Influence of Various Acidic Beverages on Tooth Erosion. Evaluation by a New Method

Material & Methods

We have analyzed the loss of enamel and dentine after exposure to different non-alcoholic drinks with a simple new method using bovine teeth. 100 enamel and 100 dentine specimens from freshly extracted bovine incisors were randomly attributed to 10 groups (n=10 for enamel and dentine each). Prior to the start of the experiment all specimens were weighed using a precision balance. The mean initial masses (SD) were 35.8 mg (7.2) for enamel and 24.7 mg (7.0) for dentine. No statistically significant differences were found between groups for initial masses (p>0.05, ANOVA with Bonferroni post hoc test). Thereafter, all specimens of one group were simultaneously placed in 200 ml of the following fluids: Coca-Cola, Coca-Cola light, Sprite, apple juice, Red Bull, orange juice, Bonaqua Fruits (Mango-Acai), tap water, chlorinated swimming pool water, and lemon juice. Fluids were continuously ventilated at 37° C for 7 days. Thereafter the specimens were weighed again and the mean mass loss was calculated.

Results

The values were (enamel/dentine): Coca-Cola 7.5 mg/6.6 mg; Coca-Cola light 5.2 mg/3.5 mg, Sprite 26.1 mg/17.7 mg, apple juice 27.1 mg/15.2 mg, Red Bull 16.6 mg/17.0 mg, orange juice 24.3 mg/20.2 mg, Bonaqua Fruits (Mango-Acai) 17.8 mg/16.2 mg, tap water -0.2 mg/-0.3 mg, swimming pool water -0.3 mg/-0.2 mg, and lemon juice 32.0 mg/28.3 mg. From all drinks, Cola and Cola light showed the least erosivity (p<0.001, ANOVA with Bonferroni post hoc test) whereas lemon juice showed statistically significant higher erosivity than all other drinks except Sprite and apple juice (p<0.01, ANOVA with Bonferroni post hoc test).

Conclusions

In conclusion, erosivity of common non-alcoholic drinks varies widely. For example, Sprite, apple juice, and orange juice are about five times more erosive than Coca-Cola light. The findings from the present study should be taken into account in choosing a diet that provides satisfactory nutrition while minimizing tooth erosion.     

Phase I Clinical Trial of Fibronectin CH296-Stimulated T Cell Therapy in Patients with Advanced Cancer

Background

Previous studies have demonstrated that less-differentiated T cells are ideal for adoptive T cell transfer therapy (ACT) and that fibronectin CH296 (FN-CH296) together with anti-CD3 resulted in cultured cells that contain higher amounts of less-differentiated T cells. In this phase I clinical trial, we build on these prior results by assessing the safety and efficacy of FN-CH296 stimulated T cell therapy in patients with advanced cancer.

Methods

Patients underwent fibronectin CH296-stimulated T cell therapy up to six times every two weeks and the safety and antitumor activity of the ACT were assessed. In order to determine immune function, whole blood cytokine levels and the number of peripheral regulatory T cells were analyzed prior to ACT and during the follow up.

Results

Transferred cells contained numerous less-differentiated T cells greatly represented by CD27+CD45RA+ or CD28+CD45RA+ cell, which accounted for approximately 65% and 70% of the total, respectively. No ACT related severe or unexpected toxicities were observed. The response rate among patients was 22.2% and the disease control rate was 66.7%.

Conclusions

The results obtained in this phase I trial, indicate that FN-CH296 stimulated T cell therapy was very well tolerated with a level of efficacy that is quite promising. We also surmise that expanding T cell using CH296 is a method that can be applied to other T- cell-based therapies.

Trial Registration

UMIN UMIN000001835     

Bonding of Resin Cement to Zirconia with High Pressure Primer Coating

Objectives

To investigate the effect of air-drying pressure during ceramic primer coating on zirconia/resin bonding and the surface characteristics of the primed zirconia.

Methods

Two ceramic primers (Clearfil Ceramic Primer, CCP, Kuraray Medical Inc. and Z-Prime Plus, ZPP, Bisco Inc.) were applied on the surface of air-abraded zirconia (Katana zirconia, Noritake) and dried at 4 different air pressures (0.1–0.4 MPa). The primed zirconia ceramic specimens were bonded with a resin-based luting agent (SA Luting Cement, Kuraray). Micro-shear bond strengths of the bonded specimens were tested after 3 days of water storage or 5,000× thermocycling (n = 12). Failure modes of the fractured specimens were examined with scanning electron miscopy. The effects of air pressure on the thickness of the primer layers and the surface roughness (S_a) of primed zirconia were evaluated using spectroscopic ellipsometry (n = 6), optical profilometry and environmental scanning electron microscopy (ESEM) (n = 6), respectively.

Results

Clearfil Ceramic Primer air-dried at 0.3 and 0.4 MPa, yielding significantly higher µSBS than gentle air-drying subgroups (p<0.05). Compared to vigorous drying conditions, Z-Prime Plus air-dried at 0.2 MPa exhibited significantly higher µSBS (p<0.05). Increasing air-drying pressure reduced the film thickness for both primers. Profilometry measurements and ESEM showed rougher surfaces in the high pressure subgroups of CCP and intermediate pressure subgroup of ZPP.

Conclusion

Air-drying pressure influences resin/zirconia bond strength and durability significantly. Higher air-drying pressure (0.3-0.4 MPa) for CCP and intermediate pressure (0.2 MPa) for ZPP are recommended to produce strong, durable bonds between resin cement and zirconia ceramics.     

Mineralization Potential of Polarized Dental Enamel

Background

Management of human teeth has moved from a surgical to a more conservative approach of inhibiting or preventing lesion progression. Increasing enamel mineralization is crucial in this regard. A potential difficulty is the preferential mineralization of the outermost portion of the enamel that can prevent overall mineralization. We describe a strategy for increasing the mineralization potential of dental enamel.

Methodology/Principal Findings

Extracted human premolar teeth enamel (n = 5) were exposed to a high concentration of hydrogen peroxide with an energizing source. Samples were stored in artificial saliva at 37°C for 1 wk. A desktop X-ray micro-CT system was used to evaluate the mineral density of samples. Mineral distribution was polarized between the lower and the higher mineralized portion of enamel by charged oxygen free radicals due to activation of permeated hydrogen peroxide. The kinetics of energy absorption in the deeper enamel region demonstrated improvement of preferential mineralization into the region without restricting overall mineralization of the enamel. Subsequent increasing mineralization, even in the dense mineralized outer portion of enamel, was also achieved.

Conclusions/Significance

This increased mineralization may promote resistance to acidic deterioration of the structure. The present study is one of the primary steps towards the development of novel application in reparative and restorative dentistry.     

Specificity and Effector Functions of Human RSV-Specific IgG from Bovine Milk

Background

Respiratory syncytial virus (RSV) infection is the second most important cause of death in the first year of life, and early RSV infections are associated with the development of asthma. Breastfeeding and serum IgG have been shown to protect against RSV infection. Yet, many infants depend on bovine milk-based nutrition, which at present lacks intact immunoglobulins.

Objective

To investigate whether IgG purified from bovine milk (bIgG) can modulate immune responses against human RSV.

Methods

ELISAs were performed to analyse binding of bIgG to human respiratory pathogens. bIgG or hRSV was coated to plates to assess dose-dependent binding of bIgG to human Fcγ receptors (FcγR) or bIgG-mediated binding of myeloid cells to hRSV respectively. S. Epidermidis and RSV were used to test bIgG-mediated binding and internalisation of pathogens by myeloid cells. Finally, the ability of bIgG to neutralise infection of HEp2 cells by hRSV was evaluated.

Results

bIgG recognised human RSV, influenza haemagglutinin and Haemophilus influenza. bIgG bound to FcγRII on neutrophils, monocytes and macrophages, but not to FcγRI and FcγRIII, and could bind simultaneously to hRSV and human FcγRII on neutrophils. In addition, human neutrophils and dendritic cells internalised pathogens that were opsonised with bIgG. Finally, bIgG could prevent infection of HEp2 cells by hRSV.

Conclusions

The data presented here show that bIgG binds to hRSV and other human respiratory pathogens and induces effector functions through binding to human FcγRII on phagocytes. Thus bovine IgG may contribute to immune protection against RSV.     

Assessment of Still and Moving Images in the Diagnosis of Gastric Lesions Using Magnifying Narrow-Band Imaging in a Prospective Multicenter Trial

Objectives

Magnifying narrow-band imaging (M-NBI) is more accurate than white-light imaging for diagnosing small gastric cancers. However, it is uncertain whether moving M-NBI images have additional effects in the diagnosis of gastric cancers compared with still images.

Design

A prospective multicenter cohort study.

Methods

To identify the additional benefits of moving M-NBI images by comparing the diagnostic accuracy of still images only with that of both still and moving images. Still and moving M-NBI images of 40 gastric lesions were obtained by an expert endoscopist prior to this prospective multicenter cohort study. Thirty-four endoscopists from ten different Japanese institutions participated in the prospective multicenter cohort study. Each study participant was first tested using only still M-NBI images (still image test), then tested 1 month later using both still and moving M-NBI images (moving image test). The main outcome was a difference in the diagnostic accuracy of cancerous versus noncancerous lesions between the still image test and the moving image test.

Results

Thirty-four endoscopists were analysed. There were no significant difference of cancerous versus noncancerous lesions between still and moving image tests in the diagnostic accuracy (59.9% versus 61.5%), sensitivity (53.4% versus 55.9%), and specificity (67.0% versus 67.6%). And there were no significant difference in the diagnostic accuracy between still and moving image tests of demarcation line (65.4% versus 65.5%), microvascular pattern (56.7% versus 56.9%), and microsurface pattern (48.1% versus 50.9%). Diagnostic accuracy showed no significant difference between the still and moving image tests in the subgroups of endoscopic findings of the lesions.

Conclusions

The addition of moving M-NBI images to still M-NBI images does not improve the diagnostic accuracy for gastric lesions. It is reasonable to concentrate on taking sharp still M-NBI images during endoscopic observation and use them for diagnosis.

Trial registration

Umin.ac.jp UMIN-CTR000008048     

A Macaque Model of Mesial Temporal Lobe Epilepsy Induced by Unilateral Intrahippocampal Injection of Kainic Acid

Objective

In order to better investigate the cause/effect relationships of human mesial temporal lobe epilepsy (mTLE), we hereby describe a new non-human primate model of mTLE.

Methods

Ten macaques were studied and divided into 2 groups: saline control group (n = 4) and kainic acid (KA) injection group (n = 6). All macaques were implanted bilaterally with subdural electrodes over temporal cortex and depth electrodes in CA3 hippocampal region. KA was stereotaxically injected into the right hippocampus of macaques. All animals were monitored by video and electrocorticography (ECoG) to assess status epilepticus (SE) and subsequent spontaneous recurrent seizures (SRS). Additionally, in order to evaluate brain injury produced by SE or SRS, we used both neuroimaging, including magnetic resonance image (MRI) & magnetic resonance spectroscopy (MRS), and histological pathology, including Nissl stainning and glial fibrillary acid protein (GFAP) immunostaining.

Results

The typical seizures were observed in the KA-injected animal model. Hippocampal sclerosis could be found by MRI & MRS. Hematoxylin and eosin (H&E) staining and GFAP immunostaining showed neuronal loss, proliferation of glial cells, formation of glial scars, and hippocampal atrophy. Electron microscopic analysis of hippocampal tissues revealed neuronal pyknosis, partial ribosome depolymerization, an abnormal reduction in rough endoplasmic reticulum size, expansion of Golgi vesicles and swollen star-shaped cells. Furthermore, we reported that KA was able to induce SE followed by SRS after a variable period of time. Similar to human mTLE, brain damage is confined to the hippocampus. Accordingly, hippocampal volume is in positive correlations with the neuronal cells count in the CA3, especially the ratio of neuron/glial cell.

Conclusions

The results suggest that a model of mTLE can be developed in macaques by intra-hippocampal injection of KA. Brain damage is confined to the hippocampus which is similar to the human mTLE. The hippocampal volume correlates with the extension of the hippocampal damage.     

The Impact of Prior Tonsillitis and Treatment Modality on the Recurrence of Peritonsillar Abscess: A Nationwide Cohort Study

Background

Studies suggest an increased risk of peritonsillar abscess (PTA) recurrence in patients with prior tonsillitis. However, this association is inconsistent and could be confounded by different treatment modalities. This study aimed to assess the risk of recurrence among PTA patients with different degrees of prior tonsillitis and treatment modalities, and the role of tonsillectomy in current practice.

Methods

All in-patients with peritonsillar abscess between January 2001 and December 2009 were identified in a nationwide, retrospective cohort study. Recurrence was defined as the first occurrence of PTA ≧30 days from the initial PTA. Factors independently associated with recurrence were analyzed using Cox proportional hazard model after adjusting for demographic and clinical data.

Results

There were 28,837 patients, with a 5.15% recurrence rate and 4.74 years of follow-up. The recurrence rates were significantly higher among subjects with more than five prior tonsillitis or 1–4 prior tonsillitis compared to those without prior tonsillitis (adjusted hazard ratio, 2.82 [95% confidence interval, 2.39–3.33] and 1.59 [95% CI: 1.38–1.82]). The adjusted HR in patients treated with needle aspiration was 1.08 compared to those treated with incision & drainage (95% CI: 0.85–1.38). After age stratification, the adjusted HRs of more than five prior tonsillitis increased to 2.92 and 3.50 in patients aged ≦18 and 19–29 years respectively. The adjusted HR ofneedle aspiration only increased in patients ≦18 years old (aHR: 1.98 [95% CI: 0.99–3.97]). The overall tonsillectomy rate was 1.48% during our study period.

Conclusions

The risk of PTA recurrence increases with higher degrees of prior tonsillitis in all age groups and management by needle aspiration only in the pediatric population. Patients younger than 30 years old with PTA and more than five prior tonsillitis have the greatest risk of recurrence.     

Evidence-Based Health Care Policy in Reimbursement Decisions: Lessons from a Series of Six Equivocal Case-Studies

Context

Health care technological evolution through new drugs, implants and other interventions is a key driver of healthcare spending. Policy makers are currently challenged to strengthen the evidence for and cost-effectiveness of reimbursement decisions, while not reducing the capacity for real innovations. This article examines six cases of reimbursement decision making at the national health insurance authority in Belgium, with outcomes that were contested from an evidence-based perspective in scientific or public media.

Methods

In depth interviews with key stakeholders based on the adapted framework of Davies allowed us to identify the relative impact of clinical and health economic evidence; experience, expertise & judgment; financial impact & resources; values, ideology & political beliefs; habit & tradition; lobbyists & pressure groups; pragmatics & contingencies; media attention; and adoption from other payers & countries.

Findings

Evidence was not the sole criterion on which reimbursement decisions were based. Across six equivocal cases numerous other criteria were perceived to influence reimbursement policy. These included other considerations that stakeholders deemed crucial in this area, such as taking into account the cost to the patient, and managing crisis scenarios. However, negative impacts were also reported, in the form of bypassing regular procedures unnecessarily, dominance of an opinion leader, using information selectively, and influential conflicts of interest.

Conclusions

‘Evidence’ and ‘negotiation’ are both essential inputs of reimbursement policy. Yet, purposely selected equivocal cases in Belgium provide a rich source to learn from and to improve the interaction between both. We formulated policy recommendations to reconcile the impact of all factors identified. A more systematic approach to reimburse new care may be one of many instruments to resolve the budgetary crisis in health care in other countries as well, by separating what is truly innovative and value for money from additional ‘waste’.     

The abrupt climate change at the Eocene–Oligocene boundary and the emergence of South-East Asia triggered the spread of sapindaceous lineages

Background and Aims

Paleoclimatic data indicate that an abrupt climate change occurred at the Eocene–Oligocene (E–O) boundary affecting the distribution of tropical forests on Earth. The same period has seen the emergence of South-East (SE) Asia, caused by the collision of the Eurasian and Australian plates. How the combination of these climatic and geomorphological factors affected the spatio-temporal history of angiosperms is little known. This topic is investigated by using the worldwide sapindaceous clade as a case study.

Methods

Analyses of divergence time inference, diversification and biogeography (constrained by paleogeography) are applied to a combined plastid and nuclear DNA sequence data set. Biogeographical and diversification analyses are performed over a set of trees to take phylogenetic and dating uncertainty into account. Results are analysed in the context of past climatic fluctuations.

Key Results

An increase in the number of dispersal events at the E–O boundary is recorded, which intensified during the Miocene. This pattern is associated with a higher rate in the emergence of new genera. These results are discussed in light of the geomorphological importance of SE Asia, which acted as a tropical bridge allowing multiple contacts between areas and additional speciation across landmasses derived from Laurasia and Gondwana.

Conclusions

This study demonstrates the importance of the combined effect of geomorphological (the emergence of most islands in SE Asia approx. 30 million years ago) and climatic (the dramatic E–O climate change that shifted the tropical belt and reduced sea levels) factors in shaping species distribution within the sapindaceous clade.     

Quantifying the Role of Adverse Events in the Mortality Difference between First and Second-Generation Antipsychotics in Older Adults: Systematic Review and Meta-Synthesis

Background

Observational studies have reported higher mortality among older adults treated with first-generation antipsychotics (FGAs) versus second-generation antipsychotics (SGAs). A few studies examined risk for medical events, including stroke, ventricular arrhythmia, venous thromboembolism, myocardial infarction, pneumonia, and hip fracture.

Objectives

1) Review robust epidemiologic evidence comparing mortality and medical event risk between FGAs and SGAs in older adults; 2) Quantify how much these medical events explain the observed mortality difference between FGAs and SGAs.

Data sources

Pubmed and Science Citation Index.

Study eligibility criteria, participants, and interventions

Studies of antipsychotic users that: 1) evaluated mortality or medical events specified above; 2) restricted to populations with a mean age of 65 years or older 3) compared FGAs to SGAs, or both to a non-user group; (4) employed a “new user” design; (5) adjusted for confounders assessed prior to antipsychotic initiation; (6) and did not require survival after antipsychotic initiation. A separate search was performed for mortality estimates associated with the specified medical events.

Study appraisal and synthesis methods

For each medical event, we used a non-parametric model to estimate lower and upper bounds for the proportion of the mortality difference—comparing FGAs to SGAs—mediated by their difference in risk for the medical event.

Results

We provide a brief, updated summary of the included studies and the biological plausibility of these mechanisms. Of the 1122 unique citations retrieved, we reviewed 20 observational cohort studies that reported 28 associations. We identified hip fracture, stroke, myocardial infarction, and ventricular arrhythmias as potential intermediaries on the causal pathway from antipsychotic type to death. However, these events did not appear to explain the entire mortality difference.

Conclusions

The current literature suggests that hip fracture, stroke, myocardial infarction, and ventricular arrhythmias partially explain the mortality difference between SGAs and FGAs.     

Discontinuation of adalimumab after attaining disease activity score 28-erythrocyte sedimentation rate remission in patients with rheumatoid arthritis (HONOR study): an observational study

Introduction

Evidences of biologics-free disease control after discontinuing adalimumab (ADA) in rheumatoid arthritis (RA) patients in clinical practice have not been sufficiently investigated. Purpose of this study is to investigate whether disease activity score 28 (DAS28)- erythrocyte sedimentation rate (ESR) remission was preserved after discontinuation of ADA in patients with RA.

Methods

This is an observational but not a randomized controlled study. Among 197 RA patients who initiated with combination of ADA with concomitant MTX, 69 (35%) acquired DAS28 (ESR) < 2.6 for at least 24 weeks. Of those 69 patients, 51 went on ADA discontinuation with their consent, and finally 50 of those with follow-up of > 24 weeks were evaluated. The effect of discontinuing ADA on clinical disease activity, functional disability and radiographic progression were evaluated by DAS28 (ESR), the clinical disease activity index (CDAI) and the simplified disease activity index (SDAI), by a health assessment questionnaire-disability index (HAQ-DI) and by the modified total Sharp score (mTSS), respectively.

Results

The mean age of the participants was 59.5 years with the mean disease duration of 7.1 years. Out of the 50 patients, 29 (58%) were maintained in DAS28 (ESR) < 2.6 at 24 weeks after discontinuing ADA. A logistic regression analysis showed that DAS28 (ESR) at baseline significantly predicted a DAS28 (ESR) < 2.6 maintained after discontinuation of ADA, and a receiver-operating characteristic (ROC) analysis showed that the cut-off value of DAS28 (ESR) at discontinuation was 2.16. The mean HAQ-DI at six months after discontinuing ADA was 0.1 in patients who kept in DAS28 (ESR) < 2.6, and 94.9% (37/39) showed no evidence of radiographic progression (> 0.5 per year of a change in mTSS) at 1 year.

Conclusions

It was possible to maintain DAS28 (ESR) < 2.6 after discontinuation of ADA without functional and radiographic progression and very low DAS28 (ESR) at the discontinuation was associated with successful ADA-free DAS28 (ESR) < 2.6 in patients with RA.

Trial registration

University Hospital Medical Information Network Identifier: UMIN000006669.     

Effect of Er,Cr:YSGG Laser at Different Output Powers on the Micromorphology and the Bond Property of Non-Carious Sclerotic Dentin to Resin Composites

Background

The objective of this study was to investigate the influence of Er,Cr:YSGG laser irradiated at different powers on the micromorphology and the bonding property of non-carious sclerotic dentin to resin composites.

Methods

Two hundred bovine incisors characterized by non-carious sclerotic dentin were selected, and the seventy-two teeth of which for surface morphological analysis were divided into nine groups according to various treatments (A: the control group, B: only treated with the adhesive Adper Easy One, C: diamond bur polishing followed by Adper Easy One, D-I: Er,Cr:YSGG laser irradiating at 1W, 2W, 3W, 4W, 5W, 6W output power, respectively, followed by Adper Easy One). The surface roughness values were measured by the non-contact three-dimensional morphology scanner, then the surface micromorphologies of surfaces in all groups were assessed by scanning electron microscopy (SEM); meanwhile, Image Pro-Plus 6.0 software was used to measure the relative percentage of open tubules on SEM images. The rest, one hundred twenty-eight teeth for bond strength test, were divided into eight groups according to the different treatments (A: only treated with the adhesive Adper Easy One, B: diamond bur polishing followed by the above adhesive, C-H: Er,Cr:YSGG laser irradiating at 1 W, 2 W, 3 W, 4 W, 5 W, 6 W output power, respectively, followed by the above adhesive), and each group was subsequently divided into two subgroups according to whether aging is performed (immediately tested and after thermocycling). Micro-shear bond strength test was used to evaluate the bond strength.

Results

The 4W laser group showed the highest roughness value (30.84±1.93μm), which was statistically higher than the control group and the diamond bur groups (p<0.05). The mean percentages ((27.8±1.8)%, (28.0±2.2)%, (30.0±1.9)%) of open tubules area in the 4W, 5W, 6W group were higher than other groups (p<0.05). The 4W laser group showed the highest micro-shear bond strength not only in immediately tested (17.60±2.55 PMa) but after thermocycling (14.35±2.08MPa).

Conclusion

The Er,Cr:YSGG laser at 4W power can effectively improve the bonding property between non-carious sclerotic dentin and resin composites by increasing the roughness and mean percentage area of open tubules.     

A Rhinocerotid Skull Cooked-to-Death in a 9.2 Ma-Old Ignimbrite Flow of Turkey

Background

Preservation of fossil vertebrates in volcanic rocks is extremely rare. An articulated skull (cranium and mandible) of a rhinoceros was found in a 9.2±0.1 Ma-old ignimbrite of Cappadocia, Central Turkey. The unusual aspect of the preserved hard tissues of the skull (rough bone surface and brittle dentine) allows suspecting a peri-mortem exposure to a heating source.

Methodology/Principal Findings

Here we describe and identify the skull as belonging to the large two-horned rhinocerotine Ceratotherium neumayri, well-known in the late Miocene of the Eastern Mediterranean Province. Gross structural features and microscopic changes of hard tissues (bones and teeth) are then monitored and compared to the results of forensic and archaeological studies and experiments focusing on heating effects, in order to reconstruct the hypothetical peri-mortem conditions. Macroscopic and microscopic structural changes on compact bones (canaliculi and lamellae vanished), as well as partial dentine/cementum disintegration, drastic enamel-dentine disjunctions or microscopic cracks affecting all hard dental tissues (enamel, cementum, and dentine) point to continued exposures to temperatures around 400–450°C. Comparison to other cases of preservation of fossil vertebrates within volcanic rocks points unambiguously to some similarity with the 79 AD Plinian eruption of the Vesuvius, in Italy.

Conclusions/Significance

A 9.2±0.1 Ma-old pyroclastic density current, sourced from the Çardak caldera, likely provoked the instant death of the Karacaşar rhino, before the body of the latter experienced severe dehydration (leading to the wide and sustainable opening of the mouth), was then dismembered within the pyroclastic flow of subaerial origin, the skull being separated from the remnant body and baked under a temperature approximating 400°C, then transported northward, rolled, and trapped in disarray into that pyroclastic flow forming the pinkish Kavak-4 ignimbrite ∼30 km North from the upper Miocene vent.     

Phenotypic Modulation of Corpus Cavernosum Smooth Muscle Cells in a Rat Model of Cavernous Neurectomy

Background

Patients undergoing radical prostatectomy (RP) are at high risk for erectile dysfunction (ED) due to potential cavernous nerve (CN) damage during surgery. Penile hypoxia after RP is thought to significantly contribute to ED pathogenesis.

Aim

We previously showed that corpora cavernosum smooth muscle cells (CCSMCs) undergo phenotypic modulation under hypoxic conditions in vitro. Here, we studied such changes in an in vivo post-RP ED model by investigating CCSMCs in bilateral cavernous neurectomy (BCN) rats.

Methods

Sprague-Dawley rats underwent sham (n = 12) or BCN (n = 12) surgery. After 12 weeks, they were injected with apomorphine to determine erectile function. The penile tissues were harvested and assessed for fibrosis using Masson trichrome staining and for molecular markers of phenotypic modulation using immunohistochemistry and western blotting. CCSMC morphological structure was evaluated by hematoxylin-eosin (H&E) staining and transmission electron microscopy (TEM).

Results

Erectile function was significantly lower in BCN rats than in sham rats. BCN increased hypoxia-inducible factor-1α and collagen protein expression in corpora cavernous tissue. H&E staining and TEM showed that CCSMCs in BCN rats underwent hypertrophy and showed rough endoplasmic reticulum formation. The expression of CCSMC phenotypic markers, such as smooth muscle α-actin, smooth muscle myosin heavy chain, and desmin, was markedly lower, whereas vimentin protein expression was significantly higher in BCN rats than in control rats.

Conclusions

CCSMCs undergo phenotype modulation in rats with cavernous neurectomy. The results have unveiled physiological transformations that occur at the cellular and molecular levels and have helped characterize CN injury–induced ED.     

Effects of an Internet-Based Cognitive Behavioral Therapy (iCBT) Program in Manga Format on Improving Subthreshold Depressive Symptoms among Healthy Workers: A Randomized Controlled Trial

Objective

The purpose of this study was to develop a new Internet-based computerized cognitive behavior therapy (iCBT) program in Manga format, the Japanese cartoon, for workers and to examine the effects of the iCBT program on improving subthreshold depression using a randomized controlled trial (RCT) design among workers employed in private companies in Japan.

Method

All workers in a company (n = 290) and all workers in three departments (n = 1,500) at the headquarters of another large company were recruited by an invitation e-mail. Participants who fulfilled the inclusion criteria were randomly allocated to intervention or control groups (N = 381 for each group). A six-week, six-lesson iCBT program using Manga (Japanese comic) story was developed. The program included several CBT skills: self-monitoring, cognitive restructuring, assertiveness, problem solving, and relaxation. The intervention group studied the iCBT program at a frequency of one lesson per week. Depression (Beck Depression Inventory II; BDI-II) was assessed as a primary outcome at baseline, and three- and six-month follow-ups for both intervention and control groups were performed.

Results

The iCBT program showed a significant intervention effect on BDI-II (t = −1.99, p<0.05) with small effect sizes (Cohen''s d: −0.16, 95% Confidence Interval: −0.32 to 0.00, at six-month follow-up).

Conclusions

The present study first demonstrated that a computerized cognitive behavior therapy delivered via the Internet was effective in improving depression in the general working population. It seems critical to improve program involvement of participants in order to enhance the effect size of an iCBT program.

Trial Registration

UMIN Clinical Trials Registry UMIN000006210 https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000007341&type=summary&language=E     

Association of E/E′ and NT-proBNP with Renal Function in Patients with Essential Hypertension

Objectives

To evaluate the association of left ventricular (LV) diastolic function and N-terminal pro-brain natriuretic peptide (NT-proBNP) with renal function in essential hypertension.

Methods

LV diastolic function was estimated by the ratio of early diastolic velocities (E) from transmitral inflow to early diastolic velocities (E′) of tissue Doppler at mitral annulus (septal corner); NT-proBNP was measured in 207 hypertensive patients (mean age 56±14 years). The subjects were classified into 3 groups: E/E′≤10 group (n = 48), 10<E/E′≤15 group (n = 109) and E/E′>15 group (n = 50). The renal function was estimated by glomerular filtration rate (GFR) with ^99mTc-DTPA. GFR from 30 to 59 ml/min/1.73 m² was defined as Stage 3 chronic kidney disease (CKD). GFR was also estimated using the modified MDRD equation. Albuminuria was defined by urinary albumin/creatinine ratio (UACR).

Results

GFR was lower and UACR was higher in E/E′ >15 group than in 10< E/E′ ≤15 group or E/E′ ≤10 group (p<0.0001), GFR was significantly negative and UACR was positive correlated with E/E′ and NT-proBNP (p<0.0001). In multivariate stepwise linear analysis, GFR had significant correlation with age (p = 0.001), gender (p = 0.003), E/E′ (p = 0.03), lgNT-proBNP (p = 0.001) and lgUACR (p = 0.01), while eGFR had no significant correlation with E/E′ or lgNT-proBNP. Multivariate logistic regression analysis, adjusted for potential confounding factors, showed that participants in E/E′>15 group were more likely to have Stage 3 CKD compared with those in E/E′≤10 group with an adjusted odds ratio of 8.31 (p = 0.0036).

Conclusions

LV diastolic function, assessed with E/E′ and NT-proBNP is associated with renal function in essential hypertension.     

Inactivation of Fam20C in Cells Expressing Type I Collagen Causes Periodontal Disease in Mice

Background

FAM20C is a kinase that phosphorylates secretory proteins. Previous studies have shown that FAM20C plays an essential role in the formation and mineralization of bone, dentin and enamel. The present study analyzed the loss-of-function effects of FAM20C on the health of mouse periodontal tissues.

Methods

By crossbreeding 2.3 kb Col 1a1-Cre mice with Fam20C^fl/fl mice, we created 2.3 kb Col 1a1-Cre;Fam20C^fl/fl (cKO) mice, in which Fam20C was inactivated in the cells that express Type I collagen. We analyzed the periodontal tissues in the cKO mice using X-ray radiography, histology, scanning electron microscopy and immunohistochemistry approaches.

Results

The cKO mice underwent a remarkable loss of alveolar bone and cementum, along with inflammation of the periodontal ligament and formation of periodontal pockets. The osteocytes and lacuno-canalicular networks in the alveolar bone of the cKO mice showed dramatic abnormalities. The levels of bone sialoprotein, osteopontin, dentin matrix protein 1 and dentin sialoprotein were reduced in the Fam20C-deficient alveolar bone and/or cementum, while periostin and fibrillin-1 were decreased in the periodontal ligament of the cKO mice.

Conclusion

Loss of Fam20C function leads to periodontal disease in mice. The reduced levels of bone sialoprotein, osteopontin, dentin matrix protein 1, dentin sialoprotein, periostin and fibrillin-1 may contribute to the periodontal defects in the Fam20C-deficient mice.     

Reproducibility and Prognostic Value of WHO1973 and WHO2004 Grading Systems in TaT1 Urothelial Carcinoma of the Urinary Bladder

Background

European treatment guidelines of TaT1 urinary bladder urothelial carcinomas depend highly on stage and WHO1973-grade but grading reproducibility is wanting. The newer WHO2004 grading system is still debated and both systems are currently used.

Aims

To compare reproducibility and prognostic value (of stage progression) of the WHO1973 and WHO2004.

Methods

One hundred and ninety-three primary urothelial carcinomas were reviewed. Follow-up data were retrieved from the patient records. Kappa statistics and Harrell''s C-index were used.

Results

Median follow-up was 75 months (range 1–127). 17 patients (9%) progressed, 82% of these within and 18% after 60 months. The distribution of WHO73-grades 1, 2 and 3 was 23%, 51% and 26%, interobserver agreement for each individual grade was 66% (kappa = 0.68), while for grades 1&2 versus 3 89% (kappa = 0.68). Intraobserver reproducibility was 68–63% for WHO73 and 88–89% for WHO73 as 1&2 vs.3. Progression free survival rates at 5 years were 95% (grade 1), 98% (grade 2) and 82% (grade 3) and 96% and 82% for grades 1&2 versus 3 (Hazard Ratio, HR, 5.4, p = 0.003). Using WHO2004, 62% were low grade and 38% high grade, inter-observer agreement 87% (kappa = 0.70), intraobserver reproducibility 93%, and progression free 5-year survival rates 97% and 85% (HR 6.6, p = 0.004). Positive and negative predictive values for stage progression within 5 years for the WHO73 (1&2 vs. 3) were 18% and 96%, and 15% and 97% for the WHO04. Using Harrell''s C-index, none of the grading systems was prognostically superior.

Conclusion

None of the grading systems is prognostically stronger than the others. Most importantly, inter-observer reproducibility and sensitivities for stage progression of both systems are low and need improvement for optimal treatment.     

Effect of Topical Tranexamic Acid on Bleeding and Quality of Surgical Field during Functional Endoscopic Sinus Surgery in Patients with Chronic Rhinosinusitis: A Triple Blind Randomized Clinical Trial

Background

The effect of tranexamic acid (TXA) on bleeding and improvement of surgical field during functional endoscopic sinus surgery (FESS) is not clear yet. This study was conducted to answer this question.

Methods

This trial was conducted on 60 patients with chronic sinusitis at Beasat Hospital, Hamadan, Iran, from April to November 2013. Thirty patients in the intervention group received three pledgets soaked with TXA 5% and phenylephrine 0.5% for 10 minutes in each nasal cavity before surgery. Thirty patients in the control group received phenylephrine 0.5% with the same way. The amount of bleeding and the quality of surgical field were evaluated at 15, 30, and 45 minutes after the start of surgery using Boezaart grading.

Results

The quality of the surgical field in the intervention group compared to the control group was significantly better in the first quarter (P = 0.002) and the second quarter (P = 0.003) but not in the third quarter (P = 0.163). Furthermore, the amount of bleeding was much less during all periods in the intervention group than in the control group (P = 0.001).

Conclusion

Topical TXA can efficiently reduce bleeding and improve the surgical field in FESS in patients with rhinosinusitis. Based on these findings, topical TXA may be a useful method for providing a suitable surgical field during the first 30 minutes after use.

Trial Registration

Iranian Registry of Clinical Trials IRCT201212139014N15