Impact of allogeneic stem cell transplantation in childhood and adolescence on quality of adulthood life: A case-control study.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with late complications that can impair the quality of life (QoL) of patients for years after transplant. The purpose of the present study was to determine the difference in the QoL of adults that underwent allo-HSCT in childhood and adolescence compared with not transplanted adults. METHODS: In this prospective case-control cross-sectional study, we included patients aged ≥18 years that received an allo-HSCT during childhood or adolescence and subsequently survived at least 2 years after transplantation. The control group consisted of blood donors matched for age and sex. QoL assessment was performed using the Short Form-36 (SF-36) Health Survey, Portuguese version 2. RESULTS: Thirty-four transplanted patients and controls were included. 58.8% were male, and the median age at transplant was 13.5 years (range, 4-17 years). The median follow-up was 11.5 years (range, 2.0-23.0 years). The most common late effect was skeletally followed by endocrine complications. Patients with these late complications had the worst QOL in the following dimensions: physical functioning, role physical, bodily pain, general health, and mental health. When compared to the control group, patients had a lower score in two dimensions: physical functioning and role physical. CONCLUSIONS: Although skeletal and endocrine complications of transplant patients in childhood have an impact on physical functioning, most parameters of QoL of these patients in adulthood are similar to healthy individuals of the same age and gender. Early detection and long-term monitoring of late complications can prevent impairment of the QoL.

Molecular characterization of canine filarioids in a previously non-endemic area of Rio de Janeiro State, Brazil.

Dirofilaria immitis is the causative agent of canine heartworm disease, a severe health problem in dogs, especially in coastal areas of tropical and subtropical regions of the world. We employed molecular methods to investigate the occurrence of canine infection by filarioids in five municipalities of Baixada Fluminense (Magé, Duque de Caxias, Guapimirim, Nova Iguaçu, and São João de Meriti), a non-endemic area of Rio de Janeiro State, Southeast Brazil. A total of 110 canine blood samples collected from 2017 to 2018 and positive for microfilariae at the modified Knott's test were screened by cPCR targeting DNA fragments of the 12S rDNA gene for filarial nematodes. Seventy-seven samples (70%) tested positive at the molecular analysis. Of these, 72 were identified as D. immitis and 5 (4.5%) as Acanthocheilonema reconditum. Dirofilaria repens was not detected in the studied municipalities of Baixada Fluminense. This is the first record of D. immitis and A. reconditum in the Baixada Fluminense region, Rio de Janeiro State, Brazil. The prevalence of D. immitis cases in the five municipalities suggests the establishment and maintenance of its enzootic cycle in the studied region, which indicate vulnerability to the occurrence of epidemic cycles and, possibly, human cases.

Potentiating activity of Norfloxacin by synthetic chalcones against NorA overproducing Staphylococcus aureus.

Staphylococcus aureus is responsible for a series of infections occurring in both human and animal hosts. S. aureus SA1199B is a strain resistant to hydrophilic fluoroquinolone due to overproduction of the NorA efflux pump that has been used as a microbial model to evaluate if a compound act as efflux pump inhibitor. Finding substances from natural or synthetic origin able to reverse resistance mechanisms like those of efflux pumps is a challenge. The use of Chalcones and their derivatives is of great chemical and pharmacological interest, as they present a simple structure and several pharmacological activities. This study aims to evaluate the antibacterial potential of 4 synthetic chalcones, as well as to evaluate their action in the modulation of Norfloxacin resistance against the strain SA1199B strain. Microdilution assays were performed for evaluation of the antimicrobial activity. For evaluation of the modulating effect on resistance to Norfloxacin or EtBr, MIC values of these compounds were determined in the absence or presence of subinhibitory concentrations used of each chalcone. MICs values of both Norfloxacin and EtBr were significantly reduced in the presence of all tested chalcones, indicating that inhibition of the active efflux of these compounds by NorA could be a possible mechanism of action of the chalcones. These results show that the compounds studied have a high potential as a NorA inhibitor, with the best modulating effect verified for the compound 3. Pharmacokinetic and toxicity predictive studies indicated a high intestinal absorption and good volume of distribution for chalcones by oral administration, activity in the central nervous system and ease to be transported between biological membranes. Emphasizing that analogs 1 and 4 were easily metabolized by CYP3A4 enzyme, constituting a pharmacological active ingredient without toxic risk due to metabolic activation. These chalcones combined with Norfloxacin could be a promise technological strategy to be applied in the treatment of infections caused by S. aureus overproducing NorA.

Synthesis and biological evaluation of thiazolidinedione derivatives with high ligand efficiency to P. aeruginosa PhzS.

The thiazolidinone ring is found in compounds that have widespan biology activity and there is mechanism-based evidence that compounds bearing this moiety inhibit P. aeruginosa PhzS (PaPzhS), a key enzyme in the biosynthesis of the virulence factor named pyocyanin. Ten novel thiazolidinone derivatives were synthesised and screened against PaPhzS, using two orthogonal assays. The biological results provided by these and 28 other compounds, whose synthesis had been described, suggest that the dihydroquinazoline ring, found in the previous hit (A- Kd = 18 µM and LE = 0.20), is not required for PaPzhS inhibition, but unsubstituted nitrogen at the thiazolidinone ring is. The molecular simplification approach, pursued in this work, afforded an optimised lead compound (13- 5-(2,4-dimethoxyphenyl)thiazolidine-2,4-dione) with 10-fold improvement in affinity (Kd= 1.68 µM) and more than 100% increase in LE (0.45), which follows the same inhibition mode as the original hit compound (competitive to NADH).Executive summaryPhzS is a key enzyme in the pyocyanin biosynthesis pathway in P. aeruginosa.Orthogonal assays (TSA and FITC) show that fragment-like thiazolidinedione derivatives bind to PaPhzS with one-digit micromolar affinity.Fragment-like thiazolidinedione derivatives bind to the cofactor (NADH) binding site in PaPhzS.The molecular simplification optimised the ligand efficiency and affinity of the lead compound.

HCC Detection on Surveillance US: Comparing Focused Liver Protocol Using US LI-RADS Technical Guidelines to a General Complete Abdominal US Protocol.

OBJECTIVE: Focused US examinations of the liver in the routine hepatocellular carcinoma (HCC) screening reduce the time spent on evaluating other structures deemed irrelevant to the clinical setting. It is still unknown, however, if such a strategy may additionally improve the frequency of nodules detection. We aimed to assess the impact of an HCC surveillance program in high-risk patients by means of targeted liver US following LI-RADS technical guidelines in comparison to a complete upper abdominal scan. METHODS: In this IRB-approved, single-center, prospective study, patients at high-risk for HCC enrolled from 06/2016 to 09/2019 were randomly assigned to 1 of the 2 institutional protocols: Group A (targeted liver US) or Group B (complete upper abdominal scan). Twenty examiners with similar experience in abdominal US were randomly assigned to perform the examinations exclusively in 1 of the groups (10 in each group). Frequency of hepatic nodules between groups was compared by using Fisher's exact test. RESULTS: Four hundred and sixty-five patients were enrolled, with no significant differences in both groups regarding sex, age, etiology of liver disease, MELD scores, and alpha-fetoprotein levels. A significantly higher frequency of nodules detection was found in Group A (230 patients; 23 nodules detected; 10% of the sample) in comparison to Group B (235 patients; 3 nodules; 1.3% of the sample) (p <.001). Five patients in Group A and 1 in Group B were positive for HCC after full diagnostic work-up. CONCLUSION: Adopting an HCC screening program based on targeted liver US improved the detection of hepatic nodules among high-risk individuals.

Hematopoietic cell transplantation in pediatric patients with acute leukemias or myelodysplastic syndrome using unrelated adult or umbilical cord blood donors in Brazil.

The choice of alternative donors for HCT for patients without an HLA-matched related donor depends on several factors. We compared major HCT outcomes in 212 consecutive children transplanted at 11 centers in Brazil for acute leukemia or MDS from an HLA-matched unrelated donor (MUD, n = 95), mismatched unrelated donor (MMUD, n = 47) or unrelated umbilical cord blood (UCB, n = 70). Most had ALL (61%), bone marrow (57%) as the graft source and 95% received a MAC regimen. The 3-year OS probability were 57, 55, and 37% after HCT from MUD, MMUD, and UCB, respectively (HR 1.68, 95%CI 1.07-2.63; P = .02). In comparison with MUD, OS was similar after transplantation of a ≥ 6/8 HLA-matched or a high cell dose (>5 × 107 TNC/kg) CB unit (HR 1.41, 95%CI 0.88-2.27; P = .15). NRM was higher for UCB (HR 3.90, 95%CI 1.43-10.7; P = .01) but not for MMUD (HR 1.03, 95%CI 0.53-2.00; P > .20). Advanced disease (HR 2.05, 95%CI 1.26-3.33; P < .001) and UCB with high probability of being < 6/8 HLA-matched (HR 5.34, 95%CI 2.0-13.9; P < .001) were associated with higher mortality. Relapse and acute GVHD were similar among groups, while PGF was higher among UCB transplants (P = .002) and chronic GVHD among MMUD group (HR 2.88, 95% CI 1.05-7.88; P = .04). Our results suggest that in Brazil HCT outcomes performed with MMUD and MUD donors were comparable, while with UCB units < 6/8 HLA-matched were associated with higher NRM for children with acute leukemia or MDS.

Antileishmanial activity evaluation of thiazolidine-2,4-dione against Leishmania infantum and Leishmania braziliensis.

Leishmaniasis is responsible for approximately 65,000 annual deaths. Despite the mortality data, drugs available for the treatment of patients are insufficient and have moderate therapeutic efficacy in addition to serious adverse effects, which makes the development of new drugs urgent. To achieve this goal, the integration of kinetic and DSF assays against parasitic validated targets, along with phenotypic assays, can help the identification and optimization of bioactive compounds. Pteridine reductase 1 (PTR1), a validated target in Leishmania sp., is responsible for the reduction of folate and biopterin to tetrahydrofolate and tetrahydrobiopterin, respectively, both of which are essential for cell growth. In addition to the in vitro evaluation of 16 thiazolidine-2,4-dione derivatives against Leishmania major PTR1 (LmPTR1), using the differential scanning fluorimetry (ThermoFluor®), phenotypic assays were employed to evaluate the compound effect over Leishmania braziliensis (MHOM/BR/75/M2903) and Leishmania infantum (MHOM/BR/74/PP75) promastigotes viability. The ThermoFluor® results show that thiazolidine-2,4-dione derivatives have micromolar affinity to the target and equivalent activity on Leishmania cells. 2b is the most potent compound against L. infantum (EC50 = 23.45 ± 4.54 µM), whereas 2a is the most potent against L. braziliensis (EC50 = 44.16 ± 5.77 µM). This result suggests that lipophilic substituents on either-meta and/or-para positions of the benzylidene ring increase the potency against L. infantum. On the other hand, compound 2c (CE50 = 49.22 ± 7.71 µM) presented the highest selectivity index.

Stability of volatile compounds of honey during prolonged storage.

The aim of the study was to identify, via headspace solid phase microextraction and gas chromatography-mass spectrometry, volatile compounds in eight no processing Apis mellifera L. honey samples produced in the state of Santa Catarina, Brazil, and monitor their stability over 540 days of storage at 20 ± 4 °C, searching for possible degradation indicators compounds. The result of the initial analysis showed the presence of 32 volatile compounds and 24 were selected for the evaluation of the behavior over the storage. The volatiles cis- and trans-linalool oxide and hotrienol showed increased over 540 days, except for one sample, which showed a decrease in the cis- and trans- linalool oxide contents. Other compounds (ethyl acetate, 1-hexanol. 2-ethyl, benzoic acid. ethyl ester, butanoic acid. 3-methyl, butanoic acid. 2-methyl, and salicylic acid. tert.-butyl ester) were detected in at least one sample from 360 days of storage. Considering the storage system applied, the compounds cis- and trans-linalool oxide and hotrienol, which were found in all samples and times evaluated, can be considered possible indicators compounds of degradation of honey.

Genetic Diversity of 'Candidatus Liberibacter asiaticus' Revealed by Short Tandem Repeats and Prophage Typing Indicates Population Homogeneity in Brazil.

'Candidatus Liberibacter asiaticus' is the most common huanglongbing-associated bacteria, being present in Asia, South, Central, and North America. Genomic approaches enabled sequencing of 'Ca. L. asiaticus' genomes, allowing for a broader assessment of its genetic variability with the application of polymerase chain reaction (PCR)-based tools such as microsatellite or short tandem repeat (STR) analysis. Although these tools contributed to a detailed analysis of strains from Japan, China, and the United States, Brazilian strains were analyzed in either too few samples with several STRs or in several strains with only a single microsatellite and a single PCR marker. We used 573 'Ca. L. asiaticus' strains, mainly collected from São Paulo State (SPS), in our genetic analyses, employing three STRs and several prophage PCR markers. STR revealed a homogeneous population regardless of sampling year or geographic regions of SPS. Thirty-eight haplotypes were recognized with a predominance of VNTR_005 higher than 10 repeats, with VNTR_002 and VNTR_077 containing 11 and 8 repeats, respectively. This haplotype is indicated as class HE, which comprised 80.28% of strains. Classes HA and HB, predominant in Florida, were not found. A new genomic organization in the junction of prophages SC2 and SC1 is prevalent in Brazilian strains, indicating gene rearrangement and a widespread occurrence of a type 1 prophage as well as the presence of a type 2-like prophage. Our results indicate that 'Ca. L. asiaticus' populations are homogeneous and harbor a new genomic organization in prophages type 1 and 2.

Acoustic radiation force impulse (ARFI) elastography to asses maternal and foetal structures in pregnant ewes.

The aim of this study was to evaluate the stiffness of foetal lungs, liver, kidneys and placentomes by acoustic radiation force impulse (ARFI) elastography in ovine and to correlate obtained findings with foetal development. Twenty-four ewes were included, and tissue stiffness of foetal lung, liver, kidney and placentome was measured beginning with 10th gestational week by qualitative-quantitative ARFI elastography. A total of 33 healthy lambs were born. Qualitative elastographic analysis permitted to classify maternal and foetal tissues elasticity in decreasing order as follows: placentome, kidney, liver and lung. Regarding quantitative ARFI elastography data, shear wave velocity (SWV) of foetal lung and liver varied. The lung SWV decreased gradually from the 16th to the 21st gestational week (R2  = 0.80; p < 0.001), while liver SWV increased gradually from the 14th to 21st gestational week (R2  = 0.80; p < 0.001). In contrast, the kidneys and placentomes SWV's remained constant through gestation (p = 0.076; and 0.34). ARFI elastography was shown feasible for evaluation of maternal and foetal tissues stiffness in the ovine model. It can be used to demonstrate pulmonary and hepatic stiffness modifications during foetal development.

Early luteal development in Santa Inês ewes superovulated with reduced doses of porcine follicle-stimulating hormone.

The aim was to compare the early luteal development in ewes superovulated with different doses of pFSH. Twenty-nine Santa Inês ewes received a progesterone device (CIDR®) for 8 days. Gonadotrophic treatment started on Day 6: G200 (control, n = 9, 200 mg); G133 (n = 10, 133 mg); and G100 (n = 10, 100 mg of pFSH). On Day 6, all females received eCG (300 IU). B-mode and spectral Doppler ultrasonography were performed daily during the early luteal phase (Days 11-15) to monitor the development of corpora lutea (CLs; dimensions) and ovarian arteries indices. CLs were also classified as normal or prematurely regressed (PRCL) on Day 15 by videolaparoscopy. Ewes from G100 and G133 showed gradual increase in luteal diameter during the early luteal phase (p < 0.001), whereas G200 animals presented increase from Day 11 to Day 13, and then decrease on Days 14 and 15 (p < 0.001). The G200 females showed greater percentage of PRCL (45.20%) than those of the other groups (p < 0.001). The normal CLs number was greater in G100 than in G133 (p = 0.04), while the PRCL number was greater in G200 than in the other groups (p = 0.03). Resistive index (RI) was greater in G200 than in G100 (p = 0.02). RI was lower in Day 12 than Day 15 (p = 0.02). Pulsatility index (PI) was greater on Days 14 and 15 (p < 0.01). In conclusion, the lowest dose of pFSH (100 mg) can be considered sufficient for an efficient superovulatory response in sheep, producing better CLs development dynamic in early luteal phase and ovarian blood perfusion and smaller number of PRCL than the traditional (200 mg) pFSH dose.

Microbiota associated with tubes of Escarpia sp. from cold seeps in the southwestern Atlantic Ocean constitutes a community distinct from that of surrounding marine sediment and water.

As the depth increases and the light fades in oceanic cold seeps, a variety of chemosynthetic-based benthic communities arise. Previous assessments reported polychaete annelids belonging to the family Siboglinidae as part of the fauna at cold seeps, with the 'Vestimentifera' clade containing specialists that depend on microbial chemosynthetic endosymbionts for nutrition. Little information exists concerning the microbiota of the external portion of the vestimentiferan trunk wall. We employed 16S rDNA-based metabarcoding to describe the external microbiota of the chitin tubes from the vestimentiferan Escarpia collected from a chemosynthetic community in a cold seep area at the southwestern Atlantic Ocean. The most abundant operational taxonomic unit (OTU) belonged to the family Pirellulaceae (phylum Planctomycetes), and the second most abundant OTU belonged to the order Methylococcales (phylum Proteobacteria), composing an average of 21.1 and 15.4% of the total reads on tubes, respectively. These frequencies contrasted with those from the surrounding environment (sediment and water), where they represent no more than 0.1% of the total reads each. Moreover, some taxa with lower abundances were detected only in Escarpia tube walls. These data constitute on the first report of an epibiont microbial community found in close association with external surface of a cold-seep metazoan, Escarpia sp., from a chemosynthetic community in the southwestern Atlantic Ocean.

Dietary leucine supplementation minimises tumour-induced damage in placental tissues of pregnant, tumour-bearing rats.

BACKGROUND: The occurrence of cancer during pregnancy merges two complex, poorly understood metabolic and hormonal conditions. This association can exacerbate the conditions of both the mother and the foetus. The branched-chain amino acid leucine enhances cellular activity, particularly by increasing protein synthesis. This study aimed to analyse the modulatory effect of a leucine-rich diet on direct and indirect tumour-induced placental damage. This was accomplished by evaluating the expression of genes involved in protein synthesis and degradation and assessing anti-oxidant enzyme activity in placental tissues collected from pregnant, tumour-bearing rats. RESULTS: Pregnant rats were either implanted with Walker 256 tumour cells or injected with ascitic fluid (to study the indirect effects of tumour growth) and then fed a leucine-rich diet. Animals in a control group underwent the same procedures but were fed a normal diet. On the 20(th) day of pregnancy, tumour growth was observed. Dams fed a normoprotein diet showed the greatest tumour growth. Injection with ascitic fluid mimicked the effects of tumour growth. Decreased placental protein synthesis and increased protein degradation were observed in both the tumour-bearing and the ascitic fluid-injected groups that were fed a normoprotein diet. These effects resulted in low placental DNA and protein content and high lipid peroxidation (measured by malondialdehyde content). Decreased placental protein synthesis-related gene expression was observed in the tumour group concomitant with increased expression of genes encoding protein degradation-associated proteins and proteolytic subunits. CONCLUSIONS: Consumption of a leucine-rich diet counteracted the effects produced by tumour growth and injection with ascitic fluid. The diet enhanced cell signalling, ameliorated deficiencies in DNA and protein content, and balanced protein synthesis and degradation processes in the placenta. The improvements in cell signalling included changes in the mTOR/eIF pathway. In conclusion, consumption of a leucine-rich diet improved placental metabolism and cell signalling in tumour-bearing rats, and these changes reduced the deleterious effects caused by tumour growth.

Gingivitis, Psychological Factors and Quality of Life in Children.

PURPOSE: To evaluate the associations between gingivitis, emotional status and quality of life in children. MATERIALS AND METHODS: Sixty-four Brazilian students (11 to 12 years old) were examined for clinical and self-reported gingivitis. The participants were divided into two groups: those with gingivitis (n = 21) and controls (n = 43). Quality of life, anxiety and depression were measured using self-administered questionnaires. Saliva was collected 30 min after waking and at bedtime to measure the diurnal decline in salivary cortisol. The results were analysed using bivariate and multivariate analyses. RESULTS: There were significantly more female participants in the control group. Approximately 90% of the children with gingivitis had good oral hygiene and 10.5% had satisfactory oral hygiene. There was a significant positive correlation between anxiety and depression in both clinical groups. Anxiety was negatively correlated with quality of life in the control group. Depression was negatively correlated with quality of life and cortisol concentrations in the group with gingivitis, and with quality of life in the control group. Children with gingivitis were more likely to be older and males. CONCLUSIONS: Older children are more likely to experience gingival bleeding. The presence of gingivitis in children may be associated with worse psychological well-being, possibly compromising the quality of life.

External egg structure of the Pentatomidae (Hemiptera: Heteroptera) and the search for characters with phylogenetic importance.

The chorionic structure of sixteen pentatomid species is described. Morphological patterns in different taxonomic levels are discussed. In addition, egg characters useful in cladistic analyses are listed, and some of those characters are tested for congruence with two cladistic analyses previously conducted within Pentatomidae. Descriptive studies were conducted with Banasa induta, Capivaccius bufo, Catulona pensa, Chinavia armigera, Chinavia aseada, Chinavia brasicola, Chinavia runaspis, Dichelops furcatus, Euschistus heros, Euschistus riograndensis, Euschistus paranticus, Mormidea cornicollis, Podisus distinctus, Podisus nigrispinus, Serdia apicicornis, and Thoreyella maracaja. The eggs were examined and photographed under light and scanning electron microscopy. Based on literature data, a list of 40 egg characters with potential phylogenetic importance has been compiled. Some of these characters were included in the cladistic analyses of the genus Nezara (six characters) and of the Chinavia obstinata group (five characters). Both analyses were performed in TNT with equal weighting of characters. The eggs of most of the Neotropical species studied were barrel-shaped, chorion translucent and spinose, with aero-micropylar processes that were short and clubbed. The patterns of egg morphology could be identified in Carpocorini, Procleticini, and in the genera Banasa, Chinavia, Euschistus, Mormidea, and Podisus. In the cladistic analyses, the inclusion of egg characters did not affect the topology of the trees shown in the original papers. For the analyses, the egg characters were somewhat informative. At present, a total of 286 Pentatomidae species have their egg stage described. 

Cancer in buccal mucosa in patients with Fanconi anemia: Report of six cases.

INTRODUCTION: Fanconi anemia (FA) is a recessive hereditary disease characterized by bone marrow failure, and the treatment is hematopoietic stem cell transplantation (HSCT). Patients diagnosed with FA are more predisposed to develop oral squamous cell carcinoma (SCC), and this risk increases in transplant patients. The clinical characteristics of the oral manifestations of SCC in this group of patients do not differ from the lesions present in patients without the disease; however, they can be diagnosed in young patients and less common locations, such as, for example, in the buccal mucosa. OBJECTIVE: To report a case series of patients diagnosed with FA with oral SCC. METHOD: Included in this case series are six patients diagnosed with SCC in the buccal mucosa with similar clinical characteristics. FINAL CONSIDERATIONS: There are still difficulties in establishing the natural history of oral lesions in patients with FA. Thus, disclosing a series of cases with similar changes may be relevant to improving and refining the multidisciplinary team's clinical view of suspected SCC or oral potentially malignant disorders (OPMD), providing surveillance and timely management.

Mandibular fracture in medication-associated osteonecrosis following infliximab therapy: A case report.

INTRODUCTION: Medication-associated osteonecrosis of the jaws (MRONJ) is characterized by the presence of exposed bone or an intraoral or extraoral fistula in the maxillofacial region in patients with a history of treatment with anti-resorptive and anti-angiogenic drugs, such as monoclonal antibodies, and without a history of radiotherapy or metastatic diseases in the area. OBJECTIVE: The aim of this study is to report a case of a pathological mandibular fracture in an area of MRONJ in a patient diagnosed with Crohn's disease treated with infliximab. CASE REPORT: A 53-year-old male patient, an active smoker for 35 years, diagnosed with Crohn's disease, undergoing intravenous administration of infliximab 300 mg for 1 year and 3 months, with no previous history of anti-angiogenic or anti-resorptive medication, presenting with an extraoral fistula in the submandibular region for 4 months, with painful symptoms, diagnosed as MRONJ. He was initially treated conservatively, using antimicrobial photodynamic therapy (aPDT), antibiotic therapy, and the PENTO protocol. However, the patient evolved with a pathological fracture in the mandibular parasymphysis, requiring surgical reconstruction. FINAL CONSIDERATIONS: Pathological fracture of the mandible is a complication of MRONJ that compromises the patient's quality of life. The management of patients with MRONJ is complex and challenging.

Unraveling DEHP influence on hemoglobin S polymerization in sickle cell disease: Ex vivo, in vitro and in silico analysis.

Sickle cell disease (SCD) is a hereditary hemoglobinopathy, caused by a mutation at position 6 of the ß-globin chain and patients are frequently exposed to several blood transfusions in order to maintain physiological function. Transfusion blood bags are composed of PVC and phthalates (as DEHP) are often introduced to the material in order to confer malleability. In this sense, DEHP can easily elute to the blood and cause harmful effects. This study aimed to unravel DEHP effect on SCD patient's hemoglobin function. We found that HbS polymerization using whole erythrocytes is decreased by DEHP in ex vivo experiments and this effect might be mediated by the DEHP-VAL6 interaction, evaluated in silico. Isolated HbS exhibited less polymerization at low DEHP concentrations and increased polymerization rate at higher concentration. When analyzing the propensity to aggregate, HbS is more inclined to aggregate when compared to HbA due to the residue 6 mutation. Circular dichroism showed characteristic hemoglobin peaks for oxygenated HbS that are lost when oxygen is sequestered, and DEHP at higher concentration mildly recovers a peak close to the second hemoglobin one. Finally, by transmission electron microscopy we demonstrated that high DEHP concentration increased polymer formation with a more organized structure. These findings show for the first-time the beneficial effect of low-dose DEHP on HbS polymerization.

Diacetylcurcumin: a novel strategy against Enterococcus faecalis biofilm in root canal disinfection.

Aim: We evaluated Diacetylcurcumin (DAC), a derivative of curcumin, for its antibacterial and antibiofilm properties against Enterococcus faecalis. Methods: Minimum inhibitory concentration (MIC) and minimum bactericidal concentration were determined, along with antibiofilm potential and toxicity in Galleria mellonella. Additionally, in silico computational analysis was performed to understand its mechanisms of action. Results & conclusion: DAC demonstrated significant antibacterial effects, with MIC and MBC values of 15.6 and 31.25 µg/ml, respectively, and reduced biofilm formation. A synergistic effect, reducing biofilm by 77%, was observed when combined with calcium hydroxide. G. mellonella toxicity tests confirmed DAC's safety at tested concentrations, suggesting its potential for use in root canal disinfection products.

Diacetylcurcumin (DAC) comes from turmeric, a natural spice often used in food. DAC may have the ability to fight germs, including the bacteria Enterococcus faecalis. We tested DAC's ability to kill E. faecalis and stopping the formation of films of the bacteria. We found that a small amount of DAC did kill E. faecalis. When used with calcium hydroxide, DAC works even better to reduce the formation of bacterial films by 77%. DAC is safe to be used on teeth, so may be a useful ingredient for preserving mouth health.

Antimicrobial and antibiofilm activities of Brazilian organic honey against oral microorganisms.

OBJECTIVE: To evaluate the antimicrobial activity of Brazilian honeys against oral microorganisms. DESIGN: Organic honeys (OH-1 to OH-8) were diluted (%-w/v) and sterilized by filtration. Antimicrobial activity was defined by determining MIC and CBM against oral Streptococcus. The component responsible for the antimicrobial action was defined by a catalase assay. Antibiofilm activity was evaluated against the monospecies biofilm of Streptococcus mutans  (ATCC 700610). RESULTS: OHs showed antimicrobial activity principally OH-1, OH-2, OH-3, and OH-7 with MIC values ​​ranging between 10 and 25%. The mechanism of action occurs mainly by hydrogen peroxide produced by honey enzymes. OH-1, OH-2, and OH-7 showed total biofilm destruction at low concentrations. CONCLUSION: Brazilian honeys have promising antimicrobial and antibiofilm activity with the potential to control oral microbiota.