A Rare Case of Waldenstrom Macroglobulinemia of the Rectosigmoid Colon.
Waldenstrom macroglobulinemia is an uncommon mature B-cell lymphoma characterized by monoclonal immunoglobulin M protein in peripheral blood and lymphoplasmacytic cells in bone marrow and/or extramedullary sites. The gastrointestinal tract is a rare site of involvement. The diagnosis is based on clinicopathologic findings, although somatic mutations, such as MYD88, can aid in the diagnosis. We present a patient with irregular stools diagnosed with Waldenstrom macroglobulinemia involving the rectosigmoid colon by histopathology and immunohistochemistry on colonic biopsies, immunoglobulin M protein in serum, clonal plasma cells in bone marrow, and MYD88 mutation in colonic and bone marrow specimens.


Autonomy through androgyny.
The perception of contemporary nursing as being subordinate and subservient to medicine can be compared to the role of chloroform, which in its day served the purpose intended. However, like nursing, today's anesthetic agents require greater expertise to maximize their effectiveness. As nursing enters a new era in its struggle for autonomy, androgynous approaches promise increased independent thinking, action and self-esteem. Nurses possessing these qualities can address effectively, many of the challenges today's nursing practice poses.


Communicating about clinical quality with boards.
Health system and hospital boards around the country are turning their attention to their institutions' clinical performance and demanding the details on everything from surgical outcomes to cesarean rates. Administrators and quality managers, in turn, are faced with the challenge of presenting the right information succinctly and demonstrating improvement.


Complications of HIV disease and antiretroviral therapy.
Continued progress in the diagnosis, management, and prevention of complications of HIV disease and antiretroviral therapy were reported at the 16th Conference on Retroviruses and Opportunistic Infections. This year's conference brought new data on the optimal management of antiretroviral therapy in the presence of different opportunistic infections and included a number of important studies on pathogenesis and epidemiology of long-term complications. Major areas in which new information was presented are highlighted in this article.


[The prognosis of segmental type of primary sclerosing cholangitis--a prognostic study of the cases].
Our review of the cases of segmental primary sclerosing cholangitis (PSC) in Japanese literature has found nineteen cases, of which our own case in 1976 has been in good health for fifteen years and three months after resection. The prognostic study was possible in sixteen cases. In twelve cases the lesions were resected. Ten of twelve are found in good health, the average length of survival being nine years and one month. There are two cases of death and the causes are unknown. The unresected cases (4 out of 16) are all dead. It is concluded that the prognosis of segmental PSC is good if the lesion is resected.


Scientific production in cancer rehabilitation grows higher: a bibliometric analysis.
The aim of the study was to evaluate scientific production in the field of cancer rehabilitation comparing publication trends and impact factor (IF) among countries. The PubMed database was searched. Publications numbers and IF were evaluated both as absolute values and after standardization by population and gross domestic product (GDP). A dedicated software was developed to create a relational database containing all information about considered publications (Research Management System). Some 1,743 publications were retrieved from 1967 to 2008. Cancer rehabilitation publications have grown 11.6 times, while the whole field of disease rehabilitation has grown 7.8 times. Breast neoplasms, squamous cell carcinoma, treatment outcome, endosseous dental implantation, follow-up studies, and surgical flaps were the most commonly used keywords. From 1994 to 2008, 946 citations were retrieved: 36.8% came from the European Union (EU) (Germany, the UK, and the Netherlands ranking at the top) and 36.9% from the USA. The highest mean IF was reported for the USA (3.384) followed by Canada (3.265) and Australia (2.643). The EU has a mean IF of 0.839 with the Netherlands ranking first. Canada, Australia, and the USA had the best ratio between IF (sum) and resident population or GDP. Cancer rehabilitation is an expanding area with a growing scientific production. The rapidly ageing population, the higher number of cancer survivors, and the increasing need of resources for the after treatment of cancer patients contribute to explain the interest for this field.


Patient Protection and Affordable Care Act; program integrity: exchange, premium stabilization programs, and market standards; amendments to the HHS notice of benefit and payment parameters for 2014. Final rule.
This final rule implements provisions of the Patient Protection and Affordable Care Act and the Health Care and Education Reconciliation Act of 2010 (collectively referred to as the Affordable Care Act). Specifically, this final rule outlines financial integrity and oversight standards with respect to Affordable Insurance Exchanges, qualified health plan (QHP) issuers in Federally-facilitated Exchanges (FFEs), and States with regard to the operation of risk adjustment and reinsurance programs. It also establishes additional standards for special enrollment periods, survey vendors that may conduct enrollee satisfaction surveys on behalf of QHP issuers, and issuer participation in an FFE, and makes certain amendments to definitions and standards related to the market reform rules. These standards, which include financial integrity provisions and protections against fraud and abuse, are consistent with Title I of the Affordable Care Act. This final rule also amends and adopts as final interim provisions set forth in the Amendments to the HHS Notice of Benefit and Payment Parameters for 2014 interim final rule, published in the Federal Register on March 11, 2013, related to risk corridors and cost-sharing reduction reconciliation.


Using human microarrays to identify differentially expressed genes associated with increased steroidogenesis in boars.
Human microarrays are readily available, and it would be advantageous if they could be used to study gene expression in other species, such as pigs. The objectives of this research were to validate the use of human microarrays in the analysis of porcine gene expression, to assess the variability of the data generated, and to compare gene expression in boars with different levels of steroidogenesis. Cytochrome b5 (CYB5) expression was used to assess array detection sensitivity. Samples having high or low CYB5 RNA levels were hybridized to microarrays to determine if the known expression difference could be detected. Six hybridizations were conducted using human microarrays containing 3840 total spots representing 1718 characterized human ESTs. To analyze gene expression in boars with different levels of steroidogenesis, testis RNA from four boars with high levels of plasma estrone sulphate was hybridized to testis RNA from four boars with lower levels. Eight microarray hybridizations were conducted including fluor-flips. Self-self hybridizations were also conducted to assess the variability of array experiments. The Cy5 and Cy3 intensity values for each array were normalized using a locally weighted linear regression (LOESS). Statistical significance was assessed using a Student's t-test followed by the Benjamini and Hochberg multiple testing correction procedure. Quantitative real-time PCR (Q-RT-PCR) was used to verify select gene expression differences. The results show that CYB5 was significantly overexpressed in the high CYB5 sample by 1.8 fold (P < 0.05), verifying the known expression difference. The average log2 ratio of the majority of genes (1643) falls within one standard deviation of the mean, indicating the data were reproducible. In the high versus low steroidogenesis experiment, seven genes were significantly overexpressed in the high group (P < 0.05). Quantitative real-time PCR was used to validate five genes with the highest fold change, and the results corroborated those found by the microarray experiments. The results of the self-self hybridizations showed that no genes were significantly differentially expressed following the application of the Benjamini and Hochberg multiple testing correction procedure. The results presented in this report show that human arrays can be used for gene expression analysis in pigs.


Cancer preventive effects of whole cell type immunization against mice Ehrlich tumors.
Effects of whole cell type immunization on mice Ehrlich tumours were evaluated. After preliminary study, mice were divided two major groups; 1 x 1000 and 100 x 1000 live Ehrlich cell transferred major groups, each divided into four subgroups (n: 10). Study groups were immunized with Ehrlich cell lysates in 0, 3, 7, 14th days and after 30 days of last immunization, live Ehrlich cells were transferred. Mice were observed for six months and evaluated for total and cancer free days. Out of 100 x 1000 cell transferred solid type study group, all study group mean and tumour free periods were statistically longer than control groups. All 1 x 1000 Ehrlich cell transferred study groups survived significantly longer than 100 x 1000 Ehrlich cell transferred groups. Ehrlich mice tumours were prevented and survival prolonged with whole cell type immunization. Effects are related to the number of transferred tumor cells.


Alcohol reduces the activity of somatostatin interneurons in the mouse prefrontal cortex: A neural basis for its disinhibitory effect?
The prefrontal cortex (PFC) is involved in executive ("top-down") control of behavior and its function is especially susceptible to the effects of alcohol, leading to behavioral disinhibition that is associated with alterations in decision making, response inhibition, social anxiety and working memory. The circuitry of the PFC involves a complex interplay between pyramidal neurons (PNs) and several subclasses of inhibitory interneurons (INs), including somatostatin (SST)-expressing INs. Using in vivo calcium imaging, we showed that alcohol dose-dependently altered network activity in layers 2/3 of the prelimbic subregion of the mouse PFC. Low doses of alcohol (1 g/kg, intraperitoneal, i.p.) caused moderate activation of SST INs and weak inhibition of PNs. At moderate to high doses, alcohol (2-3 g/kg) strongly inhibited the activity of SST INs in vivo, and this effect may result in disinhibition, as the activity of a subpopulation of PNs was simultaneously enhanced. In contrast, recordings in brain slices using ex vivo electrophysiology revealed no direct effect of alcohol on the excitability of either SST INs or PNs over a range of concentrations (20 and 50 mM) consistent with the blood alcohol levels reached in the in vivo experiments. This dose-dependent effect of alcohol on SST INs in vivo may reveal a neural basis for the disinhibitory effect of alcohol in the PFC mediated by other neurons within or external to the PFC circuitry.


Monoaminergic Modulation of Motor Cortex Function.
Elaboration of appropriate responses to behavioral situations rests on the ability of selecting appropriate motor outcomes in accordance to specific environmental inputs. To this end, the primary motor cortex (M1) is a key structure for the control of voluntary movements and motor skills learning. Subcortical loops regulate the activity of the motor cortex and thus contribute to the selection of appropriate motor plans. Monoamines are key mediators of arousal, attention and motivation. Their firing pattern enables a direct encoding of different states thus promoting or repressing the selection of actions adapted to the behavioral context. Monoaminergic modulation of motor systems has been extensively studied in subcortical circuits. Despite evidence of converging projections of multiple neurotransmitters systems in the motor cortex pointing to a direct modulation of local circuits, their contribution to the execution and learning of motor skills is still poorly understood. Monoaminergic dysregulation leads to impaired plasticity and motor function in several neurological and psychiatric conditions, thus it is critical to better understand how monoamines modulate neural activity in the motor cortex. This review aims to provide an update of our current understanding on the monoaminergic modulation of the motor cortex with an emphasis on motor skill learning and execution under physiological conditions.


Palmitoyl protein thioesterase 1 is targeted to the axons in neurons.
Palmitoyl protein thioesterase 1 (PPT1) is a depalmitoylating enzyme whose deficiency leads to infantile neuronal ceroid lipofuscinosis. The disease is characterized by early loss of vision and massive neuronal death. Although PPT1 is expressed in many tissues, a deficiency of PPT1 damages neurons only in the cerebral and cerebellar cortexes and retina; other cell types remain relatively unaffected. We previously demonstrated that PPT1 is present in the synaptosomes and synaptic vesicles of neurons. To understand the crucial role of PPT1 for neuronal cells, we further investigated the expression and targeting of PPT1 in retinal, hippocampal, and cortical neurons during their maturation in culture. We found that PPT1 activity increases by neuronal maturation and is highest in retinal neuron cultures. In retinal neurons the expression of PPT1 precedes that of the synaptic vesicle protein 2 and synaptophysin, indicating a significant role for PPT1 in the early development of neuronal cells. We also found by quantitative confocal immunofluorescence microscopy that PPT1 is targeted preferably to axons in mature neurons, as indicated by its colocalization with the axonal marker microtubule-associated protein 1. In axons PPT1 is targeted specifically to axonal varicosities and presynaptic terminals, as indicated by its significant colocalization with growth-associated protein 43 and synaptophysin. Axonal localization of PPT1 was confirmed by double labeling with synaptophysin and postembedding immunoelectron microscopy. The polarized axonal targeting of PPT1 may well indicate a role for PPT1 in the exocytotic pathway of neurons.


Logical stochastic resonance with correlated internal and external noises in a synthetic biological logic block.
Following the advent of synthetic biology, several gene networks have been engineered to emulate digital devices, with the ability to program cells for different applications. In this work, we adapt the concept of logical stochastic resonance to a synthetic gene network derived from a bacteriophage λ. The intriguing results of this study show that it is possible to build a biological logic block that can emulate or switch from the AND to the OR gate functionalities through externally tuning the system parameters. Moreover, this behavior and the robustness of the logic gate are underpinned by the presence of an optimal amount of random fluctuations. We extend our earlier work in this field, by taking into account the effects of correlated external (additive) and internal (multiplicative or state-dependent) noise. Results obtained through analytical calculations as well as numerical simulations are presented.


[Kidney retransplantation: indications and limits].
Whether or not to consider a uremic patient for retransplantation remains a matter of debate. Donor shortage and putative poor outcomes are the main cons, improved results in the last decade and a better survival (HR 0.50) with retransplantation than dialysis stand as pros. The percentage of patients waitlisted for retransplantation or already having been retransplanted is increasing (up to 20-30%) and the absolute contraindications are limited to rare conditions (loss of previous transplant due to anti-glomerular basement antibodies in Alport's syndrome, early recurrence of GNF or hemolytic uremic syndrome). When retransplantation is considered, however, careful screening for risk factors is mandatory, whether they are related to the previous graft or to the recipient's clinical features or the donor's demographics and immunological status. In the last decade the clinical outcomes of retransplantation have significantly improved. No difference in patient survival at the fifth year has been reported between first, second and third grafts. The kidney survival at the same interval is above 70% for the second graft and 65% for the third graft. Nephrectomy of a previous graft is not necessary if not for clinical reasons. As far as the maximum number of retransplants is concerned, most transplant centers (69%) set no clear-cut limit. In conclusion, also taking into account that many patients after graft failure ask for readmission to the waiting list (75% in our experience), we think the retransplantation option should always be evaluated.


Versatility of scanning laser Doppler imaging to detect cutaneous perforators.
Several perforator-based flaps have been developed recently and, although preoperative evaluation of perforator vessels is important, the conventional method using the Doppler flowmeter is still being used. The authors tried to identify perforator vessels in the abdominal region using scanning laser Doppler imaging and then compared the results with those obtained using an ultrasonic Doppler flowmeter in 10 healthy volunteers. The scanning laser Doppler detected several perforator vessels (range, 2-5 vessels; mean, 3.1 vessels) within a 7.5 x 7.5-cm area in the abdominal region. These results suggest that scanning laser Doppler imaging is a useful tool in the identification of perforator vessels.


A New Perspective on Metabolites and Bioactive Compounds from Fungi.
Fungi play an important role in the solution to important global problems. Making use of processes and goods that are based on fungi can help promote sustainability by making the most efficient use of natural resources. Fungi stand apart from other organisms due to their extraordinary capacity to generate organic compounds. They are necessary for the psychological and physiological well-being of people worldwide. They are excellent producers of vitamins, pigments, hydrolytic enzymes, biofuels, organic acids, polysaccharides, and secondary metabolites such as antibiotics, anticancer treatments, hypocholesterolemic pharmaceuticals, and immunosuppressants. Other secondary metabolites include biofuels. In addition, polysaccharides are produced by them. We provide a condensed explanation of the significance of secondary metabolites in a variety of industries, such as the pharmaceutical industry, the food industry, the textile industry, and the transportation industry. In addition to providing a better understanding of biosynthetic regulation and the possibilities of genetic engineering, improved laboratory processes for the selection of nontoxigenic fungal strains have permitted the manufacture of larger quantities of safe commercial items. The significance of fungi in industrial settings is the topic that will be investigated in this review.


Electroconvulsive therapy for treatment of intractable seizures. Initial findings in two children.
We treated two children with intractable epilepsy with electroconvulsive therapy (ECT) for seizure control. One child showed a change in seizure pattern with treatment, which at greater intensity was also effective in stopping nonconvulsive status epilepticus. The other child showed a decrease in spontaneous seizure frequency during short-term treatment. These findings suggest a possible role for ECT in the management of intractable epilepsy in children who are not candidates for epileptic surgery.


Concomitant Therapy with Immunomodulator Enhances Infliximab Durability in Pediatric Inflammatory Bowel Disease.
Data on long-term durability of infliximab (IFX) and outcomes of concomitant therapy with immunomodulator in pediatric inflammatory bowel disease are limited. Children with inflammatory bowel disease who received IFX ± immunomodulator were retrospectively reviewed. Predictors of induction response were assessed using a binary logistic regression model and long-term outcomes evaluated by Cox proportional hazards model. Propensity score matching examined long-term efficacy of concomitant therapy in patients with Crohn's disease (CD). Among 148 patients (113 CD, 35 ulcerative colitis; median age at IFX initiation 14.09 years [interquartile range 12.16-15.65]), 91% experienced response to induction therapy; patients with CD were more likely to respond (95% versus 77%, odds ratio = 2.63, 95% confidence interval, 1.01-6.85, P = 0.048). Despite dose optimization, secondary loss of response occurred at a rate of 9.01% and 8.33% per year for patients with CD and ulcerative colitis, respectively. A Cox proportional hazards model showed that concomitant therapy >6 months significantly lowered the risk of secondary loss of response in CD (hazard ratio = 0.39, 95% confidence interval, 0.17-0.88, P = 0.025). The same trend was observed in ulcerative colitis but did not reach significance. A higher proportion of patients on IFX monotherapy stopped IFX because of loss of response or infusion reactions (55% versus 21%, P < 0.001). Propensity score analysis of patients with CD showed significantly higher steroid-free remission rates for concomitant versus monotherapy at 1 year (78% versus 54%, P = 0.020) and 2 years (68% versus 46%, P = 0.044), and durability of response (P = 0.022). These data demonstrate sustained efficacy of IFX in a cohort of pediatric patients with inflammatory bowel disease with durability of response enhanced by concomitant therapy.


Multidetector CT predictors of prosthesis-patient mismatch in transcatheter aortic valve replacement.
Prosthesis-patient mismatch (PPM) is a predictor of mortality after aortic valve replacement (AVR). We examined whether accurate 3-dimensional annular sizing with multidetector CT (MDCT) is predictive of PPM after transcatheter AVR (TAVR). One hundred twenty-eight patients underwent MDCT then TAVR. Moderate PPM was defined as an indexed effective orifice area ≤0.85 cm²/m² and severe ≤0.65 cm²/m². MDCT annular measurements (area, short and long axis) were compared with the size of the selected transcatheter heart valve (THV) to obtain (1) the difference between prosthesis size and CT-measured mean annular diameter and (2) the percentage of undersizing or oversizing (calculated as 100 × [MDCT annular area--THV nominal area]/THV nominal area). In addition, the MDCT annular area was indexed to body surface area. These measures were evaluated as potential PPM predictors. We found that 42.2% of patients had moderate PPM and 9.4% had severe PPM. Procedural characteristics and in-hospital outcomes were similar between patients with or without PPM. THV undersizing of the mean aortic annulus diameter was not predictive of PPM (odds ratio [OR], 0.84; 95% CI, 0.65-1.07; P = .16; area under the receiver-operating characteristic curve [AUC], 0.58). THV undersizing of annular area was not predictive of PPM (OR, 0.96; 95% CI, 0.80-1.16; P = .69; AUC, 0.52). Indexed MDCT annular area was, however, predictive of PPM (OR, 0.24; 95% CI, 0.10-0.59; P < .001; AUC, 0.66). PPM is frequent after TAVR. Appropriate annular oversizing does not reduce the rate or severity of PPM. Patient annulus size mismatch, identified by indexed MDCT annular area, is a significant predictor of PPM.


Effects of A1 adenosine receptor agonism using N6-cyclohexyl-2'-O-methyladenosine in patients with left ventricular dysfunction.
The role of adenosine as a neuromodulator in heart failure was studied with the use of a selective adenosine A1 receptor agonist, N6-cyclohexyl-2'-O-methyladenosine (SDZ-WAG 994). Fifty patients with heart failure symptoms and moderate left ventricular systolic dysfunction had a balloon flotation catheter inserted. Patients received placebo or a single oral dose of either 1, 2, or 5 mg SDZ-WAG 994. After baseline measurements were obtained, hemodynamic and electrophysiological recordings were repeated at 30-minute intervals for the next 4 hours, then every 6 hours for the next 24 hours. Blood samples for norepinephrine, epinephrine, aldosterone, atrial natriuretic peptide, and plasma renin activity were drawn at baseline and 2 hours after drug administration. A adenosine receptor agonism produced no important effects on systemic, right atrial, pulmonary artery, or pulmonary capillary wedge pressures; cardiac index; respiratory rate; or heart rate. The PR interval (a reflection of A1 receptor-mediated activity) increased significantly in a stepwise fashion. At the 5-mg dose of SDZ-WAG 994, significant increases in atrial natriuretic peptide (216 +/- 137 to 407 +/- 146 pg/mL) and norepinephrine (477 +/- 243 to 618 +/- 237 pg/mL) levels were noted. A1 adenosine receptor agonism with SDZ-WAG 994 resulted in no significant hemodynamic changes at rest in this subset of patients with left ventricular dysfunction. An increase in the PR interval and atrial natriuretic peptide level, consistent with adenosine A1 receptor-mediated activity, was observed. In addition, an increase in the norepinephrine level was observed, suggesting a role for adenosine as a peripheral nervous system neuromodulator.


Mass lead intoxication from informal used lead-acid battery recycling in dakar, senegal.
Between November 2007 and March 2008, 18 children died from a rapidly progressive central nervous system disease of unexplained origin in a community involved in the recycling of used lead-acid batteries (ULAB) in the suburbs of Dakar, Senegal. We investigated the cause of these deaths. Because autopsies were not possible, the investigation centered on clinical and laboratory assessments performed on 32 siblings of deceased children and 23 mothers and on 18 children and 8 adults living in the same area, complemented by environmental health investigations. All 81 individuals investigated were poisoned with lead, some of them severely. The blood lead level of the 50 children tested ranged from 39.8 to 613.9 microg/dL with a mean of 129.5 microg/dL. Seventeen children showed severe neurologic features of toxicity. Homes and soil in surrounding areas were heavily contaminated with lead (indoors, up to 14,000 mg/kg; outdoors, up to 302,000 mg/kg) as a result of informal ULAB recycling. Our investigations revealed a mass lead intoxication that occurred through inhalation and ingestion of soil and dust heavily contaminated with lead as a result of informal and unsafe ULAB recycling. Circumstantial evidence suggested that most or all of the 18 deaths were due to encephalopathy resulting from severe lead intoxication. Findings also suggest that most habitants of the contaminated area, estimated at 950, are also likely to be poisoned. This highlights the severe health risks posed by informal ULAB recycling, in particular in developing countries, and emphasizes the need to strengthen national and international efforts to address this global public health problem.


Epoprostenol therapy for primary pulmonary hypertension.
Although a rare disease, PPH is deadly. Until recently, patients had little hope for remission of this disease. Originally viewed as a "bridge to transplantation," new research findings suggest that epoprostenol significantly improves PPH so that transplantation may not be necessary. Treatment with epoprostenol is difficult to manage, however, because it requires continuous central infusion. Nurses have a key role in ensuring that patients safely and effectively manage this therapy.


Longitudinal MRI Evaluation of Ischemic Stroke in the Basal Ganglia of a Rhesus Macaque (Macaca mulatta) with Seizures.
An adult rhesus macaque developed seizures after the induction of ischemic stroke. Initially, on the day of surgery, a focal ischemic lesion was present exclusively in the right caudate nucleus. By 48 h after stroke induction, the lesion had extended into the putamen, when a seizure was observed. Our report highlights the temporal changes in infarction of unilateral basal ganglia after acute stroke and the accompanying clinical symptoms. This unusual case may provide additional information regarding the involvement of the basal ganglia in seizures, given that prior case reports and studies usually have not described the temporal and spatial evolution of the lesion before clinical symptoms emerge.


Orcokinin in the central complex of the locust Schistocerca gregaria: Identification of immunostained neurons and colocalization with other neuroactive substances.
The central complex is a group of highly interconnected neuropils in the insect brain. It is involved in the control of spatial orientation, based on external compass cues and various internal needs. The functional and neurochemical organization of the central complex has been studied in detail in the desert locust Schistocerca gregaria. In addition to classical neurotransmitters, immunocytochemistry has provided evidence for a major contribution of neuropeptides to neural signaling within the central complex. To complement these data, we have identified all orcokinin-immunoreactive neurons in the locust central complex and associated brain areas. About 50 bilateral pairs of neurons innervating all substructures of the central complex exhibit orcokinin immunoreactivity. Among these were about 20 columnar neurons, 33 bilateral pairs of tangential neurons of the central body, and seven pairs of tangential neurons of the protocerebral bridge. In silico transcript analysis suggests the presence of eight different orcokinin-A type peptides in the desert locust. Double label experiments showed that all orcokinin-immunostained tangential neurons of the lateral accessory lobe cluster were also immunoreactive for GABA and the GABA-synthesizing enzyme glutamic acid decarboxylase. Two types of tangential neurons of the upper division of the central body were, furthermore, also labeled with an antiserum against Dip-allatostatin I. No colocalization was found with serotonin immunostaining. The data provide additional insights into the neurochemical organization of the locust central complex and suggest that orcokinin-peptides of the orcokinin-A gene act as neuroactive substances at all stages of signal processing in this brain area.


Issues in esthetic dentistry for older adults.
Esthetic dentistry offers a myriad of opportunities for older adults wishing to improve their smile, oral function, and self-esteem. The challenge for dental professionals is to maintain oral health throughout the patient's lifetime, even through periods of dependence that may include residence in a nursing home. Dental professionals will have increasing opportunities to share their knowledge and expertise about the relation between oral health and overall health, with a variety of health professionals who care for the aging population.


Development of a multi-functional concurrent assay using weak cation-exchange solid-phase extraction (WCX-SPE) and reconstitution with a diluted sample aliquot for anti-doping analysis.
In addition to the development of adequate screening methods for multiple compounds, the World Anti-Doping Agency (WADA) requires anti-doping laboratories to analyze prohibited substances and their metabolites from various classes. This task presents a difficult challenge for all agencies and interests involved in the field of doping control. A screening method is reported in which hybrid sample preparation was performed using a combination of weak cation-exchange solid-phase extraction (WCX-SPE) and the 'Dilute and Shoot' strategy in order to take advantage of both the methodologies. Target substances were extracted using a WCX cartridge and reconstituted with a diluted sample aliquot that included 20% of an untreated urine sample. The target substances were further analyzed by high-performance liquid chromatography/triple quadrupole mass spectrometry (LC/MS). The SPE procedure was optimized using a cartridge-washing step, elution conditions, and elution volume. The cartridge-washing step, which was performed using 10% methanol, improved the overall recovery of target substances. Since the recovery was observed to vary according to the pH of the eluting solution, we applied an elution step using both an acid and a basic organic solvent to achieve complementary recovery. Reconstitution of the diluted aliquot sample was performed to recover the polar substances. The method was validated and applied to real samples in accordance with the external quality assessment scheme of WADA and to the previously reported samples that had provided positive test results. This novel method using hybrid sample preparation and LC/MS could be useful to screen multiple classes of the 264 targeted substances in anti-doping analysis.


Interferon-gamma inhibition of human thyrotropin receptor gene expression.
To evaluate the role of interferon-gamma (IFN gamma) on human thyroid-specific gene expression, the effect of IFN gamma on TSH- and cAMP-induced TSH receptor gene expression was studied using cultured thyroid cells obtained from normal thyroid glands and those from patients with Graves' disease. Incubation of Graves' thyroid cells with 1.0 U/L bovine TSH or 1.0 mM 8-bromo-cAMP resulted in a 2-fold increase in TSH receptor mRNA expression, which was markedly inhibited in the presence of IFN gamma in a dose- and time-dependent manner. This inhibitory effect was completely neutralized by monoclonal antibody against IFN gamma. IFN alpha and -beta had no influence on TSH- and cAMP-stimulated TSH receptor mRNA expression. Paranodular normal thyroid cells showed the same results as those obtained using Graves' thyroid cells. Scatchard analysis of the [125I]TSH binding study showed that IFN gamma inhibited the number of TSH receptors up-regulated by TSH on the cell surface at the low affinity binding site (4.1 vs. 8.2 x 10(5)/cell). These results indicate that IFN gamma suppresses TSH- and cAMP stimulated human TSH receptor gene expression, resulting in a decrease in the number of TSH receptors. In conclusion, IFN gamma interacts via an intermediate pathway of TSH signal transduction and attenuates TSH receptor synthesis in normal and Graves' thyroid cells.


Creating accountable hospital service areas in China: a case analysis of health expenditure in the metropolis of Chengdu.
To delineate hospital service areas (HSAs) using the Dartmouth approach in China and identify the hypothesised demand-side, supply-side and region-specific factors of health expenditure within HSAs. Population-based descriptive study. We selected the metropolis of Chengdu, one of the three most populous cities in China as a case for the analysis, where approximately 16.33 million residents living. Individual-level in-patient discharge records (n=904 298) during the fourth quarter of 2018 (from 1 September to 31 December) were extracted from Sichuan Health Commission. Cases of non-residents of Chengdu were excluded from the datasets. We conducted three sets of analyses: (1) apply Dartmouth approach to delineate HSAs; (2) use Geographic Information System (GIS)-based method to demonstrate health expenditure variations across delineated HSAs and (3) employ a three-level multilevel linear model to examine the association between health expenditure and demand-side, supply-side and region-specific factors. A total of 113 HSAs with a median population of 60 472 (ranging from 7022 to 827 750) was delineated. Total in-patient expenditure per admission varied more than threefold across HSAs after adjusting for age and gender. Apart from a list of demand-side factors, an increased number of physicians, healthcare facilities at higher levels and for-profit healthcare facilities were significantly associated with increased total in-patient expenditures. At the HSA level, the proportion of private healthcare facilities located in a single HSA was associated with increased total in-patient expenditure generated by that HSA, while the increased number of healthcare facilities in a HSA was negatively associated with the total in-patient expenditures. HSAs were delineated to help establish an accountable healthcare delivery system, which serves as local hospital markets to provide in-patient healthcare via connecting demanders with suppliers inside particular HSAs. Policy-makers should adopt HSAs to identify variations of total in-patient expenditures among different areas and the potential associated factors. Findings from the HSA-based analysis could inform the formulation of relevant health policies and the optimisation of healthcare resource allocations.


Analysis of luminol-dependent chemiluminescence from granule depleted neutrophil cytoplasts reveals two different light-emitting mechanisms.
When neutrophil cytoplasts (granule-free vesicles of cytoplasm enclosed by plasmalemma) were exposed to the chemotactic peptide formylmethionyl-leucyl-phenylalanine, no luminol-dependent chemiluminescence was detected, despite a pronounced production of superoxide anions and hydrogen peroxide. Addition of purified myeloperoxidase (MPO) or human serum albumin (HSA) to the cytoplasts before the stimulus resulted in a chemiluminescence response. In contrast to the bimodal response obtained from normal PMNL, only a single peak of chemiluminescence was obtained from the cytoplasts responding to the peptide. The time-course of the response obtained in the presence of albumin was more prolonged than the response obtained in the presence of MPO. Furthermore, the involvement of different oxidative metabolites in the MPO and the HSA systems, respectively, was demonstrated by the accumulated chemiluminescence effect obtained when MPO, but not HSA, was introduced in the measuring system after FMLP addition. From these results it can be concluded that there are at least two different light-generating mechanisms in FMLP-induced luminol-dependent chemiluminescence of neutrophil cytoplasts. One of these is dependent on myeloperoxidase and possibly related to the myeloperoxidase-hydrogen peroxide reaction, whereas the other one is hydrogen peroxide independent.


Recovery from aphasia: a longitudinal study on language recovery, lateralization patterns, and attentional resources.
Despite the large body of evidence on the neural basis of the recovery from aphasia, the role of either cerebral hemisphere remains controversial. This paper reports the results of a longitudinal single-case study on the patterns of lateralization for lexical semantic processing during the recovery from aphasia. The experimental protocol included a lateralized lexical decision task (LDT), an attentional task and a language test. There was no presentation site effect on the LDT, and the performance was jointly influences by attentional and language factors. These findings suggest that the recovery of lexical semantic processing may be sustained by both cerebral hemispheres, and highlights the importance of experimental protocols that allow examining both language and attentional factors modulating factors modulating the recovery from aphasia.


Vitamin D receptor is a novel transcriptional regulator for Axin1.
Axin1 is a scaffold protein in the β-catenin destruction complex, which, if disrupted, contributes to pathogenesis of various human diseases, including colorectal carcinogenesis and inflammatory bowel diseases (IBD). We have previously demonstrated that Salmonella infection promotes the degradation and plasma sequestration of Axin1, leading to bacterial invasiveness and inflammatory responses. Vitamin D and the vitamin D receptor (VDR) appear to be important regulators of IBD and colon cancer. Although VDR and Axin1 are all involved in intestinal inflammation, it remains unclear whether these processes are related or function independently. In the current study, we hypothesize that VDR is an important regulator for the maintenance of physiological level of Axin1. Using the intestinal epithelial conditional VDR knockout mouse model (VDRΔIEC) and cultured cell lines, influences of VDR status on the expression of Axin1 was evaluated by Western blots and real-time PCR. Loss- and gain-of-function assays were used to investigate the regulation of VDR on Axin1 at the transcriptional and translational levels. Cells were treated with cycloheximide or actinomycin for molecular mechanistic studies. Candidate genomic VDR binding sites for Axin1 were tested by chromatin immunoprecipitation (ChIP) assay. Physical interactions among VDR, Axin1, and β-catenin were tested by immunoprecipitation. Cellular localization of Axin1 with different VDR status was determined by fractionation and immunohistochemistry. We found that VDR deletion led to lower protein and mRNA levels of Axin1, whereas knockdown of Axin1 did not change the expression level of VDR protein. Immunoprecipitation data did not support physical interaction between VDR and Axin1. The VDR regulation of Axin1 was through a VDR genomic binding site for Axin1 gene on the regulatory region. Fractionation data showed that cytosolic Axin1 was significantly reduced due to VDR deletion, leaving the nuclear fraction unchanged. In ileum, Axin1 was distributed in the cytosol of apical epithelium and crypts. VDR is important for the maintenance of physiological level of Axin1. The discovery of Axin1 as a VDR target gene provides novel and fundamental insights into the interactions between the VDR and β-catenin signaling pathways.


Computer simulation of apolar bent-core and rodlike molecules.
Bent-core molecules have received much interest due to their biaxiality and novel phase ordering. It is, therefore, of interest to model the characteristic shape of these molecules and observe the effect on liquid crystal mesophase formation in a computer simulation study. A simple model of the interaction employed a two-site Gay-Berne potential with the sites separated by +/-0.5 reduced units for all models. The angle between the two sites, 180 degrees -gamma, was varied from gamma=0 degrees to gamma=70 degrees and influenced the phase behavior markedly. The rodlike model formed isotropic, nematic, smectic-A, and smectic-B, phases. Results for the bent-core models show that as the angle gamma increases the transition temperature to the ordered phase decreases. As gamma increases the nematic phase is first destabilized then stabilized with respect to the smectic phase and a tilted smectic-B phase is seen at gamma=20 degrees. For gamma=40 degrees a "TGB-like" phase is identified as the system cools whereas for gamma=70 degrees no ordered phase is formed.


Blind tests of RNA-protein binding affinity prediction.
Interactions between RNA and proteins are pervasive in biology, driving fundamental processes such as protein translation and participating in the regulation of gene expression. Modeling the energies of RNA-protein interactions is therefore critical for understanding and repurposing living systems but has been hindered by complexities unique to RNA-protein binding. Here, we bring together several advances to complete a calculation framework for RNA-protein binding affinities, including a unified free energy function for bound complexes, automated Rosetta modeling of mutations, and use of secondary structure-based energetic calculations to model unbound RNA states. The resulting Rosetta-Vienna RNP-ΔΔG method achieves root-mean-squared errors (RMSEs) of 1.3 kcal/mol on high-throughput MS2 coat protein-RNA measurements and 1.5 kcal/mol on an independent test set involving the signal recognition particle, human U1A, PUM1, and FOX-1. As a stringent test, the method achieves RMSE accuracy of 1.4 kcal/mol in blind predictions of hundreds of human PUM2-RNA relative binding affinities. Overall, these RMSE accuracies are significantly better than those attained by prior structure-based approaches applied to the same systems. Importantly, Rosetta-Vienna RNP-ΔΔG establishes a framework for further improvements in modeling RNA-protein binding that can be tested by prospective high-throughput measurements on new systems.


Access to dihydropyrano[3,2-b]pyrrol-5-ones skeletons by N-heterocyclic carbene-catalyzed [3+3] annulations.
A novel and efficient NHC-catalyzed [3+3] annulation of enals with pyrrol-4-ones was developed, thus providing the dihydropyrano[3,2-b]pyrrol-5-one core structures with broad scope and good to excellent enantioselectivities. Notably, this strategy could also expand to the synthesis of axially chiral compounds and polysubstituted indoles.


Effects of ischemia and reperfusion on production of nitrotyrosine, activation of eosinophils, and apoptosis in the large colonic mucosa of horses.
To assess the effects of ischemia and reperfusion on indicators of oxidative stress, activation of eosinophils, and apoptosis in the large colonic mucosa of horses. 40 horses. In 1 or two 20-cm-long segments of the pelvic flexure, ischemia was induced for 1 or 2 hours followed by no reperfusion or 30 minutes and 18 hours of reperfusion in anesthetized horses. Mucosal specimens were collected before (controls; n = 20 horses) and after each period of ischemia, and full-thickness tissue samples were collected after each period of reperfusion. Sections of colonic tissues were stained for histomorphometric analysis or assessment of eosinophil accumulation. Nitrotyrosine was identified immunohistochemically, and severity of apoptosis was determined via the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method. Numbers of mucosal eosinophils were similar before induction of ischemia, after ischemia, and after ischemia-reperfusion. Eosinophil nitrotyrosine production increased significantly during ischemia and continued through 30 minutes of reperfusion; production was decreased at 18 hours of reperfusion but remained greater than that of the controls. In other leukocytes, nitrotyrosine generation peaked at 1 hour of ischemia and again at 18 hours of reperfusion. Compared with control findings, epithelial apoptosis increased gradually at 1 through 2 hours of ischemia with no further progression after reperfusion. Results suggested that resident eosinophils in the large colon of horses react to mucosal injury from ischemia and reperfusion and may undergo oxidative stress under those conditions. Epithelial apoptosis could contribute to tissue damage.


Developmental Acquisition of p53 Functions.
Remarkably, the p53 transcription factor, referred to as "the guardian of the genome", is not essential for mammalian development. Moreover, efforts to identify p53-dependent developmental events have produced contradictory conclusions. Given the importance of pluripotent stem cells as models of mammalian development, and their applications in regenerative medicine and disease, resolving these conflicts is essential. Here we attempt to reconcile disparate data into justifiable conclusions predicated on reports that p53-dependent transcription is first detected in late mouse blastocysts, that p53 activity first becomes potentially lethal during gastrulation, and that apoptosis does not depend on p53. Furthermore, p53 does not regulate expression of genes required for pluripotency in embryonic stem cells (ESCs); it contributes to ESC genomic stability and differentiation. Depending on conditions, p53 accelerates initiation of apoptosis in ESCs in response to DNA damage, but cell cycle arrest as well as the rate and extent of apoptosis in ESCs are p53-independent. In embryonic fibroblasts, p53 induces cell cycle arrest to allow repair of DNA damage, and cell senescence to prevent proliferation of cells with extensive damage.


Work-related musculoskeletal complaints in massage practitioners.
Work-related musculoskeletal complaints (WMSCs) are induced or aggravated by work activities and/or work conditions. The aim was to evaluate the impact of work as a massage practitioner, with a special emphasis on WMSCs. Massage practitioners were invited to participate in the study through an advert in the rehabilitation medical clinics. The participants completed a self-administered questionnaire, collecting general data and questions about WMSCs. Thirty-seven subjects (88.09%) reported pain in at least one body part in the last 4 weeks. The most common WMSCs was pain in the neck region (69.04%), followed by pain in the shoulder region (54.76%), upper back (52.38%), lower back (40.48%), wrist-hand (33.33%) and elbow (21.43%). The massage practitioners aged between 21 and 30 years old reported significantly more frequently WMSCs localized in neck, shoulders, wrist-hand, upper back and lower back. This study shows that WMSCs are widely reported among massage practitioners. The most common complaints were reported in the neck and shoulder regions, especially in younger massage practitioners.


[Treatment of pancreatic pseudocysts].
Based on the results of treatment of a personal series of 13 cases of pseudocyst of the pancreas, between 1974 and the present day, it is suggested that the choice of therapy should be surgical. An internal shunt is preferred for pseudocysts as a result of acute pancreatitis or injury, whereas a wider cysto-wirsung jejunostomy is recommended for cysts developing during the course of chronic pancreatitis. These proposals follow analysis of immediate and long-term (mean: 51 months) follow-up, on the basis of mortality, morbidity, pain symptoms, malabsorption and postoperative diabetes.


Triceps tendon avulsion in a professional body builder. A case report.
We have reported a case of triceps tendon avulsion in a professional body builder, treated successfully by delayed repair, allowing him to return to competition. Triceps tendon ruptures, besides being rare injuries, differ from tendon ruptures in other locations. First, the injury can occur through healthy tissue. Second, the time of delay, from injury to repair, seems to have little effect on the functional outcome, as we demonstrated in our patient.


A low concentration of nitrous oxide reduces dyspnoea produced by a combination of hypercapnia and severe elastic load.
We have measured how a low concentration of nitrous oxide affected respiratory sensation and ventilation. Severe dyspnoea was induced in nine normal subjects by a combination of hypercapnia and inspiratory elastic load (50 cm H2O litre-1). Subjects were asked to rate their sensation of respiratory discomfort using a visual analogue scale (VAS) while breathing either 20% nitrous oxide or 20% nitrogen gas mixture. We compared the effects of each gas mixture on respiratory sensation and ventilation using steady-state values of ventilatory variables and VAS scores obtained before, during and after inhalation of each gas mixture. Inhalation of 20% nitrous oxide reduced the sensation of respiratory discomfort from a median VAS score of 6.5 (range 5.0-8.1) before inhalation to 3.6 (2.4-5.9) during inhalation (P < 0.05). There was no significant change in minute ventilation but tidal volume increased during inhalation of 20% nitrogen did not alter VAS scores or ventilatory variables. We found that a low concentration of nitrous oxide greatly alleviated the intensity of dyspnoea without changing respiratory load compensation.


Formation of an actin-like filament concurrent with the enzymatic synthesis of inorganic polyphosphate.
Inorganic polyphosphate (poly P), a chain of hundreds of phosphate residues linked by ATP-like bonds, is found in every cell in nature and is commonly produced from ATP by poly P kinases (e.g., PPK1). Dictyostelium discoideum, the social slime mold, possesses a PPK activity (DdPPK1) with sequence similarity to bacterial PPKs. We find here a previously unrecognized PPK (DdPPK2) in D. discoideum with the sequences and properties of actin-related proteins (Arps) that are similar to muscle actins in size, properties, and globular-filamentous structural transitions. Significantly, the unique actin inhibitors, phalloidin and DNase I, also inhibit synthesis of poly P by DdPPK2. Thus, this particular Arp complex is an enzyme that can polymerize into an actin-like filament concurrent with its synthesis of a poly P chain in a fully reversible reaction.


Prediction of Sweet Corn Seed Germination Based on Hyperspectral Image Technology and Multivariate Data Regression.
Vigor identification in sweet corn seeds is important for seed germination, crop yield, and quality. In this study, hyperspectral image (HSI) technology integrated with germination tests was applied for feature association analysis and germination performance prediction of sweet corn seeds. In this study, 89 sweet corn seeds (73 for training and the other 16 for testing) were studied and hyperspectral imaging at the spectral range of 400-1000 nm was applied as a nondestructive and accurate technique to identify seed vigor. The root length and seedling length which represent the seed vigor were measured, and principal component regression (PCR), partial least squares (PLS), and kernel principal component regression (KPCR) were used to establish the regression relationship between the hyperspectral feature of seeds and the germination results. Specifically, the relevant characteristic band associated with seed vigor based on the highest correlation coefficient (HCC) was constructed for optimal wavelength selection. The hyperspectral data features were selected by genetic algorithm (GA), successive projections algorithm (SPA), and HCC. The results indicated that the hyperspectral data features obtained based on the HCC method have better prediction results on the seedling length and root length than SPA and GA. By comparing the regression results of KPCR, PCR, and PLS, it can be concluded that the hyperspectral method can predict the root length with a correlation coefficient of 0.7805. The prediction results of different feature selection and regression algorithms for the seedling length were up to 0.6074. The results indicated that, based on hyperspectral technology, the prediction of seedling root length was better than that of seed length.


Evaluation of the formula clearance as a measure of the glomerular filtration rate in cyclosporin-treated children following renal transplantation.
Since the introduction of the nephrotoxic drug, cyclosporin, as the main immunosuppressive agent following organ transplantation, the need for an accurate method to determine the glomerular filtration rate (GFR) has arisen. In the present study the clearance of inulin has been compared to the clearance of creatinine estimated by short-term urine sampling or by the formula clearance in 29 children following renal transplantation. The children, 0.4-15.4 years of age at transplantation, were examined within 5 months following transplantation, and thereafter yearly. During the first 2 years after transplantation there was poor agreement between inulin clearance and formula clearance, while 3-4 years after transplantation there was good correlation between the two methods. However, the formula clearance generally overestimated GFR and the overestimation increased with decreasing renal function. In spite of the good correlations between the two methods after the first years following transplantation, the formula clearance in individual patients does not follow the inulin clearance changes very closely. In conclusion, formula clearance was found to be an inaccurate method of following GFR, especially during the first 2 years after transplantation. This might be caused by changes in habitus as well as an increased creatinine secretion caused by cyclosporin.


Design, synthesis and use of peptoids in the diagnosis and treatment of cancer.
Genetic variations in cancer cells are the underpinning for the development of resistance and failure of the treatment by current anticancer drugs. Thus, an ideal drug must overcome failure of treatment and prevents development of drug resistance. There are a wide variety of emerging, easy to prepare and cost effective group of drugs that are collectively called peptoids or peptidomimetics. These new set of drugs exhibit distinct features including protease resistance, are non-immunogenic, do not hinder functionality and backbone polarity, and can adopt different conformations. These drugs have shown promise as diagnostic and therapeutic tools in a wide variety of diseases. Here, we discuss the recent advancement in the design and synthesis of peptoids and use of these drugs in the diganosis and treatment of a wide number of cancers of the lung, prostate, and breast.


Congenital thrombocytopenias.
Congenital thrombocytopenias are rare bleeding disorders but must be included in the differential diagnosis when investigating a young infant with chronic thrombocytopenia. Several of these syndromes have associated defects of immune, renal, or skeletal systems in addition to thrombocytopenia. These can be categorized into two groups depending on the presence or absence of bone marrow hypoplasia. The majority of these disorders are associated with a mild bleeding tendency and thus may be missed until the affected individuals experience excessive postoperative or posttraumatic hemorrhage. In adults, this entity must be considered when evaluating a patient with thrombocytopenia who is unresponsive to the medical management of immune thrombocytopenia. Other than platelet transfusion, no specific therapy is available for these disorders. A test dose of desmopressin may be attempted in a nonbleeding patient (to see if it will shorten the bleeding time) prior to using it for treatment of a bleeding episode or surgical prophylaxis. Bone marrow transplantation may prove curative in a select group of thrombocytopenic syndromes.


Comparison of effects of two polymorphic variants of manganese superoxide dismutase on human breast MCF-7 cancer cell phenotype.
Two polymorphic variants of manganese superoxide dismutase (MnSOD), with either Ile or Thr at amino acid 58, (Ile58MnSOD or Thr58MnSOD), have been found in the human population. The MnSOD activity of these two variants and their effects on the malignant phenotype of human breast cancer MCF-7 cells were compared. It was demonstrated that MnSOD-overexpressing clones obtained from transfection of the two MnSOD cDNAs into MCF-7 cells had increased MnSOD immunoreactive protein and increased MnSOD activity. Cells overexpressing Ile58MnSOD had 3-fold higher MnSOD activity than cells overexpressing Thr58MnSOD in vivo at an equal MnSOD protein level. Tumor-suppressive effects of MnSOD-overexpressing cells were indicated by: (a) decreased plating efficiency; (b) elongated cell population doubling time; (c) lower clonogenic fraction in soft agar; and (d) complete inhibition or delayed onset of tumor formation in nude mice. When compared on the same activity basis, the suppressive effects of Ile58MnSOD were similar to those of Thr58MnSOD. However, far more Thrs58MnSOD protein was required to obtain the same amount of MnSOD activity, making the Thr58MnSOD far less effective. A dose-response suppressive effect was observed when the increase of MnSOD activity was moderate. We conclude that MnSOD is a tumor suppressor in human breast cancer, but the Thr58 form of the protein is a much less effective tumor suppressor than the Ile58 form of the protein.


Model-Based Approach for Designing an Efficient Bioequivalence Study for Highly Variable Drugs.
The statistical procedures as outlined by the European Medicines Agency (EMA) and United States Food and Drug Administration (FDA) guidelines for bioequivalence testing of highly variable drugs (HVDs) are complex. Additionally, the sample size is affected by clinical study designs or practical real-world problems, such as dropout rate or study budget. To overcome these difficulties, we propose a model-based approach for the selection of a study design with a sample size that satisfies the bioequivalence criteria using simulation studies based on a pharmacokinetic (PK) model. The designed approach was implemented using a simulation procedure considering some conventionally measured factors, such as geometric mean ratio and within-subject coefficient of variation, with various PK information important in determining bioequivalence. All simulation results were assessed according to the EMA and FDA guidelines. Furthermore, power calculations from simulation results were interpreted with regard to PK characteristics and compared among 2 × 2, 3 × 3, and 2 × 4 crossover designs to determine the efficient design considering appropriate sample size and duration of the clinical study. The proposed approach can be applied to bioequivalence studies of all drugs. However, the current study was targeted at HVDs, which are highly likely to require detailed decision making for sample size and study design.


Perceived Social Support and its Effects on Treatment Compliance and Quality of Life in Cardiac Patients.
Background: The benefits of social support are often overlooked in common management components of cardiovascular diseases. The Multidimensional Scale of Perceived Social Support (MSPSS) is self-administered and scores perceived social support (PSS). We sought to identify PSS among cardiovascular patients and the effects it may have on quality of life (QoL) and treatment compliance. Methods: A total of 96 patients were evaluated using the MSPSS in 3 categories: significant other (SO), family, and friends using a 7-point Likert scale. A supplemental lifestyle survey assessed various demographics, subjective QoL, and compliance with treatment plans. Results: Patients with high QoL reported a higher PSS Likert score in the family support category. Patients who were compliant with appointments and had high substance use avoidance (tobacco, alcohol, illicit drugs) had a higher PSS Likert score in the friend support and higher PSS Likert score in support from SO and family categories, respectively. No difference in PSS was found in compliance with medications, diet, and exercise. Conclusion: Various social support categories are directly associated with higher QoL, adherence to appointments, and substance abuse avoidance.


Population Pharmacokinetic Analysis and Dosing Optimization of Sirolimus in Children With Tuberous Sclerosis Complex.
Sirolimus is confirmed to be effective in the treatment of tuberous sclerosis complex (TSC) and related disorders. The study aims to establish a population pharmacokinetic model of oral sirolimus for children with TSC and provide an evidence-based approach for individualization of sirolimus dosing in the pediatric population. A total of 64 children were recruited in this multicenter, retrospective pharmacokinetic study. Whole-blood concentrations of sirolimus, demographic, and clinical information were collected and analyzed using a nonlinear mixed-effects population modeling method. The final model was internally and externally validated. Then Monte Carlo simulations were performed to evaluate and optimize the dosing regimens. In addition, the efficacy and safety of sirolimus therapy was assessed retrospectively in patients with epilepsy or cardiac rhabdomyomas associated with TSC. Finally, the sirolimus pharmacokinetic profile was described by a 1-compartment model with first-order absorption and elimination along with body weight and total daily dose as significant covariates. The typical population parameter estimates of apparent volume of distribution and apparent clearance were 69.48 L and 2.79 L/h, respectively. Simulations demonstrated that dosage regimens stratified by body surface area may be more appropriate for children with TSC. These findings could be used to inform individualized dosing strategies of sirolimus for pediatric patients with TSC.


Cerebral abscesses in Behcet's disease: a case report.
Behçet's disease is a multisystem relapsing inflammatory disorder of unknown cause. Neurological involvement is one of the most serious causes of long-term morbidity and mortality in Behçet's disease. Cerebral abscess is very rare in literature. A 45-yr-old man with Behçet's disease manifesting focal epileptic seizure and multiple cerebral abscesses is reported in the case. He was diagnosed with cerebral abscess and was treated with antibiotics but no improvement occurred. Excisional biopsy was performed and the lesions were consistent with abscess. The clinical state of the patient gradually improved. The patient had no further complications. The etiology, and clinical and magnetic resonance imaging findings are discussed.


Role of endothelial to mesenchymal transition in the pathogenesis of the vascular alterations in systemic sclerosis.
The pathogenesis of Systemic Sclerosis (SSc) is extremely complex, and despite extensive studies, the exact mechanisms involved are not well understood. Numerous recent studies of early events in SSc pathogenesis have suggested that unknown etiologic factors in a genetically receptive host trigger structural and functional microvascular endothelial cell abnormalities. These alterations result in the attraction, transmigration, and accumulation of immune and inflammatory cells in the perivascular tissues, which in turn induce the phenotypic conversion of endothelial cells and quiescent fibroblasts into activated myofibroblasts, a process known as endothelial to mesenchymal transition or EndoMT. The activated myofibroblasts are the effector cells responsible for the severe and frequently progressive fibrotic process and the fibroproliferative vasculopathy that are the hallmarks of SSc. Thus, according to this hypothesis the endothelial and vascular alterations, which include the phenotypic conversion of endothelial cells into activated myofibroblasts, play a crucial role in the development of the progressive fibrotic process affecting skin and multiple internal organs. The role of endothelial cell and vascular alterations, the potential contribution of endothelial to mesenchymal cell transition in the pathogenesis of the tissue fibrosis, and fibroproliferative vasculopathy in SSc will be reviewed here.


Cst, a novel mouse gene related to Drosophila Castor, exhibits dynamic expression patterns during neurogenesis and heart development.
The zinc finger transcription factor Castor plays a pivotal role during neurogenesis in the fruit fly Drosophila melanogaster. Here, we report the expression pattern of a murine Castor related gene (Cst) during embryogenesis. Cst expression is first detected at E8.0 in the developing heart where its expression is maintained throughout development. By E8.5, Cst expression starts in the lateral neural folds of the hindbrain and extends anteriorly and posteriorly to eventually cover the dorsal neural tube from the isthmus to its caudal end. From E9.5, Cst transcripts can also be detected in the dorsomedial telencephalon. In the hindbrain, Cst expression is confined to trigeminal motor neurons and to migrating facial branchiomotor neurons. In the peripheral nervous system, Cst is expressed in cranial and in dorsal root ganglia. Cst expression is also observed in the developing eye and in the nasal placode.


Relationship between Cataract Surgery and Mortality in Elderly Patients with Cataract: Nationwide Population-Based Cohort Study in South Korea.
We aimed to investigate the relationship between cataract surgery and all-cause and cause-specific mortality in Korean elderly patients with cataract using the Korean National Health Insurance Service-Senior cohort database. Elderly patients (≥60 years) diagnosed with cataract from 2002 through 2012 were included. The baseline characteristics included demographics and systemic and ocular comorbidities. Adjusted Cox regression models with time-varying covariates for cataract surgery were used to assess the relationship between cataract surgery and mortality. The study cohort included 241,062 patients, of whom 127,941 were in the cataract surgery group and 113,121 were in the cataract diagnosis group. The incidence of all-cause mortality was 3.62 deaths/100 person-years and 3.19 deaths/100 person-years in the cataract surgery and cataract diagnosis groups, respectively. Cataract surgery was associated with a decreased hazard of all-cause mortality after adjusting for demographics as well as systemic and ocular comorbidities (hazard ratio (HR), 0.93; p < 0.001). A protective association was noted between cataract surgery and mortality from vascular (HR, 0.92; p < 0.001) or neurologic (HR, 0.64; p < 0.001) causes. Patients with cataract who were 85 years of age and older, women, those who had lower income, and a Charlson comorbidity index score of 5 or more, or those without glaucoma revealed the largest reductions in mortality hazards resulting from cataract surgery.


Intra-Arterial Platelet Infusion for Intractable Hemorrhage and Refractory Thrombocytopenia in Children With Gastrointestinal Graft-Versus-Host Disease.
Acute gastrointestinal graft-versus-host disease (GVHD) refractory to first-line treatment with systemic corticosteroids results in increased morbidity and potential mortality. We retrospectively assessed the feasibility and efficacy of catheter-directed intra-arterial platelet infusion (IAPI) in two pediatric patients with steroid and transfusion refractory gastrointestinal GVHD causing intractable lower gastrointestinal hemorrhage and refractory thrombocytopenia, that were referred for salvage therapy. Immediate angiographic response was noted with a resolution of hemorrhage and decreased blood requirements. We reviewed the literature regarding this treatment modality and compared it to the available minimally invasive transcatheter techniques to control gastrointestinal hemorrhage.


An Agenda for Purely Confirmatory Research.
The veracity of substantive research claims hinges on the way experimental data are collected and analyzed. In this article, we discuss an uncomfortable fact that threatens the core of psychology's academic enterprise: almost without exception, psychologists do not commit themselves to a method of data analysis before they see the actual data. It then becomes tempting to fine tune the analysis to the data in order to obtain a desired result-a procedure that invalidates the interpretation of the common statistical tests. The extent of the fine tuning varies widely across experiments and experimenters but is almost impossible for reviewers and readers to gauge. To remedy the situation, we propose that researchers preregister their studies and indicate in advance the analyses they intend to conduct. Only these analyses deserve the label "confirmatory," and only for these analyses are the common statistical tests valid. Other analyses can be carried out but these should be labeled "exploratory." We illustrate our proposal with a confirmatory replication attempt of a study on extrasensory perception.


Magneto-switchable electrocatalytic and bioelectrocatalytic transformations.
Magnetic switching of redox reactions and bioelectrocatalytic transformations is accomplished in the presence of relay-functionalized magnetite particles (Fe(3)O(4)). The electrochemistry of a naphthoquinone (1), pyrroloquinoline quinone (2; PQQ), microperoxidase-11 (3), a ferrocene derivative (4) and a bipyridinium derivative (5), functionalized magnetic particles, is switched "ON" and "OFF" by an external magnet upon the attraction of the magnetic particles to an electrode or their retraction from the electrode, respectively. The magneto-switchable activation and deactivation of the electrochemical oxidation of the ferrocene-functionalized magnetic particles and the electrochemical reduction of the bipyridinium-functionalized magnetic particles are used for the triggering of mediated bioelectrocatalytic oxidation of glucose, in the presence of glucose oxidase (GOx), and bioelectrocatalytic reduction of nitrate (NO(3) (-)), in the presence of nitrate reductase (NR), respectively. Magnetic particles functionalized with a PQQ-NAD(+) dyad are used for the magnetic switching of the bioelectrocatalytic oxidation of lactate in the presence of lactate dehydrogenase (LDH). The coupling of these particles with a ferrocene-monolayer-functionalized electrode allows the dual and selective sensing of lactate and glucose in the presence of LDH and GOx, respectively, by using an external magnet to switch the detection mode.


Wakeful resting and listening to music contrast their effects on verbal long-term memory in dependence on word concreteness.
Wakeful resting and listening to music are powerful means to modulate memory. How these activities affect memory when directly compared has not been tested so far. In two experiments, participants encoded and immediately recalled two word lists followed by either 6 min wakefully resting or 6 min listening to music. The results of Experiment 1 show that both post-encoding conditions have a similar effect on memory after 1 day. In Experiment 2, we explored the possibility that less concrete words, i.e. lower in imageability than in Experiment 1, are differently affected by the two post-encoding conditions. The results of Experiment 2 show that, when words are less concrete, more words are retained after 1 day when encoding is followed by wakeful resting rather than listening to music. These findings indicate that the effects of wakeful resting and listening to music on memory consolidation are moderated by the concreteness of the encoded material.


Chronic caffeine treatment reverses memory impairment and the expression of brain BNDF and TrkB in the PS1/APP double transgenic mouse model of Alzheimer's disease.
The objective of this study was to investigate the effects of varying doses of caffeine on memory impairment and the expression of brain neurotrophic derived factor (BNDF) and TrkB in PS1/APP double transgenic mouse models. PS1/APP double transgenic mice were administered 0.3 ml/day of saline, 1.5 mg/day of caffeine or 0.75 mg/day of caffeine for eight weeks. A water maze test and western blotting were used to determine the memory capability and expression of hippocampal BNDF and TrkB of the mice. The results demonstrated that 0.75 mg/day and 1.5 mg/day doses of caffeine significantly increased memory capability and the expression of hippocampal BDNF and TrkB in PS1/APP mice with a dose-response effect. The results suggested that chronic caffeine treatment may reverse memory impairment in PS1/APP transgenic mice, and BDNF and its receptor TrkB, may be involved in this process.


Prime-boost immunization with DNA and modified vaccinia virus ankara vectors expressing herpes simplex virus-2 glycoprotein D elicits greater specific antibody and cytokine responses than DNA vaccine alone.
Several reports have indicated that prime-boost strategies of vaccination can enhance the level of specific immunity induced by nucleic acid vaccines. The present report describes such a strategy with herpes simplex virus (HSV)-2 glycoprotein D (gD), using combinations of plasmid vector that expresses gD (pgD2) and a recombinant modified vaccinia virus Ankara vector that expresses gD (MVA-gD2). The IgG antibody response to gD and the HSV-2 neutralizing antibody response were greatest when the MVA-gD2 vector was used as the priming immunization and then was boosted with either pgD2 or MVA-gD2. Determination of the isotype profile of MVA-gD2-primed mice revealed a much broader distribution of isotypes than that seen after DNA vaccination. In addition, antigen-stimulated spleen cells from mice primed with MVA-gD2 and boosted with either MVA-gD2 or pgD2 produced higher levels of interleukin-2 and interferon-gamma than did those from pgD2-primed mice, indicating that a prime-boost immunization strategy that uses the MVA and plasmid DNA vector dramatically enhances and diversifies the humoral and cellular immune response to HSV-2 gD.


The professionalism curriculum as a cultural change agent in surgical residency education.
Teaching professionalism effectively to fully engaged residents is a significant challenge. A key question is whether the integration of professionalism into residency education leads to a change in resident culture. The goal of this study was to assess whether professionalism has taken root in the surgical resident culture 3 years after implementing our professionalism curriculum. Evidence was derived from 3 studies: (1) annual self-assessments of the residents' perceived professionalism abilities to perform 20 defined tasks representing core Accrediting Council on Graduate Medical Education professionalism domains, (2) objective metrics of their demonstrated professionalism skills as rated by standardized patients annually using the objective structure clinical examination tool, and (3) a national survey of the Surgical Professionalism and Interpersonal Communications Education Study Group. Study 1: aggregate perceived professionalism among surgical residents shows a statistically significant positive trend over time (P = .016). Improvements were seen in all 6 domains: accountability, ethics, altruism, excellence, patient sensitivity, and respect. Study 2: the cohort of residents followed up over 3 years showed a marked improvement in their professionalism skills as rated by standardized patients using the objective structure clinical examination tool. Study 3: 41 members of the national Surgical Professionalism and Interpersonal Communications Education Study Group rated their residents' skills in admitting mistakes, delivering bad news, communication, interdisciplinary respect, cultural competence, and handling stress. Twenty-nine of the 41 responses rated their residents as "slightly better" or "much better" compared with 5 years ago (P = .001). Thirty-four of the 41 programs characterized their department's leadership view toward professionalism as "much better" compared with 5 years ago. All 3 assessment methods suggest that residents feel increasingly prepared to effectively deal with the professionalism challenges they face. Although professionalism seminars may have seemed like an oddity several years ago, residents today recognize their importance and value their professionalism skills. As importantly, department chairpersons report that formal professionalism education for residents is viewed more favorably compared with 5 years ago.


[Surveillance of the sensitivity of Plasmodium falciparum to chloroquine in Western Africa: value of in vivo tests using 5 and 10 mg/kg].
Studies on the in vivo sensitivity of Plasmodium falciparum strains to chloroquine were carried out on shrub savanna areas of Burkina Faso, West Africa and were conducted from 1982 to 1986 in asymptomatic malarial school children. From the result of 431 in vivo tests using a single dose of only 5 or 10 mg/kg b. w. chloroquine base, it was concluded that there was a high sensitive response of P. falciparum to chloroquine. In areas where clinical resistance has not been established, and where there is a high sensibility in the response of P. falciparum to chloroquine, in vivo studies with a single dose of 5 or 10 mg/kg are probably able to detect a decrease of sensitivity before the appearance of clinical resistance to higher regimens.


Association of Hypertension and Arterial Blood Pressure on Limb and Cardiovascular Outcomes in Symptomatic Peripheral Artery Disease: The EUCLID Trial.
Current guidelines recommend aggressive management of hypertension. Recent evidence suggested potential harm with low blood pressure targets in patients with peripheral artery disease. We investigated the association of a history of hypertension and office systolic blood pressure (SBP) with major adverse cardiovascular events (MACEs) and major adverse limb events (MALEs). The EUCLID trial (Examining the Use of Ticagrelor in Peripheral Artery Disease) included 13 885 participants with symptomatic peripheral artery disease; median follow-up was 30 months. Cox proportional hazards regression was used to calculate hazard ratios (HRs) for any MACE, MALE, and MALE including lower extremity revascularization. A clinical history of arterial hypertension was present in 10 857 (78%) participants, and these participants were older and more likely to be female when compared with the 3026 (22%) patients without hypertension. In patients with a history of hypertension, the adjusted hazard ratio for MACE was 0.94, 95% CI, 0.82-1.08; P=0.39, and the adjusted hazard ratio for MALE was 1.08, 95% CI, 0.96-1.23; P=0.21. During follow-up, average SBP was 135 mm Hg (125-145). Every 10 mmHg increase in SBP>125 mmHg was associated with an increased risk of MACE (HR, 1.10 [95% CI, 1.06-1.14]; P<0.001), a marginally increased risk of MALE (HR, 1.07 [95% CI, 1.00-1.15]; P=0.062), and an increased risk of MALE/lower extremity revascularization (HR, 1.08 [95% CI, 1.04-1.11]; P<0.001). Every decrease in 10 mmHg SBP ≤125 mmHg was associated with an increased risk of MACE (HR, 1.19 [95% CI, 1.09-1.31]; P<0.001) but not MALE or MALE/lower extremity revascularization (HR, 1.02 [95% CI, 0.84-1.23], P=0.824; HR, 1.04 [95% CI, 0.95-1.13], P=0.392, respectively). History of hypertension was not associated with higher hazard for MACE or MALE in patients with peripheral artery disease. In contrast, there was a higher hazard of MACE in patients with out-of-target low and high SBP. High but not low SBP was associated with an increased risk of ischemic limb events. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01732822.


Attitudes toward urinalysis drug testing within a civilian pilot training program.
This descriptive-correlational study examined civilian student pilots' attitudes toward urinalysis (UA) drug testing and the pilots' opinions regarding effectiveness, adequacy, and fairness of the method as a deterrent for substance abuse among pilots. There will be significant differences among attitudes of professional aviation student pilots in mandatory and nonmandatory UA drug tested sections of a flight program when considering the pilots' flight hours, ages, gender, anxiety produced by UA drug testing, opinions on drug and alcohol abuse by pilots on the flight schedule, and their attitudes toward the testing process. A Likert-scaled questionnaire was completed by the student pilots who were enrolled in mandatory and nonmandatory UA drug tested class sections within a large civilian aviation flight program. Pilots felt mandatory UA testing was less anxiety-producing (t = 2.25, p < 0.05) than the students in nonmandatory tested flight classes. The pilots in nonmandatory tested sections felt more strongly (t = 2.55, p < 0.01) that drug use existed among pilots on the flight schedule than mandatorily tested pilots. Significant intercorrelations (p < 0.05) emerged among the variables age, gender, flying hours, randomization of UA testing, and attitudes toward the UA testing process and its' effectiveness. Based on the results, mandatory UA drug testing appeared to decrease substance abuse among pilots on the flight schedule.


The ALK-2 and ALK-4 activin receptors transduce distinct mesoderm-inducing signals during early Xenopus development but do not co-operate to establish thresholds.
The TGFbeta family member activin induces different mesodermal cell types in a dose-dependent fashion in the Xenopus animal cap assay. High concentrations of activin induce dorsal and anterior cell types such as notochord and muscle, while low concentrations induce ventral and posterior tissues such as mesenchyme and mesothelium. In this paper we investigate whether this threshold phenomenon involves the differential effects of the two type I activin receptors ALK-2 and ALK-4. Injection of RNA encoding constitutively active forms of the receptors (here designated ALK-2* and ALK-4*) reveals that ALK-4* strongly induces the more posterior mesodermal marker Xbra and the dorsoanterior marker goosecoid in animal cap explants. Maximal levels of Xbra expression are attained using lower concentrations of RNA than are required for the strongest activation of goosecoid, and at the highest doses of ALK-4*, levels of Xbra transcription decrease, as is seen with high concentrations of activin. By contrast, the ALK-2* receptor activates Xbra but fails to induce goosecoid to significant levels. Analysis at later stages reveals that ALK-4* signalling induces the formation of a variety of mesodermal derivatives, including dorsal cell types, in a dose-dependent fashion, and that high levels also induce endoderm. By contrast, the ALK-2* receptor induces only ventral mesodermal markers. Consistent with these observations, ALK-4* is capable of inducing a secondary axis when injected into the ventral side of 32-cell stage embryos whilst ALK-2* cannot. Co-injection of RNAs encoding constitutively active forms of both receptors reveals that ventralising signals from ALK-2* antagonise the dorsal mesoderm-inducing signal derived from ALK-4*, suggesting that the two receptors use distinct and interfering signalling pathways. Together, these results show that although ALK-2* and ALK-4* transduce distinct signals, the threshold responses characteristic of activin cannot be due to interactions between these two pathways; rather, thresholds can be established by ALK-4* alone. Furthermore, the effects of ALK-2* signalling are at odds with it behaving as an activin receptor in the early Xenopus embryo.


Combined modality staging of high risk rectal cancer.
The personal experience with the radiologic staging of high risk rectal cancer undergoing preoperative treatment is reported. 61 patients shown to be affected by locally advanced (T3-T4, N+with any T) rectal tumors on combined modality staging, underwent restaging 4-5 weeks after treatment. In all patients liver US, pelvic CT and colorectal enema were performed before and after treatment. In 22 patients with low rectal cancer transrectal sonography was performed. In 19 patients pelvic MRI was performed. The 61 patients were considered operable on second staging and thus referred to surgery. Subsequent control on histology has confirmed the diagnostic accuracy of the single procedures and of their combination. US was shown to be of high accuracy in the evaluation of T (90.8%) and of high predictive value for N. CT accuracy (84%) and MRI accuracy (78.9%) was lower because both tend to overstaging in the evaluation of T of rectal tumors undergoing preoperative treatment. Low CT accuracy (64%) and MRI accuracy (58%) was observed for N. There was optimum agreement between histology and imaging in the assessment of tumor shrinkage, well visualized by rectal enema which supported combined restaging with 88% accuracy for T.


Excited-state lifetime of adenine near the first electronic band origin.
The excited-state lifetime of supersonically cooled adenine was measured in the gas phase by femtosecond pump-probe transient ionization as a function of excitation energy between 36 100 and 37 500cm(-1). The excited-state lifetime of adenine is ∼2ps around the 0-0 band of the (1)L(b) ππ(∗) state (36 105cm(-1)). The lifetime drops to ∼1ps when adenine is excited to the (1)L(a) ππ(∗) state with the pump energy at 36 800cm(-1) and above. The excited-state lifetimes of (1)L(a) and (1)L(b) ππ(∗) states are differentiated in accordance with previous frequency-resolved and computational studies.


[Cardiac and Aortic Surgery and Perioperative Management in Patients with Malignant Tumors].
Managing patients with concurrent malignant neoplasms and cardiovascular disease is an important issue, especially with aging populations;however, the optimal treatment strategy in these patients remains controversial. We report 27 patients with simultaneous cardiac and malignant disease in our institution over the past 12 years;23 patients underwent cardiovascular surgery, 4 patients underwent cardiovascular surgery after treatment for malignant disease, and 3 patients died of malignant disease. The treatment strategy for patients with concurrent cardiac and malignant disease should be chosen according to the severity of the cardiovascular disease and the expected prognosis of the malignant disease.


Psychosurgery in Italy, 1936-39.
In 1936 Egas Moniz introduced a new method for treating mental illness--psychosurgery. This new procedure was taken up immediately in a number of countries, including Italy. In most countries its introduction was slow and the numbers of operations were in single figures, but in Italy the introduction was rapid and around a dozen neuropsychiatrists reported much higher numbers of operations performed. Also in Italy the first innovations to the technique, notably the transorbital variation, were introduced. Moreover, all these activities took place without any sign of the protest seen elsewhere. Conditions that allowed the acceptance of this risky procedure seemed to be a consequence of the way in which the professions of neurology and psychiatry had been merged in Italy.


The information provided by the absence of cues: insights from Bayesian models of within and transgenerational plasticity.
Empirical studies of phenotypic plasticity often use an experimental design in which the subjects in experimental treatments are exposed to cues, while the subjects in control treatments are maintained in the absence of those cues. However, researchers have virtually ignored the question of what, if any, information might be provided to subjects by the absence of the cues in control treatments. We apply basic principles of information-updating to several experimental protocols used to study phenotypic plasticity in response to cues from predators to show why the reliability of the information provided by the absence of those cues in a control treatment might vary as a function of the subjects' experiences in the experimental treatment. We then analyze Bayesian models designed to mimic fully factorial experimental studies of trans and within-generational plasticity, in which parents, offspring, both or neither are exposed to cues from predators, and the information-states of the offspring in the different groups are compared at the end of the experiment. The models predict that the pattern of differences in offspring information-state across the four treatment groups will vary among experiments, depending on the reliability of the information provided by the control treatment, and the parent's initial estimate of the value of the state (the parental Prior). We suggest that variation among experiments in the reliability of the information provided by the absence of particular cues in the control treatment may be a general phenomenon, and that Bayesian approaches can be useful in interpreting the results of such experiments.


Age-dependent silencing of globin transgenes in the mouse.
Variegation of transgene expression, a heterocellular or mosaic pattern of expression seen in all mice in a given transgenic line, is a frequently observed but unexplained phenomenon. We have encountered variegation with globin transgenes; when lacZ expression is driven by globin control elements a proportion of erythrocytes express beta-galactosidase (beta-gal), while the remaining erythrocytes express none. The percentage of expressing cells is constant within each line (at any particular developmental stage), but varies between lines. Such variation may account for much of the line-to-line variability which has been reported in the expression of a transgene construct. We have now extended these observations by studying expression of several globin/lacZ transgenes with increasing age. Expression of beta-gal is variegated in all lines in adult mice, including those made with a beta-globin promoter and locus control region driving lacZ. The extent of variegation differs widely between lines, but in all lines there is a marked decline in the number of erythrocytes expressing beta-gal with increasing age. Progression of silencing continues long past the point at which globin switching is complete, suggesting that it is not related to this process. We observe that age-dependent silencing is most severe in high copy number animals. Increasing variegation of transgene expression with ageing of mice is likely to complicate interpretation of the developmental regulation of transgenes. We speculate that it reflects a general mechanism of epigenetic regulation.


Nitrate Reductase Regulates Expression of Nitrite Uptake and Nitrite Reductase Activities in Chlamydomonas reinhardtii.
In Chlamydomonas reinhardtii mutants defective at the structural locus for nitrate reductase (nit-1) or at loci for biosynthesis of the molybdopterin cofactor (nit-3, nit-4, or nit-5 and nit-6), both nitrite uptake and nitrite reductase activities were repressed in ammonium-grown cells and expressed at high amounts in nitrogen-free media or in media containing nitrate or nitrite. In contrast, wild-type cells required nitrate induction for expression of high levels of both activities. In mutants defective at the regulatory locus for nitrate reductase (nit-2), very low levels of nitrite uptake and nitrite reductase activities were expressed even in the presence of nitrate or nitrite. Both restoration of nitrate reductase activity in mutants defective at nit-1, nit-3, and nit-4 by isolating diploid strains among them and transformation of a structural mutant upon integration of the wild-type nit-1 gene gave rise to the wild-type expression pattern for nitrite uptake and nitrite reductase activities. Conversely, inactivation of nitrate reductase by tungstate treatment in nitrate, nitrite, or nitrogen-free media made wild-type cells respond like nitrate reductase-deficient mutants with respect to the expression of nitrite uptake and nitrite reductase activities. Our results indicate that nit-2 is a regulatory locus for both the nitrite uptake system and nitrite reductase, and that the nitrate reductase enzyme plays an important role in the regulation of the expression of both enzyme activities.


Long-Lived Afterglow from Elemental Sulfur Powder: Synergistic Effects of Impurity and Structure.
Elemental sulfur is not traditionally considered as an afterglow material, even though it can be endowed with fluorescence properties through processing it into nanodots. Herein, we discovered that elemental sulfur powder could emit room temperature phosphorescence (RTP) with a lifetime of 3.7 ms. A long-lived (>12 s) afterglow emission at 77 K could also be observed by the naked eye. Detailed investigations suggested that such a special phenomenon was attributed to impurity-related traps coupled with conduction and valence bands. After the sulfur is processed into nanodots, the rigid environment formed by the cross-linking of the surface ligands could stabilize the excited charges from quenching. This results in the promotion of RTP intensity and lifetime to achieve an emission lifetime of 200 ms. These results confirm the unique RTP of elemental sulfur powder, and also suggest the potential of sulfur-based materials as versatile components for the development of RTP materials.


Improving the Detection of Urine Sediment with a Modified Urinalysis Review Procedure.
Currently, numerous review procedures are applied to perform the urine sediment examination. Clinical technologists and nephrologists use different procedures for the determination of specimen concentration and for particle counting. These techniques may underestimate the formed elements such as pathological casts (CASTs) and renal tubular epithelial (RTE) cells and might interfere with clinical diagnosis. The aim of this study was to evaluate a modified review procedure for urinary analysis and to narrow the gap between nephrologists and technologists by increasing the detection positivity rate for pathological formed elements. We implemented a modified urinalysis procedure between October 2016 and January 2017 based on strict manual microscopic criteria and the currently available equipment. We confirmed the agreement between methods using a review procedure and Sysmex UF-1000i urinary flow cytometer (Pairwise Agreement > 0.88 for WBCs, RBCs, CASTs, and SRCs). Then we derived the review procedure that was based on the optimal sensitivity and specificity as follows: RBC > 26.1/µL, WBC > 37.0/µL, CAST > 1.0/µL, SRC > 8.2/µL, XTAL > 1.5/µL, YLC > 10.0/µL, BACT > 287.5/µL. Of the 317 specimens investigated, 17.4% (26/149) and 31.5% (39/124) of the specimens for RTEs and Path. CASTs, respectively, were correctly detected using the proposed review procedure. Sensitivity and specificity for this procedure was 96.9% and 46.2%, respectively. In addition, we verified the ability of the procedure to detect the pathological elements with technologists and nephrologists and the agreement was satisfactory. This modified review procedure can significantly improve the quality of urinalysis and reduce the risk of underestimating the detection of pathological particles.


[Pre-septal orbital cellulitis from odentogenic origin--combined surgical and endodontic approach: a case report].
Orbital abscesses are common infectious diseases. The etiology of orbital abscesses may vary from common sinusitis in most of the cases, to cocaine sniffing. As a result of the proximity to the brain, orbital abscesses may complicate to life threatening situations. The infectious process spreads to the orbit in several ways: hematogenous, via anatomic spaces in the maxillofacial region, direct invasion. The treatment philosophy combines surgical and Antibiotic therapy to resolve the acute phase of the disease, followed by elimination of the source. The purpose of this paper is to report a case of pre septal orbital cellulitis, that was treated surgically combined with endodontic therapy. To describe the different subtypes of orbital abscesses, differential diagnosis, imaging and treatment options.


Adult T-cell leukemia/lymphoma in Taiwan. A clinicopathologic observation.
The retrovirus-associated adult T-cell leukemia/lymphoma (ATL) has not been previously documented in Taiwan. Five cases identified recently by the authors are reported. Three of the patients were women, and their ages ranged from 36 to 60 years. The most important diagnostic clue was the observation of polylobated lymphoid cells in the peripheral blood. Other variably observed significant features included hypercalcemia, cutaneous eruptions, osteolytic bone lesion, hepatomegaly, and lymphadenopathy. Surface marker studies revealed that the leukemic or lymphoma cells were T-helper cells. Histopathologic examination revealed one case of pleomorphic type and three cases of medium-sized cell type. No tissue was available for study in one case. The diagnosis of ATL was confirmed by the indirect immunofluorescence test on MT-1 cell for antibodies to adult T-cell leukemia virus-associated antigen (ATLA). Three patients were dead within 6 months, and two patients had been in clinical remission for 7 and 10 months, respectively. These two latter cases were similar to the so-called smoldering type of ATL. Two descendents among nine relatives of the patients were also positive for anti-ATLA (22%). Two husbands were negative. Four of the five patients lived in the same county in northeastern coastal Taiwan, which suggested a possible clustering of ATL in that region.