Nanoscale osseointegration of zirconia evaluated from the interfacial structure between ceria-stabilized tetragonal zirconia and cell-induced hydroxyapatite.

BACKGROUND: The osseointegration of zirconia implants has been evaluated based on their implant fixture bonding with the alveolar bone at the optical microscopic level. Achieving nano-level bonding between zirconia and bone apatite is crucial for superior osseointegration; however, only a few studies have investigated nanoscale bonding. This review outlines zirconia osseointegration, including surface modification, and presents an evaluation of nanoscale zirconia-apatite bonding and its structure. HIGHLIGHT: Assuming osseointegration, the cells produced calcium salts on a ceria-stabilized zirconia substrate. We analyzed the interface between calcium salts and zirconia substrates using transmission electron microscopy and found that 1) the cell-induced calcium salts were bone-like apatite and 2) direct nanoscale bonding was observed between the bone-like apatite and zirconia crystals without any special modifications of the zirconia surface. CONCLUSION: Structural affinity exists between bone apatite and zirconia crystals. Apatite formation can be induced by the zirconia surface. Zirconia bonds directly with apatite, indicating superior osseointegration in vivo.

Faster surgery initiation in oral cancer patients during the COVID-19 pandemic in Osaka, Japan.

BACKGROUND: We investigated the impact of the COVID-19 pandemic on oral cancer (OC), comparing diagnosis and number of pre-operative days in the diagnosis of OC in 2019 (pre-COVID-19) and that in 2020 (during the COVID-19 pandemic). METHODS: Using data from a cancer registry-based study on the impact of COVID-19 on cancer care in Osaka (CanReCO), we collected details of sex, age, residential area, cancer site, date of diagnosis, clinical stage at first treatment and number of pre-operative days in OC patients. RESULTS: A total of 1470 OC cases were registered. Incidence of OC before and during COVID-19 was 814 and 656 cases, respectively. During the first wave of the pandemic (March to May 2020), incidence was about half that in the same period in 2019 (2019; n = 271, 2020; n = 145). Number of pre-operative days (median number of days between the first hospital visit and surgery date) was significantly shorter during the COVID-19 year (24.5 days) than in the pre-COVID-19 year (28 days, p = 0.0015). CONCLUSIONS: Incidence of OC during the COVID-19 pandemic was lower than in pre-COVID-19. Despite disruption in the healthcare system, the number of pre-operative days for OC cases was shorter during the pandemic.

Early Detection of Radiation Pneumonitis on Cone-Beam CT Images During a Course of Radiotherapy: A Case Series Report.

Background and aim Radiation pneumonitis (RP) is a critical pulmonary toxicity following dose delivery to the lung, and it is usually diagnosed after radiotherapy courses are completed. Because RP may result in a lethal complication, a practical method for detecting early-phase RP is awaited. In this article, we describe our experience through a variety of clinical cases and discuss treatment decisions and lessons we have made and learned. Materials and methods A daily cone-beam computed tomography (CBCT) scan was employed with a lung window setting to detect the early-phase RP during treatment courses. For the past five years, thirty patients were diagnosed with RP, and eight patients were detected during radiotherapy courses on the CBCT images. Our best efforts were made in detecting early ground-glass opacity and early RP on CBCT images prior to symptoms. The eight cases were described in more detail with CBCT or CT images. Results and discussion Initially, RP was detected at 50 Gy or greater. However, more careful CBCT observation resulted in earlier detection at around 40 Gy. Then, a new problem arose whether the treatment should be terminated. It was reported that early RP development was associated with higher-grade complications, and therefore it is preferable to terminate radiotherapy once we detect even early-phase RP. However, termination in the middle of the treatment course may significantly reduce the therapeutic effect. In our experience, patients with favorable clinical status may continue to receive radiotherapy with careful observation of lung parenchyma on CBCT images and clinical data, such as Krebs Von den Lungen-6 (KL-6) and C-reactive protein (CRP). Conclusion We have shown that early detection of RP may be feasible during radiotherapy courses by daily monitoring of CBCT lung images. Further studies are awaited to proceed.

Cementum is key to periodontal tissue regeneration: A review on apatite microstructures for creation of novel cementum-based dental implants.

The cementum is the outermost layer of hard tissue covering the dentin within the root portion of the teeth. It is the only hard tissue with a specialized structure and function that forms a part of both the teeth and periodontal tissue. As such, cementum is believed to be critical for periodontal tissue regeneration. In this review, we discuss the function and histological structure of the cementum to promote crystal engineering with a biochemical approach in cementum regenerative medicine. We review the microstructure of enamel and bone while discussing the mechanism underlying apatite crystal formation to infer the morphology of cementum apatite crystals and their complex structure with collagen fibers. Finally, the limitations of the current dental implant treatments in clinical practice are explored from the perspective of periodontal tissue regeneration. We anticipate the possibility of advancing periodontal tissue regenerative medicine via cementum regeneration using a combination of material science and biochemical methods.

Travel patterns of patients seeking cancer care during the COVID-19 pandemic: Multi-centre cohort study in Osaka, Japan.

BACKGROUND: In Japan, provision of equal access to cancer care is intended to be achieved via secondary medical areas (SMAs). However, the percentage of patients receiving care within the residential area varies by SMA in Osaka Prefecture. We aimed to assess the effect size of factors associated with patient mobility, and whether patient mobility was affected by the COVID-19 pandemic. METHODS: Records of patients diagnosed with stomach, colorectal, lung, breast, cervical, oesophageal, liver or pancreatic cancer during 2019-2020 were extracted from multi-centre hospital-based cancer registry data. Odds ratios of whether a patient received care within the SMA of residence were set as the outcome. A multivariable model was built using generalised estimating equations with multiple imputation for missing data. Change in patient mobility after the pandemic was examined by deriving age- and SMA-specific adjusted ORs (aORs). RESULTS: A total of 78,839 records were included. Older age, more advanced stage and palliative care had up to 1.69 times higher aORs of receiving care within their own area. Patients with oesophageal, liver or pancreatic cancer tended to travel outside their area with aORs ranging from 0.71 to 0.90. Patients aged ≤ 79 and living in the East and South SMAs tended to remain in their area with aORs ranging from 1.05 to 1.11 after the pandemic. CONCLUSION: Patient mobility decreased for higher age and stage. It also varied by SMA, cancer site and treatment type. POLICY SUMMARY: Our results need to be linked with resource inputs to help policymakers decide whether to intervene to address current efficiency or equity issues.

Patterns of staging, treatment, and mortality in gastric, colorectal, and lung cancer among older adults with and without preexisting dementia: a Japanese multicentre cohort study.

BACKGROUND: Little is known about dementia's impact on patterns of diagnosis, treatment, and outcomes in cancer patients. This study aimed to elucidate the differences in cancer staging, treatment, and mortality in older cancer patients with and without preexisting dementia. METHODS: Using cancer registry data and administrative data from 30 hospitals in Japan, this multicentre retrospective cohort study examined patients aged 65-99 years who were newly diagnosed with gastric, colorectal, or lung cancer in 2014-2015. Dementia status (none, mild, and moderate-to-severe) at the time of cancer diagnosis was extracted from clinical summaries in administrative data, and set as the exposure of interest. We constructed multivariable logistic regression models to analyse cancer staging and treatment, and multivariable Cox regression models to analyse three-year survival. RESULTS: Among gastric (n = 6016), colorectal (n = 7257), and lung (n = 4502) cancer patients, 5.1%, 5.8%, and 6.4% had dementia, respectively. Patients with dementia were more likely to receive unstaged and advanced-stage cancer diagnoses; less likely to undergo tumour resection for stage I, II, and III gastric cancer and for stage I and II lung cancer; less likely to receive pharmacotherapy for stage III and IV lung cancer; more likely to undergo tumour resection for all-stage colorectal cancer; and more likely to die within three years of cancer diagnosis. The effects of moderate-to-severe dementia were greater than those of mild dementia, with the exception of tumour resection for colorectal cancer. CONCLUSION: Older cancer patients with preexisting dementia are less likely to receive standard cancer treatment and more likely to experience poorer outcomes. Clinicians should be aware of these risks, and would benefit from standardised guidelines to aid their decision-making in diagnosing and treating these patients.

Association between a low response to rubella vaccination and reduced anti-severe acute respiratory syndrome coronavirus 2 immune response after vaccination with BNT162b2: a cross-sectional study.

OBJECTIVES: Some vaccinated individuals fail to acquire an adequate immune response against infection. We aimed to determine whether mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination could induce a sufficient immune response against SARS-CoV-2 in low responders to other vaccinations. METHODS: Using data from health-care workers who received two doses of the BNT162b2 vaccine (BioNTech/Pfizer), we conducted a single-centre, cross-sectional study to determine whether low responders to measles, rubella, and hepatitis B virus (HBV) vaccinations could acquire sufficient antibodies after SARS-CoV-2 vaccination. From May 2021 to June 2021, participants were tested for anti-SARS-CoV-2 spike (anti-S) IgG antibodies at least 2 weeks after the second dose of BNT162b2. The association between a low response to measles, rubella, and HBV vaccinations and the post-vaccination anti-S IgG titre was evaluated using the multivariable linear regression analysis. RESULTS: All 714 participants were positive for the anti-S IgG titre (≥50.0 AU/mL) after two doses of BNT162b2 (median, 7126.8 AU/mL; interquartile range, 4496.2-11 296.8). There were 323 (45.2%), 131 (18.3%), and 43 (6.0%) low responders to measles, rubella, and HBV vaccinations, respectively. In the multivariable linear regression analysis, low responders to rubella vaccination had significantly low acquisition of the anti-S IgG titre after two doses of the BNT162b2 vaccine (standardized coefficient ß, -0.110; 95% CI, -0.175 to -0.044). CONCLUSIONS: A low response to rubella vaccination is a potential predictor of a reduced response to SARS-CoV-2 vaccination. Further studies are needed to determine whether a low response to rubella vaccination is associated with the durability of SARS-CoV-2 vaccination-induced immune response.

Socioeconomic disparities in cancer survival: Relation to stage at diagnosis, treatment, and centralization of patients to accredited hospitals, 2005-2014, Japan.

BACKGROUND: Cancer survival varies by socioeconomic status in Japan. We examined the extent to which survival disparities are explained by factors relevant to cancer control measures (promoting early-stage detection, standardizing treatment, and centralizing patients to government-accredited cancer hospitals [ACHs]). METHODS: From the Osaka Cancer Registry, patients diagnosed with solid malignant tumors during 2005-2014 and aged 15-84 years (N = 376,077) were classified into quartiles using the Area Deprivation Index (ADI). Trends in inequalities were assessed for potentially associated factors: early-stage detection, treatment modality, and utilization of ACH (for first contact/diagnosis/treatment). 3-year all-cause survival was computed by the ADI quartile. Multivariable Cox regression models were used to assess survival disparities and their trends through a series of adjustment for the potentially associated factors. RESULTS: During 2005-2014, the most deprived ADI quartile had lower rates than the least deprived quartile for early-stage detection (42.6% vs. 48.7%); receipt of surgery (58.1% vs. 64.1%); and utilization of ACH (83.5% vs. 88.4%). While rate differences decreased for receipt of surgery and utilization of ACH (Annual Percent Change = -3.2 and - 11.9, respectively) over time, it remained unchanged for early-stage detection. During 2012-2014, the most deprived ADI quartile had lower 3-year survival than the least deprived (59.0% vs. 69.4%) and higher mortality (Hazard Ratio [HR] = 1.32, adjusted for case-mix): this attenuated with additional adjustment for stage at diagnosis (HR = 1.23); treatment modality (HR = 1.20); and utilization of ACH (HR = 1.19) CONCLUSIONS: Despite improvements in equalizing access to quality cancer care during 2005-2014, survival disparities remained. Interventions to reduce inequalities in early-stage detection could ameliorate such gaps.

Impact of coexisting diabetes on survival and risk of developing second primary cancer in diabetes patients receiving drug therapy: A multicenter retrospective cohort study of patients with cancer in Japan.

AIMS/INTRODUCTION: We investigated the association between coexisting diabetes at the time of cancer diagnosis, and the overall survival and incidence of second primary cancer in patients with cancer and receiving drug therapy for diabetes. MATERIALS AND METHODS: We used cancer registry and administrative data of patients diagnosed with cancer at designated cancer care hospitals in Osaka Prefecture between 2010 and 2015. The presence of diabetes was identified from the prescription records of antidiabetic drugs in Diagnosis Procedure Combination System data. After adjusting for patient characteristics, we compared overall survival between patients with cancer with coexisting diabetes and those without coexisting diabetes using the Cox proportional hazards model. In addition, the impact of coexisting diabetes on the risk of developing second primary cancer was evaluated using a competing risk analysis. RESULTS: Of the 131,701 patients with cancer included in the analysis, 6,135 (4.7%) had coexisting diabetes. The 5-year survival rates for patients with and without coexisting diabetes were 56.2% (95% confidence interval 54.8-57.6) and 72.7% (95% confidence interval 72.4-73.0), respectively. Coexisting diabetes was associated with a higher risk of developing second primary cancer (subdistribution hazard ratio 1.23; 95% confidence interval 1.08-1.41). In site-specific analysis, coexisting diabetes was associated with an increased risk for the development of second primary cancer of multiple myeloma, and cancer of the uterus, pancreas and liver. CONCLUSIONS: Coexisting diabetes was associated with a higher mortality and risk of developing second primary cancer in Japanese patients with cancer and on drug therapy for diabetes.

Incidence of second primary cancers among survivors of childhood cancer: A population-based study, Osaka, Japan, 1975-2015.

Second primary cancer (SPC) is one of the most life-threatening late effects of childhood cancers. We investigated the incidence and survival outcomes of SPC in childhood cancer patients in Japan. Data were obtained from the population-based Osaka Cancer Registry. Individuals diagnosed with cancer at age 0-14 years during 1975-2014 and survived 2 months or longer were followed through December 2015. The risk of developing SPC was assessed with standardized incidence ratio (SIR), excess absolute risk (EAR, per 100,000 person-years), and cumulative incidence. Multivariable Poisson regression analysis was carried out to assess relative risks of SPC by treatment method. Survival analysis was undertaken using the Kaplan-Meier method. Of 7229 childhood cancer survivors, 101 (1.4%) developed SPC after a median of 11.6 years. Overall SIR was 5.0, which corresponded with 84.3 EAR. The cumulative incidence was 0.9%, 2.1%, and 3.4% at 10, 20, and 30 years, respectively. Among all SPCs, the type that contributed most to the overall burden was cancers in the central nervous system (EAR = 28.0) followed by digestive system (EAR = 15.1), thyroid (EAR = 8.3), and bones and joints (EAR = 7.8); median latency ranged from 2.0 years (lymphomas) to 26.6 years (skin cancers). Patients treated with radiotherapy alone were at a 2.58-fold increased risk of developing SPC compared to those who received neither chemotherapy nor radiotherapy. Among patients who developed SPCs, 5-year and 10-year survival probabilities after SPC diagnosis were 61.7% and 52.0%, respectively. Risk-based long-term follow-up planning is essential to inform survivorship care and help reduce the burden of SPCs in childhood cancer survivors.

Diagnosis and treatment of digestive cancers during COVID-19 in Japan: A Cancer Registry-based Study on the Impact of COVID-19 on Cancer Care in Osaka (CanReCO).

BACKGROUND: The coronavirus disease 2019 (COVID-19) affected cancer care in Japan, but the detailed impact on cancer diagnosis and treatment is not well-understood. We aimed to assess the impact of COVID-19 on digestive cancer care in Osaka Prefecture, which has a population of 8.8 million. METHODS: We conducted a multi-center cohort study, using hospital-based cancer registry (HBCR) data linked to administrative data from 66 designated cancer care hospitals in Osaka. Records of patients diagnosed with cancer of the stomach, colorectum, esophagus, liver, gallbladder or pancreas were extracted from the HBCR data. Baseline characteristics, such as the number of diagnoses, routes to diagnosis and clinical stage, were compared between patients diagnosed in 2019 and those in 2020. We also compared treatment patterns such as the number of treatments (operations, endoscopic surgeries, chemotherapies, radiotherapies), pathological stage and time to treatment for each digestive cancer. RESULTS: In total, 62,609 eligible records were identified. The number of diagnoses decreased in 2020, ranging from -1.9% for pancreatic cancer to -12.7% for stomach cancer. Screen-detected cases decreased in stomach and colorectal cancer. The percentage of clinical stage III slightly increased across different cancers, although it was only significant for colorectal cancer. Among 52,741 records analyzed for treatment patterns, the relative decrease in radiotherapy was larger than for other treatments. The median time from diagnosis to operation was shortened by 2-5 days, which coincided with the decrease in operations. CONCLUSION: The impact of COVID-19 on cancer care in 2020 was relatively mild compared with other countries but was apparent in Osaka. Further investigation is needed to determine the most affected populations.

Trends in age-standardised net survival of stomach cancer by subsite and stage: A population-based study in Osaka, Japan, 2001-2014.

INTRODUCTION: The burden of stomach cancer remains high, particularly among Asian countries. Although Japan is known to achieve high survival from stomach cancer, little is known regarding the survival trends for recent years and survival by subsite and stage. We report age-standardised 1-, 3-, 5- and 10-year net survival for patients diagnosed with stomach cancer in Osaka, Japan. METHODS: We analysed patients diagnosed with primary stomach cancer and registered in the population-based cancer registry in Osaka Prefecture between 2001 and 2014. We used the non-parametric Pohar Perme method to derive net survival for each year. Both cohort and period approaches were used. Age was standardised using weights of the external population of the International Cancer Survival Standard. Multiple imputation was applied to handle missing information on subsite and stage before estimating age-standardised net survival by subsite (cardia and non-cardia) and stage (localised, regional and distant metastasis). We then examined general trends in the cohort-based survival estimates, as well as by subsite and stage, using linear regression. RESULTS: A total of 97,276 patients were included in the analysis. Age-standardised net survival improved steadily (mean annual absolute change ≥1.2%). Net survival for both subsites improved, but cardia cancer showed 7-23% lower survival than non-cardia cancer throughout the study period. Five-year net survival remained high (≥80%) in the localised stage from the beginning of this study. Net survival increased steeply (≥1.4% per year) in the regional stage. Although 1-year net survival increased by 14% in the distant stage, 5-year and 10-year net survival remained below 10%. CONCLUSION: Age-standardised net survival for stomach cancer in Japan improved during the study period owing to an increase in the number of patients with localised stage at diagnosis and improved treatment. Monitoring both short- and long-term survival should be continued as management of stomach cancer progresses.

Mental health in Japanese children during school closures due to the COVID-19.

BACKGROUND: Changes in relationships, sleep rhythms, and physical activity caused by school closures instituted to curb the spread of COVID-19 influenced children's mental health. We explored changes in children's daily life and effects on their mental health during school closures. METHODS: Participants included elementary and junior high school students 9 years of age and older seen in the outpatient clinic during school closures and were required to complete the Japanese version of WHO Five Well-Being Index (WHO-5-J). The results were compared with those of students seen after schools reopened. RESULTS: Participants included 78 students in the school closure group and 113 in the school reopening group. Although those in the closure group devoted more time to family and sleep, their sleep rhythms, eating habits, and physical activities were disrupted. Although there were no significant differences between the two groups in total WHO-5-J scores, single WHO-5-J items such as activity and vigor and interest were significantly worse and rest was significantly better in the school closure group. CONCLUSION: Although school closures resulted in elementary and junior high school students spending more time with family and sleeping, their sleep rhythms, eating habits, and physical activities were disrupted. As the children's living environment changed, they felt less active and vigorous and had difficulty finding things that interested them. However, their sleep improved and overall, the number of children with potential mental health problems did not change.

Repurposing MDZ as a tool for tissue regeneration in dental cells.

BACKGROUND: Several recent studies have focused on the utility of drug repurposing to expand clinical application of approved therapeutics. Here, we investigate the efficacy of midazolam (MDZ) and cytokines for regenerating calcified tissue, using immortalized porcine dental pulp (PPU7) and mouse skeletal muscle derived myoblast (C2C12) cells, with the goal of repurposing MDZ as a new treatment to facilitate calcified tissue regeneration. HIGHLIGHTS: We noted that PPU7 and C2C12 cells cultured with various MDZ regimens displayed increased bone morphogenic protein (BMP-2), transforming growth factor beta (TGF-ß), and alkaline phosphatase activity. These increases were highest in PPU7 cells cultured with MDZ alone, and in C2C12 cells cultured with MDZ and BMP-2. PPU7 cells cultured under these conditions demonstrated markedly elevated expression of odontoblastic gene markers, indicating their likely differentiation into odontoblasts. Expression levels of osteoblastic gene markers also increased in C2C12 cells, suggesting that MDZ potentiates the effect of BMP-2, inducing osteoblast differentiation in these cells. Newly formed calcified deposits in both PPU7 and C2C12 cells were identified as hydroxyapatite via crystallographic and crystal engineering analyses. CONCLUSION: MDZ increases ALP activity, inducing expression of specific marker genes for both odontoblasts and osteoblasts while promoting hydroxyapatite production in both PPU7 and C2C12 cells. These responses were cell type specific. MDZ treatment alone could induce these changes in PPU7 cells, but C2C12 cell differentiation required BMP-2 addition.

Efficacy and safety associated with the infusion speed of intravenous immunoglobulin for the treatment of Kawasaki disease: a randomized controlled trial.

BACKGROUND: High-dose intravenous immunoglobulin (IVIG) is the mainstay of treatment for Kawasaki disease (KD). Usually, 2 g/kg of IVIG is administered over 10-24 h, depending on the institution or physician, but the association between infusion speed and effectiveness has not been reported. In this study, we evaluated the differences in efficacy and safety between two different IVIG administration speeds. METHODS: This was a multicenter, unblinded, randomized controlled study. Patients newly diagnosed with KD were randomized into two groups: one who received IVIG over 12 h (12H group, double speed), and one that received IVIG over 24 h (24H group, reference speed). The endpoints included the duration of fever, incidence of coronary artery abnormalities (CAAs) and of adverse events. Laboratory data were evaluated before and after IVIG administration. RESULTS: A total of 39 patients were enrolled. There was no difference between groups in fever duration after the initiation of IVIG (21 h vs. 21.5 h, p = 0.325), and no patient experienced CAAs. Two adverse events were observed in the 12H group (elevation of aspartate aminotransferase and vomiting), however no severe adverse events requiring treatments or extension of hospital stay were observed in either group. After initial IVIG administration, the change ratio of inflammatory markers, such as white blood cell counts, neutrophils, C-reactive protein, and albumin, did not show significant differences between the two groups. On the other hand, a greater increase of serum immunoglobulin G from its baseline level was observed in the 24H group compared to the 12H group (3037 ± 648 mg/dl vs. 2414 ± 248 mg/dl, p < 0.01). CONCLUSION: The efficacy and safety of IVIG administered over 12 h (double speed) were similar to those administered over 24 h (reference speed). TRIAL REGISTRATION: University Hospital Medical Information Network ( UMIN000014665 ). Registered 27 July 2014 - Prospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000017058.

Clinical evidence that a dysregulated master neural network modulator may aid in diagnosing schizophrenia.

There are no validated biomarkers for schizophrenia (SCZ), a disorder linked to neural network dysfunction. We demonstrate that collapsin response mediator protein-2 (CRMP2), a master regulator of cytoskeleton and, hence, neural circuitry, may form the basis for a biomarker because its activity is uniquely imbalanced in SCZ patients. CRMP2's activity depends upon its phosphorylation state. While an equilibrium between inactive (phosphorylated) and active (nonphosphorylated) CRMP2 is present in unaffected individuals, we show that SCZ patients are characterized by excess active CRMP2. We examined CRMP2 levels first in postmortem brains (correlated with neuronal morphometrics) and then, because CRMP2 is expressed in lymphocytes as well, in the peripheral blood of SCZ patients versus age-matched unaffected controls. In the brains and, more starkly, in the lymphocytes of SCZ patients <40 y old, we observed that nonphosphorylated CRMP2 was higher than in controls, while phosphorylated CRMP2 remained unchanged from control. In the brain, these changes were associated with dendritic structural abnormalities. The abundance of active CRMP2 with insufficient opposing inactive p-CRMP2 yielded a unique lowering of the p-CRMP2:CRMP2 ratio in SCZ patients, implying a disruption in the normal equilibrium between active and inactive CRMP2. These clinical data suggest that measuring CRMP2 and p-CRMP2 in peripheral blood might reflect intracerebral processes and suggest a rapid, minimally invasive, sensitive, and specific adjunctive diagnostic aid for early SCZ: increased CRMP2 or a decreased p-CRMP2:CRMP2 ratio may help cinch the diagnosis in a newly presenting young patient suspected of SCZ (versus such mimics as mania in bipolar disorder, where the ratio is high).

Socioeconomic gaps over time in colorectal cancer survival in England: flexible parametric survival analysis.

BACKGROUND: Despite persistent reports of socioeconomic inequalities in colorectal cancer survival in England, the magnitude of survival differences has not been fully evaluated. METHODS: Patients diagnosed with colon cancer (n=68 169) and rectal cancer (n=38 267) in England (diagnosed between January 2010 and March 2013) were analysed as a retrospective cohort study using the National Cancer Registry data linked with other population-based healthcare records. The flexible parametric model incorporating time-varying covariates was used to assess the difference in excess hazard of death and in net survival between the most affluent and the most deprived groups over time. RESULTS: Survival analyses showed a clear pattern by deprivation. Hazard ratio of death was consistently higher in the most deprived group than the least deprived for both colon and rectal cancer, ranging from 1.08 to 1.17 depending on the model. On the net survival scale, the socioeconomic gap between the most and the least deprived groups reached approximately -4% at the maximum (-3.7%, 95% CI -1.6 to -5.7% in men, -3.6%, 95% CI -1.6 to -5.7% in women) in stages III for colon and approximately -2% (-2.3%, 95% CI -0.2 to -4.5% in men, -2.3%, 95% CI -0.2 to -4.3% in women) in stage II for rectal cancer at 3 years from diagnosis, after controlling for age, emergency presentation, receipt of resection and comorbidities. The gap was smaller in other stages and sites. For both cancers, patients with emergency presentation persistently had a higher excess hazard of death than those without emergency presentation. CONCLUSION: Survival disparities were profound particularly among patients in the stages, which benefit from appropriate and timely treatment. For the patients with emergency presentation, excess hazard of death remained high throughout three years from the diagnosis. Public health measures should be taken to reduce access inequalities to improve survival disparities.

Evaluating the mental health of children in a local hospital outpatient clinic.

BACKGROUND: The 30-item Questionnaire for Triage and Assessment (QTA30) is a standardized triage and assessment tool for assessing pediatric psychosomatic disorders. It is estimated that one in 10 children in Japan experience difficulties in their school life. Using the QTA30 we evaluated mental health in children at an outpatient clinic in a local hospital. METHODS: All elementary and junior high school students (≥9 years) who visited our institution between December 1 2019 and March 31 2020 were asked to complete the QTA30. RESULT: A total of 372 children responded. Half of the children with a psychosomatic disorder and 9% of children with other chronic disorders were suspected to have poor mental health. Suspected poor mental health was associated with higher odds of female gender (odds ratio [OR]: 1.89, 95% confidence interval [CI]: 1.07-3.39), junior high school students (OR: 3.73, 95% CI: 2.11-6.73), and not enjoying exercise (OR: 2.13, 95% CI: 1.16-3.9). The mean ± standard deviation total QTA30 score was significantly worse in children with psychosomatic disorders (38.0 ± 19.1) among children with other chronic diseases; however, only the score in children with central precocious puberty (27.4 ± 13.7) showed no difference. CONCLUSION: Based on our survey, the percentage of children suspected to have mental health problems manifesting as non-psychosomatic chronic disorders was similar to the proportion of children suspected to experience difficulties with their school life. Pediatricians should carefully consider the possibility of mental health problems when children are seen in regular visits to the outpatient clinic.

New insights into bioactivity of ceria-stabilized zirconia: Direct bonding to bone-like hydroxyapatite at nanoscale.

Osseointegration resulting from biomineralization means tight bone-implant attachment, which is clinically essential for successful dental implant treatment. The osseointegration ability of ceria-stabilized zirconia, a promising implant material, has been questionable and is unclear despite its clinical use due to zirconia's bioinert nature. The purpose of this research was to investigate the osseointegration ability of ceria-stabilized zirconia by clarifying its bioactivity. Here we show that ceria-stabilized zirconia is highly bioactive, contrary to the general consensus. Transmission electron microscopy observation revealed that the zirconia nanocrystals of a ceria-stabilized zirconia substrate directly bonded to osteoblastic cell-precipitated hydroxyapatite crystals at lattice fringe scale. This bonding was achieved without chemical treatment of the substrate surface before use. Hydroxyapatite crystals exhibited a morphology of flexible nanofibers less than 10 nm wide with nanometer-thick plates filling the spaces between nanofibers. Elemental analysis of the hydroxyapatites showed that they contained alkaline metal cations (Na, Mg, and K) as minor elements and that their average Ca/P atomic % ratio was ~1.40, similar to those of bone apatite. High bioactivity of ceria-stabilized zirconia resulted in direct bonding to bone-like hydroxyapatite, suggesting nanoscale direct osseointegration with bone in vivo that contributes to improving the success rate of dental implant treatment.

Coherent surface structure induces unique epitaxial overgrowth of metastable octacalcium phosphate on stable hydroxyapatite at critical fluoride concentration.

The phase transformation from soluble calcium phosphates to less-soluble hydroxyapatite (HAP) is a thermodynamically natural route. This process is irreversible, and effective use of poorly reactive HAP to repair teeth that have no cellular metabolism remains challenging. However, this thermodynamically controlled transformation may apparently be reversed through the fast nucleation and growth of metastable phases, leading to a reactive HAP surface. Here, the assembled HAP-nanorod phase is demonstrated to change into the metastable octacalcium phosphate (OCP) phase in a calcium phosphate solution containing 0.8 ppm fluoride. Grown OCPs display parallel surface streaks and their 11¯0 and 00l (l: odd) electron-diffraction spots are often not visible. The streaked, elongated OCP gradually grows into large plates with flat surfaces that exhibit an intense11¯0 spot. Crystal-structure models reveal that the unique epitaxial overgrowth of OCP on HAP occurs since both materials share coherent {100} faces, resulting in the distinctive disappearance of 11¯0 and 00l OCP spots. A polysynthetic twin model that reliably explains this disappearance is proposed for the growth of OCP. This apparent reverse phase transformation produces hybrid calcium phosphates consisting of HAP cores and highly reactive outer OCP layers that are promising for the repair of dentin caries. STATEMENT OF SIGNIFICANCE: This paper demonstrates important and interesting finding regarding formation of calcium phosphates in relation to their crystal structures. We first show that hydroxyapatite (HAP), the major constituent of human teeth and bone, can reversely change to its precursor, octacalcium phosphate (OCP), contrary to thermodynamic-stability rule. This apparent reverse phase transformation occurs through sharing the coherent {100} faces of both materials under controlled fluoride concentration. Nanoscale similarity of two crystal surfaces enables structurally shared epitaxial overgrowth of OCP on HAP aided by faster growth rate of OCP than that of HAP. This reaction produces hybrid crystal consisting of outer OCP and core HAP, that has not been known before and is able to be applied to dentin caries repair.