Dacryolith after a Le Fort I fracture: case report.

A dacryolith is a rare finding and can be considered as a complication of a Le Fort I fracture. A case of dacryolith and nasolacrimal duct obstruction after surgery for a Le Fort I fracture is described, and the reasons for and prevention of this condition are discussed.

MSTO1 mutations cause mtDNA depletion, manifesting as muscular dystrophy with cerebellar involvement.

MSTO1 encodes a cytosolic mitochondrial fusion protein, misato homolog 1 or MSTO1. While the full genotype-phenotype spectrum remains to be explored, pathogenic variants in MSTO1 have recently been reported in a small number of patients presenting with a phenotype of cerebellar ataxia, congenital muscle involvement with histologic findings ranging from myopathic to dystrophic and pigmentary retinopathy. The proposed underlying pathogenic mechanism of MSTO1-related disease is suggestive of impaired mitochondrial fusion secondary to a loss of function of MSTO1. Disorders of mitochondrial fusion and fission have been shown to also lead to mitochondrial DNA (mtDNA) depletion, linking them to the mtDNA depletion syndromes, a clinically and genetically diverse class of mitochondrial diseases characterized by a reduction of cellular mtDNA content. However, the consequences of pathogenic variants in MSTO1 on mtDNA maintenance remain poorly understood. We present extensive phenotypic and genetic data from 12 independent families, including 15 new patients harbouring a broad array of bi-allelic MSTO1 pathogenic variants, and we provide functional characterization from seven MSTO1-related disease patient fibroblasts. Bi-allelic loss-of-function variants in MSTO1 manifest clinically with a remarkably consistent phenotype of childhood-onset muscular dystrophy, corticospinal tract dysfunction and early-onset non-progressive cerebellar atrophy. MSTO1 protein was not detectable in the cultured fibroblasts of all seven patients evaluated, suggesting that pathogenic variants result in a loss of protein expression and/or affect protein stability. Consistent with impaired mitochondrial fusion, mitochondrial networks in fibroblasts were found to be fragmented. Furthermore, all fibroblasts were found to have depletion of mtDNA ranging from 30 to 70% along with alterations to mtDNA nucleoids. Our data corroborate the role of MSTO1 as a mitochondrial fusion protein and highlight a previously unrecognized link to mtDNA regulation. As impaired mitochondrial fusion is a recognized cause of mtDNA depletion syndromes, this novel link to mtDNA depletion in patient fibroblasts suggests that MSTO1-deficiency should also be considered a mtDNA depletion syndrome. Thus, we provide mechanistic insight into the disease pathogenesis associated with MSTO1 mutations and further define the clinical spectrum and the natural history of MSTO1-related disease.

Biofilm Formation Plays a Role in the Formation of Multidrug-Resistant Escherichia coli Toward Nutrients in Microcosm Experiments.

In this study, microcosms were established to determine the effect of nitrogen (N) and phosphorus (P) on the multidrug resistance and biofilm-forming abilities of Escherichia coli. The expression of biofilm-formation-related genes was detected to establish correlations between genotype and phenotype. Different concentrations of N and P were added to make one control group and four treatment groups. The glass tube method was used to determine biofilm-forming capabilities. Real-time PCR was used to detect the mRNA abundance of six biofilm-formation-related genes in E. coli. No resistant strains were isolated from the control group; meanwhile, multidrug resistance rates were high in the treatment groups. Expression of the biofilm-associated genes luxS, flhD, fliA, motA, and fimH was detected in all treatment groups; however, there was no expression of mqsR. The expression of luxS, flhD, fliA, motA, and fimH significantly correlated with the concentration of N and P, as well as with the appearance and duration of multidrug resistance in different groups. Overall, the results of this study suggest that biofilm-forming ability plays a key role in the formation of multidrug resistance in E. coli after the addition of N and P to a microcosm.

18F-NaF PET/CT for the evaluation of temporomandibular joint disorder.

AIM: To investigate the usefulness of a quantitative parameter (maximum standardised uptake value [SUVmax]) of 18F-sodium fluoride (NaF) positron-emission tomography (PET)/computed tomography (CT) for the evaluation of temporomandibular joint (TMJ) disorder (TMD). MATERIALS AND METHODS: Seventy-six TMD patients (male: female=14:62, age=40.3±17.1 years, bilateral: unilateral=40:36) with 152 TMJs were enrolled. The 18F-NaF PET/CT parameter (SUVmax) was compared with the presence of TMJ arthralgia (arthralgic=86, non-arthralgic=66) and clinical subtypes based on the Research Diagnostic Criteria for TMD Axis I (TMD osteoarthritis=49, non-TMD osteoarthritis=67, and asymptomatic TMJ=36). Splint therapy was applied to 48 patients for 6 months without considering 18F-NaF PET/CT findings. Post-splint therapy 18F-NaF PET/CT was performed in 32 patients and clinical responses to the therapy were classified into improvement (n=33), no change (n=10), or aggravation (n=7) for 50 TMJs excluding asymptomatic TMJs (n=14). RESULTS: SUVmax was significantly greater in arthralgic TMJs than in non-arthralgic TMJs (6.62±3.56 versus 4.32±1.53, p<0.0001). SUVmax was also significantly greater in TMD osteoarthritis (6.75±3.85) than in non-TMD osteoarthritis (5.21±2.70) and asymptomatic TMJs (4.86±1.99; p=0.0386). After splint therapy, SUVmax was significantly increased in aggravated TMJs (from 7.80±3.72 to 11.00±5.74, p=0.0156), whereas no significant change in SUVmax was observed in improved (from 6.16±2.68 to 6.09±2.60, p=0.4915) and unchanged (from 6.46±4.19 to 6.77±4.32, p=0.3223) TMJs. CONCLUSIONS: 18F-NaF PET/CT is a useful imaging tool for TMD evaluation because SUVmax showed a fair diagnostic performance for arthralgic TMJ and TMD osteoarthritis, and a correlation with the therapeutic response.

Binding of prorenin to (pro)renin receptor induces the proliferation of human umbilical artery smooth muscle cells via ROS generation and ERK1/2 activation.

INTRODUCTION: Since the discovery of the (pro)renin receptor (PRR), it has been considered as a novel bioactive molecule of the renin-angiotensin system (RAS). The activation of PRR can elicit a series of angiotensin II (AngII)-independent effects. MATERIALS AND METHODS: In this study, we investigated the effects of prorenin and PRR on the proliferation of human umbilical artery smooth muscle (HUASM) cells and explored the possible mechanisms underlying these effects. RESULTS: The binding of prorenin to PRR can promote proliferation and upregulate the anti-apoptotic protein Bcl-2 and downregulate the pro-apoptotic protein Bax independently of AngII in HUASM cells. In addition, the binding of prorenin to PRR can also increase the production of reactive oxygen species (ROS) and the phosphorylation of extracellular signal-regulated kinase (ERK1/2) independently of AngII. The pretreatment of HUASM cells with an NADPH oxidase inhibitor DPI decreased the production of ROS and also decreased the phosphorylation of ERK1/2. Furthermore, pretreatment of HUASM cells with DPI and the ERK1/2 inhibitor PD98059 significantly attenuated the prorenin-induced proliferation and regulation of apoptosis factors. CONCLUSION: Binding of prorenin to PRR can induce HUASM cell proliferation via the ROS generation and ERK1/2 activation.

The lysine gingipain adhesin domains from Porphyromonas gingivalis interact with erythrocytes and albumin: Structures correlate to function.

The crystal structure of the K1 domain, an adhesin module of the lysine gingipain (Kgp) expressed on the cell surface by the periodontopathic anaerobic bacterium, Porphyromonas gingivalis W83, is compared to the previously determined structures of homologues K2 and K3, all three being representative members of the cleaved adhesin domain family. In the structure of K1, the conformation of the most extensive surface loop is unexpectedly perturbed, perhaps by crystal packing, and is displaced from a previously reported arginine-anchored position observed in K2 and K3. This displacement allows the loop to become free to interact with other proteins; the alternate flipped-out loop conformation is a novel mechanism for interacting with target host proteins, other bacteria, or other gingipain protein domains. Further, the K1 adhesin module, like others, is found to be haemolytic in vitro, and so, functions in erythrocyte recognition thereby contributing to the haemolytic function of Kgp. K1 was also observed to selectively bind to haem-albumin with high affinity, suggesting this domain may be involved in gingipain-mediated haem acquisition from haem-albumin. Therefore, it is most likely that all cleaved adhesin domains of Kgp contribute to the pathogenicity of P. gingivalis in more complex ways than simply mediating bacterial adherence.

Propofol suppresses proliferation, invasion and angiogenesis by down-regulating ERK-VEGF/MMP-9 signaling in Eca-109 esophageal squamous cell carcinoma cells.

BACKGROUND AND AIMS: Propofol (2,6-diisopropylphenol), one of the most commonly used intravenous anaesthetic agents during cancer resection surgery, has been reported to have the ability of influencing the invasion of human cancer cells. However, the mechanisms are not very clear. In this study, we investigated the effects of propofol on the proliferation, invasion and angiogenesis of human Eca-109 cells, and explored the mechanism. METHODS: The human Eca-109 cells was treated with propofol at the concentrations of 10-100 µmol/L for 72 hours or at the concentration of 100 µmol for 8-72 hours. Cell viability was determined by the MTT assay; the effect of propofol on apoptosis by 5'-triphosphate-biotin nick end labeling (TUNEL) staining. The effect of propofol on angiogenesis was determined by the chicken chorioallantoic membrane (CAM) angiogenesis assay. The effect of propofol on cell invasion using a modified Matrigel Boyden chamber assay. ERK1/2, MMP-9 and VEGF leves was detected by western blotting assay. RESULTS: In human Eca-109 cells, propofol significantly promoted cell apoptosis and inhibited proliferation in a dose and time-dependent manner. Furthermore, propofol inhibited dose and time-dependent invasion and angiogenesis. Propofol significantly dose and time-dependently down-regulated gene expression and protein production of ERK/pERK, VEGF and MMP-9. The functional effects and MMP-9/VEGF inhibition were shown to be dependent on the ERK/VEGF and ERK/MMP-9 signaling pathways. It was noteworthy that the ERK activator (phorbol 12-myristate 13-acetate [PMA]) treatment increased the MMP-9/VEGF levels after propofol treatment, and led to significant increase of proliferation, invasion and angiogenesis. CONCLUSIONS: These findings indicate that propofol inhibited proliferation, invasion and angiogenesis of human Eca-109 cells in vitro through modulation of ERK-VEGF /MMP-9 signaling. Propofol not only can be an anesthesia agent which reduces pain but plays an important role of inhibiting the migration and angiogenesis of ESCC cells in the therapy of ESCC patients.

Identification of an emulsifier and conditions for preparing stable nanoemulsions containing the antioxidant astaxanthin.

In this study, oil-in-water nanoemulsions of astaxanthin were prepared by high-pressure homogenization. The influence of emulsifying conditions including emulsifier type, concentration, passing time, astaxanthin concentration and coantioxidants were optimized. The stabilities of nanoemulsions were measured using zetasizer, FF-SEM, TEM, colorimeter and particle size analyzer. The mean diameter of the dispersed particles containing astaxanthin ranged from 160 to 190 nm. The size distribution was unimodal and extended from 100 to 200 nm. The nanoemulsions prepared with glyceryl citrate/lactate/linoleate/oleate (glyceryl ester) had smaller particle size and narrower size distribution than the emulsion prepared with hydrogenated lecithin. Stable incorporation of astaxanthin in nanoemulsion was performed and checked using HPLC, FF-SEM and TEM. The nanoemulsion was not significantly affected during storage under light and thermal condition for one month indicating that the nanoemulsion had a zeta potential of less than -41 mV, indicating a stable colloid.

Effectiveness of bone scans in the diagnosis of osteoarthritis of the temporomandibular joint.

OBJECTIVE: The objective of this study was to evaluate the usefulness of bone scan procedures for the diagnosis of temporomandibular joint (TMJ) osteoarthritis. METHODS: From February 2009 to June 2009, 22 patients (4 males and 18 females) from Seoul National University Bundang Hospital, Republic of Korea, were diagnosed with TMJ disorder. They were examined by clinical examination, plain radiograph and bone scan and were categorized into three groups: normal, internal derangement and osteoarthritis. TMJ uptake ratios and asymmetrical indices were calculated. RESULTS: There were no significant differences in uptake ratios associated with pain and bone change. However, significant results were obtained when comparing uptake ratios between the osteoarthritis and non-osteoarthritis groups. CONCLUSION: It was concluded from this study that bone scans may help to diagnose osteoarthritis when increased uptake ratios are observed.

Geographical, meteorological and vectorial factors related to malaria re-emergence in Huang-Huai River of central China.

BACKGROUND: Malaria still represents a significant public health problem in China, and the cases dramatically increased in the areas along the Huang-Huai River of central China after 2001. Considering spatial aggregation of malaria cases and specific vectors, the geographical, meteorological and vectorial factors were analysed to determine the key factors related to malaria re-emergence in these particular areas. METHODS: The geographic information of 357 malaria cases and 603 water bodies in 113 villages were collected to analyse the relationship between the residence of malaria cases and water body. Spearman rank correlation, multiple regression, curve fitting and trend analysis were used to explain the relationship between the meteorological factors and malaria incidence. Entomological investigation was conducted in two sites to get the vectorial capacity and the basic reproductive rate to determine whether the effect of vector lead to malaria re-emergence. RESULTS: The distances from household of cases to the nearest water-body was positive-skew distributed, the median was 60.9 m and 74% malaria cases were inhabited in the extent of 60 m near the water body, and the risk rate of people live there attacked by malaria was higher than others(OR = 1.6, 95%CI (1.042, 2.463), P < 0.05). The annual average temperature and rainfall may have close relationship with annual incidence. The average monthly temperature and rainfall were the key factors, and the correlation coefficients are 0.501 and 0.304(P < 0.01), respectively. Moreover, 75.3% changes of monthly malaria incidence contributed to the average monthly temperature (T(mean)), the average temperature of last two months(T(mean01)) and the average rainfall of current month (R(mean)) and the regression equation was Y = -2.085 + 0.839I1 + 0.998T(mean0) - 0.86T(mean01) + 0.16R(mean0). All the collected mosquitoes were Anopheles sinensis. The vectorial capacity and the basic reproductive rate of An. sinensis in two sites were 0.6969, 0.4983 and 2.1604, 1.5447, respectively. CONCLUSION: The spatial distribution between malaria cases and water-body, the changing of meteorological factors, and increasing vectorial capacity and basic reproductive rate of An. sinensis leaded to malaria re-emergence in these areas.

Are we ready to utilize non-heart-beating donors for clinical allotransplantation in China?

The concept of brain death has not been accepted by the majority of Chinese. Importantly, it is not recognized as a legal entity. We have developed a non-heart-beating donation protocol based on literature searches (Medline, Ovid, and CNKI) and issues related to Chinese customs and ethics. The principles guiding protocol development included: separation of the decision to terminate life support from the donation decision, family-centered donation, freedom of conflict interest, and prohibition of organ sales. This protocol covers donation policy, potential donor identification and evaluation, family consent, determination of death, procurement, and special legal documents/organ distribution policy. A random survey was performed regarding donation. There have been several arguments about the development of this protocol. First, do donor family members have the right to make a decision to withdraw life support? Another issue is whether family members have the right to consent to donation without a will from the donor. Our survey found that over 96.1% of people do not have a will and have not discussed their interests in donation with family members. The last issue is whether the hospital can financially help for the funeral after donation. We have debated these issues nationwide with various opinions. We hope to find the right solutions through international debate. We believe that the use of non-heart-beating-donor organs has potential in China. We are hopeful that it will become a major organ source that is developed in such a way so as to be accepted internationally as well as in China.

Gait analysis of donor leg after free fibular flap transfer.

The purpose of this study was to demonstrate gait disturbance after fibular flap transfer using preoperative and postoperative gait analysis. The gait performance of 20 patients was assessed at the Laboratory for Biomechanics, Seoul National University Hospital. Kinematic and kinetic data were collected simultaneously while walking on a 25-m walkway. One month postoperatively, a significant (p<0.05) decrease in the time-distance parameter as well as a significant (p<0.05) decrease in the peak plantarflexion and dynamic range was seen. Only peak plantarflexion in swing was significantly (p<0.05) decreased until 3 months postoperatively. On the basis of the gait analysis results, it was concluded that normalization of the patients' gaits would be expected within 3 months after the operation. There were no permanent pathological changes in the donor site.

Long-term follow up on recurrence of 305 ameloblastoma cases.

The aim of this study was to determine the appropriate treatment for ameloblastoma by considering the factors associated with recurrence, and to make a quantitative prediction of the risk factors for recurrence. Data on age and gender distribution, location of the tumour, histopathological findings, treatment method, and whether or not patients had a preoperative biopsy confirmation report were collected in 305 cases (239 patients; M: 139, F: 100) of ameloblastoma diagnosed and treated in 1985-2002. After initial statistical evaluation (chi(2)-test and Fisher's exact test), logistic regression analysis was performed to check relative significance and predict recurrence. The disease-free survival function curves of the patients with or without recurrence were obtained by the Kaplan-Meier method and compared using univariate regression analysis. The correlation between recurrence and the treatment method or histopathological type was significant. The differences between the 'conservative' and 'resection with bone margin' and between the 'conservative' and 'segmental resection or maxillectomy' groups in terms of disease-free survival were highly significant. The difference between the 'resection with bone margin' and 'segmental resection or maxillectomy' groups was not significant. A resection with safety margin is the best method to treat most proven ameloblastomas, and conservative treatment is reasonable for patients in their first decade or with unicystic or plexiform ameloblastoma.

Correlation of proliferative markers (Ki-67 and PCNA) with survival and lymph node metastasis in oral squamous cell carcinoma: a clinical and histopathological analysis of 113 patients.

The purposes of this study were to examine the correlations between proliferation markers and survival rate in oral squamous cell carcinoma (OSCC) patients, and to evaluate the efficacy of proliferation markers in predicting lymph node metastasis. The patients' age, gender, T score, clinical stage, PCNA and Ki-67 index were analysed. Univariate analysis showed that T score had a significant influence on survival, and stage 4 group had a significantly lower survival rate. Lymph node metastasis was also a significant predictor of survival. Using a cut-off point of 25%, those patients with lower Ki-67 scores had survival advantage over those with higher Ki-67 scores. PCNA did not show any differences in survival with a cut-off point of 50%. Ki-67 and PCNA were significantly higher in the primary tumours associated with lymph node metastasis (pN+) than in those without lymph node metastasis (pN0). Multivariate analysis showed that clinical stage and Ki-67 were independent prognostic factors for survival in OSCC patients. From this result, it can be postulated that the cancer staging based on the TNM stage was a powerful prognostic variable and Ki-67 had a significant effect on the cumulative survival rate.

Physical mapping and microsynteny of Brassica rapa ssp. pekinensis genome corresponding to a 222 kbp gene-rich region of Arabidopsis chromosome 4 and partially duplicated on chromosome 5.

We constructed a bacterial artificial chromosome (BAC) library, designated as KBrH, from high molecular weight genomic DNA of Brassica rapa ssp. pekinensis (Chinese cabbage). This library, which was constructed using HindIII-cleaved genomic DNA, consists of 56,592 clones with average insert size of 115 kbp. Using a partially duplicated DNA sequence of Arabidopsis, represented by 19 and 9 predicted genes on chromosome 4 and 5, respectively, and BAC clones from the KBrH library, we studied conservation and microsynteny corresponding to the Arabidopsis regions in B. rapa ssp. pekinensis. The BAC contigs assembled according to the Arabidopsis homoeologues revealed triplication and rearrangements in the Chinese cabbage. In general, collinearity of genes in the paralogous segments was maintained, but gene contents were highly variable with interstitial losses. We also used representative BAC clones, from the assembled contigs, as probes and hybridized them on mitotic (metaphase) and/or meiotic (leptotene/pachytene/metaphase I) chromosomes of Chinese cabbage using bicolor fluorescence in situ hybridization. The hybridization pattern physically identified the paralogous segments of the Arabidopsis homoeologues on B. rapa ssp. pekinensis chromosomes. The homoeologous segments corresponding to chromosome 4 of Arabidopsis were located on chromosomes 2, 8 and 7, whereas those of chromosome 5 were present on chromosomes 6, 1 and 4 of B. rapa ssp. pekinensis.

Phase II randomized trial of autologous formalin-fixed tumor vaccine for postsurgical recurrence of hepatocellular carcinoma.

PURPOSE: We conducted a Phase II clinical trial with randomized patients to determine whether autologous formalin-fixed tumor vaccine (AFTV) protects against postsurgical recurrence of hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: Forty-one patients with HCC who had undergone curative resection were randomly allocated to the vaccine treatment (n = 19) or no adjuvant control group (n = 22). Three intradermal vaccinations were administered at 2-week intervals beginning 4-6 weeks after hepatic resection. A delayed-type hypersensitivity test was performed before and after vaccination. Primary and secondary end points are recurrence-free survival and overall survival, respectively. Observation continued until the majority of surviving patients had lived >12 months after the curative resection. RESULTS: In a median follow-up of 15 months, the risk of recurrence in vaccinated patients was reduced by 81% (95% confidence interval, 33-95%; P = 0.003). Vaccination significantly prolonged the time to first recurrence (P = 0.003) and improved recurrence-free survival (P = 0.003) and overall survival rates (P = 0.01). AFTV played a significant role in preventing recurrence in patients with small tumors. Adverse effects were limited to grade 1 or 2 skin toxicities such as erythema, dry desquamation, and pruritus. CONCLUSIONS: AFTV therapy is a safe, feasible, and effective treatment for preventing postoperational recurrence of HCC. Patients with low tumor burdens benefit from the treatment. This treatment should be advanced to a large-scale randomized trial.

Hydrolysis of interleukin-12 by Porphyromonas gingivalis major cysteine proteinases may affect local gamma interferon accumulation and the Th1 or Th2 T-cell phenotype in periodontitis.

Porphyromonas gingivalis cysteine proteinases (gingipains) have been associated with virulence in destructive periodontitis, a disease process variously considered to represent an unregulated stimulation of either T helper type 1 (Th1)- or Th2-type cells. Critical in maintaining Th1 activity is the response of T lymphocytes to environmental interleukin 12 (IL-12) in the form of up-regulation of gamma interferon (IFN-gamma) production. Here we demonstrate that in the presence or absence of serum, gingipains were able to hydrolyze IL-12 and reduce the IL-12-induced IFN-gamma production from CD4+ T cells. However, the induction of IL-12 receptors on T cells by gingipains did not correlate with the enhancement of IFN-gamma production. The gingipains cleaved IL-12 within the COOH-terminal region of the p40 and p35 subunit chains, which leads to IL-12 inactivity, whereas IL-2 in these assays was not affected. Inactivation of IL-12 by the gingipains could disrupt the cytokine balance or favor Th2 activities in the progression of periodontitis.

[Experimental circumferential tracheal replacement with rib and costal muscle ring in dog.].

BACKGROUND: To evaluate the feasibility of using vascularized rib and costal muscle ring to repair large circumferential defect of thoracic trachea in dog. METHODS: Eighteen adult mongrel dogs were used in this study. The third rib with adjacent intercostal muscles was engineered to a ring with vascular pedicle , which replaced five or eight rings of trachea. RESULTS: Eleven of eighteen dogs were alive after operation , and the longest one had survived for 14 months. These dogs were active , although a slight stricture at the newly formed trachea was found. Microscopic examination showed the trachea had good blood supply , and the substitution of pleural epithelium by ciliated epithelium was observed. CONCLUSIONS: Circumferential tracheal replacement with vascularized rib and intercostal muscle ring is easily managed and has less complications. The results suggest that this technique might be clinically used in the future.

Quantitative assessment of cerebrospinal fluid hydrodynamics using a phase-contrast cine MR image in hydrocephalus.

This investigation was undertaken to characterize CSF flow at the level of the aqueduct of Sylvius with a phase-contrast cine MR pulse sequence in 28 healthy volunteers. Sixteen patients with obstructive hydrocephalus and 11 patients with normal pressure hydrocephalus (NPH) were investigated with the same sequence before and after CSF diversion. The peak CSF flow velocity and stroke volume in the aqueduct increased significantly in the NPH group and decreased significantly in the obstructive hydrocephalus group. After lumboperitoneal shunting in the NPH group, the retrograde flow of CSF was anterogradely converted and the peak flow velocities decreased somewhat. The clinical diagnosis of NPH was well correlated with the results of cine MRI. After endoscopic III ventriculostomy in the obstructive hydrocephalus group we noted increased CSF flow velocity with markedly increased stroke volume at the prepontine cistern. Phase-contrast cine MR is useful in evaluating CSF dynamics in patients with hyperdynamic aqueductal CSF or aqueductal obstruction.