Host Genetic Associations with Salivary Microbiome in Oral Cancer.

Despite the growing recognition of a host genetic effect on shaping gut microbiota composition, the genetic determinants of oral microbiota remain largely unexplored, especially in the context of oral diseases. Here, we performed a microbiome genome-wide association study in 2 independent cohorts of patients with oral squamous cell carcinoma (OSCC, n = 144 and 67) and an additional group of noncancer individuals (n = 104). Besides oral bacterial dysbiosis and signatures observed in OSCC, associations of 3 loci with the abundance of genus-level taxa and 4 loci with ß diversity measures were detected (q < 0.05) at the discovery stage. The most significant hit (rs10906082 with the genus Lachnoanaerobaculum, P = 3.55 × 10-9 at discovery stage) was replicated in a second OSCC cohort. Moreover, the other 2 taxonomical associations, rs10973953 with the genus Kingella (P = 1.38 × 10-9) and rs4721629 with the genus Parvimonas (P = 3.53 × 10-8), were suggestive in the meta-analysis combining 2 OSCC cohorts. Further pathway analysis revealed that these loci were enriched for genes in regulation of oncogenic and angiogenic responses, implicating a genetic anchor to the oral microbiome in estimation of casual relationships with OSCC. Our findings delineate the role of host genotypes in influencing the structure of oral microbial communities.

Prognostic impact of circumferential resection margin in esophageal cancer with or without neoadjuvant chemoradiotherapy.

The prognostic impact of circumferential resection margin (CRM) in surgically resected esophageal squamous cell carcinoma (ESCC) has been controversial. This investigation assessed the prognostic impact of CRM in surgically resected pathologic T3 ESCC patients with or without neoadjuvant chemoradiotherapy (nCRT). We reviewed consecutive p/yp T3 ESCC patients undergoing esophagectomy from two medical centers between January 2009 and December 2016. The cohort was divided into two groups: upfront esophagectomy (upfront surgery) and nCRT followed by esophagectomy (nCRT + surgery). CRM status was assessed and divided into CRM > 1 mm, 0 < CRM < 1 mm, and tumor at CRM. A total of 217 p/yp T3 ESCC patients undergoing esophagectomy (138 patients in the upfront surgery group and 79 in the nCRT + surgery group) were enrolled. In the upfront surgery group, patients with 0 < CRM < 1 mm showed equivalent overall survival to those with CRM > 1 mm (log-rank P = 0.817) and significantly outlived those with tumor at CRM (log-rank P < 0.001). However, in the nCRT + surgery group, CRM > 1 mm failed to show survival superiority to CRM between 0 and 1 mm or involved by cancer (log-rank P = 0.390). In conclusion, a negative CRM, even though being <1 mm, is adequate for pT3 ESCC patients undergoing upfront esophagectomy. In contrast, the CRM status is less prognostic in ypT3 ESCC patients undergoing nCRT followed by esophagectomy.

Impact of HOTAIR Gene Polymorphism and Environmental Risk on Oral Cancer.

Genetic and acquired factors are thought to be interrelated and imperative to estimate the risk and prognosis of oral squamous cell carcinoma (OSCC). HOX transcript antisense intergenic RNA ( HOTAIR) plays crucial roles in gene regulation and is regulated in a variety of cancers. Polymorphisms in HOTAIR have been recently linked to the predisposition to diverse malignancies. In the present study, we aimed to evaluate the influences of HOTAIR gene polymorphisms, combined with environmental triggers, on the susceptibility to oral tumorigenesis. Four single-nucleotide polymorphisms of the HOTAIR gene- rs920778, rs1899663, rs4759314, and rs12427129-were tested in 1,200 control participants and 907 patients with OSCC. We detected a significant association of rs1899663 with the risk of OSCC (adjusted odds ratio, 2.227; 95% confidence interval [95% CI], 1.197 to 4.146; P = 0.012) after adjustment for 3 potential confounders: smoking, betel quid chewing, and alcohol consumption. In further analyses where habitual exposure to each of 3 environmental factors was excluded, we found that, in addition to rs1899663, non-betel quid users who carried the polymorphic allele of rs920778 were more prone to develop OSCC than were those homozygous for wild-type allele (TC: odds ratio [OR], 1.472; 95% CI, 1.069 to 2.029; P = 0.018; TC+CC: OR, 1.448; 95% CI, 1.060 to 1.977; P = 0.020). Moreover, in exploring the relationship between HOTAIR gene polymorphisms and the clinical status of only patients with OSCC who were non-betel quid chewers (excluding the advanced clinical stage), we found that rs920778 and rs4759314 were correlated with the development of large-size tumors (OR, 1.891; 95% CI, 1.027 to 3.484; P = 0.04) and increased lymph node metastasis (OR, 4.140; 95% CI, 1.785 to 9.602; P = 0.001), respectively. Further functional assessments link rs920778 to the regulation of HOTAIR expression and epigenetic status. Our results reveal an interactive effect of HOTAIR gene polymorphisms and betel quid chewing on the development and progression of oral cancer.

Allergic rhinitis, rather than asthma, is a risk factor for dental caries.

OBJECTIVES: The association between AS (asthma) and dental caries is controversial, while that between allergic rhinitis (AR) and caries has not been established. This study aimed to verify the relationship among AR, AS and dental caries. DESIGN: Retrospective cohort study. SETTING: Data from Health Insurance Database of the Taiwan's National Health Insurance Research Database. PARTICIPANTS: Nine thousand and thirty-eight children born in 2004 were obtained. Their claims data were evaluated from birth to the age of 9 years. MAIN OUTCOME MEASURES: The frequencies of clinical visits for dental caries were calculated for primary teeth (age 1-5) and for dental transitional period (age 6-9). Differences in the frequencies of clinical visits for caries in AR vs non-AR and AS vs non-AS children were compared. Correlation between AR, AS and caries frequencies was studied, and the influences of AR drugs on the development of caries were evaluated. RESULTS: After adjusting for confounding factors and AS case, the frequencies of clinical visits for caries were higher in AR (increased by 13%-25% and P<.001 at different age periods). The AR frequencies significantly correlated with caries frequencies in children with AR. Different AR drugs also correlated with caries formation. After adjusting for confounding factors and AR case, there was no relationship between AS and caries in children. CONCLUSION: Asthma is not associated with dental caries, but AR can increase the frequency of clinical visits for caries. Medications for AR may also play a role in caries formation. Thus, AR may be a risk factor for childhood dental caries.

Oxidation and modification of extracellular matrix and its role in disease.

There is accumulating evidence that damage to extracellular materials and particularly the extracellular matrix, can play a major role in multiple human pathologies. In contrast to cells, the extracellular compartment of most biological tissues is relatively poorly equipped to prevent or repair damage caused by oxidation due to lower levels of antioxidant defenses (low molecular mass and enzymatic) and repair systems (both catabolic and enzymatic). The extracellular compartment is therefore likely to be subject to both an increased extent of damage and an overall accumulation of damage due to slow turnover and/or poor repair. The nature and consequences of damage to the extracellular matrix is poorly understood, despite evidence that changes in matrix structure influences not only structural integrity, but also cell adhesion, proliferation, migration and signaling, and cytokine and growth factor binding. In this article the nature of the extracellular matrix is briefly reviewed, together with evidence for the presence of matrix modifications in cardiovascular disease. The oxidants and mechanisms that are known to damage extracellular matrix are reviewed, together with the limited data available to date on how such changes affect structural properties and cellular behavior.

Differentiation of bacteria cell wall using Raman scattering enhanced by nanoparticle array.

We have fabricated surface-enhanced Raman scattering (SERS) substrates based on arrays of silver nanoparticles grown on porous anodic alumina templates. Using this nanotechnology platform, label-free and high-speed detection of bacteria are achieved. SERS spectra of various bacteria including Staphylococcus Aureus (Gram-positive bacterium), Klebsiella Pneumoniae (Gram-negative bacterium), and Mycobacterium Smegmatis (Mycobacterium) were recorded. The highly reproducible SERS-based technological platform is capable of differentiating different kinds of bacteria by PCA, LDA, clustering analysis, and SVM methods, which provides promising opportunity for biosensing of clinical microbes.

Accumulation of radium in relation to some chemical analogues in Dicranopteris linearis.

This study elucidates the uptake and accumulation of radium in the field-growing fern Dicranopteris linearis by relating the radium concentration to some potential chemical analogues, including alkaline earth metals, rare earth elements, and some important heavy metals. Time-dependent accumulation of radium and these chemical analogues for D. linearis were described by the (228)Th/(228)Ra activity ratio, an index for inferring plant age. The correlation between radium and these elements was assessed by statistical analysis and used as a reference to elucidate the uptake and accumulation of radium in relation to the chemical analogues. Analytical and statistical results showed that the concentrations of alkaline earth metals (except for Mg) rare earth elements and some heavy metals in D. linearis increased linearly with plant age. These elements, exhibiting a similar accumulation pattern to radium and significant correlation coefficients with radium, were considered as the chemical analogues to radium. Additionally, the plant/soil concentration ratios (CRs) for radium and most of these analogues in D. linearis exceeded 1, consistent with the definition of hyper-accumulator plants.

Intracavernosal pressure characteristics analyzed by power spectral density for identifying the phase of penile erection.

Knowledge of the time course of penile erection is very important to understanding erection physiology. The changes in the intracavernosal pressure (ICP) and the different phases of an erection are pivotal to the ability to produce and maintain a rigid penile erection. This study investigated an objective and low-invasiveness method for identifying different erection phases based on an innovative ICP analysis technique. Blood infuses into the corpora cavernosa and causes the ICP to increase. The ICP usually exhibits tiny oscillations at the frequency of the heartbeat when it increases from diastole to systole. The characteristic oscillation amplitudes corresponding to the period when the full and rigid erection phases begin can be extracted by power spectral density analysis. The reliability and accuracy of the proposed method was verified by the Bland-Altman graphs indicating a good agreement with the existing method that compares the ICP with the arterial pressure. Moreover, all of the intraclass correlation coefficient values were close to 1.00, with the lower limit of the 95% confidence interval exceeding 0.75. The described novel objective and low-invasiveness method can therefore be used for identifying the full and rigid erection phases of the penis in urological investigations during different erection phases.

Using medical accelerators and photon activation to determine Sr/Ca concentration ratios in teeth.

This paper describes a photon activation method, studied by using two medical accelerators (energies: 15 and 18 MeV) as photon sources, for determining Sr and Ca levels and Sr/Ca ratios in tooth samples. The radionuclides formed by various photonuclear reactions were measured and identified using a gamma-spectrometry with HPGe detection system. The yields of the corresponding photonuclear reactions and the detection sensitivities for the alkaline earth metals (e.g., Ca, Sr) were surveyed and estimated in relation to the radiation dose. The minimum detectable amount of Sr was estimated to be less than 1 microg g(-1), allowing the Sr/Ca ratios in teeth to be determined conveniently. The Sr/Ca ratios in deciduous and permanent tooth samples obtained from local dental clinics were 0.390 and 0.565 mg g(-1), respectively. This photon activation method of determining Sr/Ca ratio in bones and teeth using medical accelerators for cancer treatment is thought to be useful also in biological and archaeological studies.

Relationship between radioactivity of radium and concentrations of barium and lead in hokutolite.

Hokutolite consists of barite (BaSO(4)) and anglesite (PbSO(4)), and contains significant amounts of radium isotopes as a radioactive mineral. Photon activation and gamma-ray spectrometry were employed to determine Ba, Pb and (226)Ra contents in hokutolite samples and to investigate the correlation between (226)Ra activity and both Ba and Pb content. (226)Ra activity in 30 hokutolite samples were estimated in the range of 40-65Bq/g and was positively related to Ba content (r=0.859, p<0.001), but independent of Pb content (r=-0.236, p=0.217). Experimental results implied that (226)Ra preferably precipitated with Ba over Pb. The (226)Ra activity in hokutolite from the Peitou Hot Spring was experimentally estimated based on the Ba/Pb ratio and expressed as (226)Ra (Bq/g)=14.67 (Ba/Pb)(molar)+14.13.

Dosage prediction via estimation of shell thickness and concentration of drug carrier with microbubbles.

For drug delivery applications, dosage prediction before release and estimation after release are required functions. In this study, we attempted to establish a method to evaluate liposome concentrations and liposome shell thickness for dosage prediction. We use the Trilling model with parameter of phospholipids bilayers to simulate the frequency responses under the different acoustic pressure and establish an experimental protocol to evaluate the liposome concentrations and the liposome shell thickness. Our results illustrate the changes on the signal strength for different concentrations and show that it is relatively stable to estimate the concentrations when the cycles are lower (15 cycles). Besides, it is verified that the second harmonic signal is more sensitive in analyzing different concentrations. On the other hand, it is proved that the liposome shell thickness affect signal strength and thinner thickness will increase the second harmonic response. Therefore, in accordance with the theoretical and experimental results, we would be able to estimate the concentration and the shell thickness of the liposomes. By numerical analysis methods, dosage prediction would be built.

Life expectancy of patients with newly-diagnosed HIV infection in the era of highly active antiretroviral therapy.

BACKGROUND: Limited data are available on the life expectancy of patients with newly-diagnosed HIV infection in the era of highly active antiretroviral therapy (HAART). AIM: To provide such an estimate using a semi-parametric projection. DESIGN: Statistical analysis. METHODS: Follow-up data for patients newly diagnosed with HIV infection in Taiwan (HIV/AIDS Cohort) from 1 May 1997 to 30 April 2003 (n = 3351, only 1% are injecting drug users) were analysed using the Kaplan-Meier method. The survival function for an age- and gender-matched reference population was generated by the Monte Carlo method from the life-table of the general population. A constant excess hazard model was used to project long-term survival of HIV-infected patients, with linear extrapolation of a logit-transformed curve of survival ratio between HIV-infected patients and the reference population. RESULTS: The 5-year survival rate was 58% in patients who had already developed AIDS at diagnosis (AIDS group), and 89% in those who had not (non-AIDS group). Extrapolation yielded an expected mean survival time of 10.6 years after diagnosis for the AIDS group, and 21.5 years after diagnosis for the non-AIDS group. DISCUSSION: Our results support the expansion of HIV screening programs to minimize delay in diagnosis. With continuing advances in HAART, this estimate of survival in initially asymptomatic patients may be conservative. Their long life expectancy raises questions about what kind of preventive heath services should be offered. These should be addressed through further analysis of overall benefit and cost-effectiveness.

Derivation, characterization and differentiation of human embryonic stem cells: comparing serum-containing versus serum-free media and evidence of germ cell differentiation.

BACKGROUND: This study was designed to establish human embryonic stem cell (hESC) lines, to identify the differences when maintained in serum-containing versus serum-free medium and to test their potential of in vitro differentiation. METHODS: Procedures including immunosurgery were performed on 11 donated human blastocysts to establish hESC lines. The cell lines were characterized and maintained using either serum-free or serum-containing media to compare their morphology, Oct-4 expression, apoptosis and growth speed. Differentiation of these lines was evaluated by the morphology and the expression of genes belonging to the three embryonic germ layers and the germ cell lineage. RESULTS: Three hESC lines were established, and they grew at similar speed in both media (serum-containing or serum-free), but hESC cultured in serum-containing medium yielded significantly higher percentages of morphologically good colonies and cells expressing Oct-4. These cell lines differentiated spontaneously in vitro into cells expressing markers belonging to all three embryonic germ layers and germ cell markers, including c-Kit, STELLA, VASA and growth differentiation factor 9 (GDF9), in directly adherent culture. CONCLUSIONS: Three hESC lines with Taiwanese ancestry have been established, and they retain the in vitro differentiation potential with or without embryoid body (EB) formation. The data support that hESC may be capable of differentiation into germ cells although further confirmation is needed. It is also suggested that strategies such as stepwise adaptation will be needed before implementing a serum-free culture condition for hESC lines that have previously been derived in a medium containing serum.

Double-clad Cr4+:YAG crystal fiber amplifier.

A novel double-clad Cr4+:YAG crystal fiber is demonstrated by use of a codrawing laser-heated pedestal growth method. Up to 10 dB of gross gain at a wavelength of 1.52 microm is achieved at a pump power of 0.83 W, which, to our knowledge, is the first Cr4+-doped fiber amplifier in the optical fiber communication band.

Comparison between the right side and subxiphoid bilateral approaches in performing video-assisted thoracoscopic extended thymectomy for myasthenia gravis.

BACKGROUND: This study aimed to compare the efficacy of the right thoracoscopic (RtT) approach and the subxiphoid bilateral thoracoscopic (SxBiT) approach in performing thymectomy for myasthenia gravis. METHODS: Between March 2001 and April 2003, 27 myasthenic patients were enrolled in this prospective study. The operations were conducted by two surgical teams in a single institute. The surgical procedures included RtT for 12 patients and SxBiT for 15 patients. The operation time, resected thymus weights, and thoracic drainage periods were compared. RESULTS: Subxiphoid video-assisted thoracoscopic extended thymectomy (SxVATET) and right-side thoracoscopic extended thymectomy (RtVATET) were performed for 27 consecutive myasthenic patients. The mean operation time, weights of resected specimens, and duration of hospital stay for the SxVATET and RtVATET groups were, respectively, 151.3 min (range, 120-200 min) versus 191.5 min (range, 120-225 min) (p = 0.0012), 73.3 g (range, 40-90 g) versus 50.8 g (range, 5-90 g) (p = 0.0029), and 3.1 days (range, 2-4 days) versus 3.8 days (range, 2-4 days) (p = 0.914). Ten patients (37%) had complete remission, observed during a mean follow-up period of 18.5 months (range, 6-30 months). CONCLUSIONS: During this consecutive experience, both the RtT and SxBiT approaches showed satisfactory results for nonthymomatous myasthenic patients. However, a better view of the bilateral pleural cavities and more radical thymectomy could be achieved only by the SxBiT approach.

Experiences in thoracoscopic sympathectomy for axillary hyperhidrosis and osmidrosis: focusing on the extent of sympathectomy.

HYPOTHESIS: A more selective sympathectomy can improve the outcome of axillary hyperhidrosis and osmidrosis and minimize the potential sequelae. DESIGN: Retrospective cohort. SETTING: Tertiary care center. PATIENTS: Between July 1, 1996, and May 30, 2000, 171 patients with axillary hyperhidrosis and osmidrosis were studied. INTERVENTIONS: T3-4 sympathectomies were performed in 40 patients (group 1), T4 sympathectomies were performed in 56 patients (group 2), and T4-5 sympathectomies were performed in 75 patients (group 3). MAIN OUTCOME MEASURES: The surgical outcomes were evaluated by direct patient interview in the outpatient clinic or by telephone or mail questionnaires. The results were categorized as excellent (significant or complete disappearance of symptoms), good (>/=50% improvement), or poor (<50% improvement). RESULTS: There were no surgical mortalities in this study. Twenty-eight group 1 patients (70%), 16 group 2 patients (29%), and 22 group 3 patients (29%) developed compensatory perspiration (P<.001). Six group 1 patients (15%), 1 group 2 patient (2%), and 1 group 3 patient (1%) developed dry hands (P =.02). In the group 1 patients, the surgical outcomes were excellent in 21 (52%), good in 6 (15%), and poor in 13 (32%). In the group 2 patients, the surgical outcomes were excellent in 29 (52%), good in 10 (18%), and poor in 17 (30%). In the group 3 patients, the surgical outcomes were excellent in 53 (71%), good in 11 (15%), and poor in 11(15%) (P =.04). (Percentages may not sum to 100 because of rounding.) CONCLUSION: T4-5 sympathectomies provide higher patient satisfaction rates in treating axillary hyperhidrosis and osmidrosis, with fewer sequelae.

Hydroxychloroquine sulphate inhibits in vitro apoptosis of circulating lymphocytes in patients with systemic lupus erythematosus.

The serological hallmark of systemic lupus erythematosus (SLE) is the presence of antibodies against double-stranded DNA. However, several studies have suggested that it is not DNA itself, but nucleosomes that are the immunogenic particles involved both in the induction of anti-DNA antibodies, and in the pathophysiology of SLE. Meanwhile, It has been demonstrated that there is an accelerated in vitro apoptosis of lymphocytes from patients with SLE. Therefore, one can postulate that the process of apoptosis may provide a source of nuclear antigens to drive the autoantibody response seen in SLE. Our study has demonstrated that hydroxychloroquine exhibits an anti-apoptotic action and this anti-apoptotic effect is dependent on monocyte coexistence. We used both morphology assessment and fluorescent antibody cell sorter (FACS) analysis to measure the apoptotic percentage of lymphocytes from 25 SLE patients in medium alone (control) or with the addition of different concentrations of hydroxychloroquine. Our results have shown that there is a significant decrease in the percentage of apoptosis at the therapeutic concentration (10(-6) M) as compared with the control (p < 0.05). It has been reported that the anti-rheumatic properties of hydroxychloroquine result from its interference with antigen processing in macrophages and other antigen-presenting cells. We propose that this results in decreased stimulation of autoreactive lymphocytes reactive with self-peptides, and consequently diminution of activation-induced cell death (apoptosis) of mature peripheral lymphocytes.

Reciprocal regulatory interaction between human herpesvirus 8 and human immunodeficiency virus type 1.

Human herpesvirus 8 (HHV8) is the primary viral etiologic agent in Kaposi's sarcoma (KS). However, individuals dually infected with both HHV8 and human immunodeficiency virus type 1 (HIV-1) show an enhanced prevalence of KS when compared with those singularly infected with HHV8. Host immune suppression conferred by HIV infection cannot wholly explain this increased presentation of KS. To better understand how HHV8 and HIV-1 might interact directly in the pathogenesis of KS, we queried for potential regulatory interactions between the two viruses. Here, we report that HHV8 and HIV-1 reciprocally up-regulate the gene expression of each other. We found that the KIE2 immediate-early gene product of HHV8 interacted synergistically with Tat in activating expression from the HIV-1 long terminal repeat. On the other hand, HIV-1 encoded Tat and Vpr proteins increased intracellular HHV8-specific expression. These results provide molecular insights correlating coinfection with HHV8 and HIV-1 with an unusually high incidence of KS.

Expression of apoptosis-regulating proteins p53, Bcl-2, and Bax in primary resected esophageal squamous cell carcinoma.

Apoptosis plays a key role in the pathogenesis, aggressiveness, and therapy responsiveness of cancer. Proteins of the Bcl-2 family as well as p53 are important regulators of apoptosis. The present study retrospectively examines the expression of apoptosis-regulating proteins in primary resected esophageal squamous cell carcinoma (ESCC) and the correlation between the outcome of patients' treatment and the expression of the proteins. We used antibodies specific for the human p53, Bcl-2 and Bax proteins to examine the expression of these apoptosis-regulating proteins in 40 archival specimens of patients with primary resected esophageal squamous cell carcinoma. The overall expression of p53, Bcl-2, and Bax was 73%, 18%, and 100%, respectively. No significant correlations were found between the expression of p53, Bcl-2, and Bax. The expression of Bcl-2 had a negative influence on survival in this population of primary resected ESCC patients (p=0.03). But no differences in survival were observed in relation to the expression of p53 or Bax. In conclusion, Bcl-2 expression may provide additional and prognostic information for the clinical course of the disease and therefore to be developed as a prognostic indicator for primary resected esophageal squamous cell carcinoma.