Serum dopamine beta-hydroxylase activity in menstrual migraine.
Migraine has been considered a manifestation of sympathetic dysfunction. Serum dopamine beta-hydroxylase (D beta H) has been shown to be an index of peripheral sympathetic activity by some workers and there are two reports of elevated activity of the enzyme during the migraine headache as well as in the headache-free interval. We studied the enzyme in seven women complaining of regular attacks of menstrual migraine and eleven controls during the mid-follicular (days 10 +/- 2) and premenstrual (days 28 +/- 2) phases of the menstrual cycle. Although levels were on average 26% and 10% higher respectively than in control subjects, the difference failed to reach statistical significance because of the large normal range for enzyme activity. However, the premenstrual results were significantly lower (p less than 0.001) than the mid-follicular measurements in the migraine group, little difference being found in controls. This finding, and the effects of successful therapy with anovulatory doses of oestradiol implants in not only significantly lowering serum D beta H but also significantly reducing the difference in enzymic activity between the early and late phases of the menstrual cycle, suggest that if this enzyme is an index of sympathetic activity, it is excessive fluctuations of the sympathetic nervous system that may be relevant in menstrual migraine.


Voluntary wheel running alters markers of amyloid-beta precursor protein processing in an ovarian hormone depleted model.
Aberrant cleavage of the transmembrane protein, amyloid-beta precursor protein (ABPP), results in the overproduction of amyloid-beta (AB) peptides which can form senile plaques in the brain. These plaques can get lodged within synapses and disrupt neuronal communication ultimately leading to rampant neuron death. The rate-limiting enzyme in AB production is beta-site ABPP cleaving enzyme 1 (BACE1). In females, estrogen loss is associated with increases in AB and BACE1 content and activity. Exercise is known to have anti-amyloidogenic effects and may be able to alter BACE1 in cases of ovarian hormone depletion. This study aimed to examine the effects of physical activity on BACE1 in intact and ovariectomized female mice. Female C57BL/6 mice (24 weeks old) underwent bilateral ovariectomy (OVX; n=20) or SHAM surgery (SHAM; n=20). Mice were assigned to one of four groups (n=10/group) for 8 weeks: (1) sham (SHAM), (2) sham with a wheel (SHAM VWR), (3) ovariectomized (OVX), or (4) ovariectomized with a wheel (OVX VWR). Novel object recognition testing demonstrated that OVX mice had a lower percentage of novel object investigation time compared to SHAM. OVX mice also had higher prefrontal cortex BACE1 activity compared to SHAM (p<0.0001), while the OVX+VWR activity was not different from SHAM. Our results demonstrate that voluntary wheel running in an ovariectomized model prevented increases in BACE1 activity, maintained memory recall, and may provide a method of slowing the progression of Alzheimer's disease.


High resolution spectroscopy of the 12Lambda B hypernucleus produced by the (e,e'K+) reaction.
High-energy, cw electron beams at new accelerator facilities allow electromagnetic production and precision study of hypernuclear structure, and we report here on the first experiment demonstrating the potential of the (e,e'K+) reaction for hypernuclear spectroscopy. This experiment is also the first to take advantage of the enhanced virtual photon flux available when electrons are scattered at approximately zero degrees. The observed energy resolution was found to be approximately 900 keV for the (12)(Lambda)B spectrum, and is substantially better than any previous hypernuclear experiment using magnetic spectrometers. The positions of the major excitations are found to be in agreement with a theoretical prediction and with a previous binding energy measurement, but additional structure is also observed in the core excited region, underlining the future promise of this technique.


Dizziness in discus throwers is related to motion sickness generated while spinning.
While both discus and hammer throwing involve rotating movements resulting in the throw of an object, discus throwers sometimes report dizziness, a condition never experienced by hammer throwers. We investigated whether this susceptibility was related to the sensitivity of the thrower or to the type of throwing achieved. For the latter, we compared the determining features of gesture, gaze stabilization and projectile trajectory in both sports. A total of 22 high-level sportsmen in these 2 disciplines, half of them practising both sports, were interviewed. Slow motion video recordings of discus and hammer throwing were examined to determine the visual referential, head movements and plantar surface support area involved at each stage of the motions. Discomfort was reported by 59% of the sportsmen while throwing discus, but by none while throwing hammer. Because several individuals practised both sports, these results exclude the hypothesis of individual susceptibility to dizziness. Video analysis evidenced that during hammer throwing, visual bearings can be used more easily than during discus throwing. Moreover, there is a loss of plantar afferents and generation of head movements liable to induce motion sickness, such as Coriolis acceleration. In conclusion, although hammer and discus-throwing present numerous similarities, we demonstrate here that crucial differences in the specific execution of each sport are responsible for the dizziness experienced by discus throwers.


Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemia.
beta-Thalassemia and sickle cell disease both display a great deal of phenotypic heterogeneity, despite being generally thought of as simple Mendelian diseases. The reasons for this are not well understood, although the level of fetal hemoglobin (HbF) is one well characterized ameliorating factor in both of these conditions. To better understand the genetic basis of this heterogeneity, we carried out genome-wide scans with 362,129 common SNPs on 4,305 Sardinians to look for genetic linkage and association with HbF levels, as well as other red blood cell-related traits. Among major variants affecting HbF levels, SNP rs11886868 in the BCL11A gene was strongly associated with this trait (P < 10(-35)). The C allele frequency was significantly higher in Sardinian individuals with elevated HbF levels, detected by screening for beta-thalassemia, and patients with attenuated forms of beta-thalassemia vs. those with thalassemia major. We also show that the same BCL11A variant is strongly associated with HbF levels in a large cohort of sickle cell patients. These results indicate that BCL11A variants, by modulating HbF levels, act as an important ameliorating factor of the beta-thalassemia phenotype, and it is likely they could help ameliorate other hemoglobin disorders. We expect our findings will help to characterize the molecular mechanisms of fetal globin regulation and could eventually contribute to the development of new therapeutic approaches for beta-thalassemia and sickle cell anemia.


A new severe acute necrotizing pancreatitis model induced by L-ornithine in rats.
Intraperitoneal administration of large doses of L-arginine is known to induce severe acute pancreatitis in rats. We therefore set out to determine whether metabolites of L-arginine (L-ornithine, L-citrulline, and nitric oxide) cause pancreatitis. The authors conducted an in vivo animal study. This study was conducted at a university research laboratory. Study subjects were male Wistar rats. Dose-response and time course changes of laboratory and histologic parameters of pancreatitis were determined after L-arginine, L-ornithine, L-citrulline, or sodium nitroprusside (nitric oxide donor) injection. Intraperitoneal injection of 3 g/kg L-ornithine but not L-citrulline or nitroprusside caused severe acute pancreatitis; 4 to 6 g/kg L-ornithine killed the animals within hours. Serum and ascitic amylase activities were significantly increased, whereas pancreatic amylase activity was decreased after intraperitoneal injection of 3 g/kg L-ornithine. The increase in pancreatic trypsin activity (9-48 hrs) correlated with the degradation of IkappaB proteins and elevated interleukin-1beta levels. Oxidative stress in the pancreas was evident from 6 hrs; HSP72 synthesis was increased from 4 hrs after L-ornithine administration. Morphologic examination of the pancreas showed massive interstitial edema, apoptosis, and necrosis of acinar cells and infiltration of neutrophil granulocytes and monocytes 18 to 36 hrs after 3 g/kg L-ornithine injection. One month after L-ornithine injection, the pancreas appeared almost normal; the destructed parenchyma was partly replaced by fat. Equimolar administration of L-arginine resulted in lower pancreatic weight/body weight ratio, pancreatic myeloperoxidase activity, and histologic damage compared with the L-ornithine-treated group. L-ornithine levels in the blood were increased 54-fold after intraperitoneal administration of L-arginine. We have developed a simple, noninvasive model of acute necrotizing pancreatitis in rats by intraperitoneal injection of 3 g/kg L-ornithine. Interestingly, we found that, compared with L-arginine, L-ornithine was even more effective at inducing pancreatitis. Large doses of L-arginine produce a toxic effect on the pancreas, at least in part, through L-ornithine.


Phenotypes of cough in children: A latent class analysis.
Distinguishing phenotypes among children with cough helps understand underlying causes. Using a statistical data-driven approach, we aimed to identify and validate cough phenotypes based on measurable traits, physician diagnoses, and prognosis. We used data from the Swiss Paediatric Airway Cohort and included 531 children aged 5-16 years seen in outpatient clinics since 2017. We included children with any parent-reported cough (i.e. cough without a cold, cough at night, cough more than other children, or cough longer than 4 weeks) without current wheeze. We applied latent class analysis to identify phenotypes using nine symptoms and characteristics and selected the best model using the Akaike information criterion. We assigned children to the most likely phenotype and compared the resulting groups for parental atopy history, comorbidities, spirometry, fractional exhaled nitric oxide (FeNO), skin prick tests and specific IgE, physician diagnoses, and 1-year prognosis. We identified four cough phenotypes: non-specific cough (26%); non-allergic infectious and night cough with snoring and otitis (4%); chronic allergic dry night cough with snoring (9%); and allergic non-infectious cough with rhino-conjunctivitis (61%). Children with the allergic phenotype often had family or personal history of atopy and asthma diagnosis. FeNO was highest for the allergic phenotype [median 17.9 parts per billion (ppb)] and lowest for the non-allergic infectious phenotype [median 7.0 parts per billion (ppb)]. Positive allergy test results differed across phenotypes (p < .001) and were most common among the allergic (70%) and least common among the non-specific cough (31%) phenotypes. Subsequent wheeze was more common among the allergic than the non-specific phenotype. We identified four clinically relevant cough phenotypes with different prognoses. Although we excluded children with current wheeze, most children with cough belonged to allergy-related phenotypes.


Isoflavone profile and biological activity of soy bread.
The present study examines the ability of isoflavone extracts from whole soy bread and two soy bread fractions, crumb and crust, to modulate the proliferation of human prostate cancer PC-3 cells. Total isoflavone content in the two fractions of soy bread were similar (3.17 micromol/g dry basis). However, their conjugate patterns were altered. Both fractions of soy bread contained a similar level of isoflavone aglycones ( approximately 24%). Low concentrations of soy bread extracts increased PC-3 cell proliferation as much as 47% compared to untreated control. This proliferative effect in cell growth was reduced at higher extract concentration. Soy bread crust extract (10 mg/mL) reduced PC-3 cell proliferation by 15% compared to untreated control. Interestingly, wheat bread extracts increased cell proliferation at all concentrations tested. Although extracts from both breads possessed biological activity, only soy bread crust extract reduced PC-3 cell proliferation. This observation may be related to the presence of soy in this bread.


Does the Amount of Stable Isotope Dose Influence Retinol Kinetic Responses and Predictions of Vitamin A Total Body Stores by the Retinol Isotope Dilution Method in Theoretical Children and Adults?
To minimize both cost and perturbations to the vitamin A system, investigators limit the amount of stable isotope administered when estimating vitamin A total body stores (TBS) by retinol isotope dilution (RID). We hypothesized that reasonable increases in the mass of stable isotope administered to theoretical subjects would have only transient impacts on vitamin A kinetics and minimal effects on RID-predicted TBS. We adapted previously used theoretical subjects (3 children, 3 adults) with low, moderate, or high assigned TBS and applied compartmental analysis to solve a steady state model for tracer and tracee using assigned values for retinol kinetic parameters and plasma retinol. To follow retinol trafficking when increasing amounts of stable isotope were administered [1.39-7 (children) and 2.8-14 μmol retinol (adults)], we added assumptions to an established compartmental model so that plasma retinol homeostasis was maintained. Using model-simulated data, we plotted retinol kinetics versus time and applied the RID equation TBS = FaS/SAp [Fa, fraction of dose in stores; S, retinol specific activity (SA) in plasma/SA in stores; SAp, SA in plasma] to calculate vitamin A stores. The model predicted that increasing the stable isotope dose caused transient early increases in hepatocyte total retinol; increases in plasma tracer were accompanied by decreases in tracee to maintain plasma retinol homeostasis. Despite changes in kinetic responses, RID accurately predicted assigned TBS (98-105%) at all loads for all theoretical subjects from 1 to 28 d postdosing. Results indicate that, compared with doses of 1.4-3.5 μmol used in recent RID field studies, doubling the stable isotope dose should not affect the accuracy of TBS predictions, thus allowing for experiments of longer duration when including a super-subject design (Ford et al., J Nutr 2020;150:411-8) and/or studying retinol kinetics.


Prediction of protein-protein interactions using distant conservation of sequence patterns and structure relationships.
Given that association and dissociation of protein molecules is crucial in most biological processes several in silico methods have been recently developed to predict protein-protein interactions. Structural evidence has shown that usually interacting pairs of close homologs (interologs) physically interact in the same way. Moreover, conservation of an interaction depends on the conservation of the interface between interacting partners. In this article we make use of both, structural similarities among domains of known interacting proteins found in the Database of Interacting Proteins (DIP) and conservation of pairs of sequence patches involved in protein-protein interfaces to predict putative protein interaction pairs. We have obtained a large amount of putative protein-protein interaction (approximately 130,000). The list is independent from other techniques both experimental and theoretical. We separated the list of predictions into three sets according to their relationship with known interacting proteins found in DIP. For each set, only a small fraction of the predicted protein pairs could be independently validated by cross checking with the Human Protein Reference Database (HPRD). The fraction of validated protein pairs was always larger than that expected by using random protein pairs. Furthermore, a correlation map of interacting protein pairs was calculated with respect to molecular function, as defined in the Gene Ontology database. It shows good consistency of the predicted interactions with data in the HPRD database. The intersection between the lists of interactions of other methods and ours produces a network of potentially high-confidence interactions.


Enhanced fluorescence sensing using microstructured optical fibers: a comparison of forward and backward collection modes.
A general model of excitation and fluorescence recapturing by the forward and backward modes of filled microstructured optical fibers (MOFs) is presented. We also present experimental results for both backward and forward fluorescence recapturing within a MOF as a function of fiber length and demonstrate a good qualitative agreement between the numerical model and experimental results. We demonstrate higher efficiency of fluorescence recapturing into backward modes in comparison with that of forward modes.


Current status of transurethral thermotherapy at the Mayo Clinic.
With the ever-expanding elderly population in the United States, benign prostatic hyperplasia (BPH) has become a widespread condition. Although surgical intervention (open prostatectomy and transurethral resection of the prostate) was the typical management approach for BPH in the past, other options currently include drug therapy and transurethral thermotherapy, a minimally invasive procedure that involves the targeting of heat deep within the prostate transition zone while cooling the surrounding anatomic structures with circulating water. Two thermo-therapy-devices--the Prostatron and the T3 transurethral thermoablation therapy catheter--have been studied in randomized controlled clinical trials at the Mayo Clinic. Both devices were shown to be effective in a substantial subset of patients with BPH: symptom scores decreased, peak urinary flow rates increased, and total serum prostate-specific antigen levels increased, an indication of destruction of adenomatous tissue. All patients were able to complete the treatment without the need for general or regional anesthesia, and thermotherapy was associated with few postprocedural events. Although this therapeutic strategy is currently used selectively in patients with lateral lobe prostatic adenoma, improvements in technology and understanding of the thermoregulatory properties of the prostate should broaden the application of thermotherapy devices in the management of BPH.


Exclusion of a luminous red giant as a companion star to the progenitor of supernova SN 2011fe.
Type Ia supernovae are thought to result from a thermonuclear explosion of an accreting white dwarf in a binary system, but little is known of the precise nature of the companion star and the physical properties of the progenitor system. There are two classes of models: double-degenerate (involving two white dwarfs in a close binary system) and single-degenerate models. In the latter, the primary white dwarf accretes material from a secondary companion until conditions are such that carbon ignites, at a mass of 1.38 times the mass of the Sun. The type Ia supernova SN 2011fe was recently detected in a nearby galaxy. Here we report an analysis of archival images of the location of SN 2011fe. The luminosity of the progenitor system (especially the companion star) is 10-100 times fainter than previous limits on other type Ia supernova progenitor systems, allowing us to rule out luminous red giants and almost all helium stars as the mass-donating companion to the exploding white dwarf.


Glycyrrhizin attenuates tissue injury and reduces neutrophil accumulation in experimental acute pancreatitis.
Leukocyte infiltration and acinar cell injury are characteristic features of acute pancreatitis (AP). However, the signaling pathways regulating inflammation and accumulation of leukocytes into pancreas tissue remains poorly elucidated. In the current study, we investigated the effects of Glycyrrhizin (GZ) on cerulein-induced AP in mice. AP was induced in male C57BL/6 by intraperitoneal injection of 50 μg/kg cerulein hourly, with a total of 7 times. 1 hour after the last injection of cerulean, mice were treated with either 35 or 70 mg/kg of GZ. Serum amylases and lipases were measured using automated chromogenic assay, MCP-1 and MIP-2 concentrations were measured in the serum by ELISA, and the number of infiltrated inflammatory cells in the pancreas were evaluated by flow cytometry. We found that GZ treatment resulted in reduction (i) both amylase and lipase activities, (ii) the serum levels of both MCP-1 and MIP-2; and (iii) markedly attenuated cerulein-induced histopathological alternations and water contents. Furthermore, we observed that GZ significantly decreased the number of infiltrated monocytes and neutrophils into the pancreas tissue. In conclusion, we demonstrate that GZ attenuates AP signs and inhibits inflammatory cell recruitments into pancreas.


Sugammadex for reversal of moderate-to-deep rocuronium block in a clinical setting: A retrospective report of 10 dogs.
To compare recovery times of sugammadex with spontaneous recovery from rocuronium-induced neuromuscular block (NMB) in dogs. Retrospective, unmatchedcase-control study. A total of 10 dogs administered sugammadex and 10 dogs recovering spontaneously from rocuronium-induced NMB. Files of dogs administered rocuronium between March and August 2023 were inspected. The train-of-four (TOF) count at the time of sugammadex administration and the time between administration and TOF ratio >90% (recovery time) were recorded. The recovery time for those not administered reversal agents was considered from the first TOF value >0 until TOF ratio >90%. The dose of sugammadex and the cumulative dose of rocuronium were recorded. Rocuronium doses and recovery times were compared using Mann-Whitney tests. The coefficient of determination (R2) between the cumulative rocuronium dose and sugammadex dose and the recovery time were calculated. Dogs in the sugammadex and spontaneous recovery groups were administered intravenously (IV) 0.76 (0.4-2.6) and 0.61 (0.3-2.9) mg kg-1 of rocuronium, respectively (p = 0.325). Recovery time after 3.9 (2.9-5.5) mg kg-1 of sugammadex IV was 1 (1-3) minutes and was 20 (10-35) min for spontaneous recovery (p < 0.0001). The R2 for rocuronium and sugammadex doses and recovery times were 0.19 (p = 0.2) and 0.012 (p = 0.758). Sugammadex 2.9-5.5 mg kg-1 reversed moderate (TOF count 1-3) or deep (TOF count 0) rocuronium-induced NMB within 3 minutes, substantially faster than spontaneous recovery.


Lack of Automatic Vocal Response Learning While Reading Aloud.
Research on implicit sequence learning with the Serial Reaction Task (SRT) has demonstrated that people automatically acquire knowledge about fixed repeating sequences of responses and can transfer response sequence knowledge to novel stimuli. Such demonstrations are, however, mostly limited to setups with visual stimuli and manual responses. Here we systematically follow up on scarce attempts to demonstrate implicit sequence learning in word reading. While the literature on implicit sequence learning can be taken to suggest that sequence knowledge is acquired and affecting performance in word reading, we show that neither is the case in a series of four experiments. Sequence knowledge was acquired and affecting performance in color naming but not in word reading. On the one hand, we observed slowing of voice-onset times in off-sequence as compared to regularly sequenced trials when people named the color of a centrally presented disk. Yet, hardly any effect was observed when the very same sequence of words was verbalized in word reading instead. Transfer of sequence knowledge to and from color naming was not observed, either. This contrasts with sequence learning studies with manual responses, which have been taken to suggest that a fixed and repeating sequence of responses is sufficient for learning to occur even in fast choice reaction tasks and to transfer across stimuli as long as the sequence of responses remains intact. Rather, in line with dimensional action accounts of task performance, the results underline the role of translation between processing streams for implicit sequence learning.


Physical activity level is an independent predictor of the diurnal variation in blood pressure.
The aim of this study was to define the relationship between physical activity and the magnitude of the percentage fall in blood pressure at night (nocturnal dip). We simultaneously monitored 24-h ambulatory blood pressure and measured physical activity by actigraphy in 434 patients. Blood pressure was measured every 20 min; the actigraph integrated an activity score every 10 s. Mean daytime and night-time activity were calculated from mean scores for the 15 min preceding each blood pressure measurement. Nocturnal dip in systolic and diastolic blood pressure (SBP and DBP) were regressed on mean (log-transformed) daytime activity. Mean night-time activity, age, gender, smoking status, body mass index (BMI) and clinic blood pressure were added into a multiple linear regression. The patient group was heterogeneous in age, gender and mean 24-h blood pressure. Mean daytime activity level was significantly and positively associated with the magnitude of the nocturnal dip in both SBP and DBP. Increased night-time activity was significantly associated with a smaller nocturnal dip. Older patients had a smaller nocturnal dip per log unit daytime activity. Nocturnal dip in SBP was greater in males, and smaller in those taking antihypertensive medications. Smoking, BMI and clinical blood pressure level were not associated with the extent of the nocturnal dip after adjustment for other factors. Daytime and night-time physical activity levels are independently and significantly predictive of the magnitude of the nocturnal dip in blood pressure. Variation in activity may confound interpretation of 24-h ambulatory blood pressure monitoring, and contribute to the poor reproducibility of dipper status.


[Coping with the toll of heroin: 10 years of the Barcelona Action Plan on Drugs, Spain].
The epidemic of heroin use began in Barcelona, as in the rest of Spain, in the late 70's, to reach its peak by the end of the 80's. In a first period, responsible officers experimented difficulties to define the specific objectives of opiate control policies. This paper reviews the effects of the adoption of an explicit policy on drug dependence grounded on a wide consensus in the City of Barcelona (Catalonia, Spain). Over a period of twelve years, from 1986 to 1997, both demand and offer of care and harm reduction services were analyzed, as well as the evolution of the adverse effects of drug use, such as mortality from acute adverse drug reaction, human immunodeficiency virus (HIV) infection, aids incidence, and incidence of tuberculosis. Data for city residents was compared through four different stages in this period. Despite the lack of data in initial years, relevant changes are apparent. Treatment offer changes clearly, with significant increases in initial treatment, coverage of methadone maintenance programmes, and sterile syringes distribution. Therapeutic compliance of tuberculous intravenous drug users IVDU and risk of HIV infection improve. Emergency service use linked to heroin, overdose, or withdrawal syndrome decreases. Mortality rates decline, although this decline does not reach statistical significance. Service offer shows a clear increase, reflected in treatment initiation, while harm reduction services expand. With the development of this process, outcome indicators change, both reflecting changes in the toll of the heroin epidemic (cases of tuberculosis and aids among IVDUs, HIV infection). and changes in a more comprehensive care (better treatment compliance of IVDUs with tuberculosis). There is a lower distortion of emergency services. These changes occur although the predominance of white heroin in Barcelona favors parenteral use.


A practical approach to the prevention of miscarriage: Part 1--Progesterone therapy.
To show evidence that progesterone therapy is useful in preventing miscarriages in women who are more prone to having them. Vaginal progesterone therapy was evaluated in women with a previous history of miscarriage or in women with infertility related to luteal phase defects. The results favor the benefit of using progesterone to diminish the risk of miscarriage. Other methods of stimulating progesterone production, e.g., human chorionic injections, are also effective. Progesterone therapy, especially when given vaginally, is effective with few side-effects and is safe. Thus the evidence suggests that one should err on the side of over-treatment rather than under-treatment in certain circumstances, e.g., advanced woman's age, previous history of miscarriage, or the use of follicle maturing drugs.


Assessment of cerebrovascular development and intraventricular hemorrhages in preterm infants with optical measures of the brain arterial pulse wave.
Preterm infants (born at 24-34 weeks of gestational age) suffer from a high incidence of neurological complications. Cerebrovascular lesions (intraventricular hemorrhages, IVH, and ischemic injury) due to the immaturity of the vascular system and its inability to adapt to the extra-uterine environment are the major causes of adverse neurological outcomes. We investigated the feasibility of assessing cerebrovascular status in preterm infants using a novel non-invasive optical procedure, pulse-DOT, usable within the incubator. Pulse-DOT, validated in adults, provides estimates of cerebral arterial status based on optical measurements of the pulse wave. These measurements are taken with a high-density optode montage and provide accurate spatial and temporal information. We found that two pulse parameters (pulse relaxation function, PReFx, and pulse rise time, PRT) in the investigated frontotemporal region, correlated with infant's age at recording, indexing cerebrovascular development. Moreover, PRT differentiated infants with and without concurrent IVH (sensitivity = 100%, specificity = 70%). These values are at least as high as those of the resistivity index obtained with transcranial Doppler of the middle cerebral artery, the current clinical method of choice for investigating arterial elasticity in preterm infants. This makes pulse-DOT a promising tool for investigating cerebrovascular risk factors and related pathologies in preterm infants.


Patterns of practice in neonatal and pediatric respiratory care.
Because little information has been available regarding common respiratory care practices in neonatology and pediatrics, it has been difficult to develop departmental standards of care. We therefore conducted a national survey of current practices, hoping to establish whether any de facto standards exist in the U.S. A 47-item multiple-choice survey instrument was mailed in 1988 to 689 U.S. hospitals that included all neonatal and perinatal high-risk centers. Response was received from 323 hospitals, for a 47% response rate. Some de facto standards do seem to exist, notably (1) q 2 h ventilator checks, (2) continuous measurement of oxygen concentration in oxygen hoods and ventilator circuits, (3) staffing ratio of four ventilator patients to one respiratory care practitioner, and (4) changing of ventilator circuits q 48 h. While we do not claim that such de facto standards have a scientific basis, we suggest that respiratory care services whose practices vary from the de facto standards should investigate why their own practices differ and whether they can be justified.


Coexamination of site-specific transcription factor binding and promoter activity in living cells.
Previously, we have used a chromatin cross-linking and immunoprecipitation protocol for the analysis of Myc and USF binding to the cad promoter. The adaptation of this technique for the study of mammalian transcription factors was a big step forward in the analysis of transcription factor family member specificity, allowing for the first time a definitive knowledge of which factor binds to a promoter region under normal physiological conditions. However, due to limitations of the assay, our previous studies could not definitively prove that both Myc and USF bound to the exact same site on the cad promoter, nor could we directly correlate loss of in vivo binding of a particular factor with loss of transcriptional activity. Therefore, we have further modified the chromatin immunoprecipitation protocol to alleviate these problems. We have now shown that it is possible to coexamine growth-regulated transcriptional activity and promoter occupancy by using stably integrated promoter constructs. We show that both Myc and USF bind to the exact same E box on the cad promoter, suggesting that competition between these two factors for a single site occurs in living cells. We also find that cad promoter constructs that retain USF binding but lose Myc binding in vivo no longer display an increase in transcriptional activity in mid- to late G(1) phase of the cell cycle. Finally, we propose that cell cycle-regulated transcriptional activation of the cad promoter may be a stochastic, rather than a predetermined, process.


Incremental Linear Discriminant Analysis: A Fast Algorithm and Comparisons.
It has always been a challenging task to develop a fast and an efficient incremental linear discriminant analysis (ILDA) algorithm. For this purpose, we conduct a new study for linear discriminant analysis (LDA) in this paper and develop a new ILDA algorithm. We propose a new batch LDA algorithm called LDA/QR. LDA/QR is a simple and fast LDA algorithm, which is obtained by computing the economic QR factorization of the data matrix followed by solving a lower triangular linear system. The relationship between LDA/QR and uncorrelated LDA (ULDA) is also revealed. Based on LDA/QR, we develop a new incremental LDA algorithm called ILDA/QR. The main features of our ILDA/QR include that: 1) it can easily handle the update from one new sample or a chunk of new samples; 2) it has efficient computational complexity and space complexity; and 3) it is very fast and always achieves competitive classification accuracy compared with ULDA algorithm and existing ILDA algorithms. Numerical experiments based on some real-world data sets demonstrate that our ILDA/QR is very efficient and competitive with the state-of-the-art ILDA algorithms in terms of classification accuracy, computational complexity, and space complexity.


Conserved allosteric pathways for activation of TRPV3 revealed through engineering vanilloid-sensitivity.
The Transient Receptor Potential Vanilloid 1 (TRPV) channel is activated by an array of stimuli, including heat and vanilloid compounds. The TRPV1 homologues TRPV2 and TRPV3 are also activated by heat, but sensitivity to vanilloids and many other agonists is not conserved among TRPV subfamily members. It was recently discovered that four mutations in TRPV2 are sufficient to render the channel sensitive to the TRPV1-specific vanilloid agonist resiniferatoxin (RTx). Here, we show that mutation of six residues in TRPV3 corresponding to the vanilloid site in TRPV1 is sufficient to engineer RTx binding. However, robust activation of TRPV3 by RTx requires facilitation of channel opening by introducing mutations in the pore, temperatures > 30°C, or sensitization with another agonist. Our results demonstrate that the energetics of channel activation can determine the apparent sensitivity to a stimulus and suggest that allosteric pathways for activation are conserved in the TRPV family.


Activity-induced GLP-1 release in lean and obese subjects.
The aim of the study was to determine whether physical activity stimulates GLP-1 release on the short-term in normal weight and in obese subjects compared to rest and, furthermore, whether modest weight loss affects GLP-1 release or sensitivity in the obese. Normal weight (n=28; 12 males, 16 females; BMI 22.9+/-1.4; age 35+/-12.7), as well as obese subjects (n=27; 21 males, 6 females; BMI 30.9+/-2.7; age 47.1+/-11.86) were tested in a resting and a physical activity condition. Obese subjects were matched over two groups for a weight loss period of 3 months. After weight loss, the tests were repeated. The area under the curve (AUC pmol/lxmin) for GLP-1 concentrations was significantly increased in the physical activity condition compared to rest in lean subjects (P=0.05) as well as in the obese subjects after weight loss (P<0.05), but not in the obese subjects before weight loss. Physical activity-stimulated GLP-1 release in lean and obese subjects after a weight loss period supports the idea of a neuroendocrine loop in addition to distal-intestinal stimulation of GLP-1 release. Modest weight loss might be effective for increasing GLP-1 sensitivity to acute stimulation.


What destroys our restraints against suicide?
There seems to exist an inherent barrier to the achievement of any extreme biological state, be it massive intravascular coagulation, intense euphoria, or the inalterable decision to kill oneself. Moreover, defenses against suicide may in themselves be pathological, producing other types of maladaption. Indeed, certain lethality indicators possess a threshold, below which they act as a barrier against suicide. Wrist-cutting, self-treatment with drugs and alcohol, and psychosis itself all can play a defensive role in the organism's struggle for survival.


[Modification with bradykinin of membrane-bound lipid peroxidation and Ca2+-activity of the thymus and liver].
Effect of bradykinin on activity of Ca2+-ATPase and accumulation of malonic dialdehyde (MDA) was studied in proliferating and relatively non-proliferating (resting) cells of thymus and liver tissues. The peptide effect was studied in vivo and in vitro after intravenous administration into mice at a dose of 2 mg/kg or by means of addition of bradykinin (10(-6)M) to a suspension of calf thymocyte membranes. In vivo bradykinin caused the most distinct decrease in MDA accumulation and activation of Ca2+-ATPase in thymus as compared with liver tissue. In vitro incubation of thymocyte membranes with bradykinin led to prolongation of the latent period of MDA formation and to a distinct increase in the Ca2+-ATPase activity. Modification of these processes in membranes appear to be one of important functions of bradykinin in proliferation.


Room-temperature ferromagnetism of Cu-doped ZnO films probed by soft X-ray magnetic circular dichroism.
We report direct evidence of room-temperature ferromagnetic ordering in O-deficient ZnO:Cu films by using soft x-ray magnetic circular dichroism and x-ray absorption. Our measurements have revealed unambiguously two distinct features of Cu atoms associated with (i) magnetically ordered Cu ions present only in the oxygen-deficient samples and (ii) magnetically disordered regular Cu2+ ions present in all the samples. We find that a sufficient amount of both oxygen vacancies (V(O)) and Cu impurities is essential to the observed ferromagnetism, and a non-negligible portion of Cu impurities is uninvolved in the magnetic order. Based on first-principles calculations, we propose a microscopic "indirect double-exchange" model, in which alignments of localized large moments of Cu in the vicinity of the V(O) are mediated by the large-sized vacancy orbitals.


Emergency department visits in the United States for pediatric depression: estimates of charges and hospitalization.
The objective of this study was to calculate national estimates of depression-related emergency department (ED) visits and associated health care resource use among children and adolescents 17 years or younger. Another goal was to explore the effects of certain sociodemographic and health care system factors and comorbidities on ED charges and subsequent hospitalization in the United States. The authors analyzed data from the 2006 and 2009 National Emergency Department Sample (NEDS), the largest source of U.S. ED data. ED visits with all listed diagnoses (i.e., principal diagnosis plus secondary conditions) of depression were identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes 293.83, 296.2X, 296.3X, 300.4, and 311. Population-based estimates of ED visits, hospitalization, resource use, comorbidities, and demographics associated with pediatric depression were calculated. Potentially significant covariate associations were also explored using ED charges and hospital admission from the ED. The 2006 and 2009 NEDS sample contained 365,713 ED visits for pediatric depression; the majority were made by adolescents (87.9%). Of these, 27.2% were admitted to the hospital, 69.5% were treated and released, and <0.1% died in ED. The ED charges in 2012 U.S. dollars summed to a hospital bill of $443.8 million, with the ED plus inpatient charges ($1.2 billion) being more than double that amount. The median inpatient length of stay (LOS) was 4.0 days. Suicide and intentional self-inflicted injury were attempted by 31.4% of the patients. Attention-deficit, conduct, and disruptive disorders; anxiety disorders; substance use disorders; asthma; and infections were the most common comorbidities. In year 2009, a higher number of diagnoses, older age, being female, key comorbidities, and suicide and intentional self-inflicted injury were significantly associated with higher ED charges (all p < 0.05). Increased odds of hospital admission from the ED were significantly associated with a higher number of diagnoses, key comorbidities, and suicide and intentional self-inflicted injury (all p < 0.05). Pediatric depression is common in the ED and is associated with significant burden to the health care system. Certain factors such as a higher number of diagnoses, key comorbidities, and suicide and intentional self-inflicted injury are associated with increased health care costs and resource use. Special attention should be given to these factors, when present.


The application of Chat Generative Pre-trained Transformer in nursing education.
Nursing education is critical for nurses to deliver quality health care. Incorporating AI into education can enhance the learning process and better equip nurses for their health care roles. This article explores the potential applications and challenges of ChatGPT in nursing education. A comprehensive literature review was conducted to explore the potential benefits and challenges of using ChatGPT in nursing education. ChatGPT, an advanced large language model, has the potential to make valuable contributions to nursing education in various ways, including personalized learning, simulation scenarios, immediate feedback, and reducing educator workload. However, it is important to address the various challenges and limitations in order to realize its full potential. Nursing educators must carefully consider the potential uses, benefits, challenges, drawbacks, and limitations of ChatGPT to make informed decisions about its integration into nursing education.


Polyuria-polydipsia syndrome: a diagnostic challenge.
The main determinants for the maintenance of water homeostasis are the hormone arginine vasopressin (AVP) and thirst. Disturbances in these regulatory mechanisms can lead to polyuria-polydipsia syndrome, which comprises of three different conditions: central diabetes insipidus (DI) due to insufficient secretion of AVP, nephrogenic DI caused by renal insensitivity to AVP action and primary polydipsia due to excessive fluid intake and consequent physiological suppression of AVP. It is crucial to determine the exact diagnosis because treatment strategies vary substantially. To differentiate between the causes of the polyuria-polydipsia syndrome, a water deprivation test combined with desmopressin administration is the diagnostic 'gold standard'. Thereby, AVP activity is indirectly evaluated through the measurement of urine osmolality after prolonged dehydration. However, this test has several limitations and may fail to distinguish precisely between patients with primary polydipsia and mild forms of central and nephrogenic DI. The direct measurement of AVP during the water deprivation test, which was reported in the 1980s, has not been widely adopted due to availability, assay issues and diagnostic performance. Recently, copeptin, the c-terminal portion of the larger precursor peptide of AVP, has been evaluated in the setting of polyuria-polydipsia syndrome and appears to be a useful candidate biomarker for the differential diagnosis. A standardised method for the water deprivation test is presented as part of a joint initiative of the Endocrine Society of Australia, the Australasian Association of Clinical Biochemists and the Royal College of Pathologists of Australasia to harmonise dynamic endocrine tests across Australia.


Interaction of Gaseous Chlorine Dioxide and Mild Heat on the Inactivation of Salmonella on Almonds.
The interactive effects of mild heat and gaseous chlorine dioxide (ClO2) on populations of Salmonella on almonds were studied. Almonds, dip inoculated with a two-strain cocktail of attenuated Salmonella Typhimurium, were treated with three concentrations of ClO2 at ambient temperature (ca. 22°C), and at 45, 50, 55, and 60°C for 4 h and with more than 90% relative humidity. Concentrations of ClO2 during treatments were measured, and populations of Salmonella were determined following treatments. Results demonstrated that ClO2 at concentrations of more than 4 mg/L and ambient temperature only reduced populations of Salmonella by 1.46 log CFU/g. With increasing treatment temperature, the efficacy of gaseous ClO2 increased. At 55 and 60°C, >1 mg/L ClO2, and a 4-h treatment time, >4 log CFU/g Salmonella was inactivated. Reductions greater than 4 log of the bacterium by gaseous ClO2 at 55°C were confirmed using a three-strain cocktail of pathogenic Salmonella. Overall, results demonstrated that mild heating is necessary for gaseous ClO2 to achieve more than 4 log CFU/g inactivation of Salmonella on almonds.


Astrocytosis and amyloid deposition in scrapie-infected hamsters.
In scrapie infection, prion protein (PrPSc) is localized in areas where there is neurodegeneration and astrocytosis. It is thought that PrPSc is toxic to neurons and trophic for astrocytes. In our study, paraffin sections from scrapie infected (263K and 139H) and control hamsters were examined with histological and immunocytochemical staining. We found that PrPSc was present in the ependymal cells of both 263K- and 139H-infected hamsters. In 139H-infected hamsters, PrPSc was found in the cytoplasm of neurons in cerebral cortex and in hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. In contrast, neuronal cytoplasm and nuclei, were positive for PrPSc in most areas such as cortex, hippocampus, and thalamus in 263K-infected hamsters. Many aggregations of PrPSc could be seen in the cortex, hippocampus, substantia nigra and around the Pia mater, corpus callosum, fimbria, ventricles, and blood vessels in sections from 139H- and/or 263K-positive animals. Furthermore, PrPSc was also co-localized with glial fibrillary acidic protein (GFAP) in many reactive astrocytes (approximately 90%) in certain areas such as the hippocampus in 263K-infected hamsters, but not 139H-infected hamsters. The patterns of astrocytosis and PrPSc formation were different between 139H- and 263K-infected hamsters, which may be used for a diagnosis purpose. Our results suggest a hypothesis that multiple cell-types are capable of PrPSc production. Our results also confirm that reactive astrocytes can produce and/or accumulate PrPSc during some scrapie strain infections. The findings suggest a 'snowball effect', that is: astrocytosis might play an important role in amyloidosis, while amyloidosis may induce further astrocytosis at least in 263K-infected hamsters.


Adaptive evolution of Xa21 homologs in Gramineae.
The XA21 protein has broad spectrum resistance against Xanthomonas oryzae pv. oryzae. Although Xa21-mediated immunity is well characterized, little is known about the origin and evolutionary history of this gene in grasses. Therefore, we analyzed all Xa21 gene homologs in eight whole-genome sequenced rice lines, as well as in four gramineous genomes, rice, Brachypodium, sorghum and maize; using Arabidopsis Xa21 homologs as outgroups, 17, 7, 7 and 3 Xa21 homologs were detected in these four grasses, respectively. Synteny and phylogenetic analysis showed that frequent gene translocation, duplication and/or loss, have occurred at Xa21 homologous loci, suggesting that they have undergone or are undergoing rapid generation of copy number variations. Within the rice species, the high level of nucleotide diversity between Xa21-like orthologs showed a strong association with the presence/absence haplotypes, suggesting that the genetic structure of rice lines plays an important role in the variations between these Xa21-like orthologs. Strongly positive selection was detected in the core region of the leucine-rich repeat domains of the Xa21 subclade among the rice lines, indicating that the rapid gene diversification of Xa21 homologs may be a strategy for a given species to adapt to the changing spectrum of species-specific pathogens.


What is resource management?
Healthcare is changing rapidly. One of the most significant changes is the way that modern society views healthcare. In response to public demand for high-quality care at low cost, providers have to take a broader, more encompassing view of the total cost of patient care. Resource management is emerging as the discipline to integrate the healthcare delivery process. Resources comprise time, money, people, facilities, equipment, information, pharmaceuticals, and fixed assets. The central question for every healthcare provider is: "How can I optimize resources to maximize patient wellness?"


Genes as gerontological variables: uniform genotypes.
Genetic conceptualizations and procedures have become integral to the conduct of research across the spectrum of life sciences, including gerontology, even when genetics is not the focus of inquiry. Among the research tools thus provided, one of the most basic is that of inbred strains. A close approximation to genetic uniformity is achieved by a sufficient number of successive generations of matings of relatives, and, once this near-uniformity is attained, the members of an inbred strain constitute a reference group relatively stable over time and available to diverse investigators. Different inbred strains possess different genotypes, so that numerous distinctive reference groups are available. The stability of these groups enhances prospects of replication-testing, and makes possible the focused accumulation of pertinent data. Phenotypic differences among strains identify particular groups that can be most appropriate for particular subsequent research objectives (and also provide ipso facto evidence of genetic influence on the phenotype). The very substantial advantages of the uniform genotypes provided by inbred strains (and by their F1 offspring) are purchased at the cost of limited generalizability of results and constraints on assessment of co-variation among variables. Uniform genotypes are, thus, not a tool for all purposes but must be seen as a powerful basic tool within an abundant genetic tool-kit. Particular research purposes will require use of more than one tool from the kit.


Early onset gastric cancer: on the road to unraveling gastric carcinogenesis.
Gastric cancer is thought to result from a combination of environmental factors and the accumulation of specific genetic alterations due to increasing genetic instability, and consequently affects mainly older patients. Less than 10% of patients present with the disease before 45 years of age (early onset gastric carcinoma) and these patients are believed to develop gastric carcinomas with a molecular genetic profile differing from that of sporadic carcinomas occurring at a later age. In young patients, the role of genetics is presumably greater than in older patients, with less of an impact from environmental carcinogens. As a result, hereditary gastric cancers and early onset gastric cancers can provide vital information about molecular genetic pathways in sporadic cancers and may aid in the unraveling of gastric carcinogenesis. This review focuses on the molecular genetics of gastric cancer and also focuses on early onset gastric cancers as well as familial gastric cancers such as hereditary diffuse gastric cancer. An overview of the various pathways of importance in gastric cancer, as discovered through in-vitro, primary cancer and mouse model studies, is presented and the clinical importance of CDH1 mutations is discussed.


Stromal Cell-Derived CCL20 Promotes Tumor Progression and Osteolysis in Giant Cell Tumor of Bone.
Giant cell tumor of bone (GCTB), one of the most common primary bone tumors, leads to extensive bone destruction. However, the mechanisms underlying GCTB progression remain elusive and prognostic factors and treatment targets are required. In the current study, we explored the function of the chemokine family member CCL20 in GCTB progression. We explored the expression of CCL20 in stromal cells (GCTSCs) using microarray. Clinical analyses of the role of CCL20 in tumor progression were performed based on the patient cohort of our institution. The role of CCL20 in tumor proliferation was evaluated by MTS assay, migration ability was measured by a Transwell assay, and osteoclastogenesis was induced by CCL20 or GCTSC-conditioned medium. Quantitative PCR and western blot were used to measure the expression levels of mRNAs and proteins related to tumor progression. CCL20 was upregulated in GCTSCs and correlated with tumor progression and prognosis. CCL20 induced GCTSC proliferation and migration in an autocrine manner. In addition, CCL20 recruited mononuclear cells and induced osteoclastogenesis by overactivating the AKT and NF-κB signaling pathways. Antibody blockade of CCL20 abolished the exacerbated osteoclastogenesis. Taken together, our data indicate that GCTSC secretion of CCL20 acts as a key modulator in the pathological progression of GCTB. It can promote GCTSC proliferation and migration in an autocrine manner and can recruit bone marrow monocytes to the tumor microenvironment and enhance osteoclastogenesis in a paracrine manner. These findings strongly indicate the potential prognostic and therapeutic value of CCL20 in GCTB.


Hepatitis B e Antigen Induces NKG2A+ Natural Killer Cell Dysfunction via Regulatory T Cell-Derived Interleukin 10 in Chronic Hepatitis B Virus Infection.
Although persistent hepatitis B virus (HBV) infection is associated with natural killer (NK) cell dysfunction, it remains obscure whether HBV viral antigens are responsible for NK cell dysfunction in patients with chronic hepatitis B (CHB) infection. In this study, we found that the percentage of NK cells expressing the inhibitory receptor, NKG2A, was increased in CHB patients, and NKG2A blockade restored NK cell function. Furthermore, in CHB patients, the frequency of NK cells expressing NKG2A positively correlated with the number of regulatory T cells (Tregs) and production of interleukin-10 (IL-10) in these Tregs. Moreover, exposure of peripheral blood mononuclear cells (PBMCs) isolated from healthy controls to sera from CHB patients resulted in increased proportion of NKG2A+ NK cells; IL-10 blockade reduced the frequency of NKG2A+ NK cells while increasing the percentage of IFN-γ+ NK cells. In addition, stimulation of NK cells and Tregs from healthy controls with CHB sera together with anti-IL-10 antibody increased IFN-γ production in the culture supernatant. The frequencies of NKG2A+ NK cells and IL-10+ Tregs, along with serum levels of alanine transferase and HBV DNA, were significantly increased in CHB patients positive for the Hepatitis B e antigen (HBeAg, a marker of viral replication) when compared to HBeAg-negative CHB patients. Importantly, exposure of PBMCs from healthy controls to HBeAg resulted in increased IL-10 production but reduced levels of TNF and IFN-γ, and IL-10 blockade rescued the generation of TNF and IFN-γ in this assay. The reduced production of TNF and IFN-γ was also observed in NK cells and Tregs from healthy controls that were stimulated with HBeAg, while IL-10 blockade increased the secretion of these two cytokines. We conclude that HBeAg induces IL-10 production in Tregs, thereby leading to increased expression of NKG2A on NK cells, which contributes to NK cell dysfunction during CHB infection. These data suggest that HBeAg is associated with NK cell dysfunction in CHB.


Ebola virus VP35 perturbs type I interferon signaling to facilitate viral replication.
As one of the deadliest viruses, Ebola virus (EBOV) causes lethal hemorrhagic fevers in humans and nonhuman primates. The suppression of innate immunity leads to robust systemic virus replication of EBOV, leading to enhanced transmission. However, the mechanism of EBOV-host interaction is not fully understood. Here, we identified multiple dysregulated genes in early stage of EBOV infection through transcriptomic analysis, which are highly clustered to Jak-STAT signaling. EBOV VP35 and VP30 were found to inhibit type I interferon (IFN) signaling. Moreover, exogenous expression of VP35 blocks the phosphorylation of endogenous STAT1, and suppresses nuclear translocation of STAT1. Using serial truncated mutations of VP35, N-terminal 1-220 amino acid residues of VP35 were identified to be essential for blocking on type I IFN signaling. Remarkably, VP35 of EBOV suppresses type I IFN signaling more efficiently than those of Bundibugyo virus (BDBV) and Marburg virus (MARV), resulting in stable replication to facilitate the pathogenesis. Altogether, this study enriches understanding on EBOV evasion of innate immune response, and provides insights into the interplay between filoviruses and host.


Evolutionary vestigialization of sex in a clonal plant: selection versus neutral mutation in geographically peripheral populations.
The loss of traits that no longer contribute to fitness is widespread; however, the causative evolutionary mechanisms are poorly understood. Vestigialization could proceed through the fixation of selectively neutral degenerative mutations via genetic drift. Alternatively, selection may facilitate vestigialization if trait loss results in enhanced fitness. We tested these hypotheses using Decodon verticillatus, a clonal plant in which sexual sterility has arisen repeatedly in populations across the northern geographical range limit. We compared growth and survival of replicated genotypes from 7 sexually fertile and 18 sterile populations, over 3 years in a common environment. Survival of sterile genotypes was 53% greater than for fertile genotypes, but there was no difference in biomass accumulation. Almost all mortality, and hence increased performance of sterile genotypes, occurred during simulated overwinter dormancy. These observations suggest that selection has facilitated the vestigialization of sex, and thus do not support the neutral mutation hypothesis. The selective mechanism probably involves the relaxation of a genetic trade-off between sexual reproduction and survival: alleles that increase vegetative performance at the expense of sexual fertility are selected in geographically peripheral populations where sexual reproduction is suppressed by adverse environmental conditions.


Testing increases suggestibility for narrative-based misinformation but reduces suggestibility for question-based misinformation.
A number of recent studies have found that recalling details of an event following its occurrence can increase people's suggestibility to later presented misinformation. However, several other studies have reported the opposite result, whereby earlier retrieval can reduce subsequent eyewitness suggestibility. In the present study, we investigated whether differences in the way misinformation is presented can modulate the effects of testing on suggestibility. Participants watched a video of a robbery and some were questioned about the event immediately afterwards. Later, participants were exposed to misinformation in a narrative (Experiment 1) or in questions (Experiment 2). Consistent with previous studies, we found that testing increased suggestibility when misinformation was presented via a narrative. Remarkably, when misinformation was presented in questions, testing decreased suggestibility.


Growth hormone, insulin-like growth factor-I and lipid metabolism: interactions with sex steroids.
Steroid hormones usually act via specific receptors and the hormone-receptor complex then influences the transcription of genes. These effects are often permissive for the actions of peptide hormones such as insulin and growth hormone (GH). The best known effects are those of cortisol. Since cortisol is always present, the sex steroids often modify cortisol effects. In adipose tissue, lipoprotein lipase (LPL), in the presence of insulin, is expressed via a glucocorticoid receptor, increasing transcription and stabilizing the enzyme. This process is efficiently inhibited by GH via posttranslational effects, and lipolysis is markedly stimulated. Testosterone inhibits LPL expression and, in the presence of GH, markedly increases lipolysis via multiple interactions along the lipolytic cascade. In human adipose tissue, direct effects of estrogen and progesterone cannot be demonstrated, probably because of the apparent absence of specific receptors. These hormones presumably via indirect mechanisms, perhaps by interaction with other hormone receptors.


A novel lung disease phenotype adjusted for mortality attrition for cystic fibrosis genetic modifier studies.
Genetic studies of lung disease in cystic fibrosis (CF) are hampered by the lack of a severity measure that accounts for chronic disease progression and mortality attrition. Further, combining analyses across studies requires common phenotypes that are robust to study design and patient ascertainment. Using data from the North American Cystic Fibrosis Modifier Consortium (Canadian Consortium for CF Genetic Studies, Johns Hopkins University CF Twin and Sibling Study, and University of North Carolina/Case Western Reserve University Gene Modifier Study), the authors calculated age-specific CF percentile values of FEV1 which were adjusted for CF age-specific mortality data. The phenotype was computed for 2,061 patients representing the Canadian CF population, 1,137 extreme phenotype patients in the UNC/Case Western study, and 1,323 patients from multiple CF sib families in the CF Twin and Sibling Study. Despite differences in ascertainment and median age, our phenotype score was distributed in all three samples in a manner consistent with ascertainment differences, reflecting the lung disease severity of each individual in the underlying population. The new phenotype score was highly correlated with the previously recommended complex phenotype, but the new phenotype is more robust for shorter follow-up and for extreme ages. A disease progression and mortality-adjusted phenotype reduces the need for stratification or additional covariates, increasing statistical power, and avoiding possible distortions. This approach will facilitate large-scale genetic and environmental epidemiological studies which will provide targeted therapeutic pathways for the clinical benefit of patients with CF.


Efferent limb stimulation prior to loop ileostomy closure: a systematic review and meta-analysis.
Postoperative ileus (POI) remains a common phenomenon following loop ileostomy closure. Our aim was to determine whether preoperative physiological stimulation (PPS) of the efferent limb reduced POI incidence. A PRISMA-compliant meta-analysis searching PubMed, EMBASE and CENTRAL databases was performed. The last search was carried out on 30 January 2023. All randomized studies comparing PPS versus no stimulation were included. The primary endpoint was POI incidence. Secondary endpoints included the time to first passage of flatus/stool, time to resume oral diet, need for nasogastric tube (NGT) placement postoperatively, length of stay (LOS) and other complications. Random effects models were used to calculate pooled effect size estimates. Trial sequential analyses (TSA) were also performed. Three randomized studies capturing 235 patients (116 PPS, 119 no stimulation) were included. On random effects analysis, PPS was associated with a quicker time to resume oral diet (MD - 1.47 days, 95% CI - 2.75 to - 0.19, p = 0.02), shorter LOS (MD - 1.47 days, 95% CI - 2.47 to - 0.46, p = 0.004) (MD - 1.41 days, 95% CI - 2.32 to - 0.50, p = 0.002, I2 = 56%) and fewer other complications (OR 0.42, 95% CI 0.18 to 1.01, p = 0.05). However, there was no difference in POI incidence (OR 0.35, 95% CI 0.10 to 1.21, p = 0.10), the requirement for NGT placement (OR 0.50, 95% CI 0.21 to 1.20, p = 0.12) or time to first passage of flatus/stool (MD - 0.60 days, 95% CI - 1.95 to 0.76, p = 0.39). TSA revealed imprecise estimates for all outcomes (except LOS) and further studies are warranted to meet the required information threshold. PPS prior to stoma closure may reduce LOS and postoperative complications albeit without a demonstrable beneficial effect on POI. Further high-powered studies are required to confirm or refute these findings.


Increased EEG gamma band activity in Alzheimer's disease and mild cognitive impairment.
High frequency (30-70 Hz) gamma band oscillations in the human electro-encephalogram (EEG) are thought to reflect perceptual and cognitive processes. It is therefore interesting to study these measures in cognitive impairment and dementia. To evaluate gamma band oscillations as a diagnostic biomarker in Alzheimer's disease (AD) and mild cognitive impairment (MCI), 15 psychoactive drug naïve AD patients, 20 MCI patients and 20 healthy controls participated in this study. Gamma band power (GBP) was measured in four conditions viz. resting state, music listening, story listening and visual stimulation. To evaluate test-retest reliability (TRR), subjects underwent a similar assessment one week after the first. The overall TRR was high. Elevated GBP was observed in AD when compared to MCI and control subjects in all conditions. The results suggest that elevated GBP is a reproducible and sensitive measure for cognitive dysfunction in AD in comparison with MCI and controls.


Modulation of murine Lyme borreliosis by interruption of the B7/CD28 T-cell costimulatory pathway.
Recent studies have implicated cytokines associated with Th2 cells in the genetic resistance to murine Lyme borreliosis. Because the B7/CD28 costimulatory pathway has been shown to influence the differentiation of Th-cell subsets, we investigated the contribution of the B7 molecules CD80 and CD86 to the Th2 cytokine profile and development of arthritis in BALB/c mice infected with Borrelia burgdorferi. Effective blockade of CD86/CD28 interaction was demonstrated by elimination of interleukin 4 (IL-4) and upregulation of gamma interferon (IFN-gamma) responses by B. burgdorferi-specific T cells and by reduction of B. burgdorferi-specific immunoglobulin G. Despite the shift toward a Th1 cytokine pattern, which others have associated with disease susceptibility, the severity of arthritis was unchanged. Moreover, combined CD80/CD86 blockade by using anti-CD80 and anti-CD86 monoclonal antibodies or CTLA-4Ig enhanced IFN-gamma production over that seen with CD86 blockade alone, yet augmentation of this Th1-associated cytokine did not enhance disease. These results demonstrate that IL-4 production by T cells in B. burgdorferi-infected BALB/c mice is dependent upon CD86/CD28 interaction and that this cytokine does not contribute significantly to host resistance to the development of arthritis. In addition, combined CD80/CD86 blockade resulted in preferential expansion of IFN-gamma-producing T cells in B. burgdorferi infection, suggesting that costimulatory pathways other than B7/CD28 may contribute to T-cell activation during continuous antigen stimulation. These studies may provide insight into the role of the B7/CD28 pathway in other infectious and autoimmune diseases in which deviation of Th cell immune responses occurs and antigen is persistently present.


15N and 1H NMR study of histidine containing protein (HPr) from Staphylococcus carnosus at high pressure.
The pressure-induced changes in 15N enriched HPr from Staphylococcus carnosus were investigated by two-dimensional (2D) heteronuclear NMR spectroscopy at pressures ranging from atmospheric pressure up to 200 MPa. The NMR experiments allowed the simultaneous observation of the backbone and side-chain amide protons and nitrogens. Most of the resonances shift downfield with increasing pressure indicating generalized pressure-induced conformational changes. The average pressure-induced shifts for amide protons and nitrogens are 0.285 ppm GPa(-1) at 278 K and 2.20 ppm GPa(-1), respectively. At 298 K the corresponding values are 0.275 and 2.41 ppm GPa(-1). Proton and nitrogen pressure coefficients show a significant but rather small correlation (0.31) if determined for all amide resonances. When restricting the analysis to amide groups in the beta-pleated sheet, the correlation between these coefficients is with 0.59 significantly higher. As already described for other proteins, the amide proton pressure coefficients are strongly correlated to the corresponding hydrogen bond distances, and thus are indicators for the pressure-induced changes of the hydrogen bond lengths. The nitrogen shift changes appear to sense other physical phenomena such as changes of the local backbone conformation as well. Interpretation of the pressure-induced shifts in terms of structural changes in the HPr protein suggests the following picture: the four-stranded beta-pleated sheet of HPr protein is the least compressible part of the structure showing only small pressure effects. The two long helices a and c show intermediary effects that could be explained by a higher compressibility and a concomitant bending of the helices. The largest pressure coefficients are found in the active center region around His15 and in the regulatory helix b which includes the phosphorylation site Ser46 for the HPr kinase. This suggests that this part of the structure occurs in a number of different structural states whose equilibrium populations are shifted by pressure. In contrast to the surrounding residues of the active center loop that show large pressure effects, Ile14 has a very small proton and nitrogen pressure coefficient. It could represent some kind of anchoring point of the active center loop that holds it in the right place in space, whereas other parts of the loop adapt themselves to changing external conditions.


Impact of banning alcohol on outpatient visits in Barrow, Alaska.
Community availability of alcohol affects alcohol consumption patterns and alcohol-related health and social problems. In Barrow, Alaska, an isolated community at the northernmost reaches of the United States, during a 33-month period, possession and importation of alcohol were legal, completely banned, made legal again, and then banned again. To determine the impact of these public policy changes on alcohol-related outpatient visits at the area hospital. Retrospective review of outpatient records; time-series analysis of alcohol-related visits with respect to community alcohol policy. Total monthly outpatient visits for alcohol-related problems. There was a substantial decrease in the number of alcohol-related outpatient visits when the ban on possession and importation was imposed compared with baseline. When the ban was lifted, outpatient visits increased; when the ban was reimposed, the number of outpatient visits again decreased. Interrupted time-series analyses confirm that the alcohol ban, its lifting, and its reimposition had a statistically significant and negative effect on the number of alcohol-related outpatient visits (P<.05). In a geographically isolated community, the prohibition of alcohol can be an effective public health intervention, reducing the health problems associated with alcohol use.


Inhibition of α-hemolysin activity of Staphylococcus aureus by theaflavin 3,3'-digallate.
The ongoing rise in antibiotic resistance, and a waning of the introduction of new antibiotics, has resulted in limited treatment options for bacterial infections, including these caused by methicillin-resistant Staphylococcus aureus, leaving the world in a post-antibiotic era. Here, we set out to examine mechanisms by which theaflavin 3,3'-digallate (TF3) might act as an anti-hemolytic compound. In the presented study, we found that TF3 has weak bacteriostatic and bactericidal effects on Staphylococcus aureus, and strong inhibitory effect towards the hemolytic activity of its α-hemolysin (Hla) including its production and secretion. A supportive SPR assay reinforced these results and further revealed binding of TF3 to Hla with KD = 4.57×10-5 M. Interestingly, TF3 was also able to protect human primary keratinocytes from Hla-induced cell death, being at the same time non-toxic for them. Further analysis of TF3 properties revealed that TF3 blocked Hla-prompting immune reaction by inhibiting production and secretion of IL1β, IL6, and TNFα in vitro and in vivo, through affecting NFκB activity. Additionally, we observed that TF3 also markedly attenuated S. aureus-induced barrier disruption, by inhibiting Hla-triggered E-cadherin and ZO-1 impairment. Overall, by blocking activity of Hla, TF3 subsequently subdued the inflammation and protected the epithelial barrier, which is considered as beneficial to relieving skin injury.


The therapeutic efficacy of dexpanthenol on sciatic nerve injury in a rat model.
Objective: The aim of this study was to evaluate histopathological, functional and bone densitometry examinations of the beneficial effects of dexpanthenol (DEX) on nerve regeneration in a rat model of peripheral nerve crush injury.Methods: Thirty adult Sprague-Dawley rats were divided equally into three groups. A crush injury was simulated in all rats by clamping the right sciatic nerve for one minute. In group 1, one day before the surgical procedure, 500 mg/kg DEX administered via intraperitoneally (ip) was initiated and continued three times in a week during the experiment period as 28 days. In group 2, rats received a dose of 10 mg/kg DEX to investigate possible effects of DEX alone. Group 3 served as the control (sciatic nerve injury) and was not given any drugs.Results: Performance was significantly lower in group 3 compared to the drug treatment groups during the rotarod test (30 rpm and 40 rpm) (p < 0.05). After a while, the rats which were able to remain on the rod was significantly lower in group 3 during the acceleration test (p < 0.05). Hot plate latency test results in group 3 were significantly lower when compared to the other groups (p < 0.05).Conclusion: DEX appears to be useful as a supportive clinical agent for the treatment of pain and nerve damage.


Exploring patterns of movement suspension in pedestrian mobility.
One of the main tasks in analyzing pedestrian movement is to detect places where pedestrians stop, as those places usually are associated with specific human activities, and they can allow us to understand pedestrian movement behavior. Very few approaches have been proposed to detect the locations of stops in positioning data sets, and they often are based on selecting the location of candidate stops as well as potential spatial and temporal thresholds according to different application requirements. However, these approaches are not suitable for analyzing the slow movement of pedestrians where the inaccuracy of a nondifferential global positioning system commonly used for movement tracking is so significant that it can hinder the selection of adequate thresholds. In this article, we propose an exploratory statistical approach to detect patterns of movement suspension using a local indicator of spatial association (LISA) in a vector space representation. Two different positioning data sets are used to evaluate our approach in terms of exploring movement suspension patterns that can be related to different landscapes: players of an urban outdoor mobile game and visitors of a natural park. The results of both experiments show that patterns of movement suspension were located at places such as checkpoints in the game and different attractions and facilities in the park. Based on these results, we conclude that using LISA is a reliable approach for exploring movement suspension patterns that represent the places where the movement of pedestrians is temporally suspended by physical restrictions (e.g., checkpoints of a mobile game and the route choosing points of a park).


Dynamics of the major histocompatibility complex class I processing and presentation pathway in the course of malaria parasite development in human hepatocytes: implications for vaccine development.
Control of parasite replication exerted by MHC class I restricted CD8+ T-cells in the liver is critical for vaccination-induced protection against malaria. While many intracellular pathogens subvert the MHC class I presentation machinery, its functionality in the course of malaria replication in hepatocytes has not been characterized. Using experimental systems based on specific identification, isolation and analysis of human hepatocytes infected with P. berghei ANKA GFP or P. falciparum 3D7 GFP sporozoites we demonstrated that molecular components of the MHC class I pathway exhibit largely unaltered expression in malaria-infected hepatocytes until very late stages of parasite development. Furthermore, infected cells showed no obvious defects in their capacity to upregulate expression of different molecular components of the MHC class I machinery in response to pro-inflammatory lymphokines or trigger direct activation of allo-specific or peptide-specific human CD8+ T-cells. We further demonstrate that ectopic expression of circumsporozoite protein does not alter expression of critical genes of the MHC class I pathway and its response to pro-inflammatory cytokines. In addition, we identified supra-cellular structures, which arose at late stages of parasite replication, possessed the characteristic morphology of merosomes and exhibited nearly complete loss of surface MHC class I expression. These data have multiple implications for our understanding of natural T-cell immunity against malaria and may promote development of novel, efficient anti-malaria vaccines overcoming immune escape of the parasite in the liver.


Benchmarking patient satisfaction.
Asking the patient is a critical step-but the format of a patient satisfaction survey has a significant impact on your perceptions. Design it carefully.


Effect on LTAS of vocal loudness variation.
Long-term-average spectrum (LTAS) is an efficient method for voice analysis, revealing both voice source and formant characteristics. However, the LTAS contour is non-uniformly affected by vocal loudness. This variation was analyzed in 15 male and 16 female untrained voices reading a text 7 times at different degrees of vocal loudness, mean change in overall equivalent sound level (Leq) amounting to 27.9 dB and 28.4 dB for the female and male subjects. For all frequency values up to 4 kHz, spectrum level was strongly and linearly correlated with Leq for each subject. The gain factor, that is to say, the rate of level increase, varied with frequency, from about 0.5 at low frequencies to about 1.5 in the frequency range 1.5-3 kHz. Using the gain factors for a subject, LTAS contours could be predicted at any Leq within the measured range, with an average accuracy of 2-3 dB below 4 kHz. Mean LTAS calculated for an Leq of 70 dB for each subject showed considerable individual variation for both males and females, SD of the level varying between 7 dB and 4 dB depending on frequency. On the other hand, the results also suggest that meaningful comparisons of LTAS, recorded for example before and after voice therapy, can be made, provided that the documentation includes a set of recordings at different loudness levels from one recording session.


Parvalbumin and calbindin D-28 k immunoreactivity in dorsal root ganglia in acquired immunodeficiency syndrome.
Various degrees of neuronal degeneration have been found in lumbosacral dorsal root ganglia of patients with acquired immunodeficiency syndrome (AIDS). To characterize the subpopulations of primary sensory neurons affected in AIDS, we immunostained dorsal root ganglion tissues from 11 AIDS patients and six controls using antibodies to the calcium binding proteins, parvalbumin and calbindin D-28 k. In controls, the proportion of neurons containing parvalbumin and calbindin was 18.0% and 22.4%, respectively. The majority of parvalbumin-positive neurons, which are thought to be proprioceptive neurons, were of medium to large size, while calbindin was found in both large- and small-sized neurons. The density of parvalbumin-immunoreactive neurons was reduced by 7.3% in AIDS patients, but the density of calbindin-immunoreactive neurons was preserved. Furthermore, in AIDS cases, the number of parvalbumin-positive neurons was reduced more in dorsal root ganglia in which human immunodeficiency virus (HIV) antigen was detected than in HIV-negative ganglia. These results suggest that specific subpopulations of sensory neurons positive for parvalbumin may be differentially affected over the course of AIDS, and that this could be related to peripheral neuropathy which frequently occurs in the late stages of AIDS.


Screening and monitoring in men prescribed testosterone therapy in the U.S., 2001-2010.
The Endocrine Society recommends testosterone therapy only in men with low serum testosterone levels, consistent symptoms of hypogonadism, and no signs of prostate cancer. We assessed screening and monitoring patterns in men receiving testosterone therapy in the U.S. We conducted a retrospective cohort study of 61,474 men aged ≥40 years, and with data available in one of the nation's largest commercial insurance databases, who received at least one prescription for testosterone therapy from 2001 to 2010. In the 12 months before initiating treatment, 73.4% of male testosterone users received a serum testosterone test and 60.7% received a prostate-specific antigen (PSA) test. Among men who were tested, 19.5% did not meet Endocrine Society guidelines for low testosterone. In the 12 months after initiating treatment, 52.4% received a serum testosterone test and 43.3% received a PSA test. Multivariable analyses showed that those seen by either an endocrinologist or urologist were more likely to receive appropriate tests. A substantial number of men prescribed testosterone therapy did not receive testosterone or PSA testing before or after initiating treatment. In addition, almost one out of five treated men had baseline serum testosterone values above the threshold defined as normal by the Endocrine Society. Men treated by endocrinologists and urologists were more likely to have been treated according to guideline recommendations than men treated by other specialties, including primary care.


Ultrastructural localization of anaplasmal antigens (Pawhuska isolate) with ferritin-conjugated antibody.
Antibodies from a cow with an experimentally induced infection of the Pawhuska isolate of bovine anaplasmosis were conjugated with ferritin and used to label antigenic sites in preparations of parasitized erythrocytes. Intact erythrocytes did not label on the extracellular surface. Ferritin-conjugated antibody did not pass through the intact erythrocyte to label the parasite, probably due to the large molecular size of the antibody. Damage to erythrocytic plasmalemma and inclusion body in the hemolyzed erythrocytes and complement-fixation antigen allowed labeling of anaplasmal inclusion structures. The positively labeled structures were outer surface of the pellicle, chromatin of the initial body, and inclusion appendage. Unlabeled structures included inner organismic membrane of the initial body, inclusion membrane, fibrillar protoplasmic network of the initial body, and small electron-dense bodies derived from the initial body.


Autoantibody profiles in systemic sclerosis: predictive value for clinical evaluation and prognosis.
Systemic sclerosis (SSc) is thought to be an autoimmune disease, as autoantibodies against a variety of extractable nuclear antigens can be detected in patient sera. Subgrouping patients based on the type of autoantibodies present can be useful in diagnosis and management. Anti-centromere antibodies (ACA) and anti-topoisomerase I antibodies (anti-topo I) are the classic autoantibodies associated with SSc. ACA are associated with limited cutaneous involvement and isolated pulmonary hypertension, whereas anti-topo I are associated with diffuse skin involvement and pulmonary fibrosis. ACA are predictors for a favorable prognosis, while anti-topo I are correlated with a poor prognosis and SSc-related mortality. Additionally, anti-RNA polymerase antibodies (anti-RNAP) are associated with diffuse cutaneous disease and renal involvement. Anti-nucleolar antibodies define multiple subgroups of patients with SSc. Of these, anti-Th/To antibodies (anti-Th/To) and anti-PM-Scl antibodies (anti-PM-Scl) are associated with limited cutaneous SSc (lSSc), whereas anti-U3RNP antibodies (anti-U3RNP) are associated with diffuse cutaneous SSc (dSSc). In addition, anti-Th/To and anti-U3RNP can be predictors for a less favorable prognosis with a higher frequency of organ involvement, such as pulmonary fibrosis, pulmonary hypertension and renal crisis. Other autoantibodies are less frequently reported: anti-Ku antibodies, anti-U1RNP antibodies, anti-human upstream-binding factor, and anti-U11/U12 antibodies. These antibodies are generally less specific to SSc, but also define clinically distinct patient subsets. Thus, characterization of autoantibodies in SSc together with knowledge of disease characteristics intrinsic to distinct patient populations is helpful for assessing the clinical presentation and prognosis of this disease, and for monitoring patients with SSc.


Glyphosate herbicide formulation: a potentially lethal ingestion.
Glyphosate surfactant herbicide (GlySH) toxicity is an uncommon poisoning. We report two fatalities involving suicidal ingestion of this herbicide. Both deaths occurred despite early recognition of the serious nature of the poisoning and aggressive treatment. The deaths in this series are analysed in the context of a review of existing literature. Although traditionally regarded as minimally toxic, many deaths have been reported following suicidal ingestion. Severe GlySH toxicity may be refractory even to the most intensive supportive care. The triad of pulmonary oedema, metabolic acidosis and hyperkalaemia portends poor outcome. While containing a carbon phosphorus moiety, GlySH does not exhibit organophosphate toxicity. A clinical guide to assessing severity of GlySH toxicity is proposed and treatment modalities discussed.


Techno-economic and life cycle assessment of agrivoltaic system (AVS) designs.
Land use competition between agricultural activities and ground-mounted solar photovoltaic (PV) deployment has increased worldwide attention to hybrid agriculture, and PV systems known as agrivoltaic systems (AVS) in efforts to increase the efficiency of energy and food production and minimize the land use competition. However, little is known about AVS's economic feasibility and environmental tradeoffs. Here we aim to evaluate the techno-economic and environmental impacts of four AVS configurations (full density, half density, mono-axial tracking, and bi-axial tracking) and compare their performance against PV-only systems. We used the life cycle revenue generated from a hectare of land area ($/ha) as a functional unit of our analysis. We found that all AVS configurations outperformed PV-only systems in the economic feasibility assessment, where bi-axial tracking was the best-performing AVS. Further, we developed a case scenario for agricultural farmers to determine the minimum selling price of electricity required for AVS to compete with the economic performance of crop-only farms. We found that the AVS designs require additional incentives (2¢ - 6¢ per kWh of electricity generation) to be as competitive as the crop-only farms. The life cycle environmental assessment demonstrated that the AVS has better environmental performance than PV-only systems, with ~15-55 % less environmental impacts per functional unit. On average, electricity generation accounts for ~80 % of AVS environmental impacts, while food production and water demand account for ~20 %. Additionally, a sensitivity analysis conducted on various uncertain parameters, such as crop yield, water demand, electricity selling price, crop selling prices, discount, and inflation rates, while varying these parameters across broader ranges, indicates that AVS designs become a more economically and environmentally sustainable alternative over PV-only systems in the majority (>66 %) of the data analyzed.


The impact of teacher responsivity education on preschoolers' language and literacy skills.
This study examined the extent to which teacher responsivity education affected preschoolers' language and literacy development over an academic year. Additional aims were to determine whether children's initial language abilities and teachers' use of responsivity strategies were associated with language outcomes, in particular. In this randomized controlled trial, preschool centers were assigned to a responsivity education intervention (n = 19 centers, 25 teachers, and 174 children) or a "business-as-usual" control condition (n = 19 centers, 24 teachers, and 156 children). Teachers within the intervention centers received training focused on a set of strategies designed to promote children's engagement and participation in extended conversational interactions across the school day. Hierarchical linear models showed no main effects on children's language skills, although moderating effects were observed such that the intervention appeared to have positive effects for children with relatively high initial language abilities. In addition, teacher use of responsivity strategies was positively associated with vocabulary development. With regard to children's literacy skills, there was a significant main effect of the intervention on print-concept knowledge. Although teacher responsivity education is viewed as benefitting children's language and literacy development, the impacts of this type of intervention on children's skills warrant further investigation.


Prolonged persistence of IgM against dengue virus detected by commonly used commercial assays.
Initial symptoms of dengue fever are non-specific, and thus definite diagnosis requires laboratory confirmation. Detection of IgM against dengue virus (DENV) has become widely used for dengue diagnosis. Understanding the persistence of anti-DENV IgM in subjects after acute infection is essential in order to interpret test results correctly. Although the longevity of anti-DENV IgM has been vehemently investigated in symptomatic children, anti-DENV IgM persistence in adults and in asymptomatically infected people have seldom been reported. We prospectively investigated 44 adults with detectable anti-DENV IgM in a serosurvey conducted in the 2015 dengue epidemic in Tainan, Taiwan. Among subjects within the cohort, 17 were classified to be symptomatic and 27 were asymptomatic. The enzyme-linked immunosorbent assay (ELISA) from Standard Diagnostic (SD) and Focus Diagnostic were used to detect anti-DENV IgM for specimens collected initially, at 6 and 12 months. Regression analyses were used to estimate the duration of anti-DENV IgM fell below the detectable level. Rapid dengue tests from Standard Diagnostics had been widely adopted to detect anti-DENV IgM in Taiwan during the 2015 dengue outbreak. As such, collected specimens were also evaluated with the SD rapid dengue test in parallel. Anti-DENV IgM was detectable in 70.5 and 46.2% of the 44 subjects at 6 months and 12 months by the SD ELISA, respectively, while 13.6 and 7.7%, respectively, by the Focus ELISA. There was no significant difference in anti-DENV IgM detection for the follow-up specimens between subjects with symptomatic and asymptomatic infections. The regression analysis estimated that anti-DENV IgM persistence fell to the undetectable level at 338.3 days (95% CI 279.7-446.9) by SD ELISA, while at 175.7 days (95% CI 121.9-221.1) by Focus ELISA. The detectable frequency of anti-DENV IgM by rapid tests was 86.4%, 68.2 and 35.9% at initial, 6 and 12 months, respectively. Anti-DENV IgM was found to persist much longer than previously thought, suggesting a necessity of re-evaluation of the use of anti-DENV IgM for both the diagnosis of dengue and serological surveillance, especially when large outbreaks have occurred in the preceding year.


Joint study of extracranial arterial occlusion. IX. Transient ischemic attacks in the carotid territory.
This prospective analysis of 79 patients with transient carotid ischemic attacks (TIAs) showed that only 15% of them subsequently had strokes causing serious disability or death. They were followed up from one to nine years. All had arteriography during initial evaluation. Most of the patients who suffered strokes had at least one additional risk factor for stroke, such as hypertension or a cardiac problem. Today it is probably impossible to collect data on the natural history of untreated TIAs, inasmuch as virtually all patients are receiving either specific medical or surgical therapy.


A Single Bout of Ultra-Endurance Exercise Reveals Early Signs of Muscle Aging in Master Athletes.
Middle-aged and master endurance athletes exhibit similar physical performance and long-term muscle adaptation to aerobic exercise. Nevertheless, we hypothesized that the short-term plasticity of the skeletal muscle might be distinctly altered for master athletes when they are challenged by a single bout of prolonged moderate-intensity exercise. Six middle-aged (37Y) and five older (50Y) master highly-trained athletes performed a 24-h treadmill run (24TR). Vastus lateralis muscle biopsies were collected before and after the run and assessed for proteomics, fiber morphometry, intramyocellular lipid droplets (LD), mitochondrial oxidative activity, extracellular matrix (ECM), and micro-vascularisation. Before 24TR, muscle fiber type morphometry, intramyocellular LD, oxidative activity, ECM and micro-vascularisation were similar between master and middle-aged runners. For 37Y runners, 24TR was associated with ECM thickening, increased capillary-to-fiber interface, and an 89% depletion of LD in type-I fibers. In contrast, for 50Y runners, 24TR did not alter ECM and capillarization and poorly depleted LDs. Moreover, an impaired succinate dehydrogenase activity and functional class scoring of proteomes suggested reduced oxidative phosphorylation post-24TR exclusively in 50Y muscle. Collectively, our data support that middle-aged and master endurance athletes exhibit distinct transient plasticity in response to a single bout of ultra-endurance exercise, which may constitute early signs of muscle aging for master athletes.


Social and personal resources and the prevalence of phobic disorder in a community population.
Phobic disorder is one of the most prevalent psychiatric disorders in community populations and much attention has focused on the association of sociodemographic factors and social resources with the disorder. There has been little investigation of the more personal resources such as self-confidence, religiosity, social support and self-perceived health that may increase vulnerability. We used a sample of 2914 community residents aged 18 or older who participated in the Duke University Epidemiologic Catchment Area Study to explore the relationship between both social and personal resources and the prevalence of DIS/DSM-III phobic disorder. The 1-month prevalence of any phobic disorder was 7.6%. In bivariate analyses, we found both race/ethnicity and gender differences in prevalence, with a higher prevalence of phobic disorder in African-Americans and females. Lower socio-economic status, rural residence and unmarried status were also associated with current prevalence. No association was found for social network and social interaction. Impaired subjective social support, low self-confidence, perceived poorer physical health and co-morbid psychiatric disorder were significantly associated with current prevalence in uncontrolled analyses, while associations between lack of a confidant as well as religiosity and phobic disorder were not. Female gender (OR = 1.7), perceived low self-confidence (OR = 2.0), and two interaction terms, age x co-morbid psychiatric disorder and race/ethnicity x perceived physical health were associated with phobic disorder in controlled analyses using logistic regression. We conclude that both social and personal resources, particularly self-confidence, co-morbidity and perceived physical health are important correlates of phobic disorder.


Tricyclic pyrazoles. Part 6. Benzofuro[3,2-c]pyrazole: a versatile architecture for CB2 selective ligands.
A new series of 1H-benzofuro[3,2-c]pyrazole-3-carboxamides was synthesized. The novel compounds (15-24) were evaluated for their affinity to CB2 and CB1 cannabinoid receptors. The synthesis of the title compounds takes advantage of the acid-catalysed thermal cyclization of bicyclic hydrazone ethyl 2-(2-(2,4-dichlorophenyl)hydrazono)-2-(6-methyl-3-oxo-2,3-dihydrobenzofuran-2-yl)acetate to tricyclic ethyl 1-(2,4-dichlorophenyl)-6-methyl-1H-benzofuro[3,2-c]pyrazol-3-carboxylate. All the obtained derivatives showed high affinity to CB2 receptors. Moreover, significant selectivity for CB2 over CB1 receptors was highlighted for lead derivatives amongst the novel series. The best binding profiles were determined for homologues bearing monocyclic and bicyclic monoterpenic substituents at the carbamoyl group at 3 position of the pyrazole ring (KiCB2 < 4 nM). In particular, the isopinocampheyl-substituted derivative 22 exhibited the highest selectivity for CB2 receptors with Ki values of 3.7 and 2398 nM for CB2 and CB1 receptors, respectively. Preliminary functional assays evidenced CB2 agonism behaviour for all the assayed novel derivatives.