida albicans biofilms.

Fluconazole-sensitive (CaS) and -resistant (CaR) C. albicans were grown as single-species and dual-species biofilms with Lactobacillus casei (Lc) and Lactobacillus rhamnosus (Lr). Single-species Lc and Lr were also evaluated. Biofilm analysis included viable plate counts, the extracellular matrix components, biomass, and structural organization. Lc reduced the viability of CaS, water-soluble polysaccharides, and eDNA in CaS + Lc biofilm. Lc biofilm presented more eDNA than CaS. The total biomass of CaS + Lc biofilm was higher than the single-species biofilms. The viability of Lc and Lr was reduced by CaR dual-species biofilms. The total and insoluble biomass in CaS + Lr was higher than in single-species CaS biofilms. Lc hindered the growth of CaS, and their association hampered matrix components linked to the structural integrity of the biofilm. These findings allow understanding of how the implementation of probiotics influences the growth of C. albicans biofilms and thereby helps with the development of novel approaches to control these biofilms.

Consecutive treatments with photodynamic therapy and nystatin altered the expression of virulence and ergosterol biosynthesis genes of a fluconazole-resistant Candida albicans in vivo.

This investigation assessed the effect of five consecutive daily topical treatments of antimicrobial photodynamic therapy (aPDT), nystatin (NYS), and an association of treatments on a fluconazole-resistant strain of Candida albicans colonizing the tongues of mice. After the last treatments application, colonies of C. albicans were recovered from the tongues and used to determine their fluconazole susceptibility. After 24 hours of the last treatment, the mice tongues were processed to evaluate the expression of C. albicans genes related to the virulence and ergosterol production. The fluconazole susceptibility test yielded a resistance profile similar for all treatment groups and the control group (no treatment). The treatments aPDT, NYS, NYS+aPDT, and aPDT+NYS promoted a reduction in ALS1, EFG1, CAP1, SOD1, SAP1, and LIP3 expression. The expression of HWP1 was higher in the three groups containing nystatin. In contrast, the treatments produced a significative increase in CAT1 gene expression, mainly in the groups in which aPDT was performed. The expression of genes related to ergosterol production was significantly reduced by the treatments evaluated (aPDT, NYS, NYS+aPDT, and aPDT+NYS). Thus, the consecutive topical treatments performed on mice tongues promoted a reduction in the expression of virulence and ergosterol biosynthesis genes of a fluconazole-resistant C. albicans.

Successive applications of Antimicrobial Photodynamic Therapy effects the susceptibility of Candida albicans grown in medium with or without fluconazole.

Antimicrobial Photodynamic Therapy (aPDT) was introduced as a therapy due to resistance that microorganisms have developed to conventional drugs. The study aimed to evaluate the potential of successive applications of aPDT in effecting Candida albicans susceptibility and also whether the presence of fluconazole effected the recovery of the fungi in the culture medium. Planktonic cultures and biofilm were subjected to successive applications of Photodithazine-mediated (25 mg/L) LED-associated aPDT (660 nm, 34 mW/cm2). Plating was performed on Sabouraud Dextrose Agar supplemented or not with fluconazole to recover colony-forming units per milliliter (CFU/mL). Surviving cells were recovered, recultivated, and again exposed to the treatment. The treatments were performed until not enough colonies were available for recultivation and continuation of the protocol. The complete inactivation of the fungus was obtained after three and five applications for planktonic culture and biofilm, respectively. A reduction of 6.3 log10 was observed after third applications in the planktonic cultures grown on medium without fluconazole, while there was a 7 log10 reduction of these cultures grown on fluconazole medium. However, a reduction of 6.1 log10 occurred for biofilms after fifth applications for cultures grown on medium without fluconazole, while a reduction of 6.7 log10 was observed for cultures grown on medium with the antifungal. Thus, aPDT was potentiated by fluconazole. C. albicans in planktonic and biofilm cultures are susceptible to successive applications of PDZ-mediated aPDT, and tolerance to aPDT is higher in the biofilm.

Antimicrobial photodynamic therapy reduces gene expression of Candida albicans in biofilms.

The present study evaluated whether the oxidative stress caused by antimicrobial photodynamic therapy (aPDT) affects the expression of C. albicans genes related to adhesion and biofilm formation (ALS1 and HPW1) and oxidative stress response (CAP1, CAT1, and SOD1). The aPDT was mediated by two photosensitizing agents (PSs) Photodithazine® (PDZ at 100 and 200 mg/L) or Curcumin (CUR at 40 and 80 µM) and LED (37.5 J/cm2 or 50 J/cm2). The quantification of the expression was performed by Reverse Transcription-Quantitative Polymerase Chain Reaction (RT-qPCR) using specific primers for the target genes. The data were analyzed by Analysis of Variance (α = 0.05), followed by Tukey's post-test. It was observed reduction in the expression of ALS1, HWP1, CAP1, CAT1, and SOD1 when aPDT was performed using 200 mg/L PDZ and 80 µM CUR associated to LED (37.7 and 50 J/cm2, respectively) and using 100 mg/L PDZ and 40 µM CUR with LED of 50 J/cm2 (versus control). Also, the expression of CAP1 and SOD1 genes was reduced after aPDT using 100 mg/L PDZ and LED of 37.5 J/cm2. There was a significant reduction in the expression of genes HWP1, CAP1, and SOD1 after aPDT using 40 µM CUR and 37.5 J/cm2 (versus the control group). The application of LED only at 37.5 and 50 J/cm2 promoted down-regulation of ALS1, CAP1, CAT1, and SOD1 genes (versus the control group). Therefore, aPDT mediated by LED -associated PSs PDZ and CUR promoted a reduction in the expression of the five C. albicans genes evaluated.

Antimicrobial photodynamic therapy effectiveness against susceptible and methicillin-resistant Staphylococcus aureus biofilms.

BACKGROUND: Staphylococcus aureus have a great ability to become rapidly resistant to conventional antimicrobial therapies. This study evaluated the efficacy of antimicrobial photodynamic therapy (aPDT) mediated by Curcumin (Cur) and light-emitting diode (LED) in the inactivation of biofilms of methicillin susceptible and resistant S. aureus (MSSA and MRSA, respectively). METHODS: Biofilms were treated with Cur (20, 40 or 80 µM) and illuminated with LED source (455 ± 3 nm; 5.28 J/cm2) (aPDT groups), or treated either with Cur or LED only. Other samples were not exposed to Cur or LED (negative control). The biofilms viability after all experimental conditions were evaluated by counting the number of colonies (CFU/mL) and XTT assay. Additional samples were also evaluated by LIVE/DEAD® staining using confocal laser scanning microscopy (CLSM). Data were analyzed by ANOVAs followed by the Games-Howell post hoc test (α = 0.05). RESULTS: For both strains, all aPDT groups significantly reduced both CFU/mL and metabolic activity of biofilms compared to the negative control (p < 0.001). The results were enhanced when 80 µM of Cur was used. CLSM images showed that both bacteria biofilms submitted to aPDT had a large number of red-stained colonies, especially at aPDT80. In general, MRSA biofilms tended to be less susceptible to aPDT than MSSA biofilms. CONCLUSIONS: It can be concluded that aPDT mediated by Cur and LED was an efficient method to inactivate 48 -h biofilms of both S. aureus strains.

Can surface protection prevent the loss of hardness on dentin and composite resin surfaces exposed to erosive challenges? / ¿Puede la protección de la superficie prevenir la pérdida de dureza en las superficies de dentina y resina compuesta expuestas a erosión?

Objective: This study investigated the effect of endogenous erosion on the microhardness of dentine and a nanofilled composite resin. Procedures for preventing erosion were also studied. Materials and Methods: 90 bovine dentine specimens were divided into three groups in accordance with the method for preventing: negative control, topical application of fluoride and resin-modified glass ionomer varnish. 120 composite resin specimens were distributed into four groups, which also included a resin sealant, among the preventive procedures. Specimens were then randomly divided into three sub-groups according to the exposure to simulate gastric acid solution and subsequent remineralization: negative control, 9 and 18 cycles. Surface analysis was carried out by measuring the Knoop hardness. The data obtained were statistically analyzed using 2-way ANOVA and Tukey test. Result: The mean hardness of dentine and of the composite specimens resin exhibited lower hardness after 18 cycles. However, the resin-modified glass ionomer varnish resulted in greater values compared to the other preventive procedures. Conclusion: A resin-modified glass ionomer varnish seems to be a promising method for minimizing the damage caused by endogenous acid, but its protection can be reduced depending on the intensity of the erosive challenge.

Objetivo: Este estudio investigó el efecto de la erosión endógena sobre la microdureza de la dentina y una resina compuesta de nanorrelleno. También se estudiaron los procedimientos para prevenir la erosión. Materiales and Métodos:90 muestras de dentina bovina se dividieron en tres grupos de acuerdo con el método para prevenir: control negativo, aplicación tópica de fluoruro y barniz de ionómero de vidrio modificado con resina. Se distribuyeron 120 muestras de resina compuesta en cuatro grupos, que también incluían un sellador de resina, entre los procedimientos preventivos. Las muestras se dividieron al azar en tres subgrupos de acuerdo con la exposición para simular la solución de ácido gástrico y la remineralización posterior: control negativo, 9 y 18 ciclos. El análisis de la superficie se realizó midiendo la dureza Knoop. Los datos obtenidos se analizaron estadísticamente mediante ANOVA de 2 vías y prueba de Tukey. Resultados: La dureza media de la dentina y de la resina de muestras compuestas exhibió una dureza más baja después de 18 ciclos. Sin embargo, el barniz de ionómero de vidrio modificado con resina resultó en valores mayores en comparación con los otros procedimientos preventivos. Conclusión: Un barniz de ionómero de vidrio modificado con resina parece ser un método prometedor para minimizar el daño causado por el ácido endógeno, pero su protección puede reducirse dependiendo de la intensidad del desafío erosivo.

Depression and quality of life in older adults on hemodialysis

Objective: Depression is highly prevalent in hemodialysis patients, but few studies have evaluated older hemodialysis patients. The aim of this study was to evaluate the prevalence of depression, its associated factors and its impact on quality of life in an older population on hemodialysis. Methods: This was a cross-sectional study including 173 hemodialysis patients aged 60 years or older in Recife, Brazil. Depression was evaluated using the Mini-International Neuropsychiatric Interview when depressive symptoms (according to the 5-item Geriatric Depression Scale) were present. Quality of life was assessed with the Control, Autonomy, Self-realization and Pleasure Questionnaire (CASP-16). Data were also collected on sociodemographic, laboratory (albumin, parathormone, hemoglobin, and phosphorus) and dialysis (dialysis vintage, vascular access and hemodialysis adequacy) characteristics. Results: Depression was present in 22.5% of the sample. Depressed patients presented low CASP-16 quality of life scores (31.6 vs. 24.2, p < 0.001), twice the odds of albumin levels < 3.8 g/dL (OR 2.36; 95%CI 1.10-5.07; p = 0.027) and higher parathormone levels (OR 1.06; 95%CI 1.00-1.13; p = 0.05). Conclusion: Older hemodialysis patients have a high prevalence of depression. Depressed patients presented poor quality of life, lower serum albumin and higher parathormone levels. Teams dealing with older hemodialysis patients should include depression and quality of life assessments in care protocols.

Quality of life may be a more valuable prognostic factor than depression in older hemodialysis patients.

PURPOSE: Depression and impairment of quality of life (QoL) reduce the survival of individual on hemodialysis (HD). However, few studies evaluated the impact of these conditions on the survival of older patients undergoing HD. METHODS: A retrospective cohort study was performed including patients aged ≥ 60 years on HD in Recife, Brazil, assessed in 2013 and monitored until 2017. Depression was evaluated with the Mini-International Neuropsychiatric Interview and QoL with the Control, Autonomy, Self-realization, and Pleasure Questionnaire (CASP-16). Survival differences according to the depression and QoL status were measured by Kaplan-Meier analysis and Cox regression. Death Certificates were analyzed to assess the cause of death. RESULTS: A total of 171 patients were included (mean age 68.7 ± 6.9 years). The mean follow-up time was 3 years (maximum 4.5 years) and there were 98 deaths (57.3% of the sample). In a multivariate model that included depression and QoL, only QoL impairment was associated with a higher risk of death (HR 1.62, p = 0.035). Among CASP domains, only "Control" was associated with survival (HR 0.90, p = 0.014). Depression was unrelated to the cause of death, but there was a trend for death by endocrine diseases if QoL was impaired (p = 0.057). CONCLUSION: QoL impairment is a key predictor of prognosis in older patients on HD and may be more important than depression. It is important that teams dealing with this population include in protocols an assessment of QoL, in order to offer a range of care according to the needs of these patients.