Total ankle arthroplasty improves discrete and continuous stance phase gait symmetry.

BACKGROUND: Total ankle arthroplasty (TAA) is used to treat symptomatic end-stage ankle arthritis (AA). However, little is known about TAA's effects on gait symmetry. RESEARCH QUESTION: Determine if symmetry changes from before surgery through two years following TAA utilizing the normalized symmetry index (NSI) and statistical parametric mapping (SPM). METHODS: 141 patients with end-stage unilateral AA were evaluated from a previously collected prospective database, where each participant was tested within two weeks of surgery (Pre-Op), one year and two years following TAA. Walking speed, hip extension angle and moment, hip flexion angle, ankle plantarflexion angle and moment, ankle dorsiflexion angle, weight acceptance (GRF1), and propulsive (GRF2) vertical ground reaction forces were calculated for each limb. Gait symmetry was assessed using the NSI. A linear mixed effects model with a single response for each gait symmetry variable was used to examine the fixed effect of follow-up time (Pre-Op, Post-1 yr, Post-2 yr) and the random effect of participant with gait speed as a covariate in the model. A one-dimensional repeated measures analysis of variance (ANOVA) statistical parameter mapping (SPM) was completed to examine differences in the time-series NSI to determine regions of significant differences between follow-up times. RESULTS: Relative to Pre-Op values, GRF1, and GRF2 showed increased symmetry for discrete metrics and the time-series NSI across sessions. Hip extension moment had the largest symmetry improvement. Ankle plantarflexion angle was different between Pre-Op and Post-2 yr (p=0.010); and plantarflexion moment was different between Pre- Op and each post-operative session (p<0.001). The time-series Ankle Angle NSI was greater during the early stance phase in the Pre-Op session compared to Post-2 yr. SIGNIFICANCE: Symmetry across most of the stance phase improved following TAA indicating that TAA successfully improves gait symmetry and future work should determine if these improvements restore symmetry to levels equivalent with health age-match controls.

The effectiveness of the total-maxillary-arch-distalization approach in treating class II division 1 malocclusion: A systematic review.

OBJECTIVE: The objective of this review is to assess the effect of total maxillary arch distalization (TMAD) treatment on the dental, skeletal, soft tissues, and airways during non-extraction camouflage treatment of class II division 1 patients. METHODS: We performed a systematic review of the published data in four electronic databases up to April 2023. We considered studies for inclusion if they were examining the effects of TMAD during treatment of class II division 1 malocclusion in the permanent dentition. Study selection, data extraction, risk of bias assessment, and assessment of the strength of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool were performed in duplicate. RESULTS: Out of the 27 articles that met the initial eligibility criteria, 19 studies were finally selected. Fair to relatively good quality evidence was identified after the risk of bias assessment of the included studies. Out of the 19 selected studies, 5 studies used inter-radicular TADs, 10 studies used modified C- palatal plate (MCPP), 3 studies used infra zygomatic crest (IZC) TADs, 1 study compared buccal TADs versus MCPP, and 1 study compared between cervical headgear and MCPP. The maximum amount of maxillary arch distalization using buccal TADs, MCPP, IZC TADs, and headgear was 4.2mm, 5.4mm, 5mm, and 2.5mm respectively. Different results regarding the amount of dental, skeletal, and soft tissue changes were observed. CONCLUSIONS: The current low to very low certainty level of evidence suggests that TMAD is effective in camouflaging class II division 1 malocclusion. Future well-conducted and clearly reported randomized controlled trials that include a control group are needed to make robust recommendations regarding the effect of TMAD with different appliances on dental, skeletal, and soft tissue structures. CLINICAL RELEVANCE: TMAD should be given priority with caution in class II patients who refuse the extraction of premolars. TMAD may be considered an adjunctive approach to solve cases associated with high anchorage need or anchorage loss.

Evaluation of the C-lingual Retractor and the Conventional Lingual Orthodontic Brackets in Terms of Speech Performance and Oral Discomfort: A Randomized Controlled Trial.

Background The C-lingual retractor (CR) is an alternative lingual technique to retract anterior teeth with minimum torque expression loss. Although the effects of lingual braces upon speech and oral comfort have been studied previously, there is no published data about the C-lingual retractor in this aspect. The aims of this trial were to compare (1) speech performance based on objective acoustic analysis and (2) levels of oral impairment between C-lingual retractor and conventional lingual brackets (LBs). Materials and methods A parallel-group randomized controlled trial was conducted on patients with class II division 1 malocclusion who sought orthodontic treatment at the Department of Orthodontics, Hama University Dental School. Thirty-six patients who met inclusion criteria were randomly selected and divided into two groups. Eighteen patients in the C-lingual retractor group (CR group) were treated with a C-lingual retractor, whereas eighteen patients in the lingual brackets group (LB group) were treated with conventional lingual brackets (Stealth H, American Orthodontics, Sheboygan, WI, USA). Fricative /s/ sound spectrograms were analyzed before (T0), immediately after (T1), one month after (T2), and three months after appliance placement (T3). The levels of oral discomfort were assessed using standardized questionnaires to evaluate speech, irritation, chewing difficulties, and other oral impacts. Results At all assessment times, the C-lingual retractor caused significant deteriorations in articulation, whereas in the lingual brackets group these deteriorations were statistically significant at T1 and T2 (P<0.001) but not significant at T3 (P=0.073). No intergroup differences were detected. Questionnaire analysis revealed that irritation of the tongue was significantly higher in the lingual brackets group after 24 hours of appliances' placement (P=0.007), whereas speech and mastication problems were insignificantly higher in the C-lingual retractor group. Conclusions The findings indicate that the C-lingual retractor has insignificantly a little more interaction with sound production than lingual brackets. Although the levels of oral impacts were almost similar among both groups, more tongue irritation was observed in the lingual brackets group. However, the oral discomfort decreased over the observation period in both groups.

Neurological manifestations of COVID-19: A potential gate to the determinants of a poor prognosis.

BACKGROUND: Several investigations were carried out during the pandemic, demonstrating a number of neurological symptoms linked to coronavirus disease 2019 (COVID-19) infection. OBJECTIVES: The goal of this review is to discuss COVID-19 disease's neurological signs and squeals. METHODOLOGY: From December 2019 to May 2020, data were retrieved from PubMed, Scopus, and ScienceDirect, as well as a manual search using Google Scholar. COVID-19, neurological symptoms, cranial nerves, motor system were among the key phrases utilized in the search. RESULTS: The intensity of respiratory involvement increases the likelihood of neurological symptoms and consequences. According to some research, it might range from 34% to 80%. The central and peripheral neural systems are both affected, resulting in cranial nerve palsies and limb paralysis. CONCLUSION: COVID-19 neurologic complications are key drivers of patient severity and mortality. Headache, convulsions, mental and psychic disorders, delirium, and insomnia are just some of the symptoms that the virus can cause. The olfactory nerve is the most commonly damaged cranial nerve, resulting in anosmia. Stroke (mostly infarction), encephalitis, meningitis, Guillain-Barre syndrome, relapse of multiple sclerosis, and transverse myelitis are all symptoms and squeals.

Evaluation of the open-bite Bionator versus the removable posterior bite plane with a tongue crib in the early treatment of skeletal anterior open bite: A randomized controlled trial.

BACKGROUND: Several treatment approaches can be found in the literature about early treatment of open bite. However, no studies have addressed the use of a removable posterior bite plane with a tongue crib (RPBP/C), compared with functional appliances, for treating open-bite cases. The objectives of this trial was to compare the effectiveness of the open-bite Bionator (OBB) and the RPBP/C as an early intervention to correct skeletal open-bite cases in children, in terms of limiting excessive vertical growth of the craniofacial skeletal components and normalizing the developement of the anterior dentoalveolar region. MATERIALS AND METHODS: Two-arm, parallel-group randomized controlled trial was conducted. Forty patients with a skeletal anterior open bite (age range: 7.5-10.5 years) were treated at the University of xxxx School of Dentistry in xxxx, xxxx. They were distributed randomly into 2 equal groups: the OBB group (20 patients; mean age: 8.8 ± 1.5 years) and the RPBP/C group (20 patients; mean age: 8.6 ± 1.1 years). Randomization was based on a computer-generated sequence of random numbers. Primary outcome measures were the skeletal and dentoalveolar variables, whereas the secondary outcome measures were the soft-tissue parameters assessed on standardized lateral cephalograms collected before and after 12 months of treatment. Mann-Whitney U tests were used to detect significant differences between the 2 groups. RESULTS: Both the OBB and the RPBP/C appliances induced favorable dental effects. A statistically significant difference was found between the 2 groups in the overbite (P = 0.003). Open bite in the OBB group showed a mean closure of 4.91 mm (SD 0.4 mm), and a mean closure of 3.43 mm (SD 0.3 mm) was observed in the RPBP/C group. Dentoalveolar changes at the anterior region were evident, with statistically significant extrusion, and lingual tipping of the maxillary and mandibular incisors (P ≤ 0.05). The results showed no significant differences in the skeletal changes between the 2 groups. CONCLUSIONS: The OBB and the upper posterior bite plane with crib were both effective in the early treatment of the skeletal anterior open bite. However, closure of the anterior open bite was mainly due to the dentoalveolar changes at the anterior region of the dental arches.

SOX2 Drives Bronchial Dysplasia in a Novel Organotypic Model of Early Human Squamous Lung Cancer.

RATIONALE: Improving the early detection and chemoprevention of lung cancer are key to improving outcomes. The pathobiology of early squamous lung cancer is poorly understood. We have shown that amplification of sex-determining region Y-box 2 (SOX2) is an early and consistent event in the pathogenesis of this disease, but its functional oncogenic potential remains uncertain. We tested the impact of deregulated SOX2 expression in a novel organotypic system that recreates the molecular and microenvironmental context in which squamous carcinogenesis occurs. OBJECTIVES: (1) To develop an in vitro model of bronchial dysplasia that recapitulates key molecular and phenotypic characteristics of the human disease; (2) to test the hypothesis that SOX2 deregulation is a key early event in the pathogenesis of bronchial dysplasia; and (3) to use the model for studies on pathogenesis and chemoprevention. METHODS: We engineered the inducible activation of oncogenes in immortalized bronchial epithelial cells. We used three-dimensional tissue culture to build an organotypic model of bronchial dysplasia. MEASUREMENTS AND MAIN RESULTS: We recapitulated human bronchial dysplasia in vitro. SOX2 deregulation drives dysplasia, and loss of tumor promoter 53 is a cooperating genetic event that potentiates the dysplastic phenotype. Deregulated SOX2 alters critical genes implicated in hallmarks of cancer progression. Targeted inhibition of AKT prevents the initiation of the dysplastic phenotype. CONCLUSIONS: In the appropriate genetic and microenvironmental context, acute deregulation of SOX2 drives bronchial dysplasia. This confirms its oncogenic potential in human cells and affords novel insights into the impact of SOX2 deregulation. This model can be used to test therapeutic agents aimed at chemoprevention.

A comparison between two lingual orthodontic brackets in terms of speech performance and patients' acceptance in correcting Class II, Division 1 malocclusion: a randomized controlled trial.

OBJECTIVE: To compare speech performance and levels of oral impairment between two types of lingual brackets. METHODS: A parallel-group randomized controlled trial was carried out on patients with Class II, Division 1 malocclusion treated at the University of Hama School of Dentistry in Hama, Syria. A total of 46 participants (mean age: 22.3 ± 2.3 years) with maxillary dentoalveolar protrusion were randomly distributed into two groups with 23 patients each (1:1 allocation ratio). Either STb (Ormco) or 7th Generation (Ormco) lingual brackets were applied. Fricative sound/s/ spectrograms were analyzed directly before intervention (T0), one week following premolar extraction prior to bracket placement (T1), within 24 hours of bracket bonding (T2), one month after (T3), and three months after (T4) bracket placement. Patients' acceptance was assessed by means of standardized questionnaires. RESULTS: After bracket placement, significant deterioration in articulation was recorded at all assessment times in the 7th Generation group, and up to T3 in the STb group. Significant intergroup differences were detected at T2 and T3. No statistically significant differences were found between the two groups in reported tongue irritation levels, whereas chewing difficulty was significantly higher in the 7th Generation group one month after bracket placement. CONCLUSIONS: 7th Generation brackets have more interaction with sound production than STb ones. Although patients in both groups complained of some degree of oral impairment, STb appliances appeared to be more comfortable than the 7th Generation ones, particularly within the first month of treatment.

A comparison between two lingual orthodontic brackets in terms of speech performance and patients' acceptance in correcting Class II, Division 1 malocclusion: a randomized controlled trial

ABSTRACT Objective: To compare speech performance and levels of oral impairment between two types of lingual brackets. Methods: A parallel-group randomized controlled trial was carried out on patients with Class II, Division 1 malocclusion treated at the University of Hama School of Dentistry in Hama, Syria. A total of 46 participants (mean age: 22.3 ± 2.3 years) with maxillary dentoalveolar protrusion were randomly distributed into two groups with 23 patients each (1:1 allocation ratio). Either STb (Ormco) or 7th Generation (Ormco) lingual brackets were applied. Fricative sound/s/ spectrograms were analyzed directly before intervention (T0), one week following premolar extraction prior to bracket placement (T1), within 24 hours of bracket bonding (T2), one month after (T3), and three months after (T4) bracket placement. Patients′ acceptance was assessed by means of standardized questionnaires. Results: After bracket placement, significant deterioration in articulation was recorded at all assessment times in the 7th Generation group, and up to T3 in the STb group. Significant intergroup differences were detected at T2 and T3. No statistically significant differences were found between the two groups in reported tongue irritation levels, whereas chewing difficulty was significantly higher in the 7th Generation group one month after bracket placement. Conclusions: 7th Generation brackets have more interaction with sound production than STb ones. Although patients in both groups complained of some degree of oral impairment, STb appliances appeared to be more comfortable than the 7th Generation ones, particularly within the first month of treatment.

RESUMO Objetivo: comparar dois tipos de braquetes linguais, em termos de influência na fala e comprometimento da dicção. Métodos: foi realizado um estudo clínico randomizado com grupos paralelos, em pacientes portadores de má oclusão de Classe II, divisão 1, tratados na Faculdade de Odontologia da University of Hama, em Hama, na Síria. No total, 46 participantes (idade média de 22,3 ± 2,3 anos), com protrusão dentoalveolar maxilar foram aleatoriamente distribuídos em dois grupos com 23 pacientes cada (coeficiente de alocação = 1:1). Foram utilizados braquetes linguais STb (Ormco) ou braquetes linguais 7th Generation (Ormco). Foram analisados espectrogramas do som fricativo /s/ imediatamente antes da intervenção (T0), uma semana após a extração dos pré-molares previamente à colagem dos braquetes (T1), após 24 horas da colagem dos braquetes (T2), um mês depois (T3) e três meses depois (T4) da colagem dos braquetes. A aceitação dos pacientes foi avaliada por meio de questionários padronizados. Resultados: após a inserção dos braquetes, registrou-se deterioração significativa da dicção, em todos os intervalos de avaliação, no grupo com os braquetes 7th Generation; e até o intervalo T3, no grupo com braquetes STb. Foram identificadas diferenças intergrupos significativas em T2 e T3. Não foram encontradas diferenças estatisticamente significativas entre os dois grupos quanto aos níveis de irritação lingual relatados, ao passo que as dificuldades na mastigação foram significativamente maiores no grupo com braquetes 7th Generation um mês após serem inseridos. Conclusões: os braquetes 7th Generation apresentam maior interferência na dicção do que os braquetes STb. Embora os pacientes dos dois grupos tenham reclamado de um certo grau de comprometimento da dicção, os braquetes STb parecem ser mais confortáveis do que os braquetes 7th Generation, principalmente durante o primeiro mês de tratamento.

Assessment of Minimal Residual Disease in Standard-Risk AML.

BACKGROUND: Despite the molecular heterogeneity of standard-risk acute myeloid leukemia (AML), treatment decisions are based on a limited number of molecular genetic markers and morphology-based assessment of remission. Sensitive detection of a leukemia-specific marker (e.g., a mutation in the gene encoding nucleophosmin [NPM1]) could improve prognostication by identifying submicroscopic disease during remission. METHODS: We used a reverse-transcriptase quantitative polymerase-chain-reaction assay to detect minimal residual disease in 2569 samples obtained from 346 patients with NPM1-mutated AML who had undergone intensive treatment in the National Cancer Research Institute AML17 trial. We used a custom 51-gene panel to perform targeted sequencing of 223 samples obtained at the time of diagnosis and 49 samples obtained at the time of relapse. Mutations associated with preleukemic clones were tracked by means of digital polymerase chain reaction. RESULTS: Molecular profiling highlighted the complexity of NPM1-mutated AML, with segregation of patients into more than 150 subgroups, thus precluding reliable outcome prediction. The determination of minimal-residual-disease status was more informative. Persistence of NPM1-mutated transcripts in blood was present in 15% of the patients after the second chemotherapy cycle and was associated with a greater risk of relapse after 3 years of follow-up than was an absence of such transcripts (82% vs. 30%; hazard ratio, 4.80; 95% confidence interval [CI], 2.95 to 7.80; P<0.001) and a lower rate of survival (24% vs. 75%; hazard ratio for death, 4.38; 95% CI, 2.57 to 7.47; P<0.001). The presence of minimal residual disease was the only independent prognostic factor for death in multivariate analysis (hazard ratio, 4.84; 95% CI, 2.57 to 9.15; P<0.001). These results were validated in an independent cohort. On sequential monitoring of minimal residual disease, relapse was reliably predicted by a rising level of NPM1-mutated transcripts. Although mutations associated with preleukemic clones remained detectable during ongoing remission after chemotherapy, NPM1 mutations were detected in 69 of 70 patients at the time of relapse and provided a better marker of disease status. CONCLUSIONS: The presence of minimal residual disease, as determined by quantitation of NPM1-mutated transcripts, provided powerful prognostic information independent of other risk factors. (Funded by Bloodwise and the National Institute for Health Research; Current Controlled Trials number, ISRCTN55675535.).

Microdroplet digital PCR: detection and quantitation of biomarkers in archived tissue and serial plasma samples in patients with lung cancer.

INTRODUCTION: There is much interest in the use of noninvasive biomarkers in the management of lung cancer, particularly with respect to early diagnosis and monitoring the response to intervention. Cell-free tumor DNA in patients with cancer has been shown to hold potential as a noninvasive biomarker, in which the response to treatment may be evaluated using a blood test only. Multiple technologies have been suggested as being appropriate to measure cell-free tumor DNA. Microdroplet digital polymerase chain reaction (mdPCR) has a number of attributes that suggest it may be a useful tool for detecting clinically relevant genetic events. It offers precise and accurate quantitation of mutant alleles, including rare variants. METHODS: We evaluate the performance of mdPCR in the analysis of DNA extracted from reference standards, tumor biopsies, and patient plasma. RESULTS: The potential of mdPCR to detect clinically relevant mutations is demonstrated, in both formalin-fixed paraffin-embedded material and plasma. Furthermore, we show that mdPCR can be used to track changes in peripheral blood biomarkers in response to treatment and to detect the emergence of drug-resistant clones. CONCLUSIONS: MdPCR has potential as a tool to detect and quantify tumor-derived mutational events in cell-free DNA from patients with lung cancer.

Maxillary dental arch changes following the leveling and alignment stage with lingual and labial orthodontic appliances: a preliminary report of a randomized controlled trial.

BACKGROUND: No randomized controlled trial has tried to compare transverse dental arch changes between the lingual and labial orthodontic fixed appliances in the early stage of treatment. OBJECTIVE: To compare upper dental arch changes between lingual and labial fixed orthodontic appliances after leveling and alignment. DESIGN, SETTING: Parallel-groups randomized controlled trial on patients with class I moderate crowding teeth treated at the University of Al-Baath Dental School in Hamah, Syria. PARTICIPANTS: About 102 patients with crowded teeth and class I malocclusion were evaluated and 58 patients fulflled the inclusion criteria. Randomization was performed using computer generated tables; allocation was concealed using sequentially numbered opaque and sealed envelopes. About 52 participants were analyzed (mean age 21.5 ± 3.2 years). They were randomly distributed into two groups with 26 patients in each (1:1 allocation ratio). INTERVENTION: Lingual vs labial fixed orthodontic appliances were used. MAIN OUTCOME MEASURE: Intercanine width, interpremolar width, intermolar width, and arch length were measured on study models before brackets' placement (T1), at the end of leveling and alignment stage (T2). RESULTS: Statistically significant increase was detected in the intercanine width in the lingual group (1.99 mm, p < 0.001) and in the labial group (1.22 mm, p < 0.001). The interpremolar width had a significant decrease in the lingual group (-0.70 mm, p < 0.001), whereas there was a significant increase in this width in the labial group (1.73 mm, p < 0.001). A significant decrease in intermolar width was detected in the lingual group (-0.79 mm, p < 0.001) whereas a significant increase was observed in the labial group (0.81 mm, p < 0.001). The differences between the two groups were significant for all comparisons (p < 0.001). CONCLUSION: The labial appliance produced a significant increase in all horizontal transverse arch dimensions, whereas in the lingual appliance group the intercanine width increased significantly in conjunction with a significant narrowing of posterior segments. FUNDING: The University of Al-Baath Postgraduate Research Budget (UBDS-00786223-PG).

Development and validation of a stability-indicating assay including the isolation and characterization of degradation products of metaxalone by LC-MS.

A stability-indicating reverse-phase high-performance liquid chromatography-mass spectrometric method was developed and validated for the assay of metaxalone through forced degradation under acidic, alkaline, photo, oxidative and peroxide stress conditions. Separation of degradation products was accomplished on a reverse-phase Phenomenex C18 (250 × 4.6 mm, 5 µm) column thermostated at 25 °C using 10 mM aqueous ammonium acetate: methanol (35:65 v/v) as mobile phase in an isocratic mode of elution. The eluents were detected at 275 nm by photo diode array detector and mass detectors connected in series. Two unknown base hydrolysis products of metaxalone were identified and characterized as (a) methyl 3-(3,5-dimethylphenoxy)-2-hydroxypropylcarbamate and (b) 1-(3,5-dimethylphenoxy)-3-aminopropan-2-ol by MS, (1)H NMR and FTIR spectroscopy. The method was validated as per International Conference on Harmonization guidelines and metaxalone was selectively determined in presence of its degradation impurities, demonstrating its stability-indicating nature.

Speech performance and oral impairments with lingual and labial orthodontic appliances in the first stage of fixed treatment.

OBJECTIVES: To compare (1) speech performance based on an auditive analysis and sonagraphy and (2) levels of oral impairment between fixed lingual and labial orthodontic appliances. MATERIALS AND METHODS: Thirty-four patients with Class I division 1 malocclusion and moderate crowding of upper teeth were distributed randomly into two groups. Seventeen patients in group A (mean age: 20.6 years; standard deviation [SD]: 2.9 years) were treated with fixed lingual appliances (Stealth®, AO, Sheboygan, Wisc), whereas 17 patients in group B (mean age: 21.8 years; SD: 3.3 years) were treated with conventional fixed labial appliances. Speech performance was tested using spectrographic analysis of fricative /s/ sound before, immediately after (T1), 1 month after, and 3 months after bracket placement. The levels of oral impairment were assessed using standardized questionnaires. RESULTS: A significant deterioration in articulation was recorded at all assessment times in group A but only at T1 in group B. Significant intergroup differences were recorded at all assessment times (P < .001). Speech difficulties were significantly higher in the lingual brackets group after 1 month of bracket placement (P < .001). Soft tissue irritation and chewing difficulty were significantly higher in the lingual appliance group after 24 hours of bracket placement (P < .001). CONCLUSIONS: The lingual appliance is more problematic than the labial one in terms of speech articulation. Although patients with both appliances suffered from different degrees of oral impairment, patients with lingual appliances had more untoward effects, particularly during the first month of treatment.