Influence of root shape on canal complexity at the mandibular molar apical surgical resection level: A micro-CT study.

OBJECTIVES: This study aimed to investigate the relationship between the aspect ratios of mandibular molar roots at the apical 3-mm level and their root canal complexity. DESIGN: This study used micro-CT imaging to analyze 163 two-rooted mandibular molars. The aspect ratios of the roots at the apical 3-mm level were categorized as "< 2.75" or "≥ 2.75" (mesial) and "< 1.75" or "≥ 1.75" (distal). A two-dimensional (2D) analysis focused on four apical axial cross-section levels to determine the presence of main and accessory canals and isthmus. Additionally, a three-dimensional (3D) assessment of the apical 4-mm of both roots examined main and accessory canals, apical foramina, apical deltas, and middle mesial canals. RESULTS: Mesial roots with aspect ratios ≥ 2.75 showed a higher number of main canals at all levels compared to those with aspect ratios < 2.75 at the 3-mm level. Additionally, the ≥ 2.75 group exhibited more accessory canals and a higher average number of accessory canals. The 3D assessment confirmed significantly more accessory canals and apical foramina in the ≥ 2.75 group. The prevalence of roots with apical deltas was nearly double in the ≥ 2.75 group, and middle mesial canals were exclusively found in this group. In the distal root, the ≥ 1.75 group showed a significantly higher number of main canals at all axial levels. No significant differences were observed between groups in terms of accessory canals, apical foramina, or deltas. CONCLUSIONS: A higher root aspect ratio is related to higher anatomical complexity.

Barriers to clinical remission in severe asthma.

Severe asthma is associated with an increased risk for exacerbations, reduced lung function, fixed airflow obstruction, and substantial morbidity and mortality. The concept of remission in severe asthma as a new treatment goal has recently gained attention due to the growing use of monoclonal antibody therapies, which target specific pathologic pathways of inflammation. This review evaluates the current definitions of asthma remission and unveils some of the barriers for achieving this state in the severe asthma population. Although there is no unified definition, the concept of clinical remission in asthma should be based on a sustained period of symptom control, elimination of oral corticosteroid exposure and exacerbations, and stabilization of pulmonary function. The conjugation of these criteria seems a realistic treatment target in a minority of asthmatic patients. Some unmet needs in severe asthma may affect the achievement of clinical remission. Late intervention with targeted therapies in the severe asthma population may increase the risk of corticosteroid exposure and the development of irreversible structural airway changes. Moreover, airway infection is an important component in persistent exacerbations in patients on biologic therapies. Phenotyping exacerbations may be useful to guide therapy decisions and to avoid the liberal use of oral corticosteroids. Another challenge associated with the aim of clinical remission in severe asthma is the multifaceted interaction between the disease and its associated comorbidities. Behavioural factors should be evaluated in case of persistent symptoms despite optimised treatment, and assessing biomarkers and targeting treatable traits may allow for a more objective way of reaching remission. The concept of clinical remission will benefit from an international consensus to establish unifying criteria for its assessment, and it should be addressed in the future management guidelines.

Spontaneous Primary Pneumothorax as A Complication of Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF1) is a genetic disorder that affects the skin and the neurological, ocular and skeletal systems. Many are unaware of the extent of pulmonary involvement, including lung cysts and emphysematous bullae, which enhances the risk of secondary spontaneous pneumothorax (SSP). We report the case of an 18-year-old male with NF1 who presented with acute dyspnoea and chest pain due to a right-sided pneumothorax caused by the rupture of lung apical bullae. The patient received supplemental oxygen and a chest tube of 18F was inserted, with a complete resolution of the pneumothorax. He was discharged on the third day of hospital stay. This case highlights the importance of considering SSP as a possible clinical manifestation and complication of NF1. Early recognition and appropriate management of this condition can prevent serious complications and improve patient outcomes. LEARNING POINTS: NF1 is a genetic disease that results in cutaneous conditions, including neurofibroma, axillary, inguinal lentigines and café au lait spots. In some cases (5-20%) it can also affect the lungs, causing neurofibroma, infiltrative and cystic lesions, emphysema or bullae, leading to chronic respiratory failure.SSP is a clinical presentation of NF1 caused by the rupture of lung cysts or bullae, with an unclear relationship to smoking.Early diagnosis of pulmonary manifestations in patients with NF1 is crucial as surgical removal of lung cysts and bullae seems to prevent recurrence of SSP.

Factors associated with non-invasive positive pressure ventilation failure in a COVID-19 intermediate care unit.

BACKGROUND: The use of non-invasive positive pressure ventilation (NIPPV) in COVID-19 patients with hypoxaemia is still under debate. The aim was to evaluate the efficacy of NIPPV (CPAP, HELMET-CPAP or NIV) in COVID-19 patients treated in the dedicated COVID-19 Intermediate Care Unit of Coimbra Hospital and University Centre, Portugal, and to assess factors associated with NIPPV failure. METHODS: Patients admitted from December 1st 2020 to February 28th 2021, treated with NIPPV due to COVID-19 were included. Failure was defined as orotracheal intubation (OTI) or death during hospital stay. Factors associated with NIPPV failure were included in a univariate binary logistic regression analysis; those with a significance level of p < 0.001 entered a multivariate logistic regression model. RESULTS: A total of 163 patients were included, 64.4% were males (n = 105). The median age was 66 years (IQR 56-75). NIPPV failure was observed in 66 (40.5%) patients, 26 (39.4%) were intubated and 40 (60.6%) died during their hospital stay. The highest CRP (OR 1.164; 95%CI 1.036-1.308) and morphine use (OR 24.771; 95%CI 1.809-339.241) were identified as predictors of failure after applying multivariate logistic regression. Adherence to prone positioning (OR 0.109; 95%CI 0.017-0.700) and a higher value of the lowest platelet count during hospital stay (OR 0.977; 95%CI 0.960-0.994) were associated with a favorable outcome. CONCLUSIONS: NIPPV was successful in over half of patients. Highest CRP during hospital stay and morphine use were predictors of failure. Adherence to prone positioning and a higher value of the lowest platelet count during hospital stay were associated with a favourable outcome.

Hospital admissions for urticaria in a pediatric emergency department of a tertiary care hospital.

BACKGROUND: Urticaria is a common disorder, estimated to affect 2.1 to 6.7% of children and adolescents, and is a frequent cause of emergency department (ED) admissions. METHODS: The aim of this study was to retrospectively characterize the clinical features of children and adolescents with a diagnosis of urticaria, evaluated in a tertiary care pediatric ED between 2015 and 2019. Statistical analysis was performed using IBM SPSS Statistics®, version 27.0. RESULTS: A total of 2254 episodes of urticaria were counted with 98.1% corresponding to acute urticaria (AU). A suspected trigger factor was identified in 51.6% of the episodes, namely infections (27.8%), drugs (9.9%) and food (7.6%). From these episodes, excluding infections, only 59.2% were referred to an Allergy Consultation for further study, with only 18.8% (drug) and 28.3% (food) confirmed as the AU trigger. Of the 43 episodes of chronic urticaria (CU), 79% were referred to consultation, with 23 being diagnosed with chronic spontaneous urticaria, 8 with inducible urticaria and 3 with both entities. Older age (p < 0.001), personal history of atopy (p = 0.019) and angioedema (p = 0.003) were factors associated with CU, while the presence of other accompanying symptoms (p = 0.007) was associated with AU. Older age (OR = 1.2; p < 0.001) and the presence of angioedema (OR = 2.7; p = 0.007) were identified as independent factors for CU. CONCLUSION: The majority of episodes corresponded to AU. Infections were the main suspected trigger, followed by drugs and food, with an overall confirmation rate ranging from 18 to 30%, highlighting the importance of an allergologic follow-up evaluation.

Hospital admissions for urticaria in a pediatric emergency department of a tertiary care hospital

Background: Urticaria is a common disorder, estimated to affect 2.1 to 6.7% of children and adolescents, and is a frequent cause of emergency department (ED) admissions. Methods: The aim of this study was to retrospectively characterize the clinical features of children and adolescents with a diagnosis of urticaria, evaluated in a tertiary care pediatric ED between 2015 and 2019. Statistical analysis was performed using IBM SPSS Statistics®, version 27.0. Results: A total of 2254 episodes of urticaria were counted with 98.1% corresponding to acute urticaria (AU). A suspected trigger factor was identified in 51.6% of the episodes, namely infections (27.8%), drugs (9.9%) and food (7.6%). From these episodes, excluding infections, only 59.2% were referred to an Allergy Consultation for further study, with only 18.8% (drug) and 28.3% (food) confirmed as the AU trigger. Of the 43 episodes of chronic urticaria (CU), 79% were referred to consultation, with 23 being diagnosed with chronic spontaneous urticaria, 8 with inducible urticaria and 3 with both entities. Older age (p < 0.001), personal history of atopy (p = 0.019) and angioedema (p = 0.003) were factors associated with CU, while the presence of other accompanying symptoms (p = 0.007) was associated with AU. Older age (OR = 1.2; p < 0.001) and the presence of angioedema (OR = 2.7; p = 0.007) were identified as independent factors for CU. Conclusion: The majority of episodes corresponded to AU. Infections were the main suspected trigger, followed by drugs and food, with an overall confirmation rate ranging from 18 to 30%, highlighting the importance of an allergologic follow-up evaluation (AU)

Influence of Dissolved Oxygen Level on Chitin-Glucan Complex and Mannans Production by the Yeast Pichia pastoris.

The yeast Pichia pastoris was cultivated under different dissolved oxygen (DO) levels (5, 15, 30 and 50% of the air saturation) to evaluate its impact on the production of the cell-wall polysaccharide chitin-glucan complex (CGC) and mannans. Decreasing the DO level from 50 to 15% had no significant impact on cell growth but substrate conversion into biomass was improved. Under such conditions, a mannans content in the biomass of 22 wt% was reached, while the CGC content in the biomass was improved from 15 to 18 wt%, confirming that the DO level also impacted on P. pastoris cell-wall composition. Overall mannans and CGC volumetric productivity values of 10.69 and 8.67 g/(L. day) were reached, respectively. On the other hand, the polymers' composition was not significantly affected by decreasing the DO level. These results demonstrated that considerable energy savings can be made in the polysaccharide production process by reducing the DO level during cultivation of P. pastoris by improving the overall polymers' productivity without altering their composition. This has impact on the polysaccharide production costs, which is of considerable relevance for process scale-up and products' commercialization.

Optimization of medium composition for production of chitin-glucan complex and mannose-containing polysaccharides by the yeast Komagataella pastoris.

Komagataella pastoris was recently proposed as a source of valuable polysaccharides, namely, the co-polymer chitin-glucan complex (CGC) and mannose-containing polymers (mannans), that are extracted from its cell-wall. In this study, a novel cultivation medium, Medium K, was developed envisaging the simultaneous production of both types of cell-wall polysaccharides. The use of Medium K for the cultivation of K. pastoris resulted in high contents of CGC (19 wt%) and mannans (21 wt%) in the biomass, corresponding to significantly higher products' volumetric productivities (17.5 and 19.2 g/L day, respectively) compared to previous studies. The produced CGC had a chitin:ß-glucan molar ratio of 12:88, similarly to previously reported values for K. pastoris CGC (11:89-19:81), while the mannans were mainly composed of mannose units, with a protein content of 10 wt%. These results demonstrated that the developed optimized medium was suitable for cultivation of K. pastoris and the production of both CGC and mannans. It comprised fewer components with considerably reduced salts content, thus representing a significant simplification of the bioprocess with no precipitation problems, without impacting on the polymers' composition.

Implementation of a repeated fed-batch process for the production of chitin-glucan complex by Komagataella pastoris.

The yeast Komagataella pastoris was cultivated under different fed-batch strategies for the production of chitin-glucan complex (CGC), a co-polymer of chitin and ß-glucan. The tested fed-batch strategies included DO-stat mode, predefined feeding profile and repeated fed-batch operation. Although high cell dry mass and high CGC production were obtained under the tested DO-stat strategy in a 94h cultivation (159 and 29g/L, respectively), the overall biomass and CGC productivities were low (41 and 7.4g/Lday, respectively). Cultivation with a predefined profile significantly improved both biomass and CGC volumetric productivity (87 and 10.8g/Lday, respectively). Hence, this strategy was used to implement a repeated fed-batch process comprising 7 consecutive cycles. A daily production of 119-126g/L of biomass with a CGC content of 11-16wt% was obtained, thus proving this cultivation strategy is adequate to reach a high CGC productivity that ranged between 11 and 18g/Lday. The process was stable and reproducible in terms of CGC productivity and polymer composition, making it a promising strategy for further process development.

Myocarditis in Paediatric Patients: Unveiling the Progression to Dilated Cardiomyopathy and Heart Failure.

Myocarditis is a challenging and potentially life-threatening disease associated with high morbidity in some paediatric patients, due to its ability to present as an acute and fulminant disease and to ultimately progress to dilated cardiomyopathy. It has been described as an inflammatory disease of the myocardium caused by diverse aetiologies. Viral infection is the most frequent cause of myocarditis in developed countries, but bacterial and protozoal infections or drug hypersensitivity may also be causative agents. The prompt diagnosis in paediatric patients is difficult, as the spectrum of clinical manifestation can range from no myocardial dysfunction to sudden cardiac death. Recent studies on myocarditis pathogenesis have revealed a triphasic nature of this disease, which influences the diagnostic and therapeutic strategies to adopt in each patient. Endomyocardial biopsy remains the gold standard for diagnosing myocarditis, and several non-invasive diagnostic tools can be used to support the diagnosis. Intravenous immunoglobulin has become part of routine practice in the treatment of myocarditis in paediatric patients at many centres, but its true effect on the cardiac function has been the target of many studies. The aim of this review is to approach the recently discovered facets of paediatric myocarditis regarding its progression to dilated cardiomyopathy.

Chitin-glucan complex production by Komagataella pastoris: Downstream optimization and product characterization.

Purified chitin-glucan complex (CGCpure) was extracted from Komagataella pastoris biomass using a hot alkaline treatment, followed by neutralization and repeated washing with deionized water. The co-polymer thus obtained had a ß-glucan:chitin molar ratio of 75:25 and low protein and inorganic salts contents (3.0 and 0.9 wt%, respectively). CGCpure had an average molecular weight of 4.9 × 10(5)Da with a polydispersity index of 1.7, and a crystallinity index of 50%. Solid-state NMR provided structural insight at the co-polymer. X-ray diffraction suggests that CGCpure has α-chitin in its structure. CGCpure presented an endothermic decomposition peak at 315°C, assigned to the degradation of the saccharide structures. This study revealed that K. pastoris CGC has properties similar to other chitinous biopolymers and may represent an attractive alternative to crustacean chitin derived-products, being a reliable raw material for the development of new/improved pharmaceutical, cosmetic or food products.

Chitin-glucan complex production by Komagataella (Pichia) pastoris: impact of cultivation pH and temperature on polymer content and composition.

Chitin-glucan complex (CGC) is a valuable biomaterial that can be extracted from the cell wall of several yeast and fungi. In this work, the yeast Komagataella (Pichia) pastoris was grown on glycerol as the sole carbon source in batch cultivation experiments to evaluate the effect of pH (3.5-6.5) and temperature (20-40°C) on CGC production and polymer composition. The CGC content in the biomass and the volumetric productivity (rp) were not significantly affected within the tested pH and temperature ranges. Nevertheless, both parameters could be maximized (CGC ≥14wt% and rp ≥ 3.0 gCGC L(-1)day(-1)) for temperatures within 27-34°C and pH above 6.0 or below 4.0. In contrast, the effect of pH and temperature on the polymer's chitin:ß-glucan molar ratio was more pronounced. The highest chitin:ß-glucan molar ratio (>14:86) was obtained for the mid-range pH (4.5-5.8) and temperatures (26-33°C), while a drastic reduction of chitin to ≤ 6%mol was observed outside those ranges. Therefore, a compromise between maximal CGC production and the synthesis of polymers enriched in chitin must be achieved, depending on the final application of this product.

Improvement on the yield of polyhydroxyalkanotes production from cheese whey by a recombinant Escherichia coli strain using the proton suicide methodology.

In this work Escherichia coli strain CML3-1 was engineered through the insertion of Cupriavidus necator P(3HB)-synthesis genes, fused to a lactose-inducible promoter, into the chromosome, via transposition-mediated mechanism. It was shown that polyhydroxyalkanotes (PHAs) production by this strain, using cheese whey, was low due to a significant organic acids (OA) synthesis. The proton suicide method was used as a strategy to obtain an E. coli mutant strain with a reduced OA-producing capacity, aiming at driving bacterial metabolism toward PHAs synthesis. Thirteen E. coli mutant strains were obtained and tested in shake flask assays, using either rich or defined media supplemented with lactose. P8-X8 was selected as the best candidate strain for bioreactor fed-batch tests using cheese whey as the sole carbon source. Although cell growth was considerably slower for this mutant strain, a lower yield of OA on substrate (0.04 Cmol(OA)/Cmol(lac)) and a higher P(3HB) production (18.88 g(P(3HB))/L) were achieved, comparing to the original recombinant strain (0.11 Cmol(OA)/Cmol(lac) and 7.8 g(P(3HB))/L, respectively). This methodology showed to be effective on the reduction of OA yield by consequently improving the P(3HB) yield on lactose (0.28 Cmol (P(3HB))/Cmol(lac) vs 0.10 Cmol(P(3HB))/Cmol(lac) of the original strain).