Orofacial Deformities in 3 Related Rhesus Monkeys (Macaca mulatta) Resembling Human Binder's Syndrome.

Binder's syndrome is a rare congenital deformity characterized by midface hypoplasia, particularly around the nasomaxillary area. Genetic etiology or developmental failure caused by prenatal exposure to teratological agents has been considered. In this article, we present 3 related rhesus monkeys born with orofacial deformities similar to those found in infants with the Binder phenotype. For the first time, a primate biomodel for this condition is presented. The clinical description and association with management and environmental factors are discussed. These findings reinforce the knowledge about the relationship between possible vitamin K metabolism interference and Binder's syndrome.

Congenital adactyly and oligodactyly with metatarsal hypoplasia in two rhesus monkeys.

Congenital digital defects, particularly adactyly and oligodactyly, have been reported frequently in humans, however, their occurrence in rhesus monkeys is rare, mainly in the hind limbs. We present here for the first time, two female rhesus monkeys with unilateral congenital toe defects with metatarsal involvement. One showing adactyly and the other oligodactyly. In this report, we present the clinical/radiological details of these cases as well as discuss the risk factors possibly involved, such as contact with pesticides and genetic factors.

Malocclusion in Children Aged 8 to 10 Years Old With Operated Isolated Cleft Palate.

ABSTRACT: This study aims to characterize dental malocclusion in children with operated isolated cleft palate aged 8 to 10 years old. Cross-sectional study with medical charts and complementary orthodontics exams and a sample for convenience. The study population was children aged 8 to 10 years registered at a Brazilian center from 2005 to 2009, diagnosed with isolated cleft palate and operated. the population of children registered at a Brazilian center from 2005 to 2009, diagnosed with isolated cleft palate. The data obtained from clinical records were analyzed by 2 orthodontists using the initial orthodontic documentation. The variables were: isolated cleft, sex, time of palatoplasty, malocclusion. The statistics included chi-square and Fisher exact tests (error 5%) to assess the malocclusion according to sex, type of cleft palate and time at palatoplasty. The sample resulted in 28 children (50% males, 50% females), average 8.5 years of age; the inter arch Class III relation was predominant (41.7%); a normal transverse relation was present in 48.1% of the sample; the majority presented a normal position of the upper incisors (61.5%);anterior open bite and excessive overjet was observed in 15.4% each and anterior cross-bite in 40.7%. There was no significant association between malocclusion with cleft type and surgery timing. The association between malocclusion and sex was significant (P = 0.049). Class III malocclusion was observed in most cases and females showed worse occlusal relations. Early orthodontic treatment is necessary in these patients.

Therapeutic Effects of Anti-Inflammatory N-Acylhydrazones in the Resolution of Experimental Colitis.

Inflammatory bowel diseases are caused by inflammation of the gastrointestinal tract, which may or may not have a specific cause or pathogen. They affect millions of people around the world and there are still few effective treatments. The aim of this work is to investigate the anti-inflammatory effect of the IKK-ß inhibitor LASSBio-1524 and its three analogs, LASSBio-1760, LASSBio-1763, and LASSBio-1764, on mediator production and expression of inflammatory enzymes using experimental animal models of intestinal inflammatory diseases. Colitis was performed using two different models, which mimic Crohn disease (induced by dinitrobenzene acid) and ulcerative colitis (induced by sodium dextran sulfate) in mice. In both models, a therapeutic protocol with a daily dose of 1, 3, or 30 µmol/kg was performed. LASSBio-1524 and its three analogs reduced the secretion of tumor necrosis factor-α, IL-1ß, IL-6, IL-12, and IFN-γ and increased secretion of IL-10, protecting gastrointestinal homeostasis. All compounds reduced macro- and microscopic colonic damage caused by experimental colitis and p38 mitogen-activated protein kinase expression in the colon, as well as leukocytosis and anemia resulting from the disease. Our data may suggest LASSBio-1524 and its analogs (LASSBio-1760, LASSBio-1763, and LASSBio-1764) as promising candidates for new prototypes designed to treat inflammatory bowel diseases. SIGNIFICANCE STATEMENT: Three new N-acylhydrazones were synthetized as analogs of LASSBio-1524. All new substances were evaluated in dextran sulfate- and dinitrobenzene acid-induced colitis, with LASSBio-1760, LASSBio-1762, and LASSBio-1763 presenting a significant effect in both models of colitis without toxic effects. The new substances could be considered as a new prototype for the development of new anti-inflammatory treatments of colitis.

Towards precision medicine in breast imaging: A novel open mammography database with tailor-made 3D image retrieval for AI and teaching.

This project addresses the global challenge of breast cancer, particularly in low-resource settings, by creating a pioneering mammography database. Breast cancer, identified by the World Health Organization as a leading cause of cancer death among women, often faces diagnostic and treatment resource constraints in low- and middle-income countries. To enhance early diagnosis and address educational setbacks, the project focuses on leveraging artificial intelligence (AI) technologies through a comprehensive database. Developed in collaboration with Ambra Health, a cloud-based medical image management software, the database comprises 941 mammography images from 100 anonymized cases, with 62 % including 3D images. Accessible through http://mamografia.unifesp.br, the platform facilitates a simple registration process and an advanced search system based on 169 clinical and imaging variables. The website, customizable to the user's native language, ensures data security through an automatic anonymization system. By providing high-resolution, 3D digital images and supplementary clinical information, the platform aims to promote education and research in breast cancer diagnosis, representing a significant advancement in resource-constrained healthcare environments.

Copaiba Oil Resin Exerts an Additive Effect to Babassu Oil on Behavioral Changes in Human Endometriotic Cell Cultures.

BACKGROUND: Current drugs for the treatment of endometriosis are not able to completely cure the condition, and significant side effects hinder the continuation of treatment. Therefore, it is necessary to search for new drug candidates. In the present paper, the use of plant extracts is highlighted. Babassu oil and Copaiba oil resin have several therapeutic properties. We investigated the in vitro effects of two nanoemulsions containing oil extracted from Babassu (Orbignya speciosa) nuts (called SNEDDS-18) and/or oil resin extracted from Copaiba trunk (Copaifera langsdorffii) (called SNEDDS-18/COPA) on cultured human eutopic endometrium stromal cells from endometrial biopsies of patients without (CESC) and with (EuESC) endometriosis as well as human stromal cells from biopsies of endometriotic lesions (EctESC). METHODS: CESC, EuESC, and EctESC were taken and treated with SNEDDS-18 and SNEDDS-18/COPA to evaluate their effects on cytotoxicity, cell morphology, proliferation, and signaling pathways. RESULTS: After 48 h of incubation with SNEDDS-18 and SNEDDS-18/COPA, cell viability and proliferation were inhibited, especially in EctESC. The lowest concentration of both nanoemulsions reduced cell viability and proliferation and broke down the cytoskeleton in EctESCs. After 24 h of treatment a decrease in IL-1, TNF-α, and MCP-1 was observed, as well as an increase in IL-10 production. CONCLUSIONS: Both nanoemulsions can affect endometriotic stromal cell behaviors, thus revealing two potential candidates for new phytotherapeutic agents for the management of endometriosis.

Effects of fibrin, thrombin, and blood on breast capsule formation in a preclinical model.

BACKGROUND: The root cause of capsular contracture (CC) associated with breast implants is unknown. Recent evidence points to the possible role of fibrin and bacteria in CC formation. OBJECTIVES: The authors sought to determine whether fibrin, thrombin, and blood modulated the histological and microbiological outcomes of breast implant capsule formation in a rabbit model. METHODS: The authors carried out a case-control study to assess the influence of fibrin, thrombin, and blood on capsule wound healing in a rabbit model. Eighteen New Zealand white rabbits received four tissue expanders. One expander acted as a control, whereas the other expander pockets received one of the following: fibrin glue, rabbit blood, or thrombin sealant. Intracapsular pressure/volume curves were compared among the groups, and histological and microbiological evaluations were performed (capsules, tissue expanders, rabbit skin, and air). The rabbits were euthanized at two or four weeks. RESULTS: At four weeks, the fibrin and thrombin expanders demonstrated significantly decreased intracapsular pressure compared to the control group. In the control and fibrin groups, mixed inflammation correlated with decreased intracapsular pressure, whereas mononuclear inflammation correlated with increased intracapsular pressure. The predominant isolate in the capsules, tissue expanders, and rabbit skin was coagulase-negative staphylococci. For fibrin and thrombin, both cultures that showed an organism other than staphylococci and cultures that were negative were associated with decreased intracapsular pressure, whereas cultures positive for staphylococci were associated with increased intracapsular pressure. CONCLUSIONS: Fibrin application during breast implantation may reduce rates of CC, but the presence of staphylococci is associated with increased capsule pressure even in the presence of fibrin, so care should be taken to avoid bacterial contamination.

Effects of coagulase-negative staphylococci and fibrin on breast capsule formation in a rabbit model.

BACKGROUND: The etiology and ideal clinical treatment of capsular contracture (CC) remain unresolved. Bacteria, especially coagulase-negative staphylococci, have been previously shown to accelerate the onset of CC. The role of fibrin in capsule formation has also been controversial. OBJECTIVE: The authors investigate whether fibrin and coagulase-negative staphylococci (CoNS) modulate the histological, microbiological, and clinical outcomes of breast implant capsule formation in a rabbit model and evaluate contamination during the surgical procedure. METHODS: Thirty-one New Zealand white female rabbits were each implanted with one tissue expander and two breast implants. The rabbits received (1) untreated implants and expanders (control; n = 10), (2) two implants sprayed with 2 mL of fibrin and one expander sprayed with 0.5 mL of fibrin (fibrin; n = 11), or (3) two implants inoculated with 100 µL of a CoNS suspension (10(8)CFU/mL-0.5 density on the McFarland scale) and one expander inoculated with a CoNS suspension of 2.5 × 10(7) CFU/mL (CoNS; n = 10). Pressure/volume curves and histological and microbiological evaluations were performed. Operating room air samples and contact skin samples were collected for microbiological evaluation. The rabbits were euthanized at four weeks. RESULTS: In the fibrin group, significantly decreased intracapsular pressures, thinner capsules, loose/dense (<25%) connective tissue, and negative/mild angiogenesis were observed. In the CoNS group, increased capsular thicknesses and polymorph-type inflammatory cells were the most common findings. Similar bacteria in capsules, implants, and skin were cultured from all the study groups. One Baker grade IV contracture was observed in an implant infected with Micrococcus spp. CONCLUSIONS: Fibrin was associated with reduced capsule formation in this preclinical animal model, which makes fibrin an attractive potential therapeutic agent in women undergoing breast augmentation procedures. Clinical strategies for preventing bacterial contamination during surgery are crucial, as low pathogenic agents may promote CC.

New 2-amino-pyridinyl-N-acylhydrazones: Synthesis and identification of their mechanism of anti-inflammatory action.

AIMS: The main aim of this paper was the synthesis and the evaluation of the anti-inflammatory activity of LASSBio-1828 (an amino-pyridinyl-N-acylhydrazone) and its respective hydrochloride, based on a p38α MAPK inhibitor (LASSBio-1824) previously synthesized by our group. MAIN METHODS: The compounds were tested regarding their cell viability effect and on acute models of inflammation such as formalin-induced licking test, cell migration and inflammatory mediators quantification. KEY FINDINGS: Treatment with the compounds inhibited p38α, reduced inflammatory pain, cell migration and inflammatory mediators that participate on the MAPK pathway such as TNF-α and IL-1ß. SIGNIFICANCE: Taken together, these results suggest that the synthesis of the corresponding hydrochloride of LASSBio-1828 enhanced its potency as a p38 inhibitor, and also that this compound could be considered a good anti-inflammatory drug candidate after further studies.

Aristolochia trilobata: Identification of the Anti-Inflammatory and Antinociceptive Effects.

Aristolochia trilobata, popularly known as "mil-homens," is widely used for treatment of stomach aches, colic, asthma, pulmonary diseases, diabetes, and skin affection. We evaluated the antinociceptive and anti-inflammatory activities of the essential oil (EO) and the main constituent, 6-methyl-5-hepten-2-yl acetate (sulcatyl acetate, SA). EO and SA (1, 10, and 100 mg/kg, p.o.) were evaluated using chemical (formalin-induced licking) and thermal (hot-plate) models of nociception or inflammation (carrageenan-induced cell migration into the subcutaneous air pouch, SAP). The mechanism of antinociceptive activity was evaluated using opioid, cholinergic receptor antagonists (naloxone and atropine), or nitric oxide synthase inhibitor (L-NAME). EO and SA presented a central antinociceptive effect (the hot-plate model). In formalin-induced licking response, higher doses of EO and SA also reduced 1st and 2nd phases. None of the antagonists and enzyme inhibitor reversed antinociceptive effects. EO and SA reduced the leukocyte migration into the SAP, and the cytokines tumor necrosis factor and interleukin-1 (TNF-α and IL-1ß, respectively) produced in the exudate. Our results are indicative that EO and SA present peripheral and central antinociceptive and anti-inflammatory effects.

Discovery of naphthyl-N-acylhydrazone p38α MAPK inhibitors with in vivo anti-inflammatory and anti-TNF-α activity.

Protein kinases constitute attractive therapeutic targets for development of new prototypes to treat different chronic diseases. Several available drugs, like tinibs, are tyrosine kinase inhibitors; meanwhile, inhibitors of serine/threonine kinases, such as mitogen-activated protein kinase (MAPK), are still trying to overcome some problems in one of the steps of clinical development to become drugs. So, here we reported the synthesis, the in vitro kinase inhibitory profile, docking studies, and the evaluation of anti-inflammatory profile of new naphthyl-N-acylhydrazone derivatives using animal models. Although all tested compounds (3a-d) have been characterized as p38α MAPK inhibitors and have showed in vivo anti-inflammatory action, LASSBio-1824 (3b) presented the best performance as p38α MAPK inhibitor, with IC50  = 4.45 µm, and also demonstrated to be the most promising anti-inflammatory prototype, with good in vivo anti-TNF-α profile after oral administration.

Agarose-silver particles films: Effect of calcium ascorbate in nanoparticles synthesis and film properties.

New nanoparticles containing biomaterials are emerging as versatile active platforms in a great number of applications, for example, as skin substitutes and therapeutic media. The present study describes the preparation of silver nanoparticles (AgNPs) embedded in agarose films and the impact of calcium ascorbate in the formation of ANPs as well as in the final properties of the films. Colloidal AgNPs were synthetized by two chemical reduction routes: (i) applying calcium ascorbate and NaBH4 and (ii) applying only NaBH4. AgNPs synthetized using NaBH4 showed sizes ranging from 5 to 18 nm while AgNPs were calcium ascorbate was used showed micrometer from 164 to 955 nm size. Films were prepared in three formulations: agarose control film (A1); agarose + AgNPs without calcium ascorbate (A2) and agarose + AgNPs with calcium ascorbate (A3). The characterization of films by SEM and EDS showed agarose agglomerates in A2 and unreacted calcium ascorbate crystals on surface of A3. Thus, the presence of calcium ascorbate influenced the properties of A3 film. In addition, the antimicrobial analysis showed a silver particles release dependence on the film composition and only the A3 presented activity against Staphylococcus aureus. The results found in this study open an important way for development of new biomaterials, economically competitive, and with medical application.

Discovery of Novel Orally Active Tetrahydro-Naphthyl-N-Acylhydrazones with In Vivo Anti-TNF-α Effect and Remarkable Anti-Inflammatory Properties.

LASSBio-1524 was designed as inhibitor of the IKK-ß (kappa ß kinase inhibitor) enzyme, which participates in the activation of the nuclear factor κB (NF-κB) canonical pathway, and its three N-acylhydrazone new analogues, LASSBio-1760, LASSBio-1763 and LASSBio-1764 are now being tested on their anti-inflammatory potential. The activity of these compounds was evaluated with the subcutaneous air pouch induced by carrageenan and by subsequent measurement of tumor necrosis factor-α (TNF-α), nitric oxide (NO) and reactive oxygen species (ROS). In the acute inflammation model, the oral pretreatment with doses from 0.3 to 30 mg/kg of N-acylhydrazone derivatives was able to significantly reduce leukocyte migration to the cavity. Pretreatment with LASSBio-1524 and its analogues also decreased NO, TNF-α and ROS biosynthesis an events closely involved with NF-kB pathway. The tetrahydronaphthyl-N-acylhydrazone derivative LASSBio-1764 was the most promising compound from this series, surpassing even LASSBio-1524. Additionally, none of the compounds demonstrated myelotoxicity or cytotoxicity. Cell viability was assayed and these compounds demonstrated to be safe at different concentrations. Western blot analysis demonstrated that LASSBio-1524 and LASSBio-1760 inhibited NF-κB expression in RAW 264.7 cell lineage. Our data indicate that the tested compounds have anti-inflammatory activity, which may be related to inhibition of leukocyte migration, reducing the production of NO, TNF-α and ROS. LASSBio-1524 and LASSBio-1760, in addition to these features, also reduced p65 nuclear expression assessed by western blot in RAW 264.7 murine cells.

Dermoscopic hemorrhagic dots: an early predictor of response of psoriasis to biologic agents.

BACKGROUND: Biologic agents are routinely used in the treatment of severe psoriasis. The evaluation of treatment response is mainly based on the physician's global clinical assessment. OBJECTIVE: To investigate whether dermoscopy might enhance the assessment of response of psoriasis to treatment with biologic agents. METHODS: Patients with severe psoriasis scheduled to receive a biologic agent were enrolled in the study. A target lesion from each patient was clinically and dermoscopically documented at baseline and after one, two and six months. The clinical response was evaluated by the recruiting clinicians at all visits, while dermoscopic images were evaluated by two independent investigators, blinded to the clinical information. Chi Square test was used for cross-tabulation comparisons, while odds ratios, 95% confidence intervals and p values were calculated using univariate logistic regression. RESULTS: Overall, there was a significant correlation between clinical response and vessel distribution at all time points: a regular vessel distribution correlated with no response, a clustered distribution with partial response, and the dermoscopic absence of vessels with complete response. The presence of dermoscopic hemorrhagic dots was a potent predictor of favorable clinical response at the subsequent visit at all time points. Among lesions initially clinically responding and later recurring, 87.5% displayed dermoscopic dotted vessels despite the macroscopic remission. CONCLUSION: Dermoscopy might be a useful additional tool for evaluating the response of psoriatic patients to biologic agents. Hemorrhagic dots represent an early predictor of clinical response, while the persistence or reappearance of dotted vessels might predict clinical persistence or recurrence, respectively.

LASSBio-1829 Hydrochloride: Development of a New Orally Active N-Acylhydrazone IKK2 Inhibitor with Anti-inflammatory Properties.

Inhibitor of nuclear factor κB kinase 2 (IKK2) is suggested to be a potential target for the development of novel anti-inflammatory and anticancer drugs. In this work, we applied structure-based drug design to improve the potency of the inhibitor (E)-N'-(4-nitrobenzylidene)-2-naphthohydrazide (LASSBio-1524, 1 a: IC50 =20 µm). The molecular model built for IKK2 together with the docking methodology employed were able to provide important and consistent information with respect to the structural and chemical inhibitor characteristics that may confer potency to IKK2 inhibitors, providing important guidelines for the development of a new N-acylhydrazone (NAH) derivative. (E)-N'-(4-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzylidene)-2-naphthohydrazide hydrochloride (LASSBio-1829 hydrochloride, 10) is a 7-azaindole NAH able to inhibit IKK2 with an IC50 value of 3.8 µm. LASSBio-1829 hydrochloride was found to be active in several pharmacological inflammation tests in vivo, showing its potential as an anti-inflammatory prototype.

Sentinel lymph node biopsy in cases of skin melanoma: initial experiences at a center in northeastern Brazil.

The incidence of skin melanoma is increasing worldwide. The presence of lymph node metastasis is the most important prognostic factor of this disease, the thicker the lesion the greater the likelihood of lymph node involvement. Approximately 20% of patients with Breslow depth 1-4 mm have lymph node metastasis. Sentinel lymph node biopsy is standard procedure in the management of patients with skin melanoma, reflecting progress in the treatment of this disease since this procedure avoids an unnecessary radical lymphadenectomy, thus reducing the morbidity of treatment. This paper describes a series of cases involving sentinel lymph node biopsy in melanoma patients in Teresina, Piauí, Brazil between 2008 and 2009.

Iconografia das festas populares em Cândido Portinari: sentidos/significados das expressões carnavalescas / Iconography of popular festivals in Cândido Portinari: Senses/expressions meanings of carnival

O texto apresenta a pesquisa realizada sobre a iconografia das festas populares em Cândido Portinari, identificando como as imagens criam sentidos para o entendimento da cultura popular e de suas expressões simbólicas. Para tanto, foi necessário apresentar as telas pintadas por Portinari que caracterizam o sub-tema “festas populares”, mais especificamente, as telas relacionadas ao “carnaval”. Procuramos entender a iconografia de Portinari numa dimensão pedagógica voltada à educação física. Trata-se de um estudo do tipo iconográfico desenvolvido a partir da observação e descrição das imagens em telas, bem como da interpretação acerca do que elas permitem revelar, garantindo a análise objetiva e subjetiva do material de coleta. Tal investigação, enveredando-se pela cultura popular brasileira, reafirma a ideia de que as imagens do corpo festivo em Portinari são densa fonte de pesquisa e recurso pedagógico à área de educação física, merecendo ser potencializadas no processo de formação dos educandos.

The study presents research on the iconography of popular festivals in Cândido Portinari, identifying how images create meaning for the understanding of popular culture and its symbolic expressions. Thus, it was necessary to present the paintings painted by Portinari that characterize the sub-theme festivals, more specifically, the screens related to the carnival. We were understand its iconography the Portinari in a pedagogical dimension focused on physical education. This is a study of the iconographic type evolved from observation and description of the images on screens, as well as the interpretation of what they allow to reveal, ensuring objective analysis and subjective material collection. This research, by venturing to Brazilian popular culture, reaffirms the idea that the body images in festive Portinari are dense source of research and teaching resource for the area of physical education and deserve to be leveraged in the process of training of students.

Linfonodo sentinela em melanoma: experiência inicial de um centro do nordeste brasileiro / Sentinel lymph node biopsy in cases of skin melanoma: initial experiences at a center in northeastern Brazil

A incidência do melanoma cutâneo é crescente em todo o mundo. A presença de metástases em linfonodos é o mais importante fator prognóstico, sendo que a probabilidade de envolvimento linfonodal é maior nas lesões de maior espessura, ocorrendo em 20 por cento dos pacientes com Breslow, de 1 a 4mm. A pesquisa do linfonodo sentinela já é padrão em melanoma e representou um avanço no tratamento da doença, por evitar linfonodectomias radicais desnecessárias, diminuindo a morbidade do tratamento. Apresentamos uma série de casos de pesquisa de linfonodo sentinela em pacientes com melanoma, em Teresina-Piauí, nos anos de 2008 e 2009.

The incidence of skin melanoma is increasing worldwide. The presence of lymph node metastasis is the most important prognostic factor of this disease, the thicker the lesion the greater the likelihood of lymph node involvement. Approximately 20 percent of patients with Breslow depth 1-4 mm have lymph node metastasis. Sentinel lymph node biopsy is standard procedure in the management of patients with skin melanoma, reflecting progress in the treatment of this disease since this procedure avoids an unnecessary radical lymphadenectomy, thus reducing the morbidity of treatment. This paper describes a series of cases involving sentinel lymph node biopsy in melanoma patients in Teresina, Piauí, Brazil between 2008 and 2009.