Endotoxin activity and leukocytic STAT3 mRNA alterations differ according to age in lipopolysaccharide-challenged calves.

The objective of this study was to investigate the age difference in the response to endotoxin in calves related to the plasma endotoxin activity and mRNA expression of cytokines. Fifteen calves were divided into three groups: control (191 ± 21 days), weaning (162.4 ± 17.5 days), and calf (22.4 ± 8.2 days). The weaning and calf groups received 2.5 µg/kg of ultrapure O111:B4 LPS in 10 mL of each autologous serum, whereas the control calves received a similar volume of saline. Blood samples were collected at 0, 0.5, 1, 2, 4, 8, 12, and 24 h. Liver samples were collected by ultrasound-guided liver biopsy at 0, 2, 4, and 24 h. Plasma endotoxin activity was measured by the limulus amebocyte lysate kinetic turbidimetric assay. The mRNA expression level of GAPDH, TLR-4, NF-κB2, TNF-α, IL-6, and STAT3 in leukocytes and the liver was measured by real-time PCR. Following LPS challenge, the maximal plasma endotoxin activity, and leukocytic expression of TLR4, NF-κB2, TNF-α, and STAT3 were reached at 0.5, 4, 2-4, 2-4, and 4 h, respectively, in weaning and calf groups. The endotoxin activity in calf remained high until 2 h. Furthermore, the expression of leukocytic STAT3 mRNA in calf was not significantly different from the pre-value. In contrast, STAT3 mRNA in weaning markedly increased at 2 and 4 h. Therefore, this study provides new information to the literature of immune and inflammatory responses in calves.

Imaging of electrostatic field vector distribution.

This paper reports on the visualization of a two-dimensional distribution of electrostatic field vectors around an electrified object using the electric field imager (EFIM) device. The EFIM device is made of a virtually connected pair of plate electrodes in parallel and in proximity, between which an electronic circuit for detection and optical indication is embedded. The EFIM device is not only accurately sensitive to the electrostatic field but also possessed of agility and mobility together with directivity and noninvasiveness. It was successfully demonstrated that electrostatic field vectors were visualized quantitatively, and their spatial distributions were mapped in combination with rather simple, mobile, and low-cost equipment. The advantages and disadvantages of the EFIM visualization scheme are discussed together with the future prospect of the EFIM device.

A statistical model for activation of Factor C by binding to LPS aggregates.

Published data on Factor C activity at various LPS and Lipid A concentrations (Nakamura et al. in Eur J Biochem 176:89, 1988; Kobayashi et al. in J Biol Chem 37:25987, 2014) were rearranged to show that Factor C exhibited its maximum activity at a specific concentration of LPS. A statistical model was proposed for examining whether a single LPS molecule binding activates Factor C (monomeric activation) or dimerization of Factor C is necessary for the activation (dimeric activation). In the monomeric activation model the plots of the relative activity of Factor C against the molar ratio of LPS to Factor C were different from those in the published data. The plots in the dimeric activation model lie on a bell-shaped curve, whatever the Factor C concentration, matching the published data and indicating the appropriateness of that model. We suggest that Factor C is activated by multiple molecular interactions of Factor C with LPS aggregates on which it dimerises and that this explains why larger aggregates are less effective at activating Factor C than smaller ones.

Levobupivacaine-dextran mixture for transversus abdominis plane block and rectus sheath block in patients undergoing laparoscopic colectomy: a randomised controlled trial.

We performed a randomised controlled double-blinded study of patients having laparoscopic colectomy with bilateral transversus abdominis plane block plus rectus sheath block, comparing a control group receiving 80 ml levobupivacaine 0.2% in saline with a dextran group receiving 80 ml levobupivacaine 0.2% in 8% low-molecular weight dextran. Twenty-seven patients were studied in each group. The mean (SD) maximum plasma concentration of levobupivacaine in the control group (1410 (322) ng.ml(-1) ) was higher than the dextran group (1141 (287) ng.ml(-1) ; p = 0.004), and was reached more quickly (50.6 (30.2) min vs 73.2 (24.6) min; p = 0.006). The area under the plasma concentration-time curve from 0 min to 240 min in the control group (229,124 (87,254) ng.min.ml(-1) ) was larger than in the dextran group (172,484 (50,502) ng.min.ml(-1) ; p = 0.007). The median (IQR [range]) of the summated numerical pain rating score at rest during the first postoperative 24 h in the control group (16 (9-20 [3-31]) was higher than in the dextran group (8 (2-11 [0-18]); p = 0.0001). In this study, adding dextran to levobupivacaine decreased the risk of levobupivacaine toxicity while providing better analgesia.

Early optimization of antimicrobial therapy improves clinical outcomes of patients administered agents targeting methicillin-resistant Staphylococcus aureus.

WHAT IS KNOWN AND OBJECTIVE: Antimicrobial stewardship is required to ensure the appropriate use of antimicrobials. However, no reports have been published on clinical outcomes of implementation of antimicrobial stewardship in patients receiving pathogen-specific antibiotics. METHOD: To evaluate the clinical outcomes of patients who received drugs, we conducted a single-centre, retrospective study of the effects of an antimicrobial stewardship programme targeting methicillin-resistant Staphylococcus aureus (MRSA). RESULTS: The time to administer effective antimicrobials was significantly (median number of days, 3 before vs. 0 after, P < 0·001) shortened, and the rate of de-escalation was significantly elevated (47·1% vs. 96·2%, P < 0·001) after implementation of daily review. The 60-day clinical failure associated with Gram-positive bacterial infection was significantly reduced (33·3% vs. 17·6%, P = 0·007) after intervention. WHAT IS NEW AND CONCLUSIONS: Daily review of administration of antimicrobials targeting MRSA was highly effective in improving clinical outcomes by optimizing early antimicrobial therapy.

Wnt3a signaling induces murine dental follicle cells to differentiate into cementoblastic/osteoblastic cells via an osterix-dependent pathway.

BACKGROUND AND OBJECTIVE: Dental follicle cells, putative progenitor cells for cementoblasts, osteoblasts and periodontal ligament cells, interplay with Hertwig's epithelial root sheath (HERS) cells during tooth root formation, in which HERS is considered to have an inductive role in initiating cementogenesis by epithelial-mesenchymal interaction. However, the specific mechanisms controlling the cementoblast/osteoblast differentiation of dental follicle cells are not fully understood. Canonical Wnt signaling has been implicated in increased bone formation by controlling mesenchymal stem cell or osteoblastic cell functions. This study examined the possible expression of canonical Wnt ligand in HERS and the role of Wnt signaling during the cementoblast/osteoblast differentiation of dental follicle cells. MATERIAL AND METHODS: The expression of Wnt3a, a representative canonical Wnt ligand, in HERS was assessed by immunohistochemistry. The differentiation and function of immortalized murine dental follicle cells were evaluated by measuring alkaline phosphatase (ALP, Alpl) activity and osteogenic gene expression. RESULTS: We identified the expression of Wnt3a in HERS during mouse tooth root development by immunohistochemistry as well as in cultured human epithelial rest cells of Malassez by real-time polymerase chain reaction, while no expression of Wnt3a was detected in cultured dental mesenchymal cells. Exposure of immortalized murine dental follicle cells to Wnt3a-induced ALP activity as well as expression of the Alpl gene. Pretreatment of cells with Dickkopf-1, a potent canonical Wnt antagonist, markedly attenuated the effect of Wnt3a on ALP expression. Furthermore, Wnt3a induced transcriptional activity of runt-related transcription factor 2 (Runx2) and expression of osterix at gene and/or protein levels. Treatment with osterix-small interfering RNA significantly inhibited Wnt3a-induced ALP expression at gene and protein levels. CONCLUSION: These findings suggest that HERS has a potential role in stimulating cementoblast/osteoblast differentiation of dental follicle cells via the Wnt/ß-catenin signaling pathway.

Bone marrow lesions, subchondral bone cysts and subchondral bone attrition are associated with histological synovitis in patients with end-stage knee osteoarthritis: a cross-sectional study.

OBJECTIVE: The aim of this study was to examine the osteoarthritis (OA)-related structural changes associated with histological synovitis in end-stage knee OA patients. METHODS: Forty end-stage knee OA patients (female: 88%, mean age: 71.8 y) were enrolled. All participants underwent 3.0-T MRI. The structural changes, such as cartilage morphology, subchondral bone marrow lesion (BML), subchondral bone cyst (SBC), subchondral bone attrition (SBA), osteophytes, meniscal lesion and synovitis, were scored using the whole-organ MRI scoring (WORMS) method. Synovial samples were obtained from five regions of interest (ROIs) of the knee joint during total joint replacement surgery. The associations between the histological synovitis score (HSS) and WORMS or the synovial expression levels of cyclooxygenase (COX)-2, interleukin (IL)-1ß, IL-6 and transforming growth factor (TGF)-ß were examined using Spearman's correlation coefficient. RESULTS: Among the seven OA-related structural changes, the BML, SBC, SBA and synovitis were significantly associated with the HSS (r = 0.33, 0.35, 0.48 and 0.36, respectively), while other morphological changes were not. Although synovial COX-2, IL-1ß or IL-6 expression levels were not associated with the HSS, the synovial TGF-ß expression levels were associated with the HSS. CONCLUSION: The presence of BML, SBC and SBA was associated with histological synovitis in end-stage knee OA patients.

Expression of umami-taste-related genes in the tongue: a pilot study for genetic taste diagnosis.

OBJECTIVE: Expression of taste-related genes in the tongue was analysed to develop a technique for genetic diagnosis of umami taste disorders. MATERIALS AND METHODS: Tissue samples were collected from healthy volunteers by scraping the foliate papillae of the tongue. Immunocytochemistry staining of gustducin, a taste-cell-specific G protein, and gene expression analysis by real-time polymerase chain reaction of ß-actin, gustducin (GNAT3) and umami receptors (T1R1, T1R3 and mGluR1) were performed. Changes in umami receptor expression following application of umami substances onto the tongue were analysed. RESULTS: Gustducin-positive cells were observed in the samples, indicating the presence of taste cells. Gene expression of ß-actin, GNAT3, T1R1 and T1R3 was detected in all seven samples tested, while that of mGluR1 was detected in four samples. Sequence analysis by NCBI Blast showed that each polymerase chain reaction product had a 99% rate of identification of its target sequence. Stimulation of the tongue with monosodium glutamate significantly upregulated the gene expression levels of T1R1 and T1R3, indicating that this method can detect alterations in umami-related gene expression. CONCLUSION: Evaluation of the expression of the umami receptor genes, T1R1 and T1R3, in the tongue may be clinically useful for objective genetic diagnosis of umami taste disorders.

CHIP buffers heterogeneous Bcl-2 expression levels to prevent augmentation of anticancer drug-resistant cell population.

Many types of cancer display heterogeneity in various features, including gene expression and malignant potential. This heterogeneity is associated with drug resistance and cancer progression. Recent studies have shown that the expression of a major protein quality control ubiquitin ligase, carboxyl terminus of Hsc70-interacting protein (CHIP), is negatively correlated with breast cancer clinicopathological stages and poor overall survival. Here we show that CHIP acts as a capacitor of heterogeneous Bcl-2 expression levels and prevents an increase in the anticancer drug-resistant population in breast cancer cells. CHIP knockdown in breast cancer cells increased variation in Bcl-2 expression levels, an antiapoptotic protein, among the cells. Our results also showed that CHIP knockdown increased the proportion of anticancer drug-resistant cells. These findings suggest that CHIP buffers variation in gene expression levels, affecting resistance to anticancer drugs. In single-cell clones derived from breast cancer cell lines, CHIP knockdown did not alter the variation in Bcl-2 expression levels and the proportion of anticancer drug-resistant cells. In contrast, when clonal cells were treated with a mutagen, the variation in Bcl-2 expression levels and proportion of anticancer drug-resistant cells were altered by CHIP knockdown. These results suggest that CHIP masks genetic variations to suppress heterogeneous Bcl-2 expression levels and prevents augmentation of the anticancer drug-resistant population of breast cancer cells. Because genetic variation is a major driver of heterogeneity, our results suggest that the degree of heterogeneity in expression levels is decided by a balance between genetic variation and the buffering capacity of CHIP.

Preoperative hydroperoxide concentrations are associated with a risk of postoperative complications after cardiac surgery.

This study aimed to assess whether preoperative oxidative stress levels can predict postoperative complications in patients undergoing cardiac surgery. Ninety-five cardiac surgery patients received an assessment of preoperative oxidative stress by measurement of hydroperoxide values in blood via the d-Rom test. Area under the receiver operating characteristic curve and also multivariate logistic regression were used to evaluate the prognostic significance of preoperative hydroperoxide concentrations in predicting the occurrence of major organ morbidity and mortality (MOMM). MOMM included death, deep sternal infection, reoperation, stroke, renal failure requiring haemodialysis and prolonged ventilation (>48 hours). The ability of preoperative hydroperoxide concentrations to predict MOMM was not significantly different from that of the European system for cardiac operative risk evaluation (EuroSCORE) (area under the receiver operating characteristic curve 0.822 versus 0.821 respectively, P=0.983). The optimal threshold value of hydroperoxide concentration to differentiate between patients with and without MOMM was 450 UCarr (sensitivity, 87.0%; specificity, 81.9%). Duration of intensive care unit stay, mechanical ventilation time and hospital stay were significantly longer in patients with preoperative hydroperoxide concentrations ≥450 UCarr (H group) compared to those patients with preoperative hydroperoxide concentrations <450 UCarr (L group). An increase in preoperative hydroperoxide concentrations remained associated with an increased risk of MOMM (odds ratios: 1.01, 95% confidence interval: 1.00 to 1.03) and prolonged intensive care unit stay (odds ratio 1.01, 95% confidence interval: 1.00 to 1.02), after adjusting for age, gender and EuroSCORE. In conclusion, an increased hydroperoxide concentration before cardiac surgery is an independent risk factor for severe postoperative complications.

The factors associated with pain severity in patients with knee osteoarthritis vary according to the radiographic disease severity: a cross-sectional study.

OBJECTIVES: Knee osteoarthritis (OA) pain is suggested to be associated with inflammation and detrimental mechanical loading across the joint. In this cross-sectional study, we simultaneously examined the inflammation and alignment of the lower limb and examined how the pain components varied depending on the disease progression. DESIGN: One-hundred sixty female medial type of early- [n = 74 in Kellgren-Lawrence (K/L) 2] to advanced-stage (n = 96 in K/L >2) knee OA subjects (70.5 years on average) were enrolled. Knee pain was evaluated using a pain visual analog scale (VAS) and the pain-related subcategory of the Japanese Knee Osteoarthritis Measure (JKOM-pain). The serum interleukin (sIL)-6 level reflecting synovitis, and the high sensitivity C-reactive protein (hs-CRP) level were measured to evaluate the severity of inflammation. The anatomical axis angle (AAA) was measured as an alignment index. The ß-coefficient was estimated after adjusting for age and the body mass index (BMI) using a multiple linear regression analysis. RESULTS: Multiple linear regression analyses showed that the sIL-6 levels, but not AAA, associated with the pain VAS [ß = 10.77 (95% confidence interval (CI): 4.14-17.40), P < 0.01] and JKOM-pain scores [ß = 3.19 (95% CI: 1.93-4.44), P < 0.001] in the early stage. Conversely, AAA, but not the sIL-6 levels, was found to be associated with the pain VAS [ß = -1.29 (95% CI: -2.51 to -0.08), P < 0.05] and JKOM-pain scores [ß = -0.49 (95% CI: -0.82 to -0.16), P < 0.01] in the advanced stage. CONCLUSIONS: The presence of a higher level of sIL-6 and the varus alignment of the joint is associated with pain in early- and advanced-stage knee OA patients, respectively.

Ultrasound-guided single shot caudal block anesthesia reduces postoperative urinary catheter-induced discomfort.

BACKGROUND: Urinary catheter-induced discomfort during the postoperative period can be distressing, and sometimes results in severe restlessness and agitation, especially in middle-aged and elderly male patients. Recent advances in ultrasound technology have increased the consistency, safety, and ease of a caudal block even in older patients. We speculated that an ultrasound-guided caudal block would be reliable and safe as treatment for such postoperative discomfort. METHODS: Adult male patients (ASA I-II) undergoing cervical laminoplasty were allocated to either the caudal block (CB, N.=24) or non-block (NB, N.=24) group. Following anesthesia induction, urinary catheterization was performed using a 16 French Foley catheter. Thereafter, an ultrasound-guided caudal block was performed with 8 ml of 0.3% ropivacaine and 100 µg of fentanyl for patients in group CB, while group NB did not receive a caudal block. We assessed urinary catheter-induced discomfort as mild, moderate, or severe at 0, 2, 6, 10, and 18 hours after surgery, and compared the incidence and severity of discomfort between the groups using a randomized double-blind design. RESULTS: All caudal blocks were successfully performed with 1 or 2 needle insertions. The incidence of urinary catheter-induced discomfort was significantly reduced in group CB as compared to NB at 0, 2, and 6 hours, while severity was also reduced at 0 and 2 hours. No patient required re-catheterization due to urinary retention after catheter removal. There were no other complications related to the caudal block. CONCLUSION: Preoperative ultrasound-guided single shot caudal block anesthesia safely reduced postoperative urinary catheter-induced discomfort in our male patients.

Transversus abdominis plane block in combination with general anesthesia provides better intraoperative hemodynamic control and quicker recovery than general anesthesia alone in high-risk abdominal surgery patients.

BACKGROUND: Patients with severe cardiovascular disease are frequently hemodynamically unstable during abdominal surgery. Improving the safety of such patients by stabilizing intraoperative hemodynamics remains a major concern for anesthesiologists. Transversus abdominis plane (TAP) block in combination with general anesthesia may facilitate optimum anesthetic management of these high-risk patients. METHODS: Patients with cardiovascular disease classified as American Society of Anesthesiologists (ASA) physical status 3 were enrolled. The patients were undergoing elective abdominal surgery and were randomized to a group receiving general anesthesia and TAP block (Group T, N.=33) or a group receiving general anesthesia alone (Group G, N.=35). We compared the groups for intraoperative hemodynamic stability, anesthesia emergence time, amounts of anesthetics and opioids given, and frequency of emergency treatment with cardiovascular agents. A preliminary study demonstrated that systolic blood pressure and heart rate were maintained stable within 70-110% of their preanesthesia values throughout surgery in ASA 1 elderly patients without cardiovascular disease. Thus, the hemodynamically stable time was defined as the time when systolic blood pressure and heart rate were 70-110% of their preanesthesia values. The ratio of hemodynamically stable time to total operative time was used as an index of hemodynamic stability. RESULTS: The median (minimum-maximum) percentage of hemodynamically stable time was longer in Group T (91[50-100]%) than Group G (79[40-91]%, P<0.01). The mean sevoflurane concentration, amount of fentanyl given and frequency of vasopressor use were lower in Group T than Group G (P<0.05). Anesthesia emergence time was shorter in Group T (14[4-30] min) than Group G (18[9-52] min, P<0.01). No worsening of cardiovascular complications was observed. CONCLUSION: For abdominal surgery in patients with severe cardiovascular disease, combining TAP block with general anesthesia promotes intraoperative hemodynamic stability and early emergence from anesthesia.

Is the 7/2(1)- isomer state of 43S spherical?

We report on the spectroscopic quadrupole moment measurement of the 7/2(1)(-) isomeric state in (16)(43)S(27) [E*=320.5(5) keV, T(1/2)=415(3) ns], using the time dependent perturbed angular distribution technique at the RIKEN RIBF facility. Our value, |Q(s)|=23(3) efm(2), is larger than that expected for a single-particle state. Shell model calculations using the modern SDPF-U interaction for this mass region reproduce remarkably well the measured |Q(s)|, and show that non-negligible correlations drive the isomeric state away from a purely spherical shape.

Coexistence of fibrotic and chondrogenic process in the capsule of idiopathic frozen shoulders.

OBJECTIVE: To analyze changes in the capsule from idiopathic frozen shoulders and clarify their etiology. MATERIALS AND METHODS: Samples (the rotator interval capsule, middle glenohumeral ligament (MGHL), and inferior glenohumeral ligament (IGHL)) were collected from 12 idiopathic frozen shoulders with severe stiffness and 18 shoulders with rotator cuff tears as a control. The number of cells was counted and the tissue elasticity of the samples was calculated by scanning acoustic microscopy (SAM). The amount of glycosaminoglycan content was assessed by alcian blue staining. Gene and protein expressions related to fibrosis, inflammation, and chondrogenesis were analyzed by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Furthermore, the total genes of the two groups were compared by DNA microarray analysis. RESULTS: The number of cells was significantly higher and the capsular tissue was significantly stiffer in idiopathic frozen shoulders compared with shoulders with rotator cuff tears. Staining intensity of alcian blue was significantly stronger in idiopathic frozen shoulders. Gene expressions related to fibrosis, inflammation, and chondrogenesis were significantly higher in idiopathic frozen shoulders compared with shoulders with rotator cuff tears assessed by both qPCR and DNA microarray analysis. CONCLUSION: In addition to fibrosis and inflammation, which used to be considered the main pathology of frozen shoulders, chondrogenesis is likely to have a critical role in pathogenesis of idiopathic frozen shoulders.

Pleth variability index predicts hypotension during anesthesia induction.

BACKGROUND: The pleth variability index (PVI) is a new algorithm used for automatic estimation of respiratory variations in pulse oximeter waveform amplitude, which might predict fluid responsiveness. Because anesthesia-induced hypotension may be partly related to patient volume status, we speculated that pre-anesthesia PVI would be able to identify high-risk patients for significant blood pressure decrease during anesthesia induction. METHODS: We measured the PVI, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) in 76 adult healthy patients under light sedation with fentanyl to obtain pre-anesthesia control values. Anesthesia was induced with bolus administrations of 1.8 mg/kg propofol and 0.6 mg/kg rocuronium. During the 3-min period from the start of propofol administration, HR, SBP, DBP, and MAP were measured at 30-s intervals. RESULTS: HR, SBP, DBP, and MAP were significantly decreased after propofol administration by 8.5%, 33%, 23%, and 26%, respectively, as compared with the pre-anesthesia control values. Linear regression analysis that compared pre-anesthesia PVI with the decrease in MAP yielded an r value of -0.73. Decreases in SBP and DBP were moderately correlated with pre-anesthesia PVI, while HR was not. By classifying PVI >15 as positive, a MAP decrease >25 mmHg could be predicted, with sensitivity, specificity, positive predictive, and negative predictive values of 0.79, 0.71, 0.73, and 0.77, respectively. CONCLUSION: Pre-anesthesia PVI can predict a decrease in MAP during anesthesia induction with propofol. Its measurement may be useful to identify high-risk patients for developing severe hypotension during anesthesia induction.

An exploration of unmet information needs among breast cancer patients in Japan: a qualitative study.

Informational need assessment has become an important part of health care in order to provide information effectively in clinical settings. Literature on information needs in the West suggests that breast cancer (BC) patients needed more information than doctors had provided, and information that fully met their needs was associated with patients' long-term well-being. Since few studies on this issue have been conducted in Japan, where the general consultation style is less open and more indirect, compared with that in the West, the application of the findings in the West is questionable. The purpose of this qualitative study was to explore perceived information needs among female BC patients in Japan. Twelve Japanese women with BC participated in semi-structured face-to-face interviews. Grounded theory using verbatim transcripts extracted two main themes: information needed to minimize physical and psychological impacts of treatment and information needed for the resumption of normal life. These were closely related at two time points. Physical support after discharge was perceived as relatively insufficient, especially by women experiencing post-operative arm complications. More open and direct communication was preferred between patients and doctors/family members in the recovery phase. Unmet needs for information may lead to patients' distress.

Help-seeking patterns in Chinese women with symptoms of breast disease: a qualitative study.

BACKGROUND: Prompt utilization of health services on detecting breast symptoms can improve breast cancer (BC) survival. Little is known about Chinese women's help-seeking behaviour. Our aim was to determine patterns of self-referral among Hong Kong Chinese women with self-detected breast symptoms. METHODS: We recruited 37 women awaiting their first consultation at public hospitals for breast symptoms. Interviews were transcribed and analysed based on the grounded theory approaches. RESULTS: A two-stage help-seeking model provided the best interpretation of the data. Symptom recognition was triggered by symptom interpretation, symptom progression and social messages. Painful lumps were seen as symptomatic, but atypical symptoms were often dismissed as benign as they responded to dietary change. Symptom intensification and discussions with someone who had faced BC prompted consultation. Service utilization involved fear of consequences, confirmation need, symptom distress, lay referral, media prompts and opportunistic presentation. Fearing cancer as incurable delayed consultation. Utilization barriers included cost, uncertainty about referral pathways, competing priorities and embarrassment. CONCLUSIONS: Atypical and painless presentation was more common among women delaying presentation. Barriers included cost, access, time and embarrassment. Education should emphasize atypical symptoms, the high-cure rate and the need for early presentation. Reduced cost and improved access to clinics would enhance early consultation.

XBP1 may determine the size of the ameloblast endoplasmic reticulum.

Ameloblasts progress through defined stages of development as enamel forms on teeth. Pre-secretory ameloblasts give rise to tall columnar secretory ameloblasts that direct the enamel to achieve its full thickness. During the maturation stage, the ameloblasts shorten and direct the enamel to achieve its final hardened form. Here we ask how the volume of selected ameloblast organelles changes (percent volume per ameloblast) as ameloblasts progress through six defined developmental stages. We demonstrate that mitochondria volume peaks during late maturation, indicating that maturation-stage ameloblasts maintain a high level of metabolic activity. Also, the endoplasmic reticulum (ER) volume changes significantly as a function of developmental stage. This prompted us to ask if X-box-binding protein-1 (XBP1) plays a role in regulating ameloblast ER volume, as has been previously demonstrated for secretory acinar cells and for plasma cell differentiation. We demonstrate that Xbp1 expression correlates positively with percent volume of ameloblast ER.