Analysis of treatment goal alignment between Japanese psoriasis patients and their paired treating physicians.

BACKGROUND: Appropriate goal-oriented treatment strategies are important for optimal treatment outcomes and may prevent under-treatment. As treatment goals vary by patient, a study to examine treatment goals is more meaningful when patients and their physicians are paired. There has not been any study that examines alignment between paired psoriasis patients and physicians in real-world clinical practice using skin clearance as a treatment goal indicator. OBJECTIVES: To evaluate treatment goal alignment between psoriasis patients and their paired physicians, and to quantitatively identify factors associated with goal misalignment. METHODS: The study was a nationwide multicenter cross-sectional observational study. Subjects were physician-reported moderate-to-severe psoriasis patients with a history of systemic treatments, directly paired with their treating physicians. Subjects completed surveys independently. Treatment goals included seven categories, and patient-physician pairs were grouped as 'aligned' or 'misaligned' when the answers were the same or different, respectively. RESULTS: A total of 425 pairs (mean response rate, 94.7%) of responses were collected from 54 sites (64.8% general practitioners or clinics; 35.2% university or large hospitals). Treatment goal misalignment was found in 67.9% of the patient-physician pairs. The misalignment was mainly 'patient predominant' (60.9%) indicating that patients had higher goals ('complete clearance') than physicians. In the multivariate logistic regression analyses, patients' treatment expectation for 'complete clearance' [odds ratio (OR): 1.927; 95% confidential interval (CI): 1.232-3.016] and physician rating of 'level of understanding on treatment options' being low (OR: 1.552, 95% CI; 1.082-2.227) were significant factors for treatment goal misalignment. CONCLUSIONS: The majority of treatment goal misalignment was found between paired psoriasis patients and their treating physicians in Japan. The most important contributing factors to misalignment were patients' treatment expectation for 'complete clearance' and physicians' rating of their patients' 'level of understanding on treatment options' being low.

Correlation between dietary glycemic index and cardiovascular disease risk factors among Japanese women.

OBJECTIVE: To examine the correlation between dietary glycemic index (GI) and cardiovascular disease (CVD) risk factors among subjects who consume white rice as a staple food. DESIGN: A cross-sectional study was conducted to explore the associations between dietary GI, dietary glycemic load (GL) and dietary intakes, and CVD risk factors. Dietary GI and GL were calculated from a 3-day (including two consecutive weekdays and one holiday) dietary records. SETTING: A weight-reduction program at a municipal health center in Tokyo, Japan. SUBJECTS: A total of 32 women aged 52.5+/-7.2 y participated in the weight-reduction program. RESULT: The GI food list made for the current study calculated for 91% of carbohydrate intakes measured. The mean dietary GI was 64+/-6, and the mean dietary GL was 150+/-37. Individuals in the highest tertile of GI consumed more carbohydrate, mostly from white rice (P<0.001), and less fat (P<0.01). Individuals in all three groups by tertile of GL showed similar tendencies. In the lowest GI tertile, the highest concentration of HDL-cholesterol and lowest concentration of triacylglycerol and immunoreactive insulin were observed (P<0.01). In the lowest GL tertile, the highest concentration of HDL-cholesterol and the lowest concentration of triacylglycerol were observed (P<0.05). CONCLUSION: Calculated dietary GI and GL were positively associated with CVD risk factors among the Japanese women who consumed white rice as a staple food.

Glycemic index of single and mixed meal foods among common Japanese foods with white rice as a reference food.

OBJECTIVE: The objectives were to examine the feasibility of using white rice as a reference food in the study of glycemic index (GI) and to examine the GI values of both single and mixed meal foods among rice species, processed rice products, beans, and dairy products. DESIGN: Subjects were served with 50 g carbohydrate content of white rice at least two times (maximum three times) and test food once after separate overnight fasts. Capillary blood glucose measurements were carried out before and during 120 min after each food load. SETTING: The study was carried out in an outpatient setting. SUBJECTS: A total of 58 (38 females and 20 males) nondiseased subjects, mean aged 37 y and mean BMI 22 kg/m(2) were included. RESULT: The correlation between incremental area under curve of white rice and glucose was r=0.853 (n=10, P <0.0001) and white rice was considered suitable to be used as a reference food. Among mixed meal foods, the combination of carbohydrate foods with vinegar, dairy products, and bean products significantly decreased the GI value of white rice of 20-40%. The reduction of GI occurred whether the foods were taken together, before or after rice intake. GI of noodles such as udon, soba, and spaghetti showed low GI values. CONCLUSION: White rice could be used as a reference food in determining GI values of foods. A total of 32 single and mixed meal Japanese common food products were examined for their GI values.

Photosynthetic oxygen evolution at low water potential in leaf discs lacking an epidermis.

Land plants encountering low water potentials (low psiw) close their stomata, restricting CO2 entry and potentially photosynthesis. To determine the impact of stomatal closure, photosynthetic O2 evolution was investigated in leaf discs from sunflower (Helianthus annuus L.) plants after removing the lower epidermis at low psiw. Wounding was minimal as evidenced by O2 evolution nearly as rapid as that in intact discs. O2 evolution was maximal in 1% CO2 in the peeled discs and was markedly inhibited when psiw was below -1.1 MPa. CO2 entered readily at all psiw, as demonstrated by varying the CO2 concentration. Results were the same whether the epidermis was removed before or after low psiw was imposed. Due to the lack of an epidermis and ready movement or CO2 through the mesophyll, the loss in O2 evolving activity was attributed entirely to photosynthetic metabolism. Intact leaf discs showed a similar loss in activity when measured at a CO2 concentration of 5%, which supported maximum O2 evolution at low psiw. In 1% CO2, however, O2 evolution at low psiw was below the maximum, presumably because stomatal closure restricted CO2 uptake. The inhibition was larger than in peeled discs at psiw between -1 and -1.5 MPa but became the same as in peeled discs at lower psiw. Therefore. as photosynthesis began to be inhibited by metabolism at low psiw, stomatal closure added to the inhibition. As psiw became more negative, the inhibition became entirely metabolic.

Neonatal exposure to novel environment enhances hippocampal-dependent memory function during infancy and adulthood.

Early life experience affects behavior and brain mechanisms. Handling rats during the first three weeks in life can slow age-related cognitive decline (as measured by a hippocampal-dependent spatial learning task) and reduce age-related hippocampal neuron loss. It is not clear, however, whether this early environmental influence on learning is selective for old age or is more general, affecting cognitive development during infancy and young adulthood as well. We briefly exposed neonatal rats to a novel non-home environment for 3 min daily during the first three weeks of life (as a component of the handling method). We found that this brief early environmental manipulation resulted in enhanced hippocampal-dependent learning immediately after weaning and that this learning enhancement persisted into adulthood. These results suggest that subtle early life events can affect cognitive development in all developmental stages and that changes in neural mechanisms other than neuron number are likely to mediate the learning enhancement at multiple developmental stages.

Neonatal exposure to a novel environment enhances the effects of corticosterone on neuronal excitability and plasticity in adult hippocampus.

Electrophysiological studies have shown that activation of glucocorticoids receptors (GRs) influences neuronal excitability and activity dependent synaptic plasticity. In developmental studies, early life stimulation such as neonatal handling results in an up-regulation of glucocorticoid-receptor (GR) binding in the hippocampus that persists into adulthood. It is, therefore, hypothesized that early environment-induced changes in receptor sensitivity to corticosterone (CORT) might have functional effects on adult neuronal excitability and synaptic plasticity. To test this hypothesis, we exposed rats daily from post-natal days 1-21 to a non-home environment for 3 min. When the animals became adults, we studied the effects of glucocorticoid hormone corticosterone (CORT) on population spike (PS) amplitude and long-term potentiation of population spikes (PS-LTP) in vitro in the hippocampal CA1 region following activation of the Schaffer collateral fibers. Bath application of CORT reduced PS amplitude and subsequent induction of PS-LTP. This inhibitory effect of CORT was significantly greater in the slices from the novelty exposed rats (Novel) than the control rats that remained in their home cage (Home). Inhibition of population spike amplitude during CORT perfusion was 28.0+/-5.3% of baseline in Novel slices, and 9.1+/-4.4% in Home slices. CORT pre-exposure (20 min) also inhibited the subsequent induction of PS-LTP in Novel slices by 57.7+/-17.7% and by 7.5+/-12.1% in Home slices. These results provide electrophysiological evidence that neonatal novelty exposure results in functional increases in receptor sensitivity to CORT that enhances the inhibitory effects of CORT on field CA1 neuronal excitability and plasticity.

Effects of cholinergic modulation on responses of neocortical neurons to fluctuating input.

Neocortical neurons in vivo are spontaneously active and intracellular recordings have revealed strongly fluctuating membrane potentials arising from the irregular arrival of excitatory and inhibitory synaptic potentials. In addition to these rapid fluctuations, more slowly varying influences from diffuse activation of neuromodulatory systems alter the excitability of cortical neurons by modulating a variety of potassium conductances. In particular, acetylcholine, which effects learning and memory, reduces the slow alterhyperpolarization, which contributes to spike frequency adaptation. We used whole-cell patch-clamp recordings of pyramidal neurons in neocortical slices and computational simulations to show, first, that when fluctuating inputs were added to a constant current pulse, spike frequency adaptation was reduced as the amplitude of the fluctuations was increased. High-frequency, high-amplitude fluctuating inputs that resembled in vivo conditions exhibited only weak spike frequency adaptation. Second, bath application of carbachol, a cholinergic agonist, significantly increased the firing rate in response to a fluctuating input but minimally displaced the spike times by < 3 ms, comparable to the spike jitter observed when a visual stimulus is repeated under in vivo conditions. These results suggest that cholinergic modulation may preserve information encoded in precise spike timing, but not in interspike intervals, and that cholinergic mechanisms other than those involving adaptation may contribute significantly to cholinergic modulation of learning and memory.

Expression of dipeptidyl aminopeptidase IV activity in thyroid tumours: a possible marker of thyroid malignancy.

The role of dipeptidyl aminopeptidase IV (DAP IV) activity staining in the investigation of a thyroid mass was explored. The study consisted of two parts: the first part involved DAP IV staining performed on various thyroid lesions sampled from operative specimens. These included frozen tissues or cytologic smears. The second part of the study, which is ongoing, prospectively examines the DAP IV activity in fine-needle aspiration (FNA) specimens from patients with a thyroid mass. Results from part 1 of the study indicated that DAP IV activity staining was a useful adjunct in distinguishing differentiated carcinoma from benign lesions, particularly the "follicular lesions." Preliminary findings of the second part of the study suggest that DAP IV staining can be applied to FNA specimens. The measure of DAP IV activity and its influence on the diagnostic accuracy of FNA remain to be seen.

Effect of long term baclofen treatment on recognition memory and novelty detection.

We studied the effect of long term baclofen treatment on recognition memory and novelty detection in rats using a habituation paradigm in an open field setting. Rats pretreated with 3 weeks' daily baclofen injection (0, 2 and 5 mg/kg) were tested in four 10 min sessions (familiarization session and three testing sessions: S1, S2 and S3) with 10-min intersession intervals. During S1, S2 and S3, rats were repeatedly exposed to the same two odor stimuli. During S3, for half of the rats in each treatment group, the spatial locations of the two stimuli were switched (Change) and for the other half the stimuli were replaced in the same locations (No Change). Two habituation scores were measured for each subject: H1 = N1 - N2; H2 = N2 - N3 (Ni the number of contacts made during Si). Baclofen at the highest dose (5 mg/kg) reduced the amount of habituation between S1 and S2 (H1) and increased responses to novel spatial arrangement, measured as the difference between H2 for the No-Change and Change groups. These results suggest a simultaneous impairment of recognition memory and enhancement of spatial novelty detection.

Selective suppression of intrinsic but not afferent fiber synaptic transmission by baclofen in the piriform (olfactory) cortex.

The GABAB agonist baclofen has been shown to suppress synaptic transmission in subregions of the hippocampus and in the piriform (olfactory) cortex. Here we report a laminar selectivity of suppression of synaptic potentials in the olfactory cortex. In brain slice preparations, baclofen suppresses extracellularly recorded field potentials at the intrinsic fiber synapses proximal to the superficial pyramidal cell bodies (layer Ib) while leaving the afferent fiber synaptic potentials recorded at the distal dendrites (layer Ia) little affected. This dose-dependent selective suppression of intrinsic fiber synaptic transmission is also correlated with an increase of paired-pulse facilitation. These results suggest that afferent and intrinsic synaptic inputs may be differentially modulated by the activation of GABAB receptors and that this selective suppression is at least partially mediated via a presynaptic mechanism.

The association of human papillomavirus with Schneiderian papillomas: a DNA in situ hybridization study.

Human papillomavirus has been identified with DNA hybridization techniques in Schneiderian papillomas, though results reported in the literature have been conflicting. This study investigated 33 cases of Schneiderian papilloma (26 inverted papillomas, seven fungiform papillomas). In situ hybridization using a cocktail of human papillomavirus (HPV) probes 6/11, 16/18, 31/33/35 failed to identify HPV genome in any of the inverted papillomas. This is contrasted by the detection of HPV 6/11 in six of seven fungiform papillomas. Of the 26 cases of inverted papilloma, 10 had recurrences, five were associated with dysplasia, and two were associated with squamous cell carcinoma. Of the seven cases of fungiform papillomas, two had recurrences, and two were associated with dysplasia, but not malignancy was found. This study supports the concept that fungiform papilloma and inverted papilloma are two distinct lesions: the former is associated with HPV 6/11.

Consistency in nervous systems: trial-to-trial and animal-to-animal variations in the responses to repeated applications of a sensory stimulus in Aplysia.

What is the internal noise in a nervous system? We studied this question by determining the trial-to-trial consistency of the neuronal response in the abdominal ganglion of Aplysia californica. Because our voltage-sensitive dye recordings detected the spike activity from a large fraction of the neurons in the ganglion, these results provide a reasonably complete characterization of the consistency of the response to a sensory stimulus. The consistency of each neuron was evaluated by the number and timing of spikes in the response. The variability in the spike count was described using the coefficient of variation. The spike count variations follow a Poisson distribution, indicating that most of these variations were the result of a random process. For each neuron the reliability of the response to touch was measured in two ways; both measures indicated a broad distribution of reliabilities within the neuron population. The time of the maximum response also varied substantially in some animals. These timing variations were in part due to random processes and in part due to systematic effects (changes in activity of many neurons that were highly correlated). The time course of the activity of individual neurons was compared with the time course of the gill withdrawal. In some animals the activity of individual neurons was only poorly correlated with the behavior; in contrast, the summed activity of groups of neurons matched the behavior quite well. This implies that the behavioral output of the system may be a distributed combination of the activity of many neurons. The differences between animals were substantially larger than the trial-to-trial differences in one animal. The responses made by different preparations differed along many dimensions.

Nonuniform expression of habituation in the activity of distinct classes of neurons in the Aplysia abdominal ganglion.

Global observations of neuronal response in the Aplysia abdominal ganglion were made during habituation of the gill withdrawal reflex using voltage-sensitive dye recording. This technique makes it possible to measure the spike activity of 30-50% of the 1000 neurons present in the ganglion. Our experiments address the issue of how habituation is expressed in the activity of the population of neurons responding to siphon stimulation. Several classes of neurons exhibited characteristically distinct responses to the stimuli and to habituation training. One class of neurons (group I) responded to the onset and offset of the sensory stimulus although they are probably not primary sensory neurons. They habituate only partially when the behavioral reflex has already habituated completely. Two other classes (groups II and III) both have sustained responses to the touch, but habituate differently. Members of group III habituate completely while those in group II habituate only partially. Another class of neurons are inhibited by the stimulus (group IV). They become less inhibited after habituation. The response of both group I and group IV are new classes of response that have not been previously reported.