Evaluating the design of a family practice healthcare clinic using discrete-event simulation.
With increased pressures from governmental and insurance agencies, today's physician devotes less time to patient care and more time to administration. To assist physician clinics in evaluating potential operating procedures that improve operating efficiencies and better satisfy patients, an object-oriented discrete-event simulation model has been constructed using the Visual Simulation Environment (VSE). The research presented herein describes a methodology for determining appropriate staffing and physical resources in a clinical environment using this simulation model. This methodology takes advantage of several simulation-based statistical techniques, including batch means: fractional factorial design: and simultaneous ranking, selection, and multiple comparisons. A clinic effectiveness measure is introduced that captures several objectives within a health care clinic, including profitability and patient satisfaction. An explanation of the experimental design is provided and results of the experimentation are presented. Based upon the experimental results, conclusions are drawn and recommendations are made for an appropriate staffing and facility size for a two physician family practice healthcare clinic.


Primary structure and functional analysis of the soluble transducer protein HtrXI in the archaeon Halobacterium salinarium.
Signal transduction in the archaeon Halobacterium salinarium is mediated by a family of 13 soluble and membrane-bound transducers. Here, we report the primary structure and functional analysis of one of the smallest halobacterial putative transducers, HtrXI. Hydropathy plot analysis of the primary structure predicts no membrane-spanning segments in HtrXI. The fractionation of the H. salinarium proteins confirmed that HtrXI is a soluble protein. Capillary assay with an HtrXI deletion mutant and a complemented strain revealed that this soluble transducer is involved in Asp and Glu taxis. In vivo analysis of the methylesterase activity of the htrXI-1 deletion mutant suggests that HtrXI plays an important role in the adaptation of the chemotactic responses to His, Asp, and Glu, which are attractants for halobacteria. Stimulation by Asp and Glu causes demethylation of HtrXI and of another putative transducer, HtrVII. But addition of His to halobacterial cells increases HtrXI methylation together with that of other putative transducers. In the absence of HtrXI, stimulation by either Glu or His does not decrease or increase the methylation of any putative transducers. Therefire, the HtrXI transducer appears to have a complex role in chemotaxis signal transduction.


Developmental changes in trak-mediated mitochondrial transport in neurons.
Previous studies established that the kinesin adaptor proteins, TRAK1 and TRAK2, play an important role in mitochondrial transport in neurons. They link mitochondria to kinesin motor proteins via a TRAK acceptor protein in the mitochondrial outer membrane, the Rho GTPase, Miro. TRAKs also associate with enzyme, O-linked N-acetylglucosamine transferase (OGT), to form a quaternary, mitochondrial trafficking complex. A recent report suggested that TRAK1 preferentially controls mitochondrial transport in axons of hippocampal neurons whereas TRAK2 controls mitochondrial transport in dendrites. However, it is not clear whether the function of any of these proteins is exclusive to axons or dendrites and if their mechanisms of action are conserved between different neuronal populations and also, during maturation. Here, a comparative study was carried out into TRAK-mediated mitochondrial mobility in axons and dendrites of hippocampal and cortical neurons during maturation in vitro using a shRNA gene knockdown approach. It was found that in mature hippocampal and cortical neurons, TRAK1 predominantly mediates axonal mitochondrial transport whereas dendritic transport is mediated via TRAK2. In young, maturing neurons, TRAK1 and TRAK2 contribute similarly in mitochondrial transport in both axons and dendrites in both neuronal types. These findings demonstrate maturation regulation of mitochondrial transport which is conserved between at least two distinct neuronal subtypes.


Perianth bottom-specific blue color development in Tulip cv. Murasakizuisho requires ferric ions.
The entire flower of Tulipa gesneriana cv. Murasakizuisho is purple, except the bottom, which is blue. To elucidate the mechanism of the different color development in the same petal, we prepared protoplasts from the purple and blue epidermal regions and measured the flavonoid composition by HPLC, the vacuolar pH by a proton-selective microelectrode, and element contents by the inductively coupled plasma (ICP) method. Chemical analyses revealed that the anthocyanin and flavonol compositions in both purple and blue colored protoplasts were the same; delphinidin 3-O-rutinoside (1) and major three flavonol glycosides, manghaslin (2), rutin (3) and mauritianin (4). The vacuolar pH values of the purple and blue protoplasts were 5.5 and 5.6, respectively, without any significant difference. However, the Fe(3+) content in the blue protoplast was approximately 9.5 mM, which was 25 times higher than that in the purple protoplasts. We could reproduce the purple solution by mixing 1 with two equimolar concentrations of flavonol with lambda(vismax) = 539 nm, which was identical to that of the purple protoplasts. Furthermore, addition of Fe(3+) to the mixture of 1-4 gave the blue solution with lambda(vismax) = 615 nm identical to that of the blue protoplasts. We have established that Fe(3+) is essential for blue color development in the tulip.


Amphibian breeding phenology trends under climate change: predicting the past to forecast the future.
Global climate warming is predicted to hasten the onset of spring breeding by anuran amphibians in seasonal environments. Previous data had indicated that the breeding phenology of a population of Fowler's Toads (Anaxyrus fowleri) at their northern range limit had been progressively later in spring, contrary to generally observed trends in other species. Although these animals are known to respond to environmental temperature and the lunar cycle to commence breeding, the timing of breeding should also be influenced by the onset of overwintering animals' prior upward movement through the soil column from beneath the frost line as winter becomes spring. I used recorded weather data to identify four factors of temperature, rainfall and snowfall in late winter and early spring that correlated with the toads' eventual date of emergence aboveground. Estimated dates of spring emergence of the toads calculated using a predictive model based on these factors, as well as the illumination of the moon, were highly correlated with observed dates of emergence over 24 consecutive years. Using the model to estimate of past dates of spring breeding (i.e. retrodiction) indicated that even three decades of data were insufficient to discern any appreciable phenological trend in these toads. However, by employing weather data dating back to 1876, I detected a significant trend over 140 years towards earlier spring emergence by the toads by less than half a day/decade, while, over the same period of time, average annual air temperature and annual precipitation had both increased. Changes in the springtime breeding phenology for late-breeding species, such as Fowler's Toads, therefore may conform to expectations of earlier breeding under global warming. Improved understanding of the environmental cues that bring organisms out of winter dormancy will enable better interpretation of long-term phenological trends.


A network meta-analysis on the effects of information technology application on preoperative knowledge of patients.
The application of information technology in health education plan in Taiwan has existed for a long time. The purpose of this study is to explore the relationship between information technology application in health education and patients' preoperative knowledge by synthesizing existing researches that compare the effectiveness of information technology application and traditional instruction in the health education plan. In spite of claims regarding the potential benefits of using information technology in health education plan, results of previous researches were conflicting. This study is carried out to examine the effectiveness of information technology by using network meta-analysis, which is a statistical analysis of separate but similar studies in order to test the pooled data for statistical significance. Information technology application in health education discussed in this study include interactive technology therapy (person-computer), group interactive technology therapy (person-person), multimedia technology therapy and video therapy. The result has shown that group interactive technology therapy is the most effective, followed by interactive technology therapy. And these four therapies of information technology are all superior to the traditional health education plan (leaflet therapy).


Correlation between liver morphology and portal pressure in alcoholic liver disease.
In 14 alcoholic patients, the degree of hepatic architectural destruction was graded (preserved architecture; nodules alternating with preserved architecture; totally destroyed architecture) and related to portal pressure. A positive correlation was found between the degree of architectural destruction and both wedged hepatic vein pressure (r = 0.72, p less than 0.01) and wedged-to-free hepatic vein pressure (r = 0.67, p less than 0.02). Degree of fatty change, fibrosis, inflammation, necrosis and occurrence of Mallory bodies showed no correlation with portal pressure. After morphometrical evaluation of liver biopsies, no significant correlation was found between mean hepatocyte volume or relative sinusoidal vascular volume and portal pressure. To test whether an increase in hepatocyte volume compresses the vascular structures and causes portal hypertension, the ratio of relative sinusoidal vascular volume to mean hepatocyte volume, which expresses the compression of the vascular structures exerted by enlargement of hepatocytes, was related to portal pressure. No significant correlation was found. Further, mean hepatocyte volume was not significantly correlated to relative sinusoidal vascular volume. The present findings are in accordance with the hypothesis that elevated hepatic vascular resistance and portal pressure in alcoholic liver disease are in part determined by the severity of the hepatic architectural destruction and subsequent distorsion and compression of the efferent vein system. Parenchymal changes, including changes in hepatocyte volume, seem to be of minor importance.


Fishing for new genes in skin biology: impact of cytogenetics on gene discovery.
Research into the field of skin biology has grown exponentially over the past two decades. Even though the fundamental molecular pathways are still not fully understood, there have been significant advances in our understanding of the underlying mechanisms involved in the pathogenesis of genodermatosis. The cloning of many candidate genes involved in the etiology of skin diseases has been facilitated by initial cytogenetic evidence. This review will synthesize recent findings that led to the discovery of candidate genes for anhidrotic ectodermal dysplasia, Williams-Beuren syndrome, neurofibromatosis-I and tricho-rhino-phalangeal syndrome.


Comparison of tinidazole given as a single dose and on 2 consecutive days for the treatment of nonspecific bacterial vaginosis.
Nonspecific bacterial vaginosis, defined as the presence of clue cells, was treated in a randomized, double-blind study with (1) tinidazole 2 g as a single dose (82 patients), (2) tinidazole 2 g on 2 consecutive days (84 patients), and (3) with placebo (81 patients). The cure rates, both clue cells and Gardnerella vaginalis absent, were 51, 74 and 4%, respectively. A closer clinical and microbiological evaluation showed the 2-day regimen to be superior.


Use of phi(glp-lac) in studies of respiratory regulation of the Escherichia coli anaerobic sn-glycerol-3-phosphate dehydrogenase genes (glpAB).
Expression of the glpA operon encoding the extrinsic membrane anaerobic sn-glycerol-3-phosphate dehydrogenase complex of Escherichia coli K-12 was studied in five strains carrying independent glpA-lac operon fusions. The location of the fusions was confirmed by transduction. Two of the strains produced an enzymatically active anaerobic sn-glycerol-3-phosphate dehydrogenase that accumulated in the cytoplasmic fraction of the cells. This suggests the loss of a specific membrane anchor subunit encoded by a distal gene, glpB, which was disrupted by the insertion. beta-Galactosidase in all five strains carrying phi(glpA-lac) was highly inducible by glycerol only anaerobically. A mutation in fnr, a pleiotropic activator gene, prevented full induction of the phi(glpA-lac), demonstrating that the Fnr protein is a positive regulator of the primary dehydrogenase as well as of the terminal reductases of anaerobic respiratory chains. Low concentrations of the respiratory poison KCN had a permissive effect on aerobic expression of phi(glpA-lac). Aerobic expression of the hybrid operon was also enhanced in isogenic derivatives of the fusion strains deficient in protoporphyrin biosynthesis (hemA). Thus, heme proteins may play a role in mediating aerobic repression of the anaerobic respiratory chain.


Enhanced anticancer effect of oncostatin M combined with salinomycin in CD133+ HepG2 liver cancer cells.
Oncostatin M (OSM) induces the differentiation of liver cancer stem cells (LCSCs) and increases sensitivity to the chemotherapeutic agent 5-fluorouracil, whereas salinomycin (Sal) induces apoptosis in cancer stem cells and inhibits the proliferation of liver cancer cells. However, there have been no studies investigating the anticancer effects of combination treatment with OSM and Sal. In the present study, we investigated the synergistic effects of OSM and Sal on LCSCs, the CD133+ subpopulations from HepG2 human liver cancer cells. CD133+ LCSCs were isolated using an immunomagnetic bead technique and identified through colony formation. After incubating with OSM and Sal, the ability of LCSC proliferation and invasion, as well as apoptosis rates were evaluated, and the expression of stemness-related genes was examined by quantitative real-time polymerase chain reaction. Additionally, the secretion of α-fetoprotein (AFP) and albumin (ALB) were analyzed by enzyme-linked immunosorbent assay. Our results indicated that OSM combined with Sal significantly suppressed LCSC proliferation and invasion and induced apoptosis, as determined by flow cytometry and increases in cleaved caspase-3 levels detected by western blotting. The results of the JC-1 staining assay indicated that this effect involved the mitochondrial pathway. Moreover, combination treatment reduced the expression of CD133 in LCSCs and suppressed stemness-related gene expression. Furthermore, the LCSCs produced lower levels of AFP and higher levels of ALB following combination treatment. In all experiments, combination treatment elicited more efficient anticancer effects on LCSCs as compared with single-drug treatment; therefore, our results demonstrated that combined treatment with OSM and Sal inhibited proliferation and induced differentiation and apoptosis in LCSCs, suggesting combined use of OSM and Sal as a therapeutic strategy for liver cancer.


Selectin ligands promote ultrasound contrast agent adhesion under shear flow.
Contrast-enhanced ultrasound imaging has shown promise in the field of molecular imaging. This technique relies upon the adhesion of ultrasound contrast agent (UCA) to targeted molecular markers of disease. This is accomplished by coating the surface of the contrast agent with a ligand that specifically binds to the intended molecular marker. Most UCA particles remain in the blood space, and their retention is influenced by the forces imposed by blood flow. For a UCA bound to a molecular target on the vascular endothelium, blood flow imposes a dislodging force that counteracts retention. Additionally, contrast agent adhesion to the molecular marker requires rapid binding kinetics, especially in rapid blood flow. The ability of a ligand:target bond complex to mediate fast adhesion and withstand dislodging force is necessary for efficient ultrasound-based molecular imaging. In the current study, we describe a flow-based adhesion assay which, combined with a novel automated tracking algorithm, enables quick determination of the ability of a targeting ligand to mediate effective contrast agent adhesion. This system was used to explore the adhesion of UCA targeted to the proinflammatory endothelial protein P-selectin via four targeting ligands, which revealed several interesting adhesive behaviors. Contrast agents targeted with glycoconjugate ligands modeled on P-selectin glycoprotein ligand 1 exhibited primarily unstable or transient adhesion, while UCA targeted with an anti-P-selectin monoclonal antibody exhibited primarily firm adhesion, although the efficiency with which these agents were recruited to the target surface was relatively low.


Cerebral venous sinus thrombosis complicated by subdural hematomas: Case series and literature review.
Cerebral venous sinus thrombosis (CVST) can cause elevated intracranial pressure, hemorrhagic venous infarct, and cortical subarachnoid hemorrhage. We present a case series and literature review to illustrate that CVST can also present with subdural hematoma (SDH). Chart review was completed on a retrospective case series of CVST with spontaneous SDH. We also conducted a literature search. Over a 6 year interval, three patients with CVST and SDH were admitted to the neurointensive care unit. A 38-year-old woman had both SDH and a hemorrhagic venous infarct associated with a transverse sinus thrombosis. She was managed conservatively with long-term anticoagulation. A 68-year-old woman presented with an acute SDH requiring craniotomy and a thrombosed cortical vein was noted intraoperatively. Computed tomography venography showed thrombosis of the superior sagittal sinus. She had polycythemia vera with the V617 Jak2 gene mutation and was managed with aspirin and hydroxyurea. A 60-year-old male had recurrence of a spontaneous convexity SDH requiring reoperation. Neuroimaging identified ipsilateral transverse sinus thrombosis with retrograde flow into the opposite sinus. Manometry demonstrated elevated venous pressures and these normalized after thrombectomy. Angiography performed after endovascular treatment demonstrated a normal venous drainage pattern. There have been limited reports of SDH complicating CVST in the literature. This case series and literature review demonstrates that CVST can also present with spontaneous SDH with or without associated venous infarctions. Treatment must be individualized. This is the first published description of endovascular thrombectomy for recurrent symptomatic SDH due to CVST.


Efficiency of traditional chewing sticks in oral hygiene programs among Ethiopian schoolchildren.
The effect of oral hygiene programs was studied in 248 children from five schoolclasses in Asella, Ethiopia. All children received professional toothcleaning after an initial clinical examination, and were again examined after a trial period of 3 months. The classes were assigned to the following procedures: one class received information and instruction in the use of the toothbrush, and a second class in the use of the mefaka, a wooden chewing stick traditionally used for oral cleaning. The children were advised to clean their teeth daily. Two other classes received similar information and instruction with regard to the toothbrush and the mefaka. Oral cleaning was then performed daily under direction and supervision, in one class with the toothbrush and in the other class with the mefaka. The fifth class was used as control. Instruction only was found to have no effect on the amount of oral deposits. Supervised oral cleaning, on the other hand, improved the oral hygiene of the schoolchildren significantly. The mefaka was found to be as effective as the toothbrush in removing oral deposits. It was concluded that the mefaka should be recommended for use in preventive dental programs in Ethiopia since it is effective, inexpensive, and familiar to the population.


Structured follow-up by general practitioners after deliberate self-poisoning: a randomised controlled trial.
General Practitioners (GPs) play an important role in the follow-up of patients after deliberate self-poisoning (DSP). The aim was to examine whether structured follow-up by GPs increased the content of, adherence to, and satisfaction with treatment after discharge from emergency departments. This was a multicentre, randomised trial with blinded assignment. Five emergency departments and general practices in the catchment area participated. 202 patients discharged from emergency departments after DSP were assigned. The intervention was structured follow-up by the GP over a 6-month period with a minimum of five consultations, accompanied by written guidelines for the GPs with suggestions for motivating patients to follow treatment, assessing personal problems and suicidal ideation, and availability in the case of suicidal crisis. Outcome measures were data retrieved from the Register for the control and payment of reimbursements to health service providers (KUHR) and by questionnaires mailed to patients and GPs. After 3 and 6 months, the frequency and content of GP contact, and adherence to GP consultations and treatment in general were registered. Satisfaction with general treatment received and with the GP was measured by the EUROPEP scale. Patients in the intervention group received significantly more consultations than the control group (mean 6.7 vs. 4.5 (p = 0.004)). The intervention group was significantly more satisfied with the time their GP took to listen to their personal problems (93.1% vs. 59.4% (p = 0.002)) and with the fact that the GP included them in medical decisions (87.5% vs. 54. 8% (p = 0.009)). The intervention group was significantly more satisfied with the treatment in general than the control group (79% vs. 51% (p = 0.026)). Guidelines and structured, enhanced follow-up by the GP after the discharge of the DSP patient increased the number of consultations and satisfaction with aftercare in general practice. Consistently with previous research, there is still a need for interventional studies. ClinicalTrials.gov Identifier: NCT01342809. Registered 18 April 2011.


Plasma-assisted interface engineering of boron nitride nanostructure films.
Today many aspects of science and technology are progressing into the nanoscale realm where surfaces and interfaces are intrinsically important in determining properties and performances of materials and devices. One familiar phenomenon in which interfacial interactions play a major role is the wetting of solids. In this work we use a facile one-step plasma method to control the wettability of boron nitride (BN) nanostructure films via covalent chemical functionalization, while their surface morphology remains intact. By tailoring the concentration of grafted hydroxyl groups, superhydrophilic, hydrophilic, and hydrophobic patterns are created on the initially superhydrophobic BN nanosheet and nanotube films. Moreover, by introducing a gradient of the functional groups, directional liquid spreading toward increasing [OH] content is achieved on the films. The resulting insights are meant to illustrate great potentials of this method to tailor wettability of ceramic films, control liquid flow patterns for engineering applications such as microfluidics and biosensing, and improve the interfacial contact and adhesion in nanocomposite materials.


Ethical issues in adolescent and parent informed consent for pediatric asthma research participation.
This article reviews the empirical literature related to knowledge, competence, volition, and financial compensation in the biomedical research decision-making of children, adolescents, and parents. Research findings indicate there are differences in adolescent and parent understanding and appreciation of research risks and procedures, that opinions about decision-making authority and physician influence for research participation are different in adolescents and parents, and that financial compensation can be a salient factor in the research-related decision-making process. Pediatric asthma researchers can consider these psychological factors involved in adolescent and parent research participation decision-making processes to develop effective informed consent procedures.


Oxidative Stress and Mitochondrial Dysfunction Associated with Peripheral Neuropathy in Type 1 Diabetes.
Significance: This review highlights the many intracellular processes generating reactive oxygen species (ROS) in the peripheral nervous system in the context of type 1 diabetes. The major sources of superoxide and hydrogen peroxide (H2O2) are described, and scavenging systems are explained. Important roles of ROS in regulating normal redox signaling and in a disease setting, such as diabetes, contributing to oxidative stress and cellular damage are outlined. The primary focus is the role of hyperglycemia in driving elevated ROS production and oxidative stress contributing to neurodegeneration in diabetic neuropathy (within the dorsal root ganglia [DRG] and peripheral nerve). Recent Advances: Contributors to ROS production under high intracellular glucose concentration such as mitochondria and the polyol pathway are discussed. The primarily damaging impact of ROS on multiple pathways including mitochondrial function, endoplasmic reticulum (ER) stress, autophagy, and epigenetic signaling is covered. Critical Issues: There is a strong focus on mechanisms of diabetes-induced mitochondrial dysfunction and how this may drive ROS production (in particular superoxide). The mitochondrial sites of superoxide/H2O2 production via mitochondrial metabolism and aerobic respiration are reviewed. Future Directions: Areas for future development are highlighted, including the need to clarify diabetes-induced changes in autophagy and ER function in neurons and Schwann cells. In addition, more clarity is needed regarding the sources of ROS production at mitochondrial sites under high glucose concentration (and lack of insulin signaling). New areas of study should be introduced to investigate the role of ROS, nuclear lamina function, and epigenetic signaling under diabetic conditions in peripheral nerve.


Does fragility of glass formation determine the strength of Tg-nanoconfinement effects?
Nanoscale confinement has been shown to alter the glass transition and associated mechanical and transport properties of glass-forming materials. Inspired by expected interrelations between nanoconfinement effects, cooperative dynamics in supercooled liquids, and the "fragility" (or temperature-abruptness) of the glass transition, it is commonly expected that nanoconfinement effects on Tg should be more pronounced for more fragile glass formers. Here we employ molecular dynamics simulations of glass formation in the bulk and under nanoconfinement of model polymers in which we systematically tune fragility by several routes. Results indicate that a correlation between fragility and the strength of nanoconfinement effects is weak to modest at best when considering all systems but can appear to be stronger when considering a subset of systems. This outcome is consistent with a reanalysis of the Adam-Gibbs theory of glass formation indicating that fragility does not necessarily track in a universal way with the scale of cooperative motion in glass-forming liquids. Finally, we find that factors such as composition gradients or variability in measurement sensitivity to different parts of the dynamic gradient have the potential to significantly confound efforts to identify trends in Tg-nanoconfinement effects with variables such as fragility, emphasizing the importance of employing diverse data sets and multiple metrologies in the study of this problem.


Computational Approaches for the Design of (Mutant-)Selective Tyrosine Kinase Inhibitors: State-of-the-Art and Future Prospects.
Kinases remain one of the major attractive therapeutic targets for a large number of indications such as cancer, rheumatoid arthritis, cardiac failure and many others. Design and development of kinase inhibitors (ATP-competitive, allosteric or covalent) is a clinically validated and successful strategy in the pharmaceutical industry. The perks come with limitations, particularly the development of resistance to highly potent and selective inhibitors. When this happens, the cycle needs to be repeated, i.e., the design and development of kinase inhibitors active against the mutated forms. The complexity of tumor milieu makes it awfully difficult for these molecularly-targeted therapies to work. Every year newer and better versions of these agents are introduced in the clinic. Several computational approaches such as structure-, ligand-based or hybrid ones continue to live up to their potential in discovering novel kinase inhibitors. New schools of thought in this area continue to emerge, e.g., development of dual-target kinase inhibitors. But there are fundamental issues with this approach. It is indeed difficult to selectively optimize binding at two entirely different or related kinases. In addition to the conventional strategies, modern technologies (machine learning, deep learning, artificial intelligence, etc.) started yielding the results and building success stories. Computational tools invariably played a critical role in catalysing the phenomenal progress in kinase drug discovery field. The present review summarized the progress in utilizing computational methods and tools for discovering (mutant-)selective tyrosine kinase inhibitor drugs in the last three years (2017-2019). Representative investigations have been discussed, while others are merely listed. The author believes that the enthusiastic reader will be inspired to dig out the cited literature extensively to appreciate the progress made so far and the future prospects of the field.


Prognostic value of hyperintense vessel signals on fluid-attenuated inversion recovery sequences in acute cerebral ischemia.
Fluid-attenuated inversion recovery (FLAIR) sequences may reveal hyperintense vessel signals (HVS) at the acute stage of cerebral ischemia. The aim of this study was to test the hypothesis that HVS are associated with a worse outcome. We included 30 consecutive patients admitted within 12 h after onset of hemispheric cerebral ischemia. The outcome was assessed with the modified Rankin Scale at month 1. Proximal HVS were present in 9 patients and distal HVS in 16. All patients with proximal occlusions on time-of-flight sequences had distal HVS on FLAIR. Patients with poor outcome at month 1 (modified Rankin Scale 3-6) more frequently had had HVS on MRI (12/13 vs. 4/17; p< 0.001). Distal HVS found on FLAIR sequences within 12 h of acute cerebral ischemia are associated with a worse 1-month outcome.


The Dopaminergic System Modulates the Electrophysiological Activity of the Suprachiasmatic Nucleus Dependent on the Circadian Cycle.
The suprachiasmatic nucleus of the hypothalamus (SCN) controls mammalian circadian rhythms. Circadian rhythms influence the dopaminergic system, and dopaminergic tone impresses the physiology and behavior of the circadian clock. However, little is known about the effect of dopamine and dopamine receptors, especially D1-like dopamine receptors (D1Rs), in regulating the circadian rhythm and the SCN neuron's activity. Therefore, the present study aimed to investigate the role of the D1Rs in SCN neural oscillations during the 24-h light-dark cycle using local field potential (LFP) recording. To this end, two groups of rats were given the SKF-38393 (1 mg/kg; i.p.) as a D1-like receptor agonist in the morning or night. LFP recording was performed for ten minutes before and two hours after the SKF-38393 injection. The obtained results showed that diurnal changes affect LFP oscillations so that delta relative power declined substantially, whereas upper-frequency bands and Lempel-Ziv complexity (LZC) index increased at night, which is consistent with rodents' activity cycles. The D1Rs agonist administration in the morning dramatically altered these intrinsic oscillations, decreasing delta and theta relative power, and most of the higher frequency bands and LZC index were promoted. Some of these effects were reversed at the night after the SKF-38393 injection. In conclusion, findings showed that the SCN's neuronal activities are regulated based on the light-dark cycle in terms of population neural oscillatory activity which could be affected by dopaminergic stimulation in a time-dependent way.


Chromosome aberrations in bone marrow cells of C3H/He mice at an early stage after whole-body irradiation.
Murine acute myeloid leukemia is characterized by chromosome 2 aberrations, and genesis of the marker chromosome 2 by radiation is suspected to be an initiating event of radiation leukemogenesis. A detailed analysis of the type and frequency of chromosome 2 aberrations in murine bone marrow cells at an early stage after irradiation is provided here. A total of 40 male C3H/He mice was exposed to 137Cs gamma-ray at a dose of 1, 2 or 3 Gy, and sacrificed 24 hours after irradiation. Metaphase samples prepared from bone marrow cells were Q-banded for karyotyping or painted with DNA probes specific to chromosome 2. In 5 mice analyzed by karyotyping, one mouse showed high frequency of the marker aberrations as well as other chromosome 2 aberrations. Chromosome painting analysis for the rest of the mice also detected 3 animals showing significantly high frequencies of chromosome 2 aberrations. Dose-dependence of the frequencies was observed even among those mice that tended to be sensitive. The results indicated that there was a subgroup of mice carrying hypersensitive chromosome 2. The subgroup could be leukemia-sensitive if radiation-induced chromosome aberrations are responsible for an early change in myeloid leukemogenesis.


Cost-precision trade-off relation determines the optimal morphogen gradient for accurate biological pattern formation.
Spatial boundaries formed during animal development originate from the pre-patterning of tissues by signaling molecules, called morphogens. The accuracy of boundary location is limited by the fluctuations of morphogen concentration that thresholds the expression level of target gene. Producing more morphogen molecules, which gives rise to smaller relative fluctuations, would better serve to shape more precise target boundaries; however, it incurs more thermodynamic cost. In the classical diffusion-depletion model of morphogen profile formation, the morphogen molecules synthesized from a local source display an exponentially decaying concentration profile with a characteristic length λ. Our theory suggests that in order to attain a precise profile with the minimal cost, λ should be roughly half the distance to the target boundary position from the source. Remarkably, we find that the profiles of morphogens that pattern the Drosophila embryo and wing imaginal disk are formed with nearly optimal λ. Our finding underscores the cost-effectiveness of precise morphogen profile formation in Drosophila development.


Antihyperglycemic activity and chemical constituents of Eysenhardtia platycarpa.
The methanolic extracts from branches (BEP) and leaves (LEP) of Eysenhardtia platycarpa significantly decreased the blood glucose levels in normal and streptozotocin (STZ)-induced diabetic rats. One new flavone, (1"R)-5,4',1"-trihydroxy-6,7-(3",3"-dimethylchroman)flavone (1), together with the known compounds 5,7-dihydroxy-6-methyl-8-prenylflavanone (3), 5,7-dihydroxy-8-methyl-6-prenylflavanone (4), 5,7-dihydroxy-6-prenylflavanone (5), 5,7-dihydroxy-8-prenylflavanone (6), 3-O-acetyloleanolic acid (7), oleanolic acid, 3beta-acetoxy-11alpha,12alpha-epoxy-oleanan-28,13beta-olide, lupeol, betulinic acid, beta-sitosterol, beta-sitosteryl beta-D-glucopyranoside, beta-sitosteryl palmitate, and 3-O-methyl-myo-inositol were isolated from BEP. Additionally, one new flavanone, (2S)-4'-O-methyl-6-methyl-8-prenylnaringenin (2), as well as the known compounds 3, 4, 6, 4'-O-methyl-8-prenylnaringenin (8), and 5-hydroxy-7-methoxy-8-prenylflavanone (9) were isolated from LEP. 3-O-Acetyloleanolic acid (7), identified as the major constituent of BEP, showed a significant decrease (31 mg/kg of body weight, P < 0.05) in the glucose level of STZ-induced diabetic rats. The obtained results correlate with the traditional use of this species.


Are institutional deliveries promoted by Janani Suraksha Yojana in a district of West Bengal, India?
'Janani Suraksha Yojana (JSY)' was implemented in India to promote institutional deliveries among the poorer section of the society. A cross-sectional study was conducted in Bankura district among 324 women who delivered in last 12 months selected through 40 cluster technique to find out institutional delivery rate, utilization of JSY during antenatal period and relation between cash benefit under JSY during antenatal period and institutional delivery. Overall institutional delivery rate was 73.1% and utilization of JSY among eligible women was 50.5%. Institutional delivery (84.0%), consumption of 100 iron-folic acid tablets (46.0%) and three or more antenatal check-ups (91.0%) were better in women who received financial assistance from JSY during antenatal period than other women. After adjustment for socio-demographic factors, JSY utilization came out to be significantly (P=0.031) associated with institutional deliveries. The study showed that cash incentive under JSY in antenatal period had positive association on institutional deliveries.


Perspectives of physicians in general and ophthalmologists in particular about restarting services post-COVID-19 lockdown.
To assess the perspectives of physicians in general and ophthalmologists in particular about restarting elective out-patient (OP) and operating (OT) services after relaxation of lockdown for COVID-19. An online survey, containing 31 questions, was conducted among medical doctors using a secure Google forms link. The survey was open for 48 hours from 16th-18th April 2020. Responses were received from 556 physicians (including 266 ophthalmologists). About a third (n = 205) wanted to start OP immediately after lockdown. In OP, mask of any kind for patient (60.8%), 3-ply for assistants (52.7%) and N95 for doctors (72.7%) were most common preferences. In OP, 31.5% and 46.6% felt full PPE and gloves alone were sufficient respectively. Ophthalmologists were more likely to start immediately after lockdown compared to other specialists (P = 0.004). Among 299 surgeons, an almost equal number (27%) wanted to start routine OT services immediately and 2 weeks post lockdown. A large majority (76.9%) would mandate COVID-19 tests before elective surgeries. In OT, 34.1% wanted N95 for surgical team and 3-ply for patient, 23.4% wanted 3-ply masks for everyone. 40.5% felt additional personal protective equipment (PPE) is not required and 33.1% felt that full PPE is required for everyone in OT. Ophthalmic surgeons preferred 3-ply masks and were less inclined to use full PPE (P < 0.001). Perspectives of doctors vary, especially with regarding to timing of restarting services and precautions to be taken in the OT. Ophthalmologists may tend to err on the side of taking lesser stringent precautions when restarting services post lockdown.


Fluctuations due to association and dissociation processes at nanowire-biosensor surfaces and their optimal design.
In this work, we calculate the effect of the binding and unbinding of molecules at the surface of a nanowire biosensor on the signal-to-noise ratio of the sensor. We model the fluctuations induced by association and dissociation of target molecules by a stochastic differential equation and extend this approach to a coupled diffusion-reaction system. Where possible, analytic solutions for the signal-to-noise ratio are given. Stochastic simulations are performed wherever closed forms of the solutions cannot be derived. Starting from parameters obtained from experimental data, we simulate DNA hybridization at the sensor surface for different target molecule concentrations in order to optimize the sensor design.


Understanding the Role of Orexin Neuropeptides in Drug Addiction: Preclinical Studies and Translational Value.
Orexins (also known as hypocretins) are neuropeptides that participate in the regulation of energy metabolism, homeostasis, sleep, feeding, stress responses, arousal, and reward. Particularly relevant to the scope of the present review is the involvement of the orexin system in brain mechanisms that regulate motivation, especially highly motivated behavior, arousal, and stress, making it an ideal target for studying addiction and discovering treatments. Drug abuse and misuse are thought to induce maladaptive changes in the orexin system, and these changes might promote and maintain uncontrolled drug intake and contribute to relapse. Dysfunctional changes in this neuropeptidergic system that are caused by drug use might also be responsible for alterations of feeding behavior and the sleep-wake cycle that are commonly disrupted in subjects with substance use disorder. Drug addiction has often been associated with an increase in activity of the orexin system, suggesting that orexin receptor antagonists may be a promising pharmacological treatment for substance use disorder. Substantial evidence has shown that single orexin receptor antagonists that are specific to either orexin receptor 1 or 2 can be beneficial against drug intake and relapse. Interest in the efficacy of dual orexin receptor antagonists, which were primarily developed to treat insomnia, has grown in the field of drug addiction. Treatments that target the orexin system may be a promising strategy to reduce drug intake, mitigate relapse vulnerability, and restore "normal" physiological functions, including feeding and sleep. The present review discusses preclinical and clinical evidence of the involvement of orexins in drug addiction and possible beneficial pharmacotherapeutic effects of orexin receptor antagonists to treat substance use disorder.


Effects of aerobic training in patients with mitochondrial myopathies.
We studied the physiologic adaptation of patients with mitochondrial myopathies to aerobic training. Ten patients underwent individually supervised, moderate-intensity aerobic training on a treadmill for 8 weeks. Biochemical and functional measures improved with training. Estimated aerobic capacity increased by 30%. Blood lactate concentrations at rest and after exercise decreased by 30%. Muscle phosphorus magnetic resonance spectroscopy measurements of adenosine diphosphate recovery after exercise improved by more than 60%. Fatigue and tolerance to daily activities also improved. Although the improvement in exercise tolerance may be due in part to reversal of the effects of secondary deconditioning, this uncontrolled clinical trial suggests that aerobic training can benefit patients with mitochondrial myopathies.


Neuropeptides in skin from patients with atopic dermatitis: an immunohistochemical study.
The distribution and localization of several neuropeptides were investigated in the lichenified lesions of 11 patients with atopic dermatitis using indirect immunofluorescence. Substance P-positive nerve fibres were observed in most of the cases of atopic dermatitis, but not in normal controls. Somatostatin immunoreactive nerves were not found in the skin of atopic dermatitis, whereas a normal pattern of immunoreactivity could be detected in most of the healthy subjects. Neuropeptide Y-positive dendritic epidermal cells were observed in lesional skin from patients with atopic dermatitis, but not in controls. Calcitonin gene-related peptide and vasoactive intestinal polypeptide immunoreactivity in patients with atopic dermatitis did not differ from that in healthy subjects. With galanin antiserum a diffuse intracellular staining was observed in the epidermis of both atopic patients and controls, while no positive staining was found with either neurotensin or neurokinin A antibodies in either group. These findings suggest a possible involvement of some neuropeptides in the pathomechanisms of atopic dermatitis.


Changes in immunoglobulin levels in zinc-deficient mice infected with Trypanosoma musculi.
A metabolic imbalance technique was used to study the effects of zinc deficiency on immunoglobulin levels in mice infected with Trypanosoma musculi or immunized with parasite products. Zinc-deficient mice developed higher numbers of parasitemia earlier and exhibited prolonged infection. Irrespective of the diet, higher IgG1, IgG2b, and IgM levels, lower IgG2a and IgA levels, and uniform IgG3 levels were exhibited primarily by mice infected with T musculi and to a lesser extent by mice immunized with parasite products. Zinc-deficient mice showed smaller increases in IgG1 and IgM, but larger gains in IgG2b compared with mice on full-complement and pair-fed diets. However, IgG2a decreased significantly in zinc-deficient mice.


What is optimal nutritional support?
Nutritional support of the seriously ill patient has evolved with time and reflects new developments in the field of critical care. Current information suggests that optimal nutritional support can be provided by supplying at least 80% of energy requirements with at least 70% of the energy given as carbohydrate and the remaining 30% or less administered as fat (with > or = 3% of energy requirements as essential fatty acids). The caloric load may be reduced to 50% of requirements if growth factors (e.g., growth hormone) are utilized and the patient has adequate fat stores. Protein should be given as 1.5 g/kg/day; more catabolic patients, such as patients with burn injury, should receive 2 g/kg/day. All protein or amino acid feeding should include glutamine. There is an increased need for vitamins (especially A, C, and E) and minerals (zinc, selenium, and magnesium). The preferred route of feeding should be enteral, followed by enteral plus supplemental parenteral nutrition. If the gastrointestinal tract cannot be used, parenteral nutrition should be given. Nutrients should be administered early in the catabolic course, especially glucose, sodium, potassium, vitamins, and minerals. Over time (approximately 7 days) amino acids should be added and approximately 50% of caloric support should be provided. Finally, full nutritional support should be provided (by 7 to 10 days) if the catabolic course is expected to continue.


Concurrent and lagged physiological synchrony during mother-child interaction and their relationship to positive affect in 8- to 10-year-old children.
Mother-child interaction has been characterized by a fine-tuning of behavior and physiological activity. Yet, little is known about the dynamics of mother-child physiological synchrony during early school age and their associations to positive affect. To investigate these processes, 42 mother-child dyads, with children aged 8 to 10 years, played an interactive game while their interbeat intervals (IBI) and respiratory sinus arrhythmia (RSA) were measured simultaneously. IBI/RSA synchrony was calculated using cross-correlations of the IBI/RSA second-by-second time series for lags - 3 to + 3 seconds. Mother's and child's individual and shared positive affect were microcoded. During the interactive tasks, IBI and RSA synchrony significantly increased compared to control conditions. RSA and affect synchrony were significantly stronger for negative compared to positive lags indicating a stronger child leads/mother follows covariation. Further, dyad's IBI and RSA synchrony were significantly associated to mother's and child's individual positive affect. Our data suggest that in low-risk community samples, mothers may respond to their children's positive affect by matching their own affect and physiology. Investigating these temporally precise, concurrent and lagged synchrony processes may open up new avenues for understanding the ways in which parent-child interactions contribute to child developmental outcomes.


A live, attenuated Bordetella pertussis vaccine provides long-term protection against virulent challenge in a murine model.
Despite successful mass vaccination programs, whooping cough remains a significant cause of neonatal mortality. Immunity induced by current vaccines wanes in adolescence, requiring additional immunizations to prevent resurgence. There is a need for a new generation of vaccines capable of conferring long-lasting immunity from birth. Recently, a live, attenuated whooping cough vaccine, BPZE1, has been developed. Here, an established murine immunization model was used to examine the induction and longevity of immunological memory. In this predictive model, BPZE1 conferred a level of protection against virulent bacterial challenge comparable to that conferred by recovery from prior infection, up to 1 year after immunization. One year after immunization with BPZE1, a pertussis-specific persistent response, with high levels of gamma interferon (IFN-γ), could be detected from spleen cells restimulated with inactivated Bordetella pertussis. BPZE1 induced low levels of interleukin-17 (IL-17) and no IL-10 or IL-5. BPZE1 immunization induced long-lasting, efficacious memory B-cell and specific antibody responses dominated by IgG2a, which were boosted by subsequent challenge. Finally, the antibody induced by BPZE1 was functionally relevant and could clear a virulent B. pertussis infection in antibody-deficient mice following passive transfer. This study suggests that BPZE1 is capable of conferring a high level of long-lived effective protection against virulent B. pertussis.


Reassessment of hepatitis B virus window periods for two transcription-mediated amplification assays using screening data of South African blood donors.
Transcription-mediated amplification assays for HBV DNA detection have transitioned from the Ultrio to the Ultrio Plus assay, which features increased analytic sensitivity due to inclusion of a target enhancer reagent. The impact on HBV detection for different categories of HBV infection has not been fully evaluated. Hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HBsAg) detection rates as well as viral load (VL) distributions in HBV nucleic acid test (NAT)-yield samples were compared during 1 year of screening of South African blood donors with the Ultrio assay and the subsequent year by the Ultrio Plus version. HBV-DNA concentration at the HBsAg seroconversion point was established by regression analysis using a set of antibody to hepatitis B core antigen-negative acute viremic samples. Ultrio Plus detected twofold more window-period (WP) NAT yield donations and 1.7-fold more occult HBV infections than Ultrio. The VL distribution data indicated that Ultrio not only missed samples of less than 100 copies/mL, but also a substantial number higher than this level. The VL at the HBsAg seroconversion point was estimated at 916 copies/mL, whereas the VL at the NAT-conversion points was calculated at 63 and 4.1 copies/mL for Ultrio and Ultrio Plus. This reduced the infectious WP (compared to HBsAg testing) by 10.3 and 20.4 days, respectively. The higher-than-expected increase in HBV-NAT yields after introduction of the Ultrio Plus assay is likely attributable to variable sensitivity of the former Ultrio assay for different HBV samples. Therefore, previously published HBV WP reduction and residual risk estimates based on analytical sensitivity of the Ultrio assay need to be revised.


An investigation of the biological activity of parathyroid hormone in pseudohypoparathyroidism: comparison with vitamin D deficiency.
Circulating parathyroid hormone was studied in patients with pseudohypoparathyroidism and compared with that in normal subjects and patients with hypocalcaemia due to postsurgical or idiopathic hypoparathyroidism or vitamin D deficiency. The cytochemical bioassay was used to measure bioactivity and an amino-terminal specific immunoradiometric assay was used to measure immunoreactivity. In normal subjects (n = 12) the concentration of bioactive parathyroid hormone was 1.1-5.9 pg/ml. It was higher in patients with newly diagnosed, untreated pseudohypoparathyroidism (n = 4, range 20-53 pg/ml) and similarly raised in patients with untreated vitamin D deficiency (n = 9, range 23-74 pg/ml). The degree of hypocalcaemia was similar in these two groups of patients. By contrast, the concentration of bioactive parathyroid hormone was low (less than 0.6 pg/ml) in four patients with untreated postsurgical or idiopathic hypoparathyroidism. Restoration of normocalcaemia reduced the concentrations of bioactive PTH in both pseudohypoparathyroidism and vitamin D deficiency. Thus, in this respect the parathyroid glands in both conditions appeared to respond to the circulating calcium concentration. Immunoreactive PTH was also raised in patients with untreated pseudo-hypoparathyroidism and vitamin D deficiency, but restoration of normocalcaemia did not always reduce immunoreactive PTH to normal in these patients. Thus, there can be dissociation between bioactivity and immunoreactivity even when the PTH is measured in an amino-terminal specific assay.


Stability Profiles and Therapeutic Effect of Cu/Zn Superoxide Dismutase Chemically Coupled to O-Quaternary Chitosan Derivatives against Dextran Sodium Sulfate-Induced Colitis.
Superoxide dismutase (SOD) has attracted considerable attention on treatment of reactive oxygen species (ROS)-related disorders. We previously conjugated Cu/Zn SOD to O-quaternary chitosan derivatives (O-HTCC) to yield a polymer-enzyme conjugate O-HTCC-SOD that demonstrated superior therapeutic effect to native SOD. The present study demonstrated that O-HTCC-SOD had wider pH activity range, better thermal stability, excellent long-term stability for storage, as well as unique reinstatement of activity exposure to proteolytic degradation that was helpful for longer half-life in vivo. O-HTCC-SOD exerted significant anti-inflammatory effects on lipopolysaccharides (LPS)-stimulated mouse peritoneal macrophages by down-regulating production of pro-inflammatory cytokines and intracellular ROS. O-HTCC-SOD significantly attenuated dextran sodium (DSS)-induced colitis in mice as observed by the colitis severity, neutrophil infiltration and histopathological damage, whereas native SOD failed to do so. In conclusion, conjugation of O-HTCC conferred SOD with better stability and enhanced therapeutic potential, offering a promising option in treatment of inflammatory bowel disease.


Characterization of a somatostatin-28 containing the (Tyr-7, Gly-10) derivative of somatostatin-14: a terminal active product of prosomatostatin II processing in anglerfish pancreatic islets.
Anglerfish (Lophius piscatorius) Brockmann organs contain a form of somatostatin-14, identical to the hypothalamic tetradecapeptide, and two distinct forms of somatostatin-28, which can be separated by reversed-phase high-pressure liquid chromatography (HPLC). Analysis of the NH2-terminal amino acid sequence and comparison of the ability to incorporate 125I indicate that one of these forms corresponds to an octacosapeptide including in its sequence the (Tyr-7, Gly-10) derivative of somatostatin-14 (somatostatin II). Exposure of this somatostatin-28 species to an endopeptidase activity from the rat brain cortex generates a peptide immunologically related to somatostatin and undistinguishable from synthetic (Tyr-7, Gly-10) somatostatin-14 II by HPLC. This somatostatin-28 II exhibits a potent inhibitory effect on growth hormone release by rat anterior pituitary cells, comparable to the other somatostatin-28 form. Since (Tyr-7, Gly-10) somatostatin-14 II cannot be detected in anglerfish pancreatic islets, these results indicate that somatostatin-28 II represents the terminal active product of prosomatostatin II processing, whose structure was predicted from the cDNA nucleotide sequence corresponding to the second mRNA cloned from anglerfish Brockmann organs [Hobart, P., Crawford, R., Shen, L. P., Pictet, R. & Rutter, W. J. (1980) Nature (London) 288, 137-141].


Ectopic expression of tea MYB genes alter spatial flavonoid accumulation in alfalfa (Medicago sativa).
Flavonoids are one of the largest secondary metabolite groups, which are widely present in plants. Flavonoids include anthocyanins, proanthocyanidins, flavonols and isoflavones. In particular, proanthocyanidins possess beneficial effects for ruminant animals in preventing lethal pasture bloat. As a major legume forage, alfalfa (Medicago sativa) contains little proanthocyanidins in foliage to combat bloat. In an attempt to improve proanthocyanidin content in alfalfa foliage, we over-expressed two MYB transcription factors (CsMYB5-1 and CsMYB5-2) from tea plant that is rich in proanthocyanidins. We showed that, via targeted metabolite and transcript analyses, the transgenic alfalfa plants accumulated higher levels of flavonoids in stems/leaves than the control, in particular anthocyanins and proanthocyanidins. Over-expression of CsMYB5-1 and CsMYB5-2 induced the expression levels of genes involved in flavonoid pathway, especially anthocyanin/proanthocyanidin-specific pathway genes DFR, ANS and ANR in stems/leaves. Both anthocyanin/proanthocyanidin content and the expression levels of several genes were conversely decreased in flowers of the transgenic lines than in control. Our results indicated that CsMYB5-1 and CsMYB5-2 differently regulate anthocyanins/proanthocyanidins in stems/leaves and flowers. Our study provides a guide for increasing anthocyanin/proanthocyanidin accumulation in foliage of legume forage corps by genetic engineering. These results also suggest that it is feasible to cultivate new varieties for forage production to potentially solve pasture bloat, by introducing transcription factors from typical plants with high proanthocyanidin level.


Coordination environment of a site-bound metal ion in the hammerhead ribozyme determined by 15N and 2H ESEEM spectroscopy.
Although site-bound Mg2+ ions have been proposed to influence RNA structure and function, establishing the molecular properties of such sites has been challenging due largely to the unique electrostatic properties of the RNA biopolymer. We have previously determined that, in solution, the hammerhead ribozyme (a self-cleaving RNA) has a high-affinity metal ion binding site characterized by a K(d,app) < 10 microM for Mn2+ in 1 M NaCl and speculated that this site has functional importance in the ribozyme cleavage reaction. Here we determine both the precise location and the hydration level of Mn2+ in this site using ESEEM (electron spin-echo envelope modulation) spectroscopy. Definitive assignment of the high-affinity site to the activity-sensitive A9/G10.1 region is achieved by site-specific labeling of G10.1 with 15N guanine. The coordinated metal ion retains four water ligands as measured by 2H ESEEM spectroscopy. The results presented here show that a functionally important, specific metal binding site is uniquely populated in the hammerhead ribozyme even in a background of high ionic strength. Although it has a relatively high thermodynamic affinity, this ion remains partially hydrated and is chelated to the RNA by just two ligands.


Case definition and power in case-control studies.
A narrow case definition can lead to greater in clarity in case-control studies, but it can also lead to either a gain or a loss in the power of statistical tests. Under plausible assumptions, the loss of power can be in excess of 30 per cent, and the gain can be in excess of 50 per cent. If at least one third of the total study size consists of narrowly defined cases, the loss of power will often be negligible, whereas the gain can be substantial.


An economic evaluation of radiotherapy for patients with symptomatic Ledderhose disease.
Evidence for effectiveness of radiotherapy for Ledderhose disease was demonstrated in the LedRad-study. However, the health economic impact of Ledderhose disease is unclear. Therefore, an economic evaluation alongside the LedRad-study was planned. The economic evaluation was performed as a cost-effectiveness and cost-utility analysis from the societal perspective. Primary outcome parameters were pain burden and Quality Adjusted Life Years (QALY), until 12 months after the end of treatment. Secondary analyses were performed with outcomes until 18 months. Incremental cost-effectiveness (ICER) and cost-utility ratios (ICUR) were calculated to express costs per unit improvement in pain burden and costs per QALY gained, for radiotherapy compared to sham-radiotherapy. Bootstrap replication was used to assess uncertainty surrounding the ratios and to construct cost-effectiveness acceptability curves for QALY gain. Previous analysis showed a statistically significant improvement in pain- and QoL scores in favour of radiotherapy at 12 and 18 months. At these timepoints and excluding treatment costs, cumulative total costs were considerably lower in the radiotherapy group. The ICER until 12 months after treatment was 4987 euro per unit of pain burden reduction. The ICUR was 14249 euro per QALY gained. Most of the bootstrap replications were in the upper right quadrant, indicating that health gain can be achieved at higher costs. At increasing levels of willingness to pay for a gain in QALY, the probability of cost-utility gradually increased to approximately 85%. In patients with symptomatic Ledderhose disease, radiotherapy, at a moderate threshold for willingness to pay, is cost-effective in terms of QoL gain.


Mechanism of the chaperone-like and antichaperone activities of amyloid fibrils of peptides from αA-crystallin.
The amyloid fibril of a fragment of the substrate binding site of αA-crystallin (αAC(71-88)) exhibited chaperone-like activity by suppressing the aggregation of alcohol dehydrogenase (ADH) and luciferase. By contrast, the amyloid fibril of the cytotoxic fragment of amyloid β protein (Aβ(25-35)) facilitated the aggregation of the same proteins. We have determined the zeta potential of the amyloid fibril by measuring their electrophoretic mobility to study the effects of the surface charge on the modulation of protein aggregation. The αAC(71-88) amyloid possesses a large negative zeta potential value which is unaffected by the binding of the negatively charged ADH, indicating that the αAC(71-88) amyloid is stable as a colloidal dispersion. By contrast, the Aβ(25-35) amyloid possesses a low zeta potential value, which was significantly reduced with the binding of the negatively charged ADH. The canceling of the surface charge of the amyloid fibril upon substrate binding reduces colloidal stability and thereby facilitates protein aggregation. These results indicate that one of the key factors determining whether amyloid fibrils display chaperone-like or antichaperone activity is their electrostatic interaction with the substrate. The surface of the αAC(71-88) amyloid comprises a hydrophobic environment, and the chaperone-like activity of the αAC(71-88) amyloid is best explained by the reversible substrate binding driven by hydrophobic interactions. On the basis of these findings, we designed variants of amyloid fibrils of αAC(71-88) that prevent protein aggregation associated with neurodegenerative disorders.


On the photobehaviour of curcumin in biocompatible hosts: The role of H-abstraction in the photodegradation and photosensitization.
Curcumin (CUR) is a naturally occurring pigment extensively studied due to its therapeutic activity and delivered by suitable nanocarriers to overcome poor solubility in aqueous media. The significant absorption of CUR in the visible blue region has prompted its use as a potential phototherapeutic agent in treating infectious and cancer diseases, although the mechanism underlying the phototoxic effects is still not fully understood. This contribution investigates the photobehaviour of CUR within polymeric micelles, microemulsions, and zein nanoparticles, chosen as biocompatible nanocarriers, and human serum albumin as a representative biomolecule. Spectroscopic studies indicate that in all host systems, the enolic tautomeric form of CUR is converted in a significant amount of the diketo form because of the perturbation of the intramolecular hydrogen bond. This leads to intermolecular H-abstraction from the host components by the lowest excited triplet state of CUR with the formation of the corresponding ketyl radical, detected by nanosecond laser flash photolysis. This radical is oxidized by molecular oxygen, likely generating peroxyl and hydroperoxyl radical species, unless in Zein, reasonably due to the poor availability of oxygen in the closely packed structure of this nanocarrier. In contrast, no detectable formation of singlet oxygen was revealed in all the systems. Overall these results highlight the key role of the H-abstraction process over singlet oxygen sensitization as a primary photochemical pathway strictly dictated by the specific features of the microenvironment, providing new insights into the photoreactivity of CUR in biocompatible hosts that can also be useful for a better understanding of its phototoxicity mechanism.


Community knowledge of law at the end of life: availability and accessibility of web-based resources.
Objective The aim of the present study was to identify online resources community members may access to inform themselves about their legal duties and rights in end-of-life decision making. Methods Resource mapping identified online resources that members of the public in New South Wales, Victoria and Queensland are likely to identify, and assessed the ease or difficulty in locating them. Resources were then critically analysed for accessibility of language and format using the Patient Education Materials Assessment Tool (PEMAT). Results Identified resources differed considerably based on whether search terms identified by community members or experts were used. Most resources focused on advance directives, enduring powers of attorney and substitute decision making. Relatively few provided information about legal duties (e.g. powers and responsibilities of substitute decision makers) or resolving conflict with health practitioners. Accessibility (understandability and actionability) of resource content varied. Conclusions Although numerous resources on end-of-life law are available online, community members may not be able to identify relevant resources or find resource content accessible. What is known about the topic? Research on participation by patients in decision making about their treatment has focused primarily on medical rather than legal knowledge. What does this paper add? The present study investigated which online resources community members may access to inform themselves about the law on end-of-life decision making. The resources identified were analysed for ease of location and content accessibility. What are the implications for practitioners? Authors of online resources on end-of-life decision making should consider whether their resources can be: (1) identified by search terms used by the public; (2) understood by a general audience; and (3) readily used to promote reader action.


Substitutive administration of thyroxine in patients after strumectomy.
The aim of the study is to present practical suggestions as to substitutive administration of thyroxine in patients who underwent strumectomy. Hypothyerosis due to strumectomy is an indication for starting treatment with thyroxine. Until thyroid cancer is excluded on the basis of histopathological examinations the patient should not take thyroxine, as there may be a possibility for the need of scinthigraphy of the whole body. Proper management of the patient with hypothyreosis includes informing the patient about the necessity of regular taking the hormone and undergoing regular check-ups.


A Max-Flow Based Algorithm for Connected Target Coverage with Probabilistic Sensors.
Coverage is a fundamental issue in the research field of wireless sensor networks (WSNs). Connected target coverage discusses the sensor placement to guarantee the needs of both coverage and connectivity. Existing works largely leverage on the Boolean disk model, which is only a coarse approximation to the practical sensing model. In this paper, we focus on the connected target coverage issue based on the probabilistic sensing model, which can characterize the quality of coverage more accurately. In the probabilistic sensing model, sensors are only be able to detect a target with certain probability. We study the collaborative detection probability of target under multiple sensors. Armed with the analysis of collaborative detection probability, we further formulate the minimum ϵ-connected target coverage problem, aiming to minimize the number of sensors satisfying the requirements of both coverage and connectivity. We map it into a flow graph and present an approximation algorithm called the minimum vertices maximum flow algorithm (MVMFA) with provable time complex and approximation ratios. To evaluate our design, we analyze the performance of MVMFA theoretically and also conduct extensive simulation studies to demonstrate the effectiveness of our proposed algorithm.


[Distribution of Clostridium tetani in topsoil from Sagamihara, central Japan].
Despite reports of Clostridium tetani being isolated from soil in Kanazawa, Okinawa, and Tokyo, Japan, little has been studied about C. tetani distribution in other regions. We studied C. tetani in topsoil samples collected from private gardens, public road shoulders, a university campus, mountains, and fields in Sagamihara. C. tetani occurred in 8 of 35 soil samples (22.9%) and tetanus toxin in 7 of the 8 C. tetani-positive samples (87.5%). Contamination was clearly higher in soils from mountains near Tsukui-gun (Kanagawa Prefecture), Minamitsuru-gun, and Uenohara and Koshu cities (Yamanashi Prefecture) than in other regions. These findings suggest that tetanus toxin-producing strains of C. tetani tend to inhabit the topsoil of western Sagaminaha region, as a geographical feature.


'Fogging' resulting in normal MRI 3 weeks after ischaemic stroke.
CT of the brain is often negative in acute stroke. The absence of changes suggestive of infarction on MRI of the brain in the setting of a recent stroke is unusual. An otherwise fit and well 69-year-old Caucasian man presented to the hospital with a 26-h history of acute mild right hemiparesis. CT brain on arrival showed no abnormality. MRI brain was also normal 3 weeks post stroke with abnormality seen only at 11 weeks. Stroke remains a clinical diagnosis. The time of the stroke must be taken into consideration when interpreting MRI brain images. Infarct may be 'invisible' on MRI in the subacute phase of ischaemic stroke.


Thyroid hormone depletion inhibits astrocytoma proliferation via a p53-independent induction of p21 (WAF1/CIP1).
Clinical hypothyroidism has been associated with prolonged survival in several types of malignancies, but the mechanism of this effect is unknown. In vitro studies of thyroid hormone depletion (via culture in medium containing 5% thyroid hormone-depleted fetal bovine serum (FBS)) were carried out using a human glioblastoma cell line (WITG3) which expresses a mutant, non-functional p53. Thyroid hormone depletion inhibited WITG3 proliferation compared to control medium containing 5% euthyroid FBS. There was no evidence of apoptosis and viability was not compromised. Cell cycle analysis by flow cytometry indicated that thyroid hormone depletion accumulated WITG3 cells in G1, with fewer cells progressing into S than in euthyroid medium. By immunoblotting, p21 (WAF1/CIP1) was only slightly detectable in lysates from WITG3 cells grown in control euthyroid medium; however, in thyroid hormone-depleted FBS, a marked induction of p2 1 occurred which could be reversed by exogenous thyroid hormone These data indicate that thyroid hormone depletion may cause a G, arrest in astrocytoma mediated by a p53-independent induction of p21 (WAF1/CIP1). Results suggest a mechanism which may explain the effect of hypothyroidism on suppression of tumor cell growth.


Troponin elevation as a marker of short deterioration and one-year death in a high-risk surgical patient cohort in a low and middle income country setting: a postoperative approach to increase surveillance.
Myocardial injury after noncardiac surgery is common and mostly asymptomatic. The ideal target population that will benefit from routine troponin measurements in low and middle income countries (LMICs) is unclear. This study aims to evaluate the clinical outcomes of a cohort of high-risk surgical patients according to high-sensitivity troponin T (hsTnT) in an LMIC setting. We conducted a prospective cohort study of 442 high-risk patients undergoing noncardiac surgery at a Brazilian hospital between February 2019 and March 2020. High-sensitivity troponin T levels were measured preoperatively, 24 hr, and 48 hr after surgery and stratified into three groups: normal (< 20 ng·L-1); minor elevation (20-65 ng·L-1); and major elevation (> 65 ng·L-1). We performed survival analysis to determine the association between myocardial injury and one-year mortality. We described medical interventions and evaluated unplanned intensive care unit (ICU) admission and complications using multivariable models. Postoperative myocardial injury occurred in 45% of patients. Overall, 30-day mortality was 8%. Thirty-day and one-year mortality were higher in patients with hsTnT ≥ 20 ng·L-1. One-year mortality was 18% in the unaltered troponin group vs 31% and 41% for minor and major elevation groups, respectively. Multivariable analysis of one-year survival showed a hazard ratio (HR) of 1.94 (95% confidence interval [CI], 1.22 to 3.09) for the minor elevation group and a HR of 2.73 (95% CI, 1.67 to 4.45) for the troponin > 65 ng·L-1 group. Patients with altered troponin had more unplanned ICU admissions (13% vs 5%) and more complications (78% vs 48%). This study supports evidence that hsTnT is an important prognostic marker and a strong predictor of all-cause mortality after surgery. Troponin measurement in high-risk surgical patients could potentially be used as tool to scale-up care in LMIC settings. ClinicalTrials.gov (NCT04187664); first submitted 5 December 2019.


Effect of protein kinase C on proliferation and apoptosis of T lymphocytes in idiopathic thrombocytopenic purpura children.
It is well-documented that T lymphocyte proliferation and apoptosis are abnormal in idiopathic thrombocytopenic purpura (ITP) children. However, the underlying regulation mechanisms especially in terms of signal transduction remain unknown. In this paper, we reported the changes of protein kinase C (PKC) activity in peripheral blood T lymphocytes and the effect of PKC on T lymphocyte proliferation and apoptosis. We demonstrated that in ITP children, the activator (PMA) and inhibitor (H-7) of PKC affected on T lymphocyte proliferation and apoptosis dramatically, but they altered little in healthy children. PKC activity was significantly enhanced in ITP children together with an increased expression of FasL on CD3+T, CD4+T and CD8+T cells, resulting in a positive correlation between PKC activity and the expression of FasL on T cells. While the PKC activity and the platelet count were negatively correlated. Taken together, our findings suggest that the PKC activation may enhance T lymphocytes activity, suppress T cell apoptosis and be involve in thrombocytes damage as a mechanism related to immune pathogenesis of ITP.


Surgery for traumatic rupture of the thoracic aorta.
Between 1975 and 1980, 9 patients with traumatic rupture of the thoracic aorta were operated at our institution. All patients showed additional multiple limb and internal organ injuries. Leading symptoms of aortic rupture were mediastinal widening (8), left-sided hemothorax (6), and acute aortic coarctation (2). Aortic rupture was proven by angiography in 8 patients and during exploratory thoracotomy in another. The time interval between trauma and operation was one to 48 hours, in 6 patients less than 4 hours. Atrio-femoral bypass was used in 3 patients, TDMAC-heparin shunt in 4 patients and 2 patients were operated without bypass. Prosthesis interposition was required in 3 patients while direct suture was possible in 6 patients. Long-term survival was achieved in 7 patients, one patient died from shock sequelae and another had suffered inoperable multiple rupture along the ascending and transverse aorta. It is concluded that patients with traumatic aortic rupture have a relatively good prognosis if diagnosis is established immediately and if surgery is feasible. The operative result is influenced substantially by the degree of preoperative shock and the presence of additional injuries.


Working Memory Requires a Combination of Transient and Attractor-Dominated Dynamics to Process Unreliably Timed Inputs.
Working memory stores and processes information received as a stream of continuously incoming stimuli. This requires accurate sequencing and it remains puzzling how this can be reliably achieved by the neuronal system as our perceptual inputs show a high degree of temporal variability. One hypothesis is that accurate timing is achieved by purely transient neuronal dynamics; by contrast a second hypothesis states that the underlying network dynamics are dominated by attractor states. In this study, we resolve this contradiction by theoretically investigating the performance of the system using stimuli with differently accurate timing. Interestingly, only the combination of attractor and transient dynamics enables the network to perform with a low error rate. Further analysis reveals that the transient dynamics of the system are used to process information, while the attractor states store it. The interaction between both types of dynamics yields experimentally testable predictions and we show that this way the system can reliably interact with a timing-unreliable Hebbian-network representing long-term memory. Thus, this study provides a potential solution to the long-standing problem of the basic neuronal dynamics underlying working memory.


Extraction and immunochemical characterization of cholecystokinin-like peptides from pig and rat brain.
Two major classes of immunoreactive cholecystokinin peptides (iCCK) have been identified in rat and pig brains: (i) large basic peptides (big iCCK) resembling the 33-amino acid porcine cholecystokinin (pCCK33) in size and charge; (ii) small acidic peptides (small iCCK) resembling the COOH-terminal fragments of CCK. Boiling 0.1 M HCl maximally extracts big iCCK; boiling 0.1 M NaOH maximally extracts small iCCK. The differences in hormonal forms removed by these extractants are not likely to be due to enzymatic conversion during the extraction procedures. Fractionation on Sephadex G-50 and starch gel electrophoresis combined with radioimmunoassay using three antisera of different specificities--(i) directed towards the NH2 terminus of pCCK33, (ii) produced by immunization with COOH-terminal fragment CCK8, (iii) produced by immunization with COOH-terminal fragment CCK4--are consistent with the hypothesis that a major fraction of big iCCK may represent intact cholecystokinin with a COOH-terminal extension, as has recently been suggested for gastrin, a molecule having a COOH-terminal pentapeptide identical with that of cholecystokinin.


Motivation and intelligence drive auditory perceptual learning.
Although feedback on performance is generally thought to promote perceptual learning, the role and necessity of feedback remain unclear. We investigated the effect of providing varying amounts of positive feedback while listeners attempted to discriminate between three identical tones on learning frequency discrimination. Using this novel procedure, the feedback was meaningless and random in relation to the listeners' responses, but the amount of feedback provided (or lack thereof) affected learning. We found that a group of listeners who received positive feedback on 10% of the trials improved their performance on the task (learned), while other groups provided either with excess (90%) or with no feedback did not learn. Superimposed on these group data, however, individual listeners showed other systematic changes of performance. In particular, those with lower non-verbal IQ who trained in the no feedback condition performed more poorly after training. This pattern of results cannot be accounted for by learning models that ascribe an external teacher role to feedback. We suggest, instead, that feedback is used to monitor performance on the task in relation to its perceived difficulty, and that listeners who learn without the benefit of feedback are adept at self-monitoring of performance, a trait that also supports better performance on non-verbal IQ tests. These results show that 'perceptual' learning is strongly influenced by top-down processes of motivation and intelligence.


Theoretical analysis of urban runoff pollutographs: identification of characterization variables and impact.
This research presents a novel methodology to determine runoff water retention volumes that allow the design of storage tanks for storm sewer overflows. It is based on the use of the Stormwater Management Model (SWMM) to generate hydrographs and runoff pollutographs of a fictional urban basin. Three pollutants (TS, BOD5 and TN) are simulated for a given set of rains and the values taken by a proposed set of characterization variables for the pollutographs obtained are analysed. Correlation and determination coefficients that exist between the different variables are analysed while also performing a multivariate characterization using PCA and cluster analysis. In the case study presented, using IDF curves of the studied city, a probability of occurrence (Tr) is assigned to the values taken by the proposed characterization variables. To assess the impact and identify the most unfavourable pollutographs within the set of selected rains, impact evaluation variables (IEV's) are established, based on the proposed characterization variables and by simulating the discharge to a receiving water body (river with initial concentration and constant flow). Finally, a storm sewer overflow is simulated, deriving a maximum flow for purification, and dimensioning retention tanks for different fractions of the total volume of runoff to control the maximum values of a specific IEV impact evaluation variable. Taking a design return period Trssd ≥ 10 years, the results obtained in the study case were 146.50 m3/ha imp for a 100% retention of the total runoff volume and 117.20 m3/ha imp for an 80% retention.


Small-scale dynamo with finite correlation times.
Fluctuation dynamos occur in most turbulent plasmas in astrophysics and are the prime candidates for amplifying and maintaining cosmic magnetic fields. A few analytical models exist to describe their behavior, but they are based on simplifying assumptions. For instance, the well-known Kazantsev model assumes an incompressible flow that is δ-correlated in time. However, these assumptions can break down in the interstellar medium as it is highly compressible and the velocity field has a finite correlation time. Using the renewing flow method developed by Bhat and Subramanian (2014), we aim to extend Kazantsev's results to a more general class of turbulent flows. The cumulative effect of both compressibility and finite correlation time over the Kazantsev spectrum is studied analytically. We derive an equation for the longitudinal two-point magnetic correlation function in real space to first order in the correlation time τ and for an arbitrary degree of compressibility (DOC). This generalized Kazantsev equation encapsulates the original Kazantsev equation. In the limit of small Strouhal numbers St∝τ we use the Wentzel-Kramers-Brillouin approximation to derive the growth rate and scaling of the magnetic power spectrum. We find the result that the Kazantsev spectrum is preserved, i.e., M_{k}(k)∼k^{3/2}. The growth rate is also negligibly affected by the finite correlation time; however, it is reduced by the finite magnetic diffusivity and the DOC together.


Computationally Efficient Direction Finding for a Mixture of Circular and Strictly Noncircular Sources with Uniform Rectangular Arrays.
In this paper, a novel two-dimensional (2D) direction-of-arrival (DOA) estimation algorithm for the mixed circular and strictly noncircular sources is proposed. A general array model with a mixture of signals is firstly built based on uniform rectangular arrays (URAs), and then, the approach, which uses the rank-reduction-based ROOT-MUSIC, can solve 2D DOA estimation problem. Besides, the theoretical error of the proposed algorithm, a criterion of the performance for evaluation, is analyzed by the first-order Taylor expression using second-order statistics. As verified by the simulation results, a better DOA estimation performance and a lower computational complexity are achieved by the proposed algorithm than the existing methods resorting to the noncircularity of the incoming signals.


Night-to-night variability in obstructive sleep apnea severity: relationship to overnight rostral fluid shift.
Overnight rostral fluid shift from the legs to the neck may narrow the pharynx and contribute to obstructive sleep apnea (OSA) pathogenesis. We hypothesized that night-to-night changes in the apnea-hypopnea index (AHI) would be associated with changes in overnight rostral fluid shift. Twenty-six patients with OSA (AHI ≥10) underwent two polysomnograms 14 days apart with measurement of neck and leg fluid volumes (LFV), neck circumference and upper-airway cross-sectional area before and after sleep. Although mean AHI did not differ between polysomnograms, 35% of patients had a difference in AHI >10, indicating significant intra-individual variability. There were direct correlations between change in non-rapid-eye movement (NREM), but not REM AHI and change in evening LFV between polysomnograms (r = 0.440, p = 0.036 and r = 0.005, p = 0.982, respectively) and between change in supine, but not non-supine AHI and change in evening LFV (r = 0.483, p = 0.020 and r = 0.269, p = 0.280, respectively). An increase in evening LFV between polysomnograms was associated with a greater overnight decrease in LFV (r = 0.560, p = 0.005) and a greater overnight increase in neck fluid volume (r = 0.498, p = 0.016). Additionally, a greater overnight increase in neck circumference was associated with a greater overnight increase in neck fluid volume between polysomnograms (r = 0.453, p = 0.020) and a greater overnight decrease in upper-airway cross-sectional area (r = -0.587, p = 0.005). Intra-individual variability in OSA severity may be partly explained by day-to-day changes in evening leg fluid volume and overnight rostral fluid shift, which may be most important in the pathogenesis of OSA during NREM and supine sleep.


A Novel In Vitro Technique for Assessing Dental Implant Osseointegration.
By definition, osseointegration means close contact between bone and implant. Bone response is related to implant surface properties. Various surfaces have been studied and applied to improve the biological properties of the implant and thereby favor the mechanism of osseointegration. This strategy aims to promote osseointegration by means of a faster and stronger bone formation, improving stability during the healing process, and thus allowing for earlier loading of the implant. Dental implant osseointegration has so far been studied in various animal models. The development of a method based on tissue engineering for assessing the osseointegration process in vitro could prove a valid biomimetic alternative to sacrificing animals. In this study, flat cylindrical dental implants with moderately rough surfaces and machined implants were set in bovine bone blocks. Then, adipose-derived stem cells (ADSCs) were three dimensionally cultured onto these blocks in osteo-endothelial medium for up to 30 days to mimic the osseointegration process in vitro. Scanning electron microscopy (SEM) and gene expression were used to examine stem cell commitment. Mechanical pull-out tests were also performed. SEM analysis identified cells with an osteoblast morphology adhering to the surface of the implants after their removal. Gene expression analysis showed that ADSCs seeded onto the bone blocks were able to express osteoblast and endothelial markers. The implants with the moderately rough surface generated higher pull-out strengths when compared with the machined implants. Nevertheless, the pull-out test values were higher for implants placed in bone blocks with ADSCs than for those set in scaffolds without stem cells. Our results demonstrate the validity of the method adopted and its potential for use in the in vitro assessment of the biological behavior of dental implant surfaces.


[Comparative experimental study of inverting and everting sutures in the colon].
The authors carried out 88 sutures of the ascending colon in Wistar rats, 44 in inversion and the remainder in eversion. The suture material used was monofilament 9/0 nylon. The intestinal diameter was measured using an instrument and the healing process studied by means of the following parameters: granulocytes, oedema, fibrin, fibroblasts and re-epithelialisation of the mucosa, on histology. The results prove that inverted sutures heal within 10 days, whereas everted sutures are not healed after 17 days. Furthermore, we demonstrated the fact that, after 72 hours, the intestinal caliber above the suture showed no appreciable differences compared with that of the normal colon.


Influenza vaccination in the elderly: can efficacy be enhanced?
Influenza remains a major cause of illness and death in geriatric populations, especially in the frail elderly and those who live in nursing homes. Influenza vaccine has been useful in reducing morbidity and mortality; however, the vaccine is not uniformly successful in preventing infection, particularly in those people who are immunocompromised. In this article, the rationale and expectations for the current vaccine are reviewed and strategies to enhance vaccine efficacy are presented.


Nitric oxide and zinc homeostasis in acute lung injury.
Among putative small molecules that affect sensitivity to acute lung injury, zinc and nitric oxide are potentially unique by virtue of their interdependence and dual capacities to be cytoprotective or injurious. Nitric oxide and zinc appear to be linked via an intracellular signaling pathway involving S-nitrosation of metallothoinein--itself a small protein known to be an important inducible gene product that may modify lung injury. In the present article, we summarize recent efforts using genetic and fluorescence optical imaging techniques to: (1) demonstrate that S-nitrosation of metallothionein affects intracellular zinc homeostasis in intact pulmonary endothelial cells; and (2) reveal a protective role for this pathway in hyperoxic and LPS-induced injury.


Tumor mitochondrial transfer ribonucleic acids: the nucleotide sequence of Morris hepatoma 5123D mitochondrial tRNA GUC Asp.
A mitochondrial aspartate tRNA (anticodon GUC) was isolated from a transplantable rat tumor, Morris hepatoma 5123D, and sequenced. The sequence, pGAGAUAUUm(1)AGUAAAAUAAUUACA psi AACCUUGUCAAGGUUAAGUUAUAGACUUAAAUCUAUAUAUCUUACCAOH, can be arranged in a cloverleaf structure. The RNA exhibits a number of unusual features, such as lack of the constant -G-G- and -T-psi-C- sequences in loops I and IV, respectively, small size of these loops, lack of the constant G.C base pair adjacent to loop IV, predominance of A.U base pairs in general, and presence of m1A in position 9. The RNA exhibits 82 and 70% homology with the DNA-derived putative sequences of human placenta and beef heart mitochondrial tRNA Asp, respectively, and bears little resemblance to other sequenced aspartate tRNAs of non-mitochondrial origin.


[Plexiform neurofibroma of the bladder associated with neurofibromatosis type 1: a case report].
Neurofibromatosis type 1 (NF1) is an autosomal dominant disease with multiple neurofibroma and café-au-lait spots. We report a case of plexiform neurofibroma of the bladder associated with NF1. A 34-year-old female was referred to our hospital for thickness of the bladder wall. Multiple café-au-lait spots and neurofibroma was found on her skin,and she was diagnosed with neurofibromatosis type 1. Ultrasound examination demonstrated bladder wall thickening,and cystoscopy revealed an irregular and erythematous mucosa. Transurethral biopsy of the bladder wall was performed. Histopathological diagnosis was plexiform neurofibroma of the bladder.


Identification of intracellular bacteria in the basal plate of the human placenta in term and preterm gestations.
Bacteria have been identified in different regions of the placenta. Here, we tested the hypothesis that the maternal basal plate of the placenta harbors microbes that may be associated with adverse pregnancy outcomes. We performed a cross-sectional study of pregnancies from a single tertiary care hospital. Maternal medical and obstetric characteristics were obtained and pregnancies followed up prospectively for outcomes and placental collection. After delivery, systematic random sampling of the placental basal plate was performed. Paraffin sections of basal plates were stained with 4 histologic stains and scored for morphological evidence of bacteria. Of 195 total patients in the study, Gram-positive and -negative intracellular bacteria of diverse morphologies were documented in the basal plates of 27% of all placentas. Of the patients, 35% delivered preterm. No difference was noted between placental basal plates from preterm or term gestations. Intracellular bacteria were found in the placental basal plates of 54% spontaneous preterm deliveries <28 weeks, and in 26% of term spontaneous deliveries (P = .02). Intracellular bacteria were also documented in placentas without clinical or pathologic chorioamnionitis. A total of 27% of placentas demonstrated intracellular bacteria in the placental basal plate using morphological techniques. Thus, the maternal basal plate is a possible source of intrauterine colonization and placental pathological examination could include examination for bacteria in this important maternal-fetal interface.


Regulation of fluoroquinolone uptake by human neutrophils: involvement of mitogen-activated protein kinase.
Although human neutrophils actively internalize fluoroquinolones, the precise uptake mechanism is not fully understood. In this study, we investigated the role of protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) in fluoroquinolone uptake in neutrophils. Spontaneous grepafloxacin uptake was significantly enhanced by SB203580, a p38 MAPK inhibitor, in a dose-dependent manner, but not by PD98059, a specific inhibitor of the upstream kinase that activates p44/42 MAPK. Neither inhibitor affected spontaneous ciprofloxacin or ofloxacin uptake. Phorbol myristate acetate (PMA) treatment enhanced ciprofloxacin uptake, whereas it reduced grepafloxacin uptake. These effects by PMA were significantly inhibited by the pretreatment of neutrophils with GF109203X, a specific inhibitor of PKC. PMA had no effect on ofloxacin uptake. The PMA-induced enhancement of ciprofloxacin uptake was inhibited by PD98059, but not by SB203580. On the other hand, the PMA-induced reduction of grepafloxacin uptake was not inhibited by either MAPK inhibitor. Grepafloxacin, but not ciprofloxacin or ofloxacin, strongly phosphorylated p38 MAPK. This phosphorylation of p38 MAPK was not inhibited by GF109203X pretreatment. None of these three fluoroquinolones phosphorylated p44/42 MAPK. PMA phosphorylated both p38 and p44/42 MAPK. These findings indicate that grepafloxacin negatively regulates its uptake in neutrophils, and p38 MAPK activation is involved in this down-regulation of grepafloxacin uptake. Ciprofloxacin uptake is positively regulated by the activation of PKC, and p44/42 MAPK activation is involved in this up-regulation. Neither PKC, p38 nor p44/42 MAPK is involved in the regulation of ofloxacin uptake.


Correlation of normal thyroid ultrasonography with thyroid tests.
Thyroid disorders are frequently seen in the community. Thyroid ultrasonography (US) is commonly used in the diagnosis of thyroid diseases. The relationship between heterogeneous echogenicity of thyroid gland and thyroid tests are well known. The aim of this study is to evaluate the correlation of normal US with the thyroid tests. A total of 681 individuals were enrolled in the study. Individuals were separated into two groups as normal (group 1) and hypoechoic (group 2) according to the echogenicity in US. Subjects with nodular thyroid lesions were excluded from the study. Thyroid stimulating hormone (TSH), free T4 (fT4), thyroid peroxidase antibody (TPOAb) and anti-thyroglobulin antibody (TgAb) values were recorded in both groups and thyroid stimulating hormone receptor antibody (TRAb) was recorded in individuals with low TSH. 86.1% of individuals in group 1 had normal TSH, 93.7% had normal thyroid antibodies and in 77.6% of individuals, all thyroid tests performed were normal. In the 6.9% of the group 2, all reviewed thyroid tests were normal (P<0.001). Our study shows that US is correlated with normal thyroid function tests and is a valuable tool in the prediction of normal thyroid function.