Additive manufacturing of bioactive and biodegradable poly (lactic acid)-tricalcium phosphate scaffolds modified with zinc oxide for guided bone tissue repair.

Bioactive and biodegradable scaffolds that mimic the natural extracellular matrix of bone serve as temporary structures to guide new bone tissue growth. In this study, 3D-printed scaffolds composed of poly (lactic acid) (PLA)-tricalcium phosphate (TCP) (90-10 wt. %) were modified with 1%, 5%, and 10 wt. % of ZnO to enhance bone tissue regeneration. A commercial chain extender named Joncryl was incorporated alongside ZnO to ensure the printability of the composites. Filaments were manufactured using a twin-screw extruder and subsequently used to print 3D scaffolds via fused filament fabrication (FFF). The scaffolds exhibited a homogeneous distribution of ZnO and TCP particles, a reproducible structure with 300 µm pores, and mechanical properties suitable for bone tissue engineering, with an elastic modulus around 100 MPa. The addition of ZnO resulted in enhanced surface roughness on the scaffolds, particularly for ZnO microparticles, achieving values up to 241 nm. This rougher topography was responsible for enhancing protein adsorption on the scaffolds, with an increase of up to 85% compared to the PLA-TCP matrix. Biological analyses demonstrated that the presence of ZnO promotes mesenchymal stem cell (MSC) proliferation and differentiation into osteoblasts. Alkaline phosphatase (ALP) activity, an important indicator of early osteogenic differentiation, increased up to 29%. The PLA-TCP composite containing 5% ZnO microparticles exhibited an optimized degradation rate and enhanced bioactivity, indicating its promising potential for bone repair applications.

Seasonality of the incidence of bronchiolitis in infants - Brazil, 2016-2022: An interrupted time-series analysis.

OBJECTIVE: To evaluate the seasonality of acute bronchiolitis in Brazil during the 2020-2022 season and compare it with the previous seasons. METHODS: Data from the incidence of hospitalizations due to acute bronchiolitis in infants <1 year of age were obtained from the Department of Informatics of the Brazilian Public Health database for the period between 2016 and 2022. These data were also analyzed by macro-regions of Brazil (North, Northeast, Southeast, South, and Midwest). To describe seasonal and trend characteristics over time, we used the Seasonal Autoregressive Integrated Moving Averages Model. RESULTS: Compared to the pre-COVID-19 period, the incidence of hospitalizations related to acute bronchiolitis decreased by 97% during non-pharmacological interventions (March 2020 - August 2021) but increased by 95% after non-pharmacological interventions relaxation (September 2021 - December 2022), resulting in a 16% overall increase. During the pre-COVID-19 period, hospitalizations for acute bronchiolitis followed a seasonal pattern, which was disrupted in 2020-2021 but recovered in 2022, with a peak occurring in May, approximately 4% higher than the pre-COVID-19 peak. CONCLUSIONS: This study underscores the significant influence of COVID-19 interventions on acute bronchiolitis hospitalizations in Brazil. The restoration of a seasonal pattern in 2022 highlights the interplay between public health measures and respiratory illness dynamics in young children.

Benzbromarone as adjuvant therapy for cystic fibrosis lung disease: a pilot clinical trial.

OBJECTIVE: Cystic fibrosis (CF) affects multiple organs, the most severe consequences being observed in the lungs. Despite significant progress in developing CF transmembrane conductance regulator-specific treatments for CF lung disease, exploring alternative CF-targeted medications seems reasonable. We sought to evaluate the potential beneficial effects of oral benzbromarone as an adjuvant therapy in CF patients with reduced lung function. METHODS: This was a prospective open-label pilot study of oral benzbromarone (100 mg/day) administered once daily for 90 days. Patients were followed at a tertiary referral center in southern Brazil. Safety was assessed by the number of reported adverse events. Secondary objectives included percent predicted FEV1 (FEV1%) and pulmonary exacerbations. RESULTS: Ten patients were enrolled. Benzbromarone was found to be safe, with no serious drug-related adverse events. Eight patients completed the study; the median relative change in FEV1% tended to increase during the treatment, showing an 8% increase from baseline at the final visit. However, a nonparametric test showed that the change was not significant (p = 0.06). Of a total of ten patients, only one experienced at least one pulmonary exacerbation during the study. CONCLUSIONS: Oral benzbromarone appears to be safe, and improved FEV1% has been observed in patients with CF. Further assessment in larger trials is warranted to elucidate whether oral benzbromarone can be a potential adjuvant therapy for CF.

Accuracy of early pregnancy diagnosis and determining pregnancy loss using different biomarkers and machine learning applications in dairy cattle.

This study aimed to compare the accuracy of IFN-τ stimulated gene abundance (ISGs) in peripheral blood mononuclear cells (PBMCs), CL blood perfusion by Doppler ultrasound (Doppler-US), plasma concentration of P4 on Day 21 and pregnancy-associated glycoproteins (PAGs) test on Day 25 after timed-artificial insemination (TAI) for early pregnancy diagnosis in dairy cows and heifers. Holstein cows (n = 140) and heifers (n = 32) were subjected to a hormonal synchronization protocol and TAI on Day 0. On Day 21 post-TAI, blood samples were collected for PBMC isolation and plasma concentration of P4. The CL blood perfusion was evaluated by Doppler-US. Plasma samples collected on Day 25 were assayed for PAGs. The abundance of ISGs (ISG15 and RSAD2) in PBMCs was determined by RT-qPCR. Pregnancy was confirmed on Days 32 and 60 post-TAI by B-mode ultrasonography. Statistical analyses were performed by ANOVA using the MIXED procedure and GLIMMIX in SAS software. The pregnancy biomarkers were used to categorize the females as having undergone late luteolysis (LL); early embryonic mortality (EEM); late embryonic mortality (LEM); or late pregnancy loss (LPL). The abundance of ISGs, CL blood perfusion by Doppler-US, and concentrations of P4 on Day 21, and PAGs test on Day 25 were significant (P < 0.05) predictors of early pregnancy in dairy cows and heifers. Dairy cows had a greater (P = 0.01) occurrence of LL than heifers, but there was no difference (P > 0.1) for EEM, LEM, and LPL in heifers compared to cows. Cows with postpartum reproductive issues had a greater (P = 0.008) rate of LEM and a lesser (P = 0.01) rate of LPL compared to cows without reproductive issues. In summary, the CL blood perfusion by Doppler-US had the highest accuracy and the least number of false negatives, suggesting it is the best predictor of pregnancy on Day 21 post-TAI. The PAGs test was the most reliable indicator of pregnancy status on Day 25 post-TAI in dairy heifers and cows. The application of machine learning, specifically the MARS algorithm, shows promise in enhancing the accuracy of predicting early pregnancies in cows.

Haptic devices as an educational approach for oral and maxillofacial surgical procedures.

OBJECTIVE: Developing the skills of a proficient surgeon with a deep understanding of force requires extensive training and repetitive practice. Traditionally, dental students and surgical trainees observed and participated in procedures using models, animals, or cadavers under expert supervision before performing the procedures independently. To address these challenges, interactive simulators with visuo-haptic features have been introduced in surgical training, providing visual and tactile feedback that replicates the sense of touch through applied forces, vibrations, or motions. STUDY DESIGN: Two independent reviewers employed a specific search strategy to explore online databases such as PubMed, Scopus, and Web of Science (WoS). This strategy included keywords such as "haptic device," "education," "oral surgery," "surgery," and "maxillofacial surgery." All types of studies related to maxillofacial surgery, except for case reports, reviews, and eBooks, were considered for inclusion. RESULTS: A total of 22 articles meeting the screening criteria were identified. The use of haptic devices for training dental students in oral surgery, anesthesia, as well as oral and maxillofacial trainees and surgeons in various surgical procedures, was evaluated. CONCLUSION: Incorporating tactile devices into the training of residents and maxillofacial surgeons offers numerous advantages, including improved technical skills and enhanced patient safety.

The butterfly effect in oral and maxillofacial surgery: Understanding and applying chaos theory and complex systems principles.

The present paper provides a historical context for chaos theory, originating in the 1960s with Edward Norton Lorenz's efforts to predict weather patterns. It introduces chaos theory, fractal geometry, nonlinear dynamics, and the butterfly effect, highlighting their exploration of complex systems. The authors aim to bridge the gap between chaos theory and oral and maxillofacial surgery (OMFS) through a literature review, exploring its applications and emphasizing the prevention of minor deviations in OMFS to avoid significant consequences. A comprehensive literature review was conducted on PubMed, Web of Science, and Google Scholar databases. The selection process adhered to the PRISMA-ScR guidelines and Leiden Manifesto principles. Articles focusing on chaos theory principles in health sciences, published in the last two decades, were included. The review encompassed 37 articles after screening 386 works. It revealed applications in outcome variation, surgical planning, simulations, decision-making, and emerging technologies. Potential applications include predicting infections, malignancies, dental fractures, and improving decision-making through disease prediction systems. Emerging technologies, despite criticisms, indicate advancements in AI integration, contributing to enhanced diagnostic accuracy and personalized treatment strategies. Chaos theory, a distinct scientific framework, holds potential to revolutionize OMFS. Its integration with advanced techniques promises personalized, less traumatic surgeries and improved patient care. The interdisciplinary synergy of chaos theory and emerging technologies presents a future in which OMFS practices become more efficient, less traumatic, and achieve a level of precision never seen before.

Frontal facial analysis of female celebrity attractiveness standards through artificial intelligence.

The contemporary significance of celebrities' facial aesthetics underscores their heightened importance in shaping attractiveness standards. This retrospective study aimed to investigate the impact of patterns on aesthetic canons in the profile views of female celebrities, using artificial intelligence. The study sought to compare different races and propose standards for attractive faces. In this retrospective cohort study, a Python-based algorithm was used to analyze frontal patterns and evaluate their influence on aesthetic norms in publicly accessible images of female global celebrities. Ten ideal angular or proportional measures were gathered from the literature, and were trained to serve as a benchmark for the analysis of facial attractiveness. Demographic characteristics were described statistically. A one-way ANOVA test was employed to assess data distribution. Differences in means between groups were evaluated using nonparametric independent-sample tests, with statistical significance set at < 0.05. The study involved facial analyses for 115 female celebrities. It revealed variations in facial features among races. The mean golden ratio differed, with African and Asian individuals showing lower ratios. Symmetry varied, with Latin and Caucasian faces considered the most symmetrical. The zygomatic-to-mandibular width ratio was similar across races, with a ratio close to 80% being associated with more attractive faces. Differences in nose-to-mouth ratio, lips, alar base width, and chin angle were noted among race groups. The study concluded that, regardless of race, an attractive female face is characterized by specific ratios and angles. Facial symmetry, though desirable, is not strictly necessary. Irrespective of race background, an appealing female face is characterized by a zygomatic-to-mandibular width ratio nearing 80%, a mid-facial third that is slightly larger than the lower third, and a distinctive chin angle of approximately 138°, contributing to a trapezoidal facial shape. The findings contribute valuable insights into attractiveness standards and the impact of frontal patterns on aesthetic canons in female celebrities.

Mechanistic Framework to Predict Maternal-Placental-Fetal Pharmacokinetics of Nifedipine Employing Physiologically Based Pharmacokinetic Modeling Approach.

Nifedipine is used for treating mild to severe hypertension and preventing preterm labor in pregnant women. Nevertheless, concerns about nifedipine fetal exposure and safety are always raised. The aim of this study was to develop and validate a maternal-placental-fetal nifedipine physiologically based pharmacokinetic (PBPK) model and apply the model to predict maternal, placental, and fetal exposure to nifedipine at different pregnancy stages. A nifedipine PBPK model was verified with nonpregnant data and extended to the pregnant population after the inclusion of the fetoplacental multicompartment model that accounts for the placental tissue and different fetal organs within the Simcyp Simulator version 22. Model parametrization involved scaling nifedipine transplacental clearance based on Caco-2 permeability, and fetal hepatic clearance was obtained from in vitro to in vivo extrapolation encompassing cytochrome P450 3A7 and 3A4 activities. Predicted concentration profiles were compared with in vivo observations and the transplacental transfer results were evaluated using 2-fold criteria. The PBPK model predicted a mean cord-to-maternal plasma ratio of 0.98 (range, 0.86-1.06) at term, which agrees with experimental observations of 0.78 (range, 0.59-0.93). Predicted nifedipine exposure was 1.4-, 2.0-, and 3.0-fold lower at 15, 27, and 39 weeks of gestation when compared with nonpregnant exposure, respectively. This innovative PBPK model can be applied to support maternal and fetal safety assessment for nifedipine at various stages of pregnancy.

3D printed bioabsorbable composite scaffolds of poly (lactic acid)-tricalcium phosphate-ceria with osteogenic property for bone regeneration.

The fabrication of customized implants by additive manufacturing has allowed continued development of the personalized medicine field. Herein, a 3D-printed bioabsorbable poly (lactic acid) (PLA)- ß-tricalcium phosphate (TCP) (10 wt %) composite has been modified with CeO2 nanoparticles (CeNPs) (1, 5 and 10 wt %) for bone repair. The filaments were prepared by melt extrusion and used to print porous scaffolds. The nanocomposite scaffolds possessed precise structure with fine print resolution, a homogenous distribution of TCP and CeNP components, and mechanical properties appropriate for bone tissue engineering applications. Cell proliferation assays using osteoblast cultures confirmed the cytocompatibility of the composites. In addition, the presence of CeNPs enhanced the proliferation and differentiation of mesenchymal stem cells; thereby, increasing alkaline phosphatase (ALP) activity, calcium deposition and bone-related gene expression. Results from this study have shown that the 3D printed PLA-TCP-10%CeO2 composite scaffold could be used as an alternative polymeric implant for bone tissue engineering applications: avoiding additional/revision surgeries and accelerating the regenerative process.

Gastric plication surgery changes gastrointestinal and metabolic parameters in an obesity-induced high-fat diet model.

BACKGROUND: Obesity treatment includes less invasive procedures such as gastric plication (GP) surgery; however, its effects on gastrointestinal (GI) motility parameters are underestimated. We aimed to verify the metabolic and gastrointestinal effects of GP surgery in the rat obesity model. METHODS: A high-fat diet-induced obesity was used. Animals were allocated to four experimental groups: control sham (n = 6); control GP (n = 10); obese sham (n = 6); and obese GP (n = 10). Nutritional and murinometric parameters, gastric motility, glucose tolerance, histopathology, fat depots, leptin, and lipoproteins levels were evaluated 30 days after surgery. Data were analyzed by ANOVA followed by post Tukey or Kruskal-Wallis test followed by Dunn's multiple comparisons test. KEY RESULTS: Gastric plication decreased leptin levels, feed efficiency, and body weight gain. GP does not improve lipid profile in obese animals and however, ameliorates glucose tolerance in control and obese rats. GP did not improve the gastric emptying time or normalize the frequency of contractions disturbed by obesity. Surgery provides a remodeling process in the mucosa and muscularis mucosa layers, evidenced by leukocyte infiltration mainly in the mucosa layer. CONCLUSIONS & INFERENCES: Our study revealed the influence of the gastrointestinal tract on obesity is underestimated with pieces of evidence pointing out its important role as a target for surgical treatment.

Effect of Silicon Dioxide and Magnesium Oxide on the Printability, Degradability, Mechanical Strength and Bioactivity of 3D Printed Poly (Lactic Acid)-Tricalcium Phosphate Composite Scaffolds.

BACKGROUND: Poly (lactic acid) (PLA) is a biodegradable polyester that has been exploited for a variety of biomedical applications, including tissue engineering. The incorporation of ß-tricalcium phosphate (TCP) into PLA has imparted bioactivity to the polymeric matrix. METHODS: We have modified a 90%PLA-10%TCP composite with SiO2 and MgO (1, 5 and 10 wt%), separately, to further enhance the material bioactivity. Filaments were prepared by extrusion, and scaffolds were fabricated using 3D printing technology associated with fused filament fabrication. RESULTS: The PLA-TCP-SiO2 composites presented similar structural, thermal, and rheological properties to control PLA and PLA-TCP. In contrast, the PLA-TCP-MgO composites displayed absence of crystallinity, lower polymeric molecular weight, accelerated degradation ratio, and decreased viscosity within the 3D printing shear rate range. SiO2 and MgO particles were homogeneously dispersed within the PLA and their incorporation increased the roughness and protein adsorption of the scaffold, compared to a PLA-TCP scaffold. This favorable surface modification promoted cell proliferation, suggesting that SiO2 and MgO may have potential for enhancing the bio-integration of scaffolds in tissue engineering applications. However, high loads of MgO accelerated the polymeric degradation, leading to an acid environment that imparted the composite biocompatibility. The presence of SiO2 stimulated mesenchymal stem cells differentiation towards osteoblast; enhancing extracellular matrix mineralization, alkaline phosphatase (ALP) activity, and bone-related genes expression. CONCLUSION: The PLA-10%TCP-10%SiO2 composite presented the most promising results, especially for bone tissue regeneration, due to its intense osteogenic behavior. PLA-10%TCP-10%SiO2 could be used as an alternative implant for bone tissue engineering application.

Impact of COVID-19 social distancing recommendations on pulmonary function, nutritional status, and morbidity in patients with cystic fibrosis / Impacto das recomendações de distanciamento social por COVID-19 sobre a função pulmonar, estado nutricional e morbidade em pacientes com fibrose cística

ABSTRACT Objective: To evaluate the impact of COVID-19 social distancing recommendations on nutritional status, pulmonary function, and morbidity in patients with cystic fibrosis (CF). Methods: A retrospective cohort study including patients older than six years with a diagnosis of CF was performed. Demographic and clinical data, anthropometric measurements, pulmonary function, days of antibiotic use, and length of hospital stay were recorded. Variables were recorded at three time points relative to the baseline for implementation of social distancing measures: T-1 (14 months before implementation), T0 (baseline), and T1 (14 months after implementation). Delta (Δ) was calculated for each period: Δ1 (pre-pandemic T0-T-1) and Δ2 (pandemic T1-T0). Results: The study included 25 patients, with a mean age of 11.7±4.3 years. The mean forced expiratory volume in the first second (FEV1) was 85.6±23.6%, and body mass index (BMI) was 17.5±3.0 kg/m2. When comparing the two periods (Δ1 and Δ2), there was a significant increase in the FEV1/forced vital capacity (FVC) ratio (p=0.013) and in the forced expiratory flow between 25 and 75% of vital capacity (FEF25-75%) (p=0.037) in the pandemic period. There was also a significant reduction (p=0.005) in the use of antibiotics in the pandemic period compared with the pre-pandemic period. The Δ1 and Δ2 values did not differ significantly for BMI, FEV1, or length of hospital stay. Conclusions: COVID-19 social distancing recommendations had a positive impact (decrease) on morbidity (use of antibiotics) and small airway obstruction (FEF25-75%) in patients with CF.

RESUMO Objetivo: Avaliar o impacto das recomendações de medidas de distanciamento social por COVID-19 sobre estado nutricional, função pulmonar e morbidade em pacientes com fibrose cística (FC). Métodos: Estudo de coorte, retrospectivo, que incluiu pacientes com diagnóstico de FC e idade superior a seis anos. Foram registrados os dados demográficos, antropométricos, clínicos, de função pulmonar e o total de dias de uso de antibiótico e de hospitalizações. As variáveis foram registradas em três momentos relativos ao início das recomendações de distanciamento social: T-1 (14 meses antes), T0 (início das recomendações) e T1 (14 meses depois). Foram calculados deltas (Δ) para cada um dos períodos: Δ1 (pré-pandemia T0-T-1) e Δ2 (pandemia T1-T0). Resultados: Vinte e cinco pacientes, com média de idade de 11,7±4,3 anos, sendo 76% homozigotos para Δf508 e 28% colonizados por Pseudomonas aeruginosa, foram incluídos. A média do volume expiratório forçado no primeiro segundo (VEF1) foi de 85,6±23,6 (% do previsto) e o índice de massa corporal (IMC) foi de 17,5±3,0 kg/m2. Ao compararmos os períodos (Δ1 e Δ2), houve aumento significativo do VEF1/CVF (p=0,013) e do FEF25-75% (p=0,037) no período das recomendações de distanciamento. Também se observou redução significativa (p=0,005) do uso de antibióticos no período da pandemia em comparação ao período anterior a ela. Não houve diferenças significativas nos deltas para o IMC, VEF1 e dias de hospitalização. Conclusões: As recomendações de distanciamento social por COVID-19 tiveram impacto positivo (redução) sobre a morbidade (uso de antibióticos) e a obstrução de vias aéreas de menor calibre (FEF25-75%) em pacientes com FC.

Sleep and quality of life characteristics in a pediatric population with chronic obstructive respiratory diseases.

PURPOSE: To describe sleep and quality of life of pediatric patients with chronic obstructive respiratory diseases and to ascertain whether or not sleep quality correlates with quality of life in this population. METHODS: Participants aged 5 to 18 years with cystic fibrosis (CF), severe asthma, or postinfectious bronchiolitis obliterans (PIBO) receiving regular follow-up at a pediatric respiratory medicine center were recruited. Two questionnaires were used: the Brazilian version of the Sleep Disturbance Scale for Children (SDSC) and the Pediatric Quality of Life Inventory (Peds-QL). RESULTS: A total of 46 individuals were included: 30 with CF, 9 with severe asthma, and 7 with PIBO. Almost two-thirds of the patients and their parents or guardians scored at least 39 points on the SDSC, suggesting poor sleep quality. Significantly higher overall median scores were observed in those with severe asthma. Patients and their parents or guardians scored a median of 77 and 80 points respectively on the Peds-QL, with parents of patients with CF scoring higher than any other group. There was a moderate inverse correlation between sleep disorders and quality of life (r = - 0.532 for patients and r = - 0.606 for parents; p < 0.001). CONCLUSION: Children and adolescents with chronic obstructive respiratory diseases experience impairment in their sleep quality and quality of life. Sleep disorders and quality of life have a moderate negative correlation.

Late patient-fitted total orbital reconstruction for facial gunshot wound sequelae.

Late reconstructions of gunshot wounds (GSWs) in the orbital area are a true challenge to the oral and maxillofacial surgeon. Usually, the wall defects are large in size and commonly present loss of orbital volume, which can cause ocular dystopia. The only exceptions are when there is an explosion of the orbital walls-that is, blow-out fractures. We encountered a patient with a two-year sequelae after GSW in the face that caused the destructed orbit to have a 2.5 bigger size than the contralateral orbit, requiring meticulous planning of a patient-specific implant (PSI) to correctly reconstruct the orbit volume and bone projection. The PSI was developed using titanium and it had three pieces that could reconstruct all four walls of the orbit. After surgery, the patient regained orbital volume and malar projection, allowing him to benefit from facial symmetry. The PSI can be used to reconstruct all the orbital walls in cases of complex bone defects.