Impact of bone-anchored maxillary protraction on the quality of life of subjects with complete unilateral cleft lip and palate.

INTRODUCTION: This study aimed to evaluate the influence of bone-anchored maxillary protraction (BAMP) on the oral health-related quality of life (OHRQOL) in subjects with complete unilateral cleft lip and palate (UCLP) and moderate-to-severe maxillary deficiency. METHODS: A longitudinal observational study was conducted with a sample of 20 patients (13 males, 7 females) aged 10-14 years (mean age, 11.8 years) with Goslon 3, 4, and 5. To assess the patient's perception of their OHRQOL, the Quality of Life Questionnaire for Orthosurgical Patients was administered in 2 stages: after the installation of the protraction plates (T1) and 18 months after the protraction therapy started (T2). The questionnaire was composed of 4 domains, distributed over 22 questions: social aspects, facial esthetics, oral function, and awareness of facial deformity. RESULTS: The treatment protocol improved the OHRQOL in 75% of the patients who presented UCLP. The domain social aspects of the deformity were the only one that showed a significant difference from T1 to T2 and indicated an improvement in self-esteem. The girls had worse OHRQOL than boys at T1, which was statistically significant only for the domains of social aspects of deformity and awareness of deformity. After BAMP therapy, the effect size indicated a larger change in OHRQOL in girls than in boys. CONCLUSIONS: BAMP therapy positively impacted the OHRQOL and self-esteem of patients with UCLP during adolescence.

"Green Is the Color": An Update on Ecofriendly Aspects of Organoselenium Chemistry.

Organoselenium compounds have been successfully applied in biological, medicinal and material sciences, as well as a powerful tool for modern organic synthesis, attracting the attention of the scientific community. This great success is mainly due to the breaking of paradigm demonstrated by innumerous works, that the selenium compounds were toxic and would have a potential impact on the environment. In this update review, we highlight the relevance of these compounds in several fields of research as well as the possibility to synthesize them through more environmentally sustainable methodologies, involving catalytic processes, flow chemistry, electrosynthesis, as well as by the use of alternative energy sources, including mechanochemical, photochemistry, sonochemical and microwave irradiation.

Ozonation and UV photolysis for removing anticancer drug residues from hospital wastewater.

The present study investigates the use of UV light and the ozone process for doxorubicin, daunorubicin, epirubicin, and irinotecan degradation. The process was carried out using different pH values in hospital wastewater. The use of UV radiation reduces the concentration of anticancer drugs, but in all cases, this technology was not able enough to remove on the whole these contaminants from hospital wastewater. The best condition was achieved when using pH 9 for most of the analytes. Doxorubicin, daunorubicin, and epirubicin were degraded at 97.3%, 88.3%, and 99.0%, respectively. Irinotecan showed the lowest degradation, just 55.6%; a slightly higher degradation (63.8%) was obtained when pH 5 was used. Complete removal of doxorubicin, daunorubicin, epirubicin, and irinotecan was achieved when ozone treatment was used for all the pH studied. The results indicated that UV light and the ozone process can be used as a tertiary treatment to reduce the concentration of anticancer drugs in the effluents. Ozonation, therefore, proved to be more efficient than the photolysis process, when considering the percentual degradation of the original compounds in shorter timespans.

Influence of clinical and demographic factors on the oral health-related quality of life of patients with cleft lip and palate undergoing orthodontic treatment: a systematic review and meta-analysis.

OBJECTIVE: The purpose of this study was to evaluate the influence of orthodontic treatment on the oral health-related quality of life (OHRQoL) of patients with cleft lip and palate. SEARCH METHODS: Electronic searches were conducted in Pubmed, Scopus, Web of Science, Cochrane Library, VHL, and OpenGrey databases, completed in January 2021. SELECTION CRITERIA: Cross-sectional and longitudinal observational studies that presented an assessment of OHRQoL in cleft patients undergoing orthodontic treatment were included, according to PRISMA guidelines. Contacts via email were made with authors, to clarify inaccuracies or request additional data. DATA COLLECTION AND ANALYSIS: The entire process was accomplished by two authors, in case of disagreement, a third author mediated the discussion until there was a consensus. Risk assessment was performed by the Fowkes and Fulton qualifier, and the quality of evidence, assessed by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tool. A meta-analysis was performed considering the domains combined into three large groups (physical, psychological, and social). The questionnaires were standardized as to the scores and their direction. RESULTS: A total of 3822 studies were retrieved. After excluding duplicates, the titles and abstracts of the remaining articles were analysed. Twenty-eight articles were read in full; 13 met the eligibility criteria; 12 articles showed sufficient methodological quality and 7 were included in the quantitative assessment. The included studies were published between 2011 and 2019. The samples comprised 19 to 183 patients of both sexes. GRADE showed low evidence when compared to the control group, sexes, age, and types of cleft and very low evidence among longitudinal articles. CONCLUSIONS: The OHRQoL is lower in orthodontic patients with cleft than in those without. The OHRQoL of patients with cleft undergoing orthodontic treatment is not influenced by gender or age group, considering children and adolescents, but it is influenced by the type of cleft. The OHRQoL of patients with CLP does not undergo significant changes during orthodontic treatment. LIMITATIONS: The variety of instruments for measuring OHRQoL rendered meta-analysis difficult. REGISTRATION: PROSPERO database number CRD42017054764.

The Effect of Diabetes and Prediabetes on Mycobacterium tuberculosis Transmission to Close Contacts.

BACKGROUND: It is unknown whether dysglycemia is associated with Mycobacterium tuberculosis transmission. METHODS: We assessed epidemiological and clinical characteristics of patients with culture-confirmed pulmonary tuberculosis and their close contacts, enrolled in a multicenter prospective cohort in Brazil. Contacts were investigated at baseline and 6 months after enrollment. QuantiFERON positivity at baseline and conversion (from negative to positive at month 6) were compared between subgroups of contacts according to glycemic status of persons with tuberculosis (PWTB) as diabetes mellitus (DM) or prediabetes. Multivariable mixed-effects logistic regression models were performed to test independent associations with baseline QuantiFERON positive and QuantiFERON conversion. RESULTS: There were 592 PWTB (153 DM, 141 prediabetes, 211 normoglycemic) and 1784 contacts, of whom 658 were QuantiFERON-positive at baseline and 106 converters. Multivariable analyses demonstrated that tuberculosis-prediabetes cases, acid-fast bacilli-positive, pulmonary cavities, and living with someone who smoked were independently associated with QuantiFERON positive in contacts at baseline. DM, persistent cough, acid-fast bacilli-positive, and pulmonary cavities in tuberculosis source cases were associated with QuantiFERON conversion. CONCLUSIONS: Contacts of persons with pulmonary tuberculosis and dysglycemia were at increased risk of being QuantiFERON positive at baseline or month 6. Increased focus on such close contacts could improve tuberculosis control.

Flow Biocatalysis: A Challenging Alternative for the Synthesis of APIs and Natural Compounds.

Biocatalysts represent an efficient, highly selective and greener alternative to metal catalysts in both industry and academia. In the last two decades, the interest in biocatalytic transformations has increased due to an urgent need for more sustainable industrial processes that comply with the principles of green chemistry. Thanks to the recent advances in biotechnologies, protein engineering and the Nobel prize awarded concept of direct enzymatic evolution, the synthetic enzymatic toolbox has expanded significantly. In particular, the implementation of biocatalysts in continuous flow systems has attracted much attention, especially from industry. The advantages of flow chemistry enable biosynthesis to overcome well-known limitations of "classic" enzymatic catalysis, such as time-consuming work-ups and enzyme inhibition, as well as difficult scale-up and process intensifications. Moreover, continuous flow biocatalysis provides access to practical, economical and more sustainable synthetic pathways, an important aspect for the future of pharmaceutical companies if they want to compete in the market while complying with European Medicines Agency (EMA), Food and Drug Administration (FDA) and green chemistry requirements. This review focuses on the most recent advances in the use of flow biocatalysis for the synthesis of active pharmaceutical ingredients (APIs), pharmaceuticals and natural products, and the advantages and limitations are discussed.

Pharmacological treatment of violence in schizophrenia.

Chronic aggression and violence in schizophrenia are rare, but receive disproportionate negative media coverage. This contributes to the stigma of mental illness and reduces accessibility to mental health services. Substance Use Disorders (SUD), antisocial behavior, non-adherence and recidivism are known risk factors for violence. Treatment with antipsychotic medication can reduce violence. Aside from clozapine, long-acting injectable antipsychotics (LAI) appear to be superior to oral antipsychotics for preventing violence, addressing adherence and recidivism. LAI also facilitate the implementation of functional skills training. For the high-risk recidivist target population with schizophrenia, better life skills have the potential to also reduce the risk for contact with the legal system, including an improved ability to live independently in supported environments and interact appropriately with others. High-risk patients who are resistant to treatment with other antipsychotics should receive treatment with clozapine due to its direct positive effects on impulsive violence, along with a reduction in comorbid risk factors such as SUDs.

Inhibitory and Cooperative Effects Regulated by pH in Host-Guest Complexation between Cationic Pillar[5]arene and Reactive 2-Carboxyphthalanilic Acid.

The study of host-guest complexation between reactive 2-carboxyphthalanilic acid (CPA) and two cationic pillararenes has been carried out. Host-guest complexation with significant kinetic effects was observed only with the smaller cavity size pillararene (P5A). Kinetics in the pH range 1.50-6.40, ESI-MS, 1H NMR titration, and ROESY experiments were performed to characterize the complexes. High binding stoichiometry (H:G2) was observed for all CPA protonation states. The system is pH-dependent, and inversion of cooperativity (negative to positive) occurs by increasing the dianionic CPA2- concentration (allosteric behavior). Toward physiological pH, association constant K1:1 does not change (104 M-1), and K1:2 increased from 102 to 104 M-1, as well as the inhibitory effect increased up to 222-fold. NMR results elucidated the structure of the complex and allowed us to create a map of H-H interactions that describes well the diversity and number of interactions in the complex.

Optical coherence tomography imaging of melanoma skin cancer.

No consensus guidelines exist on the use of optical coherence tomography (OCT) for diagnosis of cutaneous melanoma. The objectives of this review are to provide a descriptive review of the literature on characteristics of cutaneous melanomas seen on high-definition OCT (HD-OCT), speckle variance OCT (SV-OCT), and conventional OCT and to compare their diagnostic ability with that of histopathology. A review of PubMed and Google Scholar identified all available literature on OCT in melanoma skin cancer that included all in vivo and ex vivo studies on human or human tissues and excluded all studies on non-human subjects or animal studies. Two hundred nine abstracts were considered for evaluation, 31 abstracts were selected for manuscript review, and 14 abstracts were included that met all criteria. Diagnoses of MIS and MM using HD-OCT and SV-OCT were consistently reported to correlate with histopathology. However, accuracy of diagnosis using conventional OCT varied. Most authors agreed that it was difficult to differentiate MM from benign nevi using conventional OCT. HD-OCT, SV-OCT, and conventional OCT show promise for visualizing cutaneous melanoma. The use of OCT in diagnosis of melanoma is rarely reported in the literature. There is a need to increase and standardize reporting of OCT for diagnosis of cutaneous melanoma.

Norepinephrine Controls Effector T Cell Differentiation through ß2-Adrenergic Receptor-Mediated Inhibition of NF-κB and AP-1 in Dendritic Cells.

Despite accumulating evidence indicating that neurotransmitters released by the sympathetic nervous system can modulate the activity of innate immune cells, we still know very little about how norepinephrine impacts signaling pathways in dendritic cells (DC) and the consequence of that in DC-driven T cell differentiation. In this article, we demonstrate that ß2-adrenergic receptor (ß2AR) activation in LPS-stimulated DC does not impair their ability to promote T cell proliferation; however, it diminishes IL-12p70 secretion, leading to a shift in the IL-12p70/IL-23 ratio. Although ß2AR stimulation in DC induces protein kinase A-dependent cAMP-responsive element-binding protein phosphorylation, the effect of changing the profile of cytokines produced upon LPS challenge occurs in a protein kinase A-independent manner and, rather, is associated with inhibition of the NF-κB and AP-1 signaling pathways. Moreover, as a consequence of the inverted IL-12p70/IL-23 ratio following ß2AR stimulation, LPS-stimulated DC promoted the generation of CD4(+) T cells that, upon TCR engagement, produced lower amounts of IFN-γ and higher levels of IL-17. These findings provide new insights into molecular and cellular mechanisms by which ß2AR stimulation in murine DC can influence the generation of adaptive immune responses and may explain some aspects of how sympathetic nervous system activity can modulate immune function.

The role of zinc in the treatment of acne: A review of the literature.

Acne vulgaris is a chronic disease of the pilosebaceous units presenting as inflammatory or noninflammatory lesions in individuals of all ages. The current standard of treatment includes topical formulations in the forms of washes, gels, lotions, and creams such as antibiotics, antibacterial agents, retinoids, and comedolytics. Additionally, systemic treatments are available for more severe or resistant forms of acne. Nevertheless, these treatments have shown to induce a wide array of adverse effects, including dryness, peeling, erythema, and even fetal defects and embolic events. Zinc is a promising alternative to other acne treatments owing to its low cost, efficacy, and lack of systemic side effects. In this literature review, we evaluate the effectiveness and side-effect profiles of various formulations of zinc used to treat acne.

Diphenyl diselenide derivatives inhibit microbial biofilm formation involved in wound infection.

BACKGROUND: Organoselenium compounds have antimicrobial activity against some bacteria and fungi; furthermore, the antioxidant activity of diselenides has been demonstrated. The aim of the present work was to examine the in vitro minimal inhibitory concentration of a panel of differently substituted diselenides and their effectiveness in inhibiting biofilm formation and dispersing preformed microbial biofilm of Staphylococcus epidermidis, Staphylococcus aureus, Streptococcus pyogenes and Pseudomonas aeruginosa and the yeast Candida albicans, all involved in wound infections. Moreover, the cytotoxicity of the compounds was determined in human dermal fibroblast and keratinocytes. In closing, we tested their direct antioxidant activity. RESULTS: Diselenides showed different antimicrobial activity, depending on the microorganism. All diselenides demonstrated a good antibiofilm activity against S. aureus and S. epidermidis, the compounds camphor diselenide, bis[ethyl-N-(2'-selenobenzoyl) glycinate] and bis[2'-seleno-N-(1-methyl-2-phenylethyl) benzamide] were active against S. pyogenes and C. albicans biofilm while only diselenides 2,2'-diselenidyldibenzoic acid and bis[ethyl-N-(2'-selenobenzoyl) glycinate] were effective against P. aeruginosa. Moreover, the compounds bis[ethyl-N-(2'-selenobenzoyl) glycinate] and bis[2'-seleno-N-(1-methyl-2-phenylethyl) benzamide] showed an antioxidant activity at concentrations lower than the 50 % of cytotoxic concentration. CONCLUSIONS: Because microbial biofilms are implicated in chronic infection of wounds and treatment failure, the combination of antimicrobial activity and potential radical scavenging effects may contribute to the improvement of wound healing. Therefore, this study suggests that bis[ethylN-(2'-selenobenzoyl) glycinate] and bis[2'-seleno-N-(1-methyl-2-phenylethyl) benzamide] are promising compounds to be used in preventing and treating microbial wound infections.

Beta2-adrenergic receptor signaling in CD4+ Foxp3+ regulatory T cells enhances their suppressive function in a PKA-dependent manner.

Beta2-adrenergic receptor (B2AR) signaling is known to impair Th1-cell differentiation and function in a cAMP-dependent way, leading to inhibition of cell proliferation and decreased production of IL-2 and IFN-γ. CD4(+) Foxp3(+) Treg cells play a key role in the regulation of immune responses and are essential for maintenance of self-tolerance. Nevertheless, very little is known about adrenergic receptor expression in Treg cells or the influence of noradrenaline on their function. Here we show that Foxp3(+) Treg cells express functional B2AR. B2AR activation in Treg cells leads to increased intracellular cAMP levels and to protein kinase A (PKA)-dependent CREB phosphorylation. We also found that signaling via B2AR enhances the in vitro suppressive activity of Treg cells. B2AR-mediated increase in Treg-cell suppressive function was associated with decreased IL-2 mRNA levels in responder CD4(+) T cells and improved Treg-cell-induced conversion of CD4(+) Foxp3(-) cells into Foxp3(+) induced Treg cells. Moreover, B2AR signaling increased CTLA-4 expression in Treg cells in a PKA-dependent way. Finally, we found that PKA inhibition totally prevented the B2AR-mediated increase in Treg-cell suppressive function. Our data suggest that sympathetic fibers are able to regulate Treg-cell suppressive activity in a positive manner through B2AR signaling.

Design, synthesis and evaluation of seleno-dihydropyrimidinones as potential multi-targeted therapeutics for Alzheimer's disease.

In this paper we report the design, synthesis and evaluation of a series of seleno-dihydropyrimidinones as potential multi-targeted therapeutics for Alzheimer's disease. The compounds show excellent results as acetylcholinesterase inhibitors, being as active as the standard drug. All these compounds also show very good antioxidant activity through different mechanisms of action.

Microwave-assisted UV digestion of starch and skimmed milk powder: Environmentally friendly protocol for essential and toxic elements determination.

The present work evaluated a microwave-assisted wet digestion method using diluted HNO3 with in situ UV radiation for the digestion of starch and skimmed milk powder for further metals determination by spectrometric plasma-based techniques. The sample digestion was conducted using an in situ UV lamp (electrodeless discharge lamp), and the digestion efficiency was improved by employing O2 (20 bar) and 2 mL 30 % H2O2 as auxiliary reagents. The accuracy of the proposed digestion method was evaluated by metals determination (Ca, Cd, Cu, Fe, K, Mg, Mo, Mn, Na, Pb, and Zn) in certificated reference material, which agreed with certified values (Student t-test <0,05). With the use of a UV lamp an environmentally friendly protocol was developed for starch and skimmed milk powder digestion using 0.1 mol L-1 HNO3 with auxiliary reagents (H2O2 or O2). The RCC value ranged from 0.9 to 1.2 % (starch and skimmed milk powder, respectively). The simultaneous cooling approach further improved the digestion efficiency (RCC <0,3 % for both samples), allowing to use milder digestion conditions, or even just water, being environmentally friendly, reducing the waste generation and reagents consumption, allowing food quality control through a greener approach.

New Chalcogen-Functionalized Naphthoquinones: Design, Synthesis, and Evaluation, In Vitro and In Silico, against Squamous Cell Carcinoma.

Due to the growth in the number of patients and the complexity involved in anticancer therapies, new therapeutic approaches are urgent and necessary. In this context, compounds containing the selenium atom can be employed in developing new medicines due to their potential therapeutic efficacy and unique modes of action. Furthermore, tellurium, a previously unknown element, has emerged as a promising possibility in chalcogen-containing compounds. In this study, 13 target compounds (9a-i, 10a-c, and 11) were effectively synthesized as potential anticancer agents, employing a CuI-catalyzed Csp-chalcogen bond formation procedure. The developed methodology yielded excellent results, ranging from 30 to 85%, and the compounds were carefully characterized. Eight of these compounds showed promise as potential therapeutic drugs due to their high yields and remarkable selectivity against SCC-9 cells (squamous cell carcinoma). Compound 10a, in particular, demonstrated exceptional selectivity, making it an excellent choice for cancer cell targeting while sparing healthy cells. Furthermore, complementing in silico and molecular docking studies shed light on their physical features and putative modes of action. This research highlights the potential of these compounds in anticancer treatments and lays the way for future drug development efforts.

Younger Researchers of the Brazilian Chemical Society: a network fostering representation, communication, and collaboration.

The Younger Researchers of the Brazilian Chemical Society committee supports early career researchers promoting communication, collaboration, education, networking, representation, and career development.

Demonstrating the interference of tissue processing in the evaluation of tissue biomarkers: The case of PD-L1.

The immunohistochemical (IHC) expression of PD-L1 in cancer models is used as a predictive biomarker of response to immunotherapy. We aimed to evaluate the impact of the usage of 3 different tissue processors in the IHC expression of PD-L1 antibody clones: 22C3 and SP142. Three different topographies of samples (n = 73) were selected at the macroscopy room: 39 uterine leiomyomas, 17 placentas and 17 palatine tonsils. Three fragments were collected from each sample and were inked with a specific color that represented their separate processing in a different tissue processor (A, B or C). During embedding, the 3 fragments with distinct processing were ensemble in the same cassette for sectioning of 3 slides/each: hematoxylin-eosin, 22C3 PDL1 IHC staining and SP142 PD-L1 IHC staining, that were blindly observed by 2 pathologists under digital environment. All but one set of 3 fragments were considered adequate for observation even in the presence of artifacts associated with processing issues that were recorded as high as 50.7 % for processor C. The occurrence of background non-specific staining and the presence of false positive results appear to be unrelated with the PD-L1 clone or the type of tissue processing. 22C3 PD-L1 was more frequently considered adequate for evaluation than SP142 PD-L1 that, in 29.2 % of WSIs (after tissue processor C) were considered not adequate for observation due to lack of the typical pattern of expression. Similarly, the intensity of PD-L1 staining was significantly decreased in fragments processed by C (both PD-L1 clones) in tonsil and placenta specimens, and by A (both clones) in comparison with those processed by B. This study demonstrates the need to standardize the tissue processing in pathology to cope with the growing needs of precision medicine quantifications and the production of high-quality material necessary for computational pathology usage.

BACE-1 Inhibitors Targeting Alzheimer's Disease.

The accumulation of amyloid-ß (Aß) is the main event related to Alzheimer's disease (AD) progression. Over the years, several disease-modulating approaches have been reported, but without clinical success. The amyloid cascade hypothesis evolved and proposed essential targets such as tau protein aggregation and modulation of ß-secretase (ß-site amyloid precursor protein cleaving enzyme 1 - BACE-1) and γ-secretase proteases. BACE-1 cuts the amyloid precursor protein (APP) to release the C99 fragment, giving rise to several Aß peptide species during the subsequent γ-secretase cleavage. In this way, BACE-1 has emerged as a clinically validated and attractive target in medicinal chemistry, as it plays a crucial role in the rate of Aß generation. In this review, we report the main results of candidates in clinical trials such as E2609, MK8931, and AZD-3293, in addition to highlighting the pharmacokinetic and pharmacodynamic-related effects of the inhibitors already reported. The current status of developing new peptidomimetic, non-peptidomimetic, naturally occurring, and other class inhibitors are demonstrated, considering their main limitations and lessons learned. The goal is to provide a broad and complete approach to the subject, exploring new chemical classes and perspectives.

Green Approach for the Synthesis of Chalcogenyl- 2,3-dihydrobenzofuran Derivatives Through Allyl-phenols/ Naphthols and Their Potential as MAO-B Inhibitors.

This work presents the design, synthesis, and MAO-B inhibitor activity of a series of chalcogenyl-2,3-dihydrobenzofurans derivatives. Using solvent- and metal-free methodology, a series of chalcogen-containing dihydrobenzofurans 7-9 was obtained with yields ranging from 40% to 99%, using an I2 /DMSO catalytic system. All compounds were fully structurally characterized using 1 H and 13 C NMR analysis, and the unprecedented compounds were additionally analyzed using high-resolution mass spectrometry (HRMS). In addition, the mechanistic proposal that iodide is the most likely species to act in the transfer of protons along the reaction path was studied through theoretical calculations. Finally, the compounds 7b-e, 8a-e, and 9a showed great promise as inhibitors against MAO-B activity.