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We have developed a novel radiopaque tiltmeter (ROT) that can indicate patient tilt during a radiography examination and display it on X-ray images. This study evaluated the effect of variation of patient tilt on the reproducibility of Fowler's position for chest radiography and the accuracy of the ROT.We evaluated the reproducibility of Fowler's position based on changes from the first day in the central venous catheter (CVC) tip position and the cardiothoracic ratio (CTR) with and without a digital tiltmeter to verify its efficacy in patients who underwent mobile chest radiography. The ROT contains radiopaque liquid consisting of white barium sulfate solution and oil and has a scale bar of 15°-75° with increments of 15° to indicate ROT tilt. The ROT tilt was increased from 10° to 80° in increments of 10°. We then evaluated (1) the difference between the ROT tilt and the tilt measured with a digital tiltmeter, and (2) the ROT tilt displayed on the X-ray image.With regard to reproducibility in Fowler's position, changes in the CVC tip position were 2.8 ± 3.9 mm and 10.7 ± 10.6 mm with and without the tiltmeter, respectively (p 0.05) and the respective rates of change in the CTR were 0.7% ± 0.6% and 4.0% ± 2.1% (p 0.05). Differences between the ROT tilt and the tilt measured by the digital tiltmeter were within ±2.5°. All ROT tilts displayed on the X-ray images were recognized exactly as each tilt.Our novel ROT had the potential to accurately indicate patient tilt during chest radiography, which could be helpful in terms of reproducibility and precise follow-up.Use of the ROT for determination of patient tilt can improve reproducibility in Fowler's position, allowing more accurate serial X-ray imaging.

OBJECTIVE: We previously established a descriptive dietary record method that accurately quantifies habitual water intake from food and beverages, to ascertain the relationship between water intake and health. Here, we verified the validity of a selective recall method, which is easy for users to answer and analyze. PATIENTS AND METHODS: Japanese men and women aged 20-44 years (n = 16) and 45-64 years (n = 16) participated over three working days and one non-working day. The day following each of the surveyed days, participants collected their first morning urine for urinalysis and completed a selective recall and descriptive dietary record questionnaire. RESULTS: The two methods of determining water intake were positively correlated (r = 0.94, p < 0.0001). Water intake volumes from non-alcoholic beverages (r = 0.94, p < 0.0001), alcoholic beverages (r = 1.00, p < 0.0001), and food (r = 0.72, p < 0.0001), calculated using the two methods, exhibited strong correlation. No correlation was observed between urinalysis parameters and total water intake. A significant, negative correlation was observed between urine osmolarity and total water intake in men (r = -0.55, p = 0.0011) and women (r = -0.51, p = 0.0032) aged 20-44 years. CONCLUSIONS: Selective recall is a valid method for assessing water intake from food and beverages.

Purpose: The optimal power load is defined as the load that maximizes power output in a given exercise. This load can be determined through the use of various instruments, under different testing protocols. Specifically, the "optimum power load" (OPL) is derived from the load-velocity relationship, using only bar force and bar velocity in the power computation. The OPL is easily assessed using a simple incremental testing protocol, based on relative percentages of body mass. To date, several studies have examined the associations between the OPL and different sport-specific measures, as well as its acute and chronic effects on athletic performance. The aim of this brief review is to present and summarize the current evidence regarding the OPL, highlighting the main lines of research on this topic and discussing the potential applications of this novel approach for testing and training. Conclusions: The validity and simplicity of OPL-based schemes provide strong support for their use as an alternative to more traditional strength-power training strategies. The OPL method can be effectively used by coaches and sport scientists in different sports and populations, with different purposes and configurations. Sin financiación 4.211 JCR (2021) Q1, 20/88 Sport Sciences 1.623 SJR (2021) Q1, 11/294 Orthopedics and Sports Medicine No data IDR 2021 UEM

BACKGROUND Surgery is the gold standard for basal cell carcinomas (BCC). Current recommended surgical margins for BCCs are determined from studies in Caucasian populations. However, the appropriate surgical margins for BCCs in non-white races are unclear. OBJECTIVES To investigate the accuracy of preoperative determination of clinical tumour borders and appropriate surgical margins in Japanese patients with BCC. METHODS The maximum calculated differences in distance between the preoperatively determined surgical margins and the actual histologic tumour side margins were considered as 'accuracy gaps' of clinical tumour borders. Estimated side margin positivity rates (ESMPRs) with narrower (2 and 3 mm) surgical margins were calculated on the basis of the accuracy gaps. RESULTS Overall, 1000 surgically excised BCCs from 980 Japanese patients were included. The most frequent histologic subtype was nodular BCC (67%). The median accuracy gap was 0.3 mm [interquartile range (IQR): -0.5 to +1 mm]. The ESMPRs with 2- and 3-mm surgical margins were 3.8% and 1.4%, respectively. Only the ESMPRs between the well-defined (n = 921) and poorly defined clinical tumour border groups (n = 79) showed statistical difference [2-mm margin: 3.1% vs. 11.7%, OR: 3.89, 95% confidential interval (CI): 1.41-10.71, P

Mucosal melanoma (MM) is a rare melanoma subtype with distinct biology and poor prognosis. Data on the efficacy of immune checkpoint inhibitors (ICIs) are limited. We determined the efficacy of ICIs in MM, analyzed by primary site and ethnicity/race.A retrospective cohort study from 25 cancer centers in Australia, Europe, USA and Asia was carried out. Patients with histologically confirmed MM were treated with anti-programmed cell death protein 1 (PD-1) ± ipilimumab. Primary endpoints were response rate (RR), progression-free survival (PFS), overall survival (OS) by primary site (naso-oral, urogenital, anorectal, other), ethnicity/race (Caucasian, Asian, Other) and treatment. Univariate and multivariate Cox proportional hazards model analyses were conducted.In total, 545 patients were included: 331 (63%) Caucasian, 176 (33%) Asian and 20 (4%) Other. Primary sites included 113 (21%) anorectal, 178 (32%) urogenital, 206 (38%) naso-oral and 45 (8%) other. Three hundred and forty-eight (64%) patients received anti-PD-1 and 197 (36%) anti-PD-1/ipilimumab. RR, PFS and OS did not differ by primary site, ethnicity/race or treatment. RR for naso-oral was numerically higher for anti-PD-1/ipilimumab [40%, 95% confidence interval (CI) 29% to 54%] compared with anti-PD-1 (29%, 95% CI 21% to 37%). Thirty-five percent of patients who initially responded progressed. The median duration of response (mDoR) was 26 months (95% CI 18 months-not reached). Factors associated with short PFS were Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥3 (P0.01), lactate dehydrogenase (LDH) more than the upper limit of normal (ULN) (P = 0.01), lung metastases (P0.01) and ≥1 previous treatments (P0.01). Factors associated with short OS were ECOG PS ≥1 (P0.01), LDHULN (P = 0.03), lung metastases (P0.01) and ≥1 previous treatments (P0.01).MM has poor prognosis. Treatment efficacy of anti-PD-1 ± ipilimumab was similar and did not differ by ethnicity/race. Naso-oral primaries had numerically higher response to anti-PD-1/ipilimumab, without difference in survival. The addition of ipilimumab did not show greater benefit over anti-PD-1 for other primary sites. In responders, mDoR was short and acquired resistance was common. Other factors, including site and number of metastases, were associated with survival.

Gorlin syndrome is a rare autosomal dominant disease caused by mutations in the PTCH1, PTCH2, and SUFU genes. Each symptom of the disease has a different time point of onset, which makes early diagnosis based solely on symptoms challenging. In this study, a gene panel was developed to overcome the challenges in the diagnosis of Gorlin syndrome and allow diagnosis using a single test. A custom panel was generated for four genes associated with Gorlin syndrome: PTCH1, PTCH2, SMO, and SUFU. Twenty-seven samples from 12 patients with Gorlin syndrome and three asymptomatic blood relatives of the patients were examined. This panel was highly reliable with a high Q30 quality score, on-target ratio, and coverage. The panel was time- and cost-efficient and enabled the detection of more mutations than whole-exome sequencing for the same patient. Pathogenic mutations in both PTCH1 and PTCH2 were detected in five of the 12 patients with Gorlin syndrome who were diagnosed based on clinical symptoms. Using this panel, the same mutation was identified in the patients and their blood relatives. In summary, this panel facilitated the highly reliable genetic diagnosis of Gorlin syndrome at a low cost, using only blood samples.

The baseline sagittal vertical axis (SVA) and pelvic tilt (PT) are independent risk factors of osteoporosis-related fractures in women with osteoporosis. We clarified the SVA and PT to predict the incidence of osteoporosis-related fractures.Sagittal alignment with osteoporosis women deteriorates with advancing age and sagittal alignment may indicate osteoporosis-related fractures in the future. However, whether the sagittal alignment predicts future osteoporosis-related fracture in patients with osteoporosis has not been clarified. We aimed to investigate the association between sagittal alignment and future osteoporosis-related fractures.This was a retrospective cohort study. Of the 313 participants (mean follow-up period, 2.9 years), 236 were included in the analysis. At baseline, we measured bone mineral density (BMD) of the lumbar spine and the femoral neck, sagittal vertical axis (SVA), thoracic kyphosis, pelvic incidence minus lumbar lordosis, sacral slope, pelvic tilt (PT), geriatric locomotive function scale (GLFS), two-step value, and stand-up test. The information on medications and the duration of treatment were reviewed from the medical records. Additionally, participants reported their history of falls at baseline. Multiple logistic regression analysis was used to determine the association of future osteoporosis-related fracture, and adjusted Odds ratios (OR) and 95% confidence interval (CI) were calculated with all predictors as covariates. All continuous variables were calculated using standardized OR (sOR).Osteoporosis-related fractures occurred in 33 of 313 participants (10.5%). Multiple logistic regression analysis showed that a history of falls (OR =4.092, 95% CI: 1.029-16.265, p =0.045), SVA (sOR =4.228, 95% CI: 2.118-8.439, p0.001), and PT (sOR =2.497, 95% CI: 1.087-5.733, p =0.031) were independent risk factors for future osteoporosis-related fractures.This study revealed the SVA and PT to predict osteoporosis-related fractures.UMIN000036516 (April 1, 2019).

This study aimed to develop a predictive explanatory model for the 1,000-m time-trial (TT) performance in young national-level kayakers, from biomechanical and physiological parameters assessed in a maximal graded exercise test (GXT). Twelve young male flat-water kayakers (age 16.1 ± 1.1 years) participated in the study. The design consisted of 2 exercise protocols, separated by 48 h, on a kayak ergometer. The first protocol consisted of a GXT starting at 8 km.h−1 with increments in speed of 1 km.h−1 at each 2-min interval until exhaustion. The second protocol comprised the 1,000-m TT.Results: In the GXT, they reached an absolute V∙O2max of 3.5 ± 0.7 (L.min−1), a maximum aerobic power (MAP) of 138.5 ± 24.5 watts (W) and a maximum aerobic speed (MAS) of 12.8 ± 0.5 km/h. The TT had a mean duration of 292.3 ± 15 s, a power output of 132.6 ± 22.0 W and a V∙O2max of 3.5 ± 0.6 (L.min−1). The regression model [TT (s) = 413.378–0.433 × (MAP)−0.554 × (stroke rate at MAP)] presented an R2 = 84.5%.Conclusion: It was found that V∙O2max, stroke distance and stroke rate during the GXT were not different from the corresponding variables (V∙O2peak, stroke distance and stroke rate) observed during the TT. The MAP and the corresponding stroke rate were strong predicting factors of 1,000 m TT performance. In conclusion, the TT can be useful for quantifying biomechanical parameters (stroke distance and stroke rate) and to monitor training induced changes in the cardiorespiratory fitness (V∙O2max).

Background & aims: Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease. Methods: We performed a chrX-wide association study, including genotype data from 5 genome-wide association studies (from Italy, United Kingdom, Canada, China, and Japan; 5244 case patients and 11,875 control individuals). Results: Single-marker association analyses found approximately 100 loci displaying P < 5 × 10-4, with the most significant being a signal within the OTUD5 gene (rs3027490; P = 4.80 × 10-6; odds ratio [OR], 1.39; 95% confidence interval [CI], 1.028-1.88; Japanese cohort). Although the transethnic meta-analysis evidenced only a suggestive signal (rs2239452, mapping within the PIM2 gene; OR, 1.17; 95% CI, 1.09-1.26; P = 9.93 × 10-8), the population-specific meta-analysis showed a genome-wide significant locus in East Asian individuals pointing to the same region (rs7059064, mapping within the GRIPAP1 gene; P = 6.2 × 10-9; OR, 1.33; 95% CI, 1.21-1.46). Indeed, rs7059064 tags a unique linkage disequilibrium block including 7 genes: TIMM17B, PQBP1, PIM2, SLC35A2, OTUD5, KCND1, and GRIPAP1, as well as a superenhancer (GH0XJ048933 within OTUD5) targeting all these genes. GH0XJ048933 is also predicted to target FOXP3, the main T-regulatory cell lineage specification factor. Consistently, OTUD5 and FOXP3 RNA levels were up-regulated in PBC case patients (1.75- and 1.64-fold, respectively). Conclusions: This work represents the first comprehensive study, to our knowledge, of the chrX contribution to the genetics of an autoimmune liver disease and shows a novel PBC-related genome-wide significant locus.

Acral melanoma (AM) is an epidemiologically and molecularly distinct entity that is underrepresented in clinical trials on immunotherapy in melanoma. We aimed to analyze the efficacy of anti-programmed cell death 1 (anti-PD-1) antibodies in advanced AM.We retrospectively evaluated unresectable stage III or stage IV AM patients treated with an anti-PD-1 antibody in any line at 21 Japanese institutions between 2014 and 2018. The clinicobiologic characteristics, objective response rate (ORR, RECIST), survival estimated using Kaplan-Meier analysis, and toxicity (Common Terminology Criteria for Adverse Events 4.0.) were analyzed to estimate the efficacy of the anti-PD-1 antibodies.In total, 193 patients (nail apparatus, 70; palm and sole, 123) were included in the study. Anti-PD-1 antibody was used as first-line therapy in 143 patients (74.1%). Baseline lactate dehydrogenase (LDH) was within the normal concentration in 102 patients (52.8%). The ORR of all patients was 16.6% (complete response, 3.1%; partial response, 13.5%), and the median overall survival (OS) was 18.1 months. Normal LDH concentrations showed a significantly stronger association with better OS than abnormal concentrations (median OS 24.9 versus 10.7 months; P0.001). Although baseline characteristics were similar between the nail apparatus and the palm and sole groups, ORR was significantly lower in the nail apparatus group [6/70 patients (8.6%) versus 26/123 patients (21.1%); P = 0.026]. Moreover, the median OS in this group was significantly poorer (12.8 versus 22.3 months; P = 0.03).Anti-PD-1 antibodies have limited efficacy in AM patients. Notably, patients with nail apparatus melanoma had poorer response and survival, making nail apparatus melanoma a strong candidate for further research on the efficacy of novel combination therapies with immune checkpoint inhibitors.

Background Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a severe adverse drug reaction commonly associated with the reactivation of human herpesvirus 6 (HHV-6). There are currently no adequate biomarkers for the early diagnosis and detection of DIHS/DRESS. Notably, OX40 (CD134) has an important role in allergic inflammation and functions as a cellular receptor for HHV-6 entry. We previously reported that the membrane-bound form of OX40 in CD4+ T cells was upregulated in DIHS/DRESS. Objective We sought to investigate the clinical significance of serum soluble OX40 (sOX40) in DIHS/DRESS. Methods Serum sOX40 levels in patients with DIHS/DRESS (n = 39), maculopapular exanthema/erythema multiforme (n = 17), Stevens-Johnson syndrome/toxic epidermal necrolysis (n = 13), or autoimmune bullous diseases (n = 5), and levels in healthy volunteers (n = 5) were examined by enzyme-linked immunosorbent assay. Copy numbers of HHV-6, HHV-7, and cytomegalovirus in peripheral blood mononuclear cells were quantified using real-time PCR. Results Serum sOX40 levels in patients with DIHS/DRESS in the acute stage were elevated in parallel with high OX40 expression on CD4+ T cells. Serum sOX40 levels were significantly positively correlated with disease severity and serum levels of thymus and activation-regulated chemokine, IL-5, and IL-10. Human herpesvirus 6–positive patients had higher sOX40 levels than did HHV-6–negative patients, and serum sOX40 levels were correlated with HHV-6 DNA loads. Conclusions Serum sOX40 levels can be a useful diagnostic marker for DIHS/DRESS that reflect disease severity. Elevated serum sOX40 levels also predict HHV-6 reactivation in patients with DIHS/DRESS.

Background Inflammatory Bowel Disease (IBD) constitutes a huge burden for patients and studies show that IBD patients have difficulties remaining in employment. Because there is no data about the unemployment of IBD patients in Japan. Methods We surveyed a representative sample of 1068 Japanese IBD patients regarding their employment status. Results We found that the labor force participation rate is lower and unemployment higher for patients with IBD compared to the general population. Factors associated with unemployment in the IBD sample are older age, female gender, and the prevalence of depression. Discussion IBD constitutes a high burden for patients in Japan regarding employment outcome.

Background A reduction in mortality with the early use of tranexamic acid has been demonstrated in severely injured patients who are bleeding. However, the modest treatment effect with no reduction in blood transfusion has raised concerns. The aim of the present study was to estimate the effectiveness of regular use of tranexamic acid in severely injured patients. Methods This multicentre observational study used retrospectively collected data from consecutive injured patients (Injury Severity Score at least 16) treated in 15 Japanese academic institutions in 2012. A propensity score-matched analysis compared patients who did or did not receive tranexamic acid administration within 3 h of injury. Study outcomes included 28-day all-cause and cause-specific mortality, and need for blood transfusion. Results Of 796 eligible subjects, 281 were treated with tranexamic acid. Propensity score matching selected a total of 500 matched subjects (250 in each group). Tranexamic acid administration was associated with lower 28-day mortality (10·0 versus 18·4 per cent; difference −8·4 (95 per cent c.i. –14·5 to −2·3) per cent) and lower 28-day mortality from primary brain injury (6·0 versus 13·2 per cent; difference −7·2 (−12·3 to −2·1) per cent). However, there was no significant difference between groups in the need for blood transfusion (33·2 versus 34·8 per cent; difference −1·6 (−9·9 to 6·7) per cent). Conclusion Early tranexamic acid use was associated with reduced mortality in severely injured patients, in particular those with a primary brain injury.

Drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS) is a severe adverse drug-induced reaction with reactivation of human herpesvirus 6 (HHV-6).1-3 We previously reported that serum thymus and activation-regulated chemokine (TARC) levels were markedly increased in patients with DIHS and suggested TARC as a useful diagnostic marker of DIHS in the early stage.4,5 In this study, we determined whether serum TARC levels correlate with the severity of clinical symptoms and laboratory data in patients with DRESS/DIHS. This article is protected by copyright. All rights reserved.

Objectives Vaginal mesh complications necessitating excision are increasingly prevalent. We aim to study whether subclinical chronically infected mesh contributes to the development of delayed-onset mesh complications or recurrent urinary tract infections (UTIs). Methods Women undergoing mesh removal from August 2013 through May 2014 were identified by surgical code for vaginal mesh removal. Only women undergoing removal of anti-incontinence mesh were included. Exclusion criteria included any women undergoing simultaneous prolapse mesh removal. We abstracted preoperative and postoperative information from the medical record and compared mesh culture results from patients with and without mesh extrusion, de novo recurrent UTIs, and delayed-onset pain. Results One hundred seven women with only anti-incontinence mesh removed were included in the analysis. Onset of complications after mesh placement was within the first 6 months in 70 (65%) of 107 and delayed (≥6 months) in 37 (35%) of 107. A positive culture from the explanted mesh was obtained from 82 (77%) of 107 patients, and 40 (37%) of 107 were positive with potential pathogens. There were no significant differences in culture results when comparing patients with delayed-onset versus immediate pain, extrusion with no extrusion, and de novo recurrent UTIs with no infections. Conclusions In this large cohort of patients with mesh removed for a diverse array of complications, cultures of the explanted vaginal mesh demonstrate frequent low-density bacterial colonization. We found no differences in culture results from women with delayed-onset pain versus acute pain, vaginal mesh extrusions versus no extrusions, or recurrent UTIs using standard culture methods. Chronic prosthetic infections in other areas of medicine are associated with bacterial biofilms, which are resistant to typical culture techniques. Further studies using culture-independent methods are needed to investigate the potential role of chronic bacterial infections in delayed vaginal mesh complications.

Introduction Elderly kidney donors have recently become more common in living related kidney transplantation in Japan. Therefore, it is important to evaluate whether kidney function in elderly donors after nephrectomy is preserved over long periods of time. Doppler ultrasonography measurement is practical for donors after nephrectomy because it involves simple and noninvasive examinations. Doppler ultrasonography can detect compensatory hypertrophy and blood flow parameters, namely resistive index (RI) and pulsatility index (PI), of the preserved kidney in living donors. Patients and Methods Our study included 58 donors, divided into 2 groups according to age; the elderly donor group was comprised of those 65 years old or older. We measured length, width, and short diameter of the preserved kidney using Doppler ultrasonography, and calculated kidney volume. Results The elderly group was comprised of 13 patients. In this group, the median preserved kidney volume was 145.0 cm 3 (101.8–193.5) before nephrectomy, and 127.6 cm 3 (99.0–183.4) and 145.5 cm 3 (141.3–148.6) at 1 and 12 months after nephrectomy, respectively. We did not observe significant compensatory hypertrophy in the preserved kidneys of elderly donors postoperatively. Both the mean PI and RI values of elderly donors increased progressively after nephrectomy. No compensatory hypertrophy occurred in the preserved kidneys of elderly donors, although the PI and RI did increase in these donors. Conclusion Our results indicate that nephrectomy caused nephrosclerosis in the preserved kidneys of elderly donors and that prevention of hypertension may be important after nephrectomy in elderly donors.

Background To increase the number of cadaveric kidney transplants in Japan, it is necessary to proactively perform transplantation from marginal donors. We had the opportunity to frequently perform kidney transplantation from expanded-criteria donors (ECDs), and it is anticipated that there will be increases in the number of ECD kidney transplants. Methods In our institution, 18 patients underwent cadaveric kidney transplantation from January 2001 to December 2011. Sixteen of those patients were classified into 2 groups according to donation after brain death (BD) or after cardiac death (CD). We also classified donors as ECDs or standard-criteria donors (SCDs). Results Kidney graft survival and engraftment were observed in all of the patients. Renal function at 1 year after transplantation was significantly better in the BD group than in the CD group. However, there was no significant difference between the groups in renal function at 3 and 5 years. Renal function at 1 and 3 years after transplantation was significantly better in the SCD group than in the ECD group, but there was no difference in renal function between the SDC and ECD groups at 5 years. Conclusions The results were good for all of the patients. There are many reports that graft survival rate at 3–5 years after transplantation from ECDs is poorer than from SCDs. However, no statistically significant difference was found in kidney function at ≥5 years between the ECD and SCD groups in our patients.

C-reactive protein (CRP) and many fatty acids (FAs) have been linked to cardiovascular disease. Associations of serum CRP with FAs in different populations have not been established.Participants were 926 men aged 40-49 (2002-2006) from a population-based sample; 310 Whites from Pennsylvania, U.S., 313 Japanese from Shiga, Japan, and 303 Japanese Americans from Hawaii, U.S. Serum CRP (mg/L) was measured using immunosorbent assay while serum FAs (%) were measured using capillary-gas-liquid chromatography.Whites had CRP (mg/L) levels higher than Japanese with Japanese Americans in-between (age-adjusted geometric mean "GM" 0.96, 0.38, 0.66, respectively). Whites had also higher levels of total n-6 FAs (%) and trans fatty acids (TFAs) but lower levels of marine-derived n-3 FAs compared to Japanese (41.78 vs. 35.05, 1.04 vs. 0.58, and 3.85 vs. 9.29, respectively). Japanese Americans had FAs levels in-between the other two populations. Whites had significant inverse trends between CRP and tertiles of total n-6 FAs (GM 1.20, 0.91 and 0.80; p=0.002) and marine-derived n-3 FAs (GM 1.22, 1.00 and 0.72; p0.001) but a significant positive trend with TFAs (GM 0.80, 0.95 and 1.15; p=0.007). Japanese had a significant inverse trend between CRP and only total n-6 FAs (GM 0.50, 0.35 and 0.31; p0.001). Japanese Americans had CRP associations with n-3 FAs, n-6 FAs, and TFAs similar to but weaker than Whites.With the exception of consistent inverse association of CRP with total n-6 FAs, there are considerable variations across the three populations in the associations of CRP with different FAs.

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Background To increase the number of cadaveric kidney transplants in Japan, it is necessary to proactively use organs from all donors. Since the revision of the Organ Transplant Law, the number of organ donors after cardiac death (DCD) has decreased but the number of organ donors after brain death (DBD) has increased; however, the number of donor organs and awareness of cadaveric transplantation have increased. Methods At our institution, 28 patients underwent cadaveric kidney transplantation from January 2001 to December 2016. These patients were classified into 2 groups according to DBD or DCD. Furthermore, 10 patients received transplants from expanded criteria donors (ECD) and 18 received them from standard criteria donors (SCD). Results Kidney graft survival and engraftment were observed for all patients. There were no significant differences in renal function at 6 months for DBD and DCD transplant recipients. Renal function at 1, 3, and 5 years and serum creatinine levels were better for the ECD group. Renal function at 5 years after transplantation was significantly better for the SCD group than for the ECD group; however, there was no difference in delayed graft function between the SCD and ECD groups. Comparisons of the 3 groups showed good renal function for transplants from DBDs, but there was no significant difference in survival rates. Conclusions Results were good for all patients. There were no significant differences in outcomes of our patients who received transplants from ECD or SCD.

The patient was a 45-year-old man with underlying alcoholic liver cirrhosis. Two years prior, he was repeatedly hospitalized for liver failure symptoms and requested a living-donor liver transplantation (LDLT) because of end-stage cirrhosis. A pretransplantation blood test revealed a high 1,3-beta-d-glucan (BDG) value of 102.0 pg/mL (reference value

Degeneration of the lumbar intervertebral discs is irreversible, with no treatment currently available. Building upon experimental studies that demonstrated the importance of the nucleus pulposus (NP) in preserving disc structure, we demonstrated that reinsertion of NP cells slowed further disc degeneration and that direct cell-to-cell contact co-culture with mesenchymal stromal cells (MSCs) significantly upregulated the viability of NP cells in basic and pre-clinical studies in vitro and in vivo using animal models and human cells. Here, we report a 3-year result of a prospective clinical study, aimed to assess the safety and efficacy of activated NP cell transplantation in the degenerate lumbar intervertebral disc. Candidates were 9 patients aged 20-29 years who had Pfirrmann’s grade III disc degeneration at the level adjacent to the level scheduled for posterior lumbar intervertebral fusion. Viable NP cells from the fused disc were co-cultured in direct contact with autologous bone marrow-derived MSCs. One million activated NP cells were transplanted into the degenerated disc adjacent to the fused level at 7 d after the first fusion surgery. No adverse effects were observed during the 3-year follow-up period. Magnetic resonance imaging did not show any detrimental effects to the transplanted discs and revealed a mild improvement in 1 case. No cases reported any low back pain. Our clinical study confirmed the safety of activated NP cell transplantation, and the findings suggest the minimal efficacy of this treatment to slow the further degeneration of human intervertebral discs.

To investigate the influence of cycloplegia with topical cyclopentolate on wavefront aberrations in myopic children. This is a prospective, comparative study. Twenty-eight myopic children with a mean age of 7.25±2.55 were enrolled in this study. We evaluated refraction and wavefront aberrations before and after cycloplegia with 1% cyclopentolate hydrochloride. Ocular and corneal aberrations were simultaneously measured and compared with each other. Individual Zernike components were also analyzed up to the sixth order. All these parameters were compared before and after cycloplegia. Ocular higher-order aberrations (HOAs) significantly increased after cycloplegia (P=0.012 for spherical-like and P=0.015 for total HOAs). Corneal HOAs did not change after cycloplegia. When corneal and ocular HOAs were compared, the ocular HOAs were significantly smaller than the corneal HOAs in spherical-like aberrations (P

Na(+)/H(+) exchanger (NHE) 1 is a member of the solute carrier superfamily, which regulates intracellular ionic homeostasis. NHE1 is known to require cellular ATP for its activity, despite there being no requirement for energy input from ATP hydrolysis. In this study, we investigated whether NHE1 is an ATP-binding protein. We designed a baculovirus vector carrying both epitope-tagged NHE1 and its cytosolic subunit CHP1, and expressed the functional NHE1-CHP1 complex on the surface of Sf9 insect cells. Using the purified complex protein consisting of NHE1 and CHP1 from Sf9 cells, we examined a photoaffinity labeling reaction with 8-azido-ATP-biotin. UV irradiation promoted the incorporation of 8-azido-ATP into NHE1, but not into CHP1, with an apparent Kd of 29.1 µM in the presence of Mg(2+). The nonlabeled nucleotides ATP, GTP, TTP and CTP all inhibited this crosslinking. However, ATP had the strongest inhibitory effect, with an apparent inhibition constant (IC50) for ATP of 2.2 mM, close to the ATP concentration giving the half-maximal activation of NHE1 activity. Importantly, crosslinking was more strongly inhibited by ATP than by ADP, suggesting that ATP is dissociated from NHE1 upon ATP hydrolysis. Limited proteolysis with thrombin and deletion mutant analysis revealed that the 8-azido-ATP-binding site is within the C-terminal cytoplasmic domain of NHE1. Equilibrium dialysis with NHE1-derived peptides provided evidence that ATP directly binds to the proximal cytoplasmic region (Gly542-Pro598), which is critical for ATP-dependent regulation of NHE1. These findings suggest that NHE1 is an ATP-binding transporter. Thus, ATP may serve as a direct activator of NHE1.

This case report describes common oral inflammatory findings leading to the identification of Chediak-Higashi syndrome (CHS). A 15-year-old girl presented with an enlarging and painful mass on the upper lip. Two weeks after the initial visit, the mass showed further protrusion in the absence of fever. Magnetic resonance imaging revealed a well-circumscribed cystic lesion with a thick capsule, and suggested an abscess derived from the mucous cyst in the upper lip. Inflammation indices were not elevated; however neutrophils were significantly lower than the normal level. Giant cytoplasmic granules in neutrophils, eosinophils, and lymphocytes, which are pathognomonic of CHS, were noted. The patient displayed brownish-red hair with some grey hair, and partial oculocutaneous albinism. Hepatosplenomegaly was evident on ultrasonography. The final diagnosis was of an oral infection facilitated by the adolescent form of CHS (gene CHS1/LYST at 1q42.1-2). This report offers a reminder that lip swelling may represent the initial manifestation of the inflammatory response in a patient with loss of immunocompetence due to pathologies such as CHS, and may rarely present as the patient's main complaint.

As well as pre-operative roadmapping by (18)F-Fluoro-2-deoxy-2-D-glucose (FDG) positron emission tomography, intra-operative localization of the tracer is important to identify local margins for less-invasive surgery, especially FDG-guided surgery. The objective of this paper is to develop a laparoscopic Compton camera and system aimed at use for intra-operative FDG imaging for accurate and less-invasive dissections. The laparoscopic Compton camera consists of four layers of a 12-pixel cross-shaped array of GFAG crystals ([Formula: see text] mm(3)) and through silicon via multi-pixel photon counters and dedicated individual readout electronics based on a dynamic time-over-threshold method. Experimental results yielded a spatial resolution of 4 mm (FWHM) for a 10 mm working distance and an absolute detection efficiency of 0.11 cps kBq(-1), corresponding to an intrinsic detection efficiency of ∼0.18%. In an experiment using a NEMA-like well-shaped FDG phantom, a [Formula: see text] mm cylindrical hot spot was clearly obtained even in the presence of a background distribution surrounding the Compton camera and the hot spot. We successfully obtained reconstructed images of a resected lymph node and primary tumor ex vivo after FDG administration to a patient having esophageal cancer. These performance characteristics indicate a new possibility of FDG-directed surgery by using a Compton camera intra-operatively.

The purpose of this study was to analyze the effects of four weeks of training cessation (TC) on specific endurance performance, resting and postexercise heart rate variability (HRV) and neuromuscular capacities of high-level endurance runners.Eighteen endurance runners, 8 men and 10 women (25.5±7.5 years; 166.9±7.6 cm; 54.2±6.9 kg), took part in this study. The 3000 m time trial performance, resting HRV, 5'-5' test, squat and countermovement jumps (SJ and CMJ, respectively) and mean propulsive power in the jump squat exercise relative to body mass (MPP JS REL) were performed pre and immediately following the 4-week TC. The inference based on magnitudes were used to analyze the differences between pre and post values.The time in the 3000 m time-trial was almost certainly higher after TC. A very likely decrease was noticed in the resting HRV Index after the TC period. The differences in all variables analyzed during the 5'-5' test were rated as unclear. No differences were observed in SJ and CMJ comparing the pre and post moments of TC, while the MPP JS REL was very likely improved after the TC period.The resting HRV accompanied the reductions in the specific endurance performance while the 5'-5' test variables did not. The lack of training stimulus led to improvement in the MPP JS REL, possibly due to the withdrawal of specific endurance training, which strongly concurs with neuromuscular performance.

To assess the effects of the diclofenac suppository pretreatment in prevention of vasovagal reflex-associated complications for infertile women undergoing local endometrial injury (LEI).Eighty-six infertile outpatients with repeated implantation failure following transfer of morphologically good embryos and/or blastocysts underwent single curettage LEI to improve the pregnancy outcome in the subsequent embryo/blastocyst transfer cycle. Of them, 35 patients chose diclofenac suppository administration prior to LEI, whereas 51 patients did not. The occurrence of palpitations, bradycardia, hypotension, presyncope, and requirement of bed rest was compared between the two groups.There were no significant differences in the demographics between the two groups. The prevalence of presyncope and requirement of bed rest was significantly lower in the diclofenac suppository group than in the control group. The pregnancy outcome was similar between the two groups.The diclofenac suppository administration is a low-cost effective method to reduce the risk of the vasovagal reflex-associated complications in infertile women undergoing LEI.

Although B lymphoblastoid cell lines (B-LCLs) are thought to maintain their original genomic structures during long-term culture, there has been considerable disagreement on the actual genomic stability of these cells. This study was initiated to determine whether B-LCLs develop cell populations with abnormal genomes during culture and to search for factors important to the maintenance of the original genome. We established continuous cultures of B-LCLs for more than 6 months and analyzed the cells using array-based comparative genome hybridization (CGH) analysis, conventional karyotyping and analysis of V(D)J recombination in the immunoglobulin (Ig) gene. We found that one B-LCL acquired an extra chromosome 4 without any other genomic rearrangements at passage 16 of continuous culture. At the Ig light- and heavy-chain loci, analysis of the major cell population showed a difference between cultures at early and later passages. Another aneuploid line was detected among B-LCLs established elsewhere and deposited previously into the RIKEN Cell Bank. Our findings indicate that some of the genomic rearrangements in B-LCLs are not caused by gradual accumulation of mutations and rearrangements during the B-LCL establishment processes, but rather as a result of a change in the cell population from clones with a normal genome to clones with de novo rearrangements. It is therefore feasible to maintain B-LCLs with a normal genomic structure by cell cloning or similar treatment.

Survival and germination rate of Bacillus subtilis C-3102 spores were investigated in a stomach and small intestine model (TIM-1), while the impact of C-3102 cells that had passed through TIM-1 on human colon microbiota was evaluated in a model of the large intestine (TIM-2). The survival of C-3102 spores in TIM-1 was 99%; 8% of the spores had germinated. Effluent of TIM-1 was subsequently introduced into TIM-2 and a micro-array platform was employed to assess changes in the microbiota composition. The effluent, which contained germinated C-3102 cells, increased some Bifidobacterium species and decreased some Clostridium groups. These changes were greater compared to those obtained by adding C-3102 spores directly to TIM-2. The present study suggests that oral doses of B. subtilis C-3102 spores have the potential to modulate the human colon microbiota. This effect may be caused by germination of the spores in the gastrointestinal tract.

The calcineurin A (CaNA) subunit was identified as a novel binding partner of plasma membrane Na(+)/H(+) exchanger 1 (NHE1). CaN is a Ca(2+)-dependent phosphatase involved in many cellular functions, including cardiac hypertrophy. Direct binding of CaN to the (715)PVITID(720) sequence of NHE1, which resembles the consensus CaN-binding motif (PXIXIT), was observed. Overexpression of NHE1 promoted serum-induced CaN/nuclear factor of activated T cells (NFAT) signaling in fibroblasts, as indicated by enhancement of NFAT promoter activity and nuclear translocation, which was attenuated by NHE1 inhibitor. In neonatal rat cardiomyocytes, NHE1 stimulated hypertrophic gene expression and the NFAT pathway, which were inhibited by a CaN inhibitor, FK506. Importantly, CaN activity was strongly enhanced with increasing pH, so NHE1 may promote CaN/NFAT signaling via increased intracellular pH. Indeed, Na(+)/H(+) exchange activity was required for NHE1-dependent NFAT signaling. Moreover, interaction of CaN with NHE1 and clustering of NHE1 to lipid rafts were also required for this response. Based on these results, we propose that NHE1 activity may generate a localized membrane microdomain with higher pH, thereby sensitizing CaN to activation and promoting NFAT signaling. In cardiomyocytes, such signaling can be a pathway of NHE1-dependent hypertrophy.

Many patients with hypertension have difficulty achieving their target blood pressure (BP). Therefore combination therapy, for example with an angiotensin II receptor blocker (ARB) and a diuretic, may be recommended. We previously evaluated the efficacy and safety of losartan (LOS) 50 mg - hydrochlorothiazide (HCTZ) 12.5 mg, as well as its effect on the plasma concentration of B-type natriuretic peptide (BNP, a prognostic marker for cardiovascular events), in patients with hypertension uncontrolled by ≥3 months of ARB-based therapy. The present subanalysis used data from patients who received LOS-based therapy before switching to LOS-HCTZ. Efficacy, safety, and changes in blood biochemical variables including BNP were evaluated. After excluding 4 patients with protocol violations, data from 35 patients (aged 36-79 years, mean 63 years; 66% male) were used in the safety analysis. The efficacy analysis used data from the 30 patients who were followed up for 12 months. Systolic/diastolic BP decreased from 156±12/87±11 mmHg at baseline to 125±11/73±10 mmHg at 12 months (p0.001). After 12 months, half of the patients achieved their target BP as defined by the Japanese Society of Hypertension Guidelines for the Management of Hypertension 2004. In 12 patients with baseline plasma BNP concentration ≥20 pg/mL, BNP decreased from 78.3±18.8 pg/mL to 57.3±17.7 pg/mL (p0.01). 3 patients experienced adverse events, one of which was cardiovascular. LOS-HCTZ is efficacious, has a good safety profile, and decreases plasma BNP concentration.

We identified the factors associated with home blood pressure (BP) variability in 1933 patients treated with hypertensive drugs (mean age, 67 years; women, 55%). Multivariate regression analysis showed that female gender, advanced age, home BP value, and home heart rate variability were positively associated with home BP variability, whereas home heart rate, body mass index, and duration of antihypertensive treatment were negatively associated with home BP variability. Moreover, not being medicated with amlodipine and being medicated with angiotensin II receptor blockers were associated with increased home systolic BP variability only among patients who were treated for less than 12 months.

The aim of this study was to examine the physical and physiological demands of top-class soccer field (FR; n = 7) and assistant (AR; n = 7) referees during America's Cup. The FR and AR were equipped with a global positioning system (GPS) and a heart rate (HR) monitor for the recording of displacements and cardiovascular stress, respectively, every 5 and 15 minutes, halves, and entire match. High-intensity accelerations (ACs) and a new index of performance efficiency (Effindex) were also examined during each match. The FR completed longer distances for all walking and running activities and exhibited a greater match HR compared with the AR. The FR exhibited a significant reduction in the mean number of ACs during the second half (40 vs. 28), with a significantly worse Effindex at the end of both halves for FR and at the end of the second half for AR. A significant correlation between FR and AR for the number (r = 0.336; p = 0.03) and distance (r = 0.367; p = 0.017) of ACs performed each 5-minute period indicated a synchronization of officials' activities. In conclusion, top-class American FR and AR exhibited similar physical demands as previously reported by their European counterparts during international tournaments. The high number of AC observed, the effect of fatigue on these actions over the match, and the AC's synchronization between FR and AR suggest that ACs should be considered for the preparation of referees and team sport athletes. The Effindex may provide an important tool for the evaluation of referees' and players' performance that requires further investigation.

To evaluate the effectiveness of the portable laparoscopic trainer in improving skills in subjects who have had no previous laparoscopic experience.Twenty-nine medical students were given a pretest of three tasks on a standardized laparoscopic trainer. Subjects were evaluated objectively and subjectively. Fifteen subjects were randomized to receive a portable laparoscopic trainer and 14 subjects were assigned to the standardized laparoscopic trainers at our facility. The portable trainer group subjects were advised but not required to complete at least 3 hours of training. The group at the facility had a proctored 1-hour session each week for 3 weeks. Each subject was then retested and evaluated with the same pretest tasks. Objective and subjective improvements between the groups were compared.Baseline demographics and pretest scores were similar between both groups. All students in the facility group completed the three 1-hour proctored sessions. The portable trainer group reported an average 204 minutes of practice. The facility group did objectively better on the post-test in overall time, and in two exercises. Subjectively, the facility group had a significant improvement compared with the portable trainer group (4.6 vs 2.4 point average increase, P=0.03).Both groups showed objective and subjective improvement after a 3-week period of training. The portable trainer group did report longer average practice time, but this made no significant difference in subjective or objective improvement. The portable laparoscopic trainer is comparable to the standard trainer for improvement of basic laparoscopic skills.

Calcium (Ca(2+)) is an important intracellular messenger, regulating myocyte contraction via excitation-contraction (EC) coupling and gene transcription underlying hypertrophy in the heart. Although the mechanisms of EC coupling in the immature heart are believed to be different from those in the adult heart because of the structural immaturity of the sarcoplasmic reticulum in the young heart, the details of these mechanisms are not completely understood. Neuronal Ca(2+) sensor-1 (NCS-1) is an EF-hand Ca(2+)-binding protein that is highly expressed in young hearts; however, little is known about its cardiac functions. In this review, we summarize our recent findings indicating that NCS-1 acts as a novel regulator enhancing Ca(2+) signals in the heart and hence promoting contraction in the immature heart and hypertrophy in the adult heart. Possible signal transduction pathways are also discussed.

ABO-incompatible kidney transplantation has increased the possibility of finding suitable living donors for patients with renal failure. However, there are inevitable immunological risks, including a high risk of early post-transplantation complications. The purpose of this study was to evaluate recipient outcomes following ABO-incompatible kidney transplantation.Seventy-one patients who had undergone living-donor kidney transplantation (LDKT) at our center between January 2008 and December 2013 were divided into ABO-incompatible (ABOi; n = 21) and ABO-compatible (ABOc; n = 50) groups. Baseline data, graft function, immunosuppressant use, and the results of biopsy 1 year after LDKT were compared between the groups.Recipient preemptive LDKT rates were significantly different between groups (P = .017). Graft function, incidence of infection, and rates of T-cell-mediated rejection and borderline changes requiring medication were not significantly different. There was no acute antibody-mediated rejection. Selectivity of the immunosuppressant, tacrolimus, was significantly different between groups (P .01); however, steroid withdrawal rates, mycophenolate mofetil doses, and calcineurin inhibitor trough levels were not different. Regarding biopsy data, interstitial fibrosis scores were significantly different between groups (P = .011), as were interstitial fibrosis and tubular atrophy scores (P = .045) and arteriolar hyalinosis score (P = .022).ABOi LDKT was relatively safe, with no significant difference in the incidence of rejection compared to ABOc LDKT. Managing chronic pathological changes and arteriolar hyalinosis prophylaxis after ABOi LDKT may result in more successful outcomes.

Incontinence after radical prostatectomy is common yet poorly defined in the current literature. We aimed to accurately characterize incontinence after robot-assisted radical prostatectomy to achieve improved preoperative patient counseling.After receiving institutional review board approval we performed a cross-sectional survey of the first 600 patients with prostate cancer who underwent robot-assisted radical prostatectomy at our institution. The International Consultation on Incontinence Modular Questionnaire-Lower Urinary Tract Symptoms Quality of Life and Urinary Incontinence Short Form were used to evaluate incontinence and quality of life after robot-assisted radical prostatectomy. Surveys were mailed by a third party. Data were analyzed on the prevalence of incontinence after robot-assisted radical prostatectomy. More specifically we characterized in detail the nature of incontinence and its effect on quality of life.The response rate was 68% (408 of 600 participants). Response time since surgery was 2.5 months to 4 years. Overall incontinence bother scores and ratings of life interference were quite low. Patients reported that most incontinence occurred during physical activity but 35% reported interference with sleep. Of the patients 31% experienced some anxiety due to urinary difficulties and 51% had to occasionally change clothes due to leakage. Patients did not report much interference with traveling, visiting friends or family and family life. The most bothersome aspects of incontinence were its effects on partner relationship, sexual life and energy levels.Despite patient concerns of incontinence after prostatectomy they report little interference with quality of life.

To determine if different approaches to an inguinal hernia repair (robotic, laparoscopic, or open) results in different outcomes during a simultaneous robot-assisted radical prostatectomy (RARP).We performed a retrospective review of a prospectively generated database of all RARPs performed at our institution. Patients who had a simultaneous inguinal hernia repair were identified. We compared them to an age-matched and body mass index-matched cohort who underwent RARP alone. We also compared outcomes between robotic versus laparoscopic versus open inguinal hernia repair.A total of 1224 RARPs were performed between March 2004 and September 2009. Eighteen patients had simultaneous inguinal hernia repairs during their RARP performed by a general surgeon (5 laparoscopic, 8 open, and 5 robotic). When compared with the cohort who underwent RARP only, there were no statistically significant differences in blood loss, length of stay, or complications. The control group had a significantly shorter OR time (179.5 vs. 215.5 minutes, p = 0.007). When comparing the different approaches of an inguinal hernia repair, the only statistically significant differences noted were body mass index and operative time. Operative time was longer in open versus robotic inguinal hernia repair (74 vs. 31.6 minutes, p = 0.006). There were only two recurrences, both after the simultaneous open inguinal hernia repair.Simultaneous inguinal hernia repair is a safe and feasible operation to perform during RARP. Although it does extend overall operative time, approaching the repair robotically is quicker than an open approach. A randomized study is needed to truly determine if one approach has better outcomes than the rest.

Nine patients treated with primary signet ring cell carcinoma of the prostate were identified among 29,783 cases of prostate cancer evaluated at Mayo Clinic from January 15, 1970, until January 2, 2009. A PubMed search of the English-language literature published from January 1, 1980, to January 1, 2010, was then performed using the key words signet ring cell and prostate, identifying 42 cases. This study reviews those cases, along with the additional 9 reported herein, and evaluates clinical characteristics, histologic diagnoses, treatment modalities, and outcomes. Mean age at diagnosis was 68 years (range, 50-85 years), and mean prostate-specific antigen level was 95.3 ng/mL (range, 1.9-536.0 ng/mL; to convert to μg/L, multiply by 1). Most patients (66%) had non–stage IV carcinoma, the most common Gleason sum was 8 (33%), and mean survival was 29 months. The presence of a primary signet ring cell carcinoma of the prostate was best confirmed by negative findings on gastrointestinal work-up, a positive stain for prostate-specific acid phosphatase, and negative carcinoembryonic antigen test results.

This study compares relationships between each of morning home blood pressure (BP), evening home BP and office BP with electrocardiographic (ECG) abnormalities among treated hypertensive Japanese patients. We defined ECG left ventricular hypertrophy (LVH) as Sokolow-Lyon voltage and/or Cornell voltage duration product. Abnormal T waves and ST segment depression were categorized based on the Minnesota code. Office BP was calculated as the mean of four readings taken during two visits. Morning and evening home BP were calculated as the mean of five readings measured once each morning and evening for 5 days, respectively. Multivariate analysis showed that ECG-LVH in 747 hypertensives (mean age: 72 years; women: 63%) was more closely associated with morning home BP than with either office or evening home BP. Even the first reading of morning home BP on day 1 was significantly associated with ECG-LVH independently of office BP. The association between home BP and ECG-LVH increased with the cumulative number of home BP measurements. The results for abnormal T waves were similar. Home and office BP did not significantly differ between patients with and without ST segment depression. Morning home BP was more closely associated with ECG-LVH and abnormal T waves than either office or evening home BP among treated hypertensive Japanese patients.

Objective: The aim of this study was to develop a new reporting format for endometrial cytology that would standardize the diagnostic criteria and the terminology used for reporting. Methods: In previous studies, cytoarchitectural criteria were found to be useful for the cytological assessment of endometrial lesions. To apply these criteria, an appropriate cytological specimen is imperative. In this article, the requirements of an adequate endometrial cytological specimen for the new diagnostic criteria are first discussed. Then, the diagnostic criteria, standardized on a combination of conventional and cytoarchitectural criteria, are presented. Third, terminology that could be used, not only for reporting the histopathological diagnosis, but also for providing better guidance for the gynaecologist to determine further clinical action, is introduced. The proposed reporting format was investigated using endometrial cytology of 58 cases that were cytologically underestimated or overestimated compared to the histopathological diagnosis made on the subsequent endometrial biopsy or surgical specimens. Results: Of the 58 cases, 12 were reassessed as being unsatisfactory for evaluation. Among the remaining 46 cases, 25 of the 27 cases, which had been underestimated and subsequently diagnosed as having endometrial carcinoma or a precursor stage on histopathological examination,were reassessed as recommended for endometrial biopsy. On the other hand, 19 cases overestimated by cytology were all reassessed as not requiring biopsy. Conclusions: The reporting format for endometrial cytology proposed in this article may improve diagnostic accuracy and reduce the number of patients managed inappropriately.

This study investigated the effects of mitiglinide in 16 patients with type 2 diabetes mellitus treated with 30 mg/day mitiglinide, divided into three doses given just before each meal, for approximately 12 months. A 450 kcal meal tolerance test was performed at baseline and after 3, 6 and 12 months, and levels of plasma glucose and immunoreactive insulin were measured. Various parameters of glucose metabolism and lipid metabolism, urinary albumin and markers of atherosclerosis, coagulation and fibrinolysis were also determined. Mitiglinide showed a rapid stimulatory effect on insulin secretion and reduced the levels of plasma glucose. The free fatty acid level significantly decreased at 60 min after the meal tolerance test. Mitiglinide also significantly lowered glycosylated haemoglobin and raised 1,5-anhydroglucitol after 6 months, and significantly decreased urinary albumin after 12 months. These data indicate that mitiglinide may have beneficial effects not only on glycaemic control but also on lipid metabolism and urinary albumin excretion, and may have a role in the prevention of the vascular complications of diabetes.

Lung cancer remains the leading cause of cancer-related deaths worldwide (Jemal et al, 2007). Approximately 30% of non-small-cell lung cancer (NSCLC) patients present with locally advanced lung cancer (van Meerbeeck, 2001). A number of randomised clinical trials support the conclusion that combined-modality approaches improve survival compared with radiotherapy alone for locally advanced lung cancer (Le Chevalier et al, 1991; Non-Small Cell Lung Cancer Collaborative Group, 1995). Depending on the strategy used, chemotherapy may have a cytotoxic role by eradicating distant micrometastases, may have a radiosensitising role by improving local control, or it perhaps may have a role in both effects. Recently, two randomised trials using cisplatin plus older agents from the 1980s compared sequential with concurrent chemoradiotherapy and showed superior survival with the concurrent approach (Furuse et al, 1999; Curran et al, 2003). However, distant metastases remain the major site of failure and it is also likely that more effective chemotherapy will be required for further improvement in results. During the last decade, several new agents, such as paclitaxel, gemcitabine, vinorelbine, and docetaxel, have been proven to be more effective in metastatic NSCLC than the old regimens (Bunn and Kelly, 1998; Johnson, 1999; Hoffman et al, 2000). Because of dose-limiting toxicities (Choy et al, 1998; Vokes et al, 2002; Gandara et al, 2003; Zatloukal et al, 2004; Fournel et al, 2005; Bedano et al, 2006; Kiura et al, 2008), these new agents have been tested using a reduced dose or split dose within the newer concurrent chemoradiation regimens. As yet, however, these new strategies have not been proven to be more effective than the older regimens. S-1 is a new oral fluoropyrimidine agent designed to enhance anticancer activity and to reduce gastrointestinal toxicity through the combined use of an oral fluoropyrimidine agent (tegafur), a dihydropyrimidine dehydrogenase inhibitor (5-chloro-2,4-dihydroxypyridine), and an orotate phosphoribosyl transferase inhibitor (potassium oxonate; Shirasaka et al, 2000). S-1 has been shown to have one of the highest levels of response as a single agent for metastatic NSCLC (Kawahara et al, 2001). Moreover, two phase II trials of S-1 plus cisplatin for advanced NSCLC (stage IIIB without any indications for radiotherapy or stage IV) showed a response rate of 32.7–47% and a median survival time of 11–16 months. In addition, it shows very few severe gastrointestinal or haematological toxicities (Ichinose et al, 2004; Endo et al, 2006). If the same doses of S-1 plus cisplatin used for advanced NSCLC could be concurrently used with thoracic radiotherapy (TRT), this regimen would be expected to have several advantages over previous regimens. First, the radiation-sensitising effect of 5-FU is well known clinically and S-1 also has been shown to act as a radiosensitiser in preclinical models (Fukushima et al, 1998; Harada et al, 2004). Second, in order to achieve radiosensitisation, prolonged exposure is desirable, and as such, oral administration is the most appealing route of administration. In addition, phase I studies have shown that the half-life of 5-FU after oral S-1 administration has been found to be markedly prolonged compared with that of 5-FU after intravenous administration (van Groeningen et al, 2000; Yamada et al, 2003). Therefore, we conducted a phase II trial using S-1 and cisplatin chemotherapy with concurrent TRT for locally advanced NSCLC.

Cultured fibroblasts from familial Alzheimer's disease patients were characterized. Familial Alzheimer fibroblasts showed the same appearance by phase microscopy and the and the same growth rate with the control fibroblasts cultured from the age-matched healthy control subjects. Fibroblasts cultured from familial Alzheimer's disease patients showed decreased efficiency in adhesion to substrata in limited periods. While 80% of the control fibroblasts finished adhesion within 30 minutes incubation, only 30% of Alzheimer fibroblasts completed adhesion within the same period. When fibroblasts from familial Alzheimer's disease were kept under serum-free media more than ten days, they showed a unique aberration of vimentin fiber distribution, while other cytoskeletal fibers were remained intact. It is indicated that fibroblasts cultured from patients with familial Alzheimer's disease can be used to study pathological processes which affect the cytoskeletal organization in the fibroblasts as well as in the cells of the central nervous system.

Androgens are reported to be actively produced in situ in human prostate cancer. These locally produced androgens are also demonstrated to play important role in the pathogenesis and development of human prostate cancer. The status of locally produced androgen inactivation and metabolism, however, remains unclear. Therefore, it is important to examine the status of this in situ androgen metabolism and inactivation in order to improve clinical response to endocrine therapy in the patients diagnosed with prostate cancer. 17beta-hydroxysteroid dehydrogenase type 11 (Pan1b) was demonstrated to display greatest activity with 5alpha-androstan-3alpha, 17beta-diol (3alpha-diol) as substrate in several human androgen metabolizing tissues, suggesting that this enzyme may play important role in androgen metabolism. However, its details including the expression level of Pan1b have not been studied in human prostate cancer. In this study, we evaluated immunolocalization of Pan1b in human prostate cancer specimens obtained from surgery (n=40), and correlated the findings with clinicopathological features of the patients in order to study its clinical significance. Pan1b immunoreactivity was detected in 19 cases (48%) and was significantly associated with cancer of seminal vesicle invasion (P

Although several studies have reported on the relation between high blood pressure (BP) and impaired activities of daily living (ADL), only a few studies have reported on the relation of high BP in middle-aged subjects with future impaired ADL. Furthermore, no studies reported an excess impaired ADL due to non-normal BP. Using ADL 1999 data, we compared data from NIPPON DATA80 survivors without impaired ADL (N=1816) with those with impaired ADL (N=75) using baseline BP information collected in 1980. We analysed participants who were aged 47-59 years at baseline. Multiple adjusted logistic regression analyses were used to estimate the risk of impaired ADL, according to baseline BP categories using Joint National Committee 7 guidelines (normal BP, prehypertension, stage 1 hypertension (HT) and stage 2 HT). Subjects who used antihypertensive medications were classified as having stage 2 HT. We calculated excess impaired ADL due to non-normal BP. Compared with normal BP categories, the adjusted odds ratio (OR) and 95% confidence interval (CI) of having impaired ADL was higher in subjects with prehypertension (OR=1.50, 95% CI: 0.55-4.09), stage 1 HT (OR=1.56, 95% CI: 0.56-4.32) and stage 2 HT (OR=2.96, 95% CI: 1.09-8.05). Non-normal BP explained 45% (33.7/75) of impaired ADL. A positive relation of BP categories with the composite end point of mortality and impaired ADL was also observed. In conclusion, controlling BP in middle age may prevent deaths and future ADL decline.

Activation of the sarcolemmal Na + /H + exchanger (NHE)1 is increasingly documented as a process involved in cardiac hypertrophy and heart failure. However, whether NHE1 activation alone is sufficient to induce such remodeling remains unknown. We generated transgenic mice that overexpress a human NHE1 with high activity in hearts. The hearts of these mice developed cardiac hypertrophy, contractile dysfunction, and heart failure. In isolated transgenic myocytes, intracellular pH was elevated in Hepes buffer but not in physiological bicarbonate buffer, yet intracellular Na + concentrations were higher under both conditions. In addition, both diastolic and systolic Ca 2+ levels were increased as a consequence of Na + -induced Ca 2+ overload; this was accompanied by enhanced sarcoplasmic reticulum Ca 2+ loading via Ca 2+ /calmodulin-dependent protein kinase (CaMK)II-dependent phosphorylation of phospholamban. Negative force–frequency dependence was observed with preservation of high Ca 2+ , suggesting a decrease in myofibril Ca 2+ sensitivity. Furthermore, the Ca 2+ -dependent prohypertrophic molecules calcineurin and CaMKII were highly activated in transgenic hearts. These effects observed in vivo and in vitro were largely prevented by the NHE1 inhibitor cariporide. Interestingly, overexpression of NHE1 in neonatal rat ventricular myocytes induced cariporide-sensitive nuclear translocation of NFAT (nuclear factor of activated T cells) and nuclear export of histone deacetylase 4, suggesting that increased Na + /H + exchange activity can alter hypertrophy-associated gene expression. However, in transgenic myocytes, contrary to exclusive translocation of histone deacetylase 4, NFAT only partially translocated to nucleus, possibly because of marked activation of p38, a negative regulator of NFAT signaling. We conclude that activation of NHE1 is sufficient to initiate cardiac hypertrophy and heart failure mainly through activation of CaMKII–histone deacetylase pathway.

Burn rehabilitation has been a part of burn care and treatment for many years. Yet, despite of its longevity, the rehabilitation outcome of patients with severe burns is less than optimal and appears to have leveled off. Patient survival from burn injury is at an all-time high. Burn rehabilitation must progress to the point where physical outcomes parallel survival statistics in terms of improved patient well-being. This position article is a treatise on burn rehabilitation and the state of burn rehabilitation patient outcomes. It describes burn rehabilitation interventions in brief and why a need is felt to bring this issue to the forefront. The article discusses areas for change and the challenges facing burn rehabilitation. Finally, the relegation and acceptance of this responsibility are addressed.