Comparison of Dorsal Preservation Rhinoplasty Techniques: Functional and Aesthetic Review of Subdorsal Septal Strip Methods.

Objective: To compare subdorsal strip excisions in patients undergoing dorsal preservation (DP) rhinoplasty using patient-related outcome measures (PROMS). Methods: Patients were treated from 2020 to 2022 using the modified subdorsal strip method (MSSM) or Z flap approach. A two-sample t-test determined whether there was a difference in functional and aesthetic scores using the NOSE, Sinonasal Outcome Test (SNOT-22), SCHNOS, and ESS scales. Results: Seventy-one primary rhinoplasty patients met inclusion criteria at 12 months with an average age of 23 years (62 female, 9 male), with 35 (49%) undergoing the MSSM technique, while 36 (51%) receiving the Z flap. PROMS at 1, 3, 6, and 12 months postoperatively were compared. The average preoperative and postoperative NOSE score was 9.36 and -4.4 (standard deviation [SD] 3.1, p < 0.001). The average preoperative SNOT-22 score was 23.9 and -16.4 (SD 10.2, p < 0.001). ESS scores was average was 6.2 and -1.6 (SD 3.2, p = 0.01). The average SCHNOS total, functional, and cosmetic scores were 27.6 (6-47), 8.2 (0-20) and 18.7 (0-37), respectively, and -5.7 (SD 8.2, p < 0.001), -5.73 (SD 6.24, p < 0.001), -18.1 (SD 9.7, p < 0.001). No significant complications were found and no difference in PROMs among groups. Conclusion: There was no difference in septal strip techniques as evaluated by PROMS.

Postoperative Radiologic Imaging in Secondary Alveolar Bone Grafting for Cleft Lip and Palate: A Systematic Review and Meta-Analysis.

INTRODUCTION: Radiographs (XRs), computed tomography (CT) scans, and cone-beam CT (CBCT) scans are utilized for assessment of secondary alveolar bone graft (SABG) in patients with cleft lip and palate (CLP). However, the optimal choice for imaging modality remains unclear. This study compares the image fidelity and safety profile for XR, CT, and CBCT in the assessment of patients with CLP who have undergone SABG. METHODS: Articles from MEDLINE and Elsevier Embase were screened. The primary outcome was graft success rate. Secondary outcomes were percent-by-volume of graft maintained and patient safety, defined by radiation exposure. A random effects model was used to calculate the pooled outcomes for each imaging modality. Chi-squared analysis was used to compare pooled outcomes between different imaging modalities. RESULTS: Of the 149 articles identified initially, 14 were included. Computed tomography exhibited a significantly higher image fidelity demonstrated by a lower graft success rate (62.0%) compared with both XR (72.6%, P<0.01) and CBCT (69.8%, P<0.01). Cone-beam CT had the lowest reported percent-by-volume of graft maintained (32.1%). Computed tomography had a higher mean radiation dosage (39.7 milligray) than what has been reported for both XR and CBCT. CONCLUSION: Computed tomography demonstrated lower graft success rates than both XR and CBCT, possibly indicating a higher image fidelity. However, compared with CBCT, CT may have a higher radiation exposure. Randomized trials and longitudinal studies are necessary to perform a direct comparison between CT and CBCT and to correlate the image fidelity of these modalities with clinical outcomes.

Patient-Reported Outcome Measures Including Nasal Breathing Improvement After Functional Rhinoplasty Using Endonasal Septal Extension Grafting.

Objective: To measure the change perceived by patients after endonasal rhinoplasty using a, septal extension graft (SEG), as measured by patient-reported outcome measures (PROMs). Methods: A retrospective review of patients with nasal obstruction underwent septoplasty, turbinoplasty, and SEG. PROMs were assessed to compare operative outcomes for breathing (Nose Obstruction Symptom Evaluation [NOSE], Sinonasal Outcome Test [SNOT]-22, Standardized Cosmesis and Health Nasal Outcomes Survey [SCHNOS]), and sleep quality (Epworth Sleepiness Scale [ESS]) Results: Of the 34 patients undergoing rhinoplasty with Endonasal SEG, the median patient age was 38.3 years (range 17-58) and mostly male (n = 18, 52.9%). Additional procedures performed on the patients included septoplasty (n = 34, 100%) and turbinate reduction (n = 34, 100%). Average follow-up was 126.6 days (range 28-573) for a majority of PROMs. There were no complications. The average change in NOSE score was 71.5 and -49.4 (standard deviation [SD] = 19.0, p < 0.001). SNOT-22 change was 35.4 and -24.2 (SD = 14.5, p < 0.001), and ESS scores averaged 6.7 and -3.4 (SD = 4.3, p < 0.001). The average SCHNOS total, functional, and cosmetic scores were 40.6, 67.9, and 22.4, respectively, and -28.0 (SD = 19.8), -44.5 (SD = 22.9), and 17.1 (SD = 24.6) (p < 0.001). Conclusion: In this pilot study, patients reported improvement in nasal breathing after correcting a deviated caudal septum and applying an Endonasal SEG.

Mexican consensus on cow's milk protein allergy.

BACKGROUND: The aim of this study is to present the current views of a diverse group of experts on the diagnosis and treatment of Cow's Milk Protein Allergy (CMPA) in children under 2 years of age in Mexico. MATERIAL AND METHODS: The study, led by a scientific committee of five experts in CMPA, was divided into six phases, including a modified Delphi process. A total of 20 panelists, all of whom were pediatric specialists, participated in administering a comprehensive 38-item questionnaire. The questionnaire was divided into two blocks: Diagnosis and Treatment (20 items each). RESULTS: Consensus was reached on all the proposed items, with an agreement rate of over 70% for each of them. As a result, a diagnostic and treatment algorithm was developed that emphasized the reduction of unnecessary diagnostic studies and encouraged breastfeeding whenever possible. In cases where breast milk is not available, appropriate use of hypoallergenic formulas was recommended. In addition, recommendations on treatment duration and gradual reintroduction of cow's milk protein were provided. CONCLUSIONS: The recommendations endorsed by 20 Mexican pediatricians through this study are applicable to everyday clinical practice, thereby enhancing the diagnosis and treatment of children under 2 years of age with CMPA. This, in turn, will foster improved health outcomes and optimize the utilization of healthcare resources.

Mexican consensus on cow’s milk protein allergy

Background: The aim of this study is to present the current views of a diverse group of experts on the diagnosis and treatment of Cow’s Milk Protein Allergy (CMPA) in children under 2 years of age in Mexico. Material and methods: The study, led by a scientific committee of five experts in CMPA, was divided into six phases, including a modified Delphi process. A total of 20 panelists, all of whom were pediatric specialists, participated in administering a comprehensive 38-item questionnaire. The questionnaire was divided into two blocks: Diagnosis and Treatment (20 items each). Results: Consensus was reached on all the proposed items, with an agreement rate of over 70% for each of them. As a result, a diagnostic and treatment algorithm was developed that emphasized the reduction of unnecessary diagnostic studies and encouraged breastfeeding whenever possible. In cases where breast milk is not available, appropriate use of hypoallergenic formulas was recommended. In addition, recommendations on treatment duration and gradual reintroduction of cow’s milk protein were provided. Conclusions: The recommendations endorsed by 20 Mexican pediatricians through this study are applicable to everyday clinical practice, thereby enhancing the diagnosis and treatment of children under 2 years of age with CMPA. This, in turn, will foster improved health outcomes and optimize the utilization of healthcare resources (AU)

Analysing the In-Use Stability of mRNA-LNP COVID-19 Vaccines Comirnaty™ (Pfizer) and Spikevax™ (Moderna): A Comparative Study of the Particulate.

Comirnaty™ and Spikevax™ were the first vaccines approved for human use based on modified non-replicating mRNA lipophilic nanoparticle (mRNA-LNP) technology, with great success in the treatment of COVID-19. They have been used massively worldwide. One of the major inconveniences of these vaccines is related to pharmaceutical stability issues. Proper transportation, storage, and in-use handling before administration to patients are critical steps since failures can potentially reduce potency. In this research, the in-use stability of Comirnaty™ and Spikevax™ clinical samples was analysed and the results were compared. As changes in the size of the mRNA-LNPs are related to potency, these modifications were analysed by qualitative Dynamic Light Scattering (DLS) as a stability-indicating method for control and stressed vaccine samples. Strong stress factors (accelerated light irradiation, manual shaking, and vortex vibration) and conditions that mimic in-use handling (exposure to natural light and room temperature, repeated cycles of injections, and 24 h storage in syringes) were checked. The morphology of the mRNA-LNPs was analysed by Transmission Electron Microscopy (TEM) to better interpret and support the DLS results. Although the two vaccines are based on the same mRNA-LNP technology, the results demonstrate that they are characterised by very different particle size profiles and behaviours against different handling/stress conditions.

Azathioprine dose tailoring based on pharmacogenetic information: Insights of clinical implementation.

Azathioprine is commonly used as an immunosuppressive antimetabolite in the treatment of acute lymphoblastic leukemia, autoimmune disorders (such as Crohn's disease and rheumatoid arthritis), and in patients receiving organ transplants. Thiopurine-S-methyltransferase (TPMT) is a cytoplasmic trans-methylase catalyzing the S-methylation of thiopurines. The active metabolites obtained from thiopurines are hydrolyzed into inactive forms by the Nudix hydrolase 15 (NUDT15). The TPMT*2 (defined by rs1800462), *3A (defined by rs1800460 and rs1142345), *3B (defined by rs1800460), *3C (defined by rs1142345), *6 (defined by rs75543815), and NUDT15 rs116855232 genetic variant have been associated, with the highest level of evidence, with the response to azathioprine, and, the approved drug label for azathioprine and main pharmacogenetic dosing guidelines recommend starting with reduced initial doses in TPMT intermediate metabolizer (IM) patients and considering an alternative treatment in TPMT poor metabolizer (PM) patients. This study aims to assess the clinical impact of azathioprine dose tailoring based on TPMT genotyping studying the azathioprine toxicity and efficacy, treatment starts, and dose adjustments during follow-up, comparing TPMT IM/PM and normal metabolizer (NM) patients. It also studied the association of NUDT15 rs116855232 with response to azathioprine in patients receiving a tailored treatment based on TPMT and characterized the TMPT and NUDT15 studied variants in our population. Results show that azathioprine dose reduction in TPMT IM patients (TPMT*1/*2, *1/*3A, or *1/*3C genotypes) is related to lower toxicity events compared to TPMT NM (TPMT *1/*1 genotype), and lower azathioprine dose adjustments during follow-up without showing differences in the efficacy. The results support the hypothesis of existing other genetic variants affecting azathioprine toxicity.

Who's your data? Primary immune deficiency differential diagnosis prediction via machine learning and data mining of the USIDNET registry.

PURPOSE: There are currently more than 480 primary immune deficiency (PID) diseases and about 7000 rare diseases that together afflict around 1 in every 17 humans. Computational aids based on data mining and machine learning might facilitate the diagnostic task by extracting rules from large datasets and making predictions when faced with new problem cases. In a proof-of-concept data mining study, we aimed to predict PID diagnoses using a supervised machine learning algorithm based on classification tree boosting. METHODS: Through a data query at the USIDNET registry we obtained a database of 2396 patients with common diagnoses of PID, including their clinical and laboratory features. We kept 286 features and all 12 diagnoses to include in the model. We used the XGBoost package with parallel tree boosting for the supervised classification model, and SHAP for variable importance interpretation, on Python v3.7. The patient database was split into training and testing subsets, and after boosting through gradient descent, the predictive model provides measures of diagnostic prediction accuracy and individual feature importance. After a baseline performance test, we used the Class Weighting Hyperparameter, or scale_pos_weight to correct for imbalanced classification. RESULTS: The twelve PID diagnoses were CVID (1098 patients), DiGeorge syndrome, Chronic granulomatous disease, Congenital agammaglobulinemia, PID not otherwise classified, Specific antibody deficiency, Complement deficiency, Hyper-IgM, Leukocyte adhesion deficiency, ectodermal dysplasia with immune deficiency, Severe combined immune deficiency, and Wiskott-Aldrich syndrome. For CVID, the model found an accuracy on the train sample of 0.80, with an area under the ROC curve (AUC) of 0.80, and a Gini coefficient of 0.60. In the test subset, accuracy was 0.76, AUC 0.75, and Gini 0.51. The positive feature value to predict CVID was highest for upper respiratory infections, asthma, autoimmunity and hypogammaglobulinemia. Features with the highest negative predictive value were high IgE, growth delay, abscess, lymphopenia, and congenital heart disease. For the rest of the diagnoses, accuracy stayed between 0.75 and 0.99, AUC 0.46-0.87, Gini 0.07-0.75, and LogLoss 0.09-8.55. DISCUSSION: Clinicians should remember to consider the negative predictive features together with the positives. We are calling this a proof-of-concept study to continue with our explorations. A good performance is encouraging, and feature importance might aid feature selection for future endeavors. In the meantime, we can learn from the rules derived by the model and build a user-friendly decision tree to generate differential diagnoses.

Endothelial ERα promotes glucose tolerance by enhancing endothelial insulin transport to skeletal muscle.

The estrogen receptor (ER) designated ERα has actions in many cell and tissue types that impact glucose homeostasis. It is unknown if these include mechanisms in endothelial cells, which have the potential to influence relative obesity, and processes in adipose tissue and skeletal muscle that impact glucose control. Here we show that independent of impact on events in adipose tissue, endothelial ERα promotes glucose tolerance by enhancing endothelial insulin transport to skeletal muscle. Endothelial ERα-deficient male mice are glucose intolerant and insulin resistant, and in females the antidiabetogenic actions of estradiol (E2) are absent. The glucose dysregulation is due to impaired skeletal muscle glucose disposal that results from attenuated muscle insulin delivery. Endothelial ERα activation stimulates insulin transcytosis by skeletal muscle microvascular endothelial cells. Mechanistically this involves nuclear ERα-dependent upregulation of vesicular trafficking regulator sorting nexin 5 (SNX5) expression, and PI3 kinase activation that drives plasma membrane recruitment of SNX5. Thus, coupled nuclear and non-nuclear actions of ERα promote endothelial insulin transport to skeletal muscle to foster normal glucose homeostasis.

Virtual Surgical Planning for Patients with Skeletal-Dental and Obstructive Sleep Apnea Syndrome.

The integration of virtual surgical planning (VSP) for the treatment of skeletal, dental, and facial abnormalities and obstructive sleep apnea (OSA) with maxillofacial surgery has catapulted surgical planning. Although reported for treating skeletal-dental abnormalities and dental implant surgery, a paucity of knowledge existed reporting the feasibility and resultant outcome measures when VSP was employed for planning maxillary and mandibular surgery for OSA patients. The surgery-first approach is at the forefront of advancing maxillofacial surgery. Case series reporting success with the surgery-first approach for patients with skeletal-dental and sleep apnea patients have been reported. In sleep apnea patients, clinically significant reductions in apnea-hypopnea index and improvement of low oxyhemoglobin saturation have been achieved. More so, significant improvement in the posterior airway space at the occlusal and mandibular planes were achieved, while preserving aesthetic norms as measured by tooth to lip measurements. VSP is a feasible tool used for predicting surgical outcome measures in maxillomandibular advancement surgery for patients with skeletal, dental, facial, and OSA derangements.

Gut Microbiota Composition Can Predict Colonization by Multidrug-Resistant Bacteria in SARS-CoV-2 Patients in Intensive Care Unit: A Pilot Study.

The SARS-CoV-2 infection has increased the number of patients entering Intensive Care Unit (ICU) facilities and antibiotic treatments. Concurrently, the multi-drug resistant bacteria (MDRB) colonization index has risen. Considering that most of these bacteria are derived from gut microbiota, the study of its composition is essential. Additionally, SARS-CoV-2 infection may promote gut dysbiosis, suggesting an effect on microbiota composition. This pilot study aims to determine bacteria biomarkers to predict MDRB colonization risk in SARS-CoV-2 patients in ICUs. Seventeen adult patients with an ICU stay >48 h and who tested positive for SARS-CoV-2 infection were enrolled in this study. Patients were assigned to two groups according to routine MDRB colonization surveillance: non-colonized and colonized. Stool samples were collected when entering ICUs, and microbiota composition was determined through Next Generation Sequencing techniques. Gut microbiota from colonized patients presented significantly lower bacterial diversity compared with non-colonized patients (p < 0.05). Microbiota in colonized subjects showed higher abundance of Anaerococcus, Dialister and Peptoniphilus, while higher levels of Enterococcus, Ochrobactrum and Staphylococcus were found in non-colonized ones. Moreover, LEfSe analysis suggests an initial detection of Dialister propionicifaciens as a biomarker of MDRB colonization risk. This pilot study shows that gut microbiota profile can become a predictor biomarker for MDRB colonization in SARS-CoV-2 patients.

Effect of Fluoride Content of Mouthwashes on the Metallic Ion Release in Different Orthodontics Archwires.

Metal ion release studies were carried out on three of the most commonly used orthodontic wires in the clinic: austenitic stainless steel, Ti-Mo, and superelastic NiTi, using three mouthwashes with different fluoride concentrations: 130, 200, and 380 ppm. Immersions were carried out in these mouthwashes at 37 °C for 1, 4, 7, and 14 days, and the ions released were determined by inductively coupled plasma-mass spectrometry (ICP-MS). All wires were observed by scanning electron microscopy (SEM). The results showed a moderate ion release in the stainless steel wires, with nickel and chromium values of 500 and 1000 ppb in the worst conditions for the wires: concentrations of 380 ppm fluoride and 14 days of immersion. However, in the Ti-Mo and NiTi alloys, an abrupt change in release was observed when the samples were immersed in 380 ppm fluoride concentrations. Titanium releases in Ti-Mo wires reached 200,000 ppb, creating numerous pits on the surface. Under the same conditions, the release of Ni and Ti ions from the superelastic wires also exceeded 220,000 ppb and 180,000 ppb, respectively. This release of ions causes variations in the chemical composition of the wires, causing the appearance of martensite plates in the austenitic matrix after 4 days of immersion. This fact causes it to lose its superelastic properties at a temperature of 37 °C. In the case of immersion in 380 ppm mouthwashes for more than 7 days, rich-nickel precipitates can be seen. These embrittle the wire and lose all tooth-correcting properties. It should be noted that the release of Ni ions can cause hypersensitivity in patients, particularly women. The results indicate that the use of mouthwashes with a high content of fluoride should not be recommended with orthodontic archwires.

Evaluation of DNA Vaccine Candidates against Foot-and-Mouth Disease Virus in Cattle.

We evaluated four DNA vaccine candidates for their ability to produce virus-like particles (VLPs) and elicit a protective immune response against Foot-and-mouth disease virus (FMDV) in cattle. Two traditional DNA plasmids and two DNA minicircle constructs were evaluated. Both the pTarget O1P1-3C plasmid and O1P1-3C minicircle encoded a wild-type FMDV 3C protease to process the P1-2A polypeptide, whereas the O1P1-HIV-3CT minicircle used an HIV-1 ribosomal frameshift to down-regulate expression of a mutant 3C protease. A modified pTarget plasmid with a reduced backbone size, mpTarget O1P1-3CLT, used a 3C protease containing two mutations reported to enhance expression. All constructs produced mature FMDV P1 cleavage products in transfected cells, as seen by western blot analysis. Three constructs, O1P1-3C minicircles, pTarget O1P1-3C, and mpTarget O1P1-3CLT plasmids, produced intracellular VLP crystalline arrays detected by electron microscopy. Despite VLP formation in vitro, none of the DNA vaccine candidates elicited protection from clinical disease when administered independently. Administration of pTarget O1P1-3C plasmid enhanced neutralizing antibody titers when used as a priming dose prior to administration of a conditionally licensed adenovirus-vectored FMD vaccine. Further work is needed to develop these DNA plasmid-based constructs into standalone FMD vaccines in cattle.

Functional and Aesthetic Outcomes of Let Down Dorsal Preservation Rhinoplasty.

Background: Preservation rhinoplasty is a re-emerging technique that lacks data on functional and aesthetic outcomes. Objective: To measure the change in patient-reported nasal aesthetic perception, nasal breathing, and sleep and compare outcomes between two different septal cartilage manipulation techniques among patients undergoing preservation rhinoplasty. Methods: Functional and aesthetic outcomes of a let down dorsal preservation rhinoplasty using either the modified subdorsal strip method (MSSM) or subdorsal Z-flap are assessed pre- and postoperatively using the validated assessment tools Nose Obstruction Symptom Evaluation (NOSE), Sinonasal Outcome Test (SNOT-22), Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS), and Epworth Sleepiness Scale (ESS). Results: Fifty-two patients, 40 women and 12 men ages 15-69 years, underwent dorsal preservation rhinoplasty and the majority reported at 1, 3, 6, and 12 months postoperatively significant improvement based on a paired t-test in NOSE, SNOT-22, SCHNOS, and ESS scores except for ESS scores at 6 and 12 months. No significant difference based on a two-sample t-test was observed between the MSSM and Z-flap techniques implemented. Conclusion: Let down dorsal preservation rhinoplasty with either the MSSM or Z-flap cartilage manipulation technique can achieve significant improvement in nasal aesthetics, nasal breathing, and sleep according to patient responses on validated assessment tools.

International Consensus Statement on Obstructive Sleep Apnea.

BACKGROUND: Evaluation and interpretation of the literature on obstructive sleep apnea (OSA) allows for consolidation and determination of the key factors important for clinical management of the adult OSA patient. Toward this goal, an international collaborative of multidisciplinary experts in sleep apnea evaluation and treatment have produced the International Consensus statement on Obstructive Sleep Apnea (ICS:OSA). METHODS: Using previously defined methodology, focal topics in OSA were assigned as literature review (LR), evidence-based review (EBR), or evidence-based review with recommendations (EBR-R) formats. Each topic incorporated the available and relevant evidence which was summarized and graded on study quality. Each topic and section underwent iterative review and the ICS:OSA was created and reviewed by all authors for consensus. RESULTS: The ICS:OSA addresses OSA syndrome definitions, pathophysiology, epidemiology, risk factors for disease, screening methods, diagnostic testing types, multiple treatment modalities, and effects of OSA treatment on multiple OSA-associated comorbidities. Specific focus on outcomes with positive airway pressure (PAP) and surgical treatments were evaluated. CONCLUSION: This review of the literature consolidates the available knowledge and identifies the limitations of the current evidence on OSA. This effort aims to create a resource for OSA evidence-based practice and identify future research needs. Knowledge gaps and research opportunities include improving the metrics of OSA disease, determining the optimal OSA screening paradigms, developing strategies for PAP adherence and longitudinal care, enhancing selection of PAP alternatives and surgery, understanding health risk outcomes, and translating evidence into individualized approaches to therapy.

Projecting Spanish fertility at regional level: A hierarchical Bayesian approach.

The transition from a demographic regime of high mortality and high fertility to one with low mortality and low fertility is universal and comes along with the process of socio-economic modernization. The Spanish total fertility rate has decreased to below replacement levels in the last decades. The decline has persisted since the 1960s and is diverse across the country. Based on that diversity, the use of population forecasts, not only at national but at regional levels, for planning purposes (governments and private sector) with large horizons has become a must to provide essential services. Using a Bayesian hierarchical model we constructed probabilistic fertility forecasts for Spain at the regional level. Although this approach is already issued by the United Nations little research has been done focusing on the Spanish subnational level. Our objective is to disaggregate the national projections of the total fertility rate for Spain into regional forecasts. The results of this research will show the model fitting, first to the national level and then using a multifaceted and continuous evolution of fertility over time, at the regional level, to check its convergence.

Effect of Fluoride Content of Mouthwashes on Superelastic Properties of NiTi Orthodontic Archwires.

The influence of sodium fluoride (NaF) concentration in mouthwashes on the properties of superelastic NiTi orthodontic wires has been studied. In this work, 55.8%Ni and 44.2%Ti (in weight) wires were introduced in commercial mouthwashes with different NaF contents (0, 130, 200 and 380 ppm). The release of Ni2+ and Ti4+ ions was by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) at 1, 4, 7 and 14 days. Superelastic orthodontic wires present at oral temperature the austenitic phase which is transformed into a plastic phase (martensite) by cooling. The temperatures at which this occurs are influenced by the chemical composition. The release of ions from the wire will produce variations in the temperatures and stresses of the stress-induced martensitic transformation. Ms, Mf, As, Af were determined by Differential Scanning Calorimeter (DSC). The transformation stresses (austenite to stress induce martensite) were determined with a servo-hydraulic testing machine at 37 °C. The surfaces for the different times and mouthwash were observed by Scanning Electron Microscope (SEM). The release of Ni2+ in mouthwashes with 380 ppm NaF concentrations reaches 230,000 ppb in 14 days and for Ti4+ 175,000 ppb. When NaF concentrations are lower than 200 ppm the release of Ni and Ti ions is around 1500 ppb after 14 days. This variation in compositions leads to variations in Ms from 27 °C to 43.5 °C in the case of higher NaF concentration. The increasing immersion time and NaF concentrations produce a decrease of Ni in the wires, increasing Ms which exceed 37 °C with the loss of superelasticity. In the same way, the stresses (tooth position corrective) decrease from 270 MPa to 0 MPa due to the martensitic phase. The degradation can produce the growth of precipitates rich in Ti (Ti2Ni). These results are of great interest in the orthodontic clinic in order to avoid the loss of the therapeutic properties of superelastic NiTi due to long immersion in fluoride mouthwashes.

Pharmacogenetics of siponimod: A systematic review.

Multiple sclerosis is a chronic inflammatory neurological disease, and siponimod (Mayzent) is the first oral treatment option for adult patients with secondary progressive multiple sclerosis. We performed a systematic review of the pharmacogenetics of Siponimod, and we found that (430 C>T; rs1799853) and CYP2C9 * 3 (1075 A>C; rs1057910), both translated no-function alleles, have been related to a lower metabolism of siponimod by CYP2C9 enzyme. The FDA-approved drug label and EMA risk management plan for siponimod require testing patients for CYP2C9 genotype before treatment starts. The FDA drug label states that siponimod is contraindicated in patients carrying a CYP2C9 * 3/* 3 genotype, and a daily maintenance dose of 1 mg in patients with CYP2C9 * 1/* 3 and * 2/* 3 genotypes. The EMA reported the potential long-term safety implications in CYP2C9 poor metabolizer patients treated with this drug. Based on this systematic review we concluded that CYP2C9 SNPs influence on siponimod response might be stated by assessing not only CYP2C9 * 2 and CYP2C9 * 3 but other genetic variants resulting in CYP2C9 IM/PM status. CYP2C9 IM phenotype translated from the CYP2C9 * 2 genotype should be revised since it is contradictory compared to other CYP2C9 no-function alleles, and CYP2C9 * 2 might be excluded from PGx testing recommendation before treatment starts with siponimod since it is not translated into a therapeutic recommendation.

Comparative Evaluation of the Foot-and-Mouth Disease Virus Permissive LF-BK αVß6 Cell Line for Senecavirus A Research.

Senecavirus A (SVA) is a member of the family Picornaviridae and enzootic in domestic swine. SVA can induce vesicular lesions that are clinically indistinguishable from Foot-and-mouth disease, a major cause of global trade barriers and agricultural productivity losses worldwide. The LF-BK αVß6 cell line is a porcine-derived cell line transformed to stably express an αVß6 bovine integrin and primarily used for enhanced propagation of Foot-and-mouth disease virus (FMDV). Due to the high biosecurity requirements for working with FMDV, SVA has been considered as a surrogate virus to test and evaluate new technologies and countermeasures. Herein we conducted a series of comparative evaluation in vitro studies between SVA and FMDV using the LF-BK αVß6 cell line. These include utilization of LF-BK αVß6 cells for field virus isolation, production of high virus titers, and evaluating serological reactivity and virus susceptibility to porcine type I interferons. These four methodologies utilizing LF-BK αVß6 cells were applicable to research with SVA and results support the current use of SVA as a surrogate for FMDV.