CARD11 gain of function upregulates BCL2A1 expression and promotes resistance to targeted therapies combination in B-cell lymphoma.

A strategy combining targeted therapies is effective in B-cell lymphomas (BCL), such as mantle cell lymphoma (MCL), but acquired resistances remain a recurrent issue. In this study, we performed integrative longitudinal genomic and single-cell RNA-sequencing analyses of patients with MCL who were treated with targeted therapies against CD20, BCL2, and Bruton tyrosine kinase (OAsIs trial). We revealed the emergence of subclones with a selective advantage against OAsIs combination in vivo and showed that resistant cells were characterized by B-cell receptor (BCR)-independent overexpression of NF-κB1 target genes, especially owing to CARD11 mutations. Functional studies demonstrated that CARD11 gain of function not only resulted in BCR independence but also directly increased the transcription of the antiapoptotic BCL2A1, leading to resistance against venetoclax and OAsIs combination. Based on the transcriptional profile of OAsIs-resistant subclones, we designed a 16-gene resistance signature that was also predictive for patients with MCL who were treated with conventional chemotherapy, underlying a common escape mechanism. Among druggable strategies to inhibit CARD11-dependent NF-κB1 transduction, we evaluated the selective inhibition of its essential partner MALT1. We demonstrated that MALT1 protease inhibition led to a reduction in the expression of genes involved in OAsIs resistance, including BCL2A1. Consequently, MALT1 inhibition induced synergistic cell death in combination with BCL2 inhibition, irrespective of CARD11 mutational status, both in vitro and in vivo. Taken together, our study identified mechanisms of resistance to targeted therapies and provided a novel strategy to overcome resistance in aggressive BCL. The OAsIs trial was registered at www.clinicaltrials.gov #NCT02558816.

Hamamelis virginiana L. extract presents antimicrobial and antibiofilm effects, absence of cytotoxicity, anti-inflammatory action, and potential to fight infections through the nitric oxide production by macrophages.

The potential of H. virginiana L. was evaluated against Candida spp. (C. albicans, C. dubliniensis, C. glabrata, C. guilliermondii, C. krusei, and C. tropicalis) and bacteria (Acinetobacter baumannii, Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, Staphylococcus aureus, and Streptococcus mutans). Effect on murine macrophages (RAW 264.7) was also evaluated with respect to cytotoxicity and production of cytokines (IL-1ß and TNF-α) and nitric oxide (NO). The most effective concentrations of the extract were determined by microdilution broth. These concentrations were analyzed on biofilms, after 5 min or 24 h exposure. Cytotoxicity was performed by MTT assay and quantification of cytokines and NO by ELISA and Griess reagent, respectively. The extract acted against the planktonic forms and provided significant reductions of all the microbial biofilms; besides, showed no cytotoxic effect, except at 100 mg/mL, after 24 h exposure. There was cytokine production; however, a modulatory effect was observed in groups exposed to lipopolysaccharide (LPS) from E. coli. NO production was similar or higher than the control group. Thus, H. virginiana L. extract showed antimicrobial and antibiofilm effects; absence of cytotoxicity for RAW 264.7; anti-inflammatory action; and potential to fight infections through the NO production.

Effect of incorporation of calcium polyphosphate sub-microparticles in low-concentration bleaching gels on physical properties of dental enamel.

AIM: To evaluate the bleaching efficacy and effects on enamel properties of experimental gels with carbamide peroxide (CP; 10%) or hydrogen peroxide (HP; 6%) containing calcium polyphosphate sub-microparticles (CaPPs). METHODS: A total of 216 bovine tooth specimens were divided for microhardness and color analyses (n = 108) and block randomized into nine groups (n = 12): (G1) commercial CP (Whiteness Perfect, FGM; Brazil); (G2) experimental CP; (G3) CP-0.5%CaPPs; (G4) CP-1.5%CaPPs; (G5) commercial HP (Potenza Bianco, PHS; Brazil); (G6) experimental HP; (G7) HP-0.5%CaPPs; (G8) HP-1.5%CaPPs; (G9) artificial saliva. The gels' pH values were determined with a bench pH meter. Color (ΔE, ΔE00, ΔWID) and microhardness variation were evaluated before and after the therapy. Part of the specimens used for microhardness was submitted to the scanning electron microscopy (SEM) (n = 3) and energy-dispersive X-ray spectroscopy EDX (n = 3) analyses. Statistical analyses were performed in the R statistical software (α = 0.05). Linear mixed models for repeated measures in time were used to analyze microhardness and L* values. Generalized linear models were used to analyze the a*, b*, ΔE, ΔE00, and ΔWID, considering a group effect. The EDX data were analyzed using a one-way ANOVA with Tukey's test. RESULTS: The gels' pH remained over 6,0. All gels effectively bleached the specimens and did not differ significantly. When compared to the control group, the hardness was significantly lower in the G1, G2, G6, and G7 groups. The G3, G4, G5, and G8 groups did not differ significantly (p > 0.05). CONCLUSION: The incorporation of CaPPs in low-concentration whitening gels reduces its negative effects on microhardness without interfering with their bleaching efficacy.

Modeling Lysosomal Storage Disorders in an Innovative Way: Establishment and Characterization of Stem Cell Lines from Human Exfoliated Deciduous Teeth of Mucopolysaccharidosis Type II Patients.

Among the many lysosomal storage disorders (LSDs) that would benefit from the establishment of novel cell models, either patient-derived or genetically engineered, is mucopolysaccharidosis type II (MPS II). Here, we present our results on the establishment and characterization of two MPS II patient-derived stem cell line(s) from deciduous baby teeth. To the best of our knowledge, this is the first time a stem cell population has been isolated from LSD patient samples obtained from the dental pulp. Taking into account our results on the molecular and biochemical characterization of those cells and the fact that they exhibit visible and measurable disease phenotypes, we consider these cells may qualify as a valuable disease model, which may be useful for both pathophysiological assessments and in vitro screenings. Ultimately, we believe that patient-derived dental pulp stem cells (DPSCs), particularly those isolated from human exfoliated deciduous teeth (SHEDs), may represent a feasible alternative to induced pluripotent stem cells (iPSCs) in many labs with standard cell culture conditions and limited (human and economic) resources.

Linking Intensive Care Unit functional scales to the International Classification of Functioning: proposal of a new assessment approach.

BACKGROUND: There are several tools to assess functional and physical status in critical ill patients. These tools can guide rehabilitation strategies in Intensive care units (ICU). However, they are not standardized, and this can compromise their applicability. The aim of the study is to identify common contents between International Classification of Functioning, Disability and Health (ICF) and Medical Research Council sum score (MRC-ss), Functional Status Score for the ICU (FSS-ICU), and Physical Function in ICU Test-scored (PFIT-s). As well as to propose a new assessment approach based on the ICF to ICU patients. METHODS: Pilot cross-sectional study. ICU in-patients, both genders, aged between 50 and 75 years were assessed with MRC-ss, FSS-ICU, PFIT-s and the linking rules used were proposed by Cieza et al. The inter-rater agreement for the linking process was performed using the Kappa coefficient. RESULTS: The ICF categories identified in the tools covered a total of 14 items. Common contents were identified in 13 of the 14 and two were related to body functions, six to body structures and five to activities and participation. The inter-rater agreement was considered substantial for the linking of MRC-ss (k = 0.665) and PFIT-s (k = 0.749) to the ICF, and almost perfect for the FSS-ICU (k = 0.832). CONCLUSIONS: This study synthesizes and categorizes commonly used tools and presents a new proposal based on the ICF to guide future studies. The proposed model combines the ICF with the contents of the most relevant instruments used in critical care.

Sexual and reproductive health (SRH) needs for forcibly displaced adolescent girls and young women (10-24 years old) in humanitarian settings: a mixed-methods systematic review.

BACKGROUND: Globally, there are 42 million women and girls estimated to be forcibly displaced. Adolescent girls and young women in humanitarian settings have their sexual and reproductive health (SRH) neglected. This systematic review aimed to describe SRH obstacles that adolescent girls and young women (10-24 years old) face in humanitarian settings in line with the Sustainable Development Goals. METHODS: We conducted a mixed-methods systematic review in six databases, focusing on migrant women ages 10 - 24and their SRH outcomes. The mixed-methods appraisal tool was used to evaluate the quality of the studies. This review follows PRISMA and the Systematic Review Guidelines from the Centre for Reviews and Dissemination recommendations. RESULTS: Among the 1290 studies screened by abstracts, 32 met the eligibility criteria: 15 were qualitative, 10 were quantitative and seven were mixed-methods studies. Most studies were performed in the last four years, in African countries. They discussed the increased frequency of adolescent pregnancies (16-23%), lack of contraceptive use and access (8-32%), poor menstrual hygiene management (lack of water, shortage of menstrual hygiene supplies), ignorance and stigma about sexually transmitted infections and HIV, a higher number of child, early and forced marriage or partnership and sexual and gender-based violence, challenging to obtain SRH information/knowledge/access, and unmet SRH needs. CONCLUSION: Migration is a current issue. Although there is a growing number of studies on adolescent girls and young women's SRH in humanitarian settings, this population remains overlooked, and face several challenges in SRH. There is a need for targeting interventions on SRH.

This systematic review describes the available evidence on the sexual and reproductive health (SRH) challenges faced by adolescent girls and young women in humanitarian settings. Thirty-two studies were analyzed, demonstrating poor SRH outcomes: higher incidence of adolescent pregnancy, lack of access to contraceptives and low rates of its use, precarious menstrual hygiene management (MHM), ignorance and stigma about sexually transmitted infections (STIs) and HIV, higher rates of child, early and forced marriage or partnership (CEFMP) and sexual and gender-based violence (SGBV). Identifying these challenges can help humanitarian actors address the SRH needs of these populations.

Biobank of fungi from marine and terrestrial Antarctic environments.

Harsh and extreme environments, such as Antarctica, offer unique opportunities to explore new microbial taxa and biomolecules. Given the limited knowledge on microbial diversity, this study aimed to compile, analyze and compare a subset of the biobank of Antarctic fungi maintained at the UNESP's Central of Microbial Resources (CRM-UNESP). A total of 711 isolates (240 yeasts and 471 filamentous fungi) from marine and terrestrial samples collected at King George Island (South Shetland Islands, Antarctica) were used with the primary objective of investigating their presence in both marine and terrestrial environments. Among the yeasts, 13 genera were found, predominantly belonging to the phylum Basidiomycota. Among the filamentous fungi, 34 genera were represented, predominantly from the phylum Ascomycota. The most abundant genera in the marine samples were Metschnikowia, Mrakia, and Pseudogymnoascus, while in the terrestrial samples, they were Pseudogymnoascus, Leucosporidium, and Mortierella. Most of the genera and species of the CRM-UNESP biobank of Antarctic fungi are being reported as an important target for biotechnological applications. This study showed the relevance of the CRM-UNESP biobank, highlighting the importance of applying standard methods for the preservation of the biological material and associated data (BMaD), as recommended in national and international standards.

Maintenance of enamel properties after bleaching with high-concentrated hydrogen-peroxide gel containing calcium polyphosphate sub-microparticles.

OBJECTIVE: To assessed the physical and chemical properties of human-enamel after treatment with an experimental bleaching gel containing 35%-hydrogen peroxide (HP) and calcium polyphosphate sub-microparticles (CaPP). MATERIALS AND METHODS: Enamel/dentin specimens (4 × 4 × 3 mm) were obtained (n = 120) and allocated to different groups: control (saliva only); experimental (HP35%); commercial (whiteness-HP-Maxx); CaPP0.5% (HP35% + CaPP0.5wt%); CaPP1.5% (HP35% + CaPP1.5wt%). Three sessions were performed. The specimens' color was assessed using a spectrophotometer and the color (ΔE/ΔE00) and bleaching index (ΔWID) determined. The surface roughness and microhardness were assessed with a roughness tester and Knoop indenter. Raman spectroscopy was performed to obtain the ratios between the areas under the 431, 580, and 1070 cm-1 and the 960 cm-1 bands (430:960, 580:960, 1070:960). Kruskal-Wallis and Dunn compared the color, Ra, and SMH data. The Raman data was analyzed with Kruskal-Wallis and Dunn (α = 5%). RESULTS: The ΔE, ΔE00, and ΔWID were similar among the bleached groups (p > 0.05). The roughness was not different between the groups (p > 0.05). After the 3rd session, CaPP0.5% had higher microhardness than the experimental (p < 0.05). The 1070:960 was higher in the experimental than in the CaPP1.5% and control (p < 0.05). CONCLUSIONS: In human enamel, CaPP did not alter the bleaching effectiveness or roughness, and additionally, CaPP-containing gels increased the microhardness and preserved the mineral content when compared to the experimental without CaPP. CLINICAL RELEVANCE: Experimental bleaching gels containing calcium polyphosphate sub-microparticles as a mineral source reduce the mineral content alteration and superficial microhardness reduction, known potential side effects of the in-office bleaching treatments.

A Rare Case of a Large Ameloblastoma and Cervical Lynphoepitelial Cyst Treated Simultaneously by an Intraoral Approach and Immediate Reconstruction.

Ameloblastoma is a benign locally aggressive odontogenic tumor of epithelial origin with unlimited growth capacity. Cervical lymphoepithelial cyst is a developmental cyst located in the superior-lateral region of the neck with treatment consisting of surgical excision, which presents low recurrence rates. This article reports the case of patient J.G.S.L., 24 years old, female, who reported to the service with a histopathological evaluation compatible with intraosseous mandibular ameloblastoma. On physical examination, a nontender swelling was palpable along the body of left mandible where the ameloblastoma was located, with a fluctuant region detected just below it. Imaging exams confirmed the suspicion of two independent lesions. The treatment plan consisted of two stages: first, mandibular resection of the area affected by the ameloblastoma, followed by reconstruction with a titanium plate simultaneous to excisional biopsy of the as yet undiagnosed lesion, both through intraoral access; second, mandibular reconstruction with iliac crest graft. Histopathological examination of the second lesion indicated a diagnosis of cervical lymphoepithelial cyst, being the first case in the literature with these concomitant lesions. Currently, the patient is in her third postoperative year with no signs of recurrence.

Development of Engineered-U1 snRNA Therapies: Current Status.

Splicing of pre-mRNA is a crucial regulatory stage in the pathway of gene expression. The majority of human genes that encode proteins undergo alternative pre-mRNA splicing and mutations that affect splicing are more prevalent than previously thought. Targeting aberrant RNA(s) may thus provide an opportunity to correct faulty splicing and potentially treat numerous genetic disorders. To that purpose, the use of engineered U1 snRNA (either modified U1 snRNAs or exon-specific U1s-ExSpeU1s) has been applied as a potentially therapeutic strategy to correct splicing mutations, particularly those affecting the 5' splice-site (5'ss). Here we review and summarize a vast panoply of studies that used either modified U1 snRNAs or ExSpeU1s to mediate gene therapeutic correction of splicing defects underlying a considerable number of genetic diseases. We also focus on the pre-clinical validation of these therapeutic approaches both in vitro and in vivo, and summarize the main obstacles that need to be overcome to allow for their successful translation to clinic practice in the future.

Dental education profile in COVID-19 pandemic: A scoping review.

INTRODUCTION: This scoping review aimed to determine the frequency of different teaching methodologies, tools and platforms applied in dental education during the COVID-19 pandemic. MATERIALS AND METHODS: The search strategy was performed in six databases and grey literature. A total of 28 questionnaire-based studies were included, without language or time restriction, from 20 different countries. RESULTS: Six thousand five hundred sixty-five participants were assessed: 84% undergraduates, 9% of faculty members, 5% of postgraduate students/residents/trainees and 2% of dental schools/residency programs. The pooled eligible data for teaching methodologies were 62% of a combination of different methods (95% CI, 35.5% to 82.3%), 23% a combination of synchronous and asynchronous formats (95% CI, 8.2% to 50.2%) and 15% for only synchronous lectures (95% CI, 4.3% to 42.2%). The reported tools were laptops (40%), smartphones (40%), tablets (40%), desktops (20%), Blackboard (20%), Respondus Lockdown Browser (20%), eProctor (20%) and PowerPoint (20%). The most used platforms were Zoom (70.6%), Microsoft Teams (23.5%) and Cisco Webex (23.5%). A better time management (17.9%; 95% CI, 7.9% to 35.6%) and the possibility of revision with additional notes (14.3%; 95% CI, 5.7% to 31.5%) was the greatest advantages related to dental e-learning, while the increased levels of anxiety/stress/burnout/exhaustion (35.7%; 95% CI, 21% to 54.2%) and internet connection problems (35.7%; 95% CI, 21% to 54.2%) was the most cited disadvantages. CONCLUSION: This scoping review showed promising blended teaching methodologies, tools and platforms in the dental education profile. The evidence suggests that e-learning technologies can widely contribute to dental education during the COVID-19 pandemic. Therefore, this study makes a major contribution to research by assessing the impact of COVID restrictions on dental education and further studies are needed to identify how restrictions in dental practice will affect future professionals.

Reproductive seasonality of hair rams under tropical conditions: an alternative for non-seasonal lamb production?

Reproductive seasonality limits the periods of breeding on the year and, therefore, productive output. However, some breeds appear as probably non-seasonal. The aim of the study was to characterize the seasonal pattern of Santa Inês rams, including an ultrasound characterization of the reproductive tract, testosterone concentrations, and semen characteristics. Fifteen Santa Inês rams remained in a grazing system with concentrate supplementation, and measurements of the reproductive tract and ultrasound evaluation (biometrics and pixel intensity) of the testicles and accessory sex glands were monthly recorded. Computerized seminal evaluations were also performed monthly, and serum testosterone concentration was measured every 15 days. Body weight and condition remained stable throughout the year. In general, reproductive traits varied along the year and reached maximum values during autumn and minimum in spring. Despite that, as fresh semen remained with enough quality to breed all along the year, seasonality does not appear as a limiting factor to breed along the year. Therefore, Santa Inês rams can be used for all-year-round breeding or for crossbreeding when rams from other breeds decrease their fertilizing ability.

Synthesis, biological evaluation and molecular modeling studies of novel 1,2,3-triazole-linked menadione-furan derivatives as P2X7 inhibitors.

The P2X7 receptor (P2X7R) is an ion channel that promotes the passage of ions through the membrane through brief stimulation once activated by ATP, its endogenous opener. However, prolonged stimulation with ATP, which occurs in pathological processes, opens a nonselective pore in the plasma membrane, allowing the passage of large molecules and leading to cytokine release or even cell death. In this sense, the search for new inhibitors for this receptor has attracted a great deal of attention in recent years. Considering the booming of biomass upgrading reactions in recent years and the continued efforts to synthesize biologically active molecules containing the 1,2,3-triazole ring, in the present work, we aimed to investigate whether triazole-linked menadione-furan derivatives could present P2X7R inhibitory activity. The novel compounds were tested for their inhibitory activity on ATP-induced dye uptake in peritoneal macrophages. Some have shown promising results, having displayed IC50 values lower than that of the P2X7R inhibitor BBG. Molecular docking studies also indicated that the active compounds bind to an allosteric site on P2X7R, presenting potential P2X7R inhibition.

Antarctic-derived yeasts: taxonomic identification and resistance to adverse conditions.

Antarctic harsh conditions favor the development of microbial adaptations. In this study, a molecular approach was applied to identify/refine the taxonomy of five yeasts isolated from different Antarctic samples, which were tested against ranges of temperature, UV radiations, salinity, and pH. Based on sequencing and phylogenetic analysis, strain CRM 1839 was confirmed as Naganishia sp., and strains CRM 1874, CRM 1565, CRM 2571, and CRM 2576 were identified as Goffeauzyma gilvescens, Goffeauzyma gastrica, Candida atlantica, and Camptobasidium sp., respectively, being this last one possibly a new species. Growth at different temperatures indicates that these yeasts are psychrotolerant, with the exception of Camptobasidium sp., which presents psychrophilic characteristics. G. gastrica recovered from marine sediment showed the best results of resistance to UV radiation, being able to grow even after the exposure to UVB dose of 9144 J/m² and UVC dose of 6102 J/m². C. atlantica isolated from glacier soil showed high cellular growth from 3 to 10% NaCl. The majority of the strains produced higher biomass at pH 7; nevertheless, G. gilvescens showed higher biomass production at pH 9. The studied Antarctic-derived yeasts have adaptations to extreme conditions, which makes them useful for biotechnological applications and studies of extremophiles.

Risk Perception and Decision Making about Early-Onset Sepsis among Neonatologists: A National Survey.

OBJECTIVE: Many newborns are investigated and empirically treated for suspected early-onset sepsis (EOS). This study aimed to describe neonatologists' self-identified risk thresholds for investigating and treating EOS and assess the consistency of these thresholds with clinical decisions. STUDY DESIGN: Voluntary online survey, available in two randomized versions, sent to neonatologists from 20 centers of the Brazilian Network on Neonatal Research. The surveys included questions about thresholds for investigating and treating EOS and presented four clinical scenarios with varying calculated risks. In survey version A, only the scenarios were presented, and participants were asked if they would order a blood test or start antibiotics. Survey version B presented the same scenarios and the risk of sepsis. Clinical decisions were compared between survey versions using chi-square tests and agreement between thresholds and clinical decisions were investigated using Kappa coefficients. RESULTS: In total, 293 surveys were completed (145 survey version A and 148 survey version B). The median risk thresholds for blood test and antibiotic treatment were 1:100 and 1:25, respectively. In the high-risk scenario, there was no difference in the proportion choosing antibiotic therapy between the groups. In the moderate-risk scenarios, both tests and antibiotics were chosen more frequently when the calculated risks were included (survey version B). In the low-risk scenario, there was no difference between survey versions. There was poor agreement between the self-described thresholds and clinical decisions. CONCLUSION: Neonatologists overestimate the risk of EOS and underestimate their risk thresholds. Knowledge of calculated risk may increase laboratory investigation and antibiotic use in infants at moderate risk for EOS. KEY POINTS: · Neonatologists overestimate the risk of EOS.. · There is wide variation in diagnostic/treatment thresholds for EOS.. · Clinical decision on EOS is not consistent with risk thresholds.. · Knowledge of risk may increase investigation and treatment of EOS..

Synthesis of a novel naphthalenone endoperoxide and structural elucidation by nuclear magnetic resonance spectroscopy and theoretical calculation.

Sesquiterpene lactones are found in plants of Asteraceae family, and endoperoxides are known for their antimalarial activity. Structural elucidation is a relevant aspect; however, it is not uncommon to find incorrect or incomplete structural assignments in the literature. Calculations based in quantum mechanics are frequently used to compute 1 H and 13 C NMR chemical shifts, and after comparing with the experimental data, the correct structure is established from diverse candidates. Targeting the synthesis of bioactive compounds, we envisaged the synthesis of a novel endoperoxide from the natural sesquiterpene lactone α-santonin (2). Photochemical transformation of α-santonin (2) to mazdasantonin (4) followed by photooxidation catalyzed by rose bengal afforded the novel endoperoxide 5. This new endoperoxide contains five stereogenic centers and is analogous to the antimalarial agent artemisinin (1). The relative configuration of the stereogenic centers of the endoperoxide were established by nuclear magnetic resonance (NMR) analyses and confirmed by theoretical calculations. All approaches were in complete agreement, and the structure of mazdasantonin endoperoxide was established as (3S,3aS,5aS,8R,9bS)-3,6,6-trimethyl-3,3a,4,5,8,9b-hexahydro-2H-5a,8-epidioxynaphtho[1,2-b]furan-2,7(6H)-dione.

Treatment of Dentofacial Deformity Associated with Temporomandibular Joint Ankylosis Through Vertical and Sagittal Osteotomies of the Mandibular Ramus.

ABSTRACT: Ankylosis of the temporomandibular joint is a disorder resulting from fibrous, osseous, or fibro-osseous adhesion that directly affects the quality of life of the individual. The authors present a case of unilateral temporomandibular joint ankylosis treated by condilectomy and ipsilateral sliding vertical ramus osteotomy associated with contralateral sagittal osteotomy aiming to restore function and to correct dentofacial deformity class II. A 31-year-old female patient presented with a history of facial trauma and major complaint of oral opening limitation. Physical examination revealed hypoplasia of the lower third of the face, facial pattern type II, anterior open bite, and maximum mouth opening of 22.5 mm. Computed tomography showed an ankylotic mass in the right mandibular condyle with deformity of the condylar structure and fusion to the right zygomatic arch and a contralateral condylar fracture sequel. It was proposed to perform a condilectomy of the right mandibular condyle for the removal of the bone mass concomitant to the sliding vertical ramus osteotomy of the mandibular ramus for condylar reconstruction by rhytidectomy approach and the sagittal osteotomy of the left mandibular aiming the reestablishment of occlusion and the correction of dentofacial deformity. The condylar fracture was not operated because the condyle was remodeled. The patient is in her fourth year postoperative presenting satisfactory esthetic-functional re-stabilization, without clinical signs of recurrence. In conclusion, the authors believe that combined sliding vertical ramus osteotomy and sagittal osteotomy can bring satisfactory results in complex cases.

Care bundle for family interview for pediatric organ donation.

PURPOSE: to develop a care bundle for best practices in conducting the family interview for organ and tissue donation with the families of children and adolescents. DESIGN AND METHODS: methodological study, with a qualitative approach, developed in Brazil, in three stages: literature review, qualitative study with professionals and family members, and development of the care bundle. RESULTS: Nine studies were selected and 17 health professionals and nine family members were interviewed. With this data, the care bundle was developed in three categories: communication of death, emotional support and information about organ and tissue donation. The recommendations were evaluated by five external professionals and all of them assessed the bundle as having the highest possible quality. CONCLUSIONS: the care bundle was built following the stages of integrative literature review and interviews with professionals working in this scenario and family members who have already gone through a family interview for organ and tissue donation of children and adolescents. PRACTICE IMPLICATIONS: the use of this material is seen as an important resource to support the professional during the conduction of the family interview in a scenario as sensitive and challenging as the care to family members facing death and the decision of organ and tissue donation of children and adolescents. Furthermore, the care bundle can increase the quality of family interviews and impact the reduction of family refusals. DESCRIPTORS: Practice Guideline as Topic. Tissue and Organ Procurement. Patient Care Team. Nursing. Pediatrics. Communication.

The Anti-Inflammatory Properties of Licorice (Glycyrrhiza glabra)-Derived Compounds in Intestinal Disorders.

Intestinal diseases, such as inflammatory bowel diseases (IBDs) and colorectal cancer (CRC), are a significant source of morbidity and mortality worldwide. Epidemiological data have shown that IBD patients are at an increased risk for the development of CRC. IBD-associated cancer develops against a background of chronic inflammation and oxidative stress, and their products contribute to cancer development and progression. Therefore, the discovery of novel drugs for the treatment of intestinal diseases is urgently needed. Licorice (Glycyrrhiza glabra) has been largely used for thousands of years in traditional Chinese medicine. Licorice and its derived compounds possess antiallergic, antibacterial, antiviral, anti-inflammatory, and antitumor effects. These pharmacological properties aid in the treatment of inflammatory diseases. In this review, we discuss the pharmacological potential of bioactive compounds derived from Licorice and addresses their anti-inflammatory and antioxidant properties. We also discuss how the mechanisms of action in these compounds can influence their effectiveness and lead to therapeutic effects on intestinal disorders.

Development of a nanotechnological hydrogel containing desonide nanocapsules in association with acai oil: design and in vivo evaluation.

Nanotechnological products have been used as strategies to optimize the therapy and minimize the side effects of topical corticoids. The objective of this study was to develop hydrogels by the addition of sclerotium gum to the suspensions of desonide-loaded açai oil-based nanocapsules and to study their biological effect using an animal model of acute skin inflammation. The hydrogels presented a pH compatible with topical application (4.4 to 5.0), nanometric mean diameter (131 to 165 nm), pseudoplastic behavior, and stability under room conditions during 30 days. The in vitro skin permeation/penetration study demonstrated that a higher amount of desonide (p < 0.05) was retained in the epidermis from the nanotechnological-hydrogels (0.33 to 0.36 µg.cm2) in comparison to the commercial gel cream (0.16 µg.cm2). In the dermis, the nanostructured hydrogels promoted a lower DES retention compared to the non-nanostructured formulations (p < 0.05). This result may indicate a smaller amount of drug reaching the bloodstream and, thus, fewer side effects can be expected. Concerning the anti-inflammatory effect, the developed hydrogels reduced both ear edema and inflammatory cell infiltration, showing an effect comparable to the commercially available formulation, which presents twice the drug concentration. The hydrogels developed may be considered a promising approach to treat dermatological disorders.