Leishmania (Leishmania) infantum DNA detection in Nyssomyia neivai in Vale do Ribeira, Paraná, Brazil.

BACKGROUND: The incidence of visceral leishmaniasis (VL) has increased in the Southern region of Brazil in recent years, especially in the State of Paraná. New species have been suggested with potential to act as vector in VL endemic areas. OBJECTIVES: Identify the Leishmania species in sand fly specimens collected from 2016 to 2018 in the municipality of Itaperuçu, Vale do Ribeira, Paraná, Brazil. METHODS: Light traps were used for collections and for the analysis of sand fly were used the multiplex polymerase chain reaction (PCR) methodology and subsequent sequencing. FINDINGS: Among the collected specimens, 88.62% were attributed to the species Nyssomyia neivai, which were grouped into 176 pools. Three positive pools were detected: two with Leishmania (Viannia) braziliensis and one with L. (Leishmania) infantum. The positivity rate for the parasite was 0.25% based on the presence of at least one infected insect in the pool. MAIN CONCLUSIONS: The detection of L. infantum in Ny. neivai draws attention due to its abundance and anthropophily in the State of Paraná. Moreover, this finding is considered as an alert and suggests that the vector competence of Ny. neivai and the criteria for its incrimination should be carried out, given its wide distribution in southern of Brazil.

Characterisation of an area of coexistent visceral and cutaneous leishmaniasis transmission in the State of Piauí, Brazil.

BACKGROUND: In Brazil, transmission of visceral and cutaneous leishmaniasis has expanded geographically over the last decades, with both clinical forms occurring simultaneously in the same area. OBJECTIVES: This study characterised the clinical, spatial, and temporal distribution, and performed entomological surveillance and natural infection analysis of a leishmaniasis-endemic area. METHODS: In order to characterise the risk of leishmaniasis transmission in Altos, Piauí, we described the clinical and socio-demographic variables and the spatial and temporal distribution of cases of American visceral leishmaniasis (AVL) and American cutaneous leishmaniasis (ACL) cases and identified potential phlebotomine vectors. FINDINGS: The urban area concentrated almost 54% of ACL and 86.8% of AVL cases. The temporal and spatial distribution of AVL and ACL cases in Altos show a reduction in the number of risk areas, but the presence of permanent disease transmission foci is observed especially in the urban area. 3,808 phlebotomine specimens were captured, with Lutzomyia longipalpis as the most frequent species (98.45%). Of the 35 females assessed for natural infection, one specimen of Lu. longipalpis tested positive for the presence of Leishmania infantum and Leishmania braziliensis DNA. MAIN CONCLUSION: Our results indicate the presence of risk areas for ACL and AVL in the municipality of Altos and highlight the importance of entomological surveillance to further understand a possible role of Lu. longipalpis in ACL transmission.

Comprehensive Genomic Analysis of Cemento-Ossifying Fibroma.

Cemento-ossifying fibroma (COF) of the jaws is currently classified as a benign mesenchymal odontogenic tumor, and only targeted approaches have been used to assess its genetic alterations. A minimal proportion of COFs harbor CDC73 somatic mutations, and copy number alterations (CNAs) involving chromosomes 7 and 12 have recently been reported in a small proportion of cases. However, the genetic background of COFs remains obscure. We used a combination of whole-exome sequencing and RNA sequencing to assess somatic mutations, fusion transcripts, and CNAs in a cohort of 12 freshly collected COFs. No recurrent fusions have been identified among the 5 cases successfully analyzed by RNA sequencing, with in-frame fusions being detected in 2 cases (MARS1::GOLT1B and PARG::BMS1 in one case and NCLN::FZR1 and NFIC::SAMD1 in the other case) and no candidate fusions identified for the remaining 3 cases. No recurrent pathogenic mutations were detected in the 11 cases that had undergone whole-exome sequencing. A KRAS p.L19F missense variant was detected in one case, and 2 CDC73 deletions were detected in another case. The other variants were of uncertain significance and included variants in PC, ACTB, DOK6, HACE1, and COL1A2 and previously unreported variants in PTPN14, ATP5F1C, APOBEC1, HDAC5, ATF7IP, PARP2, and ACTR3B. The affected genes do not clearly converge on any signaling pathway. CNAs were detected in 5/11 cases (45%), with copy gains involving chromosome 12 occurring in 3/11 cases (27%). In conclusion, no recurrent fusions or pathogenic variants have been detected in the present COF cohort, with copy gains involving chromosome 12 occurring in 27% of cases.

Characterisation of an area of coexistent visceral and cutaneous leishmaniasis transmission in the State of Piauí, Brazil

BACKGROUND In Brazil, transmission of visceral and cutaneous leishmaniasis has expanded geographically over the last decades, with both clinical forms occurring simultaneously in the same area. OBJECTIVES This study characterised the clinical, spatial, and temporal distribution, and performed entomological surveillance and natural infection analysis of a leishmaniasis-endemic area. METHODS In order to characterise the risk of leishmaniasis transmission in Altos, Piauí, we described the clinical and socio-demographic variables and the spatial and temporal distribution of cases of American visceral leishmaniasis (AVL) and American cutaneous leishmaniasis (ACL) cases and identified potential phlebotomine vectors. FINDINGS The urban area concentrated almost 54% of ACL and 86.8% of AVL cases. The temporal and spatial distribution of AVL and ACL cases in Altos show a reduction in the number of risk areas, but the presence of permanent disease transmission foci is observed especially in the urban area. 3,808 phlebotomine specimens were captured, with Lutzomyia longipalpis as the most frequent species (98.45%). Of the 35 females assessed for natural infection, one specimen of Lu. longipalpis tested positive for the presence of Leishmania infantum and Leishmania braziliensis DNA. MAIN CONCLUSION Our results indicate the presence of risk areas for ACL and AVL in the municipality of Altos and highlight the importance of entomological surveillance to further understand a possible role of Lu. longipalpis in ACL transmission.

Leishmania (Leishmania) infantum DNA detection in Nyssomyia neivai in Vale do Ribeira, Paraná, Brazil

BACKGROUND The incidence of visceral leishmaniasis (VL) has increased in the Southern region of Brazil in recent years, especially in the State of Paraná. New species have been suggested with potential to act as vector in VL endemic areas. OBJECTIVES Identify the Leishmania species in sand fly specimens collected from 2016 to 2018 in the municipality of Itaperuçu, Vale do Ribeira, Paraná, Brazil. METHODS Light traps were used for collections and for the analysis of sand fly were used the multiplex polymerase chain reaction (PCR) methodology and subsequent sequencing. FINDINGS Among the collected specimens, 88.62% were attributed to the species Nyssomyia neivai, which were grouped into 176 pools. Three positive pools were detected: two with Leishmania (Viannia) braziliensis and one with L. (Leishmania) infantum. The positivity rate for the parasite was 0.25% based on the presence of at least one infected insect in the pool. MAIN CONCLUSIONS The detection of L. infantum in Ny. neivai draws attention due to its abundance and anthropophily in the State of Paraná. Moreover, this finding is considered as an alert and suggests that the vector competence of Ny. neivai and the criteria for its incrimination should be carried out, given its wide distribution in southern of Brazil.

Influence of the COVID-19 pandemic on sleep quality, psychosocial aspects, and physical activity levels in patients with chronic pain in Brazil: COVIDor cross-sectional study / Influência da pandemia de COVID-19 na qualidade do sono, em aspectos psicoemocionais e no nível de atividade física de pacientes com dor crônica no Brasil: estudo observacional COVIDor

ABSTRACT BACKGROUND AND OBJECTIVES: The social distancing of COVID-19 pandemic exacerbated symptoms of chronic pain patients. Furthermore, it is necessary to consider the sociocultural context of coping with the pandemic in different countries. The objective of this study was to evaluate pain, psychoemotional symptoms, sleep quality, and level of physical activity in chronic pain patients during the COVID-19 pandemic in Brazil. METHODS: Individuals with fibromyalgia, migraine and chronic low back pain were included. The survey was performed through a questionnaire elaborated by researchers on the Forms application, from Google Drive, in the period between October 2020 and March 2021, with straight and clear questions about pain, psychoemotional aspects, sleep quality, and level of physical activity. Binary or multinominal logistic regression analysis was performed to identify possible predictors. RESULTS: 973 people were evaluated, 63.5% had fibromyalgia, and 98.3% were female. Anxiety increased the odds ratio in 395% of chronic pain patients to feel pain (ß: 1.375; OR: 3.956; p=0.001) and a greater intensity of pain increases in 62.3% the chance of these individuals not performing physical activity (ß: -0.474; OR: 0.623; p=0.001). Pain intensity increased the odds ratio of having insomnia by 186.9% (ß: 0.625; OR: 1.869; p=0.001) and the chance of taking sleep drugs by 160.4% (ß: 0.472; OR: 1.604; p=0.001). CONCLUSION: The social isolation of COVID-19 pandemic maximized the vicious cycle between painful symptoms, anxiety, and sleep disorders in chronic pain patients in Brazil. The intensification of these factors is associated with the reduction of physical activity levels.

RESUMO JUSTIFICATIVA E OBJETIVOS: A pandemia de COVID-19 exacerbou os sintomas de pacientes com dor crônica. Porém, é necessário considerar o contexto sociocultural de enfrentamento da pandemia nos diferentes países. O objetivo deste estudo foi avaliar a dor, os sintomas psicoemocionais, a qualidade do sono e o nível de atividade física em pacientes com dor crônica durante a pandemia de COVID-19 no Brasil. MÉTODOS: Foram incluídos indivíduos com fibromialgia, enxaqueca e dor lombar. O levantamento foi realizado por meio de questionário elaborado pelos pesquisadores no aplicativo Forms, do Google Drive, entre outubro de 2020 e março de 2021, com perguntas diretas e claras sobre dor, aspectos psicoemocionais, qualidade do sono e nível de atividade física. Análise de regressão logística binária ou multinominal foi realizada para identificar possíveis preditores. RESULTADOS: Foram avaliadas 973 pessoas, 63,5% apresentavam fibromialgia, sendo 98,3% do sexo feminino. A ansiedade aumentou a razão de chances em 395% dos pacientes com dor crônica sentirem dor (ß: 1,375; OR: 3,956; p= 0,001) e a dor aumentou em 62,3% a chance desses indivíduos não realizarem atividade física (ß: -0,474; OR: 0,623; p=0,001). A intensidade da dor aumentou a razão de chances de ter insônia em 186,9% (ß: 0,625; OR: 1,869; p= 0,001) e a chance de tomar fármacos para dormir em 160,4% (ß: 0,472; OR: 1,604; p=0,001). CONCLUSÃO: O isolamento social da pandemia de COVID-19 maximizou o ciclo vicioso entre sintomas dolorosos, ansiedade e distúrbios do sono em pacientes com dor crônica no Brasil. A intensificação desses fatores está associada à redução de atividade física.

Artemisia vulgaris Induces Tumor-Selective Ferroptosis and Necroptosis via Lysosomal Ca2+ Signaling.

OBJECTIVE: To evaluate the chemical composition and effects of Artemisia vulgaris (AV) hydroalcoholic extract (HEAV) on breast cancer cells (MCF-7 and SKBR-3), chronic myeloid leukemia (K562) and NIH/3T3 fibroblasts. METHODS: Phytochemical analysis of HEAV was done by high-performance liquid chromatography-mass (HPLC) spectrometry. Viability and cell death studies were performed using trypan blue and Annexin/FITC-7AAD, respectively. Ferrostatin-1 (Fer-1) and necrostatin-1 (Nec-1) were used to assess the mode of HEAV-induced cell death and acetoxymethylester (BAPTA-AM) was used to verify the involvement of cytosolic calcium in this event. Cytosolic calcium measurements were made using Fura-2-AM. RESULTS: HEAV decreased the viability of MCF-7, SKBR-3 and K562 cells (P<0.05). The viability of HEAV-treated K562 cells was reduced compared to HEAV-exposed fibroblasts (P<0.05). Treatment of K562 cells with HEAV induced cell death primarily by late apoptosis and necrosis in assays using annexin V-FITC/7-AAD (P<0.05). The use of Nec-1 and Fer-1 increased the viability of K562 cells treated with HEAV relative to cells exposed to HEAV alone (P<0.01). HEAV-induced Ca2+ release mainly from lysosomes in K562 cells (P<0.01). Furthermore, BAPTA-AM, an intracellular Ca2+ chelator, decreased the number of non-viable cells treated with HEAV (P<0.05). CONCLUSIONS: HEAV is cytotoxic and activates several modalities of cell death, which are partially dependent on lysosomal release of Ca2+. These effects may be related to artemisinin and caffeoylquinic acids, the main compounds identified in HEAV.

Synergistic effect of the verapamil and amphotericin B against Cryptococcus neoformans.

Cryptococcus neoformans is an encapsulated yeast that can cause cryptococcosis and cryptococcal meningitis, which conventional treatment involves antifungal drugs such as polyenes, flucytosine, azoles, and their combinations. However, the high cost, toxicity, and increase in fungi resistance to antifungal agents stimulate the search for therapeutic strategies such as drug repurposing and combination therapy. This study evaluated the activity of the antihypertensive verapamil (VEH) alone and combined with amphotericin B (AmB) against C. neoformans. VEH exhibited antifungal activity against C. neoformans with minimum inhibitory concentration and minimum fungicidal concentration of 118 µg per mL. The combination of VEH and AmB exhibited synergism, reducing at least eightfold both drugs' concentrations. Moreover, the combination decreased the size and glucuronoxylomannnan content of C. neoformans capsule. However, no difference was observed in ergosterol levels of C. neoformans after treatment with VEH and AmB in combination. Altogether, VEH in combination with AmB exhibits potential as a candidate as for the development of anti-cryptococcal drug.

Synergistic Antibiofilm Action of Cinnamomum verum and Brazilian Green Propolis Hydroethanolic Extracts against Multidrug-Resistant Strains of Acinetobacter baumannii and Pseudomonas aeruginosa and Their Biocompatibility on Human Keratinocytes.

The accumulated dental biofilm can be a source of oral bacteria that are aspirated into the lower respiratory tract causing ventilator-associated pneumonia in hospitalized patients. The aim of this study was to evaluate the synergistic antibiofilm action of the produced and phytochemically characterized extracts of Cinnamomum verum and Brazilian green propolis (BGP) hydroethanolic extracts against multidrug-resistant clinical strains of Acinetobacter baumannii and Pseudomonas aeruginosa, in addition to their biocompatibility on human keratinocyte cell lines (HaCaT). For this, High-performance liquid chromatography analysis of the plant extracts was performed; then the minimum inhibitory and minimum bactericidal concentrations of the extracts were determined; and antibiofilm activity was evaluated with MTT assay to prevent biofilm formation and to reduce the mature biofilms. The cytotoxicity of the extracts was verified using the MTT colorimetric test, evaluating the cellular enzymatic activity. The data were analyzed with one-way ANOVA and Tukey's tests as well as Kruskal-Wallis and Dunn's tests, considering a significance level of 5%. It was possible to identify the cinnamic aldehyde in C. verum and p-coumaric, caffeic, and caffeoylquinic acids as well as flavonoids such as kaempferol and kaempferide and Artepillin-C in BGP. The combined extracts were effective in preventing biofilm formation and reducing the mature biofilms of A. baumannii and P. aeruginosa. Moreover, both extracts were biocompatible in different concentrations. Therefore, C. verum and BGP hydroethanolic extracts have bactericidal and antibiofilm action against multidrug resistant strains of A. baumannii and P. aeruginosa. In addition, the combined extracts were capable of expressively inhibiting the formation of A. baumannii and P. aeruginosa biofilms (prophylactic effect) acting similarly to 0.12% chlorhexidine gluconate.

Clinical and Psychosocial Impact of Communication about Oral Potentially Malignant Disorders: A Scoping Review.

Delivering bad news has been widely studied in cancer, thus, this scoping review aims to identify the available evidence concerning the communication of oral potentially malignant disorders (OPMDs) and their clinical and psychosocial impacts. A search was performed using electronic databases (Medline/PubMed, Scopus, Embase, and Web of Science) and one grey literature database (Google Scholar). Studies focused on communicating the diagnosis of OPMDs and the patients' perceptions were included. Study selection and data extraction were performed by two authors in a two-phase process. Five publications were included in the qualitative analysis. Differences regarding the study design, population, OPMDs assessed, and outcomes of professional-patient communication were found in each study. Protocols for OPMD communication have not yet been reported and there is a need to standardize strategies as communication skills may provide better clinical outcomes for patients diagnosed with potentially malignant disorders. Although future studies are needed, a brief list recommending the aspects that must be communicated is proposed.

Beliefs and expectations of patients with fibromyalgia about telerehabilitation during Covid-19 pandemic: A qualitative study.

BACKGROUND: Telerehabilitation as an alternative to physiotherapeutic care has been increasingly implemented in diverse populations. However, this mode of service can evoke beliefs and expectations in patients with fibromyalgia, depending on sociocultural and clinical context, that can cause poor adaptation and dropout from treatment. OBJECTIVE: To explore beliefs and expectations of individuals with fibromyalgia about physical exercises delivered through telerehabilitation. METHODS: Thirty individual semi-structured interviews were conducted via videoconference with women with fibromyalgia recruited during COVID-19 pandemic through intentional sampling. These interviews were guided by four questions addressing the beliefs and expectations about telerehabilitation. The interviews were recorded after consent and transcribed using the MAXQDA® software. The inductive approach was performed in which raw data were coded into categories and subcategories. RESULTS: Participants expect to benefit from telerehabilitation due to flexible hours, no need of travel, socialization, and lower risk of contamination. However, they believe they have difficulties related to the physical absence of the therapist, complexity of the exercises, internet connection problems, adaptation to the domestic routine and availability of schedules. CONCLUSION: Women with fibromyalgia showed positive expectations about telerehabilitation, relating better socialization with other individuals diagnosed with fibromyalgia, home care with flexible schedule and, to provide needed service to underserved. However, they listed barriers such as the physical absence of the therapist and instability of the internet connection and, the FM symptoms themselves.

The altered metabolic pathways of diffuse large B-cell lymphoma not otherwise specified.

Altered metabolic fingerprints of Diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS) may offer novel opportunities to identify new biomarkers and improve the understanding of its pathogenesis. This study aimed to investigate the modified metabolic pathways in extranodal, germinal center B-cell (GCB) and non-GCB DLBCL NOS from the head and neck. Formalin-fixed paraffin-embedded (FFPE) tissues from eleven DLBCL NOS classified according to Hans' algorithm using immunohistochemistry, and five normal lymphoid tissues (LT) were analyzed by high-performance liquid chromatography-mass spectrometry-based untargeted metabolomics. Partial Least Squares Discriminant Analysis showed that GCB and non-GCB DLBCL NOS have a distinct metabolomics profile, being the former more similar to normal lymphoid tissues. Metabolite pathway enrichment analysis indicated the following altered pathways: arachidonic acid, tyrosine, xenobiotics, vitamin E metabolism, and vitamin A. Our findings support that GCB and non-GCB DLBCL NOS has a distinct metabolomic profile, in which GCB possibly shares more metabolic similarities with LT than non-GCB DLBCL NOS.

Association between the potential distribution of Lutzomyia longipalpis and Nyssomyia whitmani and leishmaniasis incidence in Piauí State, Brazil.

BACKGROUND: Leishmaniases are vector borne diseases caused by Leishmania spp. parasites transmitted by female sandflies (Diptera: Psychodidae) whose geographic distribution is influenced by environmental factors. Among the main tools for studying the distribution of vector species, modeling techniques are used to analyze the influence of climatic and environmental factors on the distribution of these insects and their association with human cases of the disease. METHODOLOGY/PRINCIPAL FINDINGS: Here, we used a multiscale ecological niche modeling approach to assess the environmental suitability of sandfly vectors of the etiological agents of Visceral (VL) and American Cutaneous Leishmaniasis (ACL) in Piauí state, northeastern Brazil, and then evaluated their relationship with human disease incidence. For this, we obtained the geographic coordinates of the vector species Lutzomyia longipalpis and Nyssomyia whitmani through literature review, online databases and unpublished records. These data were used for the development of predictive models of the distribution of both sandflies species based on climatic and environmental variables. Finally, the environmental suitability for the presence of these vectors was compared with the incidence of both the diseases at the municipality level. The final models for each sandfly species showed good predictive powers with performance metric values of 0.889 for Lu. longipalpis and 0.776 for Ny. whitmani. The areas with greater environmental suitability for the presence of these species were concentrated in the central-north region of Piauí and coincide with the location of those municipalities presenting higher incidences of VL and ACL, situated in the central-north and extreme north of the state, respectively. The south and southeast regions of Piauí state have low incidence of these diseases and presented low environmental suitability for the presence of both vectors. CONCLUSIONS/SIGNIFICANCE: We discuss how predictive modeling can guide entomological and epidemiological surveillances and recommend an increased supervision and control activities in Teresina (capital of the state of Piaui), Altos and Pedro II, in addition to other municipalities with similar social and environmental characteristics.

Parental beliefs in and attitudes toward teething signs and symptoms: A systematic review.

BACKGROUND: Parents believe that teething is associated with signs and symptoms, which may induce them to give medications that could harm their children. Some children may require alleviation of symptoms and overall attention. AIM: To assess parents' beliefs in and attitudes toward teething. DESIGN: Through electronic databases and gray literature, this systematic review identified cross-sectional studies reporting parents' beliefs in, knowledge about, and attitudes toward the signs and symptoms of primary tooth eruption in children aged between 0 and 36 months. Three reviewers independently selected the studies, collected the information, assessed methodological quality, and checked for accuracy with disagreements solved by a fourth reviewer. The Agency of Research and Quality in Health questionnaire for cross-sectional studies was used for quality assessment. Descriptive analysis with median and interquartile ranges was adopted. RESULTS: Twenty-nine studies comprising 10 524 participants from all geographic regions were included. The methodological quality of the studies was moderate. Most parents have beliefs in signs and symptoms during dentition, the most reported symptom being the desire to bite. Oral rehydration was the most exposed attitude in the studies included. Only a small proportion of parents reported no attitude. CONCLUSIONS: The majority of parents believed in at least one sign or symptom associated with teething, and only few of them would do nothing or just wait for the signs or symptoms to pass, with no difference among countries (Protocol doi: 10.17605/OSF.IO/S2KZ3).

Effects of Calendula officinalis and Capsicum annum glycolic extracts on planktonic cells and biofilms of multidrug-resistant strains of Klebsiella pneumoniae and Pseudomonas aeruginosa.

Empirical knowledge of natural plant extracts is increasingly proving to be a promising field. The effect of Calendula officinalis L. (CO) and Capsicum annum (CA) glycolic extracts (GlExt) have potential that should be further developed in microbial tests. The effect of CO-GlExt and CA-GlExt was evaluated on eight multidrug-resistant clinical strains of Klebsiella pneumoniae and Pseudomonas aeruginosa, as well as collection strains for each bacterial. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the extract were determined in comparison with 0.12% chlorhexidine. The tests were performed on single species biofilms, at 5 min and 24 h, using the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. The MIC and MBC of the extract ranged from 1.56 to 50 mg mL-1 for all strains evaluated. Analysis of the MTT assay revealed a strong antimicrobial potential of CA-GlExt, comparable to chlorhexidine. The findings suggest that CA-GlExt is effective against multidrug-resistant strains of K. pneumoniae and P. aeruginosa in planktonic state and biofilms.

Violência interpessoal contra adolescentes: análise dos casos notificados no estado do espírito santo / Interpersonal violence against adolescents: an analysis of the cases notified in the state of espírito santo / Violencia interpersonal contra adolescentes: análisis de los casos notificados en el estado de espírito santo

RESUMO Objetivo: identificar a frequência de notificação de violência interpessoal contra adolescentes no Espírito Santo - Brasil, e os fatores associados. Método: estudo transversal com dados do Sistema de Informação de Agravos e Notificação de 2011 a 2018. As associações foram testadas pelo teste qui-quadrado de Pearson e regressão de Poisson. Resultados: a frequência de violência interpessoal foi de 72,2%. O desfecho esteve associado a adolescentes do sexo masculino; com idade de 10 a 12 anos; da raça/cor preta/parda; que não apresentavam deficiências/transtornos; à ocorrência em via pública; aos agressores do sexo masculino e que estavam sob suspeita de consumo de álcool (p< 0,05). Conclusão: a violência interpessoal é um agravo de sérias implicações ao longo da vida. Esse estudo contribui para revelar a importância da vigilância de violência, a fim de conhecer a magnitude do agravo, bem como suas características para promoção da saúde, prevenção do evento e intervenção.

ABSTRACT Objective: to identify the notification frequency of interpersonal violence against adolescents in Espírito Santo, Brazil, and its associated factors. Method: a cross-sectional study conducted with data from the Information System on Notifiable Health Problems from 2011 to 2018. The associations were tested by means of Pearson's chi-square test and Poisson regression. Results: the frequency of interpersonal violence was 72.2%. The outcome was associated with male adolescents, aged from 10 to 12 years old, of black/brown race/skin color, with no disabilities/disorders, occurrence on public roads, and male aggressors who were suspected of alcohol consumption (p<0.05). Conclusion: interpersonal violence is a problem with severe implications throughout life. This study helps to reveal the importance of surveilling violence in order to know the magnitude of the problem, as well as its characteristics for health promotion, prevention of the events and due intervention.

RESUMEN Objetivo: identificar la frecuencia de notificación de casos de violencia interpersonal contra adolescentes en Espírito Santo, Brasil, y los factores asociados. Método: estudio transversal realizado entre 2011 y 2018 con datos del Sistema de Información sobre Problemas de Salud de Notificación Obligatoria. Las asociaciones se sometieron a las pruebas chi-cuadrado de Pearson y regresión de Poisson. Resultados: la frecuencia de violencia interpersonal fue del 72,2%. El desenlace se asoció con adolescentes varones, de 10 a 12 años de edad, de raza negra/morena y sin discapacidades/trastornos; al igual que con incidentes en la vía pública y agresores del sexo masculino bajo sospecha de consumo de alcohol (p < 0,05). Conclusión: la violencia interpersonal es un problema con graves repercusiones a lo largo de la vida. Este estudio contribuye a revelar la importancia de supervisar la violencia con el fin de conocer la magnitud del daño, como también sus características para la promoción de la salud, prevención de los eventos y debida intervención.

DNA barcoding of sand flies (Diptera, Psychodidae, Phlebotominae) from the western Brazilian Amazon.

The subfamily Phlebotominae comprises important insects for public health. The use of complementary tools such as molecular taxonomy is necessary for interspecific delimitation and/or discovery of cryptic species. Here, we evaluated the DNA barcoding tool to identify different species in the southwestern Brazilian Amazon. For this, we collected sand flies in forest fragments along the highway BR-317, in the municipality of Brasiléia, state of Acre, Brazil. The specimens were DNA-barcoded using a fragment of the cytochrome c oxidase subunit I (COI) gene. The sequences were analyzed to generate K2P pairwise genetic distances and a Neighbour-joining tree. The sand fly barcodes were also clustered into Molecular Operation Taxonomic Units (MOTU) using Automatic Barcode Gap Discovery (ABGD) approach. A total of 59 COI sequences comprising 22 nominal species and ten genera were generated. Of these, 11 species had not been sequenced before, thus being new COI sequences to science. Intraspecific genetic distances ranged between 0 and 4.9%, with Pintomyia serrana presenting the highest values of genetic distance, in addition to having been partitioned into three MOTUs. Regarding the distances to the nearest neighbour, all species present higher values in relation to the maximum intraspecific distance, in addition to forming well supported clusters in the neighbour-joining analysis. The DNA barcoding approach is useful for the molecular identification of sand flies from Brasiléia, state of Acre, and was efficient in detecting cryptic diversity of five species which can be confirmed in future studies using an integrative approach. We also generated new COI barcodes for Trichophoromyia auraensis, Nyssomyia shawi, and Psychodopygus paraensis, which may play a role in the transmission of Leishmania spp. in the Brazilian Amazon.

Evolution tumour models paving the way for understanding oral carcinogenesis.

Throughout the centuries, the world's outstanding scientists and research groups have gathered their efforts to characterise the initiation and progression of malignant neoplasms. The temporal dissection of tumourigenesis provided by phylogenetic studies is one of the milestones in understanding cancer; however, some black boxes are still unsolved. Currently, there is no consensus regarding the development of oral squamous cell carcinoma (OSCC), the leading cancer of the head and neck region. Oral epithelial dysplasia (OED) may precede oral cancer and, occasionally, be clinically evident as white, red or mixed mucosal lesions, called oral potentially malignant disorders (OPMD). In a stepwise view of oral carcinogenesis, OED and OPMD have been considered harbingers of oral cancer. Nevertheless, the malignant transformation of OPMD is a rare event. Most of these disorders remain benign and can even regress, making it challenging to formulate evolutionary hypotheses for OSCC initiation. Deciphering OED evolution is vital to highlight the potential drivers of oral carcinogenesis and molecular targets for OSCC preventative and therapeutic strategies. This narrative review synthesises the main concepts of evolutionary theories and discusses which of them better explains OED development and malignant transformation.

Effect of Itraconazole-Ezetimibe-Miltefosine Ternary Therapy in Murine Visceral Leishmaniasis.

Drug combination therapy is an interesting approach to increase the success of drug repurposing for neglected diseases. Thus, the objective of this work was to evaluate binary and ternary therapies composed of itraconazole, ezetimibe and miltefosine for the treatment of visceral leishmaniasis. Intracellular Leishmania infantum amastigotes were incubated with the drugs alone or in combination for 72 h. For in vivo experiments, we tested a long-course (21 days, once per day) and a short-course treatment (5 days, twice per day) for the binary combination with itraconazole and ezetimibe. For the ternary therapy including miltefosine, we adopted the short-course treatment and varied the vehicle. None of the combinations were toxic to macrophages. Binary combination of itraconazole plus ezetimibe and ternary combination of itraconazole, ezetimibe and miltefosine had synergistic effects in intracellular amastigotes, in some of the proportions evaluated. Although the in vivo long-course therapy had been more effective than the short-course protocol, it showed hepatic toxicity signs. Ezetimibe has proven to be able to reduce the parasite burden alone or in combination. Both suspensions of the ternary combination were active, but when the drugs were suspended in the commercial ORA-Plus formulation instead of purified water, the parasite burden was reduced by 98% in the liver and spleen. Altogether, the results demonstrate for the first time the activity of ezetimibe in a viscerotropic species of Leishmania and indicate that ternary treatment composed of miltefosine, itraconazole, and ezetimibe at low doses is a promising therapeutic alternative for the treatment of visceral leishmaniasis.

Antimicrobial action of four herbal plants over mixed-species biofilms of Candida albicans with four different microorganisms.

This study aimed to evaluate the antimicrobial effect of four herbal plants glycolic extracts over mixed-species biofilm composed of Candida albicans (C. albicans) and another pathogenic bacterium as alternative therapy to be investigated. Four plants extract of Pfaffia paniculata roots; Hamamelis virginiana leaf, Stryphnodendron barbatiman tree bark and Gymnema sylvestre stem and leaves were tested over multi-species biofilm of C. albicans (ATCC 18804) and Streptococcus mutans (ATCC 35688), Staphylococcus aureus (ATCC 6538), Enterococcus faecalis (ATCC 4083) or Pseudomonas aeruginosa (ATCC 15442) for 5 min and 24 h and colony forming units per millilitre was calculated. The data were analysed using Kruskal-Wallis with Dunn's test (p ≤ 0.05). All tested extracts showed antimicrobial action over the mixed-species biofilms after 24 h. Some extracts eliminated totally the biofilms. The glycolic extract of P. paniculata, H. virginiana, S. barbatiman and G. sylvestre are effective over mixed-species biofilms and may be indicated as endodontic irrigant or intracanal medication.