Local myogenic pulp-derived cell injection enhances craniofacial muscle regeneration in vivo.

OBJECTIVES: To enhance myogenic differentiation in pulp cells isolated from extracted premolars by epigenetic modification using a DNA demethylation agent, 5-aza-2'-deoxycytidine (5-Aza), and to evaluate the potent stimulatory effect of 5-Aza-treated pulp cell injection for craniofacial muscle regeneration in vivo. SETTING AND SAMPLE POPULATION: Pulp cells were isolated from premolars extracted for orthodontic purposes from four adults (age range, 18-22.1 years). MATERIAL AND METHODS: Levels of myogenic differentiation and functional contraction response in vitro were compared between pulp cells with or without pre-treatment of 5-Aza. Changes in muscle regeneration in response to green fluorescent protein (GFP)-labelled myogenic pulp cell injection in vivo were evaluated using a cardiotoxin (CTX)-induced muscle injury model of the gastrocnemius as well as the masseter muscle in mice. RESULTS: Pre-treatment of 5-Aza in pulp cells stimulated myotube formation, myogenic differentiation in terms of desmin and myogenin expression, and the level of collagen gel contraction. The local injection of 5-Aza pre-treated myogenic pulp cells was engrafted into the host tissue and indicated signs of enhanced muscle regeneration in both the gastrocnemius and the masseter muscles. CONCLUSION: The epigenetic modification of pulp cells from extracted premolars and the local injection of myogenic pulp cells may stimulate craniofacial muscles regeneration in vivo.

Histomorphometric evaluation of maxillary molar roots and surrounding periodontium following molar intrusion in rats.

OBJECTIVES: To investigate periodontal tissue changes during and after molar intrusion in rats. SETTING AND SAMPLE POPULATION: The Department of Orthodontics at Yonsei University. Thirty 12-week-old male rats were assigned to 1 control and 5 experimental groups (n = 5 each). MATERIALS AND METHODS: In the experimental groups, two maxillary molars were intruded for 2 weeks; the control group underwent the same procedures without the intrusion force. After 2 weeks of intrusion, rats in one of the experimental groups and in the control group were killed. In the other four experimental groups, the new molar positions were either retained or not retained with an occlusal bite block for 1 or 2 weeks prior to euthanization. Histomorphometric analysis was performed for sulcus depth, osteoclast number per unit alveolar bone length, and root resorption area per unit root surface length. RESULTS: Sulcus depth increased during intrusion (P < 0.05), but decreased after 2 weeks of retention (P < 0.05). The number of osteoclasts increased during intrusion (P < 0.05), but subsequently decreased regardless of the retention regime (P < 0.05). Root resorption area increased after molar intrusion, irrespective of the retention regimen, relative to that of the control group (P < 0.05) and was the greatest after 2 weeks of retention. CONCLUSION: These results indicated that root resorption occurred during and after molar intrusion and that the surrounding periodontium remodeled accordingly as tooth positions were altered, regardless of retention regime.

Assessment of masticatory function in patients with non-sagittal occlusal discrepancies.

Non-sagittal occlusal discrepancies such as posterior cross-bite and anterior openbite are common types of malocclusion, but studies on masticatory function related to those malocclusions have been scarce. The aim of this study was to quantify the masticatory performance in patients with non-sagittal discrepancies compared to those with normal occlusion, using both objective and subjective measures. Maximum bite force and contact area using Dental Prescale(®) system as a static objective assessment, Mixing Ability Index (MAI) as a dynamic objective evaluation and food intake ability (FIA) as a subjective assessment were analysed from 21 people in normal occlusion (Group N) and 64 patients with posterior cross-bite (Group C), anterior openbite (Group O) or both (Group B). The differences of the maximum bite force, the contact area, the MAI and the FIA were compared, and their correlations were figured out. The non-sagittal malocclusion groups showed lower values in the maximum bite force, the contact area, the MAI and the FIA compared to those in the normal group (P < 0·0001). Compared to Group N, Groups C, O and B showed 61·5%, 42·1% and 40·1% of the maximum bite force, and 84%, 84% and 76% of hard food FIA, respectively. However, there were no significant differences among Groups C, O and B. The MAI showed higher correlation with the FIA (r = 0·38, P < 0·01), than with the maximum bite force and the contact area (both r = 0·24, P < 0·5). These results revealed that masticatory function in patients with non-sagittal discrepancies is significantly reduced both objectively and subjectively.

Increased breast cancer risk for patients with multiple sclerosis: a nationwide population-based cohort study.

BACKGROUND AND PURPOSE: Studies have suggested that multiple sclerosis (MS) might be linked to an overall reduced cancer rate, but a positive relationship is also found for several types of cancer. This study determines whether MS is associated with cancer risk in Taiwan. METHODS: Data from the National Health Insurance System of Taiwan were used to assess this issue. The MS cohort included 1292 patients, and each patient was randomly frequency-matched with four participants without MS, based on their age, sex and index year (control cohort). Cox proportional hazards regression analysis was conducted to estimate the influence of MS on cancer risk. RESULTS: A significantly higher risk of developing overall cancer was found amongst the MS cohort compared with the control cohort [adjusted hazard ratio (HR) 1.85, 95% confidence interval (CI) 1.26-2.74], as well as breast cancer (adjusted HR 2.23, 95% CI 1.11-4.46). CONCLUSIONS: The nationwide population-based cohort study revealed that Taiwanese patients with MS have a higher risk of developing overall cancer types and breast cancer in particular.

Genome-wide mapping of gene-microbe interactions in the murine lung microbiota based on quantitative microbial profiling.

BACKGROUND: Mammalian lungs comprise a complex microbial ecosystem that interacts with host physiology. Previous research demonstrates that the environment significantly contributes to bacterial community structure in the upper and lower respiratory tract. However, the influence of host genetics on the makeup of lung microbiota remains ambiguous, largely due to technical difficulties related to sampling, as well as challenges inherent to investigating low biomass communities. Thus, innovative approaches are warranted to clarify host-microbe interactions in the mammalian lung. RESULTS: Here, we aimed to characterize host genomic regions associated with lung bacterial traits in an advanced intercross mouse line (AIL). By performing quantitative microbial profiling (QMP) using the highly precise method of droplet digital PCR (ddPCR), we refined 16S rRNA gene amplicon-based traits to identify and map candidate lung-resident taxa using a QTL mapping approach. In addition, the two abundant core taxa Lactobacillus and Pelomonas were chosen for independent microbial phenotyping using genus-specific primers. In total, this revealed seven significant loci involving eight bacterial traits. The narrow confidence intervals afforded by the AIL population allowed us to identify several promising candidate genes related to immune and inflammatory responses, cell apoptosis, DNA repair, and lung functioning and disease susceptibility. Interestingly, one genomic region associated with Lactobacillus abundance contains the well-known anti-inflammatory cytokine Il10, which we confirmed through the analysis of Il10 knockout mice. CONCLUSIONS: Our study provides the first evidence for a role of host genetic variation contributing to variation in the lung microbiota. This was in large part made possible through the careful curation of 16S rRNA gene amplicon data and the incorporation of a QMP-based methods. This approach to evaluating the low biomass lung environment opens new avenues for advancing lung microbiome research using animal models.

Interfacial alloy hydride destabilization in Mg/Pd thin films.

Recently, a large increase in the equilibrium hydrogen pressure has been reported for MG thin films capped with a Pd layer. We show that this increase is due to intermixing of Mg and Pd, as opposed to a strain effect as previously claimed. Transmission electron microscopy and depth profiling x-ray photoemission spectroscopy are used to directly measure interfacial intermixing between Mg and Pd, and we find that intermixing and equilibrium hydrogen pressure both increase with annealing. We present a thermodynamic model of the effect of alloying on equilibrium pressure, and find that the observed equilibrium pressure increase is consistent with the observed thickness of the intermixed region, which is of the order of a few nm. We also show that stress measured during hydrogenation corresponds to a negligible increase in equilibrium pressure.

Deep Learning-Based Prediction of the 3D Postorthodontic Facial Changes.

With the increase of the adult orthodontic population, there is a need for an accurate and evidence-based prediction of the posttreatment face in 3 dimensions (3D). The objectives of this study are 1) to develop a 3D postorthodontic face prediction method based on a deep learning network using the patient-specific factors and orthodontic treatment conditions and 2) to validate the accuracy and clinical usability of the proposed method. Paired sets (n = 268) of pretreatment (T1) and posttreatment (T2) cone-beam computed tomography (CBCT) of adult patients were trained with a conditional generative adversarial network to generate 3D posttreatment facial data based on the patient's gender, age, and the changes of upper (ΔU1) and lower incisor position (ΔL1) as input. The accuracy was calculated with prediction error and mean absolute distances between real T2 (T2) and predicted T2 (PT2) near 6 perioral landmark regions, as well as percentage of prediction error less than 2 mm using test sets (n = 44). For qualitative evaluation, an online survey was conducted with experienced orthodontists as panels (n = 56). Overall, PT2 indicated similar 3D changes to the T2 face, with the most apparent changes simulated in the perioral regions. The mean prediction error was 1.2 ± 1.01 mm with 80.8% accuracy. More than 50% of the experienced orthodontists were unable to distinguish between real and predicted images. In this study, we proposed a valid 3D postorthodontic face prediction method by applying a deep learning algorithm trained with CBCT data sets.

Spectral entropy monitoring allowed lower sevoflurane concentration and faster recovery in children.

BACKGROUND: Anesthetic titration using spectral entropy monitoring reduces anesthetic requirements and shortens recovery in adult surgical patients. This study was performed to evaluate the effect of entropy monitoring on end-tidal sevoflurane concentration and recovery characteristics in pediatric patients undergoing sevoflurane anesthesia. METHODS: Seventy-eight children (aged 3-12 years) scheduled for a tonsillectomy and/or an adenoidectomy were randomly divided into one of two groups: standard practice (Standard) or entropy-guided (Entropy). In the Standard group, sevoflurane was adjusted to maintain the heart rate and systolic blood pressure (BP) within 20% of the baseline values. In the Entropy group, sevoflurane was adjusted to achieve a state entropy of 40-50. We compared the entropy values, end-tidal sevoflurane concentration and recovery times between groups. RESULTS: During maintenance of anesthesia, the entropy and BP values were higher in the Entropy group (P<0.05). The end-tidal sevoflurane concentration during maintenance was lower in the Entropy group (2.2 (0.3) vol%) compared with the Standard group (2.6 (0.4) vol%) (P<0.05). Recovery times were faster in the Entropy group (P<0.05). CONCLUSIONS: Compared with standard practice, we found that entropy-guided anesthetic administration was associated with a reduced sevoflurane concentration and a slightly faster emergence and recovery in 3-12-year-old children.

Effect of remifentanil on oculocardiac reflex in paediatric strabismus surgery.

BACKGROUND: Rapidly acting narcotics enhance the degree of bradycardia due to the oculocardiac reflex (OCR) elicited by extraocular muscle (EOM) tension during strabismus surgery. We evaluated and compared the effects of remifentanil and sevoflurane on OCR during paediatric strabismus surgery. METHODS: One hundred and twenty children, 1-9 years old, undergoing elective strabismus surgery, were randomly assigned to receive sevoflurane or remifentanil. No anticholinergic prophylaxis was administered. Anaesthesia was induced using ketamine 1.0 mg/kg or midazolam 0.15 mg/kg with 66% N(2)O in O(2). Laryngeal mask airways were placed with rocuronium 0.5 mg/kg. Anaesthesia was maintained with sevoflurane 2.0-3.0 vol% with 66% N(2)O in O(2) or remifentanil 0.75 mug/kg over 1 min and followed by the continuous infusion of remifentanil 0.5 mug/kg/min with 66% N(2)O in O(2). Heart rate (HR) and blood pressure (BP) were measured and compared. OCR was defined as a reduction in HR of >20% induced by traction of an EOM. RESULTS: During anaesthesia, HR and BP were maintained at a lower level in the remifentanil group than in the sevoflurane group (each, P<0.05). The mean percent change in HR (-23.3+/-17.0% vs. -11.2+/-13.0%; P<0.05) and the incidence of OCR (58.3% vs. 28.3%; P<0.05) following traction of an EOM were higher in the remifentanil group than in the sevoflurane group. CONCLUSIONS: Remifentanil enhanced the degree of bradycardia due to OCR as compared with sevoflurane during paediatric strabismus surgery.

The pattern and prevalence of hypodontia in Koreans.

OBJECTIVE: The objective of this study was to evaluate the pattern and prevalence of hypodontia in the Korean population along with its association with the dental and skeletal polymorphisms. SUBJECTS AND MATERIALS: The diagnostic materials including casts, panoramic radiographs, and lateral cephalograms of 1622 Korean subjects (611 males, 1011 females) were used to evaluate the pattern and prevalence of hypodontia as well as its association with the congenital absence of the third molar. The changes in the tooth size and skeletal characteristics of the hypodontia group were evaluated using cast/cephalometric analysis and compared with the standard values of normal occlusion in Koreans. RESULTS: The prevalence of hypodontia in Koreans was 11.2%. The mandibular lateral incisor and second premolar were the most frequently absent. Congenital absence of the third molar was observed more frequently in the hypodontia group than in the non-hypodontia group. The prevalence of hypodontia in Class III malocclusion was significantly higher than in Class I or Class II malocclusion. CONCLUSION: The pattern and prevalence of hypodontia can vary in different ethnic groups. In Koreans, the special features of hypodontia were its association with a higher level of congenital missing third molars and skeletal Class III malocclusion.

Effects of occlusal stimuli on alveolar/jaw bone formation.

Occlusion is known to influence the growth and development of the craniofacial complex. However, the consequences of occlusal hypofunction, or its recovery, on the amount of formation and development of alveolar bone and the jaw are not fully understood. Therefore, the present study was designed to elucidate the relationship between the occlusal stimuli and alveolar and jaw bone growth by the use of a hypofunction/recovered occlusal function model in growing rats. Bone histomorphometric analyses, including bone apposition rate and mineral apposition rate, were evaluated in double-labeled frontal sections of mandibular second molars. Results showed that occlusal hypofunction significantly suppressed alveolar and jaw bone formation compared with that in animals growing normally (p < 0.05). However, recovered occlusal function induced an enhancement in jaw bone formation. These results indicate the influence of occlusal function on alveolar and jaw bone formation during the growth period.

Long-term changes in mandibular and facial widths after mandibular setback surgery using intraoral vertical ramus osteotomy.

This study was performed to evaluate the long-term changes in mandibular width, lower facial width, and ramus angulation after intraoral vertical ramus osteotomy (IVRO) and to identify the factors influencing these changes. This retrospective study included 53 consecutive patients with mandibular prognathism who underwent IVRO with (n=33) or without (n=20) Le Fort I osteotomy. Postero-anterior cephalograms and frontal facial photographs obtained before, 1 month after, and at least 24 months after IVRO were used for measurements. A linear mixed model and paired t-tests were used to analyze temporal changes and the associated influencing factors. The mandibular width increased immediately after surgery (P<0.05), but decreased continuously thereafter. The ramus angulation showed negligible change within the first month (P>0.05) and decreased thereafter up to approximately 36 months. The amounts of mandibular setback and posterior impaction and the length of time postoperative influenced these changes. The lower facial width changed, although inconsistently, within 3mm over time (P>0.05). In conclusion, the mandibular width increased after IVRO but seemed to normalize within approximately 3 years. The lower facial width did not reflect underlying skeletal changes. Therefore, long-term transverse changes after IVRO can be considered clinically irrelevant.

Prognosis of Kidney Transplant Recipients With Pretransplantation Malignancy: A Nationwide Population-Based Cohort Study in Taiwan.

OBJECTIVE: The objective of this study was to evaluate the prognosis of kidney transplant recipients with pretransplantation malignancy and the incidence of recurrent malignancy in kidney transplant recipients using claims data from Taiwan's universal health insurance program. METHOD: A total of 4350 transplant recipients were retrospectively analyzed. The rates of pretransplantation or recurrent malignancy, which was defined by their inclusion in the catastrophic illness patient registry using the International Classification of Diseases, 9th Revision, were evaluated. Cox proportional hazard regression and Kaplan-Meier curves were used for the analyses. RESULTS: In total, there were 4350 kidney transplant recipients, 52.1% of patients were male, the mean age at transplantation was 45.8 years old, and the percentages of diabetes mellitus, hypertension, hepatitis B viral infection, and hepatitis C viral infection were 14%, 63.2%, 4.2%, and 2.4%, respectively. There were 95 patients (2.2%) with pretransplantation malignancy. The top 3 pretransplantation malignancies, in decreasing order, were urinary tract, kidney, and breast cancers. After kidney transplantation, 10 recipients had recurrent cancer. The overall cancer recurrence rate was 10.5%. These 10 cancers included urothelial carcinoma (n = 5), renal cell carcinoma (n = 3), breast cancer (n = 1), and thyroid cancer (n = 1). Eleven recipients had a secondary cancer. Patients without pretransplantation and post-transplantation malignancy had the best survival. Patients with pretransplantation malignancy had a greater occurrence of cancers and increased mortality regardless of whether or not they had recurrence of cancer. CONCLUSION: Our results suggest the higher risk of cancer, recurrent or secondary, and mortality after kidney transplantation. Adequate waiting time before transplantation and preventive strategies are strongly suggested in kidney transplant recipients with cancer history.

Previous history of tuberculosis is associated with rheumatoid arthritis.

BACKGROUND: Previous studies have suggested that mycobacterial infections could trigger autoimmune diseases, including rheumatoid arthritis (RA). OBJECTIVE: To explore the association between previous tuberculosis (TB) and RA. METHODS: We conducted a case-control study using data obtained from the National Health Insurance (NHI) system of Taiwan. We identified 26 535 adults with RA from 2002 to 2011, with the date of diagnosis as the index date. This number was randomly selected and frequency-matched four times by age, sex and the year of index date from among non-RA individuals. Odds ratios (ORs) of RA were calculated for associations with TB. RESULTS: Compared with controls, RA patients had a crude OR of 1.77 for TB (95%CI 1.61-1.94). The strength of the association between RA and TB remained at the same level after controlling for other potential risk factors (adjusted OR 1.73, 95%CI 1.57-1.90), although RA patients tended to have a higher prevalence of hypertension, coronary artery disease and kidney disease. CONCLUSION: TB was much more prevalent in RA patients than in control subjects. Prospective cohort studies are required to establish a causal relationship between previous TB and RA.

Indium-111-labeled leukocyte scan in detection of synthetic vascular graft infection: the effect of antibiotic treatment.

To determine the sensitivity and specificity of the indium-111-(111In) labeled leukocyte scan for prosthetic vascular graft infection in patients treated with antibiotic therapy, a retrospective study was performed. Of 41 consecutive 111In-labeled leukocyte scans performed to evaluate possible vascular graft infection, 23 scans were performed in patients treated with antibiotics. The average duration of antibiotic therapy was 21 days. Twelve positive and 11 negative scans for graft infection were found. By surgical and autopsy correlation of all positive cases, and clinical correlation (of all negative cases), there were 10 true-positive, 11 true-negative, 2 false-positive, and no false-negative scans for graft infections, for an overall sensitivity of 100% and specificity of 85%.

Postatelectatic ventilation-perfusion mismatch simulating a pulmonary embolus.

Ventilation-perfusion imaging was performed on a patient with chronic intermittent atelectasis of the right lung and revealed a mismatch simulating a pulmonary embolus in the right lung. A pulmonary arteriogram revealed no evidence of embolic disease; however, there was reduced capillary phase opacification of the right lung and increased pulmonary artery pressure. The findings are consistent with an isolated right pulmonary artery hypertension secondary to prolonged atelectasis causing an apparent mismatch on the ventilation-perfusion scan.

Canines as sentinel species for assessing chronic exposures to air pollutants: part 1. Respiratory pathology.

A complex mixture of air pollutants is present in the ambient air in urban areas. People, animals, and vegetation are chronically and sequentially exposed to outdoor pollutants. The objective of this first of 2 studies is to evaluate by light and electron microscopy the lungs of Mexico City dogs and compare the results to those of 3 less polluted cities in MEXICO: One hundred fifty-two clinically healthy stray mongrel dogs (91 males/61 females), including 43 dogs from 3 less polluted cities, and 109 from southwest and northeast metropolitian Mexico City (SWMMC, NEMMC) were studied. Lungs of dogs living in Mexico City and Cuernavaca exhibited patchy chronic mononuclear cell infiltrates along with macrophages loaded with particulate matter (PM) surrounding the bronchiolar walls and extending into adjacent vascular structures; bronchiolar epithelial and smooth muscle hyperplasia, peribronchiolar fibrosis, microthrombi, and capillary and venule polymorphonuclear leukocytes (PMN) margination. Ultrafine PM was seen in alveolar type I and II cells, endothelial cells, interstitial macrophages (Mtheta), and intravascular Mtheta-like cells. Bronchoalveolar lavage showed significant numbers of alveolar macrophages undergoing proliferation. Exposure to complex mixtures of pollutants-predominantly particulate matter and ozone-is causing lung structural changes induced by the sustained inflammatory process and resulting in airway and vascular remodeling and altered repair. Cytokines released from both, circulating inflammatory and resident lung cells in response to endothelial and epithelial injury may be playing a role in the pathology described here. Deep concern exists for the potential of an increasing rise in lung diseases in child populations exposed to Mexico City's environment.

Isolated lymphoma of genitourinary tract and adrenals.

With the routine use of computed tomographic imaging, intrinsic involvement of the genitourinary tract in newly diagnosed non-Hodgkin's lymphoma is seen in as many as 10 percent of patients. Incidental discovery of an extranodal, extra-lymphatic lesion in the genitourinary tract without clinical or radiographic evidence of disease elsewhere, however, is an uncommon occurrence. The clinical presentation and imaging findings in 4 patients with initial manifestation of lymphoma isolated to the kidney, ureter, bladder, and adrenals, respectively, are presented. These patients had no evidence of lymphoma elsewhere, and imaging studies mimicked the more common neoplasms affecting these organs.

Hemorrhagic myelolipoma of adrenal gland after blunt trauma.

A case of adrenal myelolipoma is reported in a patient in whom symptoms of hematuria and flank pain developed after the patient had sustained blunt trauma. Adrenal myelolipomas are usually found incidentally at autopsy. However, the symptomatic presentation of this patient was probably caused by traumatic intratumor hemorrhage. The etiology and pathogenesis of these tumors are discussed in relation to their occasional symptomatic presentation and to their differential diagnosis.

Spinal intradural cerebellar ectopia.

An ectopic cerebellum, as in Chiari malformations and ectopic cerebellar dysplastic tissue, is a common finding; however, the presence of an organized ectopic cerebellum is exceedingly rare. We describe the MR imaging, surgical, and histologic appearance of an intraspinal ectopic cerebellum in an infant.