Causes of death among patients with myasthenia gravis in Norway between 1951 and 2001.
This study investigated the causes of death among patients with myasthenia gravis (MG), with emphasis on respiratory tract and cardiac disease. The Norwegian Cause of Death Register contains information on all deaths among Norwegian citizens. In total, 249 deceased patients with MG were identified (1951-2001). These were compared with 1245 controls deceased in the same period and matched for sex and year of birth. The death certificates of patients with MG had a significantly higher occurrence of respiratory tract disease as cause of death than controls (28.1% v 20.9%, p = 0.012). The difference was most pronounced for male patients, for patients dying between 30 and 69 years of age, and for deaths occurring before 1996. For cardiac disease there was a significantly lower occurrence among patients with MG than among controls at 50-69 years of age, for both men (19.4% v 52.0%, p = 0.001) and women (14.6% v 29.6%, p = 0.036). Age and year of death were important determinants for the causes of death, but could not account for the differences between the patients with MG and controls. This study shows that patients with MG dying between 1951 and 1995 had a higher occurrence of respiratory tract disease listed as cause of death than had a matched control group. The lack of difference after 1995 probably reflects improved treatment of MG and its complications. The reduced occurrence of cardiac disease among patients with MG is probably explained by competing factors (respiratory tract disease) causing death.


Short- versus long-course antibacterial therapy for community-acquired pneumonia : a meta-analysis.
The evidence for traditionally recommended 7- to 14-day duration of antibacterial therapy for community-acquired pneumonia (CAP) is not well established. We endeavoured to assess the effectiveness and safety of shorter than traditionally recommended antibacterial therapy for CAP. We performed a meta-analysis of randomized controlled trials (RCTs) comparing short- (< or = 7 days) versus long- (> or = 2 days difference) course therapy for CAP with the same antibacterial regimens, in the same daily dosages. Five RCTs involving adults (including outpatients and inpatients who did not require intensive care) and two RCTs involving children (aged 2-59 months, residing in developing countries) were included. All RCTs were double-blind and assessed patients with CAP of mild to moderate severity. No differences were found between short- (adults 3-7 days; children 3 days) and long- (adults 7-10 days; children 5 days) course regimens (adults - amoxicillin, cefuroxime, ceftriaxone, telithromycin and gemifloxacin; children - amoxicillin) regarding clinical success at end-of-therapy (six RCTs; 5107 patients [1095 adults, 4012 children]; fixed-effect model [FEM]; odds ratio [OR] = 0.89; 95% CI 0.74, 1.07), clinical success at late follow-up, microbiological success, relapses, mortality (seven RCTs; 5438 patients; FEM; OR = 0.57; 95% CI 0.23, 1.43), adverse events (five RCTs; 3214 patients; FEM; OR = 0. 90; 95% CI 0.72, 1.13) or withdrawals as a result of adverse events. No differences were found in subset analyses of adults or children, and of patients treated with no more than 5-day short-course regimens versus at least 7-day long-course regimens. No difference was found in the effectiveness and safety of short- versus long-course antimicrobial treatment of adult and paediatric patients with CAP of mild to moderate severity.


Highly efficient 5' capping of mitochondrial RNA with NAD+ and NADH by yeast and human mitochondrial RNA polymerase.
Bacterial and eukaryotic nuclear RNA polymerases (RNAPs) cap RNA with the oxidized and reduced forms of the metabolic effector nicotinamide adenine dinucleotide, NAD+ and NADH, using NAD+ and NADH as non-canonical initiating nucleotides for transcription initiation. Here, we show that mitochondrial RNAPs (mtRNAPs) cap RNA with NAD+ and NADH, and do so more efficiently than nuclear RNAPs. Direct quantitation of NAD+- and NADH-capped RNA demonstrates remarkably high levels of capping in vivo: up to ~60% NAD+ and NADH capping of yeast mitochondrial transcripts, and up to ~15% NAD+ capping of human mitochondrial transcripts. The capping efficiency is determined by promoter sequence at, and upstream of, the transcription start site and, in yeast and human cells, by intracellular NAD+ and NADH levels. Our findings indicate mtRNAPs serve as both sensors and actuators in coupling cellular metabolism to mitochondrial transcriptional outputs, sensing NAD+ and NADH levels and adjusting transcriptional outputs accordingly.


Small molecule approaches in plants.
Small molecules offer exciting opportunities for plant science. So far, bioactive small molecules have been identified as plant hormones, herbicides, growth regulators, or taken from animal research. Recently, plant scientists have started to explore further the chemical space for novel modulators of plant hormone signalling, and have followed up this work with exciting discoveries illustrating the potential of small molecules such as brassinazole and sirtinol. New chemical genetic screens have been designed to generate chemical tools for the investigation of membrane trafficking, gravitropism and plant immunity. Further novel 'chemetic' tools to identify targets and modes of action are currently generated through an intimate interdisciplinary collaboration between biologists and small molecule chemists.


Curcumin inhibited the growth and invasion of human monocytic leukaemia SHI-1 cells in vivo by altering MAPK and MMP signalling.
Context: Curcumin, a polyphenolic compound extracted from the rhizome of the tropical plant Curcuma longa L. (Zingiberaceae), has been considered as a cancer chemopreventive drug by American National Cancer Institute.Objective: To examine the effect of curcumin on acute monocytic leukaemia SHI-1 cells in vivo.Materials and methods: The SHI-1 cells (1 × 106 cells in 0.1 mL PBS) were injected subcutaneously into the right flanks of the female SCID mice. Curcumin dissolved in olive oil (15 and 30 mg/kg) was administered (i.p.) to mice once a day for 15 days while the control group received olive oil injection. Tumour proliferation and apoptosis were examined by PCNA, TUNEL and cleaved caspase-3 staining. The expression of MAPK, NF-κB, MMP9, MMP2 and vimentin were confirmed by RT-PCR, immunohistochemistry or western blotting.Results: Administration of curcumin significantly inhibited tumour growth, as the tumour weight decreased from 0.67 g (control) to 0.47 g (15 mg/kg) and 0.35 g (30 mg/kg). Curcumin inhibited the expression of PCNA and increased the degree of TUNEL and cleaved caspase-3 staining in tumour tissue. The results of western blotting showed that curcumin treatment inhibited NF-κB and ERK signalling while activating p38 and JNK. Moreover, curcumin attenuated the mRNA transcription and protein expression of MMP2 and MMP9. Curcumin also suppressed the level of vimentin.Discussion and conclusions: Our study demonstrates that curcumin can inhibit the growth and invasion of human monocytic leukaemia in vivo, suggesting the possible use of curcumin for anti-metastasis in leukaemia and the value of determining its unique target.


What is value-accumulated reward or evidence?
Why are you reading this abstract? In some sense, your answer will cast the exercise as valuable-but what is value? In what follows, we suggest that value is evidence or, more exactly, log Bayesian evidence. This implies that a sufficient explanation for valuable behavior is the accumulation of evidence for internal models of our world. This contrasts with normative models of optimal control and reinforcement learning, which assume the existence of a value function that explains behavior, where (somewhat tautologically) behavior maximizes value. In this paper, we consider an alternative formulation-active inference-that replaces policies in normative models with prior beliefs about the (future) states agents should occupy. This enables optimal behavior to be cast purely in terms of inference: where agents sample their sensorium to maximize the evidence for their generative model of hidden states in the world, and minimize their uncertainty about those states. Crucially, this formulation resolves the tautology inherent in normative models and allows one to consider how prior beliefs are themselves optimized in a hierarchical setting. We illustrate these points by showing that any optimal policy can be specified with prior beliefs in the context of Bayesian inference. We then show how these prior beliefs are themselves prescribed by an imperative to minimize uncertainty. This formulation explains the saccadic eye movements required to read this text and defines the value of the visual sensations you are soliciting.


Care of the secondary patient in family practice. A report from the Ambulatory Sentinel Practice Network.
Care of a secondary patient (an individual other than the primary patient for an outpatient visit) is common in family practice, but the content of care of this type of patient has not been described. In a cross-sectional study, 170 volunteer primary care clinicians in 50 practices in the Ambulatory Sentinel Practice Network reported all occurrences of care of a secondary patient during 1 week of practice. These clinicians reported the characteristics of the primary patient and the secondary patient and the content of care provided to the secondary patient. Content of care was placed in 6 categories (advice, providing a prescription, assessment or explanation of symptoms, follow-up of a previous episode of care, making or authorizing a referral, and general discussion of a health condition). Physicians reported providing care to secondary patients during 6% of their office visits. This care involved more than one category of service for the majority of visits involving care of a secondary patient. Advice was provided during more than half the visits. A prescription, assessment or explanation of symptoms, or a general discussion of condition were provided during approximately 30% of the secondary care visits. Secondary care was judged to have substituted for a separate visit 60% of the time, added an average of 5 minutes to the visit, and yielded no reimbursement for 95% of visits. Care of a secondary patient reflects the provision of potentially intensive and complex services that require additional time and are largely not reimbursed or recognized by current measures of primary care. This provision of secondary care may facilitate access to care and represent an added value provided by family physicians.


Auricular acupuncture for pre-exam anxiety in medical students: a prospective observational pilot investigation.
Auricular acupuncture (AA) is effective for the treatment of preoperative anxiety. We aimed to study the feasibility and effects of AA on exam anxiety in a prospective observational pilot study. Healthy medical students received bilateral AA using indwelling fixed needles at points MA-IC1, MA-TF1, MA-SC, MA-AH7, and MA-T on the day before an anatomy exam. The needles were removed after the exam. Anxiety levels were measured using the State-Trait-Anxiety Inventory (STAI) and a 100 mm visual analogue scale (VAS-100) before and after the AA intervention and once again immediately before the exam. The duration of sleep on the night before the exam was recorded and compared to that over the preceding 1 week and 6 months (all through students' recollection). In addition, blood pressure, heart rate and the acceptability of AA to the students were recorded. Ten students (all female) were included in the final analysis. All tolerated the needles well and stated they would wish to receive AA again for exam anxiety in the future. Exam anxiety measured using both STAI and VAS-100 decreased by almost 20% after AA. AA was well accepted, the outcome measurement was feasible, and the results have facilitated the calculation of the sample size for a subsequent randomised controlled trial.


Antineuronal antibodies in movement disorders.
To determine whether children with recent onset of movement disorders (Tourette syndrome, motor and/or vocal tics, chorea, choreiform movements) show evidence of serological antibodies directed against the human central nervous system as previously documented in research on Sydenham's chorea. Serum antibodies against previously frozen human caudate nucleus sections were analyzed using a blinded design and immunofluorescent staining methods. The sera of one group of 50 children referred for evaluation of attention deficit hyperactivity disorder, behavior disorders, and learning disabilities (24 with an associated movement disorder) seen between June 1989 and June 1990 were analyzed. The study was replicated in 33 children (21 with an associated movement disorder) seen between June 1990 and November 1990. In the original sample of 50 children, those with movement disorders were significantly more likely to have evidence of antineuronal antibodies than were those without movement disorders (odds ratio [OR] 4.80, 95% confidence interval [CI] 2.58 to 8.93). Results of the replication were similar (OR 6.00, 95% CI 2.56 to 14.03). For the total group, the OR was 5.50, (95% CI 3.54 to 8.99), which is highly significant. The percentage of children with a movement disorder whose sera were strongly positive for antineuronal antibodies (44%) was very similar to that previously found in children with Sydenham's chorea (46%). Children with movement disorders were also more likely than children without movement disorders to have at least one antistreptococcal titer elevated. The data strongly suggest an association between antecedent group A beta-hemolytic streptococcal infection as inferred from elevated antistreptococcal titers and the presence of serum antineuronal antibodies, which may, in turn, be linked to childhood movement disorders.


[Functional dyspepsia: approaches to Helicobacter pylori eradication therapy].
At the present, Helicobacter-associated gastritis is not considered to be an important cause of dyspeptic symptoms. Therefore, patients with dyspeptic symptoms and proven Helicobacter-gastritis are diagnosed as having functional dyspepsia, provided that Helicobacter-associated lesions like ulcers or malignancies are absent. It is controversial whether or not to treat a patient with functional dyspepsia with Helicobacter gastritis. Conclusive controlled clinical trials are lacking. If it is assumed in a given patient, that Helicobacter could be responsible for the complaints (an assumption which can never be proven and only suspected when the patient remains asymptomatic during longterm follow-up after cure of the infection) and if the patient has not responded to a standard treatment (antisecretory or prokinetic agents), we recommend Helicobacter therapy. Presently, in spring 1995, the following treatment is, in our view, the best choice during seven (to ten) days: The patient takes 20 mg omeprazol in the morning, 250 mg clarithromycin in the morning and in the evening and 500 mg metronidazole in the morning and in the evening.


Time-lapsed, large-volume, high-resolution intravital imaging for tissue-wide analysis of single cell dynamics.
Pathologists rely on microscopy to diagnose disease states in tissues and organs. They utilize both high-resolution, high-magnification images to interpret the staining and morphology of individual cells, as well as low-magnification overviews to give context and location to these cells. Intravital imaging is a powerful technique for studying cells and tissues in their native, live environment and can yield sub-cellular resolution images similar to those used by pathologists. However, technical limitations prevent the straightforward acquisition of low-magnification images during intravital imaging, and they are hence not typically captured. The serial acquisition, mosaicking, and stitching together of many high-resolution, high-magnification fields of view is a technique that overcomes these limitations in fixed and ex vivo tissues. The technique however, has not to date been widely applied to intravital imaging as movements caused by the living animal induce image distortions that are difficult to compensate for computationally. To address this, we have developed techniques for the stabilization of numerous tissues, including extremely compliant tissues, that have traditionally been extremely difficult to image. We present a novel combination of these stabilization techniques with mosaicked and stitched intravital imaging, resulting in a process we call Large-Volume High-Resolution Intravital Imaging (LVHR-IVI). The techniques we present are validated and make large volume intravital imaging accessible to any lab with a multiphoton microscope.


Effect of a phase I Coxiella burnetii inactivated vaccine on body temperature and milk yield in dairy cows.
Q fever is a zoonotic disease caused by Coxiella burnetii. The pathogen is prevalent in ruminants (goats, sheep, cows), which are the main sources of human infection. In the cattle industry around the world, animal (15 to 20%) and herd (38 to 72%) level prevalences of C. burnetii are high. Vaccination of ruminants against Q fever is considered important to prevent spreading of the disease and risk of infection in humans. However, published information on side effects of the Q fever vaccination under field conditions is limited for cows. The objective of this study was to investigate the effect of the phase I C. burnetii inactivated vaccine Coxevac on body temperature and milk yield in dairy cows. In 2 experiments, a total of 508 cows were randomly divided into 2 groups to determine the effect of first vaccination on body temperature and milk yield. The C. burnetii serostatus of all cows was tested before vaccination with an indirect ELISA. The first experiment took place in the teaching and research barn of the Clinic of Animal Reproduction at the Freie Universität Berlin. Temperature was measured vaginally in 10 cows in a crossover design. The second experiment was conducted on a commercial dairy farm. Milk yield of 498 cows was measured 1 wk before and 1 wk after vaccination. In a subset of 41 cows, temperature was measured rectally. In both experiments, body temperature increased significantly after vaccination (1.0 ± 0.9°C and 0.7 ± 0.8°C). A significant difference was also found in body temperature between vaccinated and control cows. Thirty percent of the vaccinated animals in experiment 1 showed reversible swelling at the injection site as a reaction to the vaccination. The results indicate that vaccination against Q fever causes a transient increase of body temperature that peaks in the first 12 to 24h and declines after that. In experiment 2, vaccinated cows (26.8 ± 0.39 kg/d) produced significantly less milk than did control cows (28.2 ± 0.44 kg/d) 7d after first vaccination. The cumulative milk loss after first vaccination was influenced by an interaction between C. burnetii serostatus and average milk yield 7d before first vaccination. This was considered as part of the physiological immune response. Three out of 10 vaccinated animals in experiment 1 showed painful swelling of the skin at the injection site, which had a maximum size of 14.0 × 14.0 × 1.1cm. In conclusion, a transient increase of body temperature and a decrease in milk yield is prevalent after Coxevac vaccination.


The control of histone gene expression.
Histone proteins are essential for the packaging of DNA into chromosomes. Histone gene expression is cell-cycle-regulated and coupled to DNA replication. Control of histone gene expression occurs at the transcriptional and post-transcriptional level and ensures that a fine balance between histone abundance and DNA replication is maintained for the correct packaging of newly replicated DNA into chromosomes. In the present paper, we review histone gene expression, highlighting the control mechanisms and key molecules involved in this process.


Determination of the relationship between total antioxidant capacity and dietary antioxidant intake in obese patients.
Adipokines secreted from adipose tissue in obese individuals increase oxidative stress in the body and sufficient antioxidant consumption is recommended to reduce the effects of this stress. Consumption of foods rich in antioxidants is thought to be related to serum total antioxidant capacity (TAC) but the effect of dietary antioxidant amount on serum antioxidant capacity is not yet clear. The aim of this study was to investigate the relationship between dietary antioxidant intake and serum TAC in obese and normal-weight individuals. Around 36 obese and 24 normal weighted volunteers participated in this study. Demographic characteristics, anthropometric measurements, and antioxidant food consumption from frequency questionnaires (questionnaire TAC) of individuals were recorded. The amount of antioxidant intake from diet (dietary TAC) was calculated from food consumption records. Serum TAC values were measured calorimetrically according to the Trolox equivalent antioxidant capacity (TEAC). The dietary TAC levels of the experimental group were higher than the control group (5.45 ± 6.15 mmol/day vs. 3.20 ± 7.27 mmol/day, P = 0.006); whereas, the ratio of serum TAC per body weight was significantly lower in obese participants (0.013 ± 0.0134 mmol/L vs. 0.017 ± 0.003 mmol/L, P< 0.001). However, a positive relation (r = 0.339, P = 0.008) was observed between dietary TAC and serum TAC. Moreover, a positive correlation between the serum TAC levels of the individuals and the weight in both groups (r = 0.335, P = 0.046 in obese participants, and r = 0.523, P = 0.009 in control group), and the BMI in the experimental group (r = 0.384, P = 0.021). Likewise, there is an association between the diet TAC level and the diet protein ratio (r = 0.478, P = 0.018) in obese participants. Dietary TAC intake was significantly higher and the TAC/weight lower in the experimental group. Moreover, the relationship between diet TAC and serum TAC was significant.


Measurement of the position-dependent electrophoretic force on DNA in a glass nanocapillary.
The electrophoretic force on a single DNA molecule inside a glass nanocapillary depends on the opening size and varies with the distance along the symmetrical axis of the nanocapillary. Using optical tweezers and DNA-coated beads, we measured the stalling forces and mapped the position-dependent force profiles acting on DNA inside nanocapillaries of different sizes. We showed that the stalling force is higher in nanocapillaries of smaller diameters. The position-dependent force profiles strongly depend on the size of the nanocapillary opening, and for openings smaller than 20 nm, the profiles resemble the behavior observed in solid-state nanopores. To characterize the position-dependent force profiles in nanocapillaries of different sizes, we used a model that combines information from both analytical approximations and numerical calculations.


First report on trichomonads from true bugs.
Although the hindgut of some insects represents a rich source of intestinal trichomonads, their diversity is only poorly understood. The aim of the present study was to investigate the presence and abundance of intestinal trichomonads in true bugs (Heteroptera). We microscopically examined intestinal contents of more than 780 specimens belonging to 28 families of true bugs from localities in China, Ghana and Papua New Guinea for the presence of intestinal endosymbionts. More than 120 samples were examined also by means of PCR using trichomonad-specific primers. We determined sequences of SSU rDNA and ITS region of two isolates of the genus Simplicimonas Cepicka, Hampl et Kulda, 2010 and one isolate of Monocercomonas colubrorum (Hammerschmidt, 1844). Although our results showed that trichomonads are very rare inhabitants of the intestine of true bugs, two of three isolated flagellates belong to species specific for reptiles. The possibility of transmission of trichomonads between reptiles and true bugs is discussed.


The present and future of peptide vaccines for cancer: single or multiple, long or short, alone or in combination?
Peptide vaccines incorporate one or more short or long amino acid sequences as tumor antigens, combined with a vaccine adjuvant. Thus, they fall broadly into the category of defined antigen vaccines, along with vaccines using protein, protein subunits, DNA, or RNA. They remain one of the most immunogenic approaches, based on measures of T-cell response in the blood or in draining lymph nodes. However, existing peptide vaccines have had limited success at inducing clinical tumor regressions, despite reliable induction of T-cell responses. Several new developments offer promise for improving peptide vaccines, including use of long peptides, optimization of adjuvants including toll-like receptor agonists, and combination with systemic therapies that may reduce tumor-associated immune dysfunction, such as blockade of PD-1/PD-L1 interactions. To apply these new approaches optimally, it will be critical to study their effects in the context of defined antigens, for which peptide vaccines are optimal.


Hydrogen gas improves left ventricular hypertrophy in Dahl rat of salt-sensitive hypertension.
Hypertension is an important risk factor for death resulting from stroke, myocardial infarction, and end-stage renal failure. Hydrogen (H2) gas protects against many diseases, including ischemia-reperfusion injury and stroke. The effects of H2 on hypertension and its related left ventricular (LV) function have not been fully elucidated. The purpose of this study was to investigate the effects of H2 gas on hypertension and LV hypertrophy using echocardiography. Dahl salt-sensitive (DS) rats were randomly divided into three groups: those fed an 8% NaCl diet until 12 weeks of age (8% NaCl group), those additionally treated with 2% H2 gas (8% NaCl + 2% H2 group), and control rats maintained on a diet containing 0.3% NaCl until 12 weeks of age (0.3% NaCl group). H2 gas was supplied through a gas flowmeter and delivered by room air (2% hydrogenated room air, flow rate of 10 L/min) into a cage surrounded by an acrylic chamber. We evaluated interventricular septal wall thickness (IVST), LV posterior wall thickness (LVPWT), and LV mass using echocardiography. IVST, LVPWT, and LV mass were significantly higher in the 8% NaCl group than the 0.3% NaCl group at 12 weeks of age, whereas they were significantly lower in the 8% NaCl + 2% H2 group than the 8% NaCl group. There was no significant difference in systolic blood pressure between the two groups. Our findings suggest that chronic H2 gas inhalation may help prevent LV hypertrophy in hypertensive DS rats.


A New Species of Triumphalisnema (Nematoda: Coronostomatoidea) Parasite of Proculejus hirtus (Coleoptera: Passalidae) from Mexico, and the Position of the Family in the Oxyuridomorpha.
A new species of the nematode Triumphalisnema Kloss, 1962 (Oxyuridomorpha), is described from the wood beetle Proculejus hirtus Truqui from the mountain mesophilic forest in Hidalgo State, Mexico. Triumphalisnema zuuei n. sp. is distinguished from the other 4 congeners species by the presence of an expanded cervical ring, well-developed lateral alae, an obtuse cauda with a short and bifurcated caudal appendage, series of cuticular folds at ventral and dorsal body surface from excretory pore level to anal region, and ellipsoidal eggs ornamented with numerous small mushroom-like structures over the surface. The phylogenetic position of the new species is inferred based on a Maximum Likelihood and Bayesian Inference analysis of partial sequences of 18S SSU rRNA. The phylogenetic analysis showed that Triumphalisnema zuuei n. sp., the only representative of the Traklosiidae in our study, is closely related to Coynema poeyi and species of Longior, Hystrignathus, and Lepidonema, all of them members of Hystrignathidae. These relationships are supported by high support values. The present study increases to 5 the number of species assigned to Triumphalisnema, all of them parasites of Passalidae. Additionally, a taxonomic key to the species of the genus is provided.


Blood-Brain Barrier Dysfunction and the Pathogenesis of Alzheimer's Disease.
Brain capillary endothelial cells form the blood-brain barrier (BBB), which is covered with basement membranes and is also surrounded by pericytes and astrocyte end-feet in the neurovascular unit. The BBB tightly regulates the molecular exchange between the blood flow and brain parenchyma, thereby regulating the homeostasis of the central nervous system (CNS). Thus, dysfunction of the BBB is likely involved in the pathogenesis of several neurological diseases, including Alzheimer's disease (AD). While amyloid-β (Aβ) deposition and neurofibrillary tangle formation in the brain are central pathological hallmarks in AD, cerebrovascular lesions and BBB alteration have also been shown to frequently coexist. Although further clinical studies should clarify whether BBB disruption is a specific feature of AD pathogenesis, increasing evidence indicates that each component of the neurovascular unit is significantly affected in the presence of AD-related pathologies in animal models and human patients. Conversely, since some portions of Aβ are eliminated along the neurovascular unit and across the BBB, disturbing the pathways may result in exacerbated Aβ accumulation in the brain. Thus, current evidence suggests that BBB dysfunction may causatively and consequently contribute to AD pathogenesis, forming a vicious cycle between brain Aβ accumulation and neurovascular unit impairments during disease progression.


Single unit analysis of the human ventral thalamic nuclear group: correlation of thalamic "tremor cells" with the 3-6 Hz component of parkinsonian tremor.
Although cells firing at tremor frequency, called "tremor cells" (Guiot et al., 1962), have often been recorded in the thalamus of parkinsonian patients, the extent of correlation between these spike trains and tremor has rarely been assessed quantitatively. This paper describes spectral cross-correlation functions calculated between the activity of "tremor cells" and electromyogram (EMG) signals recorded from several muscles in the contralateral arm. The power occurring in the spike train at tremor frequency was described in absolute terms by the spike autopower, and in relation to the average for all spectral components by the spike autopower signal-to-noise ratio (spike autopower SNR). The probability of significant cross-correlation between the thalamic spike train and EMG at tremor frequency was assessed by the coherence at tremor frequency. Autopower spectra of the activity of many of these cells exhibited a concentration of power at tremor frequency, indicated by spike autopower SNRs as high as 18. Of the EMG signals studied, signals recorded from finger flexors were most often significantly correlated at tremor frequency. Significant correlation between the thalamic spike train and finger flexor EMG activity was found in 34% of cells analyzed. Tremor frequency coherence was significantly correlated with tremor frequency spike autopower (r = 0.46, p less than 0.0001) and spike autopower SNR (r = 0.533, p less than 0.0001). The proportion of cells with a spike autopower SNR greater than 2 that were significantly correlated with finger flexor EMG activity was greater than that of cells with a spike autopower SNR of less than 2 (p less than 0.001; chi-square). Therefore, cells exhibiting a large amount of power at tremor frequency were those best correlated with EMG activity during tremor. Some of these cells may be involved in the generation of tremor.


An inhibitory sex pheromone tastes bitter for Drosophila males.
Sexual behavior requires animals to distinguish between the sexes and to respond appropriately to each of them. In Drosophila melanogaster, as in many insects, cuticular hydrocarbons are thought to be involved in sex recognition and in mating behavior, but there is no direct neuronal evidence of their pheromonal effect. Using behavioral and electrophysiological measures of responses to natural and synthetic compounds, we show that Z-7-tricosene, a Drosophila male cuticular hydrocarbon, acts as a sex pheromone and inhibits male-male courtship. These data provide the first direct demonstration that an insect cuticular hydrocarbon is detected as a sex pheromone. Intriguingly, we show that a particular type of gustatory neurons of the labial palps respond both to Z-7-tricosene and to bitter stimuli. Cross-adaptation between Z-7-tricosene and bitter stimuli further indicates that these two very different substances are processed by the same neural pathways. Furthermore, the two substances induced similar behavioral responses both in courtship and feeding tests. We conclude that the inhibitory pheromone tastes bitter to the fly.


Raf-1 without MEK?
The Ras-Raf-MEK [(mitogen-activated protein kinase (MAPK) or extracellular signal-regulated kinase (ERK) kinase]-MAPK signaling pathway controls the activation of many cellular functions. Recent reports of Raf-1-deficient mice have indicated that MEK may not be an important downstream substrate for Raf-1 and that, in fact, Raf-1 is important for blocking apoptosis rather than for cell proliferation. Murakami and Morrison examine these recent findings and discuss their implications, as well as other possible conclusions that may be drawn from the published data.


Dual learning processes in interactive skill acquisition.
Acquisition of interactive skills involves the use of internal and external cues. Experiment 1 showed that when actions were interdependent, learning was effective with and without external cues in the single-task condition but was effective only with the presence of external cues in the dual-task condition. In the dual-task condition, actions closer to the feedback were learned faster than actions farther away but this difference was reversed in the single-task condition. Experiment 2 tested how knowledge acquired in single and dual-task conditions would transfer to a new reward structure. Results confirmed the two forms of learning mediated by the secondary task: A declarative memory encoding process that simultaneously assigned credits to actions and a reinforcement-learning process that slowly propagated credits backward from the feedback. The results showed that both forms of learning were engaged during training, but only at the response selection stage, one form of knowledge may dominate over the other depending on the availability of attentional resources.


Politicizing Social Inequality: Competing Narratives From the Alternative for Germany and Left-Wing Movement Stand Up.
This article investigates the link between rising levels of social inequality and years of austerity on the one hand and the rise of populist, anti-establishment protest on the other. This connection is explored by analyzing the discursive practices of activists as a way of reconstructing the key argumentative and emotional structures organizing actors' understanding of politics. Empirically the article is based on 40 narrative interviews with supporters of the German right-wing, anti-immigrant party, Alternative for Germany (AfD), and the newly established left-wing movement Stand Up. The findings of the discursive analysis point to a profound sense of exclusion amongst left- and right-wing populist affiliates defined both in socio-economic terms and with a view to being deprived of a proper political voice. At the same time, the results show that the supporters of the AfD, in contrast to those from Stand Up, develop a strong, mobilizing collective identity that is instrumental in popularizing their discontent with the political establishment: The dramatized conflict between the virtuous German people and the threatening Other-manifested primarily by immigrants and the European Union-provides an emotionally charged binary that is at the core of the contemporary populist resurgence across Western democracies. In addition, the collective identity is instrumental in offering a particular interpretation of the origins of and desirable response to growing inequality that rely more on culturalist rather than traditional class-based arguments. Building on this analysis, the article offers an interpretation of the relative weakness of the populist left that, in the German context, so far has not succeeded in using deepening socio-economic cleavages for their political mobilization effectively.


The emergence and adaptive use of prestige in an online social learning task.
Prestige-biased social learning occurs when individuals preferentially learn from others who are highly respected, admired, copied, or attended to in their group. This form of social learning is argued to reflect novel forms of social hierarchy in human societies, and, by providing an efficient short-cut to acquiring adaptive information, underpin the cumulative cultural evolution that has contributed to our species' ecological success. Despite these potentially important consequences, little empirical work to date has tested the basic predictions of prestige-biased social learning. Here we provide evidence supporting the key predictions that prestige-biased social learning is used when it constitutes an indirect cue of success, and when success-biased social learning is unavailable. We ran an online experiment (n = 269) in which participants could copy each other in real-time to score points on a general-knowledge quiz. Our implementation of 'prestige' was the number of times someone had previously been copied by others. Importantly, prestige was an emergent property of participants' behaviour during the experiment; no deception or manipulation of prestige was employed at any time. We found that, as predicted, participants used prestige-biased social learning when the prestige cue was an indirect cue of success, and when direct success information was unavailable. This highlights how people flexibly and adaptively employ social learning strategies based on the reliability of the information that such strategies provide.


Family participation in determination of FIM and Barthel indices.
Functional Independence Measure (FIM) is a basic indicator of severity of disability, and is used for measurement of functional independence. The aim of this paper is to present our initial experiences in the application of FIM. It needs to be noted that we have had an incomplete team in implementation of this project, and also that we have involved the patients and their families in the measurement of FIM. We selected a small sample of 23 patients, and measured their FIM and Barthel index both at the admission and discharge from the hospital. We do accept that this sample may be too small for the purposes of scientific verification. Therefore, we have included patients and their family members in the process of FIM measurement, along with the team members including a physiatrist, physiotherapist, nurse, and a help-nurse. Most of the subjects included in this project were patients with hemiplegia after a stroke (65.21 %), followed by quadriplegic patients (17.39 %), and patients with paraplegia (17.39 %). Gender structure shows 47.82 % male and 52.17 % female patients. The best progress (an increase in score from 4 to 53 points) in FIM was observed in patients with hemiplegia, and in Barthel index in patients with quadriplegia (an increase in score from 0 to 84). The differences are not statistically significant (p>0.05). The patients with hemiplegia were hospitalized in our clinic for the shortest period of time (around one month). Average rehabilitation time in our clinic for paraplegic patients was around 3 months, and for quadriplegic patients around 4 months (including early rehabilitation). We established that the patients who actively participated in FIM measurement had more control over their own medical assistance, and this participation had a supportive effect on patients. Their participation in FIM measurement needed constant encouragement. In order to make our claim that the FIM is a good supportive method as objective as possible, and in order to establish a correlation between disability and handicap, we intend to include a psychologist and apply Antonov SOC theory (coherency feeling) in our forthcoming research.


Vertically and horizontally directed muscle power exercises: Relationships with top-level sprint performance.
The capacity to rapidly generate and apply a great amount of force seems to play a key role in sprint running. However, it has recently been shown that, for sprinters, the technical ability to effectively orient the force onto the ground is more important than its total amount. The force-vector theory has been proposed to guide coaches in selecting the most adequate exercises to comprehensively develop the neuromechanical qualities related to the distinct phases of sprinting. This study aimed to compare the relationships between vertically-directed (loaded and unloaded vertical jumps, and half-squat) and horizontally-directed (hip-thrust) exercises and the sprint performance of top-level track and field athletes. Sixteen sprinters and jumpers (including three Olympic athletes) executed vertical jumps, loaded jump squats and hip-thrusts, and sprinting speed tests at 10-, 20-, 40-, 60-, 100-, and 150-m. Results indicated that the hip-thrust is more associated with the maximum acceleration phase (i.e., from zero to 10-m; r = 0.93), whereas the loaded and unloaded vertical jumps seem to be more related to top-speed phases (i.e., distances superior to 40-m; r varying from 0.88 to 0.96). These findings reinforce the mechanical concepts supporting the force-vector theory, and provide coaches and sport scientists with valuable information about the potential use and benefits of using vertically- or horizontally-based training exercises.


Y-chromosome haplotypes in azoospermic Israeli men.
Among azoospermic and severely oligozoospermic men, 7-15% present microdeletions of a region on the long arm of the Y chromosome that has been called AZF (azoospermia factor). Because these deletions present varying relative frequencies in different populations, we decided to ascertain whether their presence was correlated with specific Y-chromosome haplotypes. For that, we evaluated 51 infertile Israeli men, 9 of whom had microdeletions in AZF. Haplotypes were identified using a hierarchical system with eight biallelic DNA markers. We also checked for the presence of the deletion marker 50f2/C, which was absent in all seven patients with isolated AZFc deletion and also in the one patient with isolated AZFb deletion, suggesting that these microdeletions overlap. As expected, haplogroup J was the most common (47%), followed by equal frequencies of haplogroups Y* (xDE, J, K), P* (xR1a, R1b8), K* (xP), and E. In six patients with AZFc deficiencies of comparable size, three belonged to haplogroup J, two belonged to haplogroup P* (xR1a, R1b8), and one belonged to haplogroup R1a. Also, there were no significant differences in the haplotype frequencies between the groups with and without microdeletions. Thus we did not identify any association of a specific haplogroup with predisposition to de novo deletion of the AZF region in the Israeli population.


Rethoracotomy for early complications: A marker for increased morbidity and mortality.
This study aims to examine the indications, timing and risk factors of rethoracotomy, analyze the postoperative results, and give suggestions to reduce the risks. A total of 3,292 patients operated via thoracotomy between January 2006 and January 2017 were evaluated retrospectively. Demographic data, initial operative indications, surgical procedures, indications for rethoracotomy and preoperative risk factors, intraoperative findings and surgical methods, timing of rethoracotomy, morbidity and mortality results were analyzed of 66 patients (60 males, 6 females; mean age 59.4±12.4 years; range, 17 to 80 years) who were performed rethoracotomy before being discharged. Rethoracotomies performed within 72 hours after the first operation constituted the early and those performed after 72 hours constituted the late rethoracotomy group. Rethoracotomy was performed in average 4.7 days (range, 1 to 17 days). Early rethoracotomy was performed on 42 patients (1.3%) and 38 (90.4%) of these were due to hemorrhage. The most frequent indication for rethoracotomy was hemorrhage (n=41, 1.2%), followed by bronchopleural fistula (n=17, 0.5%). The other indications were chylothorax, lobe torsion, parenchymal air leak and collapse, and diaphragmatic laceration. Eight patients had rib fractures and all of these patients were over the age of 60. Eight patients who were performed rethoracotomy due to hemorrhage were using antiaggregant drugs. The postoperative morbidity and mortality rates were 33.3% (n=22) and 24.2% (n=16), respectively. Rethoracotomy still has high morbidity and mortality rates. The main cause of rethoracotomy performed due to hemorrhage may be rib fractures or antiaggregant drugs. The most remarkable indications of rethoracotomy are hemorrhage and bronchopleural fistula.


Which Personality Attributes Are Most Important in the Workplace?
Employees face a variety of work demands that place a premium on personal attributes, such as the degree to which they can be depended on to work independently, deal with stress, and interact positively with coworkers and customers. We examine evidence for the importance of these personality attributes using research strategies intended to answer three fundamental questions, including (a) how well does employees' standing on these attributes predict job performance?, (b) what types of attributes do employers seek to evaluate in interviews when considering applicants?, and (c) what types of attributes are rated as important for performance in a broad sampling of occupations across the U.S. economy? We summarize and integrate results from these three strategies using the Big Five personality dimensions as our organizing framework. Our findings indicate that personal attributes related to Conscientiousness and Agreeableness are important for success across many jobs, spanning across low to high levels of job complexity, training, and experience necessary to qualify for employment. The strategies lead to differing conclusions about the relative importance of Emotional Stability and Extraversion. We note implications for job seekers, for interventions aimed at changing standing on these attributes, and for employers.


Late quaternary environmental history of lake valencia, Venezuela.
Chemical, paleontological, and mineralogical analyses of a 7.5-meter core from the middle of Lake Valencia, Venezuela, have provided information on the paleoclimatic history of this low-elevation, low-latitude site for the last 13,000 years. The data show that dry climates existed in this region from 13,000 years before present (B.P.) until about 10,000 years B.P. The Lake Valencia Basin was occupied by intermittent saline marshes at that time. About 10,000 years B.P., a permanent lake of fluctuating salinity formed and arboreal plant communities replaced the earlier dominant xeric herbaceous vegetation and marsh plants. By 8500 years B.P., Lake Valencia reached moderate to low salinities and discharged water; the modern vegetation became established at that time. After 8500 years B.P., the lake twice ceased discharging as a result of reduced watershed moisture. The second of these drying episodes is still in progress and has been aggravated by human activities in the watershed.


Importance of suppressor T cells in cyclophosphamide-induced tolerance to the non-H-2-encoded alloantigens. Is mixed chimerism really required in maintaining a skin allograft tolerance?
Mechanisms of cyclophosphamide (CP)-induced tolerance were studied. When AKR/J Sea (AKR: H-2k) mice were primed i.v. with 5 x 10(7) spleen cells plus 1 x 10(7) bone marrow cells from [C57BL/6 Slc (B6; H-2b) x C3H/He Slc (C3H; H-2k)]F1 (B6C3F1) mice and treated i.p. with 200 mg/kg CP 2 days later, the survival of C3H skin was moderately prolonged, but the survival of either B6 or B6C3F1 skin was not prolonged. By this treatment, however, mixed chimerism of B6C3F1 cells in the AKR mice was not established. When C3H cells were used as the tolerogen, a minimal degree of mixed chimerism associated with profound tolerance to C3H skin was established. Similar results were observed in various donor-recipient combinations. When C3H skin was grafted in the AKR mice 12 wk after the treatment with C3H cells and CP, or B6C3F1 cells and CP, survival of the grafted C3H skin was prolonged remarkably or moderately, respectively, although mixed chimerism was not detectable at the timing of grafting in either of the groups. In this late stage of tolerance, a strong level of tolerogen-specific suppressor cell activity was observed in those tolerant AKR mice. The suppressor activity was mainly attributable to T cells. These results suggest that the role of Ts cells in order to maintain skin tolerance is important in our CP-induced tolerance system, especially in the late stage of tolerance. Moreover, the generation of the Ts cells does not necessarily require the establishment of a long term mixed chimeric state.


A differential dielectric affinity glucose sensor.
A continuous glucose monitor with a differential dielectric sensor implanted within the subcutaneous tissue that determines the glucose concentration in the interstitial fluid is presented. The device, created using microelectromechanical systems (MEMS) technology, consists of sensing and reference modules that are identical in design and placed in close proximity. Each module contains a microchamber housing a pair of capacitive electrodes residing on the device substrate and embedded in a suspended, perforated polymer diaphragm. The microchambers, enclosed in semi-permeable membranes, are filled with either a polymer solution that has specific affinity to glucose or a glucose-insensitive reference solution. To accurately determine the glucose concentration, changes in the permittivity of the sensing and the reference solutions induced by changes in glucose concentration are measured differentially. In vitro characterization demonstrated the sensor was capable of measuring glucose concentrations from 0 to 500 mg dL(-1) with resolution and accuracy of ~1.7 μg dL(-1) and ~1.74 mg dL(-1), respectively. In addition, device drift was reduced to 1.4% (uncontrolled environment) and 11% (5 °C of temperature variation) of that from non-differential measurements, indicating significant stability improvements. Preliminary animal testing demonstrated that the differential sensor accurately tracks glucose concentration in blood. This sensor can potentially be used clinically as a subcutaneously implanted continuous monitoring device in diabetic patients.


Inflammatory and infectious aortic diseases.
Aortitis is aortic inflammation, which can be due to inflammatory or infectious diseases. Left undiagnosed, aortitis can lead to aneurysm formation and rupture, in addition to ischemic compromise of major organs. Infectious aortic diseases include mycotic aneurysm and graft infection; the most common inflammatory diseases are Takayasu's and giant cell arteritis. We review the epidemiology, etiology, presentation and diagnosis, and treatment of these entities.


Drosophila CRY is a deep brain circadian photoreceptor.
cry (cryptochrome) is an important clock gene, and recent data indicate that it encodes a critical circadian photoreceptor in Drosophila. A mutant allele, cry(b), inhibits circadian photoresponses. Restricting CRY expression to specific fly tissues shows that CRY expression is needed in a cell-autonomous fashion for oscillators present in different locations. CRY overexpression in brain pacemaker cells increases behavioral photosensitivity, and this restricted CRY expression also rescues all circadian defects of cry(b) behavior. As wild-type pacemaker neurons express CRY, the results indicate that they make a striking contribution to all aspects of behavioral circadian rhythms and are directly light responsive. These brain neurons therefore contain an identified deep brain photoreceptor, as well as the other circadian elements: a central pace-maker and a behavioral output system.


Quantitative analysis and modeling probe polarity establishment in C. elegans embryos.
Cell polarity underlies many aspects of metazoan development and homeostasis, and relies notably on a set of PAR proteins located at the cell cortex. How these proteins interact in space and time remains incompletely understood. We performed a quantitative assessment of polarity establishment in one-cell stage Caenorhabditis elegans embryos by combining time-lapse microscopy and image analysis. We used our extensive data set to challenge and further specify an extant mathematical model. Using likelihood-based calibration, we uncovered that cooperativity is required for both anterior and posterior PAR complexes. Moreover, we analyzed the dependence of polarity establishment on changes in size or temperature. The observed robustness of PAR domain dimensions in embryos of different sizes is in agreement with a model incorporating fixed protein concentrations and variations in embryo surface/volume ratio. In addition, we quantified the dynamics of polarity establishment over most of the viable temperatures range of C. elegans. Modeling of these data suggests that diffusion of PAR proteins is the process most affected by temperature changes, although cortical flows appear unaffected. Overall, our quantitative analytical framework provides insights into the dynamics of polarity establishment in a developing system.


Ablative fractional laser resurfacing for the treatment of a third-degree burn.
Burn scars are the result of wound healing following a partial-thickness or full-thickness thermal injury. Thermal injury can frequently result in extensive scarring, which may have profound psychologic impact on the victim, serving as a visible and palpable reminder of a traumatic event. Standard treatments for scars include the use of skin grafts, intralesional steroid injections, and pulsed-dye laser treatments. The authors have previously described successful treatment of a burn scar with nonablative fractional resurfacing. Ablative fractional lasers may offer burn patients advantages over nonablative techniques, including improved function and cosmetic outcomes. In addition, ablative fractional laser may require fewer treatments, and therefore, be a more cost-effective treatment option for patients. The authors report the use of fractional ablative laser for the treatment of a disfiguring scar that was more than 50-years-old. To our knowledge, this is the first report of this technology for the treatment of a scar resulting from a third-degree burn in the literature. The demonstrated successful outcome in this case patient may indicate a progessive treatment option for many patients who have been disfigured by these types of thermal injuries.


Coriolus Versicolor and Ganoderma Lucidum Related Natural Products as an Adjunct Therapy for Cancers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Background: Cancer incidence and mortality rates keep rising globally. Coriolus versicolor and Ganoderma lucidum related natural products are commonly applied as a complementary therapeutic option for different stages and types of cancers. The aim of this study is to evaluate the efficacy and safety of the products for cancer therapy. Methods: Randomized controlled trials were identified by systematic search over seven databases from inceptions to May 10, 2019. Two independent reviewers extracted data and assessed the study quality. Meta-analyses were performed to pool hazard ratio (HR), risk ratio (RR), mean differences (MD), and 95% CI using random-effects models. The sources of heterogeneity were explored by subgroup analyses and sensitivity analyses. Publication bias was detected by Funnel plots, Begg's test, and Egger's test. Results: Twenty-three trials involving 4,246 cancer patients were included in this work. C. versicolor and G. lucidum related natural products were significantly associated with lower risks of mortality (HR: 0.82; 95% CI: 0.72, 0.94) and higher total efficacy (RR: 1.30; 95% CI: 1.09, 1.55), but not associated with control rate (RR: 1.05; 95% CI: 0.96, 1.14) compared with control treatment. There was no significant difference between C. versicolor related natural products and control treatment in the effect on relapse-free survival (HR: 1.19; 95% CI: 0.91, 1.55). Compared with control treatment, C. versicolor and G. lucidum related natural products had a favorable effect on elevated levels of CD3 (MD: 9.03%; 95% CI: 2.10, 16.50) and CD4 (MD: 9.2%; 95% CI: 1.01, 17.39), but had no effect on the levels of CD8 (MD: -5.52%; 95% CI: -23.17, 12.13), CD4/CD8 (MD: 0.73; 95% CI:-0.45, 1.91), or NK(MD: 5.87%; 95% CI: -1.06, 12.8). Conclusion: In this meta-analysis, we found that C. versicolor and G. lucidum related natural products might have potential benefits on the overall survival and quality of life in cancer patients.


Visualizing real-time influenza virus infection, transmission and protection in ferrets.
Influenza transmission efficiency in ferrets is vital for risk-assessment studies. However, the inability to monitor viral infection and transmission dynamics in real time only provides a glimpse into transmissibility. Here we exploit a replication-competent influenza reporter virus to investigate dynamics of infection/transmission in ferrets. Bioluminescent imaging of ferrets infected with A/California/04/2009 H1N1 virus (CA/09) encoding NanoLuc (NLuc) luciferase provides the first real-time snapshot of influenza infection/transmission. Luminescence in the respiratory tract and in less well-characterized extra-pulmonary sites is observed, and imaging identifies infections in animals that would have otherwise been missed by traditional methods. Finally, the reporter virus significantly increases the speed and sensitivity of virological and serological assays. Thus, bioluminescent imaging of influenza infections rapidly determines intra-host dissemination, inter-host transmission and viral load, revealing infection dynamics and pandemic potential of the virus. These results have important implications for antiviral drug susceptibility, vaccine efficacy, transmissibility and pathogenicity studies.


Metastability as a candidate neuromechanistic biomarker of schizophrenia pathology.
The disconnection hypothesis of schizophrenia proposes that symptoms of the disorder arise as a result of aberrant functional integration between segregated areas of the brain. The concept of metastability characterizes the coexistence of competing tendencies for functional integration and functional segregation in the brain, and is therefore well suited for the study of schizophrenia. In this study, we investigate metastability as a candidate neuromechanistic biomarker of schizophrenia pathology, including a demonstration of reliability and face validity. Group-level discrimination, individual-level classification, pathophysiological relevance, and explanatory power were assessed using two independent case-control studies of schizophrenia, the Human Connectome Project Early Psychosis (HCPEP) study (controls n = 53, non-affective psychosis n = 82) and the Cobre study (controls n = 71, cases n = 59). In this work we extend Leading Eigenvector Dynamic Analysis (LEiDA) to capture specific features of dynamic functional connectivity and then implement a novel approach to estimate metastability. We used non-parametric testing to evaluate group-level differences and a naïve Bayes classifier to discriminate cases from controls. Our results show that our new approach is capable of discriminating cases from controls with elevated effect sizes relative to published literature, reflected in an up to 76% area under the curve (AUC) in out-of-sample classification analyses. Additionally, our new metric showed explanatory power of between 81-92% for measures of integration and segregation. Furthermore, our analyses demonstrated that patients with early psychosis exhibit intermittent disconnectivity of subcortical regions with frontal cortex and cerebellar regions, introducing new insights about the mechanistic bases of these conditions. Overall, these findings demonstrate reliability and face validity of metastability as a candidate neuromechanistic biomarker of schizophrenia pathology.


Metabolic remodeling of human skeletal myocytes by cocultured adipocytes depends on the lipolytic state of the system.
Adipocyte infiltration of the musculoskeletal system is well recognized as a hallmark of aging, obesity, and type 2 diabetes. Intermuscular adipocytes might serve as a benign storage site for surplus lipid or play a role in disrupting energy homeostasis as a result of dysregulated lipolysis or secretion of proinflammatory cytokines. This investigation sought to understand the net impact of local adipocytes on skeletal myocyte metabolism. Interactions between these two tissues were modeled using a coculture system composed of primary human adipocytes and human skeletal myotubes derived from lean or obese donors. Metabolic analysis of myocytes was performed after coculture with lipolytically silent or activated adipocytes and included transcript and metabolite profiling along with assessment of substrate selection and insulin action. Cocultured adipocytes increased myotube mRNA expression of genes involved in oxidative metabolism, regardless of the donor and degree of lipolytic activity. Adipocytes in the basal state sequestered free fatty acids, thereby forcing neighboring myotubes to rely more heavily on glucose fuel. Under this condition, insulin action was enhanced in myotubes from lean but not obese donors. In contrast, when exposed to lipolytically active adipocytes, cocultured myotubes shifted substrate use in favor of fatty acids, which was accompanied by intracellular accumulation of triacylglycerol and even-chain acylcarnitines, decreased glucose oxidation, and modest attenuation of insulin signaling. The effects of cocultured adipocytes on myocyte substrate selection and insulin action depended on the metabolic state of the system. These findings are relevant to understanding the metabolic consequences of intermuscular adipogenesis.


Bandwidth-narrowed Bragg gratings inscribed in double-cladding fiber by femtosecond laser.
Bragg gratings with the bandwidth(FWHM) narrowed up to 79 pm were inscribed in double-cladding fiber with femtosecond radiation and a phase mask followed by an annealing treatment. With the annealing temperature below a critical value, the bandwidth of Bragg gratings induced by Type I-IR and Type II-IR index change was narrowed without the reduction of reflectivity. The bandwidth narrowing is due to the profile transformation of the refractive index modulation caused by the annealing treatment. This mechanism was verified by comparing bandwidth narrowing processes of FBGs written with different power densities.


Fish species introductions provide novel insights into the patterns and drivers of phylogenetic structure in freshwaters.
Despite long-standing interest of terrestrial ecologists, freshwater ecosystems are a fertile, yet unappreciated, testing ground for applying community phylogenetics to uncover mechanisms of species assembly. We quantify phylogenetic clustering and overdispersion of native and non-native fishes of a large river basin in the American Southwest to test for the mechanisms (environmental filtering versus competitive exclusion) and spatial scales influencing community structure. Contrary to expectations, non-native species were phylogenetically clustered and related to natural environmental conditions, whereas native species were not phylogenetically structured, likely reflecting human-related changes to the basin. The species that are most invasive (in terms of ecological impacts) tended to be the most phylogenetically divergent from natives across watersheds, but not within watersheds, supporting the hypothesis that Darwin's naturalization conundrum is driven by the spatial scale. Phylogenetic distinctiveness may facilitate non-native establishment at regional scales, but environmental filtering restricts local membership to closely related species with physiological tolerances for current environments. By contrast, native species may have been phylogenetically clustered in historical times, but species loss from contemporary populations by anthropogenic activities has likely shaped the phylogenetic signal. Our study implies that fundamental mechanisms of community assembly have changed, with fundamental consequences for the biogeography of both native and non-native species.


Use of Adeno-Associated Virus to Enrich Cardiomyocytes Derived from Human Stem Cells.
Cardiomyocytes derived from human induced pluripotent stem cells (iPSCs) show great promise as autologous donor cells to treat heart disease. A major technical obstacle to this approach is that available induction methods often produce heterogeneous cell population with low percentage of cardiomyocytes. Here we describe a cardiac enrichment approach using nonintegrating adeno-associated virus (AAV). We first examined several AAV serotypes for their ability to selectively transduce iPSC-derived cardiomyocytes. Results showed that AAV1 demonstrated the highest in vitro transduction efficiency among seven widely used serotypes. Next, differentiated iPSC derivatives were transduced with drug-selectable AAV1 expressing neomycin resistance gene. Selection with G418 enriched the cardiac cell fraction from 27% to 57% in 2 weeks. Compared with other enrichment strategies such as integrative genetic selection, mitochondria labeling, or surface marker cell sorting, this simple AAV method described herein bypasses antibody or dye labeling. These findings provide proof of concept for large-scale cardiomyocyte enrichment by exploiting AAV's intrinsic tissue tropism.


Malalignment: a possible target for prevention of incident knee osteoarthritis in overweight and obese women.
The present study aims to investigate the associations between malalignment and incident knee OA after 2.5 years in a high-risk group of 333 middle-aged overweight women (BMI ≥ 27 kg/m(2)) free of clinical and radiological knee OA at baseline. The primary outcome measure was the incidence of knee OA, defined as the incidence of radiographic knee OA (Kellgren and Lawrence grade ≥2), clinical knee OA (ACR criteria) or medial or lateral joint space narrowing (≥1.0 mm). Using generalized estimating equations, associations between valgus and varus alignment (compared with neutrally aligned knees) and the primary outcome measure and all its items separately were studied. Neither varus- nor valgus-aligned knees had a significantly increased risk for incident knee OA according to the primary outcome measure. A significantly increased risk for the development of radiographic knee OA was found for varus-aligned knees [odds ratio (OR) 3.3, 95% CI 1.5, 7.3]. Valgus-aligned knees showed a borderline increased OR (2.8, 95% CI 1.0, 8.0) for the development of radiographic knee OA. No statistically significant effects were found for varus and valgus alignment on the incidence of clinical knee OA or medial or lateral joint space narrowing. Since this study was performed in a true target population, current data suggest that malalignment might be a target for the prevention of radiographic knee OA in overweight and obese women.


Systemic reduction of functionally suppressive CD4dimCD25highFoxp3+ Tregs in human second trimester pregnancy is induced by progesterone and 17beta-estradiol.
CD4(+)CD25(high) regulatory T cells (Tregs) are implicated in the maintenance of murine pregnancy. However, reports regarding circulating Treg frequencies in human pregnancy are inconsistent, and the functionality and phenotype of these cells in pregnancy have not been clarified. The aim of this study was to determine the frequency, phenotype, and function of circulating Tregs in the second trimester of human pregnancy and the influence of progesterone and 17beta-estradiol on Treg phenotype and frequency. Based on expressions of Foxp3, CD127, and HLA-DR as determined by multicolor flow cytometry, we defined a proper CD4(dim)CD25(high) Treg population and showed, in contrast to most previous reports, that this population was reduced in second trimester of pregnancy. Unexpectedly, Foxp3 expression was decreased in the Treg, as well as in the CD4(+) population. These changes could be replicated in an in vitro system resembling the pregnancy hormonal milieu, where 17beta-estradiol, and in particular progesterone, induced, in line with the pregnancy situation, a reduction of CD4(dim)CD25(high)Foxp3(+) cells in PBMC from nonpregnant women. By coculturing FACS-sorted Tregs and autologous CD4(+)CD25(-) responder cells, we showed that Tregs from pregnant women still displayed the same suppressive capacity as nonpregnant women in terms of suppressing IL-2, TNF-alpha, and IFN-gamma secretion from responder cells while efficiently producing IL-4 and IL-10. Our findings support the view of hormones, particularly progesterone, as critical regulators of Tregs in pregnancy. Furthermore, we suggest that in the light of the results of this study, early data on circulating Treg frequencies in pregnancy need reevaluation.


A high-fat high-sugar diet in adolescent rats impairs social memory and alters chemical markers characteristic of atypical neuroplasticity and parvalbumin interneuron depletion in the medial prefrontal cortex.
Brain plasticity is a multifaceted process that is dependent on both neurons and extracellular matrix (ECM) structures, including perineuronal nets (PNNs). In the medial prefrontal cortex (mPFC) PNNs primarily surround fast-spiking parvalbumin (PV)-containing GABAergic interneurons and are central to regulation of neuroplasticity. In addition to the development of obesity, high-fat and high-sugar (HFHS) diets are also associated with alterations in brain plasticity and emotional behaviours in humans. To examine the underlying involvement of PNNs and cortical plasticity in the mPFC in diet-evoked social behaviour deficits (in this case social recognition), we exposed adolescent (postnatal days P28-P56) rats to a HFHS-supplemented diet. At P56 HFHS-fed animals and age-matched controls fed standard chow were euthanized and co-localization of PNNs with PV neurons in the prelimbic (PrL) and infralimbic (IL) and anterior cingulate (ACC) sub regions of the PFC were examined by dual fluorescence immunohistochemistry. ΔFosB expression was also assessed as a measure of chronic activity and behavioural addiction marker. Consumption of the HFHS diet reduced the number of PV+ neurons and PNNs in the infralimbic (IL) region of the mPFC by -21.9% and -16.5%, respectively. While PV+ neurons and PNNs were not significantly decreased in the ACC or PrL, the percentage of PV+ and PNN co-expressing neurons was increased in all assessed regions of the mPFC in HFHS-fed rats (+33.7% to +41.3%). This shows that the population of PV neurons remaining are those surrounded by PNNs, which may afford some protection against HFHS diet-induced mPFC-dysregulation. ΔFosB expression showed a 5-10-fold increase (p < 0.001) in each mPFC region, supporting the hypothesis that a HFHS diet induces mPFC dysfunction and subsequent behavioural deficits. The data presented shows a potential neurophysiological mechanism and response to specific diet-evoked social recognition deficits as a result of hypercaloric intake in adolescence.


IMI - Myopia Genetics Report.
The knowledge on the genetic background of refractive error and myopia has expanded dramatically in the past few years. This white paper aims to provide a concise summary of current genetic findings and defines the direction where development is needed. We performed an extensive literature search and conducted informal discussions with key stakeholders. Specific topics reviewed included common refractive error, any and high myopia, and myopia related to syndromes. To date, almost 200 genetic loci have been identified for refractive error and myopia, and risk variants mostly carry low risk but are highly prevalent in the general population. Several genes for secondary syndromic myopia overlap with those for common myopia. Polygenic risk scores show overrepresentation of high myopia in the higher deciles of risk. Annotated genes have a wide variety of functions, and all retinal layers appear to be sites of expression. The current genetic findings offer a world of new molecules involved in myopiagenesis. As the missing heritability is still large, further genetic advances are needed. This Committee recommends expanding large-scale, in-depth genetic studies using complementary big data analytics, consideration of gene-environment effects by thorough measurement of environmental exposures, and focus on subgroups with extreme phenotypes and high familial occurrence. Functional characterization of associated variants is simultaneously needed to bridge the knowledge gap between sequence variance and consequence for eye growth.


The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hand.
Clinical criteria for the classification of symptomatic idiopathic (primary) osteoarthritis (OA) of the hands were developed from data collected in a multicenter study. Patients with OA were compared with a group of patients who had hand symptoms from other causes, such as rheumatoid arthritis and the spondylarthropathies. Variables from the medical history, physical examination, laboratory tests, and radiographs were analyzed. All patients had pain, aching, or stiffness in the hands. Patients were classified as having clinical OA if on examination there was hard tissue enlargement involving at least 2 of 10 selected joints, swelling of fewer than 3 metacarpophalangeal joints, and hard tissue enlargement of at least 2 distal interphalangeal (DIP) joints. If the patient had fewer than 2 enlarged DIP joints, then deformity of at least 1 of the 10 selected joints was necessary in order to classify the symptoms as being due to OA. The 10 selected joints were the second and third DIP, the second and third proximal interphalangeal, and the trapeziometacarpal (base of the thumb) joints of both hands. Criteria derived using the "classification tree" method were 92% sensitive and 98% specific. The "traditional format" classification method required that at least 3 of these 4 criteria be present to classify a patient as having OA of the hand. The latter sensitivity was 94% and the specificity was 87%. Radiography was of less value than clinical examination in the classification of symptomatic OA of the hands.


Development and implementation of an LGBT initiative at a health sciences library: the first eighteen months.
The University of Louisville School of Medicine is the pilot site for the eQuality project, an initiative to integrate training for providing care to lesbian, gay, bisexual, and transgender (LGBT) patients into the standard medical school curriculum. Inspired by and in support of this School of Medicine initiative, Kornhauser Health Sciences Library staff have developing our own initiative. Because of past and current lack of competent provider training and the resulting need for patients to be knowledgeable self-advocates, however, our initiative was broadened to include the goal of providing LGBT individuals in our communities-both on campus and in the broader public-with the resources and tools that they need to access information about their own health. This paper describes the development of that twofold initiative and the tangible methods used in its implementation, including collection development, interdepartmental collaboration, electronic resource guide creation, and community engagement through outreach. Outcomes of the initiative to date will also be discussed, along with plans for further development.


Furosemide-induced changes in plasma and blood volume of camels (Camelus dromedarius).
This work examines the effect of treatment of camels with furosemide (1 or 2 mg/kg, intravenously) on blood volume (BV), plasma volume (PV) and the plasma concentrations of total solids (PTS), plasma total protein (PTP) haemoglobin (Hb) and haematocrit (PCV). The cumulative urine produced during the 4 h following furosemide administration (2 mg/kg) averaged 22.2 mL/kg, compared to 2.3 mL/kg in controls. None of the above parameters were significantly changed by furosemide treatment at either dose. In another experiment, the effect of the two doses of furosemide on the sequential changes on some of the above parameters was investigated at 5, 10, 15, 30, 45, 60, 75, 90, 105, 120 and 240 min after the drug administration. On the whole, there were no significant changes in any of the measured parameters, except for small but statistically significant increases in the PCV and Hb at 30 and 45 min post treatment. It is concluded that, despite the marked diuresis following furosemide administration, the camel appears to be able to maintain its bodily fluid haemostasis.


Scaling up accurate phylogenetic reconstruction from gene-order data.
Phylogenetic reconstruction from gene-order data has attracted increasing attention from both biologists and computer scientists over the last few years. Methods used in reconstruction include distance-based methods (such as neighbor-joining), parsimony methods using sequence-based encodings, Bayesian approaches, and direct optimization. The latter, pioneered by Sankoff and extended by us with the software suite GRAPPA, is the most accurate approach, but cannot handle more than about 15 genomes of limited size (e.g. organelles). We report here on our successful efforts to scale up direct optimization through a two-step approach: the first step decomposes the dataset into smaller pieces and runs the direct optimization (GRAPPA) on the smaller pieces, while the second step builds a tree from the results obtained on the smaller pieces. We used the sophisticated disk-covering method (DCM) pioneered by Warnow and her group, suitably modified to take into account the computational limitations of GRAPPA. We find that DCM-GRAPPA scales gracefully to at least 1000 genomes of a few hundred genes each and retains surprisingly high accuracy throughout the range: in our experiments, the topological error rate rarely exceeded a few percent. Thus, reconstruction based on gene-order data can now be accomplished with high accuracy on datasets of significant size.


Stability of phosphonic acid self-assembled monolayers on amorphous and single-crystalline aluminum oxide surfaces in aqueous solution.
The formation of octadecylphosphonic acid (ODPA) self-assembled monolayers (SAMs) and their stability in water has been studied on four distinctly different aluminum oxide surfaces. The aim was to improve the understanding of the state of binding between the phosphonic acid to the oxide surface and how this interaction depends on the structure and termination of the oxide surface. Single crystalline Al(2)O(3)(0001) and Al(2)O(3)(1102) surfaces were compared to amorphous oxide passive films on aluminum and physical vapor deposited (PVD) amorphous aluminum oxide films on gold. The monolayers were adsorbed from ethanol solution, characterized by means of high-resolution in situ atomic force microscopy (AFM), contact angle measurements, polarization modulated infrared reflection absorption spectroscopy (PM-IRRAS), and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), and proved to be self-assembled. On Al(2)O(3)(1102) surfaces and amorphous Al(2)O(3) surfaces, the ODPA self-assembled monolayers showed high stability in aqueous environments. However, the adsorbed ODPA monolayers were substituted by the adsorption of interfacial water on the Al(2)O(3)(0001) surface via the intermediate formation of micelles. The different stability of the monolayers in aqueous environments is explained by the variation of interfacial binding states ranging from ionic interactions between phosphonate groups and the positively charged hydrolytated oxide surface to directed coordination bonds between the phosphonate group and Al ions.


Speciation and stasis in marine ostracoda: climatic modulation of evolution.
Morphologic and paleozoogeographic analysis of Cenozoic marine Ostracoda from the Atlantic, Caribbean, and Pacific indicates that climatic change modulates evolution by disrupting long-term stasis and catalyzing speciation during sustained, unidirectional climatic transitions and, conversely, by maintaining morphologic stasis during rapid, high-frequency climatic oscillations. In the middle Pliocene, 4 to 3 million years ago, at least six new species of Puriana suddenly appeared as the Isthmus of Panama closed, changing oceanographic circulation and global climate. Since then morphologic stasis has characterized ancestral and descendant species during many glacial-interglacial cycles. The frequency and duration of climatic events have more impact on ostracode evolution than the magnitude of climatic changes.


Maternal exposure to a human relevant mixture of persistent organic pollutants reduces colorectal carcinogenesis in A/J Min/+ mice.
An increased risk of developing colorectal cancer has been associated with exposure to persistent organic pollutants (POPs) and alteration in the gut bacterial community. However, there is limited understanding about the impact of maternal exposure to POPs on colorectal cancer and gut microbiota. This study characterized the influence of exposure to a human relevant mixture of POPs during gestation and lactation on colorectal cancer, intestinal metabolite composition and microbiota in the A/J Min/+ mouse model. Surprisingly, the maternal POP exposure decreased colonic tumor burden, as shown by light microscopy and histopathological evaluation, indicating a restriction of colorectal carcinogenesis. 1H nuclear magnetic resonance spectroscopy-based metabolomic analysis identified alterations in the metabolism of amino acids, lipids, glycerophospholipids and energy in intestinal tissue. In addition, 16S rRNA sequencing of gut microbiota indicated that maternal exposure modified fecal bacterial composition. In conclusion, the results showed that early-life exposure to a mixture of POPs reduced colorectal cancer initiation and promotion, possibly through modulation of the microbial and biochemical environment. Further studies should focus on the development of colorectal cancer after combined maternal and dietary exposures to environmentally relevant low-dose POP mixtures.


Adolescent daytime sleepiness as a risk factor for adult crime.
While recent cross-sectional research has documented a relationship between sleep problems and antisocial behavior, the longitudinal nature of this relationship is unknown. This study tests both the hypothesis that adolescent daytime sleepiness is associated with later adult criminal offending, and also tests a biopsychosocial mediation model in which social adversity predisposes to sleepiness, which in turn predisposes to attentional impairment, and to adult crime. Schoolboys aged 15 years rated themselves on self-report sleepiness. Age 15 antisocial behavior was assessed by teacher ratings and self-reports, while convictions for crime were assessed at age 29. Attentional capacity at age 15 was assessed by autonomic orienting, with arousal assessed by the electroencephalogram (EEG). Sleepy adolescents were more likely to be antisocial during adolescence, and were 4.5 times more likely to commit crime by age 29. The sleepiness-adult crime relationship withstood control for adolescent antisocial behavior. Self-report sleepiness predicted to adult crime over and above objective measures of daytime sleepiness (EEG theta activity) and age 15 antisocial behavior. Poor daytime attention partly mediated the sleep-crime relationship. Mediation analyses also showed that social adversity predisposed to daytime sleepiness which was associated with reduced attention which in turn predisposed to adult crime. Findings are the first to document a longitudinal association between sleepiness in adolescence and crime in adulthood. The longitudinal nature of this relationship, controlling for age 15 antisocial behavior, is consistent with the hypothesis that adolescent sleepiness predisposes to later antisociality. Findings are also consistent with the notion that the well-established link between social adversity and adult crime is partly explained by sleepiness. Results suggest that a very brief and simple assessment of subjective daytime sleepiness may have prognostic clinical value, and that interventions to reduced sleepiness could be a useful avenue for future crime prevention.


Insulin inhibits cardiac contractility by inducing a Gi-biased β2-adrenergic signaling in hearts.
Insulin and adrenergic stimulation are two divergent regulatory systems that may interact under certain pathophysiological circumstances. Here, we characterized a complex consisting of insulin receptor (IR) and β2-adrenergic receptor (β2AR) in the heart. The IR/β2AR complex undergoes dynamic dissociation under diverse conditions such as Langendorff perfusions of hearts with insulin or after euglycemic-hyperinsulinemic clamps in vivo. Activation of IR with insulin induces protein kinase A (PKA) and G-protein receptor kinase 2 (GRK2) phosphorylation of the β2AR, which promotes β2AR coupling to the inhibitory G-protein, Gi. The insulin-induced phosphorylation of β2AR is dependent on IRS1 and IRS2. After insulin pretreatment, the activated β2AR-Gi signaling effectively attenuates cAMP/PKA activity after β-adrenergic stimulation in cardiomyocytes and consequently inhibits PKA phosphorylation of phospholamban and contractile responses in myocytes in vitro and in Langendorff perfused hearts. These data indicate that increased IR signaling, as occurs in hyperinsulinemic states, may directly impair βAR-regulated cardiac contractility. This β2AR-dependent IR and βAR signaling cross-talk offers a molecular basis for the broad interaction between these signaling cascades in the heart and other tissues or organs that may contribute to the pathophysiology of metabolic and cardiovascular dysfunction in insulin-resistant states.


Biological Well-Being and Inequality in Canary Islands: Lanzarote (Cohorts 1886-1982).
Developments in anthropometric history in the Iberian Peninsula have been remarkable in recent decades. In contrast, we barely know about the behavior of insular population groups and infants' and adults' growth during the nutritional transition in the Canary Islands. This paper analyzes the height, weight and body mass index of military recruits (conscripts) in a rural municipality from the eastern Canaries during the economic modernization process throughout the 20th century. The case study (municipality of San Bartolomé (SB) in Lanzarote, the island closest to the African continent) uses anthropometric data of military recruits from 1907-2001 (cohorts from 1886 to 1982). The final sample is composed of 1921 recruits' records that were measured and weighed at the ages of 19-21 years old when adolescent growth had finished. The long-term anthropometric study is carried out using two approaches: a malnutrition and growth retardation approach and an inequality perspective. In the first one, we use the methodology recommended by the World Health Organization (WHO) that is based on z-scores. In the second one, we implement several inequality dimensions such as the coefficient of variation (CV), percentiles and an analysis for height and BMI evolution by five socioeconomic categories. The data suggest that improvements in biological well-being were due to advances in nutrition since the 1960s. They show that infant nutrition is sensitively associated with economic growth and demographic and epidemiological changes.


Orally formulated artemisinin in healthy fasting Vietnamese male subjects: a randomized, four-sequence, open-label, pharmacokinetic crossover study.
Artemisinin derivatives are used in antimalarial drug combination therapy. Artemisinin and piperaquine have recently been proven to be prospective candidates for combination therapy in the treatment of uncomplicated Plasmodium falciparum malaria. The goal of this study was to evaluate the relative bioavailability and to characterize the pharmacokinetic properties of a new micronized powder formulation of artemisinin against the previous standard Vietnamese formulation when administered as a single oral dose or in combination with piperaquine. This was a single-center, randomized, 4-sequence, open-label, crossover study conducted in 15 healthy male Vietnamese volunteers under fasting conditions with a washout period of 3 weeks between study visits. A single oral dose of 160 or 500 mg of artemisinin was administered alone or in combination with piperaquine. Potential adverse events were monitored daily by the clinician and by using laboratory test results. Frequent blood samples were drawn for 12 hours after dose. Artemisinin was quantified in plasma using LC-MS/MS. Pharmacokinetic parameters were computed from the plasma concentration-time profiles using a noncompartmental analysis method. Pharmacokinetic parameters T(max), C(max), AUC(0-∞), V(d)/F, CL/F, and t(1/2) (mean [SD]) for the new formulation of artemisinin were 1.83 (0.88) hours, 178 (97) ng/mL, 504 (210) h × ng/mL, 1270 (780) L, 401 (260) L/h, and 2.21 (0.29) hours, respectively. The mean percentage of the test/reference formulation ratio for the logarithmically transformed values of C(max), AUC(0-last,) and AUC(0-∞) were 121% (90% CI, 92.5-158), 122% (90% CI, 101-148), and 120% (90% CI, 98.0-146), respectively. This single-dose study found that the dose-normalized C(max), AUC(0-last), and AUC(0-∞) mean geometric differences between the test and reference formulations were relatively small (<40%) and will probably not have a clinical impact in the treatment of malaria infections.


Optimal variable flip angle schemes for dynamic acquisition of exchanging hyperpolarized substrates.
In metabolic MRI with hyperpolarized contrast agents, the signal levels vary over time due to T1 decay, T2 decay following RF excitations, and metabolic conversion. Efficient usage of the nonrenewable hyperpolarized magnetization requires specialized RF pulse schemes. In this work, we introduce two novel variable flip angle schemes for dynamic hyperpolarized MRI in which the flip angle is varied between excitations and between metabolites. These were optimized to distribute the magnetization relatively evenly throughout the acquisition by accounting for T1 decay, prior RF excitations, and metabolic conversion. Simulation results are presented to confirm the flip angle designs and evaluate the variability of signal dynamics across typical ranges of T1 and metabolic conversion. They were implemented using multiband spectral-spatial RF pulses to independently modulate the flip angle at various chemical shift frequencies. With these schemes we observed increased SNR of [1-(13)C]lactate generated from [1-(13)C]pyruvate, particularly at later time points. This will allow for improved characterization of tissue perfusion and metabolic profiles in dynamic hyperpolarized MRI.


Antireflective coatings with enhanced adhesion strength.
The importance of tuning refractive index in a multilayer antireflection coating (ARC) system can not be denied. In practical applications, regulation of refractive index is complex due to limited choice and availability of appropriate materials for the trilayer AR coating assembly. To overcome this issue, we used a single inorganic material, HfO2, for the construction of a trilayer AR light harvesting moth eye, resembling hierarchical nanostructure coatings, for exploring new generation photovoltaics and optoelectronic devices. In the trilayer AR HfO2 (TAR-H) assembly, using a glancing angle deposition technique (GLAD), the dense bottom layer was steadily changed into a spongy middle layer that further changed to a highly porous top layer micmiking a moth eye, reducing the refractive index of the coating from 1.87 to 1.30. The broadband omnidirectional properties of the TAR-H coating, with superior thermal stability and improved scratch resistance, in the visible wavelength range were experimentally demonstrated. The TAR-H coating on FTO and sapphire substrates achieved reflectance of up to <1% in the visible wavelength range.


Association of number of retrieved oocytes with live birth rate and birth weight: an analysis of 231,815 cycles of in vitro fertilization.
To determine if number of retrieved oocytes correlates with live birth rate and incidence of low birth weight (LBW). Retrospective cohort. Not applicable. Women undergoing fresh embryo transfer with the use of either autologous (n = 194,627) or donor (n = 37,188) oocytes whose cycles were reported to the Society for Assisted Reproductive Technology in the years 2004-2010. None. Live birth rate, birth weight, birth weight z-score, LBW. For both autologous and donor oocyte cycles, increasing number of retrieved oocytes paralleled live birth rate and embryos available for cryopreservation in most analyses, with all models adjusted for age and previous births. For cycles achieving singleton pregnancy with the use of autologous oocytes via transfer of two embryos, a higher number of retrieved oocytes was associated with lower mean birth weight, lower birth weight z-score, and greater incidence of LBW. In contrast, for cycles using donor oocytes, there was no association of number of retrieved oocytes with measures of birth weight. A higher number of retrieved oocytes was associated with an increased incidence of LBW in autologous singleton pregnancies resulting from transfer of two embryos, but not in donor oocyte cycles. Although the effect of high oocyte number on the incidence of LBW in autologous cycles was of modest magnitude, further study is warranted to determine if a subgroup of women may be particularly vulnerable.


A survey of antibodies to hepatitis C virus in Ethiopia.
Antibodies to hepatitis C virus (HCV) were measured in 1,580 Ethiopian subjects representing urban and rural populations. Sera found positive by a repeated second generation enzyme immunoassay (EIA) were subjected to three additional confirmatory tests. The overall confirmed seroprevalence was 2.0%. Less than 1% were confirmed to be seropositive in rural communities, with 1.4% positive among blood donors, 1.6% positive among patients with dermatologic disorders, 3.6% among leprosy patients, and 6.0% among patients attending a University Hospital clinic for neurologic disorders. The patients in the groups with leprosy and neurologic disorders have most likely been in ill health for many years and have sought relief by traditional healers or treatment at poorly equipped clinics. This group of patients demonstrated a high prevalence of antibodies to HCV. In Ethiopia, especially in small clinics, there is a shortage of syringes and needles and they have to be reused many times often with inadequate sterilization. Therefore, these syringes and needles may be contaminated, thus being a risk factor for HCV and HIV infection.


Climate change affects marine fishes through the oxygen limitation of thermal tolerance.
A cause-and-effect understanding of climate influences on ecosystems requires evaluation of thermal limits of member species and of their ability to cope with changing temperatures. Laboratory data available for marine fish and invertebrates from various climatic regions led to the hypothesis that, as a unifying principle, a mismatch between the demand for oxygen and the capacity of oxygen supply to tissues is the first mechanism to restrict whole-animal tolerance to thermal extremes. We show in the eelpout, Zoarces viviparus, a bioindicator fish species for environmental monitoring from North and Baltic Seas (Helcom), that thermally limited oxygen delivery closely matches environmental temperatures beyond which growth performance and abundance decrease. Decrements in aerobic performance in warming seas will thus be the first process to cause extinction or relocation to cooler waters.


Tumor promoter 12-O-tetradecanoylphorbol-13-acetate and sn-1,2-dioctanoylglycerol increase the phosphorylation of protein kinase C in cells.
Phosphorylation of protein kinase C (PKC) may be an important mode of regulation of this enzyme that plays a key role in mouse skin tumor promotion and in mammalian cell signal transduction. To investigate this possibility, PKC was specifically immunoprecipitated from Abelson murine leukemia virus-transformed normal rat kidney cells that had been metabolically labeled with [32P]orthophosphoric acid. The Mr 80,000 phosphoprotein that was specifically immunoprecipitated from Abelson murine leukemia virus-transformed normal rat kidney cells was found to be identical with purified rat brain PKC that had undergone cell-free autophosphorylation. This is based on comparisons of peptides generated by partial proteolysis with Staphylococcus aureus V8 protease by one-dimensional polyacrylamide-sodium dodecyl sulfate gel electrophoresis and of tryptic peptides by reversed-phase high-pressure liquid chromatography. These data are consistent with phosphorylation of PKC in cells having occurred via autophosphorylation. The autophosphorylation of PKC was stimulated by treatment of C3H 10T1/2 cells with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate or sn-1,2-dioctanoylglycerol. Exposure of cells to 100 nM 12-O-tetradecanoylphorbol-13-acetate for 15 min increased the phosphorylation of PKC by 5-fold in the particulate fraction, while treatment with 100 microM dioctanoylglycerol enhanced phosphorylation of PKC only by 2-fold. Phosphorylation of PKC in response to activation may have significance for altering the sensitivity of PKC to proteolytic down-regulation and/or to subsequent activation.