Cytological features of solid variants of papillary thyroid carcinoma: a fine needle aspiration cytology study of 18 cases.

OBJECTIVE: Solid variants of papillary thyroid carcinoma (SV-PTC) are rare, and there have been few reports describing the cytological findings of such variants. METHODS: The cytological features of cellular specimens aspirated from 18 histologically confirmed SV-PTC cases were evaluated, retrospectively. RESULTS: Solid and small papillary clusters were observed in 14 (77.8%) and 13 (72.2%) cases, respectively. The incidences of large papillary clusters (11.1%) and sheet-like arrangements (11.1%) were low. Nuclear features were consistent with conventional PTC. The background was clean, and there were no colloid materials, foamy histiocytes, multinucleated giant cells, psammoma bodies, or necrotic materials. CONCLUSIONS: Solid clusters and small papillary clusters in conjunction with a clean background are diagnostic clues that indicate SV-PTC cytologically. It is thought that small papillary clusters reflect the micropapillary growth pattern seen within the lumen of middle-sized follicular structures. The presence of nuclear findings typical of conventional PTC and the absence of mitotic figures and necrotic materials are important for distinguishing SV-PTC from poorly differentiated carcinoma.

Thyroid FNA cytology in Asian practice-Active surveillance for indeterminate thyroid nodules reduces overtreatment of thyroid carcinomas.

Although Asian thyroid practices have implemented the American Thyroid Association guidelines, significant deviations in actual risk of malignancy (ROM) have been reported. With review of the literature from Asia, the authors examine the underlining reasons for actual ROMs reported in Asia being so different from western practice based on the author's perspective. Although the most popular diagnostic system for thyroid cytology used in Asian countries is the Bethesda system, the Japan Thyroid Association published clinical guidelines, including a national reporting system for thyroid cytology, to adapt conservative clinical management (active surveillance and strict triage patients for surgery) for low-risk thyroid carcinomas. As less aggressive clinical management is favoured in Asian societies, strict triage of patients with indeterminate thyroid nodules for surgery is usually applied, which ultimately reduces overtreatment of indolent thyroid tumours. As a result, low resection rates and high ROMs for indeterminate nodules were achieved in Asian practices using the same Bethesda system. Recently, borderline thyroid tumours were introduced in the thyroid tumour classification and significant decreases in ROMs have been reported in the indeterminate categories in western practice. However, ROM of indeterminate nodules remained high in Asian practice even after borderline tumours were deemed benign. These results suggested that the diagnostic threshold of papillary thyroid carcinoma-type nuclear features varied among practices (stricter in Asia than in western practice), and diagnostic surgery was not performed for a significant number of indeterminate nodules with benign clinical features in Asian practice, resulting in low rates of borderline tumours in surgically-treated patients.

Dementia with Lewy bodies can be well-differentiated from Alzheimer's disease by measurement of brain acetylcholinesterase activity-a [11C]MP4A PET study.

OBJECTIVE: To investigate the diagnostic performance of brain acetylcholinesterase (AChE) activity measurement using N-[(11) C]-methyl-4-piperidyl acetate (MP4A) and PET in patients with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). METHODS: Participants were 14 DLB patients, 25 AD patients and 18 age-matched healthy controls (HC). All subjects underwent PET scans and MP4A to measure regional brain AChE activity. We performed anatomical standardization of each brain image, and k3 values, an index of AChE activity, in each voxel were estimated by nonlinear least squares analysis. Volumes of interest (VOIs) were identified on parametric k3 images in frontal, temporal, parietal and occipital cortices, and in anterior and posterior cingulate gyri (ACG and PCG). In each VOI, the differential diagnostic performance between AD and DLB of k3 values was assessed by area under the curve (AUC) of the receiver-operating characteristic. Voxel-based statistical analyses were also performed. RESULTS: Mean cortical AChE activities in AD patients (-8.2% compared with normal mean) and DLB patients (-27.8%) were lower than HCs (p < 0.05, p < 0.001, respectively). There was a significant difference in mean cortical AChE activities between AD and DLB patients (p < 0.001). All regional brain AChE activities of defined VOIs except ACG were able to well discriminate DLB from AD, and notably performance was the most significant in PCG (AUC = 0.989, 95% CI: 0.965-1.000). CONCLUSIONS: Brain cholinergic deficit is consistently prominent in DLB compared with AD. PET measurement of brain AChE activity may be useful for the differential diagnosis between DLB and AD.

Diffuse sclerosing variant of papillary thyroid carcinoma: a study of fine needle aspiration cytology in 20 patients.

BACKGROUND: A diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is a rare variant and reports describing the cytological findings are few. PATIENTS AND METHODS: We studied 24 cytological samples from thyroid fine needle aspirates of 20 patients with DSV-PTC. The specimens were taken from 14 non-nodular lesions and 10 nodules. RESULTS: All aspirates taken from both non-nodular lesions and nodules had sufficient cellularity. The carcinoma cells frequently (70-100%) appeared as solid cell balls and hollow balls, and showed a hobnail pattern, squamous differentiation, septate cytoplasmic vacuoles and large unilocular vacuoles. Most of the carcinoma cells seem to be taken from the lumen of dilated lymph vessels. Ground glass nuclear chromatin, intranuclear cytoplasmic inclusions and grooved nuclei were infrequent (50% or less). In the background, a large number of lymphocytes and abundant psammoma bodies were almost always seen. CONCLUSIONS: Cytological findings of DSV-PTC are as follows: (1) solid cell balls and/or hollow balls containing lymphocytes; (2) hobnail cells; (3) septate cytoplasmic vacuoles; (4) large unilocular vacuoles; (5) squamous differentiation; (6) abundant psammoma bodies; (7) lymphocytic background; and (8) the absence or relative lack of characteristic nuclear features of papillary carcinoma. When DSV-PTC is suspected by ultrasound examination, the aspiration cytology from a non-nodular area of the thyroid can led us to the diagnosis of the variant.

ACTN3 R577X genotype is associated with sprinting in elite Japanese athletes.

The ACTN3 R577X genotype has been found to associate with sprint/power phenotypes in all elite athlete cohorts investigated. This association has not been extensively studied in elite Asian athletes. The present study was undertaken to investigate the association between the ACTN3 R577X genotype and elite Japanese track and field athlete status. 299 elite Japanese track and field athletes (134 sprint/power athletes; 165 endurance/middle-power athletes) and 649 Japanese controls were genotyped for the ACTN3 R577X polymorphism. All athletes were of national or international level. Sprint/power athletes showed a higher frequency of RR + RX genotype than controls (111/134 [82.8%] vs. 478/649 [73.7%], P = 0.025 under the R-dominant model), while there was no significant difference between endurance/middle-power athletes and controls (126/165 [76.4%] vs. 478/649 [73.7%], P = 0.48 under the R-dominant model). Sprinters with the RR + RX genotype had significantly faster personal best times for the 100 m than those with XX genotype (10.42 ± 0.05 s vs. 10.64 ± 0.09 s, P = 0.042); no such association was found in the 400 m sprinters (47.02 ± 0.36 s vs. 47.56 ± 0.99 s, P = 0.62). ACTN3 R577X genotype is associated with sprint/power performance in elite Japanese track and field athletes, especially short sprint performance.

Effectiveness of female community health volunteers in the detection and management of low-birth-weight in Nepal.

INTRODCTION: Low birth weight (LBW) is a major risk factor for neonatal death. However, most neonates in low-income countries are not weighed at birth. This results in many LBW infants being overlooked. Female community health volunteers (FCHVs) in Nepal are non-health professionals who are living in local communities and have already worked in a field of reproductive and child health under the government of Nepal for more than 20 years. The effectiveness of involving FCHVs to detect LBW infants and to initiate prompt action for their care was studied in rural areas of Nepal. METHODS: FCHVs were tasked with weighing all neonates born in selected areas using color-coded spring scales. Supervisors repeated each weighing using electronic scales as the gold standard comparator. Data on the relative birth sizes of the infants, as assessed by their mothers, were also collected and compared with the measured weights. Each of the 205 FCHVs involved in the study was asked about the steps that she would take when she came across a LBW infant, and knowledge of zeroing a spring scale was also assessed through individual interviews. The effect of the background social characteristics of the FCHVs on their performance was examined by logistic regression. This study was nested within a community-based neonatal sepsis-management intervention surveillance system, which facilitated an assessment of the performance of the FCHVs in weighing neonates, coverage of FCHVs' visits, and weighing of babies through maternal interviews. RESULTS: A total of 462 babies were weighed, using both spring scales and electronic scales, within 72 hours of birth. The prevalence of LBW, as assessed by the gold standard method, was 28%. The sensitivity of detection of LBW by FCHVs was 89%, whereas the sensitivity of the mothers' perception of size at birth was only 40%. Of the 205 FCHVs participating in the study, 70% of FCHVs understood what they should do when they identified LBW and very low birth weight (VLBW) infants. Ninety-six per cent could describe how to zero a scale and approximately 50% could do it correctly. Seventy-seven per cent of FCHVs weighed infants at least once during the study period, and 19 of them (12%) miscategorized infant weights. Differences were not detected between the background social characteristics of FCHVs who miscategorized infants and those who did not. On the basis of maternal reporting, 67% of FCHVs who visited infants had weighed them. CONCLUSIONS: FCHVs are able to correctly identify LBW and VLBW infants using spring scales and describe the correct steps to take after identification of these infants. Use of FCHVs as newborn care providers allows for utilization of their logistical, geographical, and cultural strengths, particularly a high level of access to neonates, that can complement the Nepalese healthcare system. Providing additional training to and increasing supervision of local FCHVs regarding birth weight measurement will increase the identification of high-risk neonates in resource-limited settings.

Polymorphisms in the control region of mitochondrial DNA associated with elite Japanese athlete status.

The control region of mitochondrial DNA (mtDNA) contains the main regulatory elements for mtDNA replication and transcription. Certain polymorphisms in this region would, therefore, contribute to elite athletic performance, because mitochondrial function is one of determinants of physical performance. The present study was undertaken to examine the effect of polymorphisms in this region on elite athlete status by sequencing the mtDNA control region. Subjects comprised 185 elite Japanese athletes who had represented Japan at international competitions (i.e., 100 endurance/middle-power athletes: EMA; 85 sprint/power athletes: SPA), and 672 Japanese controls (CON). The mtDNA control region was analyzed by direct sequencing. Frequency differences of polymorphisms (minor allele frequency ≥ 0.05) in the mtDNA control region between EMA, SPA, and CON were examined. EMA displayed excess of three polymorphisms [m.152T>C, m.514(CA)n repeat (n ≥ 5), and poly-C stretch at m.568-573 (C ≥ 7)] compared with CON. On the other hand, SPA showed greater frequency of the m.204T>C polymorphism compared with CON. In addition, none of the SPA had m.16278C>T polymorphism, whereas the frequencies of this polymorphism in CON and EMA were 8.3% and 10.0%, respectively. These findings imply that several polymorphisms detected in the control region of mtDNA may influence physical performance probably in a functional manner.

Effect of chronic kidney disease on excessive daytime sleepiness in Parkinson disease.

BACKGROUND AND PURPOSES: Excessive daytime sleepiness (EDS) is a common sleep disorder in patients with Parkinson disease (PD). Non-ergot dopamine agonists increase the risk of unanticipated sleep episodes. OBJECTIVE: We aimed to assess the influence of renal function on EDS in patients with PD. METHODS: Sixty-two patients treated with ropinirole or pramipexole were recruited for this study. We evaluated the historical and clinical characteristics including the motor symptom rating scales, Epworth Sleepiness Scale (ESS), and estimated glomerular filtration rate (eGFR). An ESS score of 10 or greater was defined as EDS. Participants with eGFR < 60 ml/min/1.73 m(2) were determined to have chronic kidney disease (CKD). Multiple logistic regression analysis was performed to determine the predictive factors of EDS. RESULTS: Chronic kidney disease was found to be a significant predictive factor for EDS in all patients (P = 0.014). We observed a negative correlation between the severity of daytime sleepiness and renal function in patients treated with pramipexole alone (r(s) = -0.637, P < 0.001). CONCLUSIONS: Chronic kidney disease may be a risk factor for EDS, especially in patients treated with pramipexole, which is directly excreted in the urine.

Treatment with cyclosporine A improves SLE disease activity of Japanese patients with diffuse proliferative lupus nephritis.

AIMS: Cyclosporine A (CyA), a representative calcineurin inhibitor, may be useful for the treatment of lupus nephritis. In contrast to knowledge about its strong effects against proteinuria, however, there is little information about the beneficial effects of CyA against clinical disease activity of diffuse proliferative lupus nephritis. METHODS: To elucidate this issue, we investigated the effects of low-dose CyA treatment (< 2.5 mg/kg/d) in 11 Japanese adult patients (1 male, 10 female) with uncontrolled diffuse proliferative lupus nephritis with severe clinical SLE disease activity. RESULTS: In addition to amelioration of the proteinuric state, the clinical SLE disease activities, estimated by serological markers and the SLE disease activity index (SLEDAI), were significantly improved in all patients within 1 month. The required amounts of corticosteroid were decreased in these patients. These favorable effects continued for 2 y without serious adverse effects. Kidney function was not changed in the patients with satisfactory kidney function prior to CyA therapy (serum creatinine < 1.1 mg/dl, and eGFR > 45 ml/ min/1.73 m2). CONCLUSION: The current study results suggest that low-dose CyA treatment could ameliorate the severe clinical SLE disease activity as well as improve proteinuria in Japanese patients with diffuse proliferative lupus nephritis. This treatment would be safe and useful for SLE patients with satisfactory kidney function.

Clinical outcomes of orthogonal plating to treat radial and ulnar fractures in toy-breed dogs.

OBJECTIVES: To describe the results of orthogonal plating (OP) as a treatment for fractures of the radius and ulna in toy-breed dogs. MATERIALS AND METHODS: The medical records (June 2011 to April 2019) of toy-breeds in which the OP technique using non-locking cuttable plates was employed to treat radial and ulnar fractures were reviewed. The inclusion criteria included a bodyweight of 3.5 kg or less, fracture of the diaphysis of the radius and ulna of one or both forelimbs, and the availability of follow-up radiographs. Revision surgeries were also included. RESULTS: Fifteen limbs that underwent initial fracture repair and five that underwent revision surgery met the inclusion criteria. The radial and ulnar fractures healed in 19 limbs at the final follow-up. Synostosis of the radius and ulna at the fracture sites was observed in one limb. Re-fracture after cranial plate removal was observed in one case. All dogs exhibited successful return of normal limb function at the final clinical and radiographic follow-up (mean, 104.7 ± 67.1 days; median, 79.5 days; range: 35 to 248 days). Long-term follow-up data obtained via telephone interviews to owners or referring veterinarians were available for 15 cases and confirmed maintenance of normal limb function in all dogs (mean, 32.5 ± 17.6 months; median, 26 months; range: 11 to 69 months). CLINICAL SIGNIFICANCE: OP allowed the successful open reduction of radial and ulnar fractures, facilitating bone union in both the radius and ulna and a return to normal limb function in a series of toy-breed dogs.

A convenient and sensitive allergy test: IgE crosslinking-induced luciferase expression in cultured mast cells.

BACKGROUND: For the detection of allergen-specific IgE in sera, solid-phase IgE-binding assays like the CAP test are commonly used. Although such immunochemical methods are very sensitive, they frequently produce false positives. Degranulation of the human IgE receptor (FcεRI)-transfected rat mast cell (RBL) lines seems to be a possible indicator for human IgE, but spontaneous mediator release from these cells in the presence of human sera is not negligible. METHODS: The nuclear factor of activated T-cells (NFAT)-responsive luciferase reporter gene was stably transfected into human FcεRI-expressing RBL-SX38 cells. One established clone (RS-ATL8) was sensitized with 1 : 100 dilution of sera from patients with egg white allergy and then stimulated with purified or a crude extract of egg white allergen. RESULTS: Sensitization with 15 pg/ml IgE was sufficient to detect IgE crosslinking-induced luciferase expression (EXiLE) by anti-IgE stimulation. Allergen-specific EXiLE was elicited by as little as 1 fg/ml of egg white protein without cytotoxicity. There was a good correlation between results with EXiLE and oral food challenge tests on patients with egg allergy (P = 0.001687, Fisher's exact test). The measured values of EXiLE and the CAP test also correlated well (R = 0.9127, Spearman's test). CONCLUSION: The EXiLE test using RS-ATL8 cells is a promising in vitro IgE test to evaluate the biological activity of the binding between IgE and allergens.

Association between altered systemic inflammatory interleukin-1beta and natural killer cell activity and subsequently agitation in patients with Alzheimer disease.

OBJECTIVE: Alzheimer's disease (AD) is a neurodegenerative disorder that is the most common cause of dementia in the elderly and is frequently accompanied by emotional disorder, including agitation. Although evidence of neuroendocrine immune and inflammatory functions during emotional changes has been accumulated, the pathogenic mechanisms in the development of agitation accompanied by AD remain to be elucidated. METHODS: To clarify the involvement of neuroendocrine and immune and inflammatory systems in agitation in AD, we examined agitation levels, circadian rhythms of behavior, cortisol, interleukin-1beta (IL-1beta), and natural killer cell activity (NKCA) in controls without dementia and 16 AD patients who were recognized to be easily agitated in their nursing homes. These behavioral and blood indicators were assessed according to the progress of the stage of agitation in 16 AD patients (stable, pre-agitation, and agitation stages). RESULTS: Elevations in night behavior and blood cortisol, IL-1beta and an reduced blood NKCA level in the evening were observed not only in the agitation stage, but also when stable in AD patients as compared to the control. Increased IL-1beta and decreased NKCA occurred in both the morning and evening in pre-agitation and agitation stages in AD. CONCLUSIONS: The increased IL-1beta and decreased NKCA with the progress of agitation in AD suggest that inflammation produces agitation and aggravates AD.

A cross-sectional study of sarcopenia in Japanese men and women: reference values and association with cardiovascular risk factors.

In this study of Japanese men and women, we determine reference values for sarcopenia and test the hypothesis that sarcopenia is associated with risk factors for cardiovascular disease, independent of waist circumference. A total of 1,488 Japanese men and women aged 18-85 years participated in this study. Appendicular muscle mass (AMM) was measured by dual-energy X-ray absorptiometry. Reference values for classes 1 and 2 sarcopenia (skeletal muscle index: AMM/height2, kg m-2) in each sex were defined as values one and two standard deviations below the sex-specific means of reference values obtained in this study from young adults aged 18-40 years. The reference values for class 1 and class 2 sarcopenia were 7.77 and 6.87 kg m-2 in men and 6.12 and 5.46 kg m-2 in women. In subjects both with class 1 and class 2 sarcopenia, body mass index and % body fat were significantly lower than in normal subjects. Despite whole-blood glycohaemoglobin A1c in men with class 1 sarcopenia was significantly higher than in normal subjects, and brachial-ankle pulse wave velocity in women both with class 1 and class 2 sarcopenia were significantly higher than in normal subjects, using one-way ANCOVA with adjustment for the covariate of waist circumference. Although sarcopenia is associated with thin body mass, it is associated with more glycation of serum proteins in men and with greater arterial stiffness in women, independent of waist circumference.

Functional participation of the IL-2 receptor gamma chain in IL-7 receptor complexes.

The gamma chain of the interleukin-2 (IL-2) receptor is shared with the functional IL-4 receptor and is causatively related to X-linked severe combined immunodeficiency (XSCID), which is ascribed to a profound T cell defect. Studies with monoclonal antibodies specific for the IL-2 receptor gamma chain showed that the gamma chain participates in the functional high-affinity receptor complexes for IL-7 that are involved in the differentiation of T and B cells. Participation of the gamma subunit in more than one receptor may enable the elucidation of the mechanisms of XSCID development and lymphocyte differentiation.

Heteromeric NMDA receptors: molecular and functional distinction of subtypes.

The N-methyl D-aspartate (NMDA) receptor subtype of glutamate-gated ion channels possesses high calcium permeability and unique voltage-dependent sensitivity to magnesium and is modulated by glycine. Molecular cloning identified three complementary DNA species of rat brain, encoding NMDA receptor subunits NMDAR2A (NR2A), NR2B, and NR2C, which are 55 to 70% identical in sequence. These are structurally related, with less than 20% sequence identity, to other excitatory amino acid receptor subunits, including the NMDA receptor subunit NMDAR1 (NR1). Upon expression in cultured cells, the new subunits yielded prominent, typical glutamate- and NMDA-activated currents only when they were in heteromeric configurations with NR1. NR1-NR2A and NR1-NR2C channels differed in gating behavior and magnesium sensitivity. Such heteromeric NMDA receptor subtypes may exist in neurons, since NR1 messenger RNA is synthesized throughout the mature rat brain, while NR2 messenger RNA show a differential distribution.

Control of kinetic properties of AMPA receptor channels by nuclear RNA editing.

AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor channels mediate the fast component of excitatory postsynaptic currents in the central nervous system. Site-selective nuclear RNA editing controls the calcium permeability of these channels, and RNA editing at a second site is shown here to affect the kinetic aspects of these channels in rat brain. In three of the four AMPA receptor subunits (GluR-B, -C, and -D), intronic elements determine a codon switch (AGA, arginine, to GGA, glycine) in the primary transcripts in a position termed the R/G site, which immediately precedes the alternatively spliced modules "flip" and "flop." The extent of editing at this site progresses with brain development in a manner specific for subunit and splice form, and edited channels possess faster recovery rates from desensitization.

Pigmentary demarcation lines associated with pregnancy.

We report three cases of pigmentary demarcation lines associated with pregnancy. In addition, we reviewed 19 cases including our 3 cases, which were reported in Japan. Most cases occurred during the latter period of pregnancy (after the seventh month), and the pigmentation faded spontaneously or disappeared a few months after delivery in all cases except one. Pigmentary demarcation lines are classified into five groups (types A-E). Of the 19 cases we reviewed, 2 cases showed lines of both types A and B, whereas all the other cases showed type B lines. Although there have only been 29 cases of pigmentary demarcation lines associated with pregnancy reported to date, before ours, we experienced 3 cases within 3 months, therefore it is possible that many such cases are overlooked. Pigmentary demarcation lines are mainly a cosmetic problem. Two of our three cases presented to obstetricians initially. We suggest that dermatologists should be aware that pigmentary demarcation lines may be associated with pregnancy.

Stroke power consistency and 2000 m rowing performance in varsity rowers.

We studied the relationship between stroke power consistency and 2000 m rowing time besides determining maximal oxygen uptake (VO(2max)) and leg extension power. The subjects (n=16, male varsity rowers) carried out an incremental test to volitional exhaustion on a rowing ergometer, and the VO(2) at each stage was determined. The stroke power consistency was assessed by the coefficient of variation of power (CVP(high)) at the highest workload at which each subject could maintain power. Besides the incremental test, 2000 m all-out rowing was performed on the ergometer and leg extension power was measured. Stepwise multiple regression analysis indicated that the 2000 m rowing time could be predicted by VO(2max), leg extension power and CVP(high) in order of strength of standardized partial correlation coefficients as explanatory variables. The CVP(high) correlated with the residual of the regression between 2000 m rowing time and VO(2max). The findings suggest that the stroke power consistency contributes to maintenance of the power during ergometer rowing.

Computational schemes for the ground-state pair density.

We reconfirm the performance of the initial scheme for calculating the ground-state pair density (Higuchi and Higuchi 2007 Physica B 387 117, 2008 Phys. Rev. B 78 125101) by using the alternative approximation of the correlating kinetic energy functional. It is shown that about 20% of the correlation energy can be reproduced by the initial scheme, irrespective of the approximate form of the correlating kinetic energy functional. On the basis of the initial scheme, various kinds of schemes that go beyond the initial one can be developed. We illustrate two kinds of computational schemes.