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ETHNOPHARMACOLOGICAL RELEVANCE: Copaifera multijuga Hayne (Leguminosae) is a tree that produces an oleoresin, which is extensively commercialized in Brazil as capsules or crude oil for the treatment of several disorders. Ethnopharmacological studies show a diversity of indications such as anti-inflammatory and epidermal wound cicatrization. AIM OF THE STUDY: In the present work three fractions obtained from Copaifera multijuga oleoresin (hexane (HF), chloroform (CF), and methanol (MF) from a KOH impregnated silica gel column chromatography, representing the three main classes of compounds in the Copaifera genus (hydrocarbon sesquiterpenes, oxygenated sesquiterpenes and acidic diterpenes), were evaluated using antinociceptive and anti-inflammatory models. MATERIALS AND METHODS: HF, CF, and MF (doses ranging between 1 and 150 mg/kg, depending on the model used), Copaifera multijuga oleoresin (CMO, 100mg/kg, p.o.) and the reference drug morphine (5mg/kg, p.o.) were evaluated using models for analgesia (acetic acid-induced contortions and tail flick) or inflammation (rat paw oedema and increase in vascular permeability). To elucidate the mechanism of action from the fractions, animals were pre-treated with naloxone (opioid receptor antagonist, 5mg/kg, i.p.). RESULTS: Fractions significantly inhibited (in a concentration-dependant way) the number of contortions induced by acetic acid and the second phase of formalin-induced licking response. Similar results were observed in the tail flick model. The central antinociceptive effect for HF and CF at the doses of 50 and 100mg/kg was higher than the one observed for morphine (1mg/kg). Administration of naloxone inhibited the antinociceptive effect of fractions indicating that HF, CF, and MF may be acting on opioid receptors. All three fractions also inhibited rat paw oedema and the increase in vascular permeability induced by several phlogistic agents (carrageenan, histamine, and serotonin). CONCLUSIONS: Our results indicate that fractions obtained from Copaifera multijuga Hayne demonstrate an antinociceptive effect probably mediated by opioid receptors, and anti-inflammatory activity through inhibition of histaminergic and serotoninergic pathways. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effect of chronic treatment with C. multijuga oil on Ehrlich tumor evolution. C. multijuga was fractionated in a KOH impregnated silica gel column chromatography to give three distinct fractions, i.e., hexanic, chloroformic, and methanolic, mainly composed by hydrocarbon sesquiterpenes, oxygenated sesquiterpenes and acidic diterpenes, respectively. Results demonstrated that the C. multijuga oil, the hexanic, and chloroformic fractions did not develop toxic effects. The oil, hexanic and chloroformic fractions (doses varying between 100 and 200mg/kg) showed antineoplasic properties against Ehrlich ascitic tumor (EAT) and solid tumor during 10 consecutive days of treatment inhibiting ascitic tumor cell number, reverting medulla and blood cell counts to values similar to control group, and inhibiting the increase on several inflammatory mediators (total protein, PGE(2), nitric oxide, and TNF) on ascitic fluid. The treatment also inhibited the increase in paw volume on tumor-inoculated mice. In conclusion, C. multijuga as well as its fractions demonstrated antineoplasic effect even after oral administration confirming its use by traditional medicine. [ABSTRACT FROM AUTHOR]

Objective: Access to crizanlizumab, a disease-modifying therapy for sickle cell disease (SCD), was provided through a managed access program (MAP, NCT03720626). The present analysis evaluated the impact of 12 months of crizanlizumab treatment on vaso-occlusive crises (VOCs), and on the use of opioids for VOC-related pain relief, in patients with SCD from the MAP., Methods: From June 2018 to January 2023, 112 patients with a history of recurrent VOCs completed 12 months of crizanlizumab (5 mg/kg) treatment and were monitored for adverse events (AEs)., Results: Crizanlizumab led to reductions of 18.0% and 36.2% in the proportions of patients having ≥ 1 home- and ≥ 1 healthcare-managed VOCs. Median absolute changes (interquartile range) from baseline in the rates of home- and healthcare-managed VOCs were -3.0 (-6.0, -1.0) and -2.0 (-4.0, 0), respectively. Data stratified by genotype and prior hydroxyurea use showed similar reductions in VOC rates. A 35.5% reduction in the proportion of patients requiring opioids was noted. AEs were consistent with earlier reports, and no new safety concerns were identified., Conclusions: Crizanlizumab demonstrated potential benefits in attenuating VOC episodes, irrespective of SCD genotype and prior hydroxyurea use, and in lowering opioid usage. The safety of crizanlizumab was consistent with earlier reports., Trial Registration: The MAP has been registered at ClinicalTrials.gov with the ID, NCT03720626., (© 2024 Novartis and The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)

Background/Objectives: Impacted teeth are a common phenomenon, in both young and adult populations, as extensively documented in the literature. This study aims to systematically assess the global prevalence of impacted third molars and to analyze their demographic predictors. Methods: The present review adheres to PRISMA guidelines and includes studies published until December 2023. Three databases (MEDLINE, LILACS, Cochrane) were searched, and studies reporting prevalence rates and demographic predictors of impacted third molars were selected for analysis. A meta-analysis was conducted using a random-effects model to calculate pooled prevalence and assess demographic variations. Results: This review yielded 98 studies involving 183,828 subjects. The pooled prevalence of impacted third molars was 36.9% [95% CI: 33.1-40.7%] per subject and 46.4% [95% CI: 36.7-56.1%] per tooth, with the highest rates in Asia (43.1% [95% CI: 34.6-51.7%]) and the lowest in Europe (24.5% [95% CI: 16.1-33.9%]). An odds ratio of 1.173 [95% CI: 1.021-1.347%] indicated a slightly higher likelihood of third molar impaction among women compared to men, and mandibular third molar impaction was more frequent than maxillary impaction. The meta-regression indicated insufficient consistency for the geographic area to be considered a source of heterogeneity in the prevalence of impacted third molars. Conclusions: The present meta-analysis highlights the substantial prevalence of impacted third molars worldwide and underscores the influence of demographic predictors. These findings may inform region-specific clinical guidelines and preventive approaches for managing impacted third molars.

Sickle cell anemia (SCA) is characterized by immune system activation and heightened susceptibility to infections. We hypothesized that SCA patients exhibit transcriptional alterations in B-cell-related genes, impacting their peripheral B-cell compartment and leading to dysregulated humoral immunity and increased infection susceptibility. Our objective was to conduct an in silico analysis of whole blood transcriptomes from SCA patients and healthy controls obtained from public repositories. We aimed to identify alterations in the adaptive immune system and validate these findings in our own SCA patient cohort. Bioinformatic analyses unveiled significant transcriptional alterations in B-cell signatures, developmental pathways, and signaling pathways. These results were validated in peripheral blood mononuclear cells from our SCA patient cohort and controls using real-time polymerase chain reaction and flow cytometry. Ninety genes exhibited differential expression, with 70 upregulated and 20 downregulated. Dysregulation in the B-cell compartment of SCA patients was evident, characterized by increased frequencies of immature and naive B-cells, and decreased percentages of memory B-cell subsets compared with healthy controls. Our findings highlight previously unexplored transcriptional and quantitative alterations in peripheral B-cells among SCA patients. Understanding these changes sheds light on the mechanisms contributing to the heightened infection risk in this population. Future studies should delve deeper into these molecular changes to develop targeted interventions and therapeutic strategies aimed at mitigating infection susceptibility in individuals with SCA., Competing Interests: Conflicts of Interest Disclosure The authors have nothing to disclose., (Copyright © 2024 International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.)

Background: Declining vaccination coverage (VC) and vaccine hesitancy among medical students are global challenges. These challenges reflect individual and logistical barriers to a sufficient adherence toward essential vaccines for healthcare professionals, as well as presenting a need for educational strategies during undergraduate training., Methods: This is a prospective study for evaluating VC rates, sociodemographic associations, and the vaccine confidence among medical students at a federal university in Brazil. The data collection included questionnaires and individual analyses of the participants' vaccination records., Results: A total of 237 medical students from all six years of an undergraduate program participated, of whom 124 (52.3%) had a vaccination record. Although the majority considered the vaccines to be "Completely Safe" (86.9%), the VC rates for complete vaccination schedules were relatively low, ranging from 87.9% (hepatitis B vaccine) to 3.2% (meningococcal B vaccine), including the vaccines from the National Immunization Program (NIP) and the private sector. Higher VC rates were found to occur among students in the final years of their undergraduate studies, in those from families with higher monthly incomes, and those from private secondary schools., Conclusions: Given the low VC rates among medical students, other factors in addition to vaccine confidence may be determinants, thus highlighting the importance of reviewing policies for the inclusion of priority groups in the NIP and in implementing educational interventions during undergraduate training.

Sickle cell disease (SCD) comprises inherited red blood cell disorders due to a mutation in the β-globin gene (c20A > T, pGlu6Val) and is characterized by the presence of abnormal hemoglobin, hemoglobin S, hemolysis, and vaso-occlusion. This mutation, either in a homozygous configuration or in compound states with other β-globin mutations, leads to polymerization of hemoglobin S in deoxygenated conditions, causing modifications in red blood cell shape, particularly sickling. Vaso-occlusive crisis (VOC) is the hallmark of the disease, but other severe complications may arise from repeated bouts of VOCs. SCD is considered a global health problem, and its incidence has increased in some areas of the world, particularly the Americas and Africa. Management of the disease varies according to the region of the world, mainly due to local resources and socioeconomic status. This review aimed to describe more recent data on SCD regarding available treatment options, especially in Brazil. New treatment options are expected to be available to all patients, particularly crizanlizumab, which is already approved in the country.

The health benefits of exercise training in a cancer setting are increasingly acknowledged; however, the underlying molecular mechanisms remain poorly understood. It has been suggested that extracellular vesicles (EVs) released from contracting skeletal muscles play a key role in mediating the systemic benefits of exercise by transporting bioactive molecules, including myokines. Nevertheless, skeletal muscle-derived vesicles account for only about 5% of plasma EVs, with the immune cells making the largest contribution. Moreover, it remains unclear whether the contribution of skeletal muscle-derived EVs increases after physical exercise or how muscle contraction modulates the secretory activity of other tissues and thus influences the content and profile of circulating EVs. Furthermore, the destination of EVs after exercise is unknown, and it depends on their molecular composition, particularly adhesion proteins. The cargo of EVs is influenced by the training program, with acute training sessions having a greater impact than chronic adaptations. Indeed, there are numerous questions regarding the role of EVs in mediating the effects of exercise, the clarification of which is critical for tailoring exercise training prescriptions and designing exercise mimetics for patients unable to engage in exercise programs. This review critically analyzes the current knowledge on the effects of exercise on the content and molecular composition of circulating EVs and their impact on cancer progression., (© 2024. The Author(s).)

Obstructive sleep apnea is the most common sleep disorder. This review aims to evaluate the effectiveness and safety of respiratory muscle training in the treatment of patients with obstructive sleep apnea. The study protocol was registered in Prospero Platform (CRD42018096980). We performed searches in the main databases: Medical Literature Analysis and Retrieval System Online (MEDLINE) via Pubmed; Excerpta Medica dataBASE (Embase) via Elsevier; Cochrane Central Register of Controlled Trials (CENTRAL) via Cochrane Library; Latin American and Caribbean Literature on Health Sciences (LILACS) through the Portal of the Virtual Health Library and Physiotherapy Evidence Database (PEDro) for all randomised-controlled trials published before July 2022. The randomised-controlled trials were assessed for risk of bias and certainty of evidence. Thirteen randomised-controlled trials were included. All studies had an overall high risk of bias. Inspiratory muscle training probably improves systolic blood pressure and sleepiness when compared with sham. However, inspiratory muscle training probably does not improve diastolic blood pressure and maximum expiratory pressure, and may not be superior to sham for apnea-hypopnea index, forced expiratory volume in 1 s, forced vital capacity, sleep quality and quality of life. In addition, it is uncertain whether there is any effect of inspiratory muscle training on maximum inspiratory pressure and physical capacity. Inspiratory muscle training may also improve maximum inspiratory pressure and maximum expiratory pressure compared with oropharyngeal exercises. However, it may not be superior for apnea-hypopnea index, sleep quality, sleepiness, quality of life and functional capacity. When associated with physical exercise, inspiratory muscle training may not be superior to physical exercise alone for maximum inspiratory pressure, maximum expiratory pressure, systolic and diastolic blood pressure, and functional capacity. At the same time, when associated with cardiac rehabilitation exercises, inspiratory muscle training may reduce apnea-hypopnea index, improve inspiratory muscle strength, sleepiness and sleep quality compared with cardiac rehabilitation alone. However, it may not be superior for improving quality of life. Regarding expiratory muscle training, it may improve expiratory muscle strength and sleep quality, but not sleepiness when compared with sham. The evidence on the effects of expiratory muscle training in apnea-hypopnea index is very uncertain., (© 2023 European Sleep Research Society.)

Background: Bladder carcinoma (BC) ranks second among the genitourinary cancers worldwide. Influence of androgens and expression of androgen receptors in neoplasms are recent findings which were implicated in the development of BC. We aimed to study androgen receptor (AR) expression in bladder urothelial neoplasms and correlate its expression with grade and stage of the tumor., Methods: Immunohistochemistry (IHC) was done on samples collected in a tertiary care hospital over one year consisting of 71 urothelial BC and 20 non-neoplastic urothelial conditions. Two pathologists graded the IHC and nuclear staining was considered as positive expression., Results: AR was expressed in 23.9% (17/71) of bladder urothelial neoplasms. AR was expressed in 25.7% and 22.3% of high and low-grade tumors and 25% and 22.3% of non muscle-invasive and muscle-invasive BC. AR expression had no significant correlation with gender, age (> 50 years), muscle invasion or grade. AR expression was significantly absent in non-neoplastic conditions (p = 0.018)., Conclusions: AR has varied expression in BC and it is relatively lower in this study population.

The polymerization of hemoglobin under deoxygenation is the main pathophysiological event in sickle cell diseases, described more than 70 years ago. The last two decades have seen a major increase in knowledge about the cascade of events that follow the polymerization of hemoglobin and the ensuing sickling of red blood cells. Several distinctive therapeutic targets have been discovered as a result, and a few drugs with innovative mechanisms of action are already on the market, while several others are the focus of ongoing trials. The aim of this narrative review is to describe some of the more recent data in the SCD literature regarding pathophysiology and novel treatments.

Rheumatoid arthritis (RA) is an inflammatory, systemic and chronic disease that mainly affects the joints. It is characterized mainly by pain, edema and joint stiffness, which can lead to significant loss of functional capacity and quality of life. Several physical therapy resources are used in the treatment of AR, such as low-level laser therapy (LLLT) and its analgesic and anti-inflammatory effects. However, the efficacy of LLLT in AR is still controversial. The objective of this study is to evaluate the efficacy of low-level laser therapy in adults with RA. Methods and findings: We searched MEDLINE, EMBASE, CENTRAL, PEDro, LILACS, IBECS, CUMED, SCIELO and ClinicalTrials.gov. Two researchers independently selected studies, extracted data, evaluated the risk of bias and assessed the certainty of evidence using GRADE approach. Disagreements were resolved by a third author. Meta-analyses were performed. Currently available evidence was from 18 RCTs, with a total of 793 participants. We found low-quality evidence suggesting there may be no difference between using infrared laser and sham in terms of pain, morning stiffness, grip strength, functional capacity, inflammation, ROM, disease activity and adverse events. The evidence is very uncertain about the effects of red laser compared to sham in pain, morning stiffness. The evidence is also very uncertain about the effects of laser acupuncture compared to placebo in functional capacity, quality of life, range of motion and inflammation. Conclusions: Thus, infrared laser may not be superior to sham in RA patients. There is insufficient information to support or refute the effectiveness of red laser, laser acupuncture and reflexology for treating patients with RA., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lourinho et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The buccal mucosa is arising within the pharmaceutical landscape as an attractive option for local and systemic drug delivery, mostly due to its high vascularization, inherent permeability and robustness. Still, one of the major challenges in bringing oromucosal preparations to market remains the accurate evaluation of permeability. During pre-clinical drug development, in vitro permeation assessment is essential, and methodologies, based on the selection of a proper membrane in a diffusion cell, have become appealing alternatives to the conventional cell-based models. The development of such methods is being constrained by the number of variables - related to study conditions, setup and formulation - that need to be optimized to accurately estimate buccal permeation. The gap of knowledge over the mentioned variables may lead to long costly developments and poorly accurate methods, especially if the empirical analytical approach is used. In this paper, a systematic risk-based analytical quality by design approach was applied to the development of a buccal in vitro permeation method, ensuring that all sources of variability affecting permeation process were identified, explained and managed by appropriate measures. Researchers are guided through a step by step model, successfully demonstrating with experimental data the impact of critical variables on method's performance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The development of advanced facemasks stands out as a paramount priority in enhancing healthcare preparedness. In this work, different polypropylene non-woven fabrics (NWF) were characterised regarding their structural, physicochemical and comfort-related properties. The selected NWF for the intermediate layer was functionalised with zinc oxide nanoparticles (ZnO NPs) 0.3 and 1.2wt% using three different methods: electrospinning, dip-pad-dry and exhaustion. After the confirmation of ZnO NP content and distribution within the textile fibres by morphological and chemical analysis, the samples were evaluated regarding their antimicrobial properties. The functionalised fabrics obtained via dip-pad-dry unveiled the most promising data, with 0.017 ± 0.013wt% ZnO NPs being mostly located at the fibre's surface and capable of total eradication of Staphylococcus aureus and Escherichia coli colonies within the tested 24 h (ISO 22196 standard), as well as significantly contributing (**** p < 0.0001) to the growth inhibition of the bacteriophage MS2, a surrogate of the SARS-CoV-2 virus (ISO 18184 standard). A three-layered structure was assembled and thermoformed to obtain facemasks combining the previously chosen NWF, and its resulting antimicrobial capacity, filtration efficiency and breathability (NP EN ISO 149) were assessed. The developed three-layered and multiscaled fibrous structures with antimicrobial capacities hold immense potential as active individual protection facemasks.

Background: The p53 and p21 proteins are important regulators of cell cycle and apoptosis and may contribute to autoimmune diseases, such as systemic lupus erythematosus (SLE). As genetic polymorphisms may cause changes in protein levels and functions, we investigated associations of TP53 and p21 (CDKN1A) polymorphisms (p53 72 G > C-rs1042522; p53 PIN3-rs17878362; p21 31 C > A-rs1801270; p21 70 C > T-rs1059234) with the development of systemic lupus erythematosus (SLE) in a Southeastern Brazilian population., Methods: Genotyping of 353 female volunteers (cases, n = 145; controls, n = 208) was performed by polymerase chain reaction, restriction fragment length polymorphism and/or DNA sequencing. Associations between TP53 and p21 polymorphisms and SLE susceptibility and clinical manifestations of SLE patients were assessed by logistic regression analysis., Results: Protective effect was observed for the genotype combinations p53 PIN3 A1/A1-p21 31 C/A, in the total study population (OR 0.45), and p53 PIN3 A1/A2-p21 31 C/C, in non-white women (OR 0.28). In Whites, p53 72 C-containing (OR 3.06) and p53 PIN3 A2-containing (OR 6.93) genotypes were associated with SLE risk, and higher OR value was observed for the combined genotype p53 72 G/C-p53 PIN3 A1/A2 (OR 9.00). Further, p53 PIN3 A1/A2 genotype was associated with serositis (OR 2.82), while p53 PIN3 A2/A2 and p53 72 C/C genotypes were associated with neurological disorders (OR 4.69 and OR 3.34, respectively)., Conclusions: Our findings showed that the TP53 and p21 polymorphisms included in this study may have potential to emerge as SLE susceptibility markers for specific groups of patients. Significant interactions of the TP53 polymorphisms with serositis and neurological disorders were also observed in SLE patients., (© 2023. Sociedade Brasileira de Reumatologia.)

Sickle cell disease (SCD) is a group of hereditary chronic diseases with a substantial impact on quality of life and morbimortality. In Brazil, it is 1 of the most common hereditary diseases; however, there are sparse epidemiological data for the country. Using data from death certificates, we aimed to estimate the median age at death, years of life lost because of SCD, and the median survival. From 2015 to 2019, we identified 3320 records of deaths of individuals with SCD, from a total of 6 553 132 death records. Among individuals with SCD, the median age at death was 37 years less than that of the general population (SCD: aged 32.0 years at death, interquartile range [IQR], 19.0-46.0; general population: aged 69.0 years at death; IQR, 53.0-81.0). Results were consistent when stratified by sex or race. Over the 5 years evaluated, crude death rates varied from 0.30 to 0.34 per 100 000 inhabitants (mean 0.32 per 100 000 inhabitants). We estimated a prevalence of 60 017 individuals living with SCD (29.02 cases per 100 000) and an average incidence of 1362 cases yearly. The median estimated survival was 40 years for individuals with SCD and 80 years for the general population. SCD was associated with an increased risk of mortality in most age ranges. Among individuals with SCD aged between 1 and 9 years and between 10 and 39 years, the risk of death was 32 and 13 times higher, respectively. The most common causes of death were sepsis and respiratory failure. These results highlight the burden of SCD in Brazil and the necessity of improved care for this population., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Urothelial carcinomas (UC) account for 6 and 2% of all cancers in men and women, respectively. Human papillomavirus (HPV) is one of the causative agents in cancers of the uterine cervix and head and neck. The role of HPV is also being studied in cancers of the urinary bladder, penis, and prostate. As p16-INK4a is a surrogate marker for high-risk HPVE7 oncoprotein, this study aims to highlight the utility of p16 immunohistochemistry (IHC) in the evaluation of HPV-associated UC., Materials and Methods: A retrospective study was conducted on UC of the bladder received in the Pathology department between January 2013 and December 2018. Bladder biopsies from non-neoplastic lesions served as controls. IHC was done for the detection of the p16 antigen. The p16 staining was recorded as positive, when there was strong staining in >50% of tumor nuclei. The p16 positive and negative tumors were compared based on age, gender, tumor size, grade, and muscle invasion. P value <0.05 was considered statistically significant., Results: The expression of p16 was analyzed in 72 UC and compared with 20 non-neoplastic cases, of which 26.4% of the cases showed p16 expression. The p16 expression was absent in the non-neoplastic lesions. While the majority (87.5%) of the low-grade tumors were negative for p16 expression, 43.8% high-grade tumors were positive. Similarly, a larger proportion of invasive carcinomas (38.8%) expressed p16 as compared to non-invasive carcinomas (13.8%). Thus, p16 expression showed a significant association with grade and stage in these malignancies (P < 0.05)., Conclusion: The p16 expression was associated with high-grade and muscle-invasive UC. The p16 was absent in all non-neoplastic and precursor lesions. Thus, it can provide essential information not only about HPV association but also on the prognostic implications for the patients.

Herein we describe the use of molecular docking simulations, quantitative structure-activity relationships studies and ADMETox predictions to analyse the molecular recognition of a series of 7-aryl-2,4-diaminoquinazoline derivatives on the inhibition of Staphylococcus aureus dihydrofolate reductase and conducted a virtual screening to discover new potential inhibitors. A quantitative structure-activity relationship model was developed using 40 compounds and two selected descriptors. These descriptors indicated the importance of pKa and molar refractivity for the inhibitory activity against Sa DHFR. The values of R 2 train , CV LOO and R 2 test generated by the model were 0.808, 0.766, and 0.785, respectively. The integration between QSAR, molecular docking, ADMETox analysis and molecular dynamics simulations with binding free energies calculation, yielded the compounds PC-124127620, PC-124127795 and PC-124127805 as promising candidates to Sa DHFR inhibitors. These compounds presented high potency, good pharmacokinetics and toxicological profile. Thus, these molecules are good potential antimicrobial agent to treatment of infect disease caused by S. aureus .Communicated by Ramaswamy H. Sarma.

Pressure injuries (PIs) are a major public health problem and can be used as quality-of-care indicators. An incipient development in the field of medical devices takes the form of Smart Health Textiles, which can possess innovative properties such as thermoregulation, sensing, and antibacterial control. This protocol aims to describe the process for the development of a new type of smart clothing for individuals with reduced mobility and/or who are bedridden in order to prevent PIs. This paper's main purpose is to present the eight phases of the project, each consisting of tasks in specific phases: (i) product and process requirements and specifications; (ii and iii) study of the fibrous structure technology, textiles, and design; (iv and v) investigation of the sensor technology with respect to pressure, temperature, humidity, and bioactive properties; (vi and vii) production layout and adaptations in the manufacturing process; (viii) clinical trial. This project will introduce a new structural system and design for smart clothing to prevent PIs. New materials and architectures will be studied that provide better pressure relief, thermo-physiological control of the cutaneous microclimate, and personalisation of care.

Background: Biofilm deposit on the composite restoration is a common phenomenon and bacterial growth follows the deposition. The study aims to evaluate Streptococcus mutans ( S. mutans ) early biofilm formation on the surfaces of various dental composite resins by using the real-time quantitative polymerase chain reaction (qPCR) technique., Materials and Methods: Thirty-two discs, where eight discs were in each group of Filtek Supreme Ultra (FSU; 3M, St. Paul, MN), Clearfil AP-X (APX; Kuraray Noritake Dental Inc., Tokyo, Japan), Beautifil II (BE2; Shofu, Inc., Kyoto, Japan), and Estelite Sigma Quick (ESQ; Tokuyama Dental, Tokyo, Japan), were fabricated and subjected to S. mutans biofilm formation in an oral biofilm reactor for 12 hours. Contact angles (CA) were measured on the freshly fabricated specimen. The attached biofilms underwent fluorescent microscopy (FM). S. mutans from biofilms were analyzed using a qPCR technique. Surface roughness (Sa) measurements were taken before and after biofilm formation. Scanning electron microscopy (SEM), including energy dispersive X-ray spectrometer (EDS) analysis, was also performed for detecting relative elements on biofilms., Results: The study showed that FSU demonstrated the lowest CA while APX presented the highest values. FM revealed that condensed biofilm clusters were most on FSU. The qPCR results indicated the highest S. mutans DNA copies in the biofilm were on FSU while BE2 was the lowest (p < 0.05). Sa test signified that APX was significantly the lowest among all materials while FSU was the highest (p < 0.05). SEM displayed areas with apparently glucan-free S. mutans more on BE2 compared to APX and ESQ, while FSU had the least. Small white particles detected predominantly on the biofilms of BE2 appeared to be Si, Al, and F extruded from the resin., Conclusion: Differences in early biofilm formation onto various composite resins are dependent on the differences in material compositions and their surface properties. BE2 showed the lowest quantity of biofilm accumulation compared to other resin composites (APX, ESQ, and FSU). This could be attributed to BE2 proprieties as a giomer and fluoride content., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Alqarni et al.)

Aim: To evaluate bone marrow fat fraction using the Dixon technique (FFDix) of magnetic resonance imaging (MRI) as a potential biomarker of haemolysis and clinical severity in the overall assessment and follow-up of sickle cell disease (SCD) patients., Material and Methods: The present study was a cross-sectional study in which healthy individuals and SCD patients (matched for age, sex, and weight) were subjected to MRI of the lumbar spine and pelvis to quantify FFDix in the bone marrow using the Dixon technique. SCD severity was analysed by clinical and laboratory data, and an online calculator. A high degree of haemolysis was defined using the cut-off values haemoglobin (Hb) ≤10 g/dl, lactate dehydrogenase (LDH) ≥325 U/l, reticulocytes ≥3% and total bilirubin (TB) ≥1.2 mg/dl. Pearson's correlation, receiver operating characteristic (ROC) curve and binary logistic regression analysis were performed., Results: Forty-eight SCD patients (26 homozygous: HbSS and 22 compound heterozygous: HbSC) and 48 healthy individuals participated in the study. FFDix was lower in SCD patients than in the control group, showing even lower values in the HbSS subtype and patients with a higher degree of haemolysis. HbSC patients with a higher degree of haemolysis using hydroxyurea (medium dosage 9.8 mg/kg/day) had lower FFDix. ROC curves and odds ratios for detecting patients with a higher degree of haemolysis at the different FFDix measurement sites demonstrated excellent performance: iliac bones (cut-off ≤16.75%, AUC = 0.824, p<0.001), femoral heads (cut-off ≤46.7%, AUC = 0.775, p=0.001), lumbar vertebrae (cut-off ≤7.8%, AUC = 0.755, p=0.002)., Conclusion: Decreased FFDix is indicative of higher degree of haemolysis and SCD severity with great potential as a non-invasive biomarker contributing to the overall assessment and follow-up of SCD patients., (Copyright © 2022 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Scedosporium and Lomentospora are a group of filamentous fungi with some clinically relevant species causing either localized, invasive, or disseminated infections. Understanding how the host immune response is activated and how fungi interact with the host is crucial for a better management of the infection. In this context, an α-glucan has already been described in S. boydii , which plays a role in the inflammatory response. In the present study, an α-glucan has been characterized in L. prolificans and was shown to be exposed on the fungal surface. The α-glucan is recognized by peritoneal macrophages and induces oxidative burst in activated phagocytes. Its recognition by macrophages is mediated by receptors that include Dectin-1 and Mincle, but not TLR2 and TLR4. These results contribute to the understanding of how Scedosporium 's and Lomentospora 's physiopathologies are developed in patients suffering with scedosporiosis and lomentosporiosis.

There is a need for novel prognostic parameters in assessing laryngeal squamous cell carcinoma (LSCC). Tumor budding is an instrumental parameter, which has hardly been studied before in this organ. This study aimed to assess tumor budding in LSCCs with routine hematoxylin and eosin (H&E) stain as well as cytokeratin (CK) immunohistochemistry (IHC). Objectives were to compare the effectiveness of both these methods to assess tumor budding, to investigate the association of tumor budding and clinicopathologic features, and to determine the prognostic significance of tumor budding in LSCCs. Fifty laryngectomy specimens were included. Tumor budding was counted (20x) on slides stained with IHC-CK, and highest count per slide was noted. The cases were classified as positive (> 1 buds) or negative (no buds present). The budding index was categorized as low (< 5 buds) or high (> 5 buds). Tumor budding on H&E was absent, low and high grade in 28%, 30% and 42% cases respectively, when compared to CK-IHC in 17%, 24% and 59% of cases, respectively. Presence of lymphoplasmacytic infiltration significantly correlated with tumor budding and higher grade. Transglottic location of tumor and pT stage was associated with high budding. Presence of lymphoplasmacytic infiltrate significantly correlated with worse prognosis. Tumor budding, an easily assessable, inexpensive histopathologic parameter has seldom been studied in LSCCs. Presence of lymphoplasmacytic infiltrate in routine preoperative biopsy reporting could be useful in prognostication. CK-IHC is helpful to detect especially cases with low-grade tumor budding., Competing Interests: Conflict of interestThe authors have no relevant financial or non-financial interests to disclose., (© Association of Otolaryngologists of India 2021.)

Antiretroviral therapy (ART) improves the quality of life of people living with HIV-1 (PLHIV) and reduces the mortality rate, but some individuals may develop metabolic abnormalities. This study evaluated changes in the nutritional status and biochemistry of PLHIV on antiretroviral therapy in a cohort that had not previously received ART and to follow up these individuals for 24 months after starting treatment. The initial cohort consisted of 110 individuals and ended with 42 people, assessed by a physical examination. A biochemical assay was performed using the colorimetric enzyme reaction technique, the proviral load was detected by qPCR and the quantification of the CD4/CD8 T lymphocytes was conducted by flow cytometry. PLHIV had increased levels of total cholesterol, LDL, triglycerides, ALT, urea and creatinine after 24 months of ART use ( p < 0.05). In the assessment of the nutritional status, PLHIV had increased measures of Triciptal Skinfold, body mass index and arm circumference after the use of ART ( p < 0.05). The viral load levels decreased and the CD4 levels increased after 24 months of ART use ( p < 0.05). The change in the nutritional status in PLHIV on antiretroviral therapy seems to be a slow process, occurring in the long term, therefore, there is the need for a constant evaluation of these people to identify patients who need a nutritional intervention.

Sickle cell disease (SCD) is an autosomal recessive genetic condition characterized by the presence of a mutated form of haemoglobin (HbS). HbS polymerises into long needle-like fibres under low oxygen conditions, leading to the erythrocytes forming sickle shaped red blood cells. With repeated sickling, the red blood cells become irreversibly sickled and trapped within the circulation, and this leads to vaso-occlusive crisis. The patient, a 25-year-old female, previously undiagnosed with SCD, presented with high grade fever, splenomegaly and succumbed due to heat exertion precipitating sickling crisis, multiorgan failure and shock.

Strategies that rely on oral mucosal administration have increased in the last decade and oromucosal products are paving the way to overcome specific challenges, namely improving drug bioavailability when compared with the conventional oral route, due to a reduction of the hepatic first-pass metabolism and pre-systemic degradation. Overall, the advantages of these products make oromucosal route of administration attractive for the development of value-added medicines, which can address more properly the unmet medical needs of specific patients. Generally, such products have an easy and convenient administration since they do not require water for ingestion, which may be particularly relevant for geriatric and pediatric groups, or non-cooperative patients. Usually, the development of these products aims to provide a faster onset of action, critical for acute or emergency treatments. Although oriented to achieve better therapeutic outcomes, today's drug development is primarily focused on patient-centered care, meaning that patients' specific characteristics/needs are an important driving force behind product-development efforts. In accordance, pharmaceutical innovation can rely not only on new drug substances but also on re-formulation of already approved ones or alternative routes of administration, enhancing patient convenience, treatment efficacy and/or safety. Throughout this review, the oromucosal drug products, approved in the last decade, and a retrospective analysis of their critical quality attributes and specifications will be described. Furthermore, trends and opportunities of the latest technologies in this field, as well as the number of ongoing clinical studies, will be presented and discussed., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Sickle cell disease (SCD) may cause several impacts to patients and the whole society. About 4% of the population has the sickle cell trait in Brazil, and 60,000 to 100,000 have SCD. However, despite recognizing the significant burden of disease, little is known about SCD costs., Objective: To estimate SCD societal costs based on disease burden modelling, under Brazilian societal perspective., Methods: A disease burden model was built considering the societal perspective and a one-year time horizon, including direct medical and indirect costs (morbidity and mortality). The sum of life lost and disability years was considered to estimate disability-adjusted life years (DALYs). Data from a public database (DATASUS) and the prevalence obtained from literature or medical experts were used to define complications prevalence and duration. Costs were defined using data from the Brazilian public healthcare system table of procedures and medications (SIGTAP) and the human capital method., Results: Annual SCD cost was 413,639,180 USD. Indirect cost accounted for the majority of burden (70.1% of the total; 290,158,365 USD vs 123,480,816 USD). Standard of care and chronic complications were the main source of direct costs among adults, while acute conditions were the main source among children. Vaso-occlusive crisis represented the complication with the highest total cost per year in both populations, 11,400,410 USD among adults and 11,510,960 USD among children., Conclusions: SCD management may impose an important economic burden on Brazilian society that may reach more than 400 million USD per year., Competing Interests: The authors have declared that no competing interests exist.

Rationale and Objectives: To compare bone marrow fat quantification using magnetic resonance spectroscopy (MRS) and six-point DIXON (6PD) techniques in patients with sickle cell disease (SCD) and healthy subjects., Materials and Methods: Prospective study, with 43 SCD patients (24 homozygous [SS], 19 double heterozygous [SC), and 41 healthy subjects paired by age, weight and sex with SCD patients. All participants underwent magnetic resonance imaging with 6PD and single voxel MRS in the L3 vertebral body. Pearson's correlation, ROC curve, and bland-altman analysis were performed, p-values ​​≤0.05 were considered statistically significant for all tests., Results: Significant linear correlation was found between fat fraction (FF) by 6PD and Total Lipids (TL) (r = 0.932; p < 0.001) and Saturated Lipids (SL) (r = 0.934; p < 0.001), in all subjects. Strong correlations were also identified considering subjects of the SS/SC subgroups. Despite high correlations, no significant difference was observed only between FF and SL in the SS subgroup (Bland-Altman analysis), indicating excellent agreement between the fat estimations in this specific situation. Significant differences were observed in all variables (FF, TL, SL) comparing the SCD and healthy subjects. The ROC curve between SCD and healthy subjects showed the following areas under the curve: FF(0.924) > TL(0.883) > SL(0.892)., Conclusions: The comparison between fat quantification by the 6PD with MRS demonstrated an excellent correlation in SCD patients, especially in the SS subgroup, which usually has a higher degree of hemolysis. The diagnostic performance of 6PD and MRS is similar, with advantages of shorter imaging processing time and larger studied area with the 6PD., (Copyright © 2021 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)