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Cannabis sativa has a long history of medicinal use, dating back to ancient times. This plant produces cannabinoids, which are now known to interact with several human proteins, including Cys-loop receptors for glycine (GlyR) and gamma-aminobutyric acid (GABA A R). As these channels are the primary mediators of inhibitory signals, they contribute to the diverse effects of cannabinoids on the nervous system. Evidence suggests that cannabinoid binding sites are located within the transmembrane domain, although their precise location has remained undetermined for over a decade. The process of identification of the binding site and the computational approaches employed are the main subjects of this Perspective, which includes an analysis of the most recently resolved cryo-EM structures of zebrafish GlyR bound to Δ 9 -tetrahydrocannabinol and the THC-GlyR complex obtained through molecular dynamics simulations. With this work, we aim to contribute to guiding future studies investigating the molecular basis of cannabinoid action on inhibitory channels.

Objective: To report on the experience of nurses from the Street Clinic in caring for the Indigenous Venezuelan population of the Warao ethnic group in Maceió/AL based on Madeleine Leininger's Transcultural Theory., Metodology: A descriptive study, of the experience report type, based on the care of the Warao Indigenous population in the light of Madeleine Leininger's Transcultural Theory, carried out during the year 2022., Results: Light technologies were used to form bonds and understand the cultural universe of the Warao people. The concepts of preservation, accommodation and cultural restructuring of care from Leininger's transcultural theory helped to elucidate the practice. Comprehensive care was offered in accordance with the programs recommended by the Ministry of Health, with transcultural care, including respect for refusal of care. The language barrier and health beliefs represented challenges in the context of singular care., Final Considerations: The experience of nurses from the Street Clinic in caring for the Indigenous population favored significant social interaction and expanded the possibilities for achieving comprehensive health care. The application of Transcultural Theory proved to be an effective and congruent device for health care.

A new design of cross-linked enzyme aggregates (CLEAs) of Burkholderia cepacia lipase (BCL) based mainly on the use of lignocellulosic residue of palm fiber as an additive was proposed. Different parameters for the preparation of active CLEAs in the hydrolysis of olive oil, such as precipitation agents, crosslinking agent concentration, additives, and coating agents were investigated. The highest activity yield (121.1 ± 0.1%) and volumetric activity (1578.1 ± 2.5 U/mL) were achieved for CLEAs prepared using the combination of a coating step with Triton ® X-100 and polyethyleneimine plus the use of palm fiber as an additive. The variations of the secondary structures of BCL-CLEAs were analyzed by second-derivative infrared spectra, mainly indicating a reduction of the α-helix structure, which was responsible for the lipase activation in the supramolecular structure of the CLEAs. Thus, these results provided evidence of an innovative design of BCL-CLEAs as a sustainable and biocompatible opportunity for biotechnology applications.

Canine visceral leishmaniosis (CVL), a parasitic disease caused by Leishmania infantum, may evolve to a chronic condition and lead to death. Evaluation of infected dogs is important to establish the clinical and laboratory parameters involved in the evolution of the disease. The objectives of the present study were to discriminate a canine population (n = 52) into sub-clinical and clinically affected dogs based on signs and scores, to evaluate the hematological, biochemical, histopathological and parasitological parameters of the two dog groups, and to analyze the results by multivariate regression analysis with the aim of establishing biomarkers of CVL clinical disease. The most common signs observed in the clinically affected dogs (n = 29) were hyperkeratosis, weight loss, onychogryphosis, pale mucosa and lymphadenomegaly. In the multivariate analysis, animals presenting high IgG avidity index and low red blood, lymphocyte and eosinophil counts, and low serum urea concentration had an increased probability of being classified as clinically affected (p <  0.05). All five parameters were considered to be strong biomarkers for monitoring the clinical disease, while IgG avidity percentage was strongly correlated with the number of clinical signs and could function as an indicator of the duration of infection. This is the first report on the application of IgG avidity and of multivariate regression analysis in establishing associations between the clinical signs of CVL and host biomarkers. Since avidity index (AI) percentages were strongly correlated with the number of clinical signs, it could be useful in clinical practice for auxiliary diagnosis of CVL and monitoring disease progression. A limitation of this study is the lack of information on co-infections by Anaplasma platys, Babesia canis vogeli, Ehrlichia canis and Hepatozoon canis. Therefore future studies should evaluate the influence of such co-infections on the associations studied using multivariate methods with larger samples., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Canine visceral leishmaniasis (CVL) is transmitted through vector, although venereal transmission has been suggested. This study aimed to compare the parasitic loads and inflammatory processes in genital tissues with ear skin from seropositive male dogs. Forty-five seropositive dogs were separated into groups containing symptomatic (n = 23) and asymptomatic (n = 22) animals. The control group (n = 2) healthy animals with seronegative and negative results in direct parasitological test. Samples of ear tip skin, prepuce, glans penis, testis, epididymis, and prostate were collected for evaluation of parasitic load and inflammatory infiltrate. Although ear tip skin was the most intensely parasitized, prepuce and epididymis revealed no difference in parasitism when compared with ear tip skin (P > 0.05). Parasitic loads in testis and prostate were lower than other tissues (P < 0.05). Parasitism in glans penis was high, similar to prepuce and epididymis, but lower than ear tip skin. High parasitism was more frequent in symptomatic dogs than asymptomatic animals. Severe inflammatory processes were more frequent within the symptomatic animals compared with asymptomatic and more predominant in prepuce and epididymis. Ear tip skin and genital tissues presented signs of chronic inflammation. There were weak and moderate positive correlations between parasitic loads and inflammatory processes. Our results demonstrate that, likewise with the ear tip skin, the genital of seropositive dogs can carry a large number of Leishmania infantum amastigotes and this process are more intense in symptomatic animals. These data have important implications for understanding the possibility of venereal transmission of CVL.

The ErbB/HER tyrosine kinase receptors family plays a key regulatory role in different cellular processes by activating several signaling pathways. In different tumor types, mutations or overexpression of the ErbB family members are a common feature, which led to the development of targeted therapies against this receptors. Although with this kind of treatment we are heading to a more personalized medicine, the development of acquired resistance is still an issue, therefore, several studies focused on discovering the mechanisms behind it. More recently, miRNAs have been described as important mediators of acquired resistance, specifically, acquired resistance to ErbB family targeted therapies. Ultimately, miRNA-based therapeutics using exosomes as a drug delivery model can revolutionize today's approach of cancer treatment.

Threaded metal pins have been used to create additional retention for large composite resin restorations. However, their dark appearance may compromise esthetic outcome. The use of small fiberglass posts has been advocated as an alternative. This clinical report describes a mini fiberglass post (MFP) used to provide additional retention in a fractured anterior tooth that received a composite resin restoration. The MFP represents a promising option for creating additional retention for large composite resin restorations., (Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Kaposi's sarcoma (KS) is a multicentric vascular neoplasm, with cutaneous and extracutaneous involvement. Different clinical and epidemiological variants have been identified. The classic form is manifested mainly in elderly men with indolent and long-term evolution, with lesions localized primarily in the lower extremities. We present two cases of classic Kaposi's sarcoma (CKS) in two female patients with extensive, exuberant skin involvement and rapid evolution, with good response to radiotherapy.

Penetrating aortic ulcer (PAU) is an atherosclerotic lesion with ulceration that penetrates the internal elastic lamina of the aortic wall. PAUs are classified as a category of acute aortic syndrome and have a reported rupture rate of up to 38%. To our knowledge, there is no prior published report of a PAU causing an aortogastric fistula. With the goal of raising awareness of this potentially catastrophic complication, we present herein a case of a PAU that ruptured into the gastric fundus, resulting in massive bleeding. The diagnosis was confirmed by computed tomography angiography, and thoracic endovascular aortic repair was used to control bleeding. Unfortunately, the patient did not survive the severe hypovolemic shock., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Darier's disease is a rare autosomal dominant genodermatosis. It has an estimated prevalence of 1 in 55,000 to 100,000 individuals, regardless of gender. It is characterized by multiple keratotic papules on the seborrheic areas of the trunk, scalp, forehead and flexures, and the clinical picture is worsened by heat, sun exposure, perspiration and mechanical trauma. Histopathology observed loss of epithelial adhesion and abnormal keratinization. About 10% of cases present in the localized form of the disease. We report a case of segmental Darier's Disease Type I and discuss the main characteristics of this condition.

Collision tumors are characterized by the coexistence of two cancers in the same anatomical site and its pathogenesis remains controversial. Although uncommon, the association of basal cell carcinoma and melanocytic nevus is the most common among combinations of skin tumors. Even rarer is the association of two malignant tumors. We report a case of tumor collision representing melanoma and basosquamous cell carcinoma, a combination not previously described in the literature, since there are no reported cases of melanoma with this type of basal cell carcinoma.

Purpose: To assess venous hemodynamics and quality of life at lest five years after varicose vein stripping., Methods: We conducted a prospective study with 39 patients (63 limbs) with primary lower limbs varicose veins. Preoperatively, all patients were subjected to clinical evaluation, duplex ultrassound, air plethysmography (APG), and CIVIQ questionnaire of quality of life. By APG, venous filling index (VFI), ejection fraction (EF), and residual volume fraction (RVF) were determined. CIVIQ addresses four domains in course of 20 questions, including states of physical, social, and psychological well-being, and pain level. Varicose veins were treated by standard venous stripping. At least five years after surgery (77.9 ± 10.9 months), patients were reassessed and had clinical examination, duplex ultrasound, APG, and CIVIQ repeated. No late follow-up data was available for 24 patients., Results: Preoperative and late postoperative VFI levels were similar, whereas EF (P=0.05) and RVF (P=0.01), as hemodynamic variables, significantly improved following surgery. In the late postoperative period, overall CIVIQ scores were significantly lower (P=0.005), as were scores in all four domains: pain (P=0.001), physical (P=0.007), social (P=0.008), and psychological (P= 0.05)., Conclusion: In a small prospective cohort, improvements in venous hemodynamics and in quality of life of patients submitted to standard varicose veins stripping were maintained five years after the procedure.

The present report describes the severe evolution of Kawasaki disease in a three-month-old infant. The ailment was initially atypical in its presentation, with the patient exhibiting only persistent fever in association with a progressive lethargy and maculopapular rash on the face, trunk and limbs erroneously diagnosed as roseola infantum. On the 10th day of the condition, mainly due to the unexplained persistence of fever, the infant was admitted to a local hospital. The typical features of KD appeared only on the 14th day of illness with the relapse of the maculopapular rash in association with non-purulent conjunctivitis; dry, reddish and fissured lips; tongue with reddish and hypertrophic papillae; erythema and edema of the palms and soles. During the following days, the ailment rapidly evolved to a catastrophic clinical picture characterized by generalized vasculitis, splenic infarction, pulmonary thrombosis, giant right and left coronary aneurysms, dilatation of common and internal iliac arteries and progressive ischemia of the distal third of the feet resulting in necrotic lesions of both halluces. Appropriate therapy was initiated, but repeated administration of intravenous immunoglobulin G (IVIG) followed by three days of administration of methylprednisolone did not abate the intense inflammatory activity. The remission of inflammation and regression of vascular lesions were only achieved during the following five weeks after the introduction of methotrexate associated with etanercept. The report of this case aims to draw attention to severe forms of KD that exhibit an unfavorable evolution and can be extremely refractory to the conventional therapy.

Objective: To draw attention to complications that might arise in any Kawasaki disease (KD) stage, risk factors contributing to the onset of complications and possible transient or permanent disease sequelae., Methods: Prospective study (clinical cohort) conducted between April 2002 and April 2009 of 115 patients with KD admitted to the Pediatric Rheumatology Clinic of the General Hospital of the Federal District, Brazil. All patients were sequentially assessed with clinical and laboratory examinations, Doppler echocardiography, imitanciometry, auditory evoked potentials, psychological evaluation, ophthalmologic examination and, in one patient with chorea, cerebral magnetic resonance angiography. In all patients, a questionnaire assessing the possible presence of cognitive, emotional, behavioral and social disorders was applied., Results: Twenty-five patients (21.7%) had coronary aneurisms. Thirty eight patients (33%) had a sensorineural auditory loss during the acute and subacute phases of the disease and 13 patients (11.3%) maintained the auditory loss six months after the first assessment. Other complications observed were as follows: facial palsy in one patient (0.9%), ataxia in acute and subacute phases in 11 (9.5%); 15 patients had ophthalmologic complications (13.2%), with uveitis in 13, papilledema in one patient, and conjunctival hemorrhage in another patient. One patient experienced chorea (0.9%), with a magnetic resonance angiography showing changes consistent with cerebral ischemia. In one patient, a thoracic aorta aneurism was found (0.9%) and another patient had a necrotizing vasculitis progressing to peripheral gangrene and tongue tip loss (0.9%). Behavioral changes over convalescence were observed in 23 children., Conclusion: KD may progress with several complications even within months of the disease acute phase, eventually resulting in permanent sequelae. The earlier the diagnosis and therapeutic intervention with IV IgG administration are, the lower will be the occurrence of complications; the presence of thrombocytosis, anemia and elevated and extended inflammatory activity are risk factors for complication arising.

Context: Previous studies have demonstrated improvement of venous hemodynamics after surgical treatment of primary varicose veins of the lower extremities using air plethysmography (APG)., Purpose: To correlate the venous hemodynamics obtained by APG with the CEAP classification after surgical treatment of primary varicose veins., Methods: We studied 63 limbs of 39 patients (35 women and 4 men) aged on average 46.3 years, operated upon at the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo, during the period from January 2001 to December 2004. The 63 limbs were divided into the three following groups according to CEAP classification: group C2 + C3 (38 limbs), group C4 (15 limbs) and group C5 + C6 (10 limbs). The patients were evaluated clinically before and 30 to 40 days after surgery by preoperative duplex ultrasonography and pre- and postoperative APG., Results: There was an apparent hemodynamic improvement after surgical treatment of the varicose veins in the two groups of lower severity, but the improvement was significant in the most severe group based on venous filling index., Conclusion: Surgical treatment was beneficial for all three groups, but the greatest hemodynamic gain was observed in the group of highest clinical severity (group C5 + C6).

Background: Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology in which the main complication is coronary arteritis. Sensorineural hearing loss (SNHL) has also been described as a complication of this disorder. The objective of this study was to evaluate the prevalence of SNHL in patients with KD and to determine the possible causative abnormality, correlating the findings with the prevalence of cardiac complications, with the use of gammaglobulin, and with the results of laboratory tests., Methods: A clinical cohort of 40 patients with KD seen between 2005 and 2007 was evaluated by acoustic immittance measurement and brainstem-evoked response audiometry that were performed within the first 30 days of disease and 6 months after the first evaluation. Patients with hearing disability after this period underwent further testing through otoacoustic emissions analysis. All patients were treated with intravenous administration of immunoglobulin., Results: Ten (25%) of the 40 patients developed coronary aneurysm, and 22 (55%) disclosed hearing loss within the first 30 days, although this problem was noticed by the parents in only 3 children. In 12 (30%), the hearing loss persisted after 6 months. Ten (83.3%) of these 12 patients also showed thrombocytosis (platelets, >500,000), 8 (66%) had anemia (hemoglobin, <10 mg/dL), and all had high erythrocyte sedimentation rate (>50 mm/hr) persisting more than 30 days., Conclusion: SNHL was more prevalent than coronary complications. A significant association was found between persistent SNHL, although often not initially noted, with a prolonged presence of thrombocytosis, anemia, and high erythrocyte sedimentation rate and the delayed use of intravenous administration of immunoglobulin after the first 10 days of illness.

Purpose: Chipping within veneering porcelain has resulted in high clinical failure rates for implant-supported zirconia (yttria-tetragonal zirconia polycrystals [Y-TZP]) bridges. This study evaluated the reliability and failure modes of mouth-motion step-stress fatigued implant-supported Y-TZP versus palladium-silver alloy (PdAg) three-unit bridges., Materials and Methods: Implant-abutment replicas were embedded in polymethylmethacrylate resin. Y-TZP and PdAg frameworks, of similar design (n = 21 each), were fabricated, veneered, cemented (n = 3 each), and Hertzian contact-tested to obtain ultimate failure load. In each framework group, 18 specimens were distributed across three step-stress profiles and mouth-motion cyclically loaded according to the profile on the lingual slope of the buccal cusp of the pontic., Results: PdAg failures included competing flexural cracking at abutment and/or connector area and chipping, whereas Y-TZP presented predominantly cohesive failure within veneering porcelain. Including all failure modes, the reliability (two-sided at 90% confidence intervals) for a "mission" of 50,000 and 100,000 cycles at 300 N load was determined (Alta Pro, Reliasoft, Tucson, AZ, USA). No difference in reliability was observed between groups for a mission of 50,000. Reliability remained unchanged for a mission of 100,000 for PdAg, but significantly decreased for Y-TZP., Conclusions: Higher reliability was found for PdAg for a mission of 100,000 cycles at 300 N. Failure modes differed between materials.

Purpose: The aim of this study was to evaluate the effectiveness of adhesive primers (APs) applied to Co-Cr and Ni-Cr metal alloys on the bond strength of resin cements to alloys., Materials and Methods: Eight cementing systems were evaluated, consisting of four resin cements (Bistite II DC, LinkMax, Panavia F 2.0, RelyX Unicem) with or without their respective APs (Metaltite, Metal Primer II, Alloy Primer, Ceramic Primer). The two types of dental alloys (Co-Cr, Ni-Cr) were cast in plate specimens (10 x 5 x 1 mm(3)) from resin patterns. After casting, the plates were sandblasted with aluminum oxide (100 microm) and randomly divided into eight groups (n = 6). Each surface to be bonded was treated with one of eight cementing systems. Three resin cement cylinders (0.5 mm high, 0.75 mm diameter) were built on each bonded metal alloy surface, using a Tygon tubing mold. After water storage for 24 hours, specimens were subjected to micro-shear testing. Data were statistically analyzed by two-way ANOVA and Tukey's studentized range test., Results: The application of Metal Primer II resulted in a significantly higher bond strength for LinkMax resin cement when applied in both metal alloys. In general, the cementing systems had higher bond strengths in Co-Cr alloy than in Ni-Cr., Conclusions: The use of AP between alloy metal surfaces and resin cements did not increase the bond strength for most cementing systems evaluated.

This is a prospective study of a cohort of 70 children with Kawasaki disease (KD) admitted from April 2002 to April 2007 to a tertiary hospital in Brasilia, Brazil. Of the 70 children, only 32 (45.7%) were referred during the acute phase of the disease and only 15 (21.4%) were referred with the correct diagnosis. Coronary aneurysms were detected in 13 (18.5%). A high suspicion index is essential in order to detect new cases as KD is probably underdiagnosed in Brazil and other developing countries, and an early diagnosis will dramatically decrease its life-threatening complications.

Objective: To test the hypothesis that dentin Hertzian contact response varies with loading rate and tubule orientation., Design: Sound teeth (n=12) were cut either parallel or perpendicular to the axial direction to expose dentin (n=6 each). The cut specimens were embedded (poly-methyl-methacrylate (PMMA) and divided into two groups: (GL) load applied parallel to dentin tubule direction and (GP) load applied perpendicular to tubule direction. A 1.5mm diameter tungsten-carbide ball was used for Hertzian contact testing with a maximum load of 150 N load and loading rates of 0.1, 1, 100, and 1000 N/s on each specimen. Indented specimens were observed microscopically and photomicrographs acquired. Hertzian contact diameter and modulus were analysed (p<0.05) by one-way ANOVA and Tukey test., Results: There were significant differences (p<0.05) in Hertzian response with respect to loading rate for GL (0.1N/s versus 1000 N/s, 0.1N/s versus 100 N/s, 1N/s versus 1000 N/s, and 1N/s versus 100 N/s), and GP (0.1N/s versus 1000 N/s, 0.1N/s versus 100 N/s, and 1N/s versus 1000 N/s). Contact modulus was higher for GL compared to GP at all loading rates (p<0.05)., Conclusion: The results suggest that dentin contact modulus is loading rate dependent. Tubule orientation of dentin did not influence contact modulus values (p>0.05).

Introduction: Disinfection of dentin surfaces is desirable so long as it does not interfere with subsequent bonding of adhesive resins., Objective: To test the null hypothesis that bond strengths to dentin are not affected by previous application of an iodine disinfecting solution., Materials and Methods: Twenty-four extracted non-carious molars were selected. Occlusal enamel was removed producing a flat dentin substrate. Test teeth were all treated with 2% Iodine disclosing/disinfecting solution (I(2)DDS) for 20 sec and rinsed for 20 sec followed by the application of self- or total- etching bonding systems, generating five adhesive groups (n=3): Single Bond; Prime & Bond NT; Clearfil SE Bond; Opti-Bond Plus. The control groups (n=3 per adhesive) had no disclosing/disinfectant application prior to adhesive application. A 4-mm thick resin restoration was built up on each tooth for microtensile testing. Statistical analyses between experimental and control groups were performed by student's t-test (alpha= 0.05)., Results: In general, experimental groups (previously treated with I(2)DDS) showed significantly lower bond strength values when compared with their respective controls (p<0.05), except for group Prime & Bond I(2) that did not significantly differ from its control (p>0.05)., Conclusion: Acetone-base adhesive systems seem not to be affected by the application of I(2)DDS prior to etching and bonding procedures.