cAMP stimulates the Na+-K+ pump in frog retinal pigment epithelium.
Adenosine 3', 5'-cyclic monophosphate (cAMP) induced increases in active Na+ secretion and K+ absorption that were blocked by apical ouabain (10(-4) M), suggesting stimulation of the Na+-K+ pump. cAMP also produced rapid membrane voltage and resistance changes that could be divided chronologically into three phases. In phase 1, the basolateral membrane depolarized at a faster rate than the apical membrane, probably as a result of an increase in basolateral membrane conductance. In phase 2, the apical membrane repolarized toward control faster than the basal membrane, whereas in phase 3 the basolateral membrane repolarized faster than the apical membrane. Apical ouabain completely inhibited the cAMP-induced repolarization of the apical membrane during phase 2. Thus the stimulation of the Na+-K+ pump occurs within minutes of cAMP elevation. Na+ removal from the basal side did not block the cAMP-induced voltage changes, indicating that the initial conductance increase is not due to Na+. In contrast, Na+ removal from the apical bath inhibited all phases of the cAMP response. This suggests that apical membrane Na+-dependent transport mechanisms mediate the stimulation of the Na+-K+ pump. cAMP also caused a significant drop in intracellular K+ activity (approximately 5 mM) that preceded phase 2. This drop could stimulate the Na+-K+ pump, as suggested by previous experiments.


Skeletal muscle is an endocrine organ.
Skeletal muscle plays a key role in postural retention as well as locomotion for maintaining the physical activities of human life. Skeletal muscle has a second role as an elaborate energy production and consumption system that influences the whole body's energy metabolism. Skeletal muscle is a specific organ that engenders a physical force, and exercise training has been known to bring about multiple benefits for human health maintenance and/or improvement. The mechanisms underlying the improvement of the human physical condition have been revealed: skeletal muscle synthesizes and secretes multiple factors, and these muscle-derived factors, so-called as myokines, exert beneficial effects on peripheral and remote organs. In this short review, we focus on the third aspect of skeletal muscle function - namely, the release of multiple types of myokines, which constitute a broad network for regulating the function of remote organs as well as skeletal muscle itself. We conclusively show that skeletal muscle is one of the endocrine organs and that understanding the mechanisms of production and secretion of myokines may lead to a new pharmacological approach for treatment of clinical disorders.


Ten-color Gegenschein-zodiacal light photometer.
A ten-color Fabry photometer was used during Skylab missions SL-2 and SL-3 to measure sky brightness and polarization associated with zodiacal light, background starlight, F region airglow, and spacecraft corona. A brief description is given of the design, calibration, and performance of the instrument.


Outcome Measurement in Adult Auditory Rehabilitation: A Scoping Review of Measures Used in Randomized Controlled Trials.
This review documented the range and nature of reported outcome measures in the context of adult auditory rehabilitative research. A scoping review conducted as a part of the development of a systematic review of the effect of interventions to improve hearing aid use. The authors searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials; PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP; and additional sources for published and unpublished randomized control trials. The date of the search was November 6, 2013. Outcomes were grouped using a framework suggested by the Cochrane Effective Practice and Organization of Care group. Patient outcomes included adherence to hearing aid use, daily hours of aid use, hearing handicap, hearing aid benefit, quality of life, and communication and psychological outcome. Satisfaction and speech perception were frequent secondary outcomes. There was diversity in measures used to report patient outcomes. Outcome categories other than patient health status and behavior were rarely reported. The timing of outcome measurement was often short term (<12 weeks), with a relative lack of evidence on long-term outcomes (>1 year). This review has highlighted considerable diversity in patient-reported outcome measurements in randomized control trials in the context of adult auditory rehabilitation. In addition, there are gaps in the literature with respect to measurement of other outcome types of potential interest to stakeholders, including policymakers and commissioners. Long-term outcome assessment is rare.


[Synaptic responses of neurons of the lateral medullary reticular formation to stimulation of the locomotor strip in the cat].
Intracellular recording of neuronal responses in the lateral medullar reticular formation to stimulation of locomotor points located rostrally and caudally of the obex was made in mesencephalic uncurarized cats. Of 114 neurons with synaptic responses to the rostral point stimulation by current up to 30 microA 40 neurons were excited antidromically from the caudal point.


Testing Genetic Pleiotropy with GWAS Summary Statistics for Marginal and Conditional Analyses.
There is growing interest in testing genetic pleiotropy, which is when a single genetic variant influences multiple traits. Several methods have been proposed; however, these methods have some limitations. First, all the proposed methods are based on the use of individual-level genotype and phenotype data; in contrast, for logistical, and other, reasons, summary statistics of univariate SNP-trait associations are typically only available based on meta- or mega-analyzed large genome-wide association study (GWAS) data. Second, existing tests are based on marginal pleiotropy, which cannot distinguish between direct and indirect associations of a single genetic variant with multiple traits due to correlations among the traits. Hence, it is useful to consider conditional analysis, in which a subset of traits is adjusted for another subset of traits. For example, in spite of substantial lowering of low-density lipoprotein cholesterol (LDL) with statin therapy, some patients still maintain high residual cardiovascular risk, and, for these patients, it might be helpful to reduce their triglyceride (TG) level. For this purpose, in order to identify new therapeutic targets, it would be useful to identify genetic variants with pleiotropic effects on LDL and TG after adjusting the latter for LDL; otherwise, a pleiotropic effect of a genetic variant detected by a marginal model could simply be due to its association with LDL only, given the well-known correlation between the two types of lipids. Here, we develop a new pleiotropy testing procedure based only on GWAS summary statistics that can be applied for both marginal analysis and conditional analysis. Although the main technical development is based on published union-intersection testing methods, care is needed in specifying conditional models to avoid invalid statistical estimation and inference. In addition to the previously used likelihood ratio test, we also propose using generalized estimating equations under the working independence model for robust inference. We provide numerical examples based on both simulated and real data, including two large lipid GWAS summary association datasets based on ∼100,000 and ∼189,000 samples, respectively, to demonstrate the difference between marginal and conditional analyses, as well as the effectiveness of our new approach.


Comparative effectiveness of liver transplant strategies for end-stage liver disease patients on renal replacement therapy.
There are complex risk-benefit tradeoffs with different transplantation strategies for end-stage liver disease patients on renal support. Using a Markov discrete-time state transition model, we compared survival for this group with 3 strategies: simultaneous liver-kidney (SLK) transplantation, liver transplantation alone (LTA) followed by immediate kidney transplantation if renal function did not recover, and LTA followed by placement on the kidney transplant wait list. Patients were followed for 30 years from the age of 50 years. The probabilities of events were synthesized from population data and clinical trials according to Model for End-Stage Liver Disease (MELD) scores (21-30 and >30) to estimate input parameters. Sensitivity analyses tested the impact of uncertainty on survival. Overall, the highest survival rates were seen with SLK transplantation for both MELD score groups (82.8% for MELD scores of 21-30 and 82.5% for MELD scores > 30 at 1 year), albeit at the cost of using kidneys that might not be needed. Liver transplantation followed by kidney transplantation led to higher survival rates (77.3% and 76.4%, respectively, at 1 year) than placement on the kidney transplant wait list (75.1% and 74.3%, respectively, at 1 year). When uncertainty was considered, the results indicated that the waiting time and renal recovery affected conclusions about survival after SLK transplantation and liver transplantation, respectively. The subgroups with the longest durations of pretransplant renal replacement therapy and highest MELD scores had the largest absolute increases in survival with SLK transplantation versus sequential transplantation. In conclusion, the findings demonstrate the inherent tension in choices about the use of available kidneys and suggest that performing liver transplantation and using renal transplantation only for those who fail to recover their native renal function could free up available donor kidneys. These results could inform discussions about transplantation policy.


[Role of antibiotic therapy in diabetic foot management].
Antibiotic therapy is not the most important component in diabetic foot ulcer management which should be based on weight bearing avoidance and arterial revascularization. However antibiotic therapy is necessary in presence of extensive deep involvement or systemic signs of infection. Initial antimicrobial treatment depends on bacteria supposed origin. For patients not coming from hospital, the initial choice antibiotic is an amoxicillin/clavulanate agent because it offers optimal coverage for most pathogens involved in those diabetic foot lesions (gram positive cocci, gram negative and anaerobic organisms). For patients at high risk to be infected with nosocomially acquired pathogens, the initial antibiotic therapy must cover methicillin-resistant staphylococci, resistant pseudomonas aeruginosa or enterobacteriae. In all cases, when definitive reliable cultures are reported, initial antibiotic regimens should be revised to narrow the coverage to specific pathogens. In presence of osteomyelitis, a temporary combination of two agents which are known to reach high bone concentrations is necessary, and antibiotic therapy should be continued for at least two months. In other cases, antibiotic treatment duration depends on clinical out come.


Plantmetabolomics.org: mass spectrometry-based Arabidopsis metabolomics--database and tools update.
The PlantMetabolomics (PM) database (http://www.plantmetabolomics.org) contains comprehensive targeted and untargeted mass spectrum metabolomics data for Arabidopsis mutants across a variety of metabolomics platforms. The database allows users to generate hypotheses about the changes in metabolism for mutants with genes of unknown function. Version 2.0 of PlantMetabolomics.org currently contains data for 140 mutant lines along with the morphological data. A web-based data analysis wizard allows researchers to select preprocessing and data-mining procedures to discover differences between mutants. This community resource enables researchers to formulate models of the metabolic network of Arabidopsis and enhances the research community's ability to formulate testable hypotheses concerning gene functions. PM features new web-based tools for data-mining analysis, visualization tools and enhanced cross links to other databases. The database is publicly available. PM aims to provide a hypothesis building platform for the researchers interested in any of the mutant lines or metabolites.


Knowledge and skills in community oriented medical education (COME) self-ratings of medical undergraduates in Karachi.
To assess the satisfaction of medical students regarding community oriented knowledge and skills that are proposed to be part of the current undergraduate medical curriculum. Competencies listed in the regulations for medical education designed by the Pakistan Medical and Dental Council (PMDC) were used to develop a self-administered questionnaire. Using the questionnaire 220 final year students of 3 public sector medical schools self-rated the knowledge and skills that should be part of the curriculum. For analysis the questions were grouped into courses of Basic, Clinical and Community Health Sciences. Students ranked their perceptions on a Likert scale of 0-4 for each question. Descriptive analysis was done to calculate the proportion of satisfied and dissatisfied students using the median of the highest possible score as the cut off. The analysis of knowledge gained found a greater proportion of satisfied students with the Basic (55.9%) and Clinical Sciences (50.9%) courses than the Community Health Sciences course (45.5%). Analysis of skills acquired uniformly showed a low percentage of satisfied students for Basic (39.1%), Clinical (29.7%) and Community Health Sciences (19.1%). The proportion of students dissatisfied with their knowledge and skills for different courses ranged from 38.2-85%. Students perceive that current medical school curricula are unable to meet the required standards. Proper implementation of community oriented curricula is the first step towards effective health care provision.


Patterns and predictors of treatment contact after first onset of psychiatric disorders.
The authors used self-report data to study patterns and predictors of treatment contact after the first onset of DSM-III-R mood, anxiety, and addictive disorders. Data from the National Comorbidity Survey, a general population survey of 8,098 respondents, were used. Disorders were assessed by using a modified version of the Composite International Diagnostic Interview. Age at onset and age at first treatment contact were assessed retrospectively. There was great variation across disorders in lifetime probability of treatment contact. Most treatment contact was delayed; the median delay time was between 6 and 14 years across the disorders considered here. Probability of treatment contact was inversely related to age at onset and increased in younger cohorts. The effects of sociodemographic variables were modest and inconsistent across disorders. The majority of people with the disorders considered here eventually make treatment contact. However, delay was pervasive. Further research is needed on the determinants of delay and on the low probability of lifetime treatment contact among people with early-onset psychiatric disorders.


TRP channels in neurogastroenterology: opportunities for therapeutic intervention.
The members of the superfamily of transient receptor potential (TRP) cation channels are involved in a plethora of cellular functions. During the last decade, a vast amount of evidence is accumulating that attributes an important role to these cation channels in different regulatory aspects of the alimentary tract. In this review we discuss the expression patterns and roles of TRP channels in the regulation of gastrointestinal motility, enteric nervous system signalling and visceral sensation, and provide our perspectives on pharmacological targeting of TRPs as a strategy to treat various gastrointestinal disorders. We found that the current knowledge about the role of some members of the TRP superfamily in neurogastroenterology is rather limited, whereas the function of other TRP channels, especially of those implicated in smooth muscle cell contractility (TRPC4, TRPC6), visceral sensitivity and hypersensitivity (TRPV1, TRPV4, TRPA1), tends to be well established. Compared with expression data, mechanistic information about TRP channels in intestinal pacemaking (TRPC4, TRPC6, TRPM7), enteric nervous system signalling (TRPCs) and enteroendocrine cells (TRPM5) is lacking. It is clear that several different TRP channels play important roles in the cellular apparatus that controls gastrointestinal function. They are involved in the regulation of gastrointestinal motility and absorption, visceral sensation and visceral hypersensitivity. TRP channels can be considered as interesting targets to tackle digestive diseases, motility disorders and visceral pain. At present, TRPV1 antagonists are under development for the treatment of heartburn and visceral hypersensitivity, but interference with other TRP channels is also tempting. However, their role in gastrointestinal pathophysiology first needs to be further elucidated.


Cloning of bullfrog thyroid-stimulating hormone (TSH) beta subunit cDNA: expression of TSHbeta mRNA during metamorphosis.
A thyroid-stimulating hormone beta subunit (TSHbeta) cDNA encoding both signal peptide and mature TSHbeta molecule was cloned from a cDNA library constructed from total RNA of the bullfrog (Rana catesbeiana) adenohypophysis. The bullfrog TSHbeta mRNA was estimated by Northern blot analysis to be approximately 1 kb. The deduced amino acid sequence showed 40-61% homologies with the sequences of TSH beta subunits of other vertebrates. Using the cDNA as a probe, we measured changes in mRNA expression in metamorphosing tadpoles of R. catesbeiana. The TSH beta subunit mRNA level increased progressively throughout prometamorphic stages, reaching its maximum at the end of prometamorphosis. The maximum level was maintained throughout early and mid climax, declining at late climax. These results, together with previously obtained data on plasma prolactin and pituitary prolactin mRNA levels, as well as thyroid hormone levels, are discussed in relation to metamorphic changes occurring in the bullfrog larvae.


[Antinuclear antibodies (ANA) in inflammatory eye diseases].
The occurrence of antinuclear antibodies was investigated in patients with chronic open-angle glaucoma, senile cataract and retinal detachment, using the indirect immunofluorescence technique. The values obtained were the same as those for a normal population. Additionally, the presence and titer levels of ANA were tested in patients with endogenous uveitis, papillitis and optic neuritis. Our results suggest that ANA do not occur more frequently in these conditions.


Bidirectional modulation of visual plasticity by cholinergic receptor subtypes in the frog optic tectum.
Cholinergic input to the optic tectum is necessary for visual map maintenance. To understand why, we examined the effects of activation of the different cholinergic receptor subtypes in tectal brain slices and determined whether the retinotectal map was affected by manipulations of their activity in vivo. Both alpha-bungarotoxin sensitive and insensitive nicotinic receptor agonists increased spontaneous postsynaptic currents (sPSCs) in a subpopulation of patch-clamped tectal cells; application of subtype selective receptor antagonists reduced nicotine-induced increases in sPSCs. Activation of alpha-bungarotoxin insensitive nicotinic receptors also induced substantial inward current in some cells. Muscarinic receptor mediated outward current responses were blocked by the M2-like muscarinic receptor antagonists himbacine or AF-DX 384 and mimicked by application of the M2-like agonist oxotremorine. A less frequently observed muscarinic response involving a change in sPSC frequency appeared to be mediated by M1-like muscarinic receptors. In separate experiments, pharmacological manipulation of cholinergic receptor subtype activation led to changes in the activity-dependent visual map created in the tectum by retinal ganglion cell terminals. Chronic exposure of the tectum to either alpha-bungarotoxin insensitive, alpha-bungarotoxin sensitive or M1-like receptor antagonists resulted in map disruption. However, treatment with the M2-like receptor antagonist, AF-DX 384, compressed the map. We conclude that nicotinic or M1-like muscarinic receptors control input to tectal cells while alpha-bungarotoxin insensitive nicotinic receptors and M2-like muscarinic receptors change tectal cell responses to that input. Blockade of the different cholinergic receptor subtypes can have opposing effects on map topography that are consistent with expected effects on tectal cell activity levels.


Transcranial random noise stimulation over the primary motor cortex in PD-MCI patients: a crossover, randomized, sham-controlled study.
Mild cognitive impairment (MCI) is a very common non-motor feature of Parkinson's disease (PD) and the non-amnestic single-domain is the most frequent subtype. Transcranial random noise stimulation (tRNS) is a non-invasive technique, which is capable of enhancing cortical excitability. As the main contributor to voluntary movement control, the primary motor cortex (M1) has been recently reported to be involved in higher cognitive functioning. The aim of this study is to evaluate the effects of tRNS applied over M1 in PD-MCI patients in cognitive and motor tasks. Ten PD-MCI patients, diagnosed according to the Movement Disorder Society, Level II criteria for MCI, underwent active (real) and placebo (sham) tRNS single sessions, at least 1 week apart. Patients underwent cognitive (Digit Span Forward and Backward, Digit Symbol, Visual Search, Letter Fluency, Stroop Test) and motor assessments (Unified Parkinson's Disease Rating Scale [UPDRS-ME], specific timed trials for bradykinesia, 10-m walk and Timed up and go tests) before and after each session. A significant improvement in motor ability (UPDRS-ME and lateralized scores, ps from 0.049 to 0.003) was observed after real versus sham tRNS. On the contrary, no significant differences were found in other motor tasks and cognitive assessment both after real and sham stimulations. These results confirm that tRNS is a safe and effective tool for improving motor functioning in PD-MCI. Future studies using a multisession tRNS applied over multitargeted brain areas (i.e., dorsolateral prefrontal cortex and M1) are required to clarify the role of tRNS regarding rehabilitative intervention in PD.


The Drosophila protein mustard tailors the innate immune response activated by the immune deficiency pathway.
In this study, we describe a Drosophila melanogaster transposon insertion mutant with tolerance to Vibrio cholerae infection and markedly decreased transcription of diptericin as well as other genes regulated by the immune deficiency innate immunity signaling pathway. We present genetic evidence that this insertion affects a locus previously implicated in pupal eclosion. This genetic locus, which we have named mustard (mtd), contains a LysM domain, often involved in carbohydrate recognition, and a TLDc domain of unknown function. More than 20 Mtd isoforms containing one or both of these conserved domains are predicted. We establish that the mutant phenotype represents a gain of function and can be replicated by increased expression of a short, nuclearly localized Mtd isoform comprised almost entirely of the TLDc domain. We show that this Mtd isoform does not block Relish cleavage or translocation into the nucleus. Lastly, we present evidence suggesting that the eclosion defect previously attributed to the Mtd locus may be the result of the unopposed action of the NF-κB homolog, Relish. Mtd homologs have been implicated in resistance to oxidative stress. However, to our knowledge this is the first evidence that Mtd or its homologs alter the output of an innate immunity signaling cascade from within the nucleus.


Nutritional strategies for treating chronic fatigue syndrome.
Despite considerable worldwide efforts, no single etiology has been identified to explain the development of chronic fatigue syndrome (CFS). It is likely that multiple factors promote its development, sometimes with the same factors both causing and being caused by the syndrome. A detailed review of the literature suggests a number of marginal nutritional deficiencies may have etiologic relevance. These include deficiencies of various B vitamins, vitamin C, magnesium, sodium, zinc, L-tryptophan, L-carnitine, coenzyme Q10, and essential fatty acids. Any of these nutrients could be marginally deficient in CFS patients, a finding that appears to be primarily due to the illness process rather than to inadequate diets. It is likely that marginal deficiencies not only contribute to the clinical manifestations of the syndrome, but also are detrimental to the healing processes. Therefore, when feasible, objective testing should identify them and their resolution should be assured by repeat testing following initiation of treatment. Moreover, because of the rarity of serious adverse reactions, the difficulty in ruling out marginal deficiencies, and because some of the therapeutic benefits of nutritional supplements appear to be due to pharmacologic effects, it seems rational to consider supplementing CFS patients with the nutrients discussed above, along with a general high-potency vitamin/mineral supplement, at least for a trial period.


Deficits in planning time but not performance in patients with multiple sclerosis.
Studies of planning ability typically involve some version of the Tower of Hanoi or Tower of London (TOL). When these tests are administered to patients with multiple sclerosis (MS), the findings pertaining to planning "performance" have been conflicting. Possible reasons for failures to find deficits in planning performance among MS patients are: (a) the patients typically have relapsing-remitting MS (RRMS) of mild severity and short duration and thus little cognitive impairment relative to those with more advanced disease; (b) the problems composing the tests are too simple and differences between patients and controls are therefore obscured by ceiling effects; and (c) the scoring system typically used permits participants to earn points for successful solutions on later trials after failing the initial attempt on each problem, thereby further diluting the difference between patients and controls. The present study compared the performance of patients with both relapsing-remitting and secondary progressive disease with that of healthy controls on a more challenging version of the TOL. Patients exhibited lengthier planning times on the test, greater disparity in their average planning times from those of controls as the difficulty level increased, and greater individual variability in their planning times across the full set of problems. However, no differences in planning performance were found between patients and controls or between RRMS and secondary progressive MS patients. Performance differences in other studies may be attributable in part to the imposition of time limits for solving each problem and the disproportionately adverse effect such time limits have on patients' performance.


Multifocal scalp abscess with subcutaneous fat necrosis and scarring alopecia as a complication of scalp mesotherapy.
Over the past several years, there has been a growing interest in the treatment method termed mesotherapy. Marketed for nonsurgical fat melting, skin rejuvenation, and hair regrowth, this technique has become increasingly popular and, in the public's view, it is considered to be a relatively benign intervention method. Mesotherapy was introduced over 50 years ago by M. Pistor, a French physician who utilized this technique initially as a novel analgesic therapeutic method for a variety of rheumatologic disorders. Since its introduction, the basic principal of locally injecting subcutaneous doses of varying chemicals has been expanded and is now utilized for the aforementioned cosmetic concerns. With its increased popularity, there has been an increase in the number of reported side effects resulting from mesotherapeutic intervention. We report multifocal scalp abscesses with subcutaneous fat necrosis as a direct result of mesotherapy; therefore, requiring extensive surgical repair.


Pre-gestational diabetes: Maternal body mass index and gestational weight gain are associated with augmented umbilical venous flow, fetal liver perfusion, and thus birthweight.
To assess how maternal body mass index and gestational weight gain are related to on fetal venous liver flow and birthweight in pregnancies with pre-gestational diabetes mellitus. In a longitudinal observational study, 49 women with pre-gestational diabetes mellitus were included for monthly assessments (gestational weeks 24-36). According to the Institute Of Medicine criteria, body mass index was categorized to underweight, normal, overweight, and obese, while gestational weight gain was classified as insufficient, appropriate or excessive. Fetal size, portal flow, umbilical venous flow and distribution to the fetal liver or ductus venosus were determined using ultrasound techniques. The impact of fetal venous liver perfusion on birthweight and how body mass index and gestational weight gain modified this effect, was compared with a reference population (n = 160). The positive association between umbilical flow to liver and birthweight was more pronounced in pregnancies with pre-gestational diabetes mellitus than in the reference population. Overweight and excessive gestational weight gain were associated with higher birthweights in women with pre-gestational diabetes mellitus, but not in the reference population. Fetuses of overweight women with pre-gestational diabetes mellitus had higher umbilical (p = 0.02) and total venous liver flows (p = 0.02), and a lower portal flow fraction (p = 0.04) than in the reference population. In pre-gestational diabetes mellitus pregnancies with excessive gestational weight gain, the umbilical flow to liver was higher than in those with appropriate weight gain (p = 0.02). The results support the hypothesis that umbilical flow to the fetal liver is a key determinant for fetal growth and birthweight modifiable by maternal factors. Maternal pre-gestational diabetes mellitus seems to augment this influence as shown with body mass index and gestational weight gain.


Cardiac sarcolemma: compositional adaptation to exercise.
Marked changes were observed in the lipid composition of highly purified plasma membranes isolated from the hearts of rats subjected to daily treadmill running. Compared to sedentary controls, sarcolemmal content of total phospholipid and phosphatidylserine in the trained group was increased 23 and 50 percent, respectively. This observation suggests a mechanism by which cardiac contractility may be enhanced by exercise.


Comparative morphology of the hemolymph vascular system in krill (Euphausiacea; Crustacea).
The phylogenetic position of Euphausiacea within Malacostraca is still under debate. Either they are seen as sister group to a taxon comprising Pancarida and Peracarida or closer related to Decapoda. Both hypotheses can be supported by characters of the circulatory system. Therefore, a comparative re-evaluation of the circulatory system seems to be feasible. Here we present the first three-dimensional data of the circulatory system of three euphausiacean species based on semi-thin sections and micro computer tomography in combination with corrosion casting. We were also able to study for the first time representatives of Bentheuphausia amblyops, the suggested sister taxon to all other euphausiaceans. The main pumping structure in the open circulatory system of Euphausiacea is the globular heart in the rear thoracic segments. From the anterior and posterior end of the heart two unpaired and four pairs of arteries emanate. The unpaired anterior aorta runs below the carapace from the anterior part of the heart into the anterior cephalothorax, where it supplies the first antennae, the brain and the eyes. The paired posterior aortae run into the pleon supplying the pleopods, uropods and the telson. The four pairs of cardiac arteries supply appendages in the cephalic region and viscera in the trunk. The unpaired descending artery connects to the subneural vessel supplying the thoracopods. A myoarterial formation of the anterior aorta is described in Bentheuphausia amblyops. The observed pattern of a globular heart situated in the posterior cephalothorax and comprising a meshwork of muscular strands (also running through its lumen) is highly likely to be homologous in Euphausiacea and Decapoda. The data are compared with the scarce literature present to date.


[Leukocyte function as one of the indices of resistance to influenza in children].
Preliminary results of comparative characterization of the functional activity of leukocytes by cytochemical, virologic, immunologic, and clinical methods of examinations in institutionalized young infants are summarized. The observations covered 100 infants varying in ages from 1 to 3 years with frequent and rare incidence of respiratory diseases. The diagnosis of influenza had been confirmed by serological methods: CFT and ELISA. Infants with positive serodiagnosis were selected for further studies. The functional status of leukocytes was determined by the interferon leukocyte test (ILT), alkaline phosphatase and myeloperoxidase activities. The results presented in the Tables have shown the infants frequently suffering from ARVD to have low values of ILT and higher values of alkaline phosphatase activity but low myeloperoxidase activity. More resistant infants with rare incidence of ARVD had high ILT, high myeloperoxidase activity and low alkaline activity. It is suggested that alkaline activity of leukocytes alone may be of informative value.


Complication rate after circumcision in a paediatric surgical setting should not be neglected.
As a consequence of the discussion on whether the health benefits of newborn male circumcision outweigh the risks and the discrepancies in reported figures of complications, we evaluated our results from a paediatric surgical department. Patient file data from children who had undergone ritual circumcision in the 1996-2003 period were retrieved. Complications recorded until December 2011 were noted. Circumcision in 315 boys aged from 3 weeks to 16 years (median five years) were evaluated. A total of 16 boys (5.1%) had significant complications, including three incomplete circumcisions requiring re-surgery, two requiring re-surgery six months and five years postoperatively due to fibrotic phimosis and two requiring meatotomy due to meatal stenosis two and three year postoperatively. Acute complications included two superficial skin infections one week postoperatively and five cases with prolonged stay or re-admissions for bleeding the first or second postoperative day, whereof two underwent operative treatment. Finally, two had anaesthesiological complications leading to a need for overnight surveillance, but no further treatment. Parents should be counselled and be required to provide informed consent that any health benefits of childhood circumcision do not outweigh the reported complication rate and that therefore they should weigh the health benefits against the risks in light of their religious, cultural and personal preferences. As ritual circumcision is legal, a strong focus on high surgical/anaesthesiological standards is needed to avoid complications. not relevant. not relevant.


Mechanistic molecular motion of transition-metal mediated β-hydrogen transfer: quasiclassical trajectories reveal dynamically ballistic, dynamically unrelaxed, two step, and concerted mechanisms.
The transfer of a β-hydrogen from a metal-alkyl group to ethylene is a fundamental organometallic transformation. Previously proposed mechanisms for this transformation involve either a two-step β-hydrogen elimination and migratory insertion sequence with a metal hydride intermediate or a one-step concerted pathway. Here, we report density functional theory (DFT) quasiclassical direct dynamics trajectories that reveal new dynamical mechanisms for the β-hydrogen transfer of [Cp*RhIII(Et)(ethylene)]+. Despite the DFT energy landscape showing a two-step mechanism with a Rh-H intermediate, quasiclassical trajectories commencing from the β-hydrogen elimination transition state revealed complete dynamical skipping of this intermediate. The skipping occurred either extremely fast (typically <100 femtoseconds (fs)) through a dynamically ballistic mechanism or slower through a dynamically unrelaxed mechanism. Consistent with trajectories begun at the transition state, all trajectories initiated at the Rh-H intermediate show continuation along the reaction coordinate. All of these trajectory outcomes are consistent with the Rh-H intermediate <1 kcal mol-1 stabilized relative to the β-hydrogen elimination and migratory insertion transition states. For Co, which on the energy landscape is a one-step concerted mechanism, trajectories showed extremely fast traversing of the transition-state zone (<50 fs), and this concerted mechanism is dynamically different than the Rh ballistic mechanism. In contrast to Rh, for Ir, in addition to dynamically ballistic and unrelaxed mechanisms, trajectories also stopped at the Ir-H intermediate. This is consistent with an Ir-H intermediate that is stabilized by ∼3 kcal mol-1 relative to the β-hydrogen elimination and migratory insertion transition states. Overall, comparison of Rh to Co and Ir provides understanding of the relationship between the energy surface shape and resulting dynamical mechanisms of an organometallic transformation.


Automatic Estimation of Multidimensional Ratings from a Single Sound-Symbolic Word and Word-Based Visualization of Tactile Perceptual Space.
Several pairs of Japanese adjective words pertaining to material's properties, such as roughness and hardness, have been used in Japanese studies to quantitatively evaluate variations in tactile sensations. This method asks observers to analyze their perceptual experiences one by one. An alternative notion is that human perceptual recognition is performed as a whole rather than by using fragmented factors. Based on this notion, we propose a system that can automatically estimate multidimensional ratings of touch from a single sound-symbolic word that has been spontaneously and intuitively expressed by a user. When a user inputs a sound-symbolic word into the system, the system refers to a database of phonemes and their auditory impressions, and calculates ratings in terms of 26 pairs of fundamental scales of touch. The estimated ratings of sound-symbolic words enable us to visualize a tactile perceptual space. Our study provides an alternative method for estimating the fine quality of tactile sensations.


Ceramide is involved in r(+)-methanandamide-induced cyclooxygenase-2 expression in human neuroglioma cells.
Cannabinoids have recently been shown to induce the expression of the cyclooxygenase-2 (COX-2) isoenzyme in H4 human neuroglioma cells. Using this cell line, the present study investigates the contribution of the second messenger ceramide to this signaling pathway. Incubation of cells with the endocannabinoid analog R(+)-methanandamide (R(+)-MA) was associated with an increase of intracellular ceramide levels. Enhancement of ceramide formation by R(+)-MA was abolished by fumonisin B1, a ceramide synthase inhibitor, whereas inhibitors of neutral sphingomyelinase (spiroepoxide, glutathione) and serine palmitoyltransferase (l-cycloserine, ISP-1) were inactive in this respect. R(+)-MA caused a biphasic activation of the p38 and p42/44 mitogen-activated protein kinases (MAPKs), with phosphorylation peaks occurring after 15-min and 4- to 8-h treatments, respectively. Inhibition of ceramide synthesis with fumonisin B1 was associated with a suppression of R(+)-MA-induced delayed phosphorylations of p38 and p42/44 MAPKs and subsequent COX-2 expression. The involvement of ceramide in COX-2 expression was corroborated by findings showing that C2-ceramide and neutral sphingomyelinase from Bacillus cereus caused concentration-dependent increases of COX-2 expression that were suppressed in the presence of 4-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridyl)imidazol (SB203580, a p38 MAPK inhibitor) or 2'-amino-3'-methoxyflavone (PD98059, a p42/44 MAPK activation inhibitor). In contrast, dihydro-C2-ceramide being used as a negative control did not induce MAPK phosphorylation and COX-2 expression. Collectively, our results demonstrate that R(+)-MA induces COX-2 expression in human neuroglioma cells via synthesis of ceramide and subsequent activation of p38 and p42/44 MAPK pathways. Induction of COX-2 expression via ceramide represents a hitherto unknown mechanism by which cannabinoids mediate biological effects within the central nervous system.


Amino acids analysis reveals serum methionine contributes to diagnosis of the Kawasaki disease in mice and children.
Kawasaki disease (KD) patients often lack early and definitive diagnosis due to insufficient clinical criteria, whereas biomarkers might accelerate the diagnostic process and treatment. The KD mouse models were established and thirteen amino acids were determined. A total of 551 serum samples were collected including KD patients (n = 134), HCs (n = 223) and KD patients after intravascular immunoglobulin therapy (IVIG, n = 194). A paired analysis of pre- and post-IVIG was employed in 10 KD patients. The pathological alterations of the aorta, myocardial interstitium and coronary artery vessel were observed in KD mice; the serum levels of methionine in KD mice (n = 40) were markedly altered and negatively correlated with the C-reactive protein levels. Consistent with the mouse model, serum methionine were significantly decreased in KD children, with the relative variation ratio of KD with HCs above 30% and AUROC value of 0.845. Serum methionine were correlated with Z-Score and significantly restored to the normal ranges after KD patient IVIG treatment. Another case-control study with 10 KD patients with IVIG sensitivity and 20 healthy controls validated serum methionine as a biomarker for KD patients with AUROC of 0.86. Elevation of serum DNMT1 activities, but no differences of DNMT3a and DNMT3b, were observed in KD patients when comparing with those in the HCs. Our study validated that serum methionine was a potential biomarker for KD, the alteration of which is associated with the activation of DNMT1 in KD patients.


Crystal structure of a new alpha-cyclodextrin hydrate form. Molecular geometry and packing features: disordered solvent contribution.
The crystallographic study of a new hydrated form of alpha-cyclodextrin (cyclohexaamylose) is reported. C36H60O30 . 11H2O; space group P2(1)2(1)2(1) with cell constants a = 13.839(3), b = 15.398(3), c = 24.209(7) A; final discrepancy index R = 0.057 for the 5182 observed reflections and 632 refined parameters. Besides four ordered water molecules placed outside alpha-cyclodextrins, the structure shows regions of severely disordered solvent mainly confined in the oligosaccharide cavities. The contribution of the observed disorder has been computed via Fourier inversions of the residual electron density and incorporated into the structure factors in further refinements of the ordered part. The alpha-cyclodextrin molecule assumes a relaxed round shape stabilised by a ring sequence of all the six possible O2 ... O3 intramolecular hydrogen bonds. The four ordered water molecules take part in an extensive network of hydrogen bonds (infinite chains and loops) without modifying the scheme of intramolecular H-bonds or the (-)gauche conformation of O-6-H hydroxyl groups. The structure shows a new molecular arrangement, for an "empty" hydrated alpha-cyclodextrin, like that "brick-type" observed for alpha-CD in the iodoanilide trihydrate complex crystallising in an isomorphous cell.


The coronal plane magnetic resonance imaging measurement of hippocampal formation volume.
The aim of this study was to provide healthy Chinese adult hippocampal formation volume data for the clinic and diagnoses of the related diseases. Three-dimensional fast spoiled gradient echo magnetic resonance imaging sequence scanning was used in 68 cases of healthy adult brain to gain the image between lateral border of bilateral fourth ventricle and vitreous body. The image then was divided into 10 equal parts in the sagittal plane. We draw the outline and then obtain the area and volume of the hippocampal formation in each part, and the data were analyzed by SPSS 17.0 software. Results of the research showed that the volume of the hippocampal in healthy Chinese adult left side is ≈ 2319.87 to 2602.47 mm3, right side is ≈ 2443.96 to 2755.89 mm3; male left side is ≈ 2135.00 to 2494.29 mm3, right side is ≈ 2350.21 to 2745.61 mm3; female left side is ≈ 2328.13 to 2748.41 mm3, right side is ≈ 2398.41 to 2909.48 mm3. The volume of hippocampal absence correlated with age (P > 0.05), youth group. The volume of hippocampal has significant sexual difference (t = 2.500, P < 0.05). The volumes of the left and right sides have significant difference (t = 2.571, P < 0.05). The female group (middle-age and youth) which the volumes of right-side hippocampal have significant difference (P < 0.05).


Determinants of Patient-Reported Psoriatic Arthritis Impact of Disease: An Analysis of the Association With Sex in 458 Patients From Fourteen Countries.
Sex differences may modify symptoms, disease expression, and treatment effects. The objective of this study was to evaluate the link between life impact and sex in psoriatic arthritis (PsA). Remission and Flare in Psoriatic Arthritis (ReFlaP; ClinicalTrials.gov identifier: NCT03119805) was a study in 14 countries of consecutive adult patients with definite PsA. Participants underwent comprehensive PsA assessment using the following measures: Disease Activity in Psoriatic Arthritis (DAPSA), Minimal Disease Activity (MDA), and Psoriatic Arthritis Impact of Disease (PsAID). Disease activity was compared by sex using t-tests or Wilcoxon tests. The association of PsAID with sex was analyzed using hierarchical generalized linear models. Of 458 participants, 50.2% were male and the mean ± SD age was 53.1 ± 12.6 years. The mean ± SD PsA duration was 11 ± 8.2 years, and 51.5% of participants were being treated with biologic disease-modifying antirheumatic drugs. Women, compared to men, had worse mean ± SD Leeds Enthesitis Index scores (0.8 ± 1.7 versus 0.3 ± 0.9), pain on a numerical rating scale (NRS; range 0-10) (4.7 ± 2.7 versus 3.5 ± 2.7), HAQ DI scores (0.9 ± 0.7 versus 0.5 ± 0.6), fatigue on an NRS (5.2 ± 3 versus 3.3 ± 2.8), and PsAID scores (4.1 ± 2.4 versus 2.8 ± 2.3) (P < 0.001 for all). Women were also less frequently at treatment target compared to men according to DAPSA (cutoffs of ≤4 for remission and >4 and ≤14 for low disease activity; mean ± SD score 16.9 ± 14.9 in women versus 12.6 ± 16.6 in men) and MDA (25.7% versus 50.0%; P < 0.001 for all) scores. High life impact (PsAID score ≥4) was associated with female sex (odds ratio [OR] 2.3), enthesitis (OR 1.34), tender joints (OR 1.10)(P < 0.001 for all), and comorbidities (OR 1.22, P = 0.002). High life impact was independently associated with female sex, enthesitis, comorbidities, and tender joints. At treatment target, women had higher life impact compared to men. It is necessary for life impact to become a part of PsA treat-to-target strategies.


State of the art and emerging drug therapies for female infertility.
At present, infertility is a key-issue. When applicable, in vitro fertilization (IVF) has become the standard approach to treat this condition but a thorough investigation and, whenever possible, the individual diagnosis of the underlying causes of infertility are required. For many female causes, indeed, efficient medical therapies are available to achieve a fast solution of the problem. This review is based on the relevant literature indexed in PubMed and SCOPUS and is focused on the most recent clinical literature on the treatment of women (and couples) affected from infertility. The reduction in IVF treatment burden and risks are now considered pivotal to set 'patient-friendly' therapies and represent crucial issues for both patients and physicians. To this end, the researchers are now focusing their attention on old drugs with new indications and new compounds with more appropriate functions, to improve the compliance of the women and reduce the burden of infertility, a condition that is becoming an important issue in the modern world, also for the Public Health System.


Stink bug species composition and relative abundance of the redbanded stink bug (Hemiptera: Pentatomidae) in soybean in the upper gulf coast Texas.
Stink bugs are the primary arthropod soybean pests in the southern United States. Historically, important stink bug species damaging soybeans in the southern United States included the southern green stink bug Nezara viridula (L.), the green stink bug Chinavia hilaris (Say), and the brown stink bug Euschistus servus (Say) (Hemiptera: Pentatomidae). The redbanded stink bug, Piezodorus guildinii (Westwood), has recently become an economic pest of soybean in the southern region of the United States, especially in Louisiana and Texas. Little is known about current stink bug species composition and relative abundance in Texan soybean agro-ecosystems. To fill this gap, commercial soybean fields in the Upper Gulf Coast of Texas were sampled weekly during the growing season using a sweep net throughout R2 (full flowering) to R7 (beginning maturity) from 2011 to 2013. Adults and nymphs (third, fourth, and fifth instars) of redbanded stink bug, southern green stink bug, green stink bug, and brown stink bug were counted per 25 sweeps. The relative abundance of redbanded stink bug was significantly higher than any other stink bug species throughout 2011-2013. Over 65% of the total population of major stink bugs collected during this period were redbanded stink bugs and ≍19% were southern green stink bugs. The highest redbanded stink bug densities and the highest ratio of redbanded stink bug nymphs to adults were recorded at R7. Results from this study show that redbanded stink bug has become the predominant stink bug species in soybean in the Upper Gulf Coast of Texas.


Species diversity and antibiotic resistance of Staphylococci isolated in children of the first month of life in children's hospitals in Nizhny Novgorod.
1235 strains of Staphylococci isolated in a multidisciplinary children's clinic were analyzed. The species and antibiotic resistance of Golden and coagulase-negative Staphylococci were studied. The most frequently identified species were: S. aureus-36.06%, S. epidermidis-23.05%, S. haemolyticus-19.7%, S. hominis-14.03%. Phenotype methicillinsensitive strains had 48.9% of the allocated staphylococci, while metitillinrezistentnykh S. aureus was identified in 25.6%, and coagulase-negative staphylococci methicillinresistant- 63.2 per cent. The frequency of associated resistance to aminoglycosides, fluoroquinolones, macrolides and tetracyclines have metitillinresictant strains 92,7%, 78,3%, 83,4% and 52,05% respectively, resistant Staphylococcus and coagulase-negative staphylococci were similar. The minimum number of resistant strains was found in relation to daptomycin, no strains resistant to vancomycin and linezolid were found. Antibiotic resistance of staphylococci in children's hospitals is determined by the presence of the mecA gene or sensitivity to cefoxitin and does not depend on the type of strain.


Climate change adaptation strategies and production efficiency: The case of citrus farmers in the Limpopo province, South Africa.
Climate change adaptation policies and strategies have inevitably become an integral component of agricultural production on a global scale. The evaluative extent to which these adaptation techniques have influenced agricultural productivity is inherently exiguous. Citrus production in tropical regions such as South Africa, is more vulnerable to climate change as the region already experience hot and dry climate, hence the need to implement different strategies for climate change adaption in these regions. This study was designed to assess the effect of adopting the following climate change adaptation measures: planting drought resistant varieties, rainwater harvesting, planting early maturing varieties, integrated pest management (IPM) , changing fertiliser type, and applying drip irrigation to manage climate challenges on the production efficiency of citrus farmers in the Limpopo province of South Africa. The stochastic frontier production function with Cobb Douglas production functional form was used to analyse the productivity of farmers' vis-à-vis adopted climate change strategies. A survey was conducted and data were collected through a semi-structured questionnaire administered to respondents from 235 production units in the five district municipalities of Limpopo. The likelihood ratio tests for profit models showed that farmers were profit efficient considering the identified adaptation strategies. The variables that influenced profit efficiency was price of fertiliser (p < 0.010) and water cost (p < 0.010). The inefficiency model showed that besides changing fertiliser as an adaptation measure, the other adaptation strategies including IPM, water harvesting and planting drought resistant varieties did not change the profit efficiency of farmers. Therefore, the results indicate that citrus farmers can still adapt to climate change and remain profit efficient.


Tanshinone IIA prevents left ventricular remodelling via the TLR4/MyD88/NF-κB signalling pathway in rats with myocardial infarction.
In this study, we aim to investigate the role of tanshinone IIA in myocardial infarction (MI), especially in left ventricular remodelling (VR) and the underlying mechanism involving the TLR4/MyD88/NF-κB signalling pathway. Sprague-Dawley (SD) rats (n = 96) were selected, and 12 of them underwent sham surgery. The remaining 84 rats were subjected to MI modelling. HE and MT staining were carried out to estimate infract size, histopathological changes and fibrosis degree. Macrophage infiltration and cardiomyocyte apoptosis were evaluated by immunohistochemistry and TUNEL staining. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to determine the expression levels of TLR4, MyD88 and NF-κB. Serum levels of IL-2, IL-6, IL-8, TNF-a, procollagen I Cpropeptide (PICP), and procollagen III N-propeptide (PIIINP) were measured using enzyme-linked immunosorbent assay (ELISA). The heart weight/body weight, mean arterial pressure (MAP), left ventricular end-systolic pressure (LVESP), +dP/dt and -dP/dt increased while the ventricular function and the left ventricular end-diastole pressure (LVEDP) decreased in MI rats. Compared with the rats undergoing sham surgery, MI rats showed larger infarct size, severer fibrosis, higher expression levels of TLR4, NF-κB-P65, MyD88, IL-2, IL-6, IL-8, TNF-a, PICP and PIIINP as well as enhanced macrophage infiltration, cardiomyocyte apoptosis. After treatment with tanshinone IIA combined with LPS for 4 weeks, the rats showed better condition than those treated with only LPS. These results indicate that tanshinone IIA attenuates MI and prevents left VR. Importantly, inhibition of TLR4/MyD88/NF-κB signalling pathway is a key step in this process.


Larynx: implants and stents.
In the human larynx, implants a primarily used for the correction of glottis insufficiency. In a broader sense laryngeal stents may be considered as implants as well. Laryngeal implants can be differentiated into injectable and solid. The most important representatives of both groups are discussed in detail along with the respective technique of application. Laryngeal stents are primarily used perioperatively. Different types and their use are presented.


Beneficial Effects of Soybean-Derived Bioactive Peptides.
Peptides present in foods are involved in nutritional functions by supplying amino acids; sensory functions related to taste or solubility, emulsification, etc.; and bioregulatory functions in various physiological activities. In particular, peptides have a wide range of physiological functions, including as anticancer agents and in lowering blood pressure and serum cholesterol levels, enhancing immunity, and promoting calcium absorption. Soy protein can be partially hydrolyzed enzymatically to physiologically active soy (or soybean) peptides (SPs), which not only exert physiological functions but also help amino acid absorption in the body and reduce bitterness by hydrolyzing hydrophobic amino acids from the C- or N-terminus of soy proteins. They also possess significant gel-forming, emulsifying, and foaming abilities. SPs are expected to be able to prevent and treat atherosclerosis by inhibiting the reabsorption of bile acids in the digestive system, thereby reducing blood cholesterol, low-density lipoprotein, and fat levels. In addition, soy contains blood pressure-lowering peptides that inhibit angiotensin-I converting enzyme activity and antithrombotic peptides that inhibit platelet aggregation, as well as anticancer, antioxidative, antimicrobial, immunoregulatory, opiate-like, hypocholesterolemic, and antihypertensive activities. In animal models, neuroprotective and cognitive capacity as well as cardiovascular activity have been reported. SPs also inhibit chronic kidney disease and tumor cell growth by regulating the expression of genes associated with apoptosis, inflammation, cell cycle arrest, invasion, and metastasis. Recently, various functions of soybeans, including their physiologically active functions, have been applied to health-oriented foods, functional foods, pharmaceuticals, and cosmetics. This review introduces some current results on the role of bioactive peptides found in soybeans related to health functions.


Tazarotene versus tazarotene plus clindamycin/benzoyl peroxide in the treatment of acne vulgaris: a multicenter, double-blind, randomized parallel-group trial.
Topical retinoids offer highly effective treatment for both inflammatory and non-inflammatory acne, with tazarotene demonstrating greater efficacy than other topical retinoids. A multicenter, double-blind, randomized, parallel-group trial has been performed to evaluate whether the adjunctive use of clindamycin/benzoyl peroxide could enhance the efficacy of tazarotene still further. Patients with moderate to severe inflammatory acne applied tazarotene 0.1% cream each evening and were randomly assigned to morning applications of vehicle gel or a ready-to-dispense formulation of clindamycin 1%/benzoyl peroxide 5 % gel containing 2 emollients. Tazarotene/clindamycin/benzoyl peroxide achieved a significantly greater reduction in comedo count than tazarotene monotherapy and, among patients with a baseline papule plus pustule count of > or =25 (the median value), a significantly greater reduction in inflammatory lesion count. The combination therapy was also at least as well-tolerated as tazarotene monotherapy. The adjunctive use of clindamycin/benzoyl peroxide gel with tazarotene cream promotes greater efficacy and may also enhance tolerability. Any improvements in tolerability could be due to the emollients in the clindamycin/benzoyl peroxide gel formulation.


[Changes in indices of carbohydrate metabolism in suspended rats].
In the experiments with 35 white rats, it is found that on Days 7 and 14 of rat suspension in the head-down position the content of glycogen in both ventricles of the heart is significantly reduced. On Day 7 of the experiment, the glycogen content in m.gastrocnemius and concentration of glucose in the blood are lessened. The level of lactate in the blood and glycogen in the liver and m.soleus is not changed. The mass of body and skeletal muscles is diminished and the mass of ventricles of the heart is not changed.


Dichotic perception and memory following electroconvulsive treatment for depression.
Verbal and visuospatial memory and dichotic listening performance were examined in 15 acutely depressed patients with no history of ECT, 17 depressed patients currently in remission, 15 remitted depressed patients who had received ECT six months or more in the past, and 20 normal controls. The neuropsychological functioning of an additional group of 10 acutely depressed patients was also studied before and two weeks after ECT. The results revealed some evidence of logical and autobiographical memory impairment two weeks following ECT, but no evidence that ECT impaired dichotic listening ability. Rather, a normalisation of hemispheric laterality was apparent on the dichotic listening task following ECT and the concomitant relief from depression. There was also no evidence of cognitive dysfunction on any task in individuals who were tested six months or more following their last ECT treatment.


Depressive symptoms among Hong Kong adolescents: relation to atypical sexual feelings and behaviors, gender dissatisfaction, pubertal timing, and family and peer relationships.
A representative community sample of Hong Kong boys (n = 1,024) and girls (n = 1,403), age 14-18 years, provided information regarding same-sex attraction, gender dissatisfaction, pubertal timing, early experience with sexual intercourse, and depressive symptoms. They also rated the quality of their family and peer relationships and self-perceived attractiveness. Depressive symptoms were higher in youths reporting same-sex attraction, gender dissatisfaction, early pubertal maturation, and early sexual intercourse. Family relationships were less satisfactory for those who reported same-sex attraction, gender dissatisfaction, and early sexual intercourse, and peer relationships were also worse for those who reported gender dissatisfaction. In multivariate analyses, same-sex attraction, early sexual intercourse, and early pubertal maturation were unique and direct contributors to depressive symptoms; however, gender dissatisfaction's association with depressive symptoms was largely accounted for by shared correlations with negative family and peer relationships. The multivariate model explained 11% of the variance of depressive symptoms. These findings offer a preliminary documentation of the prevalence and correlates of atypical sexual self-assessments and behavior among adolescents in Hong Kong. Such information is important if theories of sexual identity and risk factors for depressive symptoms are to have cross-cultural utility.


Serum adiponectin as a useful marker for metabolic syndrome in type 2 diabetic patients.
Although adiponectin is generally known as a predictor of metabolic syndrome, potential of adiponectin as a predictor for metabolic syndrome in type 2 diabetes is debated. The purpose of this study is to determine the association between adiponectin and metabolic syndrome in patients with type 2 diabetes. Adiponectin and the risk of metabolic syndrome were examined among 1013 type 2 diabetes patients who visited Huh's Diabetes Center from January 2003 to June 2006. Adiponectin levels were classified into quartile groups, and metabolic syndrome was defined according to the standard of National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III. Insulin sensitivity was directly assessed using the short insulin tolerance test (SITT) (Kitt: %/ min). Adiponectin was significantly correlated with metabolic syndrome components. The age-adjusted correlations between adiponectin and clinical parameters including metabolic components were significant; adiponectin was negatively correlated with waist circumference, diastolic blood pressure and triglyceride, and positively correlated with high-density lipoprotein (HDL) cholesterol. Subjects with metabolic syndrome showed lower adiponectin levels than those without metabolic syndrome. After multivariate adjustment, participants with lower adiponectin levels also had a higher risk for metabolic syndrome (OR for lowest quartiles 2.21; 95% CI, 1.51-3.24). Metabolic syndrome risk was stronger among those with low adiponectin and severe insulin resistance simultaneously. This study has shown additive effects of adiponectin and insulin resistance on metabolic syndrome. In type 2 diabetic patients, the adiponectin was a useful predictor of metabolic syndrome independent of potential confounding variables.


Escherichia coli catabolite gene activator protein mutants defective in positive control of lac operon transcription.
We isolated three Escherichia coli catabolite gene activator protein mutants that are defective in the positive control of transcription initiation from the lac operon promoter region yet retain negative control of transcription from other promoters. One mutant has a substitution of valine for glutamate at residue 72, which lies in the cyclic AMP binding domain and contacts cyclic AMP. The other two mutants have substitutions of asparagine and cysteine for glycine 162, which lies in a surface-exposed turn of the DNA-binding domain. Surprisingly, although all three mutants can repress the lacP2/P3 promoters through the catabolite gene activator protein target site of lac, none displays strong dominance over the ability of wild-type catabolite gene activator protein to stimulate the lacP1 promoter.


A Two-Way Interactive Text Messaging Application for Low-Income Patients with Chronic Medical Conditions: Design-Thinking Development Approach.
Two-way interactive text messaging between patient and community health workers (CHWs) through mobile phone SMS (short message service) text messaging is a form of digital health that can potentially enhance patient engagement in young adults and families that have a child with chronic medical conditions such as diabetes mellitus, sickle cell disease, and asthma. These patients have complex needs, and a user-centered way can be useful for designing a tool to address their needs. The aim of this study was to utilize the user-centered approach of design thinking to develop a two-way interactive communication SMS text messaging tool for communication between patients or caregivers and CHWs. We applied a design thinking methodology for development of the SMS text messaging tool. We collected qualitative data from 127 patients/caregivers and 13 CHWs, health care professionals, and experts. In total, 4 iterative phases were used to design the final prototype. The design thinking process led to the final SMS text messaging tool that was transformed from a one-dimensional, template-driven prototype (phases 1 and 2) into a dynamic, interactive, and individually tailored tool (phases 3 and 4). The individualized components consider social factors that influence patients' ability to engage such as transportation issues and appointment reminders. SMS text messaging components also include operational factors to support staff such as patient contact lists, SMS text messaging templates, and technology chat support. Design thinking can develop a tool to meet the engagement needs of patients with complex health care needs and be user-friendly for health care staff.


Ondansetron augmentation of serotonin reuptake inhibitors as a treatment strategy in obsessive-compulsive disorder.
Serotonin reuptake inhibitors (SRIs) are the mainstay in the treatment of obsessive-compulsive disorder (OCD). Patients who do not respond adequately to SRIs commonly receive augmentation therapy with another agent, usually an atypical antipsychotic drug. Atypical antipsychotics, however, may not be appropriate for or acceptable to all patients. Ondansetron is an experimental alternative for such patients. There have been at least 6 trials that have examined a short-term (8-12 weeks) role for ondansetron in patients with OCD. These include 1 placebo-controlled crossover trial (N = 11); 1 uncontrolled monotherapy trial (N = 8); 2 low-dose (0.5-1.0 mg/d), uncontrolled augmentation trials in patients who did not respond adequately to ongoing or earlier treatments (pooled N = 35); and 2 moderate- to high-dose (4-8 mg/d) randomized, placebo-controlled augmentation trials in patients with undocumented past treatment history (pooled N = 88). Ondansetron was modestly effective in the uncontrolled trials and strikingly effective in the controlled trials. Ondansetron was also very well tolerated in all of the studies. These enthusiastic observations must be tempered by the limitations of the reviewed data, such as small sample sizes, short study durations, lack of data on the effects of blinded ondansetron discontinuation, lack of long-term data, and study-specific limitations. At best, ondansetron (1-8 mg/d) may be considered an experimental SRI augmentation agent in OCD patients for whom augmentation with an atypical antipsychotic drug is problematic.


Discovery, modeling, and human pharmacokinetics of N-(2-acetyl-4,6-dimethylphenyl)-3-(3,4-dimethylisoxazol-5-ylsulfamoyl)thiophene-2-carboxamide (TBC3711), a second generation, ETA selective, and orally bioavailable endothelin antagonist.
Sitaxsentan (1) (Wu et al. J. Med. Chem. 1997, 40, 1690) is our first endothelin antagonist being evaluated in clinical trials. It has demonstrated biological effects in an acute hemodynamic study in CHF (Givertz et al. Circulation 2000, 101, 2922), an open-label 20-patient pulmonary hypertension trial (Barst et al. Chest 2002, 121, 1860-1868), and a 31-patient trial in essential hypertension (Calhoun et al. AHA Scientific Sessions 2000). In a phase 2b/3 pulmonary arterial hypertension trial, once a day treatment of 100 mg of sitaxsentan statistically significantly improved 6-min walk distance and NYHA class at 12 weeks (Barst et al. Am. J. Respir. Crit. Care Med. 2004, 169, 441). We have since reported on our efforts in generating follow-up compounds (Wu et al. J. Med. Chem. 1999, 42, 4485) and recently communicated that an ortho acyl group on the anilino ring enhanced oral absorption in this category of compounds (Wu et al. J. Med. Chem. 2001, 44, 1211). Here we report an expansion of this work by substituting a variety of electron-withdrawing groups at the ortho position and evaluating their effects on oral bioavailability as well as structure-activity relationships. As a result, TBC3711 (7z) was identified as our second endothelin antagonist to enter the clinic due to its good oral bioavailability (approximately 100%) in rats, high potency (ET(A) IC(50) = 0.08 nM), and optimal ET(A)/ET(B) selectivity (441 000-fold). Compound 7z has completed phase-I clinical development and was well tolerated with desirable pharmacokinetics in humans (t(1/2) = 6-7 h, oral availability > 80%).


A new perspective on transcriptional system regulation (TSR): towards TSR profiling.
It has been hypothesized that the net expression of a gene is determined by the combined effects of various transcriptional system regulators (TSRs). However, characterizing the complexity of regulation of the transcriptome is a major challenge. Principal component analysis on 17,550 heterogeneous human microarray experiments revealed that 50 orthogonal factors (hereafter called TSRs) are able to capture 64% of the variability in expression in a wide range of experimental conditions and tissues. We identified gene clusters controlled in the same direction and show that gene expression can be conceptualized as a process influenced by a fairly limited set of TSRs. Furthermore, TSRs can be linked to biological functions, as we demonstrate a strong relation between TSR-related gene clusters and biological functionality as well as cellular localization, i.e. gene products of similarly regulated genes by a specific TSR are located in identical parts of a cell. Using 3,934 diverse mouse microarray experiments we found striking similarities in transcriptional system regulation between human and mouse. Our results give biological insights into regulation of the cellular transcriptome and provide a tool to characterize expression profiles with highly reliable TSRs instead of thousands of individual genes, leading to a >500-fold reduction of complexity with just 50 TSRs. This might open new avenues for those performing gene expression profiling studies.


[New trends in immunodermatology and treatment of skin diseases].
Nowhere in the body are inflammatory reactions more apparent than in the skin. The inflammation may be beneficial, as in defence against tumours or infections, or inimical, as in allergy and psoriasis. The skin is a primary immunological organ which presents antigens to T cells, and produces many types of cytokines. The complex interplay between cells and mediators in immunologically induced skin diseases is beginning to be unveiled. Other new developments include improved immunosuppressive therapy and highly specific anti-inflammatory treatment that induces naturally occurring down-regulatory signals.


Effect of CYP2D6 genotype on duloxetine serum concentration.
Duloxetine is metabolized by cytochrome P450 (CYP)1A2 and CYP2D6. The aim of this study was to investigate the effect of the CYP2D6 genotype on duloxetine serum concentration adjusting for age and sex. Patients were included retrospectively from a therapeutic drug monitoring service. Multiple linear regression analysis was used to investigate the effect of CYP2D6 genotype, age and sex on the duloxetine concentration-to-dose (C/D) ratio. In total, 269 patients were included and assigned to the following genotype-predicted phenotype subgroups: CYP2D6 poor metabolizers (PMs, n = 23), intermediate metabolizers (IMs, n = 121), normal metabolizers (NMs, n = 120) and ultrarapid metabolizers (UMs, n = 5). Multiple linear regression analysis revealed a 95% higher duloxetine C/D ratio in PMs compared with NMs (p = 0.009). Patients ≥65 years had a 56% higher C/D ratio than younger patients (p = 0.01), while women had a 46% higher C/D ratio than men (p = 0.04). In conclusion, the CYP2D6 PM phenotype is associated with a twofold higher concentration at recommended dosing compared with the NM phenotype. CYP2D6 PM females above 65 years are at particular risk of high duloxetine levels as they may obtain a threefold higher C/D ratio compared with younger, male NMs.


Myocardial contusion following nonfatal blunt chest trauma.
Currently available diagnostic techniques for myocardial contusion following blunt chest trauma were evaluated. We investigated 30 patients prospectively over a period of 1 year for the presence of myocardial contusion. Among the 30 patients, eight were found to have myocardial contusion on the basis of abnormal electrocardiograms, elevated creatine phosphokinase MB fraction (CPK-MB), and positive myocardial scan. Myocardial scan was positive in seven of eight patients (87.5%). CPK-MB fraction was elevated in four of eight patients (50%). Definitive electrocardiographic changes were seen in only two of eight patients (25%). It appears that myocardial scan using technetium pyrophosphate and CPK-MB fraction determinations are the most reliable aids in diagnosis of myocardial contusion following blunt chest trauma.


A qualitative study of women's experiences of familial ovarian cancer screening.
One risk management strategy that women at increased familial risk of ovarian cancer may use is screening. Until recently, this has been available as part of the UK Familial Ovarian Cancer Screening Study (UKFOCSS), using ultrasound scans of the ovaries and tumour marker blood tests. The present study aimed to gain an in-depth understanding of women's experiences of participating in ovarian cancer screening. Semi-structured interviews were conducted with 48 UKFOCSS participants. Interviews were recorded, transcribed and relevant sections analysed using a framework approach. Screening provided women with reassurance which they found beneficial. A sense of privilege, as well as feeling proactive in potentially detecting ovarian cancer at an early stage was described. The wider benefit to research and the potential impact this could have on others was also important to women. Negative experiences of screening included worry about the screening tests and results, false reassurance by test results and disappointment with ineffective screening. Aspects of the screening study, such as the logistics, organisation and communication, were described as both good and problematic. When weighed up by the women, most described an overall positive experience of screening. Women reported both positive and negative experiences of screening. Overall, screening seemed to be an acceptable risk management strategy to most women who participated in this interview study. Improvements could be made particularly in helping women to understand the limitations of familial ovarian cancer screening in order to avoid false reassurance.


[Hepatotoxicity of the combination of isoniazid-rifampicin in African children. Role of malnutrition and HB virus].
Forty-seven Gabonese children with tuberculosis either limited to the lung or associated with other localizations were treated with isoniazid-rifampin (INH + RIF). They had liver tests done during the first 6 months of treatment. In 30 patients (63.8%) there was an increase in aminotransferase levels [over 100 UI/l in 14 (29.2%)]. The main factors increasing the risk of hepatic toxicity was a high dosage of INH and overall malnutrition. In fact, the weights of patients presenting with signs of hepatic toxicity were significantly lower than those in children who had no alterations of liver function. 68% of the severely malnourished (marasmus of kwashiorkor) presented with high ALAT or ASAT levels during treatment. The eventual role of the chronic HBV carrier state is discussed as 2 children presented with a chronic form of hepatitis at the time the treatment was initiated.


Newer Non-ionic A2 B2 -Type Enzyme-Responsive Amphiphiles for Drug Delivery.
A new series of nonionic gemini amphiphiles have been synthesized in a multi-step chemoenzymatic approach by using a novel A2 B2 -type central core consisting of conjugating glycerol and propargyl bromide on 5-hydroxy isophthalic acid. A pair of hydrophilic monomethoxy poly(ethylene glycol) (mPEG) and hydrophobic linear alkyl chains (C12 /C15 ) were then added to the core to obtain amphiphilic architectures. The aggregation tendency in aqueous media was studied by dynamic light scattering, fluorescence spectroscopy and cryogenic transmission electron microscopy. The nanotransport potential of the amphiphiles was studied for model hydrophobic guests, that is, the dye Nile Red and the drug Nimodipine by using UV/Vis and fluorescence spectroscopy. Evaluation of the viability of amphiphile-treated A549 cells showed them to be well tolerated up to the concentrations studied. Being ester based, these amphiphiles exhibit stimuli-responsive sensitivity towards esterases, and a rupture of amphiphilic architecture was observed in the presence of immobilized Candida antarctica lipase (Novozym 435), thus facilitating release of the encapsulated guest from the aggregate.


A multicenter, randomized, double-blind study comparing different FK778 doses (manitimus) with tacrolimus and steroids vs. MMF with tacrolimus and steroids in renal transplantation.
This multicenter phase II study in renal transplantation compared 3 concentration-controlled ranges of FK778 (manitimus) with mycophenolate mofetil (MMF) both given in combination with tacrolimus and corticosteroids. 364 patients were randomized to 12-month treatment: high-level FK778 group (H, N=87) received 4 x 600 mg/day (4 days) followed by 120 mg/day; mid-level FK778 group (M, N=92) received 3 x 600 mg/day (3 days) followed by 110 mg/day, low-level FK778 group (L, N=92) received 2 x 600 mg/day (2 days) followed by 100 mg/day, and control group received MMF 1 g/day (MMF, N=93). After week 6, FK778 doses were adjusted to trough ranges of 75-125 μg/mL (H), 50-100 μg/mL (M) and 25-75 μg/mL (L). Tacrolimus and steroids were administered at the same dose in each of the 4 groups. Biopsy proven acute rejection (BPAR) at 24 weeks, the primary study endpoint, was comparable in the L (22.8%) and MMF (17.2%) groups but higher in the H (34.5%) and M (29.3%) groups. BPAR at 12 months was comparable in the L (23.9%) and MMF (19.4%) groups but higher in the H (34.5%) and M (31.5%) groups. Graft and patient survival were lowest in the H group and renal function was poorest in the H and M groups. Premature study withdrawal was highest in the H group. Efficacy was similar between the low-level FK778 and MMF groups. Increased FK778 exposure was poorly tolerated and did not improve efficacy.


Effects of in vivo mechanical loading on large bone defect regeneration.
Fracture healing is highly sensitive to mechanical conditions; however, the effects of mechanical loading on large bone defect regeneration have not been evaluated. In this study, we investigated the effects of functional loading on repair of critically sized segmental bone defects. About 6-mm defects were created in rat femora, and each defect received 5 µg recombinant human bone morphogenetic protein-2 (rhBMP-2), delivered in alginate hydrogel. Limbs were stabilized by either stiff fixation plates for the duration of the study or compliant plates that allowed transfer of compressive ambulatory loads beginning at week 4. Healing was assessed by digital radiography, microcomputed tomography, mechanical testing, histology, and finite element modeling. Loading significantly increased regenerate bone volume and average polar moment of inertia. The response to loading was location-dependent with the polar moment of inertia increased at the proximal end of the defect but not the distal end. As a result, torsional stiffness was 58% higher in the compliant plate group, but failure torque was not altered. In single samples assessed for histology from each group, a qualitatively greater amount of cartilage and a lesser degree of remodeling to lamellar bone occurred in the loaded group compared to the stiff plate group. Finally, principal strain histograms, calculated by FE modeling, revealed that the compliant plate samples had adapted to more efficiently distribute loads in the defects. Together, these data demonstrate that functional transfer of axial loads alters BMP-induced large bone defect repair by increasing the amount and distribution of bone formed within the defect.


The clinical and economic consequences of nosocomial central venous catheter-related infection: are antimicrobial catheters useful?
Central venous catheters (CVCs) are essential for many hospitalized patients, but they are associated with important infectious complications. Recent studies have indicated that CVCs coated with antimicrobial agents reduce the incidence of catheter-related bloodstream infection (CR BSI). To estimate the clinical and economic consequences of short-term central venous catheter-related infection and the potential usefulness of antimicrobial-coated catheters, we reviewed and synthesized the available relevant literature. Statistical pooling was used to estimate the incidence of both catheter colonization and CR BSI. The attributable mortality of CR BSI was also evaluated. In addition, the economic consequences of both local and systemic catheter-related infection was estimated from literature reports that used micro-costing and other techniques. Among patients in whom standard, noncoated CVCs are in place for an average of 8 days, 24.7% are expected to develop catheter colonization (95% confidence interval [CI(95)], 22.0%-27.5%). Approximately 5.2% (CI(95), 3.9%-6.5%) will develop CR BSI. The attributable mortality of CR BSI remains unclear, but recent studies are consistent with a range from 4% to 20%. An episode of local catheter-related infection leads to an additional cost of approximately $400, whereas the additional cost of CR BSI ranges from approximately $6,005 to $9,738. Formal economic analyses indicate that CVCs coated with antibacterial agents (such as chlorhexidine-silver sulfadiazine or minocycline-rifampin) likely reduce infectious complications, yielding economic advantages. In light of the substantial clinical and economic burden of catheter-related infection, hospital personnel should adopt proven cost-effective methods to reduce this common and important nosocomial complication.


Individuals in food webs: the relationships between trophic position, omnivory and among-individual diet variation.
Among-individual diet variation is common in natural populations and may occur at any trophic level within a food web. Yet, little is known about its variation among trophic levels and how such variation could affect phenotypic divergence within populations. In this study we investigate the relationships between trophic position (the population's range and average) and among-individual diet variation. We test for diet variation among individuals and across size classes of Eurasian perch (Perca fluviatilis), a widespread predatory freshwater fish that undergoes ontogenetic niche shifts. Second, we investigate among-individual diet variation within fish and invertebrate populations in two different lake communities using stable isotopes. Third, we test potential evolutionary implications of population trophic position by assessing the relationship between the proportion of piscivorous perch (populations of higher trophic position) and the degree of phenotypic divergence between littoral and pelagic perch sub-populations. We show that among-individual diet variation is highest at intermediate trophic positions, and that this high degree of among-individual variation likely causes an increase in the range of trophic positions among individuals. We also found that phenotypic divergence was negatively related to trophic position in a population. This study thus shows that trophic position is related to and may be important for among-individual diet variation as well as to phenotypic divergence within populations.


Respiratory ill health among coal miners and telecommunication workers in south Wales.
As part of a large cross sectional epidemiological study of respiratory disease in coalminers, the respiratory health of miners in one colliery in south Wales has been compared with the health of nearby telecommunication (telecom) workers. The studies were carried out in 1981 and 1982. The answers to questionnaires on respiratory symptoms and results of lung spirometry indicate a much greater frequency of respiratory ill health among the miners than the telecom workers. The frequency of symptoms of chronic bronchitis among the current employees was 31% in the miners and 5% in the telecom workers, and these symptoms were reported as frequently by younger as by older miners. Reports of other respiratory symptoms showed similarly large differences between current miners and telecom workers. These differences were seen both within non-smoking and smoking groups. Comparisons of FEV1 with predicted values (several different predictions were used) confirmed that the differences in reported symptoms were accompanied by differences in lung function; of the order of 20% of current miners had an FEV1 less than 80% of predicted compared with 10% of current telecom workers. The excess of respiratory disease shown among these miners is not necessarily a consequence of the dust concentrations currently experienced underground, nor is the colliery necessarily representative of the coal industry generally. The findings, however, indicate the continued need for measures to improve the respiratory health of these men.


[Rapid diagnosis of dysbacteriosis by detecting beta-aspartylglycine in the feces in an experiment].
In experiments on Fischer rats (F-344), both with common microflora and germ-free, the influence of the systemic destination of different antibiotics (tetracycline + ampicillin, gentamicin + kefzol, gentamicin, fradizine) on the intestinal microflora, the content of beta-ospartylglycine in feces and the colonization resistance of the intestinal tract to Staphylococcus aureus B-243 and Pseudomonas aeruginosa No. 93 has been studied. The early appearance of beta-aspartyl-glycine in the supernatant of fecal samples has been shown to be the first sign of dysbacteriosis and to indicate the decrease of the colonization resistance of the intestine to opportunistic bacteria.


Hypnotic analgesia for combat-related spinal cord injury pain: a case study.
A U.S. Army soldier stationed in Iraq developed myriad pain problems after sustaining a high-level spinal cord injury (SCI) from a gunshot wound. These problems were negatively impacting his ability to participate fully in his physical rehabilitation and care. Ten sessions of self-hypnosis training were administered to the patient over a 5-week period to help him address these problems. Both the patient and his occupational therapist reported a substantial reduction in pain over the course of treatment, which allowed the patient to actively engage in his therapies. Six months post treatment, the patient reported continued use of the hypnosis strategies taught, which effectively reduced his experience of pain. This case study demonstrates the efficacy of hypnotic analgesia treatment for U.S. military veterans who are experiencing pain problems due to traumatic or combat-related SCIs.


Degree of conversion of light-polymerized composite resin in implant prosthesis screw access opening.
The mechanical and physical properties of implant screw access opening deteriorate if composite resin is not polymerized properly. Therefore, this study aimed to analyze the effect of using composite resin in implant access opening on the degree of conversion (DC). Two prosthetic materials (Co-Cr and zirconia), two types of composite resin (low and high viscosity), two light-cured resin depths (2 and 3 mm), and two polymerization methods (max-mode 10 s and mid-mode 20 s: 16 and 22 J/cm2 , respectively) were considered (n = 192). The DC of the polymerized composite resin was measured through Fourier-transform infrared spectroscopy. The top and bottom surfaces of the polymerized composite resin body were observed through scanning electron microscopy. Multiple linear regression analysis and analysis of variance were used to identify significant differences in DC (α = 0.05). The DC was lower when the low-viscosity composite resin (β = -0.431), light-polymerized resin depth of 2 mm (β = -0.430), zirconia prosthesis (β = -0.191), and mid-mode polymerization method (β = -0.164) were used. The resin type, depth of resin to be light-cured, prosthesis material, and polymerization method had an effect on the DC. Low-viscosity composite resin should be polymerized at a low irradiance and long polymerization time (such that the light-cured resin depth does not exceed 2 mm) to ensure proper composite resin polymerization in implant screw access opening.


Phytohemagglutinin derived from red kidney bean (Phaseolus vulgaris): a cause for intestinal malabsorption associated with bacterial overgrowth in the rat.
Plant lectins or carbohydrate binding proteins interact with membrane receptors on cellular surfaces but their antinutritional effects are poorly defined. Studies were conducted to determine the effects of phytohemagglutinin, a lectin derived from raw red kidney bean (Phaseolus vulgaris), on small intestinal absorptive function and morphology, and on the intestinal microflora. Phytohemagglutinin was isolated in purified form by thyroglobulin-sepharose 4B affinity chromatography. Red kidney bean and phytohemagglutinin (6% and 0.5%, respectively, of dietary protein) were fed in a purified casein diet to weanling rats for up to 21 days. Weight loss, associated with malabsorption of lipid, nitrogen, and vitamin B12, developed in comparison with animals pair-fed isonitrogenous casein diets. Antinutritional effects of red kidney bean were reversible on reinstitution of a purified casein diet. An increase in bacterial colonization of the jejunum and ileum occurred in red kidney bean- and phytohemagglutin-fed animals. When antibiotics were included in the diet, malabsorption of [3H]triolein and 57Co-vitamin B12 in red kidney bean-fed animals was partially reversed and, in germ-free animals, purified phytohemagglutinin had no demonstrable antinutritional effect. Mucosal disaccharidase activity was reduced in red kidney bean- and phytohemagglutinin-fed animals, but intestinal mucosal morphology was unchanged. Dietary administration of phytohemagglutinin, alone or as a component of red kidney bean, caused intestinal dysfunction, which was associated with, and dependent upon, small intestinal bacterial overgrowth. Adherence of enteric bacteria to the mucosal surface was enhanced by phytohemagglutinin which may have facilitated small intestinal bacterial overgrowth.


Assessment of scatter for the micro-CT subsystem of the trimodality FLEX Triumph preclinical scanner.
This work aims at assessing, through experimental measurements and Monte Carlo calculations, the scatter to primary ratio (SPR) for the micro-CT subsystem of the FLEX Triumph preclinical PET-CT scanner to improve its quantitative capabilities. Experimental measurements were carried out using the single blocker method, where five cylindrical blockers with diameters ranging between 3 and 11.65 mm were used to assess the SPR without the blocker through interpolation. Because of the vertical layout of the imaging device, the blocker was placed over rat-sized and mouse-sized phantoms and central and peripheral SPR values were obtained by rotating the source and detector. The influence of beam energy (30, 50, and 80 kVp), geometrical magnification (1.3 and 2.0) and phantom diameter (25 and 50 mm) and density (polyethylene and water) were investigated. Monte Carlo (MC) simulations using the MCNP4C code were also performed and compared to experimental results to validate their accuracy. The highest difference was found in the extreme peripheral region of the small phantom, while the maximum difference at the center of the phantom is about 6%, indicating that MC simulations can reproduce well the experimental results, at least in the region inside the phantom. The maximal SPR (0.562) was obtained for the large phantom at 30 kVp and a magnification of 1.3. The full SPR profile was calculated using MC simulations and used to express its dependency on beam energy (quadratic), air gap (asymptotic), and phantom diameter (quadratic). The obtained results are in good agreement with theoretical predictions. MC simulations were valuable for the evaluation of the influence of various acquisition parameters on the SPR estimates.


Energetics of obesity and weight control: does diet composition matter?
Greater average weight losses (2.5 kg over 12 weeks) have been reported for low-carbohydrate diets (<90 g/day) compared with traditional low-fat (<25% of energy), hypocaloric diets, implying a 233 kcal/day greater energy deficit. It has therefore been suggested that a low-carbohydrate diet may provide a metabolic advantage (an increase in energy expenditure), resulting in a positive effect on weight loss and maintenance. However, a review of studies in which 24-hour energy expenditure was measured did not provide evidence to support a metabolic advantage of low-carbohydrate diets and showed little evidence of a metabolic advantage of high-protein (>25% of energy) diets. Nonetheless, diets high in protein, but either low or modest in carbohydrate, have resulted in greater weight losses than traditional low-fat diets. We speculate that it is the protein, and not carbohydrate, content that is important in promoting short-term weight loss and that this effect is likely due to increased satiety caused by increased dietary protein. It has been suggested that the increased satiety might help persons to be more compliant with a hypocaloric diet and achieve greater weight loss. The current evidence, combined with the need to meet all nutrient requirements, suggests that hypocaloric weight-loss diets should be moderate in carbohydrate (35% to 50% of energy), moderate in fat (25% to 35% of energy), and protein should contribute 25% to 30% of energy intake. More studies of the efficacy of weight-loss and weight-maintenance diets that address protein content are needed. In addition, controlled studies of total energy expenditure or physical activity measured under free-living conditions that directly compare high-protein diets with those containing low and moderate carbohydrate content should also be performed.


The effects and costs of a hearing screening and rehabilitation program in residential care homes for the elderly in the Netherlands1.
This study describes the effects and costs of hearing screening and rehabilitation in residential care homes for the elderly. It was hypothesized that offering an in-house hearing screening and rehabilitation program would be an effective strategy to increase hearing aid ownership among the residents. All 705 residents of 8 residential care homes in the Netherlands were invited to participate in a hearing screening (pure-tone audiometry) and rehabilitation (hearing aids) program. Resident participation was analyzed, and the costs were calculated. A total of 243 residents (34%) participated in the screening, 222 (91%) of whom had hearing loss. Ninety-one (41%) of the screening participants with hearing loss started rehabilitation, which was successful for 50 (55%) of them. Hearing aid ownership among the residents with hearing loss increased from 28% at the start of the program to 33% at the end. The costs were €1,896 (US $2,480) per successfully rehabilitated resident. Hearing aid trials and hearing aids together accounted for 83% of the total costs. The effectiveness of the program was limited, as hearing aid ownership increased only slightly. Cost reduction measures should focus on decreasing the number of unsuccessful hearing aid trials.