Reconstruction of Bloch wavefunctions of holes in a semiconductor.

A central goal of condensed-matter physics is to understand how the diverse electronic and optical properties of crystalline materials emerge from the wavelike motion of electrons through periodically arranged atoms. However, more than 90 years after Bloch derived the functional forms of electronic waves in crystals1 (now known as Bloch wavefunctions), rapid scattering processes have so far prevented their direct experimental reconstruction. In high-order sideband generation2-9, electrons and holes generated in semiconductors by a near-infrared laser are accelerated to a high kinetic energy by a strong terahertz field, and recollide to emit near-infrared sidebands before they are scattered. Here we reconstruct the Bloch wavefunctions of two types of hole in gallium arsenide at wavelengths much longer than the spacing between atoms by experimentally measuring sideband polarizations and introducing an elegant theory that ties those polarizations to quantum interference between different recollision pathways. These Bloch wavefunctions are compactly visualized on the surface of a sphere. High-order sideband generation can, in principle, be observed from any direct-gap semiconductor or insulator. We thus expect that the method introduced here can be used to reconstruct low-energy Bloch wavefunctions in many of these materials, enabling important insights into the origin and engineering of the electronic and optical properties of condensed matter.

Wire-loop lesion is associated with serological immune abnormality, but not renal prognosis, in lupus nephritis.

BACKGROUND: Wire-loop lesion (WL) is one of the active lesions of lupus nephritis (LN). However, few reports have focused on the clinicopathological relationships of WL to serological immune abnormality and renal prognosis. METHODS: We enrolled 126 Japanese LN patients subjected to renal biopsy in 11 hospitals from 2000 to 2018. In patients with class III or IV of the International Society of Nephrology/Renal Pathology Society classification, we retrospectively compared clinicopathological findings between those with WL (WL+ group) and without WL (WL- group) to detect factors associated with WL. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate of <60 mL/min/1.73m2 for more than three months. We also compared these findings between those with CKD (CKD+ group) and without CKD (CKD- group) at the last visit to investigate factors associated with renal prognosis. RESULTS: Of 126 patients, 100 (79.4%) were classified as class III or IV. WL was found in 36 (36.0%) of them. Although the renal function did not differ, the WL+ group had a higher titre of serum anti-dsDNA antibodies and lower serum complement 3 levels than the WL- group. Linear regression analysis revealed a significant association only between anti-dsDNA antibodies and WL (ß = 0.27, 95% confidence interval (CI) 0.001-0.100, p = 0.01). Of these patients, 69 were tracked for 59.6 ± 55.1 months. Kaplan-Meier analysis showed no difference in renal prognosis between these groups. Next, the CKD+ group included 15 (22.1%) patients. They were older and had higher frequencies of hypertension and hyperuricaemia, serum creatinine (Cr) level, glomerulosclerosis, interstitial inflammation, interstitial fibrosis and tubular atrophy than the CKD- group at the time of renal biopsy. The frequency of WL was not significantly different. Cox regression analysis revealed significant associations of CKD with hypertension, hyperuricaemia, serum Cr level at the time of renal biopsy clinically and with tubular atrophy histologically. CONCLUSIONS: WL was associated with serum anti-dsDNA antibodies but not with renal prognosis, suggesting that WL reflects immune abnormality but is not an independent factor predictive of renal prognosis in LN.

The effect of aprepitant and dexamethasone combination on paclitaxel-induced hypersensitivity reaction.

PURPOSE OF INVESTIGATION: Dexamethasone (DEX) is often administered to prevent paclitaxel (PTX)-induced hypersensitivity reactions (HSR). The DEX dose is reduced when administered in combination with aprepitant (APR). However, the influence of that dose reduction on PTX-induced HSR has not been thoroughly studied. The present authors aimed to investigate the effects of the combined administration of APR and DEX on PTX-induced HSR. MATERIALS AND METHODS: Fifty-one patients who received a three-week PTX regimen in combination with APR and DEX were retrospectively analysed. The authors compared the dose of DEX with the incidence of HSR and other toxicities. RESULTS: Patients were stratified into two groups depending on the DEX dose, > 20 mg (group D, 33 patients), and < 12 mg (group reD, 26 patients). The incidence of HSR in Groups D and reD were 51.5% (17/33) and 53.8% (14/26), respectively. The frequencies of other toxicities between the groups were comparable. CONCLUSION: The findings suggest that although a reduction in DEX dose is possible when APR is co-administered, this does not affect the PTX-induced HSR. However, adverse effect should be closely monitored.

Impact of tubulointerstitial lesions on anaemia in patients with biopsy-proven diabetic nephropathy.

AIMS: To investigate the relationship between the progression of anaemia and renal pathological findings in patients with diabetic nephropathy. METHODS: A total of 223 patients with diabetes underwent renal biopsy from 1985 to 2010 and were confirmed to have pure diabetic nephropathy according to the recent classification, of whom 113 (baseline haemoglobin ≥ 11 g/dl) were enrolled in the study. Linear regression analysis was used to estimate the changes in haemoglobin levels during the follow-up period. RESULTS: In a multivariate model adjusted for clinical and histopathological variables, higher interstitial fibrosis and tubular atrophy scores were more strongly associated with a decrease in haemoglobin levels than were lower scores. Compared with an interstitial fibrosis and tubular atrophy score of 0, the standardized coefficients for interstitial fibrosis and tubular atrophy scores of 1, 2 and 3 were 0.20 (95% CI -0.31 to 0.93), 0.34 (95% CI -0.22 to 1.34) and 0.47 (95% CI 0.07 to 1.96), respectively, whereas a higher glomerular class, a higher vascular lesion score and the presence of exudative lesions were not strongly correlated with the decrease in haemoglobin. CONCLUSIONS: Tubulointerstitial lesions that are more advanced are significantly associated with the progression of anaemia in patients with diabetic nephropathy after adjustment for numerous covariates. This finding suggests that tubulointerstitial lesions may be a useful prognostic indicator for anaemia in patients with diabetic nephropathy, and that decreased erythropoietin production attributable to the progression of tubulointerstitial lesions is a major cause of anaemia in these patients.

Comparison of different aspects of BMI history to identify undiagnosed diabetes in Japanese men and women: Toranomon Hospital Health Management Center Study 12 (TOPICS 12).

AIMS: To examine current BMI and various aspects of BMI history as pre-screening tools for undiagnosed diabetes in Japanese individuals. METHODS: This cross-sectional study included 16 226 men and 7026 women aged 30-75 years without a self-reported history of clinician-diagnosed diabetes. We estimated the probability of having undiagnosed diabetes (fasting glucose ≥ 7.0 mmol/l and/or HbA1c ≥ 48 mmol/mol (≥ 6.5%) for the following variables: current BMI, BMI in the early 20s (BMI(20y)), lifetime maximum BMI (BMI(max)), change between BMI in the early 20s and current BMI (ΔBMI(20y-cur)), change between BMI in the early 20s and maximum BMI (ΔBMI(20y-max)), and change between lifetime maximum and current BMI (ΔBMI(max-cur)). RESULTS: The prevalence of undiagnosed diabetes was 3.3% (771/23252) among participants. BMI(max) , ΔBMI(20y-max) and current BMI (1-sd increments) were more strongly associated with diabetes than the other factors (multivariate odds ratio 1.58 [95% CI 1.47-1.70] in men and 1.65 [95% CI 1.43-1.90] in women for BMI(max) ; multivariate odds ratio 1.47 [95% CI 1.37-1.58] in men and 1.61 [95% CI 1.41-1.84] in women for ΔBMI(20y-max) ; multivariate odds ratio 1.47 [95% CI 1.36-1.58] in men and 1.63 [95% CI 1.40-1.89] in women for current BMI). The probability of having diabetes was markedly higher in those with both the highest tertile of BMI(max) and greatest ΔBMI(20y-max) ; however, a substantially lower likelihood of diabetes was observed among individuals with the lowest and middle tertiles of current BMI (< 24.62 kg/m² in men and < 22.54 kg/m² in women). CONCLUSIONS: Lifetime maximum BMI and BMI changes from early adulthood were strongly associated with undiagnosed diabetes. Adding BMI history to people's current BMI would improve the identification of individuals with a markedly higher probability of having undiagnosed diabetes.

A novel approach for rapid detection of bacterially contaminated platelet concentrates via sensitive measurement of microbial DNA polymerase activity.

BACKGROUND: Transfusion of bacterially contaminated platelet concentrates (PCs) can result in serious health consequences for the affected patient. Before being released from blood banking facilities, PCs are routinely screened for bacterial contamination by culture-based tests. However, culture-based PC screening methods require extended holding and incubation periods and are prone to false-negative results due to sampling error. Screening PCs closer to the time of transfusion using rapid point-of-issue tests represents an alternative approach; however, FDA-approved assays generally suffer from a lack of sensitivity. STUDY DESIGN AND METHODS: Presented herein is the feasibility of a novel approach toward rapid, sensitive, and universal detection of bacterially contaminated PCs via selective measurement of microbial DNA polymerase activity. This approach is achieved using a differential cell lysis procedure in combination with enzymatic template generation and amplification (termed ETGA-PC assay). RESULTS: Serial dilution spiking experiments revealed an approximate sensitivity of 30 to 200 colony-forming units (CFUs)/mL (mean, 85 CFUs/mL) for Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae. An additional 22 clinically relevant strains of bacteria were also detected below 200 CFUs/mL after spiking into PC aliquots. Furthermore, the ETGA-PC assay was able to accurately monitor the presence and growth of seven clinically relevant bacterial species that were spiked into PC units. CONCLUSION: Together, the data presented here demonstrate that the ETGA-PC assay is a feasible approach for rapid and sensitive detection of bacterially contaminated PCs. Experiments, aimed at simplification and/or automation of the assay procedure, are under way.

Genetic variation at a Yin-Yang 1 response site regulates the transcription of cyclin-dependent kinase inhibitor p18INK4C transcript in lupus-prone mice.

We have previously shown that a novel -74 C-to-T mutation in the promoter of the cyclin-dependent kinase inhibitor p18(Ink4c) (p18) gene was associated with a reduced p18 expression in B cells from mice carrying the Sle2c1 lupus susceptibility locus. To determine the function of the -74 C/T single nucleotide polymorphism, we have characterized the proximal promoter of the mouse p18 gene. Functional analysis of the 5' flanking region by sequential deletions revealed crucial elements between -300 and +1, confirming the in silico prediction that the -74 T allele created a novel Yin-Yang 1 (YY-1) binding site adjacent to an existing one common to both alleles. Moreover, we found that YY-1, E2F1, and Sp-1 can synergistically enhance the activity of the p18 promoter. Mutational inactivation revealed that YY-1 binding regulates the p18 activity in an allele-dependent fashion. EMSAs with splenic B cell extracts directly demonstrated that YY-1 binds to the p18 promoter with differences between the C and the T alleles. We also determined in vivo by chromatin immunoprecipitation that the T allele resulted in increased YY-1 and decreased Nrf-2 binding to the p18 promoter as compared with the C allele in B cells. Thus, YY-1 is a direct regulator of p18 gene expression in an allele-dependent fashion that is consistent with the lupus-associated T allele, inducing a lower p18 transcriptional activity by increasing YY-1 binding. These results establish the p18 -74 C/T mutation as the leading causal variant for the B1a cell expansion that characterizes the NZB and NZM2410 lupus-prone strains.

Cyclin-dependent kinase inhibitor Cdkn2c deficiency promotes B1a cell expansion and autoimmunity in a mouse model of lupus.

The lupus-prone NZM2410 mice present an expanded B1a cell population that we have mapped to the Sle2c1 lupus susceptibility locus. The expression of Cdkn2c, a gene encoding for cyclin-dependent kinase inhibitor p18(Ink4c) and located within Sle2c1, is significantly lower in B6.Sle2c1 B cells than in B6 B cells. To test the hypothesis that the B1a cell expansion in B6.Sle2c1 mice was due to a defective p18 expression, we analyzed the B1a cell phenotypes of p18-deficient C57BL/6 mice. We found a dose-dependent negative correlation between the number of B1a cells and p18 expression in B cells, with p18-deficient mice showing an early expansion of the peritoneal B1a cell pool. p18 deficiency enhanced the homeostatic expansion of B1a cells but not of splenic conventional B cells, and the elevated number of B6.Sle2c1 B1a cells was normalized by cyclin D2 deficiency. These data demonstrated that p18 is a key regulator of the size of the B1a cell pool. B6.p18(-/-) mice produced significant amounts of anti-DNA IgM and IgG, indicating that p18 deficiency contributes to humoral autoimmunity. Finally, we have shown that Sle2c1 increases lpr-associated lymphadenopathy and T cell-mediated pathology. B6.p18(-/-).lpr mice showed a greater lymphadenopathy than B6.Sle2c1.lpr mice, but their renal pathology was intermediate between that of B6.lpr and B6.Sle2c1.lpr mice. This indicated that p18-deficiency synergizes, at least partially, with lpr-mediated pathology. These results show that Cdkn2c contributes to lupus susceptibility by regulating the size of the B1a cell compartment and hence their contribution to autoimmunity.

Pre-B cell leukemia homeobox 1 is associated with lupus susceptibility in mice and humans.

Sle1a.1 is part of the Sle1 susceptibility locus, which has the strongest association with lupus nephritis in the NZM2410 mouse model. In this study, we show that Sle1a.1 results in the production of activated and autoreactive CD4(+) T cells. Additionally, Sle1a.1 expression reduces the peripheral regulatory T cell pool, as well as induces a defective response of CD4(+) T cells to the retinoic acid expansion of TGF-ß-induced regulatory T cells. At the molecular level, Sle1a.1 corresponds to an increased expression of a novel splice isoform of Pbx1, Pbx1-d. Pbx1-d overexpression is sufficient to induce an activated/inflammatory phenotype in Jurkat T cells and to decrease their apoptotic response to retinoic acid. PBX1-d is expressed more frequently in the CD4(+) T cells from lupus patients than from healthy controls, and its presence correlates with an increased central memory T cell population. These findings indicate that Pbx1 is a novel lupus susceptibility gene that regulates T cell activation and tolerance.

Investigation of the mechanisms underlying the high acetylene-reducing activity exhibited by the soil bacterial community from BC2 horizon in the permafrost zone of the East Siberian larch forest bed.

AIMS: This study addressed a microbial composition of East Siberian larch forest bed soil and focused on major nitrogen-fixing bacterial consortia showing the highest capacity to induce acetylene reduction. METHODS AND RESULTS: The ability of a soil microbial consortium to effectively reduce acetylene was investigated using gellan gum medium. In parallel, each microbial component in the medium was analysed by a 16S rRNA gene-targeting denaturing gradient gel electrophoresis (DGGE), together with an attempt to isolate pure culture of the culturable eubacteria. Six strains of the isolated bacteria were characterized as diazotrophs, and Burkholderia xenovorans was found to be one of the major nitrogen fixer in the bacterial community cultured from the BC2 horizon soil microbiota. Co-culturing of either a diazotrophic Pseudomonas sp. with a nondiazotrophic Luteibacter sp. or a diazotrophic Luteibacter sp. with a nondiazotrophic bacterium B. xenovorans resulted in a marked elevation in acetylene reduction over that observed in the pure culture of each diazotroph. CONCLUSIONS: A promotion of acetylene reduction in mixed bacterial cultures, particularly when the cultures included Luteibacter, was clearly observed due to an increase in the bacterial cell population. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study, which showed that some unculturable bacteria including anaerobic Clostridium sp. that can provide major contribution to nitrogen fixation, may provide key information useful in identifying the 'missing link' in the nitrogen cycle in the cryogenic soil ecosystem of boreal forests.

Retrospective analysis of clinical data associated with patients enrolled in a molecular diagnostic feasibility study highlights the potential utility for rapid detection of bloodstream infection.

BACKGROUND: Measurement of pathogen DNA polymerase activity by enzymatic template generation and amplification (ETGA) has shown promise in detecting pathogens in bloodstream infection (BSI). We perform an in-depth analysis of patients with clinical BSI enrolled in ETGA feasibility experiments. METHODS: In addition to hospital blood cultures, 1 study aerobic culture bottle was drawn from patients with suspected BSI. The study bottle was split into 2 bottles and was additionally subjected to ETGA analysis. Enzymatic template generation and amplification sensitivity/specificity for BSI detection was determined against the Centers for Disease Control BSI definition. When split cultures were both positive, time course analysis was performed to determine time to detection. The records of patients with BSI were reviewed for presence of systemic inflammatory response syndrome, antibiotic timing and appropriateness, and organism identification. RESULTS: Of 307 enrollees, 38 met the Centers for Disease Control BSI definition. Seventy-four percent met systemic inflammatory response syndrome criteria on admission. Antibiotic coverage was adequate in 76% of patients. Antibiotics were more often delayed in afebrile patients (odds ratio, 5). Twenty-seven of the split study culture bottles were positive in at least 1 sample, and ETGA detected microbes within all samples (sensitivity/specificity, 70.3%/99.3%). Of these, 22 were culture positive in both split study bottles and underwent ETGA time course analysis. Enzymatic template generation and amplification detected microbes within these 3-fold faster than culture. CONCLUSIONS: Patients with BSI often have diagnostic and treatment delays. Enzymatic template generation and amplification provides clinically meaningful data more rapidly than cultures. Future development should focus on real-time application of assays that detect microbes at the molecular level.

Characterization of a novel DNA polymerase activity assay enabling sensitive, quantitative and universal detection of viable microbes.

During the past 50 years, in vitro measurement of DNA polymerase activity has become an essential molecular biology tool. Traditional methods used to measure DNA polymerase activity in vitro are undesirable due to the usage of radionucleotides. Fluorescence-based DNA polymerase assays have been developed; however, they also suffer from various limitations. Herein we present a rapid, highly sensitive and quantitative assay capable of measuring DNA polymerase extension activity from purified enzymes or directly from microbial lysates. When tested with purified DNA polymerase, the assay detected as little as 2 × 10(-11)U of enzyme (∼ 50 molecules), while demonstrating excellent linearity (R(2)=0.992). The assay was also able to detect endogenous DNA polymerase extension activity down to less than 10 colony forming units (cfu) of input Gram-positive or Gram-negative bacteria when coupled to bead mill lysis while maintaining an R(2)=0.999. Furthermore, preliminary evidence presented here suggests that DNA polymerase extension activity is an indicator of microbial viability, as demonstrated by the reproducibly strong concordance between assay signal and bacterial colony formation. Together, the innovative methodology described here represents a significant advancement toward sensitive detection of potentially any microorganism containing active DNA polymerase within a given sample matrix.

Leiomyosarcoma of the broad ligament: a case report with CT and MRI images.

Primary leiomyosarcoma of the broad ligament is a very rare and highly malignant gynecological tumor. The authors report a 61-year-old postmenopausal woman with signs and symptoms of malignant ovarian tumor. Preoperative magnetic resonance imaging (MRI) was interpreted as being suspicious for malignant tumors, such as an ovarian cancer or a leiomyosarcoma of the broad ligament, so laparotomy was performed. Macroscopically, the tumor was revealed with a 18 x 13.7 x 9.5 cm degenerated, multiple cystic part and solid whitish part arising from broad ligament which on histopathology proved to be leiomyosarcoma. To the best of the authors' knowledge, primary leiomyosarcoma of the broad ligament has been documented in 21 reports or so, and no imaging findings are available. Here the authors present the MRI findings of primary leiomyosarcoma of the broad ligament.

Feasibility study demonstrating that enzymatic template generation and amplification can be employed as a novel method for molecular antimicrobial susceptibility testing.

BACKGROUND: Antimicrobial Susceptibility Testing (AST) is a methodology in which the sensitivity of a microorganism is determined via its inability to proliferate in the presence of an antimicrobial agent. Results are reported as minimum inhibitory concentrations (MICs). The present study demonstrates that measurement of DNA polymerase activity via Enzymatic Template Generation and Amplification (ETGA) can be used as a novel means of determining the MIC of a microbe to an antibiotic agent much sooner than the current standardized method. METHODS: Time course analysis of ETGA is presented from bacterial cultures containing antibiotic agents and compared to the end-point results of standard macrobroth method AST. RESULTS: MIC determinations from ETGA results at 4, 6, and 22 hours are compared to the MICs from the standard method and the results are shown to be in agreement. Additionally, reliable AST analysis using ETGA can be performed on bacteria harvested directly from spiked blood cultures. CONCLUSIONS: AST analysis with ETGA is shown to be equivalent to AST analysis using gene-specific qPCR assays against the measured microbe. Future development of this novel method for performing AST in a clinical setting is discussed.

Association of living alone with the presence of undiagnosed diabetes in Japanese men: the role of modifiable risk factors for diabetes: Toranomon Hospital Health Management Center Study 13 (TOPICS 13).

AIMS: To investigate whether living alone was associated with the presence of undiagnosed diabetes and whether this association could be attenuated by modifiable lifestyle habits. METHODS: This cross-sectional study included 6400 Japanese men without a history of diagnosed diabetes. Individuals with currently undiagnosed diabetes were identified through fasting glucose concentration ≥7.0 mmol/l or HbA1c concentration ≥ 48 mmol/mol (≥ 6.5%). Effect modification was examined using body mass index, hypertension, history of dyslipidaemia, drinking habits, smoking habits, physical activity, vegetable intake, emotional stress and depressed mood. RESULTS: Men who lived alone (n = 1098) had a significantly elevated odds ratio for having undiagnosed diabetes in an age-adjusted model (odds ratio 1.45, 95% CI 1.07, 1.96; P = 0.018). After adjustment for lifestyle factors, the association was slightly attenuated (odds ratio 1.40, 95% CI 1.02, 1.91; P = 0.036). After further adjustment for all factors mentioned above, living alone was still marginally significantly associated with the presence of undiagnosed diabetes (odds ratio 1.38, 95% CI 1.003, 1.90; P = 0.048). A significant association of living alone with the presence of undetected diabetes was particularly observed among men who were overweight, currently smoked and were physically inactive, or had any one of those three factors. CONCLUSIONS: The association between undiagnosed diabetes and living alone can be partially influenced by modifiable lifestyle factors. Men who lived alone, especially those who did not engage in favourable lifestyle habits, were more likely to have undiagnosed diabetes. Such individuals have a higher probability of having undetected diabetic hyperglycaemia and would need to undergo glucose tests to identify the disease.

Cyclin-dependent kinase inhibitor Cdkn2c regulates B cell homeostasis and function in the NZM2410-derived murine lupus susceptibility locus Sle2c1.

Sle2c1 is an NZM2410- and NZB-derived lupus susceptibility locus that induces an expansion of the B1a cell compartment. B1a cells have a repertoire enriched for autoreactivity, and an expansion of this B cell subset occurs in several mouse models of lupus. A combination of genetic mapping and candidate gene analysis presents Cdkn2c, a gene encoding for cyclin-dependent kinase inhibitor p18(INK4c) (p18), as the top candidate gene for inducing the Slec2c1-associated expansion of B1a cells. A novel single nucleotide polymorphism in the NZB allele of the Cdkn2c promoter is associated with a significantly reduced Cdkn2c expression in the splenic B cells and peritoneal cavity B1a cells from Sle2c1-carrying mice, which leads to a defective G1 cell cycle arrest in splenic B cells and increased proliferation of peritoneal cavity B1a cells. As the cell cycle is differentially regulated in B1a and B2 cells, these results suggest that Cdkn2c plays a critical role in B1a cell self-renewal and that its impaired expression leads to an accumulation of these cells with high autoreactive potential.

Effect of experimental jaw muscle pain on EMG activity and bite force distribution at different level of clenching.

Bite force at different levels of clenching and the corresponding electromyographic (EMG) activity in jaw-closing muscles were recorded in 16 healthy women before, during and after painful stimulation of the left masseter muscle. Experimental pain was induced by infusion of 5·8% hypertonic saline (HS), and 0·9% isotonic saline (IS) was infused as a control. EMG activity was recorded bilaterally from the masseter and temporalis muscles, and static bite force was assessed by pressure-sensitive films (Dental Pre-scale) at 5, 50 and 100% of maximal voluntary contraction (MVC) during each session. Visual feedback was applied by showing EMG activity to help the subject perform clenching at 5, 50 and 100% MVC, respectively. EMG activity at 100% MVC in left and right masseter decreased significantly during painful HS infusion (1·7-44·6%; P < 0·05). EMG activity at 5% and 50% MVC was decreased during HS infusion in the painful masseter muscle (4·8-18·6%; P < 0·05); however, EMG activity in the other muscles increased significantly (18·5-128·3%; P < 0·05). There was a significant increase in bite force in the molar regions at 50% MVC during HS infusion and in the post-infusion condition (P < 0·05). However, there were no significant differences in the distribution of forces at 100% MVC. In conclusion, experimental pain in the masseter muscle has an inhibitory effect on jaw muscle activity at maximal voluntary contraction, and compensatory mechanisms may influence the recruitment pattern at submaximal efforts.

Experiences that matter in bipolar disorder: a qualitative study using the capability, comfort and calm framework.

BACKGROUND: When assessing the value of an intervention in bipolar disorder, researchers and clinicians often focus on metrics that quantify improvements to core diagnostic symptoms (e.g., mania). Providers often overlook or misunderstand the impact of treatment on life quality and function. We wanted to better characterize the shared experiences and obstacles of bipolar disorder within the United States from the patient's perspective. METHODS: We recruited 24 individuals diagnosed with bipolar disorder and six caretakers supporting someone with the condition. Participants were involved in treatment or support services for bipolar disorder in central Texas. As part of this qualitative study, participants discussed their everyday successes and obstacles related to living with bipolar disorder during personalized, open-ended interviews. Audio files were transcribed, and Nvivo software processed an initial thematic analysis. We then categorized themes into bipolar disorder-related obstacles that limit the patient's capability (i.e., function), comfort (i.e., relief from suffering) and calm (i.e., life disruption) (Liu et al., FebClin Orthop 475:315-317, 2017; Teisberg et al., MayAcad Med 95:682-685, 2020). We then discuss themes and suggest practical strategies that might improve the value of care for patients and their families. RESULTS: Issues regarding capability included the struggle to maintain identity, disruptions to meaningful employment, relationship loss and the unpredictable nature of bipolar disorder. Comfort related themes included the personal perception of diagnosis, social stigma and medication issues. Calm themes included managing dismissive doctors, finding the right psychotherapist and navigating financial burdens. CONCLUSIONS: Qualitative data from patients with bipolar disorder helps identify gaps in care or practical limitations to treatment. When we listen to these individuals, it is clear that treatments must also address the unmet psychosocial impacts of the condition to improve patient care, capability and calm.

Development of a new scoring system for predicting the 5 year incidence of type 2 diabetes in Japan: the Toranomon Hospital Health Management Center Study 6 (TOPICS 6).

AIMS/HYPOTHESIS: The aims of this study were to assess the clinical significance of introducing HbA(1c) into a risk score for diabetes and to develop a scoring system to predict the 5 year incidence of diabetes in Japanese individuals. METHODS: The study included 7,654 non-diabetic individuals aged 40-75 years. Incident diabetes was defined as fasting plasma glucose (FPG) ≥7.0 mmol/l, HbA(1c) ≥6.5% (48 mmol/mol) or self-reported clinician-diagnosed diabetes. We constructed a risk score using non-laboratory assessments (NLA) and evaluated improvements in risk prediction by adding elevated FPG, elevated HbA(1c) or both to NLA. RESULTS: The discriminative ability of the NLA score (age, sex, family history of diabetes, current smoking and BMI) was 0.708. The difference in discrimination between the NLA + FPG and NLA + HbA(1c) scores was non-significant (0.836 vs 0.837; p = 0.898). A risk score including family history of diabetes, smoking, obesity and both FPG and HbA(1c) had the highest discrimination (0.887, 95% CI 0.871, 0.903). At an optimal cut-off point, sensitivity and specificity were high at 83.7% and 79.0%, respectively. After initial screening using NLA scores, subsequent information on either FPG or HbA(1c) resulted in a net reclassification improvement of 42.7% or 52.3%, respectively (p < 0.0001). When both were available, net reclassification improvement and integrated discrimination improvement were further improved at 56.7% (95% CI 47.3%, 66.1%) and 10.9% (9.7%, 12.1%), respectively. CONCLUSIONS/INTERPRETATION: Information on HbA(1c) or FPG levels after initial screening by NLA can precisely refine diabetes risk reclassification.