Can Condylectomy Alone Achieve Facial Symmetry in Patients With Hemimandibular Hyperplasia (Condylar Hyperplasia Type 2)?

The purpose of the present study was to evaluate the 3-dimensional orofacial changes occurring after proportional condylectomy in patients with unilateral condylar hyperplasia type 2 (hemimandibular hyperplasia). Eight patients underwent proportional condylectomy that was not followed by orthognathic surgery or orthodontic treatment for at least 1 year. The precondylectomy and postcondylectomy photographs and radiographs were analyzed cephalometrically and compared. The average length of the condylar segment removed was 13 mm and this resulted in almost equal heights of the ramus-condyle units of both sides. Evaluations in the vertical plane improved after surgery; however, when the preoperative asymmetry was significant, the residual asymmetry continued to be notable after condylectomy. Transverse plane evaluations improved after condylectomy, and chin position was satisfactorily centralized in all patients. In the horizontal plane, mandibular setback occurred, and this was considered favorable when the preoperative skeletal profile was class III, whereas the opposite was when the patient was class I before surgery. The occlusion improved gradually over the postoperative months by the intrusion on the affected side and extrusion on the unaffected side into a bilaterally balanced posterior contacts with residual anterior open bite. In conclusion, condylar hyperplasia type 2 patients with mild asymmetry and low esthetic demands can benefit from proportional condylectomy as the sole treatment to both stop the hyperplastic condylar growth and improve the asymmetry to some extent. Surgeons should be able to predict the change that is expected to occur after proportional condylectomy and discuss this with the patient before surgery.

Permanent Tooth Agenesis and Associated Dental Anomalies among Orthodontically Treated Children.

(1) Background: Tooth agenesis is one of the most common developmental dental anomalies often affecting the maxillary incisors area and premolar regions. (2) Purpose: The aim of this study was to assess the prevalence and distribution of permanent tooth agenesis and the associated dental abnormalities among orthodontically treated children. (3) Materials and Methods: This study was carried out utilizing 3000 pretreatment records of children who underwent orthodontic treatment, 1780 (59%) females and 1220 (41%) males, aged 10-25 years (mean age 15 years). Tooth agenesis and other dental anomalies were surveyed using their panoramic radiographs, according to gender, pattern, and location. The level of statistical significance was set at p < 0.05 using t-test or Chi-Square tests. (4) Results: The total number of missing teeth, excluding third molars, was 518 (17%) found in 326 (11%) children. The majority were the maxillary lateral incisors, which was 176 teeth (34%) (p < 0.05). Of them, 111 (63%) were in females, and 65 (37%) were in males. The second most common missing tooth was mandibular second premolars, which was 137 teeth (26%), followed by missing 73 (14%) maxillary second premolars. Impacted teeth had the highest associated dental anomaly prevalence (14.3%), while transposition showed the lowest anomaly prevalence (0.5%). (5) Conclusions: A prevalence of 11% for tooth agenesis was detected in this study. More teeth were missing in the maxilla compare with the mandible. A significant association was found between missing maxillary lateral incisors and missing premolars (p < 0.05). Associated dental anomalies included an increased number of peg-shaped maxillary lateral incisors, palatally displaced and impacted maxillary canines, ectopic teeth, and infra-occluded (submerged) primary second molars.

Immune senescence in aged APP/PS1 mice.

Objectives: To evaluate the linkage between age and deficits in innate and adaptive immunity which heralds both Alzheimer's disease (AD) onset and progression. The pathobiological events which underlie and tie these outcomes remain not fully understood. Methods: To investigate age-dependent immunity in AD, we evaluated innate and adaptive immunity in coordinate studies of regulatory T cell (Treg) function, T cell frequencies, and microglial integrity. These were assessed in blood, peripheral lymphoid tissues, and the hippocampus of transgenic (Tg) amyloid precursor protein/presenilin 1 (APP/PS1) against non-Tg mice. Additionally, immune arrays of hippocampal tissue were performed at 4, 6, 12, and 20 months of age. Results: APP/PS1 mice showed progressive impairment of Treg immunosuppressive function with age. There was partial restoration of Treg function in 20-month-old mice. Ingenuity pathway analyses of hippocampal tissues were enriched in inflammatory, oxidative, and cellular activation pathways that paralleled advancing age and AD-pathobiology. Operative genes in those pathways included, but were not limited to triggering receptor on myeloid cells 1 (TREM1), T helper type 1 (Th1), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways. Interleukin-17 (IL-17), nitric oxide, acute phase, and T cell receptor signaling pathways were also perturbed. Significant inflammation was observed at 6- and 12-months. However, at 20-months, age associated partial restoration of Treg function reduced inflammatory phenotype. Conclusions: Impaired Treg function, inflammation and oxidative stress were associated with AD pathology. Age associated partial restoration of Treg function in old mice reduced the hippocampal inflammatory phenotype. Restoring Treg suppressive function can be a therapeutic modality for AD.

Clinical biomarkers for Lewy body diseases.

Synucleinopathies are a group of neurodegenerative disorders characterized by pathologic aggregates of neural and glial α-synuclein (α-syn) in the form of Lewy bodies (LBs), Lewy neurites, and cytoplasmic inclusions in both neurons and glia. Two major classes of synucleinopathies are LB disease and multiple system atrophy. LB diseases include Parkinson's disease (PD), PD with dementia, and dementia with LBs. All are increasing in prevalence. Effective diagnostics, disease-modifying therapies, and therapeutic monitoring are urgently needed. Diagnostics capable of differentiating LB diseases are based on signs and symptoms which might overlap. To date, no specific diagnostic test exists despite disease-specific pathologies. Diagnostics are aided by brain imaging and cerebrospinal fluid evaluations, but more accessible biomarkers remain in need. Mechanisms of α-syn evolution to pathologic oligomers and insoluble fibrils can provide one of a spectrum of biomarkers to link complex neural pathways to effective therapies. With these in mind, we review promising biomarkers linked to effective disease-modifying interventions.

Amyloid-ß specific regulatory T cells attenuate Alzheimer's disease pathobiology in APP/PS1 mice.

BACKGROUND: Regulatory T cells (Tregs) maintain immune tolerance. While Treg-mediated neuroprotective activities are now well-accepted, the lack of defined antigen specificity limits their therapeutic potential. This is notable for neurodegenerative diseases where cell access to injured brain regions is required for disease-specific therapeutic targeting and improved outcomes. To address this need, amyloid-beta (Aß) antigen specificity was conferred to Treg responses by engineering the T cell receptor (TCR) specific for Aß (TCRAß). The TCRAb were developed from disease-specific T cell effector (Teff) clones. The ability of Tregs expressing a transgenic TCRAß (TCRAß -Tregs) to reduce Aß burden, transform effector to regulatory cells, and reverse disease-associated neurotoxicity proved beneficial in an animal model of Alzheimer's disease. METHODS: TCRAß -Tregs were generated by CRISPR-Cas9 knockout of endogenous TCR and consequent incorporation of the transgenic TCRAb identified from Aß reactive Teff monoclones. Antigen specificity was confirmed by MHC-Aß-tetramer staining. Adoptive transfer of TCRAß-Tregs to mice expressing a chimeric mouse-human amyloid precursor protein and a mutant human presenilin-1 followed measured behavior, immune, and immunohistochemical outcomes. RESULTS: TCRAß-Tregs expressed an Aß-specific TCR. Adoptive transfer of TCRAß-Tregs led to sustained immune suppression, reduced microglial reaction, and amyloid loads. 18F-fluorodeoxyglucose radiolabeled TCRAß-Treg homed to the brain facilitating antigen specificity. Reduction in amyloid load was associated with improved cognitive functions. CONCLUSIONS: TCRAß-Tregs reduced amyloid burden, restored brain homeostasis, and improved learning and memory, supporting the increased therapeutic benefit of antigen specific Treg immunotherapy for AD.

Pharmacological Inhibition of MMP3 as a Potential Therapeutic Option for COVID-19 Associated Acute Respiratory Distress Syndrome.

The high mortality of coronavirus disease 2019 (COVID-19) patients is due to their progression to cytokine-associated organ injuries, primarily the acute respiratory distress syndrome (ARDS). The uncertainties in the molecular mechanisms leading to the switch from the early virus infection to the advanced stage ARDS is a major gridlock in therapeutic development to reduce mortality. Previous studies in our laboratory have identified matrix metalloprotease-3 (MMP3) as an important mediator of bacterial lipopolysaccharide (LPS)-induced ARDS, particularly in the exudative phase. Our studies have also reported elevated plasma MMP3 activity levels in the ARDS patients and that inhibition of MMP3 can reduce the severity of LPS-induced ARDS in mice. Given these observations, targeting MMP3 could be a potential option to treat COVID-19 patients with ARDS, and measurement of MMP3 activity in the plasma may serve as a biomarker for the early detection of ARDS in COVID-19 patients.

Cisatracurium attenuates LPS-induced modulation of MMP3 and junctional protein expression in human microvascular endothelial cells.

Acute respiratory distress syndrome (ARDS) is a life-threatening form of acute lung injury (ALI) associated with hypoxemic lung damage and inflammation. Matrix metalloproteinase protein-3 (MMP3 or Stromelysin-1) is known to promote vascular injury in ALI/ARDS. Cisatracurium, a nicotinic neuromuscular blocker, is used in ARDS patients to decrease mechanical ventilator dyssynchrony, increase oxygenation, and improve mortality. However, the magnitude and the underlying mechanisms of these potential benefits of cisatracurium remains unclear. We investigated the effect of cisatracurium on lipopolysaccharide-induced MMP3 expression in human microvascular endothelial cells. In our results, cisatracurium treatment significantly decreased LPS-induced MMP3 expression and increased expression of cell junction proteins such as vascular endothelial cadherin (VE-cadherin) and claudin-5.

The Incidence and Nature of Malpractice Claims against Dentists for Orthodontic Treatment with Periodontal Damage in Israel during the Years 2005-2018-A Descriptive Study.

In recent years, dental malpractice claims have increased dramatically worldwide. The purpose of the present study is to analyze claims related to orthodontic treatment involving periodontal problems that resulted in legal decisions in Israel. This study analyzed legal claims registered by Medical Consultants International (MCI) between 2005 and 2018. Only closed cases of orthodontic claims involving periodontal problems in which a decision was made were included. The parameters studied included patients' demographic data, the main reasons of the claim, and complications. Statistical significance was found for aesthetic damage, which was more common in claims of females (p = 0.035) and in older claims (p = 0.004); tooth damage was more common in claims of older patients (p = 0.032); violation of autonomy was higher in private practice (p = 0.047) and in more recent claims (p = 0.001). As orthodontic treatment is becoming more popular in older patients, and as lawsuit claims become more common in recent years, the orthodontists should always analyze and document the periodontal status of their patients before and during treatment in order to maintain professional practice and avoid future claims.

Mandibular Symmetrical Bilateral Canine-Lateral Incisors Transposition: Its Early Diagnosis and Treatment Considerations.

Bilateral mandibular tooth transposition is a relatively rare dental anomaly caused by distal migration of the mandibular lateral incisors and can be detected in the early mixed dentition by radiographic examination. Early diagnosis and interceptive intervention may reduce the risk of possible transposition between the mandibular canine and lateral incisor. This report illustrates the orthodontic management of bilateral mandibular canine-lateral incisor transposition. Correct positioning of the affected teeth was achieved on the left side while teeth on the right side were aligned in their transposed position. It demonstrates the outcome of good alignment of the teeth in the dental arch.