Complete Loss of Natural Teeth and Loneliness: A Fixed-Effect Analysis.

Psychosocial properties of oral health have been reported. The present study aimed to investigate the causal effect of complete loss of natural teeth on loneliness by using fixed-effects analysis to control for confounding factors, including unmeasured time-invariant factors. Data from older adults participating in at least 2 consecutive waves of the English Longitudinal Study of Ageing in waves 3 (2006/2007), 5 (2010/2011), and 7 (2014/2015) were analyzed (N = 18,682 observations from 7,298 individuals). The association between complete loss of natural teeth and loneliness score (ranging from 3 to 9) was examined using fixed-effect linear regression analysis adjusting for time-varying confounders, including sociodemographic and health characteristics. The prevalence of complete tooth loss was 12.7%, 12.8%, and 10.6% in waves 3, 5, and 7, respectively. Individuals who transitioned to complete tooth loss during any 2 consecutive waves had an increase in loneliness score by 0.27 (95% confidence interval [CI] 0.03, 0.52), which was greater than those who maintained natural teeth (-0.03; 95% CI -0.05, -0.01). Fixed-effects analysis adjusting for time-varying confounders revealed a significant association between complete loss of natural teeth and an increase in loneliness score by 0.31 (95% CI 0.17, 0.46). Complete loss of natural teeth among older adults in England was associated with loneliness, even after accounting for measured time-varying and (un)measured time-invariant confounders. Retaining natural teeth may reduce the risk of loneliness.

Heterogeneous Association of Tooth Loss with Functional Limitations.

Tooth loss is prevalent in older adults and associated with functional capacity decline. Studies on the susceptibility of some individuals to the effects of tooth loss are lacking. This study aimed to investigate the heterogeneity of the association between tooth loss and higher-level functional capacity in older Japanese individuals employing a machine learning approach. This is a prospective cohort study using the data of adults aged ≥65 y in Japan (N = 16,553). Higher-level functional capacity, comprising instrumental independence, intellectual activity, and social role, was evaluated using the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC). The scale ranged from 0 (lowest function) to 13 (highest function). Doubly robust targeted maximum likelihood estimation was used to estimate the population-average association between tooth loss (having <20 natural teeth) and TMIG-IC total score after 6 y. The heterogeneity of the association was evaluated by estimating conditional average treatment effects (CATEs) using the causal forest algorithm. The result showed that tooth loss was statistically significantly associated with lower TMIG-IC total scores (population-average effect: -0.14; 95% confidence interval, -0.18 to -0.09). The causal forest analysis revealed the heterogeneous associations between tooth loss and lower TMIG-IC total score after 6 y (median of estimated CATEs = -0.13; interquartile range = 0.12). The high-impact subgroup (i.e., individuals with estimated CATEs of the bottom 10%) were significantly more likely to be older and male, had a lower socioeconomic status, did not have a partner, and had poor health conditions compared with the low-impact subgroup (i.e., individuals with estimated CATEs of the top 10%). This study found that heterogeneity exists in the association between tooth loss and lower scores on functional capacity. Implementing tooth loss prevention policy and clinical measures, especially among vulnerable subpopulations significantly affected by tooth loss, may reduce its burden more effectively.

Causal Effect of Tooth Loss on Cardiovascular Diseases.

Many studies suggest associations between oral health and cardiovascular diseases, but there is a lack of causal evidence. Exploiting exogenous variation in tooth loss in US adults due to differential childhood exposure to fluoridated water, this study investigated the causal effect of tooth loss on cardiovascular diseases. A total of 722,519 participants in the Behavioral Risk Factor Surveillance System (BRFSS) waves 2006, 2008, or 2010 (birth years 1940-1978) were included in the analytical sample. To identify the effect of tooth loss on having a history of coronary heart disease (CHD) or stroke, instrumental variable analysis exploited childhood exposure to drinking water fluoride as an instrument. The weighted prevalence of CHD and stroke histories was 5.1% and 2.1%, respectively. First-stage regression indicated that childhood exposure to drinking water fluoride was a strong instrument for the number of lost teeth in adulthood (coefficient -0.61; 95% confidence interval [CI] -0.80, -0.41; F = 37.47). The probability of CHD was significantly higher by 1.04 percentage points (95% CI 0.57, 1.50) per lost tooth. The effect of tooth loss on stroke was significant only for people aged ≥60 y (coefficient 0.93 percentage points; 95% CI 0.14, 1.71). These findings are supportive of a causal effect of tooth loss on cardiovascular diseases among US adults, particularly in older age.

Causal Inference: Onward and Upward!

When announcing the Sveriges Riksbank Prize in Economic Sciences in Memory of Alfred Nobel 2021, the Royal Swedish Academy emphasized how conclusions about cause and effect can be drawn from natural experiments. But what can dental research learn from this? The economist's toolbox provides a number of methods for causal inference from observational data such as instrumental variables, regression discontinuity designs, or difference-in-differences analyses. Although the relevance of improving causal inference in dental research has repeatedly been highlighted in recent years, dental research still seems to reveal major room for improvement in the application of such methods. First, there seems to be an absence of causal literature on key essential research questions for oral health. Second, the diversity and diffusion of causal inferential methods in the dental literature seem very limited so far. Third, while dental research has widely been promoting the use of directed acyclic graphs (DAGs) to help conceptualize causal thinking, comparably little attention seems to have been paid to choosing and applying appropriate data-analytic approaches for causal inference. Fourth, similar to other fields of medicine, confusion seems to persist within the dental research community as to the use of causal language. If dental research is to secure a robust evidence base for promoting effective oral health interventions, we argue that dental research needs to move beyond its current methodological echo chamber and embrace a radically different approach to causal inference. We call for editors, reviewers, and authors to embrace a much more critically reflective approach to causal inference.

Causal effect of tooth loss on depression: evidence from a population-wide natural experiment in the USA.

AIMS: Depression severely affects people's health and well-being. Oral diseases have been suggested to be associated with depression, but so far, there is no causal evidence. This study aimed to identify the causal effect of tooth loss on depression among US adults in a natural experiment study. METHODS: Instrumental variable analysis was conducted using data from 169 061 respondents born in 1940-1978 who participated in the 2006, 2008 or 2010 waves of the Behavioral Risk Factor Surveillance System (BRFSS). Random variation in tooth loss due to differential childhood exposure to drinking water fluoride was exploited as an instrument. RESULTS: US adults who were exposed to drinking water fluoride in childhood had more remaining teeth, therefore providing a robust instrument (F = 73.4). For each additional tooth loss, depressive symptoms according to the eight-item Patient Health Questionnaire depression (PHQ-8) score increased by 0.146 (95% CI 0.008-0.284), and the probability of having clinical depression (PHQ ⩾10) increased by 0.81 percentage points (95% CI -0.12 to 1.73). CONCLUSIONS: Tooth loss causally increased depression among US adults. Losing ten or more teeth had an impact comparable to adults with major depressive disorder not receiving antidepressant drugs.

Dental Pain and Worsened Socioeconomic Conditions Due to the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has led to economic contraction and significant restrictions on society. The shock to the economy could lead to a deterioration of physical health outcomes, including dental health. The present study investigated the association between worsened socioeconomic conditions due to the COVID-19 pandemic and dental pain in Japan. The mediating effects of psychological distress and oral health-related behaviors were also evaluated. Cross-sectional data from the Japan COVID-19 and Society Internet Survey conducted from August to September 2020 (n = 25,482; age range, 15-79 y) were analyzed. Multivariable logistic regression models were fitted to evaluate the independent associations of household income reduction, work reduction, and job loss due to the COVID-19 pandemic with dental pain within a month. Dental pain was reported by 9.8%. Household income reduction, work reduction, and job loss were independently associated with dental pain after adjusting for confounders (odds ratios: 1.42 [95% confidence interval (CI), 1.28-1.57], 1.58 [95% CI, 1.41-1.76], 2.17 [95% CI, 1.64-2.88], respectively). The association related to household income reduction was mediated by psychological distress, postponing dental visits, toothbrushing behavior, and between-meals eating behavior by 21.3% (95% CI, 14.0-31.6), 12.4% (95% CI, 7.2-19.6), 1.5% (95% CI, -0.01 to 4.5), and 9.3% (95% CI, 5.4-15.2), respectively. Our findings showed that worsened socioeconomic conditions due to the COVID-19 pandemic deteriorated dental health. Policies that protect income and job loss may reduce dental health problems after the pandemic.

Prognostic grade for resecting hepatocellular carcinoma: multicentre retrospective study.

BACKGROUND: Surgical treatment for hepatocellular carcinoma (HCC) is advancing, but a robust prediction model for survival after resection is not available. The aim of this study was to propose a prognostic grading system for resection of HCC. METHODS: This was a retrospective, multicentre study of patients who underwent first resection of HCC with curative intent between 2000 and 2007. Patients were divided randomly by a cross-validation method into training and validation sets. Prognostic factors were identified using a Cox proportional hazards model. The predictive model was built by decision-tree analysis to define the resection grades, and subsequently validated. RESULTS: A total of 16 931 patients from 795 hospitals were included. In the training set (8465 patients), four surgical grades were classified based on prognosis: grade A1 (1236 patients, 14.6 per cent; single tumour 3 cm or smaller and anatomical R0 resection); grade A2 (3614, 42.7 per cent; single tumour larger than 3 cm, or non-anatomical R0 resection); grade B (2277, 26.9 per cent; multiple tumours, or vascular invasion, and R0 resection); and grade C (1338, 15.8 per cent; multiple tumours with vascular invasion and R0 resection, or R1 resection). Five-year survival rates were 73.9 per cent (hazard ratio (HR) 1.00), 64.7 per cent (HR 1.51, 95 per cent c.i. 1.29 to 1.78), 50.6 per cent (HR 2.53, 2.15 to 2.98), and 34.8 per cent (HR 4.60, 3.90 to 5.42) for grades A1, A2, B, and C respectively. In the validation set (8466 patients), the grades had equivalent reproducibility for both overall and recurrence-free survival (all P < 0.001). CONCLUSION: This grade is used to predict prognosis of patients undergoing resection of HCC.

Panel of novel urine biomarkers for incident microalbuminuria in people with type 2 diabetes mellitus.

AIM: The need to identify novel biomarkers for early diagnosis and treatment of diabetic nephropathy is widely recognized. However, only a few studies have investigated the association between biomarkers and the onset of albuminuria. In this study, we aimed to investigate a panel of biomarkers suitable for predicting microalbuminuria. METHODS: Some 346 Japanese people with type 2 diabetes exhibiting normoalbuminuria were studied. The endpoint was defined as the onset of microalbuminuria. Thirty biomarkers were selected from among urinary biomarkers described in previous studies. A panel of biomarkers was selected using least absolute shrinkage and selection operator (LASSO). The prognostic performance of the developed panel was evaluated. RESULTS: During a mean follow-up of 6.2 years, 45 people progressed to microalbuminuria. A composite panel of six biomarkers (monocyte chemoattractant protein-1, osteopontin, soluble human tumour necrosis factor receptor-1, tenascin C, vascular endothelial growth factor-A and kidney injury molecule-1) was developed using LASSO. Compared with the basal model comprising estimated GFR and urinary albumin-to-creatinine ratio, addition of these six biomarkers significantly increased the overall C index from 0.773 to 0.824 (P = 0.019). Net reclassification improvement and integrated discrimination improvement were estimated to be 0.412 (P = 0.049) and 0.040 (P = 0.040), respectively. Decision curve analysis also showed that the model with the six novel biomarkers had a better prognostic value for predicting the onset of microalbuminuria. The optimism was moderate or negligible according to measures. CONCLUSIONS: The panel consisting of six novel urinary biomarkers effectively predicted incident microalbuminuria in people with type 2 diabetes.

Significance of the surgical hepatic resection margin in patients with a single hepatocellular carcinoma.

BACKGROUND: The impact of a wide surgical margin on the outcome of patients with hepatocellular carcinoma (HCC) has not been evaluated in relation to the type of liver resection performed, anatomical or non-anatomical. The aim of this study was to evaluate the impact of surgical margin status on outcomes in patients undergoing anatomical or non-anatomical resection for solitary HCC. METHODS: Data from patients with solitary HCC who had undergone non-anatomical partial resection (Hr0 group) or anatomical resection of one Couinaud segment (HrS group) between 2000 and 2007 were extracted from a nationwide survey database in Japan. Overall and recurrence-free survival associated with the surgical margin status and width were evaluated in the two groups. RESULTS: A total of 4457 patients were included in the Hr0 group and 3507 in the HrS group. A microscopically positive surgical margin was associated with poor overall survival in both groups. A negative but 0-mm surgical margin was associated with poorer overall and recurrence-free survival than a wider margin only in the Hr0 group. In the HrS group, the width of the surgical margin was not associated with patient outcome. CONCLUSION: Anatomical resection with a negative 0-mm surgical margin may be acceptable. Non-anatomical resection with a negative 0-mm margin was associated with a less favourable survival outcome.

ANTECEDENTES: El impacto de un margen quirúrgico (surgical margin, SM) amplio en el resultado de pacientes con carcinoma hepatocelular (hepatocellular carcinoma, HCC) no ha sido evaluado en relación con el tipo de resección hepática realizada: anatómica o no anatómica. El objetivo del presente estudio fue evaluar el impacto del estado del SM en los resultados en pacientes sometidos a resección anatómica o no anatómica por un HCC solitario. MÉTODOS: Los datos de pacientes con un HCC solitario sometidos a resección parcial no anatómica (grupo Hr0) o resección anatómica de un segmento de Couinaud (grupo HrS) entre 2000 y 2007 se obtuvieron a partir de una base de datos nacional de Japón. En los grupos Hr0 y HrS se evaluaron la supervivencia global y la supervivencia libre de recidiva asociadas al estado microscópico del SM y a la amplitud del SM. RESULTADOS: Se incluyeron un total de 4.457 pacientes en el grupo Hr0 y 3.507 en el grupo HrS. Un SM microscópico positivo se asoció con una pobre supervivencia global en ambos grupos. Un SM negativo, pero a una distancia de 0 mm se asoció con una peor supervivencia global y libre de recidiva en comparación con aquellos asociados a un SM más amplio, solo en el grupo Hr0. En el grupo HrS, la amplitud del SM no se asoció con los resultados del paciente. CONCLUSIÓN: La resección anatómica con un SM negativo a una distancia de 0 mm puede ser aceptable. La resección no anatómica con un SM negativo a una distancia de 0 mm se asoció con resultados de supervivencia menos favorables.

Estimating the Net Utility Gains Among Donors and Recipients of Adult Living Donor Kidney Transplant.

OBJECTIVES: Living donor kidney transplant relieves the disease burden of patients with end-stage renal disease but may shorten donor life expectancy; however, their quality of life (QOL) is preserved. Nevertheless, the magnitude of the net gain of this procedure is unknown. We evaluated the QOL of both donors and recipients concurrently and calculated the net utility gain. METHODS: We recruited 210 subjects who visited the kidney transplantation clinic of a university hospital. Subjects were asked to complete the 5-level EQ-5D-based questionnaire, and patient characteristics were extracted from their medical records. We performed multivariate tobit models analysis to evaluate the QOL change caused by transplant surgery and subsequently ran computational simulations to determine the net utility gains of donors and recipients. We also performed sensitivity analyses. RESULTS: After excluding 16 answers with missing data, we analyzed 203 answers in total. After the transplant surgery, recipients gained 0.07 in utility value while donors lost 0.04. In the net utility analysis, we found that the quality-adjusted life years gained ranged from 7.2 to 7.8 in the most favorable case observed in the combination of middle-aged recipients and elderly donors. Assuming no utility discount, the most favorable combination was that with older donors and younger recipients. CONCLUSIONS: These findings indicated that the QOL improvement in recipients was larger than the loss among donors. When calculating the net utilities, a combination of middle-aged recipients and elderly donors yielded the largest net utility, but this was likely derived from assumption in the discount of QOL.

Impact of Dental Diseases on Quality-Adjusted Life Expectancy in US Adults.

Comparing the burden of dental conditions to other health outcomes provides useful insight for public policy. We aimed to estimate quality-adjusted life expectancy (QALE) loss due to dental conditions in the US adult population. Social inequalities in QALE loss by dental conditions were also examined. Data from 3 cross-sectional waves of the National Health and Nutrition Examination Survey (NHANES waves 2001 to 2002, 2003 to 2004, and 2011 to 2012) were pooled and analyzed. The average age of study participants ( n = 9,445) was 48.4 y. Disutility scores were derived from self-rated health and the numbers of physically unhealthy days, mentally unhealthy days, and days with activity limitation, employing a previously published algorithm. The associations between the disutility scores and the numbers of decayed teeth, missing teeth, and periodontitis were examined by multiple linear regression stratified by age groups (20-39, 40-59, and ≥60 y), adjusted for other covariates (age, sex, wave fixed effect, educational attainment, smoking, and diabetes). The QALE loss due to dental conditions at the age of 20 was estimated using life tables. Decayed and missing teeth, but not periodontitis, were associated with a larger disutility score. The coefficient for decayed teeth was larger among the older population, whereas that of missing teeth was smaller among them. The estimated QALE loss was 0.43 y (95% confidence interval [CI], 0.28-0.59), which reached 5.3% of QALE loss (8.15 y; 95% CI, 8.03-8.27) due to overall morbidity. There were clear social gradients in QALE loss by dental conditions across the life course, and people with high school or less education had 0.32 y larger QALE loss in total compared with people with college or more education. This study suggests that improvements in people's dental health may yield substantial gains in population health and well-being. The necessity of more comprehensive public health strategies is highlighted.

Condoliase for treatment of lumbar disc herniation.

Lumbar disc herniation (LDH) is generally treated with a conservative therapy, and surgery is the only therapeutic option currently available for patients unresponsive to the conservative therapy. In the 1980s, chemonucleolysis with chymopapain, a protease, was widely used as the intermediate treatment between conservative therapy and surgical therapy in the Western countries. However, since chymopapain was withdrawn from the market in 2002 for non-scientific commercial reasons, chemonucleolysis has not been a therapeutic option for LDH. Condoliase (chondroitin sulfate ABC endolyase), a glycosaminoglycan-degrading enzyme, was approved by the drug regulatory authority in Japan as a newer intradiscal therapy for LDH after clinical studies conducted in Japan demonstrated efficacy and safety for patients with LDH. This review will focus on the preclinical pharmacology, pharmacokinetics, efficacy and safety of condoliase as a new option for treatment of LDH.

Dental Status and Compression of Life Expectancy with Disability.

This study examined whether the number of teeth contributes to the compression of morbidity, measured as a shortening of life expectancy with disability, an extension of healthy life expectancy, and overall life expectancy. A prospective cohort study was conducted. A self-reported baseline survey was given to 126,438 community-dwelling older people aged ≥65 y in Japan in 2010, and 85,161 (67.4%) responded. The onset of functional disability and all-cause mortality were followed up for 1,374 d (follow-up rate = 96.1%). A sex-stratified illness-death model was applied to estimate the adjusted hazard ratios (HRs) for 3 health transitions (healthy to dead, healthy to disabled, and disabled to dead). Absolute differences in life expectancy, healthy life expectancy, and life expectancy with disability according to the number of teeth were also estimated. Age, denture use, socioeconomic status, health status, and health behavior were adjusted. Compared with the edentulous participants, participants with ≥20 teeth had lower risks of transitioning from healthy to dead (adjusted HR, 0.58 [95% confidence interval (CI), 0.50-0.68] for men and 0.70 [95% CI, 0.57-0.85] for women) and from healthy to disabled (adjusted HR, 0.52 [95% CI, 0.44-0.61] for men and 0.58 [95% CI, 0.49-0.68] for women). They also transitioned from disabled to dead earlier (adjusted HR, 1.26 [95% CI, 0.99-1.60] for men and 2.42 [95% CI, 1.72-3.38] for women). Among the participants aged ≥85 y, those with ≥20 teeth had a longer life expectancy (men: +57 d; women: +15 d) and healthy life expectancy (men: +92 d; women: +70 d) and a shorter life expectancy with disability (men: -35 d; women: -55 d) compared with the edentulous participants. Similar associations were observed among the younger participants and those with 1 to 9 or 10 to 19 teeth. The presence of remaining teeth was associated with a significant compression of morbidity: older Japanese adults' life expectancy with disability was compressed by 35 to 55 d within the follow-up of 1,374 d.

Randomized clinical trial comparing two vessel-sealing devices with crush clamping during liver transection.

BACKGROUND: Previous RCTs have failed to demonstrate the usefulness of combining energy devices with the conventional clamp crushing method to reduce blood loss during liver transection. Here, the combination of an ultrasonically activated device (UAD) and a bipolar vessel-sealing device (BVSD) with crush clamping was investigated. METHODS: Patients scheduled to undergo hepatectomy at the University of Tokyo Hospital or Nihon University Itabashi Hospital were eligible for this parallel-group, single-blinded randomized study. Patients were assigned to a control group (no energy device used), an UAD group or a BVSD group. The primary endpoint was the volume of blood loss during liver transection. Outcomes of the control group and the combined energy device groups (UAD plus BVSD) were first compared. Pairwise comparisons among the three groups were made for outcomes for which the combined energy device group was superior to the control group. RESULTS: A total of 380 patients were enrolled between July 2012 and May 2014; 116 patients in the control group, 122 in the UAD group and 123 in the BVSD group were included in the final analysis. Median blood loss during liver transection was lower in the combined energy device group (245 patients) than in the control group (116 patients): median 190 (range 0-3575) versus 230 (range 3-1570) ml (P = 0·048). Pairwise comparison revealed that blood loss was lower in the BVSD group than in the control group (P = 0·043). CONCLUSION: The use of energy devices combined with crush clamping reduced blood loss during liver transection. Registration number: C000008372 (www.umin.ac.jp/ctr/index.htm).

Dynamic deformability of sickle red blood cells in microphysiological flow.

In sickle cell disease (SCD), hemoglobin molecules polymerize intracellularly and lead to a cascade of events resulting in decreased deformability and increased adhesion of red blood cells (RBCs). Decreased deformability and increased adhesion of sickle RBCs lead to blood vessel occlusion (vaso-occlusion) in SCD patients. Here, we present a microfluidic approach integrated with a cell dimensioning algorithm to analyze dynamic deformability of adhered RBC at the single-cell level in controlled microphysiological flow. We measured and compared dynamic deformability and adhesion of healthy hemoglobin A (HbA) and homozygous sickle hemoglobin (HbS) containing RBCs in blood samples obtained from 24 subjects. We introduce a new parameter to assess deformability of RBCs: the dynamic deformability index (DDI), which is defined as the time-dependent change of the cell's aspect ratio in response to fluid flow shear stress. Our results show that DDI of HbS-containing RBCs were significantly lower compared to that of HbA-containing RBCs. Moreover, we observed subpopulations of HbS containing RBCs in terms of their dynamic deformability characteristics: deformable and non-deformable RBCs. Then, we tested blood samples from SCD patients and analyzed RBC adhesion and deformability at physiological and above physiological flow shear stresses. We observed significantly greater number of adhered non-deformable sickle RBCs than deformable sickle RBCs at flow shear stresses well above the physiological range, suggesting an interplay between dynamic deformability and increased adhesion of RBCs in vaso-occlusive events.

Reductions of docosahexaenoic acid-containing phosphatidylcholine levels in the anterior horn of an ALS mouse model.

In this study, we analyzed the spatiotemporal alterations of phospholipid composition in the spinal cord of an amyotrophic lateral sclerosis (ALS) mouse model (G93A-mutated human superoxide dismutase 1 transgenic mice [SOD1(G93A) mice]) using imaging mass spectrometry (IMS), a powerful method to visualize spatial distributions of various types of molecules in situ. Using this technique, we deciphered the phospholipid distribution in the pre-symptomatic stage, early stage after disease onset, and terminal stages of disease in female SOD1(G93A) mouse spinal cords. These experiments revealed a significant decrease in levels of docosahexaenoic acid (DHA)-containing phosphatidylcholines (PCs), such as PC (diacyl-16:0/22:6), PC (diacyl-18:0/22:6), and PC (diacyl-18:1/22:6) in the L5 anterior horns of terminal stage (22-week-old) SOD1(G93A) mice. The reduction in PC (diacyl-16:0/22:6) level could be reflecting the loss of motor neurons themselves in the anterior horn of the spinal cord in ALS model mice. In contrast, other PCs, such as PC (diacyl-16:0/16:0), were observed specifically in the L5 dorsal horn gray matter, and their levels did not vary between ALS model mice and controls. Thus, our study showed a significant decrease in DHA-containing PCs, but not other PCs, in the terminal stage of ALS in model mice, which is likely to be a reflection of neuronal loss in the anterior horns of the spinal cords. Given its enrichment in dorsal sensory regions, the preservation of PC (diacyl-16:0/16:0) may be the result of spinal sensory neurons being unaffected in ALS. Taken together, these findings suggest that ALS spinal cords show significant alterations in PC metabolism only at the terminal stage of the disease, and that these changes are confined to specific anatomical regions and cell types.

Does Internet-based cognitive behavioral therapy (iCBT) prevent major depressive episode for workers? A 12-month follow-up of a randomized controlled trial.

BACKGROUND: In this study we investigated whether an Internet-based computerized cognitive behavioral therapy (iCBT) program can decrease the risk of DSM-IV-TR major depressive episodes (MDE) during a 12-month follow-up of a randomized controlled trial of Japanese workers. METHOD: Participants were recruited from one company and three departments of another company. Those participants who did not experience MDE in the past month were randomly allocated to intervention or control groups (n = 381 for each). A 6-week, six-lesson iCBT program was provided to the intervention group. While the control group only received the usual preventive mental health service for the first 6 months, the control group was given a chance to undertake the iCBT program after a 6-month follow-up. The primary outcome was a new onset of DSM-IV-TR MDE during the 12-month follow-up, as assessed by means of the web version of the WHO Composite International Diagnostic Interview (CIDI), version 3.0 depression section. RESULTS: The intervention group had a significantly lower incidence of MDE at the 12-month follow-up than the control group (Log-rank χ2 = 7.04, p < 0.01). The hazard ratio for the intervention group was 0.22 (95% confidence interval 0.06-0.75), when estimated by the Cox proportional hazard model. CONCLUSIONS: The present study demonstrates that an iCBT program is effective in preventing MDE in the working population. However, it should be noted that MDE was measured by self-report, while the CIDI can measure the episodes more strictly following DSM-IV criteria.

Feasibility of a novel diagnostic chart of intramedullary spinal cord tumors in magnetic resonance imaging.

STUDY DESIGN: Retrospective chart review. OBJECTIVES: Each type of intramedullary spinal cord tumor (IMSCT) has specific anatomical and pathological features visible on magnetic resonance (MR) imaging. The purpose of this study was to investigate the accuracy of preoperative IMSCT diagnosis using our diagnostic chart of tumor-specific MR imaging findings. SETTING: Hamamatsu, Japan. METHODS: From 2009 to 2013, 28 consecutive patients with IMSCT who underwent surgery in our university hospital were included in this study. There were 17 men and 11 women with an average age of 49 years (12-81). The pathological diagnoses were hemangioblastoma (12), ependymoma (11), astrocytoma (4) and squamous cell carcinoma (1). Tumor-specific MR imaging findings were as follows: ependymoma ((a) spinal cord swelling, (b) contrast effect with necrosis, (c) tumor in the center of the spinal cord), hemangioblastoma ((a) spinal cord swelling, (b) homogeneous contrast effect) and astrocytoma ((a) spinal cord swelling, (b) contrast effect is either, (c) eccentric tumor). Based on these features, we generated a diagnostic chart to investigate the MR imaging diagnosis accuracy for IMSCTs. RESULTS: The accuracy of preoperative diagnosis was 89% (25/28 cases). Correct diagnoses were made in 100% of hemangioblastomas (12/12 cases), 90% of ependymomas (9/11 cases) and 100% of astrocytomas (4/4 cases). CONCLUSIONS: Different types of IMSCTs exhibit unique MR imaging characteristics. These features can be used to preoperatively diagnose IMSCTs with high accuracy.

Blockade of IL-6 signaling by MR16-1 inhibits reduction of docosahexaenoic acid-containing phosphatidylcholine levels in a mouse model of spinal cord injury.

The interleukin (IL)-6 pathway plays an important role in recovery after spinal cord injury (SCI). The anti-IL-6 receptor antibody MR16-1 has been shown to suppress inflammation after SCI and promote recovery of motor function. The purpose of this study was to analyze the effects of MR16-1 on the expression patterns of phospholipids in the spinal cord in a mouse model of SCI. Eight-week-old C57BL/6JJmsSlc mice were used in this study. Laminectomy was performed at the ninth and tenth thoracic levels (T9-T10), and contusion injury of the spinal cord was induced at level T10. Immediately after SCI, mice were intraperitoneally injected with a single dose of MR16-1 (MR16-1 group) or a single dose of phosphate-buffered saline of the same volume (control group). Imaging mass spectrometry was performed to visualize phosphatidylcholine (PC) expression in the spinal cord 7 days after SCI. We found that MR16-1 treatment suppressed the infiltration of immune cells after SCI, and was able to increase the locomotor function post-injury. Phospholipid imaging revealed that the MR16-1 was able to prevent the reduction of docosahexaenoic acid (DHA)-containing PC in comparison with the control group. We also observed high levels of glial fibrillary acidic protein (GFAP) at the site of DHA-containing PC expression in the MR16-1 group. These results suggest that MR16-1 treatment influences the DHA-containing PC composition of GFAP-positive cells at the injury site as early as 7 days post-SCI.

Total spondylectomy following carbon ion radiotherapy to treat chordoma of the mobile spine.

The main form of treatment of a chordoma of the mobile spine is total en bloc spondylectomy (TES), but the clinical results are not satisfactory. Stand-alone carbon ion radiotherapy (CIRT) for bone and soft-tissue sarcomas has recently been reported to have a high rate of local control with a low rate of local recurrence. We report two patients who underwent TES after CIRT for treating a chordoma in the lumbar spine with good medium-term outcomes. At operation, there remained histological evidence of viable tumour cells in both cases. After the combination use of TES following CIRT, neither patient showed signs of recurrence at the follow-up examination. These two cases suggest that CIRT should be combined with total spondylectomy in the treatment of chordoma of the mobile spine.