Can the essential oil of rosemary (Rosmarinus officinalis Linn.) protect rats infected with itraconazole-resistant Sporothrix brasiliensis from fungal spread?

INTRODUCTION: Itraconazole is the first-choice option to treat human and animal sporotrichosis. However, the emergence of itraconazole-resistant strains has encouraged research on new active antifungals. Among them, the essential oil of rosemary (Rosmarinus officinalis Linn., Lamiaceae) has shown antifungal activity in vitro. OBJECTIVE: Assessing, for the first time, the effectiveness of rosemary essential oil in vivo in experimental cutaneous sporotrichosis, as well as its chemical composition and action mode. METHODS: Itraconazole-resistant Sporothrix brasiliensis was inoculated in the left foot pad of 30 Wistar rats, which were randomized (n=10) for treatment with saline solution (control, CONT), itraconazole (ITRA, 10 mg/kg) and rosemary oil (ROSM, 250 mg/kg) for 30 days at an oral dose of 1 mL, daily. Clinical evolution, histopathology and fungal burden were investigated. GC-MS was used for chemical analysis; sorbitol protection and ergosterol effect were used to evaluate the action mechanism of rosemary oil. RESULTS: ROSM was the only group evolving to skin lesion remission, lack of edema and exudate, and mild-to-absent yeast cells. Rosemary oil delayed fungal spreading and protected systemic organs, mainly liver and spleen. The ROSM group presented lower fungal load than that observed for the CONT and ITRA groups (p<0.05). Antifungal action took place at complexation level after ergosterol application. Most compounds were 1,8-cineole/eucalyptol (47.91%), camphor (17.92%), and α-pinene (11.52%). CONCLUSIONS: These findings have evidenced that rosemary oil is a promising antifungal to treat sporotrichosis, since it protects systemic organs from fungal spread.

Soft tissue assessment before and after mandibular advancement or setback surgery using three-dimensional images: systematic review and meta-analysis.

The aim of this systematic review was to evaluate the effects of mandibular advancement or setback surgery on the facial soft tissue assessed using three-dimensional images. An electronic search was performed in the MEDLINE, Cochrane Library, Scopus, Virtual Health Library (VHL), Web of Science, and OpenGrey databases. Inclusion criteria comprised studies that evaluated the soft tissues of adult patients before and after mandibular advancement or setback surgery using computed tomography or magnetic resonance imaging. The risk of bias was analyzed. A total of 3501 studies were retrieved. The titles and abstracts of 2071 studies were read and 2040 of them were excluded. Thirty-one articles were read in full and six fulfilled the eligibility criteria and were included. A meta-analysis was performed using three of these articles. The correlation was significant and strong in the chin area (r=0.876 and r=0.868) and moderate for the lower lip/lower incisor (r=0.690). The ratio for lower lip/infradentale was 78% and for Pog'/Pog was 98%. Due to the limited number of articles included, there is weak evidence to infer that changes in the facial soft tissue due to mandibular advancement or setback are significant, but changes in the lower lip tend to be smaller than changes in the chin area.

Three-dimensional changes to the upper airway after maxillomandibular advancement with counterclockwise rotation: a systematic review and meta-analysis.

The aim of this study was to evaluate the effect of counterclockwise (CCW) rotation and maxillomandibular advancement (MMA) on the upper airway space using three-dimensional images. An electronic search was performed in the PubMed, Cochrane Library, Scopus, Virtual Health Library, Web of Science, and OpenGrey databases (end date July 2016); a hand-search of primary study reference lists was also conducted. The inclusion criteria encompassed computed tomography evaluations of the upper airway spaces of adult patients undergoing orthognathic surgery with CCW rotation and MMA. The articles were evaluated for risk of bias with a tool for before-and-after studies. A meta-analysis was performed with the mean differences using a random-effects model. Heterogeneity was assessed with the Q-test and the I2 index. The meta-analysis revealed significant (P<0.001) increases in both the total airway volume (effect size of 6832mm3 and confidence interval of 5554-8109mm3) and the minimum axial area (effect size of 92mm2 and confidence interval of 70-113mm2). The heterogeneity was low in both comparisons (I2=38% and 7%, respectively). The technique of mandibular advancement with CCW rotation produced significant increases in the volumes and areas of the upper airway spaces.

Adverse birth outcomes associated with Zika virus exposure during pregnancy in São José do Rio Preto, Brazil.

OBJECTIVES: We aimed to report the first 54 cases of pregnant women infected by Zika virus (ZIKV) and their virologic and clinical outcomes, as well as their newborns' outcomes, in 2016, after the emergence of ZIKV in dengue-endemic areas of São Paulo, Brazil. METHODS: This descriptive study was performed from February to October 2016 on 54 quantitative real-time PCR ZIKV-positive pregnant women identified by the public health authority of São José do Rio Preto, São Paulo, Brazil. The women were followed and had clinical and epidemiologic data collected before and after birth. Adverse outcomes in newborns were analysed and reported. Urine or blood samples from newborns were collected to identify ZIKV infection by reverse transcription PCR (RT-PCR). RESULTS: A total of 216 acute Zika-suspected pregnant women were identified, and 54 had the diagnosis confirmed by RT-PCR. None of the 54 women miscarried. Among the 54 newborns, 15 exhibited adverse outcomes at birth. The highest number of ZIKV infections occurred during the second and third trimesters. No cases of microcephaly were reported, though a broad clinical spectrum of outcomes, including lenticulostriate vasculopathy, subependymal cysts, and auditory and ophthalmologic disorders, were identified. ZIKV RNA was detected in 18 of 51 newborns tested and in eight of 15 newborns with adverse outcomes. CONCLUSIONS: Although other studies have associated many newborn outcomes to ZIKV infection during pregnancy, these same adverse outcomes were rare or nonexistent in this study. The clinical presentation the newborns we studied was mild compared to other reports, suggesting that there is significant heterogeneity in congenital Zika infection.

Evaluation of gene expression levels for cytokines in ocular toxoplasmosis.

This study evaluated levels for mRNA expression of 7 cytokines in ocular toxoplasmosis. Peripheral blood mononuclear cells (PBMC) of patients with ocular toxoplasmosis (OT Group, n = 23) and chronic toxoplasmosis individuals (CHR Group, n = 9) were isolated and stimulated in vitro with T. gondii antigen. Negative controls (NC) were constituted of 7 PBMC samples from individuals seronegative for toxoplasmosis. mRNA expression for cytokines was determined by qPCR. Results showed a significant increase in mRNA levels from antigen stimulated PBMCs derived from OT Group for expressing IL-6 (at P < .005 and P < .0005 for CHR and NC groups, respectively), IL-10 (at P < .0005 and P < .005 for CHR and NC groups, respectively) and TGF-ß (at P < .005) for NC group. mRNA levels for TNF-α and IL-12 were also upregulated in patients with OT compared to CHR and NC individuals, although without statistical significance. Additionally, mRNA levels for IL-27 and IFN-γ in PBMC of patients with OT were upregulated in comparison with NC individuals. Differences between OT and NC groups were statistically significant at P < .05 and P < .0005, respectively.

How do geometry-related parameters influence the clinical performance of orthodontic mini-implants? A systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to investigate how parameters related to geometry influence the clinical performance of orthodontic mini-implants (MIs). Systematic searches were performed in electronic databases including MEDLINE, Scopus, Web of Science, Virtual Health Library, and Cochrane Library and reference lists up to March 2016. Eligibility criteria comprised clinical studies involving patients who received MIs for orthodontic anchorage, with data for categories of MI dimension, shape, and thread design and insertion site, and evaluated by assessment of primary and secondary stability. Study selection, data extraction, quality assessment, and a meta-analysis were carried out. Twenty-seven studies were included in the qualitative synthesis: five randomized, eight prospective, and 14 retrospective clinical studies. One study with a serious risk of bias was later excluded. Medium and short MIs (1.4-1.9mm diameter and 5-8mm length) presented the highest success rates (0.87, 95% CI 0.80-0.92). A maximum insertion torque of 13.28Ncm (standard error 0.34) was observed for tapered self-drilling MIs in the mandible, whereas cylindrical MIs in the maxilla presented a maximum removal torque of 10.01Ncm (standard error 0.17). Moderate evidence indicates that the clinical performance of MIs is influenced by implant geometry parameters and is also related to properties of the insertion site. However, further research is necessary to support these associations.

Single nucleotide polymorphisms in the CNTNAP2 gene in Brazilian patients with autistic spectrum disorder.

The role of some genes and their single nucleotide polymorphisms (SNPs) as genetic contributors of complex diseases is still a topic of much investigation. Research on genes related to autism susceptibility has been somewhat challenging, but also promising. Common genomic variants of CNTNAP2 have been associated with autism, and a range of autistic phenotypes such as impaired language function, abnormal social behavior, intellectual deficiency, epilepsy, and schizophrenia have been associated with this gene. Earlier findings have suggested that SNPs in the CNTNAP2 gene may be used as genetic markers for predisposition to autism spectrum disorder (ASD). We analyzed the SNPs (rs7794745 and rs2710102) in the CNTNAP2 gene of 210 individuals with idiopathic ASD and 200 non-autistic individuals by polymerase chain reaction-restriction fragment length polymorphism. The results revealed higher frequency distributions statistically significant (P = 0.034) of the homozygous SNP rs7794745 (presumed risk genotype) in ASD patients as compared with control subjects. The results also showed an association (OR = 1.802, 95%CI = 1.054-3.083, P = 0.042) between the same homozygous genotype and ASD, suggesting that it is a susceptibility factor for autism in this Brazilian population.

Upper airway dimensions in patients undergoing orthognathic surgery: a systematic review and meta-analysis.

The objective of this systematic review was to evaluate the effect of different types of orthognathic surgery on the dimensions of the upper airways assessed using three-dimensional images. An electronic search was performed in Cochrane Library, Medline, Scopus, VHL, Web of Science, and the System for Information on Grey Literature in Europe, ending January 2015. Inclusion criteria encompassed clinical studies in humans, patient age >15 years, patients submitted to maxillary or mandibular advancement or setback surgery, isolated or in combination, and presentation of airway measures, specifically volume and/or minimum cross-sectional area (CSA), obtained from computed tomography or magnetic resonance imaging. Additional searches were conducted on the references of included articles and in the NLM catalogue. An assessment of the risk of bias was performed. A total of 1180 studies were retrieved, of which 28 met the eligibility criteria; one was later excluded as it presented a high risk of bias. A meta-analysis was performed. There is moderate evidence to conclude that the upper airway minimum CSA increases significantly (124.13 mm(2)) after maxillomandibular advancement (MMA); the total volume increases significantly after MMA (7416.10mm(3)) and decreases significantly after maxillary advancement+mandibular setback (-1552.90 mm(3)) and isolated mandibular setback (-1894.65 mm(3)).

Long-term prognosis of tooth autotransplantation: a systematic review and meta-analysis.

The aim of this study was to systematically review the prognosis of autotransplanted teeth followed up for a period of 6 years or more. A literature search was conducted in five databases and the eligibility criteria were established. The outcomes evaluated were the survival rate, percentage of abnormal mobility, pulpal conditions, and percentage of root resorption. The searches identified 1848 articles, and after evaluation against the eligibility criteria, six were included. Data related to outcome measures were extracted from the studies and a meta-analysis was performed. Survival rates ranged from 75.3% to 91% and the meta-analysis showed an effect size of 81% (P<0.0001). The percentage ankylosis ranged from 4.2% to 18.2% and the effect size was 4.8% (P<0.0001). Root resorption percentages ranged from 3% to 10% and the effect size was equal to 4% (P<0.0001). It was not possible to perform a meta-analysis of data on pulpal conditions and percentage of teeth with abnormal mobility. The results of this study showed the survival rate to be excellent, considering the observation period. The rates of ankylosis and root resorption, despite their low values, influence the prognosis of transplanted teeth.

Lewis histo-blood group system phenotyping and genotyping reveal divergence in the association of Le(a-b-) phenotype and type 1 diabetes.

BACKGROUND AND OBJECTIVES: The red blood cell Le(a-b-) phenotype was proposed as risk factor for type 1 diabetes, but contradictory results were published elsewhere. This study re-examined the potential association between Lewis histo-blood group system and type 1 diabetes. MATERIAL AND METHODS: Patients and controls of both sexes, Caucasians and non-Caucasians, matched by sex, geographical origin and ethnicity were evaluated. The red blood cell Lewis phenotypes were identified by gel column agglutination and also inferred from the FUT2 and FUT3 genotyping. RESULTS: The Le(a-b-) phenotype was prevalent in patients with type 1 diabetes, and the Le(a-b+) phenotype was prevalent in controls when both were determined by gel columns agglutination. No differences were observed in the frequencies of the Le(a-b-) phenotype inferred from the FUT2 and FUT3 genotyping between patients and controls. CONCLUSIONS: The Lewis red blood cell phenotyping and genotyping reveal divergence in the association of Le(a-b-) phenotype and type 1 diabetes.

Frequencies of allele groups HLA-A, HLA-B and HLA-DRB1 in a population from the northwestern region of São Paulo State, Brazil.

The aim of this study was to estimate the HLA-A, HLA-B and HLA-DRB1 allele groups frequencies in a population of 1559 volunteer bone marrow donors from the northwestern region of São Paulo State grouped according to ethnicity. An additional objective was to compare the allele frequencies of the current study with data published for other Brazilian populations. The allele groups were characterized by the PCR-rSSO method using Luminex(®) technology. Twenty HLA-A, 32 HLA-B and 13 HLA-DRB1 allele groups were identified. The most common allele groups in European descent and mixed African and European descent samples were HLA-A*02, HLA-B*35 and HLA-DRB1*13, while HLA-A*02, HLA-B*35 and HLA-DRB1*11 were more common in African descent samples. The HLA-A*23, HLA-A*36, HLA-B*58 and HLA-B*81 allele groups were more common in sample from African descent than European descent, and the HLA-DRB1*08 was more common in mixed African and European descent than in European descent. Allele group frequencies were compared with samples from other Brazilian regions. The HLA-A*30 and HLA-A*23 were more common in this study than in the populations of Rio Grande do Sul and Paraná; and the HLA-A*01, HLA-B*18, HLA-B*57 and HLA-DRB1*11 were more common in this study than in the population of Piauí. The least frequent allele groups were HLA-A*31, HLA-B*15, HLA-B*40 and HLA-DRB1*08 for the population of Piauí, HLA-A*01 and HLA-A*11 for Parana, HLA-A*02 and -A*03 for Rio Grande do Sul and HLA-DRB1*04 for Paraná, Rio Grande do Sul and Piauí. These data provide an overview on the knowledge on HLA diversity in the population of the northwestern region of São Paulo State and show that the genes of this system are useful to distinguish different ethnic groups.

Risk factors for ocular toxoplasmosis in Brazil.

The aim of this study was to investigate risk factors for ocular toxoplasmosis (OT) in patients who received medical attention at a public health service. Three hundred and forty-nine consecutive patients, treated in the Outpatient Eye Clinic of Hospital de Base, São José do Rio Preto, São Paulo state, Brazil, were enrolled in this study. After an eye examination, enzyme-linked immunosorbent assay (ELISA) was used to determine anti-Toxoplasma gondii antibodies. The results showed that 25.5% of the patients were seronegative and 74.5% were seropositive for IgG anti-T. gondii antibodies; of these 27.3% had OT and 72.7% had other ocular diseases (OOD). The presence of cats or dogs [odds ratio (OR) 2.22, 95% confidence interval (CI) 1.24-3.98, P = 0.009] and consumption of raw or undercooked meat (OR 1.77, 95% CI 1.05-2.98, P = 0.03) were associated with infection but not with the development of OT. Age (OT 48.2 ± 21.2 years vs. OOD: 69.5 ± 14.7 years, P < 0.0001) and the low level of schooling/literacy (OT vs. OOD: OR 0.414, 95% CI 0.2231-0.7692, P = 0.007) were associated with OT. The presence of dogs and cats as well as eating raw/undercooked meat increases the risk of infection, but is not associated with the development of OT.

Cerebral and ocular toxoplasmosis related with IFN-y, TNF-a, and IL-10

This study analyzed the synthesis of Interferon gamma (IFN-γ), Tumor Necrosis Factor alpha (TNF-α), and Interleukin 10 (IL-10) in chronically infected patients which developed the symptomatic disease as cerebral or ocular toxoplasmosis. Blood from 61 individuals were divided into four groups: Cerebral toxoplasmosis/AIDS patients (CT/AIDS group) (n = 15), ocular toxoplasmosis patients (OT group) (n = 23), chronic toxoplasmosis individuals (CHR group) (n = 13) and healthy individuals (HI group) (n = 10). OT, CHR, and HI groups were human immunodeficiency virus (HIV) seronegative. The diagnosis was made by laboratorial (PCR and ELISA) and clinical subjects. For cytokine determination, peripheral blood mononuclear cells (PBMC) of each patient were isolated and stimulated in vitro with T. gondii antigen. IFN-γ, TNF-α, and IL-10 activities were determined by ELISA. Patients from CT/AIDS and OT groups had low levels of IFN-γ when were compared with those from CHR group. These data suggest the low resistance to develop ocular lesions by the low ability to produce IFN-γ against the parasite. The same patients, which developed ocular or cerebral toxoplasmosis had higher TNF-α levels than CHR individuals. High TNF-α synthesis contribute to the inflammatory response and damage of the choroid and retina in OT patients and in AIDS patients caused a high inflammatory response as the TNF-α synthesis is not affected since monocytes are the major source this cytokine in response to soluble T. gondii antigens. IL-10 levels were almost similar in CT/AIDS and OT patients but low when compared with CHR individuals. The deviation to Th2 immune response including the production of anti-inflammatory cytokines, such as IL-10 may promote the parasite's survival causing the tissue immune destruction. IL-10 production in T. gondii-infected brains may support the persistence of parasites as down-regulating the intracerebral immune response. All these indicate that OT and CT/AIDS patients produced low levels of IL-10 (Th2 response) and IFN-γ (Th1 response). They produced high TNF-α suggesting a high inflammatory response triggered by the parasite.

Population fluctuation and damage caused by phytophagous mites on three rubber tree clones.

Our aim was to investigate the population fluctuation and the damage caused by the phytophagous mites Calacarus heveae Feres, Tenuipalpus heveae Baker, and Eutetranychus banksi (McGregor) on clones FX 2784, FX 3864, and MDF 180 in rubber tree crops from southeastern Bahia, Brazil. Moreover, we tested for the influence of climatic variables on occurrence patterns of these species throughout weekly samples performed from October to April. The infestation peaks was between mid-January and late February. The clones FX 2784 and FX 3864 had the highest infestations and more severe damage possibly caused by C. heveae, which was the most frequent and abundant species in all clones. We found that sunlight duration and rainfall were the most important factors for C. heveae while T. heveae was affected by rainfall and temperature. Eutetranychus banksi was only affected by sunlight duration. However, the best models had low goodness of fit. We concluded that the clones FX 2784 and FX 3864 had a higher susceptibility to mite attack, and the association between climatic variables and favorable physiological conditions were determinant for the population increase of the species from January to April.

The emergence of wildlife species as a source of human rabies infection in Brazil.

Forty-five human rabies virus isolates from a wide geographical area of Brazil were characterized using an anti-nucleoprotein monoclonal antibody panel and by partial nucleotide sequencing analysis of the nucleoprotein gene. Three major antigenic groups related to the antigenic variants maintained in domestic dogs, vampire bats and marmosets were identified. Phylogenetic analyses revealed that the viruses from dog-related cases segregated into four sister clades: three associated with dog-endemic cycles in Brazil and one with the crab-eating fox cycle in the northeastern region of the country. The vampire bat- and marmoset-related viruses formed two independent groups. The topology of these clades was conserved when these samples were compared to virus representatives of the currently reported rabies endemic cycles in the Americas. These results indicated the presence of multiple endemic transmission cycles maintained in four different reservoirs, domestic dogs, crab-eating foxes, vampire bats and marmosets, which are being transmitted directly to humans and should be considered as a high-risk for rabies infection.

Lack of association of the G22A polymorphism of the ADA gene in patients with ankylosing spondylitis.

Genes located outside the HLA region (6p21) have been considered as candidates for susceptibility to ankylosing spondylitis. We tested the hypothesis that the G22A polymorphism of the adenosine deaminase gene (ADA; 20q13.11) is associated with ankylosing spondylitis in 166 Brazilian subjects genotyped for the HLA*27 gene (47 patients and 119 controls matched for gender, age and geographic origin). The HLA-B*27 gene and the G22A ADA polymorphism were identified by PCR with sequence-specific oligonucleotide probes and PCR-RFLP, respectively. There were no significant differences in frequencies of ADA genotypes [odds ratio (OR) = 1.200, 95% confidence interval (CI) = 0.3102-4.643, P > 0.8] and ADA*01 and ADA*02 alleles (OR = 1.192, 95%CI = 0.3155-4.505, P > 0.8) in patients versus controls. We conclude that the G22A polymorphism is not associated with ankylosing spondylitis.

Numerical analysis of the biomechanical behaviour of a weakened root after adhesive reconstruction and post-core rehabilitation.

OBJECTIVES: The purpose of this study was to perform a finite element analysis to determine whether adhesive reconstruction is able to restore the original biomechanical behaviour of weakened roots, in terms of fracture resistance, when compared with post/crown-restored teeth with intact roots. METHODS: A three-dimensional model of a maxillary central incisor was created. The model simulated an endodontically treated tooth restored with a glass-fibre post, a composite-resin core and a metal crown (Model 1). Based on Model 1, a new volume was created in the root cervical third that represented the area where the dentine structure was lost, resulting in a structurally damaged root (Model 2). A 100N load was applied to the palatal surface at 130° from the long axis of the tooth. After processing (Ansys(®) 10.0 - Canonsburg, PA, USA), the principal normal stress data were analyzed (S1, tensile; S3, compressive). RESULTS: The models demonstrated a similar S1 distribution concentrated in the lingual cervical region but different S1 levels (Model 1: 28.7MPa; Model 2: 35.3MPa). The S3 distribution indicated differences in behaviour between the models (Model 1: -18 to -27MPa along the buccal root surface; Model 2: -25 to -32MPa on the post buccal surface and along the buccal root wall). CONCLUSIONS: Although the stress distribution within the root walls remained below the ultimate stress limit of the root dentine, the adhesive reconstruction of the weakened roots did not recover the load resistance of structurally intact roots. CLINICAL SIGNIFICANCE: The decision of when to prosthetically rehabilitate weakened roots with cervical dentine structural tissue loss is a challenge for clinicians. A 'monoblock' adhesive reconstruction has been proposed for root reinforcement. During treatment planning, the possibility of restoring the mechanical resistance of the root must be evaluated if successful long-term results are to be achieved.

Pathological fractures in children.

Pathological fractures in children can occur as a result of a variety of conditions, ranging from metabolic diseases and infection to tumours. Fractures through benign and malignant bone tumours should be recognised and managed appropriately by the treating orthopaedic surgeon. The most common benign bone tumours that cause pathological fractures in children are unicameral bone cysts, aneurysmal bone cysts, non-ossifying fibromas and fibrous dysplasia. Although pathological fractures through a primary bone malignancy are rare, these should be recognised quickly in order to achieve better outcomes. A thorough history, physical examination and review of plain radiographs are crucial to determine the cause and guide treatment. In most benign cases the fracture will heal and the lesion can be addressed at the time of the fracture, or after the fracture is healed. A step-wise and multidisciplinary approach is necessary in caring for paediatric patients with malignancies. Pathological fractures do not have to be treated by amputation; these fractures can heal and limb salvage can be performed when indicated.