A Comparative Analysis of Innate Immune Responses and the Structural Characterization of Spike from SARS-CoV-2 Gamma Variants and Subvariants.

The SARS-CoV-2 P.1 variant, responsible for an outbreak in Manaus, Brazil, is distinguished by 12 amino acid differences in the S protein, potentially increasing its ACE-2 affinity and immune evasion capability. We investigated the innate immune response of this variant compared to the original B.1 strain, particularly concerning cytokine production. Blood samples from three severe COVID-19 patients were analyzed post-infection with both strains. Results showed no significant difference in cytokine production of mononuclear cells and neutrophils for either variant. While B.1 had higher cytopathogenicity, neither showed viral replication in mononuclear cells. Structural analyses of the S protein highlighted physicochemical variations, which might be linked to the differences in infectivity between the strains. Our studies point to the increased infectivity of P.1 could stem from altered immunogenicity and receptor-binding affinity.

Aspirin Affects MDA-MB-231 Vesicle Production and Their Capacity to Induce Fibroblasts towards a Pro-Invasive State.

Long-term administration of aspirin (ASA, acetylsalicylic acid) in oncogenic patients has been related to a reduction in cancer risk incidence, but its precise mechanism of action is unclear. The activation of cancer-associated fibroblasts (CAFs) is a key element in tumor progression and can be triggered by cancer-derived extracellular vesicles (EVs). Targeting the communication between cancer cells and the surrounding tumor microenvironment (TME) may control cancer progression. Our aim was to investigate the effect of ASA on breast cancer cells, focusing on EV secretion and their effect on the biological properties of CAFs. As a result, ASA was shown to reduce the amount and alter the size distribution of EVs produced by MDA-MB-231 tumor cells. Fibroblasts stimulated with EVs derived from MDA-MB-231 treated with ASA (EV-ASA) showed a lower expression of alpha-smooth muscle actin (α-SMA), matrix metalloproteinase-2 (MMP2) but not fibroblast activation protein (FAP) in respect to the ones stimulated with EVs from untreated breast cancer cells (EV-CTR). Furthermore, invasion assays using a three-dimensional (3D) fibroblast spheroid model showed reduced MDA-MB-231 invasion towards fibroblast spheroids pretreated with EV-ASA as compared to spheroids prepared with EV-CTR-stimulated fibroblasts. This suggests that ASA partially inhibits the ability of tumor EVs to stimulate CAFs to promote cancer invasion. In conclusion, ASA can interfere with tumor communication by reducing EV secretion by breast tumor cells as well as by interfering with their capacity to stimulate fibroblasts to become CAFs.

TF/PAR2 Signaling Axis Supports the Protumor Effect of Neutrophil Extracellular Traps (NETs) on Human Breast Cancer Cells.

Neutrophil extracellular traps (NETs) have been implicated in several hallmarks of cancer. Among the protumor effects, NETs promote epithelial-mesenchymal transition (EMT) in different cancer models. EMT has been linked to an enhanced expression of the clotting-initiating protein, tissue factor (TF), thus favoring the metastatic potential. TF may also exert protumor effects by facilitating the activation of protease-activated receptor 2 (PAR2). Herein, we evaluated whether NETs could induce TF expression in breast cancer cells and further promote procoagulant and intracellular signaling effects via the TF/PAR2 axis. T-47D and MCF7 cell lines were treated with isolated NETs, and samples were obtained for real-time PCR, flow cytometry, Western blotting, and plasma coagulation assays. In silico analyses were performed employing RNA-seq data from breast cancer patients deposited in The Cancer Genome Atlas (TCGA) database. A positive correlation was observed between neutrophil/NETs gene signatures and TF gene expression. Neutrophils/NETs gene signatures and PAR2 gene expression also showed a significant positive correlation in the bioinformatics model. In vitro analysis showed that treatment with NETs upregulated TF gene and protein expression in breast cancer cell lines. The inhibition of ERK/JNK reduced the TF gene expression induced by NETs. Remarkably, the pharmacological or genetic inhibition of the TF/PAR2 signaling axis attenuated the NETs-induced expression of several protumor genes. Also, treatment of NETs with a neutrophil elastase inhibitor reduced the expression of metastasis-related genes. Our results suggest that the TF/PAR2 signaling axis contributes to the pro-cancer effects of NETs in human breast cancer cells.

Hydrothermal aging affects the three-dimensional fit and fatigue lifetime of zirconia abutments.

OBJECTIVE: Evaluate the effect of aging using two different methods on the three-dimensional fit of zirconia abutments at the implant-abutment connection and estimate the probability of survival of anterior crowns supported by straight and 17-degree angled abutments. MATERIALS AND METHODS: Two different zirconia abutment designs, straight and 17-degree angled abutments (n = 63/group), were evaluated in the current study. The abutments were randomly allocated into three experimental groups according to laboratory aging condition (134°C, 2.2 bar, 20 h): (i) control, (ii) autoclave aging, and (iii) hydrothermal reactor aging. Crystalline content was determined by X-Ray diffraction (XRD) and Raman spectroscopy, and microstructure was analyzed using field-emission gun scanning electron microscope (FEG-SEM). Implant-abutment volume misfit was determined in the straight abutments by micro-computed tomography using the silicone replica technique. For fatigue testing, abutments were torqued to the implants and connected to standardized maxillary incisor zirconia crowns. The assemblies were subjected to step-stress accelerated life testing (SSALT) in water until fracture or suspension. The use level probability Weibull curves and probability of survival for a mission of 50,000 cycles at 50, 100, 150 and 200 N were calculated and plotted. Fractured samples were analyzed using a stereomicroscope and scanning electron microscope. RESULTS: The crystalline spectra depicted a zirconia system primarily composed of the tetragonal phase. Laboratory aging yielded a 20%- and 37%-increase in the monoclinic content for abutments aged in autoclave and hydrothermal reactor relative to control, respectively. A fully crystalline matrix with a regular grain size was observed in the FEG-SEM for control abutments, with a considerable presence of intergranular defects. While autoclave aging triggered no significant alteration to the microstructure, defect population was reduced after hydrothermal reactor aging. Control abutments presented a significantly higher volume misfit (2.128 ± 0.54 mm3) relative to aged abutments using autoclave (1.244 ± 0.48 mm3) or hydrothermal reactor (1.441 ± 0.41 mm3). The beta (ß) values indicated that failures were predominantly controlled by material strength rather than fatigue damage accumulation for all groups, except for straight control abutments. Irrespective of aging, the probability of survival of straight and angled zirconia abutments was up to 95% (95-100%) at 50 and 100 N. A 50N-increase in the load resulted in wider range of survival estimate, with straight autoclave abutments percentage significantly lower probability of survival (77%) than angled hydrothermal reactor abutments (99%). At 200N, angled hydrothermal reactor (97%) or autoclave (82%) aged abutments demonstrated the highest probability of survival, angled control (71%) and straight hydrothermal reactor (69%) abutments intermediate values, and straight autoclave (23%) and control (7%) abutments the lowest estimate. The failure mode predominantly involved abutment and/or abutment screw fracture for both straight and angled abutments. CONCLUSIONS: Hydrothermal aging significantly influenced volume misfit, as well as the probability of survival of zirconia abutments at higher loads for both angled and straight abutments.

Alumina-toughened zirconia for dental applications: Physicochemical, mechanical, optical, and residual stress characterization after artificial aging.

To characterize the physicomechanical properties of an alumina-toughened zirconia (ATZ). ATZ synthesis consisted of the addition of alumina particles in an yttria-stabilized tetragonal zirconia polycrystals (3Y-TZP) matrix. Specimens were obtained by uniaxial and isostatic pressing ATZ and 3Y-TZP powders and sintering at 1600°C/1 h and 1550°C/1 h, respectively. Crystalline content and residual stress were evaluated using X-ray diffraction (XRD). Microstructure was characterized by scanning electron microscopy (SEM). Optical properties were determined by reflectance test. Mechanical properties were assessed by biaxial flexural strength test. All analyses were performed before and after aging (134°C, 20 h, 2 bar). XRD and SEM revealed a typical ATZ and 3Y-TZP crystalline content, chiefly tetragonal phase, with a dense polycrystalline matrix, though a smaller grain size for ATZ. Aging triggered a similar monoclinic transformation for both systems; however, ATZ exhibited higher residual compressive stresses than 3Y-TZP. While as-processed 3Y-TZP demonstrated significantly higher characteristic strength relative to ATZ, no significant difference was observed after aging (~215 MPa increase in the ATZ strength). ATZ presented significantly higher opacity relative to 3Y-TZP, although aging significantly increased the translucency of both systems (increase difference significantly higher in the 3Y-TZP compared to ATZ). ATZ physicomechanical properties support its applicability in the dental field, with a lower detrimental effect of aging relative to 3Y-TZP.

Antileishmanial activity of the essential oils of Myrcia ovata Cambess. and Eremanthus erythropappus (DC) McLeisch leads to parasite mitochondrial damage.

Leishmania amazonensis is a species causative of cutaneous and anergic diffuse cutaneous leishmaniasis, treatment-resistant form, in the New World. Plants essential oils exhibit great potential as microbicide agents. We described the composition of the essential oils of two plants native from Brazil, Myrcia ovata, with geranial and neral as major constituents, and Eremanthus erythropappus, with α-bisabolol. In vitro effects of these essential oils on L. amazonensis promastigotes growth and ultrastructure were analysed as well as their cytotoxicity to murine macrophages. Both oils were highly active with IC50/96 h of 8.69 and 9.53 µg/mL for M. ovata and E. erythropappus against promastigotes and caused ultrastructural alterations including mitochondrial enlargement. Cytotoxicity for murine macrophages varied with the oil concentrations. The IC50 low values of both M. ovata and E. erythropappus oils against L. amazonensis and their relative low cytotoxicity to mammal host cells support their potential use against cutaneous leishmaniasis.

Three-dimensional misfit between Ti-Base abutments and implants evaluated by replica technique.

OBJECTIVE: An important factor affecting the biomechanical behavior of implant-supported reconstructions is the implant-abutment misfit. This study evaluated the misfit between Ti-Base abutments and implants by means of polyvinyl siloxane replica technique using microcomputed tomography (µCT). METHODOLOGY: Volumetric and linear (central and marginal) gaps of four Ti-base abutments (n=10/group): (i) Odontofix LTDA (OD), (ii) Singular Implants (SING), (iii) EFF Dental Components (EFF), and (iv) Control Group (S.I.N implants) compatible with an implant system (Strong SW, S.I.N Implants) were measured using µCT reconstructed polyvinyl siloxane replicas. RESULTS: The results showed significantly lower volume gap for Control S.I.N (0.67±0.29 mm3) and SING (0.69±0.28 mm3) Ti-base abutments relative to OD (1.42±0.28 mm3) and EFF groups (1.04±0.28 mm3) (p<0.033), without significant difference between them (p=0.936). While gap values were homogenous in the central region, EFF presented a significantly higher marginal gap. Accordingly, the Control S.I.N and Singular Ti-base abutments showed improved volumetric and marginal fit relative to Odontofix and EFF. CONCLUSION: The method of manufacturing abutments influenced the misfit at the implant-abutment interface.

Neutrophil Extracellular Traps (NETs) Promote Pro-Metastatic Phenotype in Human Breast Cancer Cells through Epithelial-Mesenchymal Transition.

Neutrophil extracellular traps (NETs) have been associated with several steps of tumor progression, including primary growth and metastasis. One of the key features for the acquisition of the metastatic ability is the epithelial-mesenchymal transition (EMT), a complex cellular program. In this study, we evaluated the ability of isolated NETs in modulating the pro-metastatic phenotype of human breast cancer cells. Tumor cells were treated with isolated NETs and then samples were generated for cell migration, quantitative RT-PCR, western blotting, immunofluorescence, and flow cytometry assays. RNA-seq data from The Cancer Genome Atlas (TCGA) database were assessed. NETs changed the typical epithelial morphology of MCF7 cells into a mesenchymal phenotype, a process that was accompanied by enhanced migratory properties. Additional EMT traits were observed: increased expression of N-cadherin and fibronectin, while the E-cadherin expression was repressed. Notably, NETs positively regulated the gene expression of several factors linked to the pro-inflammatory and pro-metastatic properties. Analyses of TCGA data showed that samples from breast cancer patients exhibit a significant correlation between pro-tumoral and neutrophil signature gene expression, including several EMT and pro-metastatic factors. Therefore, NETs drive pro-metastatic phenotype in human breast cancer cells through the activation of the EMT program.

ß-Lapachone enhances the antifungal activity of fluconazole against a Pdr5p-mediated resistant Saccharomyces cerevisiae strain.

OBJECTIVES: The aim of this study was to evaluate the ability of lapachones in disrupting the fungal multidrug resistance (MDR) phenotype, using a model of study which an azole-resistant Saccharomyces cerevisiae mutant strain that overexpresses the ATP-binding cassette (ABC) transporter Pdr5p. METHODS: The evaluation of the antifungal activity of lapachones and their possible synergism with fluconazole against the mutant S. cerevisiae strain was performed through broth microdilution and spot assays. Reactive oxygen species (ROS) and efflux pump activity were assessed by fluorometry. ATPase activity was evaluated by the Fiske and Subbarow method. The effect of ß-lapachone on PDR5 mRNA expression was assessed by RT-PCR. The release of hemoglobin was measured to evaluate the hemolytic activity of ß-lapachone. RESULTS: α-nor-Lapachone and ß-lapachone inhibited S. cerevisiae growth at 100 µg/ml. Only ß-lapachone enhanced the antifungal activity of fluconazole, and this combined action was inhibited by ascorbic acid. ß-Lapachone induced the production of ROS, inhibited Pdr5p-mediated efflux, and impaired Pdr5p ATPase activity. Also, ß-lapachone neither affected the expression of PDR5 nor exerted hemolytic activity. CONCLUSIONS: Data obtained indicate that ß-lapachone is able to inhibit the S. cerevisiae efflux pump Pdr5p. Since this transporter is homologous to fungal ABC transporters, further studies employing clinical isolates that overexpress these proteins will be conducted to evaluate the effect of ß-lapachone on pathogenic fungi.

Interplay Between EGFR and the Platelet-Activating Factor/PAF Receptor Signaling Axis Mediates Aggressive Behavior of Cervical Cancer.

Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase widely expressed in cervical tumors, being correlated with adverse clinical outcomes. EGFR may be activated by a diversity of mechanisms, including transactivation by G-protein coupled receptors (GPCRs). Studies have also shown that platelet-activating factor (PAF), a pro-inflammatory phospholipid mediator, plays an important role in the cancer progression either by modulating the cancer cells or the tumor microenvironment. Most of the PAF effects seem to be mediated by the interaction with its receptor (PAFR), a member of the GPCRs family. PAFR- and EGFR-evoked signaling pathways contribute to tumor biology; however, the interplay between them remains uninvestigated in cervical cancer. In this study, we employed The Cancer Genome Atlas (TCGA) and cancer cell lines to evaluate possible cooperation between EGFR, PAFR, and lysophosphatidylcholine acyltransferases (LPCATs), enzymes involved in the PAF biosynthesis, in the context of cervical cancer. It was observed a strong positive correlation between the expression of EGFR × PAFR and EGFR × LPCAT2 in 306 cervical cancer samples. The increased expression of LPCAT2 was significantly correlated with poor overall survival. Activation of EGFR upregulated the expression of PAFR and LPCAT2 in a MAPK-dependent fashion. At the same time, PAF showed the ability to transactivate EGFR leading to ERK/MAPK activation, cyclooxygenase-2 (COX-2) induction, and cell migration. The positive crosstalk between the PAF-PAFR axis and EGFR demonstrates a relevant linkage between inflammatory and growth factor signaling in cervical cancer cells. Finally, combined PAFR and EGFR targeting treatment impaired clonogenic capacity and viability of aggressive cervical cancer cells more strongly than each treatment separately. Collectively, we proposed that EGFR, LPCAT2, and PAFR emerge as novel targets for cervical cancer therapy.

Three-dimensional misfit between Ti-Base abutments and implants evaluated by replica technique

Abstract An important factor affecting the biomechanical behavior of implant-supported reconstructions is the implant-abutment misfit. Objective: This study evaluated the misfit between Ti-Base abutments and implants by means of polyvinyl siloxane replica technique using microcomputed tomography (μCT). Methodology: Volumetric and linear (central and marginal) gaps of four Ti-base abutments (n=10/group): (i) Odontofix LTDA (OD), (ii) Singular Implants (SING), (iii) EFF Dental Components (EFF), and (iv) Control Group (S.I.N implants) compatible with an implant system (Strong SW, S.I.N Implants) were measured using μCT reconstructed polyvinyl siloxane replicas. Results: The results showed significantly lower volume gap for Control S.I.N (0.67±0.29 mm3) and SING (0.69±0.28 mm3) Ti-base abutments relative to OD (1.42±0.28 mm3) and EFF groups (1.04±0.28 mm3) (p<0.033), without significant difference between them (p=0.936). While gap values were homogenous in the central region, EFF presented a significantly higher marginal gap. Accordingly, the Control S.I.N and Singular Ti-base abutments showed improved volumetric and marginal fit relative to Odontofix and EFF. Conclusion: The method of manufacturing abutments influenced the misfit at the implant-abutment interface.

Polyphenol-Rich Diets Exacerbate AMPK-Mediated Autophagy, Decreasing Proliferation of Mosquito Midgut Microbiota, and Extending Vector Lifespan.

BACKGROUND: Mosquitoes feed on plant-derived fluids such as nectar and sap and are exposed to bioactive molecules found in this dietary source. However, the role of such molecules on mosquito vectorial capacity is unknown. Weather has been recognized as a major determinant of the spread of dengue, and plants under abiotic stress increase their production of polyphenols. RESULTS: Here, we show that including polyphenols in mosquito meals promoted the activation of AMP-dependent protein kinase (AMPK). AMPK positively regulated midgut autophagy leading to a decrease in bacterial proliferation and an increase in vector lifespan. Suppression of AMPK activity resulted in a 6-fold increase in midgut microbiota. Similarly, inhibition of polyphenol-induced autophagy induced an 8-fold increase in bacterial proliferation. Mosquitoes maintained on the polyphenol diet were readily infected by dengue virus. CONCLUSION: The present findings uncover a new direct route by which exacerbation of autophagy through activation of the AMPK pathway leads to a more efficient control of mosquito midgut microbiota and increases the average mosquito lifespan. Our results suggest for the first time that the polyphenol content and availability of the surrounding vegetation may increase the population of mosquitoes prone to infection with arboviruses.

Short-term evaluation of a green tea extract-based mouthrinse / Avaliação de curto prazo de um enxaguatório bucal à base de extrato de chá verde

Introduction: mechanical hygiene is still the best method forthe maintenance of oral health and prevention of biofilm formation. However, mouthrinses have been increasingly used as an adjunct support especially for post-operatory conditions or when periodontal conditions require. In this way, a number of mouthrinses are available, presenting different active ingredients with predominant antimicrobial action. Objectives: the aim of the present study was to evaluate the topical action of a green-tea extract-based mouthwash on gingival tissue. Materials and Methods: a longitudinal double-blind comparison was performed with two groups of patients clinically evaluated and diagnosed as suffering from gingivitis (n= 40). The patients were divided into two groups, according to the mouthrinse used: GT - green tea (concentration of 20mg/ml), and P - placebo, 0.9% saline solution. Clinical examination of the mucosa, tooth staining, plaque and gingival indices were peformed before and 15 days after the continuous use of the products twice a day. Results: no mucosal or tasting alterations were found, neither tooth staining regardless the mouthrinse used. Statistical assessment did not detect differences on gingival indexes between the groups before and after mouthrinses use; however, plaque indexes were significant lower in patients of GT group, compared to the P group. Conclusions: the use of phytotherapic products with active ingredients should be investigated for biofilm control, responsible for the onset and progression of periodontal disease, as well as other various oral pathologies. Considering the period of evaluation pro-posed in this study, relevant decrease in initial phase of plaque for-mation could be observed with the green tea mouthrinse. Further long-term evaluation studies should be carried-out in order to eluci-date its continuous effects on oral structures.

Introdução: higiene mecânica ainda é o melhor método para a manutenção da saúde bucal e prevenção da formação de biofilmes. No entanto, enxagues têm sido cada vez mais usado como um suporte auxiliar especialmente para as condições pós-operatórias ou quando as condições periodontais exigem. Desta forma, um número de bochechos estão disponíveis, apresentando diferentes ingredientes ativos com predominante ação antimicrobiana. Objetivos: o objetivo do presente estudo foi avaliar a ação tópica de um bochecho à base de extrato de chá verde no tecido gengival. Materiais e Métodos: a comparação longitudinal, duplo-cego, foi realizada com dois grupos de pacientes clinicamente avaliados e diagnosticados como portadores de gengivite (n = 40). Os pacientes foram divididos em dois grupos, de acordo com o enxaguatório oral usado: CV - chá verde (concentração de 20 mg / ml), e P - placebo, solução salina a 0,9%. O exame clínico da mucosa, coloração dos dentes, índice de placa e índice gengival foram realizados antes e 15 dias após o uso contínuo dos produtos duas vezes por dia. Resultados: nenhuma alteração na mucosa ou de degustação foi encontrada, assim como não foi identificado modificação na coloração do dente. A Avaliação estatística não detectou diferenças no índice gengival entre os grupos antes e depois de usar enxaguatórios. No entanto, índice de placa inferior foi menor de forma significativa nos pacientes do grupo CV, em comparação com o grupo P. Conclusões: o uso de produtos fitoterápicos com ingredientes ativos deve ser investigado para o controle de biofilme, responsável pelo aparecimento e progressão da doença periodontal. Considerando o período de avaliação proposto, a redução correspondente na fase inicial da formação de placa pôde ser observada com o enxaguatório à base de chá verde. Além disso, estudos de avaliação de longo prazo devem ser realizados, a fim de elucidar seu efeito contínuo em longo prazo sobre as estruturas orais.

Cluster randomized pilot controlled trial of an occupational therapy intervention for residents with stroke in UK care homes.

BACKGROUND AND PURPOSE: A pilot evaluation of an occupational therapy intervention to improve self-care independence for residents with stroke-related disability living in care homes was the basis of this study. METHODS: A cluster randomized controlled trial with care home as the unit of randomization was undertaken in Oxfordshire, UK. Twelve homes (118 residents) were randomly allocated to either intervention (6 homes, 63 residents) or control (6 homes, 55 residents). Occupational therapy was provided to individuals but included carer education. The control group received usual care. Assessments were made at baseline, postintervention (3 months) and at 6-months to estimate change using the Barthel Activity of Daily Living Index (BI) scores, "poor global outcome", (defined as deterioration in BI score, or death) and the Rivermead Mobility Index. RESULTS: At 3 months BI score in survivors had increased by 0.6 (SD 3.9) in the intervention group and decreased by 0.9 (2.2) in the control group; a difference of 1.5 (95% CI allowing for cluster design, -0.5 to 3.5). At 6 months the difference was 1.9 (-0.7 to 4.4). Global poor outcome was less common in the intervention group. At 3 months, 20/63 (32%) were worse/dead in the intervention group compared with 31/55 (56%) in the control group, difference -25% (-51% to 1%). At 6 months the difference was similar, -26% (-48% to -3%). Between-group changes in Rivermead Mobility Index scores were not significantly different. CONCLUSIONS: Residents who received an occupational therapy intervention were less likely to deteriorate in their ability to perform activities of daily living.

An investigation into the utility of the Stroke Aphasic Depression Questionnaire (SADQ) in care home settings.

OBJECTIVE: To assess the utility of the Stroke Aphasia Depression Scale (SADQ) to identify emotional distress among individuals living in a care home setting. DESIGN: A prospective comparison of the SADQ and the depression subsection of the Hospital Anxiety and Depression Scale (HADS). SETTING: Care homes in Oxfordshire. PARTICIPANTS: Eighty-two care home residents without major communication or cognitive problems. MEASURES: Participants completed the HADS. The SADQ was completed on behalf of each resident by his or her principal carer. RESULTS: Spearman's rank correlation between the two measures was statistically significant (r = 0.447, P < 0.01). Receiver operator characteristics plots revealed an optimal cut-off point of 14 on the SADQ which gave sensitivity and specificity of 77% and 78% respectively. CONCLUSION: The SADQ, an observational measure, can identify emotional distress in non-aphasic patients in a care home setting. It would be reasonable to use it with people with communication and cognitive problems who are unable to take part in conventional assessments.

Experiência Clínica na avaliação de 284 casos de erisipela / Clinical experience assessing 284 cases of erisipela

Os autores analisam algumas características da erisipela no Brasil, alertando para a importância das formas de prevenção de recorrências, que podem ocasionar um quadro clínico de elefantíase, limitando muito as atividades familiares, sociais e profissionais do paciente. Fazem uma análise retrospectiva de 284 casos de erisipela no período de 1995 a 1996, analisando os seguintes fatores: sexo, idade, topografia da lesão, predisposição local e sistêmica, porta de entrada, tratamento, complicações e eventual necessidade de internação. Os resultados mostram que os homens e os obesos são mais atingidos pela doença, a faixa etária com maior incidência é a dos 60 aos 70 anos, e os membros inferiores são os locais de preferência para instalação. Nesta casuística, a tinha dos pés foi a principal porta de entrada da infecção bacteriana, e, quando o paciente apresentava bolhas necrotizantes, houve necessidade de internação hospitalar para tratamento. Como medicação de escolha e não havendo contra-indicação, a maioria dos casos foi tratada com penicilina benzatina e a cristalina