Degree of improving TMS focality through a geometrically stable solution of an inverse TMS problem.

The Transcranial Magnetic Stimulation (TMS) inverse problem (TMS-IP) investigated in this study aims to focus the TMS induced electric field close to a specified target point defined on the gray matter interface in the M1HAND area while otherwise minimizing it. The goal of the study is to numerically evaluate the degree of improvement of the TMS-IP solutions relative to the well-known sulcus-aligned mapping (a projection approach with the 90∘ local sulcal angle). In total, 1536 individual TMS-IP solutions have been analyzed for multiple target points and multiple subjects using the boundary element fast multipole method (BEM-FMM) as the forward solver. Our results show that the optimal TMS inverse-problem solutions improve the focality - reduce the size of the field "hot spot" and its deviation from the target - by approximately 21-33% on average for all considered subjects, all observation points, two distinct coil types, two segmentation types, two intracortical observation surfaces under study, and three tested values of the field threshold. The inverse-problem solutions with the maximized focality simultaneously improve the TMS mapping resolution (differentiation between neighbor targets separated by approximately 10 mm) although this improvement is quite modest. Coil position/orientation and conductivity uncertainties have been included into consideration as the corresponding de-focalization factors. The present results will change when the levels of uncertainties change. Our results also indicate that the accuracy of the head segmentation critically influences the expected TMS-IP performance.

Deep-learning-based image reconstruction in dynamic contrast-enhanced abdominal CT: image quality and lesion detection among reconstruction strength levels.

AIM: To evaluate the use of deep-learning-based image reconstruction (DLIR) algorithms in dynamic contrast-enhanced computed tomography (CT) of the abdomen, and to compare the image quality and lesion conspicuity among the reconstruction strength levels. MATERIALS AND METHODS: This prospective study included 59 patients with 373 hepatic lesions who underwent dynamic contrast-enhanced CT of the abdomen. All images were reconstructed using four reconstruction algorithms, including 40% adaptive statistical iterative reconstruction-Veo (ASiR-V) and DLIR at low, medium, and high-strength levels (DLIR-L, DLIR-M, and DLIR-H, respectively). The signal-to-noise ratio (SNR) of the abdominal aorta, portal vein, liver, pancreas, and spleen and the lesion-to-liver contrast-to-noise ratio (CNR) were calculated and compared among the four reconstruction algorithms. The diagnostic acceptability was qualitatively assessed and compared among the four reconstruction algorithms and the conspicuity of hepatic lesions was compared between <5 and ≥5 mm lesions. RESULTS: The SNR of each anatomical structure (p<0.0001) and CNR (p<0.0001) were significantly higher in DLIR-H than the other reconstruction algorithms. Diagnostic acceptability was significantly better in DLIR-M than the other reconstruction algorithms (p<0.0001). The conspicuity of hepatic lesions was highest when using 40% ASiR-V and tended to lessen as the reconstruction strength level was getting higher in DLIR, especially in <5 mm lesions; however, all hepatic lesions could be detected. CONCLUSIONS: DLIR improved the SNR, CNR, and image quality compared with 40% ASiR-V, while making it possible to decrease lesion conspicuity using higher reconstruction strength.

Development and validation of the comprehensive assessment scale for chemotherapy-induced peripheral neuropathy in survivors of cancer.

BACKGROUND: Appropriate assessment is essential for the management of chemotherapy-induced peripheral neuropathy (CIPN), an intractable symptom that cannot yet be palliated, which is high on the list of causes of distress for cancer patients. However, objective assessment by medical staff makes it easy to underestimate the symptoms and effects of CIPN in cancer survivors. As a result, divergence from subjective evaluation of cancer survivors is a significant problem. Therefore, there is an urgent need to develop a subjective scale with high accuracy and applicability that reflects the experiences of cancer patients. We developed a comprehensive assessment scale for CIPN in cancer survivors, named the Comprehensive Assessment Scale for Chemotherapy-Induced Peripheral Neuropathy in Survivors of Cancer (CAS-CIPN), and demonstrated its reliability and validity. METHODS: We developed a questionnaire based on qualitative studies of peripheral neuropathy in Japanese cancer patients and literature review. Twelve cancer experts confirmed the content validity of the questionnaire. A draft version comprising 40 items was finalized by a pilot test on 100 subjects. The participants in the present study were 327 Japanese cancer survivors. Construct validity was determined by factor analysis, and internal validity by confirmation factor analysis and Cronbach's α. RESULTS: Factor analysis showed that the structure consisted of 15 items in four dimensions: "Threatened interference in daily life by negative feelings", "Impaired hand fine motor skills", "Confidence in choice of treatment/management," and "Dysesthesia of the palms and soles." The CAS-CIPN internal consistency reliability was 0.826, and the reliability coefficient calculated using the Spearman-Brown formula [q = 2r/(1 + r)] was 0.713, confirming high internal consistency and stability. Scores on this scale were strongly correlated with Gynecologic Oncology Group-Neurotoxicity scores (r = 0.714, p < 0.01), confirming its criterion-related validity. CONCLUSIONS: The CAS-CIPN is an assessment tool with high reliability and validity for the comprehensive evaluation of CIPN in cancer survivors. The CAS-CIPN is simple to use, and can be used by medical professionals for appropriate situational assessment and intervention.

Frequency and risk factors of thoracic metastases and optimisation of the use of cross-sectional chest imaging in follow-up patients with cervical cancer.

AIM: To optimise cross-sectional chest imaging usage by identifying frequency and risk factors associated with thoracic metastases in cervical cancer patients after initial definitive treatment. MATERIALS AND METHODS: This study, conducted during 2004-2015, examined 361 consecutive patients with histopathologically proven cervical carcinoma with at least 1 year of follow-up. Electronic medical records and all available imaging modes were used to record and assess patient and tumour characteristics and timing of thoracic metastases. Associations with these characteristics and thoracic metastases were assessed using univariate and multivariable Cox proportional hazards modelling. RESULTS: Of the 361 patients, 31 developed thoracic metastases. Multivariate regression results showed that adeno/adenosquamous carcinomas (hazard ratio [HR], 2.46; 95% confidence interval [CI], 1.06 to 5.72), other histology (HR, 5.61; 95% CI, 1.81 to 17.42), high International Federation of Gynaecology and Obstetrics (FIGO) stage (HR, 2.84; 95% CI, 1.09 to 7.37), and presence of initial intra-abdominal lymph node metastases (HR, 2.46; 95% CI, 1.02 to 5.90) were associated significantly and independently with thoracic metastases. The second analysis among the subgroup of surgical treatment identified intermediate-high risk classification of recurrence (HR, 5.12; 95% CI, 1.14 to 22.94), high FIGO stage (HR, 2.73; 95% CI, 1.05 to 7.13), and other histology (HR, 11.51; 95% CI, 3.66 to 36.19) as independent predictors of thoracic metastases. Two of the 361 and 2/313 patients with thoracic metastases who did not correspond to the conditions above were in the respective evaluation groups. CONCLUSION: Assessment of negative prognostic factors for thoracic metastases might contribute to reduced need for chest cross-sectional chest computed tomography examinations.

Development of 19F-NMR chemical shift detection of DNA B-Z equilibrium using 19F-NMR.

Various DNA conformational changes are in correlation with biological events. In particular, DNA B-Z equilibrium showed a high correlation with translation and transcription. In this study, we developed a DNA probe containing 5-trifluoromethylcytidine or 5-trifluoromethylthymidine to detect DNA B-Z equilibrium using 19F-NMR. Its probe enabled the quantitative detection of B-, Z-, and ss-DNA based on 19F-NMR chemical shift change.

Characteristics of C6-7 myelopathy: assessment of clinical symptoms and electrophysiological findings.

STUDY DESIGN: This is a single-center retrospective study. OBJECTIVES: The objective of this study was to study the clinical symptoms and electrophysiological features of C6-7 myelopathy. SETTING: This study was conducted at the Department of Orthopedic surgery, Yamaguchi University Graduate school of medicine, Japan. METHODS: A total of 20 patients with cervical compressive myelopathy were determined by spinal cord-evoked potentials or a single level of obvious magnetic resonance imaging (MRI)-documented cervical spinal cord compression. Neurological examinations included manual muscle testing and investigation of deep tendon reflex, including Hoffmann sign, and of sensory disturbance areas. Motor-evoked potentials (MEPs), compound muscle action potentials (CMAPs) and F-wave were recorded from bilateral abductor digit minim and abductor halluces muscles. Central motor conduction time was calculated as follows: MEPs latency-(CMAPs latency+F latency-1)/2 (ms). RESULTS: Eighteen patients (90%) had negative Hoffmann sign. Eight patients (40%) had no sensory disturbance in the upper limbs and 8 patients (40%) had no muscle weakness in the upper limbs. We determined that patients had cervical myelopathy when their central motor conduction time measured in abductor digit minim was longer than 6.76 ms (+2 s.d.). Using this definition, the sensitivity for myelopathy was 42.8%. CONCLUSION: Patients with C6-7 myelopathy may lack clinical symptoms in their hands and central motor conduction time measured in abductor digit minim tended to be less prolonged, and it only showed symptoms in their lower limbs as gait disturbance. Surgeons should bear in mind the possibility of disorders of caudal C6-7 when they encounter patients with no or few symptoms in their hands and with leg weakness or numbness.

Locomotor improvement of spinal cord-injured rats through treadmill training by forced plantar placement of hind paws.

STUDY DESIGN: Experimental training model of rats with spinal cord injury (SCI). SETTING: Osaka, JapanObjective:To investigate the effect of forced treadmill training by plantar placement (PP), as compared with dorsal placement (DP), of the dorsal paws on the locomotor behaviors of spinal cord-injured rats. METHODS: The spinal cord was contusion-injured at the thoracic level. Rats were divided into three groups: forced training involving stepping by PP and DP and non-forced training/assistance (nT). Training began 1 week after injury and was conducted for 4 weeks. Locomotor behaviors were estimated using Basso-Beattie-Bresnahan (BBB) scores, dorsiflexion of the hind paws and footprints of the hind paws. Histological and immunohistochemical examinations of the spinal cord lesions were conducted after 4 weeks of training. RESULTS: The values, respectively, of PP, DP and nT groups at 4 weeks of training were as follows: BBB scores were 15.6±0.8, 7.7±1.3 and 10.3±0.4. The paw dorsiflexion angles were 34.1±5.2, 16.4±2.4 and 23.6±3.0 degrees, respectively. The stride angles were 5.1±0.9, 13.7±4.9 and 17.8±4.0 degrees for the left paws. Cavity volumes were 10.3±2.1, 31.0±2.0 and 28.2±4.9%. In addition to cavities, there were astrocyte-devoid areas containing some loose tissues, through which many axons extended longitudinally. CONCLUSIONS: The BBB score, dorsiflexion angle and stride angle were consistently improved in the PP group. Cavity formation was more reduced, and many axons extended through coarse tissues formed in astrocyte-devoid areas at the lesion in the PP group. Forced training by PP of the hind paws promoted the behavioral and histological improvement of rats with SCI.

Correlation of circulating betatrophin concentrations with insulin secretion capacity, evaluated by glucagon stimulation tests.

AIM: To investigate the relationship between plasma betatrophin concentrations and insulin secretion capacity in people with Type 2 diabetes. METHODS: Glucagon stimulation tests (1 mg) were performed in 70 people with Type 2 diabetes after an overnight fast. Plasma betatrophin concentrations were measured using an enzyme-linked immunosorbent assay. Insulin secretion capacity was evaluated by measuring increments of C-peptide concentration in response to glucagon stimulation, and creatinine clearance was determined by comparing creatinine concentrations in serum and 24-h urine samples. RESULTS: Plasma betatrophin concentrations were positively correlated with duration of Type 2 diabetes (r = 0.34, P = 0.003), and negatively correlated with increments of C-peptide concentration (r = 0.37, P = 0.001) and creatinine clearance (r = 0.37, P = 0.001). The correlation with increments of C-peptide concentration remained significant after adjustment for age and duration of Type 2 diabetes (r = 0.25, P = 0.037). Multivariate analysis identified age and increments of C-peptide concentration as independent factors associated with plasma betatrophin levels. CONCLUSION: Plasma betatrophin levels inversely correlate with insulin secretion capacity, suggesting that betatrophin levels are regulated by insulin secretion capacity in humans.

Occurrence of adverse events caused by valganciclovir as pre-emptive therapy for cytomegalovirus infection after allogeneic stem cell transplantation is reduced by low-dose administration.

BACKGROUND: Pre-emptive therapy with valganciclovir (VGCV) has become the standard therapy for preventing cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (HSCT). The effectiveness of low-dose VGCV (900 mg per day) has been shown to be equal to that of standard-dose VGCV (900 mg twice daily); however, individualized optimal dosing and toxicity of VGCV have not been reported. METHODS: We conducted a retrospective study to evaluate the optimal dose of VGCV as pre-emptive therapy for preventing CMV infection by comparing the frequency of adverse events (AEs) and clinical efficacy in a low-dose VGCV group with those in a standard-dose VGCV group. Thirty-eight patients who were administered VGCV because of CMV antigenemia after HSCT were analyzed. RESULTS: Neutropenia (standard-dose group: 33%, low-dose group: 15%, P = 0.26) and thrombocytopenia (standard-dose group: 39%, low-dose group: 15%, P = 0.14) were frequent AEs of VGCV, and a significantly higher frequency of overall AEs was detected in the standard-dose group than in the low-dose group (P < 0.01). In comparison of dosage based on weight, dosage of VGCV >27 mg/kg was closely related to onset of AEs (P = 0.04). CONCLUSIONS: Low-dose VGCV was not inferior in clinical efficacy, including clearance rate of CMV antigenemia and incidence of consequent CMV disease, to standard-dose VGCV as was previously reported. Initial low-dose VGCV for pre-emptive CMV therapy markedly reduces hematologic toxicity and has clinical efficacy equivalent to that of standard-dose VGCV. It is therefore reasonable for patients, except for noticeably overweight patients, to be given initial low-dose VGCV.

Randomised phase III study of neoadjuvant chemotherapy with methotrexate, doxorubicin, vinblastine and cisplatin followed by radical cystectomy compared with radical cystectomy alone for muscle-invasive bladder cancer: Japan Clinical Oncology Group Study JCOG0209.

BACKGROUND: This study aimed to determine the clinical benefit of neoadjuvant methotrexate, doxorubicin, vinblastine, and cisplatin (MVAC) in patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy. PATIENTS AND METHODS: Patients with MIBC (T2-4aN0M0) were randomised to receive two cycles of neoadjuvant MVAC followed by radical cystectomy (NAC arm) or radical cystectomy alone (RC arm). The primary end point was overall survival (OS). Secondary end points were progression-free survival, surgery-related complications, adverse events during chemotherapy, proportion with no residual tumour in the cystectomy specimens, and quality of life. To detect an improvement in 5-year OS from 45% in the RC arm to 57% in the NAC arm with 80% power, 176 events were required per arm. RESULTS: Patients (N = 130) were randomly assigned to the RC arm (N = 66) and the NAC arm (N = 64). The patient registration was terminated before reaching the initially planned number of patients because of slow accrual. At the second interim analysis just after the early stoppage of patient accrual, the Data and Safety Monitoring Committee recommended early publication of the results because the trial did not have enough power to draw a confirmatory conclusion. OS of the NAC arm was better than that of the RC arm, although the difference was not statistically significant [hazard ratio 0.65, multiplicity adjusted 99.99% confidence interval 0.19-2.18, one-sided P = 0.07]. In the NAC arm and the RC arm, 34% and 9% of the patients had pT0, respectively (P < 0.01). In subgroup analyses, OS in almost all subgroups was in favour of NAC. CONCLUSIONS: This trial showed a significantly increased pT0 proportion and favourable OS of patients who received neoadjuvant MVAC. NAC with MVAC can still be considered promising as a standard treatment. UMIN CLINICAL TRIALS REGISTRY IDENTIFIER: C000000093.

Development of a particle nanoimprinting technique by core-shell particles.

We developed a particle nanoimprinting technique assisted by the array of core-shell particles. Core-shell particles composed of a solid core of polystyrene and a soft shell were prepared by soap-free emulsion polymerization and subsequently seeded polymerization. By the Langmuir-Blodgett method, particles were arranged into a closely packed 2D array over the water surface and transferred onto a polystyrene (PS) substrate at a regular interval. The PS substrate was heated up above its glass transition temperature (Tg) by either UV irradiation using a high-pressure Hg lamp or heat treatment in a temperature-controlled incubator. It could be observed that a nanopatterned indented surface was formed through the denting of particles into the PS substrate (particle nanoindenting). By the detachment of particles from the substrate by ultrasonication in ethanol, nanoholes were produced over the surface (particle nanoimprinting). The depth and the wall of nanoholes and their interval were tunable by the shell thickness and the 2D packing ratio of core-shell particle monolayers. The contact angle decreased from 70 degrees of the pristine particle monolayer to 13 degrees by the particle nanoindenting, and again increased to 50 degrees by detaching the particles from the substrate to create the nanoholes. The use of nanoholes as zepto-litter volume vessels enabled us to produce and arrange nanocrystals, such as NaCl and CaCO3 (zepto-reactor).

Hepatitis B virus (HBV) reverse seroconversion (RS) can be prevented even in non-responders to hepatitis B vaccine after allogeneic stem cell transplantation: long-term analysis of intervention in RS with vaccine for patients with previous HBV infection.

BACKGROUND: Reactivation of hepatitis B virus (HBV) infection, reverse seroconversion (RS), is a serious complication after allogeneic stem cell transplantation (alloHSCT). We previously conducted a post-transplant hepatitis B vaccine intervention trial and demonstrated the vaccine efficacy in preventing HBV-RS. This report is an update of the hepatitis B vaccine study. METHODS: In this trial, 21 patients were enrolled and received a standard 3-dose regimen of hepatitis B vaccine after discontinuation of immunosuppressants, whereas 25 transplant recipients with previous HBV infection did not receive the vaccine and served as controls. RESULTS: None of the 21 patients in the vaccine group developed HBV-RS and 12 controls developed HBV-RS in median follow-up periods of 60 months (range 13-245). HBV vaccine resulted in a positive value of hepatitis B surface antibody (HBsAb) titer in 9 patients, while HBsAb remained negative in 12 patients. Presence of a high titer of HBsAb before vaccination was associated with conversion into HBsAb positivity after vaccination. CONCLUSION: These results demonstrated the long-term effects of HBV vaccine for preventing HBV-RS after alloHSCT. Of note, no HBV-RS occurred, even in patients who did not achieve conversion into HBsAb positivity after vaccination.

All-atom molecular dynamics calculation study of entire poliovirus empty capsids in solution.

Small viruses that belong, for example, to the Picornaviridae, such as poliovirus and foot-and-mouth disease virus, consist simply of capsid proteins and a single-stranded RNA (ssRNA) genome. The capsids are quite stable in solution to protect the genome from the environment. Here, based on long-time and large-scale 6.5 × 10(6) all-atom molecular dynamics calculations for the Mahoney strain of poliovirus, we show microscopic properties of the viral capsids at a molecular level. First, we found equilibrium rapid exchange of water molecules across the capsid. The exchange rate is so high that all water molecules inside the capsid (about 200,000) can leave the capsid and be replaced by water molecules from the outside in about 25 µs. This explains the capsid's tolerance to high pressures and deactivation by exsiccation. In contrast, the capsid did not exchange ions, at least within the present simulation time of 200 ns. This implies that the capsid can function, in principle, as a semipermeable membrane. We also found that, similar to the xylem of trees, the pressure of the solution inside the capsid without the genome was negative. This is caused by coulombic interaction of the solution inside the capsid with the capsid excess charges. The negative pressure may be compensated by positive osmotic pressure by the solution-soluble ssRNA and the counter ions introduced into it.

Radiocaesium concentrations in the muscle and eggs of salmonids from Lake Chuzenji, Japan, after the Fukushima fallout.

Approximately 18 months (September to December 2012) after the Fukushima Dai-ichi Nuclear Power Plant accident, elevated radiocaesium concentrations were measured in samples of muscle and eggs from masu salmon Oncorhynchus masou, kokanee Oncorhynchus nerka, brown trout Salmo trutta and lake trout Salvelinus namaycush from the Lake Chuzenji system, central Honshu Island, Japan (160 km from the station). Mean muscle concentrations were 142·9-249·2 Bq kg⁻¹ wet mass and mean concentrations in eggs were 38·7-79·0 Bq kg⁻¹ wet mass. There was no relationship between fork length and muscle radiocaesium concentration in any of the species, but there were significant relationships between individual muscle and egg radiocaesium concentrations from O. masou, S. trutta and S. namaycush.

Primary aldosteronism associated with subclinical Cushing syndrome.

BACKGROUND: Recently, it has been reported that the incidence of primary aldosteronism (PA) among patients with hypertension is much more frequent than previously reported. AIM: In the present study, we investigated the frequency and features of PA associated with subclinical Cushing syndrome (SCS). MATERIAL AND METHODS: Subjects included consecutive patients (no.=39) who were diagnosed as PA and performed adrenal venous sampling between 2003 and 2011 in our institute. RESULTS: In 39 subjects who were diagnosed as PA, 29 patients were operated and 5 cases (12.8%) showed no suppression in low-dose dexamethasone suppression test. Four cases of them were demonstrated to be associated with SCS, and one was associated with overt Cushing syndrome (CS). Post-operatively, 3 cases received replacement therapy of hydrocortisone, while others did not. Pathological findings indicated the diagnosis of aldosterone-producing adenoma in 4 cases associated with SCS, and of idiopathic hyperaldosteronismin in one case associated with overt CS. In all 5 cases, immunohistochemical analysis demonstrated the immunoreactivities of both 3ßHSD and P450c17 in the adrenocortical tumors, the marked cortical atrophy in the zona fasciculata and reticularis, the decreased dehydroepiandrosterone sulfotransferase expression, and suppression of hypothalamo- pituitary-adrenal axis indicating the autonomous secretion of cortisol from the tumor. CONCLUSIONS: The present study suggests that PA is frequently associated with SCS with prevalence of more than 10%, justifying the routine examinations for SCS in PA cases.

Improvement of insulin resistance following transsphenoidal surgery in patients with acromegaly: correlation with serum IGF-I levels.

AIM: The aim of this study was to determine the correlation between the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis and glucose intolerance in acromegaly during the early postoperative period. SUBJECTS AND METHODS: The study included 20 patients with acromegaly caused by GH-secreting pituitary adenoma who received transsphenoidal surgery in our hospital. Glucose tolerance was evaluated with oral glucose tolerance tests (OGTTs) performed during pre- and early postoperative periods (9 [7-18] days after surgery). Homeostasis model assessment of insulin resistance (HOMA-IR) and insulinogenic index (IGI) were calculated, and correlation analyses were performed between these values and the GH-IGF-I axis. Patients were divided according to postoperative changes of the axis, and glucose tolerance was compared between the groups. RESULTS: In preoperative OGTTs, nine patients had impaired glucose tolerance and two had diabetes mellitus patterns. Postoperatively, significant reduction was observed both in fasting plasma glucose levels (p<0.01) and in HOMA-IR (p<0.01), whereas IGI showed no significant change. HOMA-IR was significantly correlated with serum IGF-I levels both before (r=0.83, p<0.01) and after (r=0.57, p<0.01) surgery, although it was not correlated with serum GH levels. Patients who achieved more than 50% postoperative reduction in serum IGF-I levels showed significant improvement in OGTTs results (p<0.05). CONCLUSIONS: In patients with acromegaly, serum IGF-I levels, but not GH levels, were significantly correlated with insulin resistance. Early postoperative improvement of glucose tolerance is observed in patients who achieved postoperative reduction in serum IGF-I levels.

Association Between Nonadherence and Transient Hyperuricemia in Pediatric Kidney Transplantation.

BACKGROUND: Nonadherence among pediatric transplant recipients is a significant problem that reduces graft survival and leads to poor kidney graft outcomes. It is, however, extremely difficult to detect during a regular follow-up. This study, therefore, aimed to investigate the risk factors involved in nonadherence, focusing on unexplained transient hyperuricemia in pediatric kidney transplant (KTx) recipients at a single pediatric center. METHODS: This retrospective study included 167 patients who underwent KTx at our pediatric center. A Cox proportional hazards analysis was performed to evaluate the risk of nonadherence using the following factors: age, sex, body mass index SD score, transient hyperuricemia, hypertension, and follow-up period. RESULTS: Nonadherence was identified in 19 patients (11%), with the average (SD) age and post-KTx duration at diagnosis being 17.21 (4.73) years and 79.21 (38.77) months, respectively. Thirty-four patients (20%) were diagnosed with transient hyperuricemia at a median of 14 months after KTx. On multivariate Cox regression analysis, transient hyperuricemia was the only independent risk factor for nonadherence after KTx. CONCLUSIONS: Transient hyperuricemia was identified as one of the risk factors for nonadherence after KTx; therefore, careful monitoring for transient hyperuricemia may allow early detection of nonadherence.

Free energy profiles for penetration of methane and water molecules into spherical sodium dodecyl sulfate micelles obtained using the thermodynamic integration method combined with molecular dynamics calculations.

The free energy profiles, ΔG(r), for penetration of methane and water molecules into sodium dodecyl sulfate (SDS) micelles have been calculated as a function of distance r from the SDS micelle to the methane and water molecules, using the thermodynamic integration method combined with molecular dynamics calculations. The calculations showed that methane is about 6-12 kJ mol(-1) more stable in the SDS micelle than in the water phase, and no ΔG(r) barrier is observed in the vicinity of the sulfate ions of the SDS micelle, implying that methane is easily drawn into the SDS micelle. Based on analysis of the contributions from hydrophobic groups, sulfate ions, sodium ions, and solvent water to ΔG(r), it is clear that methane in the SDS micelle is about 25 kJ mol(-1) more stable than it is in the water phase because of the contribution from the solvent water itself. This can be understood by the hydrophobic effect. In contrast, methane is destabilized by 5-15 kJ mol(-1) by the contribution from the hydrophobic groups of the SDS micelle because of the repulsive interactions between the methane and the crowded hydrophobic groups of the SDS. The large stabilizing effect of the solvent water is higher than the repulsion by the hydrophobic groups, driving methane to become solubilized into the SDS micelle. A good correlation was found between the distribution of cavities and the distribution of methane molecules in the micelle. The methane may move about in the SDS micelle by diffusing between cavities. In contrast, with respect to the water, ΔG(r) has a large positive value of 24-35 kJ mol(-1), so water is not stabilized in the micelle. Analysis showed that the contributions change in complex ways as a function of r and cancel each other out. Reference calculations of the mean forces on a penetrating water molecule into a dodecane droplet clearly showed the same free energy behavior. The common feature is that water is less stable in the hydrophobic core than in the water phase because of the energetic disadvantage of breaking hydrogen bonds formed in the water phase. The difference between the behaviors of the SDS micelles and the dodecane droplets is found just at the interface; this is caused by the strong surface dipole moment formed by sulfate ions and sodium ions in the SDS micelles.

Molecular dynamics study of free energy of transfer of alcohol and amine from water phase to the micelle by thermodynamic integration method.

Free energy of transfer of methylamine, octylamine, methanol, and octanol from water phase to sodium dodecyl sulfate (SDS) micelle has been calculated using thermodynamic integration method combined with molecular dynamics calculations. Together with the results for alkanes obtained in our previous study [K. Fujimoto, N. Yoshii, and S. Okazaki, J. Chem. Phys. 133, 074511 (2010)], the effect of polar group on the partition of hydrophilic solutes between water phase and the micelle has been investigated in detail at a molecular level. The calculations showed that the molecules with octyl group are more stable in the SDS micelle than in the water phase due to their hydrophobicity of long alkyl chain. In contrast, methanol and methylamine are stable in the water phase as well as in the micelle because of their high hydrophilicity. The spatial distribution of methylamine, octylamine, methanol, and octanol has also been evaluated as a function of the distance, R, from the center of mass of SDS micelle to the solutes. The distribution shows that the methylamine molecule is adsorbed on the SDS micelle surface, while the methanol molecule is delocalized among the whole system, i.e., in the water phase, on the surface of the micelle, and in the hydrophobic core of the micelle. The octylamine and octanol molecules are solubilized in the SDS micelle with palisade layer structure and are not found in the water phase.