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(1) Background: Cleft lip and palate is the most common congenital malformation of the head and neck. After surgical closure, velopharyngeal dysfunction can arise, which has implications for phonation, sucking, swallowing, middle ear function, and interpersonal well-being. This case series aimed to present an adaptation of the conventional pharyngeal obturator design in order to allow its use with fixed orthodontic appliances. (2) Methods: A new custom-made pharyngeal obturator device was built in order to enable a correct function of the velopharyngeal valve. The fabrication of the plate was made by altering the conventional Hawley retainer, replacing the Adams hooks with 0.9 mm spherical hooks and removing the buccal arch. (3) Results: The new pharyngeal obturator design was used in six cleft patients with fixed orthodontic appliances. The appliance was well tolerated and there was a slight improvement in auditory-perceptive evaluations. (4) Conclusions: The new pharyngeal bulb design proved to have good retention during fixed orthodontic treatment. Moreover, despite the short-term follow-up, it also showed a reduction in the severity of the hypernasality sentences.

Late human immunodeficiency virus (HIV) diagnosis has been associated with missed opportunities for earlier diagnosis. We conducted a retrospective, longitudinal, single-centre cohort study evaluating these missed opportunities and their clinical repercussions in adults with a new HIV diagnosis or who were drug-naïve, who attended our Infectious Diseases Department between 2018 and 2023. We assessed missed opportunities in the two years prior to diagnosis or after the last negative HIV test. We compared clinical and laboratorial data from individuals with and without missed opportunities. The primary outcome considered was AIDS-defining conditions at diagnosis. Among the 436 included individuals, 27.1% experienced at least one missed opportunity. Those with missed opportunities were more likely to be female (p = 0.007), older at their first consultation (p < 0.001), born in Africa (p < 0.001) and in countries with a high HIV prevalence (p < 0.001), and have heterosexual transmission (p < 0.001). The adjusted analysis showed that missed opportunities were significantly associated with AIDS-defining conditions at diagnosis (OR 3.23, CI 95% [1.62–6.46], p < 0.001). These findings highlight the impact of missed opportunities on HIV severity, underscoring the need for more targeted interventions to reduce them.

Objectives: The objective of this umbrella review is to evaluate the efficacy and adverse effects of different teeth whitening techniques in-office (IO) and at-home (AH), regarding chromatic changes and teeth sensitivity. Materials and methods: The search was carried out from several databases. The included studies were all systematic reviews with or without meta-analysis of RCT or quasi-RCT. The participants were patients that underwent external dental bleaching in permanent vital teeth. The interventions were in-office (IO) bleaching techniques and at-home (AT) bleaching techniques with different bleaching agents and concentrations. Results: The search resulted in a total of 257 articles, and 28 SR were included in the qualitative analysis and nine in the quantitative analysis. There is no difference between in-office and at-home techniques in terms of color change (p = 0.95) and post-treatment sensitivity (p = 0.85). There is similarity risk and intensity of teeth sensitivity between AH and IO bleaching. IO bleaching with light-activated systems with low concentrations of bleaching agent showed similar results to IO bleaching techniques with high concentrated bleaching gels. With the application of the criteria of the AMSTAR 2 tool, the reviews were considered critically low to high. Conclusions: There are no significant differences in terms of color change between the different bleaching techniques compared. Teeth sensitivity is always present regardless of the technique used. The use of light activation systems did not increase the intensity and risk of post-operative sensitivity.

Miniscrews are devices that allow for absolute skeletal anchorage. However, their use has a higher failure rate (10–30%) than dental implants (10%). To overcome these flaws, chemical and/or mechanical treatment of the surface of miniscrews has been suggested. There is no consensus in the current literature about which of these methods is the gold standard; thus, our objective was to carry out a systematic review and meta-analysis of the literature on surface treatments of miniscrews. The review protocol was registered (PROSPERO CRD42023408011) and is in accordance with the PRISMA guidelines. A bibliographic search was carried out on PubMed via MEDLINE, Cochrane Library, Embase and Web of Science. The initial search of the databases yielded 1684 results, with 98 studies included in the review, with one article originating from the search in the bibliographic references of the included studies. The results of this systematic review show that the protocols of miniscrew surface treatments, such as acid-etching; sandblasting, large-grit and acid-etching; photofunctionalization with ultraviolet light; and photobiomodulation, can increase stability and the success of orthodontic treatment. The meta-analysis revealed that the treatment with the highest removal torque is SLA, followed by acid-etching. On the other hand, techniques such as oxidative anodization, anodization with pre-calcification and heat treatment, as well as deposition of chemical compounds, require further investigation to confirm their effectiveness.

Objetivos: A osteotomia de Le Fort I pode induzir alterações estruturais ou anatómicas nas vias aéreas superiores, particularmente ao nível dos seios maxilares. O objetivo deste estudo foi comparar o volume dos seios maxilares antes e após a osteotomia de Le Fort I de avanço. Metódos: Neste estudo retrospetivo foram incluídos 19 doentes submetidos a tratamento ortodôntico-cirúrgico com osteotomia de Le Fort I de avanço. As tomografias computorizadas de feixe cónico, pré-operatória (T0) e pós-operatória (T1), foram analisadas com recurso ao software ITK-SNAP a fim de avaliar o volume dos seios maxilares. O teste t de Student para amostras emparelhadas foi utilizado para avaliar o efeito da osteotomia de Le Fort I de avanço no volume dos seios maxilares. Considerou-se um nível de significância de p

Introduction: The SARS-CoV-2 pandemic has reshaped the global landscape as we know it and had a tremendous effect on healthcare systems around the world. However, its impact on oral healthcare is still to be fully assessed. The aim of this study was to understand if and how COVID-19 affected the demand and performance of oral healthcare, taking the Clinical and Academic Centre of Coimbra as an example, more specifically, the Department of Stomatology of the Coimbra Hospital and University Centre and the Dentistry Department of the Faculty of Medicine of the University of Coimbra. Material and Methods: An observational study was designed for collecting the data of a series of key oral healthcare indicators: number of appointments; referrals from primary healthcare; missed appointments; number of surgeries performed in the operating room; number of biopsies; number of patients admitted through the emergency department and epidemiologic parameters over two 18-month periods between September 2018 and August 2021: pre-COVID-19 and during the COVID-19 pandemic, with the latter divided in four stages. A statistical analysis which included descriptive and inferential procedures was then performed, with an established significance level of 5% and the application of parametric tests, t-Student test for a sample and for independent samples and One-Way ANOVA for the variance analysis. Results: There was a general decline in all indicators comparing the pre-COVID-19 with the COVID-19 period, with a reduction of 50.61% in the number of appointments, 44.06% in referrals, 24.41% in surgeries, 26.30% in biopsies and 32.33% in patients seen in the Emergency Room. The number of missed appointments also increased by 181.82%. All variations revealed statistically significant differences (p < 0.05). The individual COVID-19 stage analysis, when compared with the pre-COVID-19 reference, and variance analysis of these different stages also showed statistically significant differences (p < 0.05 and p < 0.001), except for the number of biopsies during the third and fourth stages. Conclusion: The results of this study suggest that the SARS-CoV-2 pandemic has had a considerable impact on oral healthcare demand and performance. However, results also show a remarkable adjustment and improvement in the provided care, with a positive evolution throughout the COVID-19 period.

Long-term stability is a crucial point in order to keep the patient’s aesthetic and functional balance. The aim of this study was to evaluate dental and skeletal relapse in patients who underwent orthodontic-surgical treatment. This retrospective study included 25 patients who corrected their dentofacial deformity through orthodontics and orthognathic surgery. The dental casts and lateral cephalograms were evaluated prior to orthodontic treatment (T0), final of orthodontic-surgical treatment (T1) and long-term retention phase (T2). The Wilcoxon test with p-value corrected by the Benjamini–Hochberg method was used to assess differences between the groups. The influence of retention duration was assessed using the Kruskal–Wallis method. The association of nominal variables and differences between quantitative variables were assessed using the Fisher and Mann–Whitney tests, respectively. No dental or skeletal variable presented statistically significant differences between the final orthodontic-surgical treatment and the long-term retention phase. Eight patients presented dental relapse (32–95% CI [12.4%; 51.7%]), but no skeletal relapse was observed in any of the 25 individuals. The type of malocclusion did not influence the relapse rate of orthodontic-surgical treatment (Fisher, p = 0.202). No differences were found between the different retention times, sex and age at the end of treatment. Orthodontic-surgical treatment showed long-term stability in the present study group.

Dual-energy X-ray absorptiometry is used to determine bone density in several pathologies, namely osteoporosis and fracture risk in post-menopausal women. The aim of this study was to identify, appraise and synthesize all available evidence about the correlation between Dual Energy X-ray Absorptiometry (DEXA) and Cone Beam Computed Tomography (CBCT) techniques through a systematic review. A systematic literature search was conducted in the following databases: PubMed via MEDLINE, Cochrane Library, EMBASE and Web of Science Core Collection, along with several sources of grey literature. The Cochrane Risk of Bias Tools were used to perform the qualitative assessment of the selected studies. A total of 913 articles were initially scrutinized and 11 were included for qualitative analysis, of which 3 were included in a meta-analysis. Most of the included studies revealed a low risk of bias (7 out of 11). A strong correlation (min r = 0.46 max r = 0.62) between DEXA and CBCT values were found. Thus, opportunistic CBCT scans may be used to assess the bone mineral density and fracture risk, improving the ability to track disease progression and providing better care.

Aim: Cleft lip and palate (CLP) patients have a greater predisposition to tooth malformation, which could affect pulp volume. The aim of this study is to evaluate the dental pulp volume of central incisors in 3D images between individuals with and without CLP. Materials and Methods: This retrospective case-control study is single-centered and was recruited between January 2016 and October 2022. Ninety-four patients who were followed in the Institute of Orthodontics were evaluated and divided into two groups: a control group of patients without CLP and a test group of patients with CLP. The 3D data were imported by 3D image semi-automatic segmenting software named ITK-SNAP to calculate tooth pulp volume. Results: The dental pulp volume for both groups, control and CLP, did not show statistically significant differences. In the cleft group, when comparing the pulp volume between the cleft side and the non-cleft side, the cleft side showed a smaller volume. Regarding age and sex, no statistically significant differences were observed. Conclusions: Although there are no differences in mean pulp volume between patients with and without CLP, there is a pulp volume reduction in the teeth on the cleft side when compared to the unaffected contralateral side.

Craniofacial bone defects are one of the biggest clinical challenges in regenerative medicine, with secondary autologous bone grafting being the gold-standard technique. The development of new three-dimensional matrices intends to overcome the disadvantages of the gold-standard method. The aim of this paper is to put forth an in-depth review regarding the clinical efficiency of available 3D printed biomaterials for the correction of alveolar bone defects. A survey was carried out using the following databases: PubMed via Medline, Cochrane Library, Scopus, Web of Science, EMBASE, and gray literature. The inclusion criteria applied were the following: in vitro, in vivo, ex vivo, and clinical studies; and studies that assessed bone regeneration resorting to 3D printed biomaterials. The risk of bias of the in vitro and in vivo studies was performed using the guidelines for the reporting of pre-clinical studies on dental materials by Faggion Jr and the SYRCLE risk of bias tool, respectively. In total, 92 publications were included in the final sample. The most reported three-dimensional biomaterials were the PCL matrix, β-TCP matrix, and hydroxyapatite matrix. These biomaterials can be combined with different polymers and bioactive molecules such as rBMP-2. Most of the included studies had a high risk of bias. Despite the advances in the research on new three-dimensionally printed biomaterials in bone regeneration, the existing results are not sufficient to justify the application of these biomaterials in routine clinical practice.

Orthognathic surgery is a procedure used to correct intermaxillary discrepancies, thus promoting significant improvements in chewing and breathing. During the surgical planning stage, orthodontists often use two-dimensional imaging techniques. The assessment is based on CBCT images and dental cast models to overcome these limitations; however, the evaluation of soft tissues remains complex. The aim of the present study was to develop a co-registration method of CBCT and photo images that would result in realistic facial image reconstruction. CBCT images were three-dimensionally rendered, and the soft tissues were subsequently segmented resulting in the cranial external surface. A co-registration between the obtained surface and a frontal photo of the subject was then carried out. From this mapping, a photorealistic model capable of replicating the features of the face was generated. To assess the quality of this procedure, seven orthodontists were asked to fill in a survey on the models obtained. The survey results showed that orthodontists consider the three-dimensional model obtained to be realistic and of high quality. This process can automatically obtain a three-dimensional model from CBCT images, which in turn may enhance the predictability of surgical-orthognathic planning.

Oronasal fistula can persist after conventional secondary alveolar bone graft surgery, which may lead to functional issues, such as regurgitation of fluids from the oral to the nasal cavity. This manuscript describes a clinical case of a patient with a bilateral cleft lip and palate that underwent tongue graft surgery for closure of an oronasal fistula after three failed local mucosa flap surgeries. The multidisciplinary treatment was comprised of orthodontic treatment, mucosa and alveolar grafts for palate closure and aesthetic rehabilitation of the anterior maxillary teeth. Smile aesthetics were noticeably improved, enhancing the patient’s self-perception and confidence.

Velopharyngeal insufficiency may occur as a result of an anatomical or structural defect and may be present in patients with cleft lip and palate. The treatment options presented in the literature are varied, covering invasive and non-invasive methods. However, although these approaches have been employed and their outcomes reviewed, no conclusions have been made about which approach is the gold-standard. This umbrella review aimed to synthesize the current literature regarding velopharyngeal insufficiency treatments in cleft lip and palate patients, evaluating their effectiveness based on systematic reviews. A standardized search was carried out in several electronic databases, namely PubMed via Medline, Web of Science, Cochrane Library, and Embase. The quality of the included studies was evaluated using AMSTAR2 and degree of overlap was analyzed using Corrected Covered Area. Thirteen articles were included in the qualitative review, with only 1 in the non-invasive method category, and 12 in the invasive method category. All reviewed articles were judged to be of low quality. In symptomatic patients, treatment did not solely comprise speech therapy, as surgical intervention was often necessary. Although there was no surgical technique considered to be the gold standard for the correction of velopharyngeal insufficiency, the Furlow Z-plasty technique and minimal incision palatopharyngoplasty were the best among reported techniques.

Background: The presence of posterior crossbite can trigger aesthetic and functional changes as mandibular asymmetry in individuals, contributing to asymmetrical muscle function. Mandibular asymmetry and respective condyle adaptation may be an etiological factor in temporomandibular disorder. This study aims to evaluate the effects of maxillary expansion on the position and angulation of the condyles as well as the intercondylar distance in children with cleft lip and palate. Methods: Twenty-five individuals with cleft lip and palate who underwent maxillary expansion were selected. Condylar changes were evaluated by cone beam computed tomography using the Pullinger and Hollender formula. To determine the statistically significant differences between the variables, the Student t-test and the Benjamini–Hochberg correction method for multiple comparisons were used. Results: No statistically significant differences between angulation and condylar position before and after maxillary expansion were found. The intercondylar distance tended to increase in growing individuals with cleft lip and palate after maxillary expansion. Conclusions: Intercondylar distance shows a tendency to increase after expansion regardless of the cleft phenotype. No differences were found in angulation and condylar position with the changes in occlusion resulting from maxillary expansion.

Background: Mandibular Advancement Devices (MADs), inserted in non-surgical treatments for obstructive sleep apnea and hypopnea syndrome (OSAHS), are used intra-orally during the sleep period, with the aim of promoting mandibular protrusion. The aim of the study is to analyze the changes in the upper airway after the use of an MAD in the treatment of OSAHS. Methods: 60 patients diagnosed with OSAHS, as established by the Sleep Medicine Service, underwent treatment with the Silensor SL device at the Stomatology Service of the University Hospital Center of Coimbra, from January 2018 to January 2019. All patients completed two polysomnographies and two lateral teleradiographies: one before starting treatment (T0) and one after 1 year of treatment (T1). In the lateral teleradiography performed after one year of treatment, the patient had the MAD placed intra-orally. The linear measurements of the airspace proposed by the Arnett/Gunson FAB Surgery cephalometric analysis were measured at four craniometric points: A, MCI, B, Pog. Results: The results demonstrate an anteroposterior airway enlargement in two of the four points studied with the MAD placed intra-orally (B and Pog point). The greatest average increase is observed at point Pog (3 mm), followed by B (1 mm), and finally, point A (0.6 mm). Conclusions: This study proved that there is an improvement in anteroposterior measurements at various points in the upper airways after treatment with MAD.

Trichinellosis is an emerging or re-emerging foodborne parasitic zoonotic disease caused by nematodes of the genus Trichinella. It represents a global food safety problem and a public health hazard. This case report aims to describe the first case of human trichinellosis in Portugal since the creation of the European Union surveillance system. Infection by Trichinella spp. is a rare cause of hypereosinophilia and hospital admission, but it can cause high morbidity. Clinical detailed history is crucial to obtain a correct diagnosis.

Mandible can be an elective bone for human identification. This study aimed to test the reproducibility of mandibular landmarks in three-dimensional reconstructions. Cone-beam computed tomography of 17 patients from 7 to 20 years were collected at University of Coimbra database and reconstructed in Mimics Innovation Suite 17.0. Twenty-five landmarks were demarcated for thirty measurements. Reproducibility was evaluated with Intraclass Correlation Coefficient (ICC) for intra-examiner agreement and Technical Error of Measurement (TEM) for inter-examiner error, with P < 0.05. Excellent intra-examiner agreements and acceptable inter-examiner errors were found for variables. The reproducibility was confirmed, validating its applicability in forensic purposes.

Three-dimensional technologies are one of the most recent and relevant advancements in the field of Dentistry. These systems, including intraoral scans, 3D imaging exams (CAT scan, CBCT and MRI), CAD/CAM 3D printing devices and 3D computer software, have enabled clinicians to greatly improve patient care along with reducing treatment planning time. The present descriptive study aims to explore possible applications of 3D technologies during the diagnosis, treatment plan, case monitoring and result assessment in orthodontics. The overall upgrade provided by these technologies can improve the clinicians’ workflow and effectiveness by simplifying conventional techniques considered to be especially arduous.

Background: There has been an increase in demand for orthodontic treatment within the adult population, who likely receive restorative treatments using ceramic structures. The current state of the art regarding the most effective method to achieve an appropriate bond strength of brackets on ceramic surfaces isn’t consensual. This systematic review aims to compare the available surface treatments to ceramics and determine the one that allows to obtain the best bond strength. Methods: This systematic review followed the PRISMA guidelines and the PICO methodology was used, with the question “What is the most effective technique for bonding brackets on ceramic crowns or veneers?”. The research was carried out in PubMed, Web of Science, Embase and Cochrane Library databases. In vitro and ex vivo studies were included. The methodological quality was evaluated using the guidelines for reporting of preclinical studies on dental materials by Faggion Jr. Results: A total of 655 articles searched in various databases were initially scrutinized. Sevety one articles were chosen for quality analysis. The risk of bias was considered medium to high in most studies. The use of hydrofluoric acid (HF), silane and laser afforded the overall best results. HF and HF plus laser achieved significantly highest bond strength scores in felsdphatic porcelain, while laser was the best treatment in lithium disilicate ceramics. Conclusions: The most effective technique for bonding brackets on ceramic is dependent on the type of ceramic.

Three-dimensional (3D) resin medical-dental devices have been increasingly used in recent years after the emergence of digital technologies. In Orthodontics, therapies with aligners have gained popularity, mainly due to the aggressive promotion policies developed by the industry. However, their systemic effects are largely unknown, with few studies evaluating the systemic toxicity of these materials. The release of bisphenol A and other residual monomers have cytotoxic, genotoxic, and estrogenic effects. This systematic review aims to analyze the release of toxic substances from 3D resins used in Orthodontics and their toxic systemic effects systematically. The PICO question asked was, “Does the use of 3D resins in orthodontic devices induce cytotoxic effects or changes in estrogen levels?”. The search was carried out in several databases and according to PRISMA guidelines. In vitro, in vivo, and clinical studies were included. The in vitro studies’ risk of bias was assessed using the guidelines for the reporting of pre-clinical studies on dental materials by Faggion Jr. For the in vivo studies, the SYRCLE risk of bias tool was used, and for the clinical studies, the Cochrane tool. A total of 400 articles retrieved from the databases were initially scrutinized. Fourteen articles were included for qualitative analysis. The risk of bias was considered medium to high. Cytotoxic effects or estrogen levels cannot be confirmed based on the limited preliminary evidence given by in vitro studies. Evidence of the release of bisphenol A and other monomers from 3D resin devices, either in vitro or clinical studies, remains ambiguous. The few robust results in the current literature demonstrate the absolute need for further studies, especially given the possible implications for the young patient’s fertility, which constitutes one of the largest groups of patients using these orthodontic devices.

(1) Background: Mandibular deficiency is one of the most common growth disorders of the facial skeleton. Recently, distraction osteogenesis has been suggested as the treatment of choice for overcoming the limitations of conventional orthognathic surgery; (2) Methods: A new custom-manufactured dental-anchored distractor was built and anchored in the first molar and lower canine. It consists of a stainless-steel disjunction screw, adapted and welded to the orthodontic bands through two 1.2 mm diameter connector bars with a universal silver-based and cadmium-free solder; (3) Results: The distractor described can be a useful tool to correct mandibular retrognathia and is better tolerated by patients, especially in severe cases; (4) Conclusions: The dental-anchored distractor increases the anterior mandibular bone segment without affecting the gonial angle or transverse angulation of the segments and avoids posterior mandibular rotation, overcoming the limitations of conventional surgical treatment.

(1) Background: Alveolar bone defects or decreased alveolar bone height and width may have different causes, such as cleft palate. Regenerative procedures in oro-dental defects are challenging due to anatomical factors and the distinct cell populations involved. The iliac crest bone graft remains the gold-standard for cleft palate closure. However, tissue regeneration approaches have been employed and their outcome reviewed, but no conclusions have been made about which one is the gold-standard. (2) Methods: this umbrella review aims to critically appraise the effectiveness of the current approaches in bone defects regeneration in non-syndromic patients with cleft palate. A search was performed in PubMed, Cochrane Library, Scopus, Web of Science and EMBASE databases. (3) Results: Systematic reviews of randomized and non-randomized controlled trials with or without meta-analysis were included. Nine articles were included in the qualitative analysis and five in the quantitative one. The included studies quality was evaluated with AMSTAR2. (4) Conclusions: The use of new regenerative strategies, such as bone morphogenic protein 2, appears to provide similar results regarding bone volume, filling, and height to the standard technique with the iliac crest bone graft.

The skeletal Class III pattern is characterized by a sagittal intermaxillary mesial discrepancy. This discrepancy may have an unfavorable impact on function and aesthetics, which can be aggravated by the presence of facial asymmetries. This case report describes the diagnosis and treatment planning of a 19-year-old male patient with a skeletal Class III, maxillary hypoplasia, anterior crossbite, and mandibular asymmetry. When the patient reached skeletal maturity at the end of puberty, the definitive diagnosis was skeletal Class III with hyperdivergent profile and mandibular asymmetry, and a surgical-orthodontic treatment was proposed. At the end of the treatment, bimaxillary surgical correction allowed a skeletal Class I with mandibular symmetry, improving the function of the stomatognathic system and facial aesthetics.

Acute bacterial meningitis has a high impact on adult mortality worldwide. Community-acquired Escherichia coli meningitis (CA-ECM) is a rare and poorly described condition and the available knowledge is based on low evidence research, mainly from case reports. We describe a case of CA-ECM in Portugal in an adult patient with discoid lupus erythematosus under immunomodulatory therapy. A 73-year-old woman was admitted to the emergency department with fever and altered mental status over 48 h. Cerebrospinal fluid analysis showed 185 leukocytes/μL, including 85% neutrophils, hypoglycorrhachia (less than 5 mg/dL) and elevated protein of 423 mg/dL with positive culture for Escherichia coli. She was treated with ceftriaxone. Imaging studies also demonstrated spondylodiscitis and arthritis. She responded well to antimicrobial therapy and completed the treatment as an outpatient. Keywords: Escherichia coli, Meningitis, Spondylodiscitis, Discoid lupus erythematosus

Pre-eruptive enamel lesions occur during tooth formation and include fluorosis, traumatic hypomineralization, and molar incisor hypomineralization. Minimally invasive treatment approaches, such as microabrasion, should be considered for these cases. This article presents a case series of three patients with pre-eruptive enamel defects in esthetically compromised tooth regions which were treated with the microabrasion technique: two fluorosis cases, moderate and advanced, and one hypomineralization case of traumatic etiology. In Cases 1 and 3, there was a significant improvement in esthetics with a total resolution of the enamel defects. However, a slight yellowish coloration may be detected at close observation. In Case 2 (advanced fluorosis), although there was no full resolution of the white spots, there was a clear improvement in esthetics. Microabrasion is a safe and effective, minimally invasive treatment for pre-eruptive enamel lesions. It does not require local anesthesia, it is less destructive than restorative interventions, and allows good esthetic outcomes with no significant postoperative sensitivity. Its efficacy is directly related to the lesions’ severity and depth. Although there are some limitations, further improvement can be achieved with dental bleaching. More invasive treatments might be considered if results are still unsatisfactory.

Objective: In this case report, the feasibility and precision of tridimensional (3D) virtual planning in one patient with craniofacial microsomia is tested using Nemoceph 3D-OS software (Software Nemotec SL, Madrid, Spain) to predict postoperative outcomes on hard tissue and produce CAD/CAM (Computer Aided Design/Computer Aided Manufacturing) surgical splints. Methods: The clinical protocol consists of 3D data acquisition of the craniofacial complex by cone-beam computed tomography (CBCT) and surface scanning of the plaster dental casts. The ''virtual patient'' created underwent virtual surgery and a simulation of postoperative results on hard tissues. Surgical splints were manufactured using CAD/CAM technology in order to transfer the virtual surgical plan to the operating room. Intraoperatively, both CAD/CAM and conventional surgical splints are comparable. A second set of 3D images was obtained after surgery to acquire linear measurements and compare them with measurements obtained when predicting postoperative results virtually. Results: It was found a high similarity between both types of surgical splints with equal fitting on the dental arches. The linear measurements presented some discrepancies between the actual surgical outcomes and the predicted results from the 3D virtual simulation, but caution must be taken in the analysis of these results due to several variables. Conclusions: The reported case confirms the clinical feasibility of the described computer-assisted orthognathic surgical protocol. Further progress in the development of technologies for 3D image acquisition and improvements on software programs to simulate postoperative changes on soft tissue are required.

O artigo reflete a partir do “Princípio Responsabilidade” de Hans Jonas visando extrair do mesmo uma fundamentação válida para uma educação ambiental que esteja para além dos espaços formais educacionais. Dado o poder ora adquirido pelo homem sob a forma de tecnociência, o qual se encontra hoje em franca expansão e que não possui controle algum sobre si senão a sua manutenção, o indivíduo viu-se conduzido a um vácuo ético inaudito. Compete-nos, portanto, repensar os fundamentos éticos hodiernos tendo como aporte a consideração máxima de valorização da vida em sua essência, vida esta que extravasa a dimensão do humano e que se configura como condição para a existência desse último. É, pois, uma tal vida o espaço de manifestação do ser que, para continuar a existir exige-nos um dever imperioso, o que faz com que esta vida (nas suas mais diversas manifestações) seja tida enquanto um bem em si. Palavras-chave: Educação ambiental. Princípio responsabilidade. Poder tecnológico. Abstract This article reflects upon the „Responsibility Principle‟, by Hans Jonas, aiming at eliciting grounding validity for an environmental education that lies beyond the formal educational field. Given the power once acquired by man, shaped as techno-science, which is under intensive growth and holds no control upon itself, except for its maintenance, individuals have been led to an unheard ethical vacuum. It is our responsibility to rethink today‟s ethical fundamentals keeping into account their major contribution to the appreciation of life in its core, wherein life goes beyond human dimension and sets itself up as a condition to the existence of the human. Therefore, there is so much life in the expression of the being that, in order to survive, it demands from us an imperative obligation, and that makes life (in its most diverse expressions) very valuable in itself. Keywords: Environmental education. Responsibility principle. Technological power.

O artigo reflete a partir do “Princípio Responsabilidade” de Hans Jonas visando extrair do mesmo uma fundamentação válida para uma educação ambiental que esteja para além dos espaços formais educacionais. Dado o poder ora adquirido pelo homem sob a forma de tecnociência, o qual se encontra hoje em franca expansão e que não possui controle algum sobre si senão a sua manutenção, o indivíduo viu-se conduzido a um vácuo ético inaudito. Compete-nos, portanto, repensar os fundamentos éticos hodiernos tendo como aporte a consideração máxima de valorização da vida em sua essência, vida esta que extravasa a dimensão do humano e que se configura como condição para a existência desse último. É, pois, uma tal vida o espaço de manifestação do ser que, para continuar a existir exige-nos um dever imperioso, o que faz com que esta vida (nas suas mais diversas manifestações) seja tida enquanto um bem em si.

The experimental approach developed in this research demonstrated how the cloud, the Internet of Things (IoT), edge computing, and Artificial Intelligence (AI), considered key technologies in Industry 4.0, provide the expected horizon for adaptive vision in Continued Process Verification (CPV), the final stage of Process Validation (PV). Pichia pastoris producing Candida rugosa lipase 1 under the regulation of the constitutive GAP promoter was selected as an experimental bioprocess. The bioprocess worked under hypoxic conditions in carbon-limited fed-batch cultures through a physiological control based on the respiratory quotient (RQ). In this novel bioprocess, a digital twin (DT) was built and successfully tested. The implementation of online sensors worked as a bridge between the microorganism and AI models, to provide predictions from the edge and the cloud. AI models emulated the metabolism of Pichia based on critical process parameters and actionable factors to achieve the expected quality attributes. This innovative AI-aided Adaptive-Proportional Control strategy (AI-APC) improved the reproducibility comparing to a Manual-Heuristic Control strategy (MHC), showing better performance than the Boolean-Logic-Controller (BLC) tested. The accuracy, indicated by the Mean Relative Error (MRE), was for the AI-APC lower than 4%, better than the obtained for MHC (10%) and BLC (5%). Moreover, in terms of precision, the same trend was observed when comparing the Root Mean Square Deviation (RMSD) values, becoming lower as the complexity of the controller increases. The successful automatic real time control of the bioprocess orchestrated by AI models proved the 4.0 capabilities brought by the adaptive concept and its validity in biopharmaceutical upstream operations.

Abstract Background Most recombinant Komagataella phaffii (Pichia pastoris) strains for protein production are generated by genomic integration of expression cassettes. The clonal variability in gene copy numbers, integration loci and consequently product titers limit the aptitude for high throughput applications in drug discovery, enzyme engineering or most comparative analyses of genetic elements such as promoters or secretion signals. Circular episomal plasmids with an autonomously replicating sequence (ARS), an alternative which would alleviate some of these limitations, are inherently unstable in K. phaffii. Permanent selection pressure, mostly enabled by antibiotic resistance or auxotrophy markers, is crucial for plasmid maintenance and hardly scalable for production. The establishment and use of extrachromosomal ARS plasmids with key genes of the glycerol metabolism (glycerol kinase 1, GUT1, and triosephosphate isomerase 1, TPI1) as selection markers was investigated to obtain a system with high transformation rates that can be directly used for scalable production processes in lab scale bioreactors. Results In micro-scale deep-well plate experiments, ARS plasmids employing the Ashbya gossypii TEF1 (transcription elongation factor 1) promoter to regulate transcription of the marker gene were found to deliver high transformation efficiencies and the best performances with the reporter protein (CalB, lipase B of Candida antarctica) for both, the GUT1- and TPI1-based, marker systems. The GUT1 marker-bearing strain surpassed the reference strain with integrated expression cassette by 46% upon re-evaluation in shake flask cultures regarding CalB production, while the TPI1 system was slightly less productive compared to the control. In 5 L bioreactor methanol-free fed-batch cultivations, the episomal production system employing the GUT1 marker led to 100% increased CalB activity in the culture supernatant compared to integration construct. Conclusions For the first time, a scalable and methanol-independent expression system for recombinant protein production for K. phaffii using episomal expression vectors was demonstrated. Expression of the GUT1 selection marker gene of the new ARS plasmids was refined by employing the TEF1 promoter of A. gossypii. Additionally, the antibiotic-free marker toolbox for K. phaffii was expanded by the TPI1 marker system, which proved to be similarly suited for the use in episomal plasmids as well as integrative expression constructs for the purpose of recombinant protein production.

Influenza pandemics are unpredictable recurrent events with global health, economic, and social consequences. The objective of this review is to provide an update on the latest developments in early diagnosis and specific treatment of the disease and its complications, particularly with regard to respiratory organ failure. Despite advances in treatment, the rate of mortality in the intensive care unit remains approximately 30%. Therefore, early identification of potentially severe viral pneumonia is extremely important to optimize treatment in these patients. The pathogenesis of influenza virus infection depends on viral virulence and host response. Thus, in some patients, it is associated with an excessive systemic response mediated by an authentic cytokine storm. This process leads to severe primary pneumonia and acute respiratory distress syndrome. Initial prognostication in the emergency department based on comorbidities, vital signs, and biomarkers (e.g., procalcitonin, ferritin, human leukocyte antigen-DR, mid-regional proadrenomedullin, and lactate) is important. Identification of these biomarkers on admission may facilitate clinical decision-making to determine early admission to the hospital or the intensive care unit. These decisions are reached considering pathophysiological circumstances that are associated with a poor prognosis (e.g., bacterial co-infection, hyperinflammation, immune paralysis, severe endothelial damage, organ dysfunction, and septic shock). Moreover, early implementation is important to increase treatment efficacy. Based on a limited level of evidence, all current guidelines recommend using oseltamivir in this setting. The possibility of drug resistance should also be considered. Alternative options include other antiviral drugs and combination therapies with monoclonal antibodies. Importantly, it is not recommended to use corticosteroids in the initial treatment of these patients. Furthermore, the implementation of supportive measures for respiratory failure is essential. Current recommendations are limited, heterogeneous, and not regularly updated. Early intubation and mechanical ventilation is the basic treatment for patients with severe respiratory failure. Prone ventilation should be promptly performed in patients with acute respiratory distress syndrome, while early tracheostomy should be considered in case of planned prolonged mechanical ventilation. Clinical trials on antiviral treatment and respiratory support measures specifically for these patients, as well as specific recommendations for different at-risk populations, are necessary to improve outcomes.