Long-term treatment of polysaccharides-based hydrogel microparticles as oral insulin delivery in streptozotocin-induced type 2 diabetic mice.
To develop a more effective and safer drug for the treatment of type 2 diabetes mellitus (T2DM), polysaccharides-based hydrogel microparticles as oral insulin delivery was prepared and explored. This study was aimed to evaluate the antidiabetic effects and hypoglycemic mechanism with long-term administration(four weeks) of oral insulin hydrogel microparticles in type 2 diabetic mice on a model of diabetes using a high fat diet combined with streptozotocin. The results revealed that the long-term treatment of oral insulin polysaccharides-based hydrogel microparticles could significantly alleviate the symptoms of polyphagia, polydipsia, polyuria and weight loss in diabetic mice. Also, oral administration of insulin hydrogel microparticles could significantly reduce fasting blood glucose levels, ameliorate insulin resistance and increase insulin sensitivity in the mice with T2DM. The concentration of plasma TG, TC, LDL-C, FFA, BUN, CRE significantly decreased and the levels of HDL-C increased showed that insulin polysaccharides-based hydrogel microparticles were effective in regulating lipid metabolism and prevent diabetic nephropathy complication in diabetic mice. In addition, the supplementation of insulin hydrogel microparticles could significant improve the antioxidant capacity by increasing the level of SOD, CAT and decreasing the level of MDA, GPT, NO, TNF-α, and reverse histological deterioration of kidney and pancreas in diabetic mice. The above outcome concluded that insulin polysaccharides-based hydrogel microparticles may exhibit promising anti-diabetic activity and the potential to be a drug candidate for T2DM.


Interaction of Delta sleep-inducing peptide and valproate on metaphit audiogenic seizure model in rats.
Effects of valproate (VPA), a conventional antiepileptic drug and natural delta sleep-inducing peptide (DSIP) on metaphit (1-[1-(3-isothiocyanatophenyl)-cyclohexyl]-piperidine)-induced audiogenic reflex epilepsy were studied. For the purpose of the study, valproate in the doses of 50 or 75 mg/kg and DSIP (1.0 mg/kg) was i.p. injected either alone or in combination to adult Wistar male rats with fully developed metaphit seizures after eight audiogenic testing. The animals were stimulated using an electric bell (100 +/- 3 dB and 5-8 kHz, for 60 s) 60 min after metaphit injection and afterwards at hourly intervals during the experiment. For EEG recording and power spectra analysis, three gold-plated screws were implanted into the scull. In EEGs of metaphit-treated animals polyspikes, spike-wave complexes and sleep-like patterns were recorded, while the power spectra were increased. Combined treatment of metaphit-induced seizures with valproate and DSIP was more effective than drugs alone especially during 4 h after administration. None of the applied dose combinations eliminated the EEG signs of metaphit-provoked epileptiform activity. Taken together, the results of the present study suggest that the combinations of valproate and DSIP should be considered as beneficial polytherapy in metaphit model of epilepsy.


Caspase-3-dependent apoptosis in Escherichia coli-infected urothelium: involvement of inducible nitric oxide synthase.
To investigate if nitric oxide (NO) derived from inducible NO synthase (iNOS) regulates apoptosis and/or cell shedding in uroepithelial cells in vivo and in vitro, as bladder epithelial cells undergo shedding during urinary tract infection, which is considered a part of the host's defence and is thought to take place via an apoptotic pathway. Bladders and kidneys of mice infected with Escherichia coli were used to study caspase-3 immunoreactivity at different times after infection. Wild-type (E. coli 1177) and type-1 recombinant (E. coli PKL4) bacteria were used. iNOS-deficient mice were used to study the association of caspase-3 with iNOS. Isolated human uroepithelial cells were used to examine the effect of the NO donor DETA/NO and the peroxynitrite generator SIN-1 on caspase-3 activity and cell shedding in vitro. Many caspase-3 immunoreactive neutrophils were found soon after infection and some superficial bladder epithelial cells were also immunoreactive for caspase-3. Caspase-3 immunoreactivity was also detected in neutrophils and bladder epithelial cells of infected iNOS-deficient mice. There was no co-expression between iNOS- and caspase-3 in bladder epithelial cells. DETA/NO and SIN-1 did not stimulate caspase-3 activity or cell shedding in isolated human uroepithelial cells. Caspase-3 and iNOS are not co-expressed in uroepithelial cells and apoptosis is evident in the absence of iNOS. Exogenous NO did not induce apoptosis or cell shedding in isolated human uroepithelial cells.


Avian-to-Human Receptor-Binding Adaptation of Avian H7N9 Influenza Virus Hemagglutinin.
Since 2013, H7N9 avian influenza viruses (AIVs) have caused more than 1,600 human infections, posing a threat to public health. An emerging concern is whether H7N9 AIVs will cause pandemics among humans. Molecular analysis of hemagglutinin (HA), which is a critical determinant of interspecies transmission, shows that the current H7N9 AIVs are still dual-receptor tropic, indicating limited human-to-human transmission potency. Mutagenesis and structural studies reveal that a G186V substitution is sufficient for H7N9 AIVs to acquire human receptor-binding capacity, and a Q226L substitution would favor binding to both avian and human receptors only when paired with A138/V186/P221 hydrophobic residues. These data suggest a different evolutionary route of H7N9 viruses compared to other AIV-subtype HAs.


Phase I and pharmacokinetic study of gefitinib and S-1 combination therapy for advanced adenocarcinoma of the lung.
A phase I dose-escalation study was performed to investigate the safety and pharmacokinetics of the combination of S-1 and gefitinib in patients with pulmonary adenocarcinoma who had failed previous chemotherapy. Patients received gefitinib at a fixed daily oral dose of 250 mg, and S-1 was administered on days 1-14 every 21 days at doses starting at 60 mg/m(2) (level 1) and escalating to 80 mg/m(2) (level 2). The primary end point of the study was determination of the recommended dose for S-1 given in combination with a fixed dose of gefitinib. Twenty patients were enrolled in the study. Two of the first six patients at dose level 2 experienced a dose-limiting toxicity (elevation of alkaline phosphatase of grade 3 in one patient; elevations of aspartate and alanine aminotransferases of grade 3 in the other). The recommended dose was thus determined as level 2, and an additional 11 patients were assigned to this level. All observed adverse events were well managed. The response rate was 50 % (10 of 20 patients), and the median progression-free survival (PFS) and overall survival times were 10.5 and 21.2 months, respectively. In EGFR mutation-positive patients (n = 9), seven patients achieved an objective response and the median PFS was 12.4 months, whereas none with wild-type EGFR (n = 6) responded. No pharmacokinetic interaction between S-1 and gefitinib was detected. The combination of S-1 and gefitinib is well tolerated and appears to possess activity against EGFR mutation-positive NSCLC.


Performance of a commercial polymerase chain reaction test for endocervical Chlamydia trachomatis infection in a university hospital population.
To examine the accuracy of a commercial polymerase chain reaction (PCR) test (Amplicor CTR, Roche Diagnostic Systems, Branchburg NJ) for identification of endocervical chlamydial infections through both laboratory evaluation and among a diverse teaching hospital patient population. Testing of reliable threshold inocula and reproducibility were carried out using laboratory stock organisms. Paired endocervical samples from patients with a wide range of indications were tested by PCR and an established culture procedure, and discrepant pairs were further analyzed to determine true results. Laboratory evaluation suggested that one copy of target DNA from a viable organism consistently yielded a positive result, and test reproducibility was very good, with an overall coefficient of variation of 15%. Compared to true results in 1,588 paired clinical samples from 1,489 women with a 10% prevalence of infection, the PCR test and culture yielded respective sensitivities of 87.4% and 78.0%, and negative predictive values of 98.6% and 97.6%. Specificity and positive predictive value for both tests were 100%. Cost per specimen was nearly identical at $18.84 and $18.88 respectively. Polymerase inhibitors and organisms lacking target DNA were not found in false-negative PCR samples. This commercial PCR test is accurate, cost-competitive, and much faster than culture for diagnosis of endocervical chlamydia infections in our population of intermediate prevalence of chlamydial infection.


Differential associations of mask mandates on COVID-19 infection and mortality by community social vulnerability.
The COVID-19 pandemic in the United States has disproportionately impacted communities deemed vulnerable to disease outbreaks. Our objectives were to test (1) whether infection and mortality decreased in counties in the most vulnerable (highest) tercile of the Social Vulnerability Index (SVI), and (2) whether disparities between terciles of SVI were reduced, as the length of mask mandates increased. Using the New York Times COVID-19 and the Centers for Disease Control and Prevention SVI and mask mandate datasets, we conducted negative binomial regression analyses of county-level COVID-19 cases and deaths from 1/2020-11/2021 on interactions of SVI and mask mandate durations. Mask mandates were associated with decreases in mid-SVI cases (IRR: 0.79) and deaths (IRR: 0.90) and high-SVI cases (IRR: 0.89) and deaths (IRR: 0.88). Mandates were associated with the mitigation of infection disparities (Change in IRR: 0.92) and mortality disparities (Change in IRR: 0.85) between low and mid-SVI counties and mortality disparities between low and high-SVI counties (Change in IRR: 0.84). Mask mandates were associated with reductions in COVID-19 infection and mortality and mitigation of disparities for mid and high-vulnerability communities. Ongoing COVID-19 response efforts may benefit from longer-standing infection control policies, particularly in the most vulnerable communities.


Current and future strategies in the treatment of hypertension.
Treatment of arterial hypertension is an important part of the medical care provided in industrialized countries today. Its rationale comes from large-scale intervention trials which have shown that lowering of elevated blood pressure reduces cardiovascular morbidity and mortality. Nevertheless, during the last few years it has been shown that treated hypertensive patients are still at an increased risk of cardiovascular morbidity and mortality compared with untreated normotensive subjects of the same age and sex. Possible explanations for this disappointing finding are that blood pressure has not been lowered to strictly normotensive levels; that some elements of the excess morbidity and mortality are not prevented by antihypertensive therapy, e.g., the part attributable to coronary artery disease; or that the drugs used may themselves have negative effects, e.g., on serum lipids, which may offset the positive effects of lowered blood pressure. It is desirable that antihypertensive treatment produces a reversal of hypertension-induced structural cardiovascular changes such as left ventricular hypertrophy or increased wall/lumen ratio in the precapillary blood vessels, but many of the current antihypertensive drug regimens have no effect on structural cardiovascular changes. Against this background it would appear logical to make renewed efforts to reduce blood pressure into the clearly normotensive range in an attempt to lower the excess risk demonstrable in treated hypertensive patients. It would also seem logical to use antihypertensive drugs that could also be expected to have positive effects on hypertension-induced structural cardiovascular changes.(ABSTRACT TRUNCATED AT 250 WORDS)


Estimating particle exposure in the Mexico City metropolitan area.
We examined whether methods for measuring exposure to airborne particles less than 10 microm in aerodynamic diameter (PM10) in the Mexico City metropolitan area give different estimates of PM10 levels, and the nature of these differences, and developed a model for estimating missing PM10 data for one measurement method. Government PM10 measurements using two different technologies at five sites (the Sierra-Anderson PM10 High-Volume Air Sampler System, Hi-Vol) (every sixth day) and the Rupprecht and Patashnik Tapered Element Oscillating Microbalance (TEOM) monitor (daily), as well as Harvard Impactor (HI) data collected for research purposes from one monitoring station were matched by day and monitoring site, then compared visually and with basic descriptive statistics. We fit linear regression models with airport visual range measurements, meteorological data, and information on other air pollutants to predict the Hi-Vol measured PM10 levels for those days when direct measurements were not available. We found relatively low correlations (r ranging from 0.46 to 0.63) between PM10 measured with the TEOM and Hi-Vol methods, and highly variable differences (0-70 microg/m(3)) between the means of these measurements, depending on monitoring site. The HI measurements had a relatively high correlation with the Hi-Vol measurements (r=0.90). The models developed for the missing Hi-Vol measurements provided a series of estimated values similar to the actual Hi-Vol measurements, although the estimated series did not have high values in the range observed in the measured data. The differences we observed in the PM10 measurements across methods in Mexico City may be important when studying health effects associated with particle exposure, evaluating method performance under conditions and operating protocols similar to those in Mexico City, and determining compliance with air quality standards. The estimated series of PM10 measures may be a useful index of exposure for use in studies of the effects of air pollution on health.


Right ventricular dysfunction in stress cardiomyopathy: The prognostic value of fractional area change.
There are limited data on the impact of right ventricular dysfunction (RVD) on the clinical outcomes in patients with stress cardiomyopathy (SC). The purpose of this study was to evaluate the impact of RVD on outcomes and to characterize the prognostic value of RV fractional area change (FAC). This study retrospectively analyzed data from 111 consecutive patients with SC. The primary endpoint, major cardiac events (MCE), was a composite of 30-day mortality, cardiogenic shock, life threatening arrhythmias, and stroke. Regression analysis was used to identify independent predictors of short (30 days)- and long-term MCE. Among the 111 patients (80.2% females, mean age 45.8 ± 11.5 years), RVD was present in 17(15.3%) patients. MCE occurred in 18(16.2%) and 22(19.8%) patients at 30 days and during long-term follow-up, respectively. RVD was an independent predictor of short (HR 1.88(1.21-15.67), P = .036)- and long (HR 1.65(1.11-9.67), P = .016)-term MCE. Compared with tricuspid annular plane systolic excursion < 15 mm (TAPSE) (sens 72.2%, spec 94.1%, AUC 0.75) and tricuspid annulus pulsed TDI-derived peak systolic velocity (S') < 9.5 cm/s (sens 67.2%, spec 94.5%, AUC 0.72), RV FAC < 30% (sens 89.1%, spec 100%, AUC 0.92) had the highest accuracy and discriminative ability to predict MCE. Furthermore, RV FAC < 30% was a significant predictor of recurrence (29.4% vs 2.1%, P = .002) and delayed recovery time (21.4 ± 6.8 vs 8.5 ± 4.3 days, P < .001). The presence of RVD in stress cardiomyopathy identifies patients at higher risk of mortality, complications, delayed recovery, and recurrence. Compared with other indices, RV FAC has the highest prognostic ability to predict these outcomes.


Legal issues and challenges in addressing the coronavirus outbreak on large cruise ships: A critical examination of port state measures.
International cruises have drawn worldwide attention since the outbreak of coronavirus (COVID-19). This article first examines the legal issues, challenges and impact of the pandemic on large cruise ships, like the Diamond Princess, and then probes into corresponding pandemic preventive measures which port states employ. A State is obliged under the International Health Regulations 2005 (IHR) to grant foreign cruise ships free pratique, but there is an exception when public health emergencies of international concern occur. Therefore, this article argues that a port state is not obliged to allow foreign cruise ships to dock at its port at the cost of its domestic public health safety. Regarding the Diamond Princess, the Japanese government has undertaken pandemic preventive measures upon passengers on board the ship and complied with its domestic laws, including the Japanese Quarantine Act. This article further evaluates whether a port state's pandemic preventive measures concerning cruise ships are appropriate from the perspective of law. More importantly, it is necessary to consider the characteristics and specialities of international cruise ships to improve future pandemic preventive measures against large passenger ships and cruise passengers.


Upstream transcription factor 1 (USF1) in risk of type 2 diabetes: association study in 2000 Dutch Caucasians.
Type 2 diabetes shares substantial genetic and phenotypic overlap with familial combined hyperlipidemia. Upstream stimulatory factor 1 (USF1), a well-established susceptibility gene for familial combined hyperlipidemia, is postulated to be such a shared genetic determinant. We evaluated two established variants in familial combined hyperlipidemia (rs2073658 and rs3737787) for association with type 2 diabetes in two Dutch case-control samples (N=2011). The first case-control sample comprised 501 subjects with type 2 diabetes from the Breda cohort and 920 healthy blood bank donors of Dutch Caucasian origin. The second case-control sample included 211 subjects with type 2 diabetes, and 379 normoglycemic controls. SNP rs2073658 and SNP rs3737787 were in perfect linkage disequilibrium. In the first case-control sample, prevalence of the major allele was higher in patients than in controls (75% versus 71%, OR=1.25, p=0.018). A similar effect-size and -direction was observed in the second case-control sample (76% versus 72%, OR=1.22, p=0.16). A combined analysis strengthened the evidence for association (OR=1.23, p=0.006). Notably, the increased risk for type 2 diabetes could be ascribed to the major allele, and its high frequency translated to a substantial population attributable risk of 14.5%. In conclusion, the major allele of rs2073658 in the USF1 gene is associated with a modestly increased risk to develop type 2 diabetes in Dutch Caucasians, with considerable impact at the population level.


Synthesis and duplex-forming property of oligonucleotides bearing a novel polyamine-modified intercalator at the terminal or the internal position.
Novel oligonucleotides bearing a polyamine-intercalator conjugate modified at the terminal or the internal position were reported. These modified oligonucleotides showed duplex-stabilization effect, and the thermodynamic analysis and the salt concentration dependency of the duplex stability revealed that the polyamine moiety also acted as the duplex stabilizer by neutralization of the phosphate negative charge.


What we have learned from an antibiotic trial in fetal fibronectin positive women.
Clinically silent upper genital tract microbial infections have been strongly associated with spontaneous preterm delivery, especially prior to 32 weeks gestational age. This condition represents a potentially preventable or reversible cause of preterm birth using safe, readily available, and inexpensive antibiotics. Fetal fibronectin detected in cervical and vaginal secretions between 22 to 24 weeks' gestation is a powerful predictor of subsequent risk for spontaneous preterm delivery. Evidence indicates that the detection of fetal fibronectin in cervical/vaginal secretions could represent a marker for clinically silent upper genital tract microbial infection. Thus, the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (NICHD MFMU) Network performed a randomized clinical trial to determine if antibiotic treatment (metronidazole plus erythromycin) of asymptomatic women with a positive cervical or vaginal fetal fibronectin test in early pregnancy will reduce the risk of spontaneous preterm delivery. No significant difference was observed between the antibiotic- and placebo-treated groups for spontaneous preterm delivery before 37 week's gestation (relative risk 1.17, 95% confidence interval 0.80-1.70). Therefore, use of the fetal fibronectin test to identify women for antibiotic treatment in an effort to prevent preterm birth should be discouraged, and current clinical use of the fetal fibronectin test should be limited to its negative predictive value.


Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial.
Nasopharyngeal carcinoma (NPC) is highly sensitive to both radiotherapy (RT) and chemotherapy. This randomized phase III trial compared concurrent cisplatin-RT (CRT) with RT alone in patients with locoregionally advanced NPC. Patients with Ho's N2 or N3 stage or N1 stage with nodal size > or = 4 cm were randomized to receive cisplatin 40 mg/m(2) weekly up to 8 weeks concurrently with radical RT (CRT) or RT alone. The primary end point was progression-free survival (PFS). Three hundred fifty eligible patients were randomized. Baseline patient characteristics were comparable in both arms. There were significantly more toxicities, including mucositis, myelosuppression, and weight loss in the CRT arm. There were no treatment-related deaths in the CRT arm, and one patient died during treatment in the RT-alone arm. At a median follow-up of 2.71 years, the 2-year PFS was 76% in the CRT arm and 69% in the RT-alone arm (P =.10) with a hazards ratio of 1.367 (95% confidence interval [CI], 0.93 to 2.00). The treatment effect had a significant covariate interaction with tumor stage, and a subgroup analysis demonstrated a highly significant difference in favor of the CRT arm in Ho's stage T3 (P =.0075) with a hazards ratio of 2.328 (95% CI, 1.26 to 4.28). For T3 stage, the time to first distant failure was statistically significantly different in favor of the CRT arm (P =.016). Concurrent CRT is well tolerated in patients with advanced NPC in endemic areas. Although PFS was not significantly different between the concurrent CRT arm and the RT-alone arm in the overall comparison, PFS was significantly prolonged in patients with advanced tumor and node stages.


Cutaneous candidosis in immunosuppressed patients.
One-hundred patients with candidosis of the skin, mucous membranes and nail plates (confirmed by cultivation) were examined. Topical or systemic antimycotic treatment was successful in 58 patients. After a complete evaluation, 42 patients were found to suffer from factors supporting candidosis--diabetes mellitus (12), anemia (3) and various local factors (10 patients); 27 patients showed a deficiency in cell-mediated immunity. In addition to intensive antimycotic therapy, successful treatment is affected by the actual immunity level and can be ensured by efficient immunomodulation treatment of immunodeficiency.


The prognostic value of serum human placental lactogen determinations in early pregnancy.
Serial serum human placental lactogen (S-HPL) determinations were done in early pregnancy on 85 high-risk cases. Normal S-HPL values with a normal ultrasonogram had a 94.8 per cent successful outcome of pregnancy. Low S-HPL values were often accompanied by an abnormal or equivocal ultrasonogram (29.6 per cent). The fetal loss in patients with low S-HPL values and a normal ultrasonogram was 36.8 per cent.


Mechanistic analysis of carbon-carbon bond formation by deoxypodophyllotoxin synthase.
Deoxypodophyllotoxin contains a core of four fused rings (A to D) with three consecutive chiral centers, the last being created by the attachment of a peripheral trimethoxyphenyl ring (E) to ring C. Previous studies have suggested that the iron(II)- and 2-oxoglutarate-dependent (Fe/2OG) oxygenase, deoxypodophyllotoxin synthase (DPS), catalyzes the oxidative coupling of ring B and ring E to form ring C and complete the tetracyclic core. Despite recent efforts to deploy DPS in the preparation of deoxypodophyllotoxin analogs, the mechanism underlying the regio- and stereoselectivity of this cyclization event has not been elucidated. Herein, we report 1) two structures of DPS in complex with 2OG and (±)-yatein, 2) in vitro analysis of enzymatic reactivity with substrate analogs, and 3) model reactions addressing DPS's catalytic mechanism. The results disfavor a prior proposal of on-pathway benzylic hydroxylation. Rather, the DPS-catalyzed cyclization likely proceeds by hydrogen atom abstraction from C7', oxidation of the benzylic radical to a carbocation, Friedel-Crafts-like ring closure, and rearomatization of ring B by C6 deprotonation. This mechanism adds to the known pathways for transformation of the carbon-centered radical in Fe/2OG enzymes and suggests what types of substrate modification are likely tolerable in DPS-catalyzed production of deoxypodophyllotoxin analogs.


Purse-string vs. linear skin closure at loop ileostomy reversal: a systematic review and meta-analysis.
There is no level 1a evidence regarding the best technique for skin closure at loop ileostomy reversal. The aim of this study was to evaluate whether purse-string skin closure (PSC) is associated with lower surgical site infection (SSI) rates as compared to linear skin closure (LC). EMBASE, MEDLINE, Pubmed, Cochrane Library, Web of Science, and CINAHL databases were systematically searched. PSC was defined as a circumferential subcuticular suture leaving a small circular skin defect allowing for free drainage, granulation, and epithelialization. In LC, the wound edges were approximated side to side with or without drainage. The primary endpoint was SSI rate. Secondary endpoints included operating time, length of hospital stay, wound healing time, and incisional hernia rates. Inclusion criterion was any observational or experimental study comparing PSC to LC in patients undergoing ostomy reversal. Twenty studies (6 experimental and 14 observational) totaling 1812 patients (826 PSC and 986 LC) were included. SSI rates were significantly lower statistically and clinically in patients with PSC [OR (95% CI) = 0.14 (0.09, 0.21); p < 0.0001; NNT = 6] in the meta-analysis of all studies. The subgroup analysis of randomized trials [OR (95% CI) = 0.10 (0.04, 0.21); p < 0.0001; NNT = 6] as well as the analysis of randomized trials including patients with loop ileostomy only [OR (95% CI) = 0.12 (0.05, 0.28); p < 0.0001; NNT = 5] confirmed this finding. This meta-analysis found that PSC was associated with significantly decreased rates of SSI in patients undergoing loop ileostomy reversal.


Systematic evaluation of label-free and super-SILAC quantification for proteome expression analysis.
Advanced implementations of mass spectrometry (MS)-based proteomics allow for comprehensive proteome expression profiling across many biological samples. The outcome of such studies critically depends on accurate and precise quantification, which has to be ensured for high-coverage proteome analysis possible on fast and sensitive mass spectrometers such as quadrupole orbitrap instruments. We conducted ultra-high-performance liquid chromatography (UHPLC)/MS experiments on a Q Exactive to systematically compare label-free proteome quantification across six human cancer cell lines with quantification against a shared reference mix generated by stable isotope labeling with amino acids in cell culture (super-SILAC). Single-shot experiments identified on average about 5000 proteins in the label-free compared to about 3500 in super-SILAC experiments. Label-free quantification was slightly less precise than super-SILAC in replicate measurements, verifying previous results obtained for lower proteome coverage. Due to the higher number of quantified proteins, more significant differences were detected in label-free cell line comparisons, whereas a higher percentage of quantified proteins was identified as differentially expressed in super-SILAC experiments. Additional label-free replicate analyses effectively compensated for lower precision of quantification. Finally, peptide fractionation by high pH reversed-phase chromatography prior to LC/MS analysis further increased the robustness and precision of label-free quantification in conjunction with higher proteome coverage. Our results benchmark and highlight the utility of label-free proteome quantification for applications such as target and biomarker discovery on state-of-the-art UHPLC/MS workflows.


Simultaneous modelling of distributional patterns in a guild of eastern-Australian cicadas.
The distributions, with respect to habitat structure, of nine species of eastern-Australian cicadas have been shown to be non-random. The most striking consequence of this non-randomness is a marked inverse relationship between habitat breadth and habitat position (terms defined in text). Eight basic models and 12 derived models were used in conjunction with a canonical space to try to account for the ways in which the species of cicadas were distributed with respect to habitat. Several models produced results that were in reasonable agreement with the observed data. The most parsimonious of these corresponds to analytical results of other workers, such as Diamond's (1975) incidence curves, occurrence sequences (Schoener and Schoener 1983), and probability functions (Adler and Wilson 1985). The distributions of cicadas can be modelled by assuming that the species occupy sites independently of one another. These species of cicadas are unlikely to engage in interspecific competition, which is consistent with independence of distributions.


Classic cadherin expressions balance postnatal neuronal positioning and dendrite dynamics to elaborate the specific cytoarchitecture of the mouse cortical area.
A unique feature of the mammalian cerebral cortex is in its tangential parcellation via anatomical and functional differences. However, the cellular and/or molecular machinery involved in cortical arealization remain largely unknown. Here we map expression profiles of classic cadherins in the postnatal mouse barrel field of the primary somatosensory area (S1BF) and generate a novel bacterial artificial chromosome transgenic (BAC-Tg) mouse line selectively illuminating nuclei of cadherin-6 (Cdh6)-expressing layer IV barrel neurons to confirm that tangential cellular assemblage of S1BF is established by postnatal day 5 (P5). When we electroporate the cadherins expressed in both barrel neurons and thalamo-cortical axon (TCA) terminals limited to the postnatal layer IV neurons, S1BF cytoarchitecture is disorganized with excess elongation of dendrites at P7. Upon delivery of dominant negative molecules for all classic cadherins, tangential cellular positioning and biased dendritic arborization of barrel neurons are significantly altered. These results underscore the value of classic cadherin-mediated sorting among neuronal cell bodies, dendrites and TCA terminals in postnatally elaborating the S1BF-specific tangential cytoarchitecture. Additionally, how the "protocortex" machinery affects classic cadherin expression profiles in the process of cortical arealization is examined and discussed.


Longitudinal surface-based spatial Bayesian GLM reveals complex trajectories of motor neurodegeneration in ALS.
Longitudinal fMRI studies hold great promise for the study of neurodegenerative diseases, development and aging, but realizing their full potential depends on extracting accurate fMRI-based measures of brain function and organization in individual subjects over time. This is especially true for studies of rare, heterogeneous and/or rapidly progressing neurodegenerative diseases. These often involve small samples with heterogeneous functional features, making traditional group-difference analyses of limited utility. One such disease is amyotrophic lateral sclerosis (ALS), a severe disease resulting in extreme loss of motor function and eventual death. Here, we use an advanced individualized task fMRI analysis approach to analyze a rich longitudinal dataset containing 190 hand clench fMRI scans from 16 ALS patients (78 scans) and 22 age-matched healthy controls (112 scans). Specifically, we adopt our cortical surface-based spatial Bayesian general linear model (GLM), which has high power and precision to detect activations in individual subjects, and propose a novel longitudinal extension to leverage information shared across visits. We perform all analyses in native surface space to preserve individual anatomical and functional features. Using mixed-effects models to subsequently study the relationship between size of activation and ALS disease progression, we observe for the first time an inverted U-shaped trajectory of motor activations: at relatively mild motor disability we observe enlarging activations, while at higher levels of motor disability we observe severely diminished activation, reflecting progression toward complete loss of motor function. We further observe distinct trajectories depending on clinical progression rate, with faster progressors exhibiting more extreme changes at an earlier stage of disability. These differential trajectories suggest that initial hyper-activation is likely attributable to loss of inhibitory neurons, rather than functional compensation as earlier assumed. These findings substantially advance scientific understanding of the ALS disease process. This study also provides the first real-world example of how surface-based spatial Bayesian analysis of task fMRI can further scientific understanding of neurodegenerative disease and other phenomena. The surface-based spatial Bayesian GLM is implemented in the BayesfMRI R package.


Thyrotropin and triiodothyronine regulate iodothyronine 5'-deiodinase messenger ribonucleic acid levels in FRTL-5 rat thyroid cells.
We investigated the regulation of type I iodothyronine 5'-deiodinase (5'-D) gene expression by TSH and T3 in FRTL-5 rat thyroid cells. Northern blot analysis revealed that these cells express a 5'-D messenger RNA (mRNA) species of 2.1 kilobases. Readdition of TSH to FRTL-5 cells, precultured in both thyroid hormones and TSH-depleted medium for 4 days, increased 5'-D mRNA levels, reaching a maximum (2.8-fold compared to control) after 12 h of TSH (10 microU/ml) stimulation. Dibutyryl cAMP (DBC) and forskolin mimicked this stimulatory effect of TSH on 5'-D mRNA levels. T3 also increased the 5'-D mRNA levels, reaching a maximum (2-fold compared to control) after 8 h of T3 (10(-9) M) stimulation. Addition of TSH (10 microU/ml) or DBC (1 mM) together with T3 (10(-9) M) further increased 5'-D mRNA levels, reaching a maximum (5-fold compared to control) after 12 h of stimulation. Examination of the rate of disappearance of 5'-D mRNA levels after inhibition of mRNA transcription by actinomycin-D revealed that neither TSH nor T3 significantly affected the rate of disappearance. Cycloheximide, a protein synthesis inhibitor, almost completely blocked the induction of 5'-D mRNA by TSH and DBC, but did not block the induction by T3. These results suggest that both TSH and T3 increase 5'-D mRNA levels probably by increasing transcription rate, and that TSH regulates it, in part via the second messenger cAMP, for which cycloheximide-sensitive de novo protein synthesis is required, whereas T3 does without requiring it.


Solvothermal conversion of spent aromatic waste to ethyl glucosides.
On-farm extraction of commercially important essential oil from aromatic crops generates huge spent aromatic waste. This massive waste is often disposed in the unregulated landfills or burned in the open air to vacate the fields. Hence, a new method for processing of aromatic spent waste has been developed to obtain platform chemicals, such as, xylose and ethyl glucosides. The thermochemical liquefaction of acid pre-treated palmarosa (cymbopogon martini) biomass furnished a mixture of ethyl glucopyranosides in good yield (∼17 wt% relative to biomass) and selectivity (∼77%) by heating with p-cymen-2-sulphonic acid (p-CSA) in the presence of ethanol as a solvent. The detection, quantification and isolation of ethyl glucosides may provide a new application of spent aromatic biomass for use as a feed stock in the production of value added chemicals.


Substance use disorder and obesogenic eating: Does working memory training strengthen ability to abstain from unwanted behaviors? A systematic review.
Abstaining from unwanted behaviors requires a sufficient balance between the executive and impulsive cognitive systems. Working memory (WM) is a vital component of both systems, identified in a wide range of research as the central and dominant component of executive function. WM potentially modulates the desires, tendencies, and behaviors specific to and seen in individuals with substance use disorder (SUD) and obesogenic eating (OE). Compared to healthy populations, research has shown individuals with SUD, as well as those who display OE, to have some degree of executive dysfunction, and both conditions have far-reaching health care implications. Additionally, these deficits are associated with impulsive behavior. Research has proposed that impulsive and so-called reward-driven responses could be altered through cognitive therapy and that both SUD and OE could benefit from working memory training (WMT). In this narrative review, we systematically align extant empirical reasoning and evidence with these assumptions. Our main aim is to ascertain and summarize the value of WMT for the treatment of both SUD and food reward consummatory behaviors. As a means to include detailed narrative accounts of all papers of potential value, our thresholds for meaningful improvements in both WM and unwanted behaviors are broad. The results from the eleven qualifying studies are as follows: Nine of ten studies show a significant positive training effect of WMT on one or more components of WM capacity; three of six eligible papers (two on alcohol and one on opioid addiction) deliver notable improvements in SUD in response to WMT. One of two suitable studies showed WMT to be a moderately efficacious form of therapy for OE. Conversely, WMT appears to have negligible therapeutic benefit for cognitive function deficits or psychopathology unrelated to WM, suggesting that WMT has unique treatment efficacy for impulsive human behaviors. In conclusion, more rigorous and uniform studies on WMT and impulsive harmful behaviors are required to give proof of the benefits of this potential useful treatment.


Genetic analysis of the TrkB gene and schizophrenia in the Japanese population: Juntendo University Schizophrenia Projects (JUSP).
The presence of cognitive and social impairments during childhood and adolescence in patients with schizophrenia has lead to the widespread hypothesis that schizophrenia may be a neurodevelopmental disorder, which suggests that risk genes for schizophrenia may act through the disruption of normal neurodevelopmental processes. Moreover, recent studies indicate that TrkB, which is receptor of neurotrophins including BDNF, might be involved in schizophrenia. The aim of this study is to evaluate the role of sequence variation at the TrkB locus on schizophrenia. We genotyped 12 single nucleotide polymorphisms (SNPs) across TrkB in 276 subjects with schizophrenia and 274 control subjects from the Japanese population and assessed whether TrkB SNPs are associated with a diagnosis of schizophrenia. In addition, we also investigated if any association exists between the TrkB SNPs and the premorbid functioning as measured by M-PAS using 62 subjects with schizophrenia. The TrkB SNPs were not significantly associated with a diagnosis of schizophrenia. Although one TrkB SNP (rs920776) showed weak association with premorbid functioning (p=0.025), the significance did not remain after Bonferroni correction. Thus, these results do not support a significant role for TrkB sequence variation in the etiology of schizophrenia.


An ultrastructural study of Porphyromonas gingivalis-induced platelet aggregation.
One of the major pathogens of periodontitis, Porphyromonas gingivalis (P. gingivalis), has the ability to aggregate human platelets. To investigate the interaction between P. gingivalis and human platelets in platelet rich plasma (PRP), platelet aggregation was measured by an aggregometer based on laser light scattering (LS) methods, and an ultrastructural study was performed using electron microscopy. A sharp and rapid increase of small-sized platelet aggregates was observed immediately after the addition of P. gingivalis to PRP, followed by the formation of medium- and large-sized aggregates in 2-3 min. In contrast, when Staphylococcus aureus (S. aureus) was used in the control experiment, only a slight increase in small-sized aggregates was detected. By electron microscopy, discoid-shaped platelets were observed prior to adding P. gingivalis. By 5 min after the addition of the bacteria, enormous platelet aggregates were observable. Most of the P. gingivalis were present between the adherent platelets, while some were internalized in platelet engulfment vacuoles. In contrast, when washed platelets were incubated with the bacteria under a non-stirring condition to prevent platelet aggregation, and stained with ruthenium red (RR) as an electron dense tracer of the cell surface including the open canalicular system (OCS), both RR-positive and -negative vacuoles containing P. gingivalis were identified in the activated platelets. Thus, this observation suggests that P. gingivalis residing in the RR-negative vacuoles is incorporated into the platelet cytoplasm by phagocytosis.


WITHDRAWN: Focused factories and boutique laboratories. The truth might lie in between.
The Publisher regrets that this article is an accidental duplication of an article that has already been published, doi:10.1016/j.clinbiochem.2010.09.001. The duplicate article has therefore been withdrawn.


A proteome map of the zebrafish (Danio rerio) lens reveals similarities between zebrafish and mammalian crystallin expression.
To characterize the crystallin content of the zebrafish lens using two-dimensional gel electrophoresis (2-DE). These data will facilitate future investigations of vertebrate lens development, function, and disease. Adult zebrafish lens proteins were separated by 2-DE, and the resulting spots were identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). The relative proportion of each crystallin was quantified by image analysis, and phosphospecific staining was used to identify phosphorylated alpha-crystallins. The proportion of each crystallin in the soluble and insoluble fraction of the lens was also determined by resolving these lens fractions separately by 2-DE. alpha-, beta-, and gamma-crystallins comprised 7.8, 36.0, and 47.2% of the zebrafish lens, respectively. While the alpha-crystallin content of the zebrafish lens is less than the amounts found in the human lens, the ratio of alphaA:alphaB crystallin is very similar. The phosphorylation pattern of zebrafish alphaA-crystallins was also similar to that of humans. The most abundant gamma-crystallins were the diverse gammaMs, comprising 30.5% of the lens. Intact zebrafish crystallins were generally more common in the soluble fraction with truncated versions more common in the insoluble fraction. While the total alpha- and gamma-crystallin content of the zebrafish lens differs from that of humans, similarities in alpha-crystallin ratios and modifications and a link between crystallin truncation and insolubility suggest that the zebrafish is a suitable model for the vertebrate lens. The proteome map provided here will be of value to future studies of lens development, function, and disease.


Polyphenols as novel interventions for depression: Exploring the efficacy, mechanisms of action, and implications for future research.
Numerous animal and human studies have assessed the relationship between polyphenols and outcomes related to depression. However, no comprehensive synthesis of the main findings has been conducted. The aim of this manuscript was to systematically review the available evidence from animal and human studies on the association and the effects of dietary polyphenols on depression and provide recommendations for future research. We based our review on 163 preclinical animal, 16 observational and 44 intervention articles assessing the relationship between polyphenols and outcomes related to depression. Most animal studies demonstrated that exposure to polyphenols alleviated behaviours reported to be associated with depression. However, human studies are less clear, with some studies reporting an inverse relationship between the intake of some polyphenols, and polyphenol rich foods and depression risk and symptoms, while others reporting no association or effect. Hence, while there has been extensive research conducted in animals and there is some supporting evidence in humans, further human studies are required, particularly in younger and clinical populations.


A case of axillary lymphadenitis caused by Mycobacterium intracellulare in an immunocompetent patient.
Axillary lymphadenitis caused by non-tuberculous mycobacteria is rare and has been reported in immunocompromised hosts. Herein, we report the case of a 67-year-old man without immunodeficiency who developed right axillary lymphadenitis caused by Mycobacterium intracellulare and showed a small nodular shadow in the left pulmonary apex. Biopsy of the right axillary lymph node revealed several epithelioid granulomas, and the culture of the lymph node aspirate yielded Mycobacterium intracellulare. The lymph node lesion and left lung apex shadow resolved spontaneously after careful outpatient monitoring. This case suggests that axillary lymphadenitis could be caused by Mycobacterium intracellulare in an immunocompetent patient.


Comparison of the ability of alternative birthweight and fetal weight standards to identify preterm newborns at increased risk of perinatal death.
To compare prediction of perinatal deaths among preterm infants based on fetal weight standards versus a new subpopulation-based birthweight standard. Population-based cohort study. France. A total of 9100 preterm singletons, born between 24 and 36 weeks of gestation in 2000-09, in Burgundy (France). We first classified all newborns as either small for gestational age (SGA) or not, based on alternative fetal weight or birthweight standards, including a new birthweight standard that excludes infants born to mothers with disease related to the weight of a fetus. Based on discrepancies between the different classifications, we then divided the newborns into four groups, and compared their risks of stillbirth and in-hospital death, using a generalised linear model with relative risks (RR). Perinatal deaths, including, in separate analyses, stillbirths and in-hospital deaths. The preterm infants classified as SGA by our new subpopulation-based birthweight standard but not by the conventional birthweight standard had a significantly higher risk of both stillbirth (RR = 2.6; 95% confidence interval [95% CI] = 1.9-3.6) and in-hospital death (RR = 2.8; 95% CI = 1.8-4.5). In contrast, no risk increase was found for infants classified as SGA by the fetal standard only (RR = 1.1; 95% CI = 0.7-1.7 for stillbirths, and RR = 0.5; 95% CI = 0.3-1.3 for in-hospital deaths). Our subpopulation-based birthweight standard identified a subgroup of preterm newborns who have significantly increased risks of perinatal death but are not classified as SGA by the conventional birthweight standard. In contrast, the subgroup classified as SGA by the fetal standards only, but not by our subpopulation-based birthweight standard, had no increased risk of mortality, compared with non-SGA infants.


Purification and properties of cytosolic alanine aminotransferase from the liver of two freshwater fish, Clarias batrachus and Labeo rohita.
Cytosolic alanine aminotransferase (c-AAT) was purified up to 203- and 120-fold, from the liver of two freshwater teleosts Clarias batrachus (air-breathing, carnivorous) and Labeo rohita (water-breathing, herbivorous), respectively. The enzyme from both fish showed similar elution profiles on a DEAE-Sephacel ion exchange column. SDS-PAGE of purified enzymes revealed two subunits of 54 and 56 kDa, in both fish. The apparent Km values for l-alanine were 18.5+/-0.48 and 23.55+/-0.60 mM, whereas for 2-oxoglutarate the Km values were observed to be 0.29+/-0.023 and 0.33+/-0.028 mM for the enzyme from C. batrachus and L. rohita, respectively. With l-alanine as substrate, aminooxyacetic acid was found to act as a competitive inhibitor with KI values of 6.4 x 10(-4) and 3.4 x 10(-4) mM with c-AAT of C. batrachus and L. rohita, respectively. However, when 2-oxoglutarate was used as substrate, aminooxyacetic acid showed uncompetitive inhibition with similar KI values for purified c-AAT from both fish. Temperature and pH profiles of the enzyme did not show any marked differences between the two fish examined. These results suggest that liver c-AAT, isolated from these two fish species adapted to different modes of life, remain unaltered structurally. However, at the kinetic level, liver c-AAT from C. batrachus exhibits significantly higher affinity for the substrate l-alanine and decreased affinity for its metabolic inhibitor, in comparison to that of the enzyme purified from L. rohita. Such functional changes seem to be of physiological significance and also provide preliminary evidence for subtle changes in the enzyme as a mark of metabolic adaptation in the fish to different physiological demands.


Culture adaptation for enhanced biogas production from birch wood applying stable carbon isotope analysis to monitor changes in the microbial community.
Birch wood is a potential feedstock for biogas production in Northern Europe; however, the lignocellulosic matrix is recalcitrant preventing efficient conversion to methane. To improve digestibility, birch wood was thermally pre-treated using steam explosion at 220 °C for 10 min. The steam-exploded birch wood (SEBW) was co-digested with cow manure for a period of 120 days in continuously fed CSTRs where the microbial community adapted to the SEBW feedstock. Changes in the microbial community were tracked by stable carbon isotopes- and 16S r RNA analyses. The results showed that the adapted microbial culture could increase methane production up to 365 mL/g VS day, which is higher than previously reported methane production from pre-treated SEBW. This study also revealed that the microbial adaptation significantly increased the tolerance of the microbial community against the inhibitors furfural and HMF which were formed during pre-treatment of birch. The results of the microbial analysis indicated that the relative amount of cellulosic hydrolytic microorganisms (e.g. Actinobacteriota and Fibrobacterota) increased and replaced syntrophic acetate bacteria (e.g. Cloacimonadota, Dethiobacteraceae, and Syntrophomonadaceae) as a function of time. Moreover, the stable carbon isotope analysis indicated that the acetoclastic pathway became the main route for methane production after long-term adaptation. The shift in methane production pathway and change in microbial community shows that for anaerobic digestion of SEBW, the hydrolysis step is important. Although acetoclastic methanogens became dominant after 120 days, a potential route for methane production could also be a direct electron transfer among Sedimentibacter and methanogen archaea.


Analysis of refractive artifacts by reconstructed three-dimensional ultrasound imaging.
Refractive artifacts are frequently encountered in clinical settings, and they have been analyzed on the basis of conventional two-dimensional (2-D) ultrasound (US) images, but this method is restricted to monoplane data and is limited by its inability to assess the three-dimensional (3-D) structure of refractive artifacts. The aim of this study was to evaluate the role of reconstructed 3-D US images in the analysis of refractive artifacts. The following representative refractive artifacts were analyzed on the basis of reconstructed 3-D US images: (a) a distorted image of a fine tube behind a cyst (balloon); (b) a deformed image of the bottom of a balloon; and (c) a duplication artifact due to the acoustic lens effect. (a) A tube was imaged as a fine echogenic line with two points of sudden interruption, unlike a curved needle, which was imaged without interruption. (b) 3-D US allowed us to visualize the mode of deformity in the image of the bottom of a fluid-filled balloon in a water bath. When the acoustic velocity in the fluid was greater than that in the surrounding water, the bottom of the balloon appeared to be shrunken. When the acoustic velocity in the fluid was less than that in the surrounding water, the bottom of the balloon appeared to be swollen. (c) When we placed two pieces of white chicken meat in front of a fine needle, the needle was duplicated in the resulting image. In this case, the needle appeared to be vague and fuzzy. In this case, 3-D US did not add further information to the 2-D images. Our study suggests that reconstructed 3-D US images provide a better understanding of the mode of refractive artifacts than do 2-D US images.


Cytogenetic and immunohistochemical evidence that giant cell fibroblastoma is related to dermatofibrosarcoma protuberans.
From cytogenetic and immunohistochemical findings in a primary giant cell fibrosarcoma and its recurrence, it is further demonstrated that a close relationship exists between this tumor and dermatofibrosarcoma protuberans. Both tumors express CD34 and show rearrangements of chromosomes 17 and 22.


Location and age of Mesolithic coastal occupation sites on Oronsay, Inner Hebrides.
The existence of at least five Mesolithic occupation sites on the island of Oronsay, Inner Hebrides, has now been established. Preliminary results of recent excavation of two of the sites were reported in 1971 (ref. 1). Since then further excavations have been made and the locations and ages of the sites in relation to the position of the shore line of the sea at the maximum of the Holocene marine transgression have been investigated. The results obtained suggest that the ages of some of the sites in relation to the former shore line cannot be established solely on stratigraphical and altitudinal evidence but require supplementary information based on radiocarbon dating. It will be some time before the full details will be published, and so a short account of the results so far obtained is presented now.


Incidence of side effects following direct puncture cervical myelography. Bed rest versus normal mobility.
After cervical myelography by direct puncture at C 1/2 level, 120 patients were randomly allocated to one of two groups, in one the patients were allowed to be fully ambulant and in the other the regimen was bed rest for 24 h. Questionnaires recording the frequency and severity of side effects were completed at intervals after the examination. Headache, nausea and vomiting were common; fits and mental changes occurred also but were uncommon. The incidence and severity of these side effects did not differ significantly between the two groups.


The effect of insulin on vascular reactivity to norepinephrine.
The effect of insulin on the vasoconstrictor response to norepinephrine of the resistance bed of the isolated perfused rat tail has been studied. Insulin produced a significant attenuation of this response in concentrations of both 120 mU./ml. and 150 micronU./ml. It is suggested that this effect may be relevant to the hypotensive action of insulin observed in diabetics.


Pubertal Bisphenol A exposure increases adult rat serum testosterone by resetting pituitary homeostasis.
Bisphenol A (BPA) is widely used by manufacturers and in consumer products. Its release in the environment may affect male reproductive function. In this study, we examined the effect of low dose (0.1 mg/kg BW), short term exposure during puberty (PD21-35) on adult rat male reproduction. The results indicated that such exposure reset growth hormone (GH) and follicular stimulating hormone (FSH) homeostasis and resulted in a significantly higher level of serum testosterone without affecting serum luteinizing hormone level. QPCR and Western blot results showed that BPA significantly up-regulated selective genes/proteins in the Leydig cell steroidogenic pathway, including steroidogenic acute regulatory protein, cytochrome P450 11A1, cytochrome P450 17A, and low-density lipoprotein receptor. RNA-Seq analysis of testicular RNAs showed that BPA significantly affected the gene profiles of multiple testicular interstitial populations without affecting germ cells. Also, GO- and KEGG-analysis suggested that IGF1-related PI3K/AKT signaling was activated, which was confirmed by the increased phosphorylation of IRS1, AKT1 and CREB. The results indicated that a low-dose, short-term BPA exposure during puberty affected the adult male rat pituitary (GH and FSH) and testis (testosterone) homeostasis.


Immunomodulatory effects of Maxadilan and Phlebotomus papatasi sand fly salivary gland lysates on human primary in vitro immune responses.
Leishmaniasis is a parasitic disease transmitted by the bite of Leishmania-infected sand flies. Here we show for the first time the ability of Maxadilan (Max), a vasodilatory peptide isolated from the sand fly Lutzomyia longipalpis, and salivary gland lysate (SGL) from Phlebotomus papatasi to decrease the secretion of Type 1 cytokines and to enhance the production of the Type 2 cytokine interleukin (IL)-6 by human peripheral blood mononuclear cells (PBMC) and monocytes. We found Max decreased the secretion of interferon (IFN)-gamma and IL-12p40 by PBMC and TNF-alpha by monocytes. SGL reduced the production of IFN-gamma by PBMC. In contrast, production of the Type 2 cytokine IL-6 was increased in Max or SGL-exposed cells. Finally, we determined that Max interacts with human cells through at least the pituitary adenylate cyclase activating polypeptide receptor. These results show that sand fly salivary gland components have an immunomodulatory effect on human cells, and this has important implications for the development of vaccines against leishmaniasis for humans.


Using LC/MS/MS to determine matrine, oxymatrine, ferulic acid, mangiferin, and glycyrrhizin in the Chinese medicinal preparations Shiau-feng-saan and Dang-guei-nian-tong-tang.
We have developed a simple, rapid, selective, and reproducible method for the quality control of traditional Chinese medicinal preparations. In this study, we used LC/MS/MS to simultaneously identify and quantify five marker compounds - matrine, oxymatrine, ferulic acid, mangiferin, and glycyrrhizin - in preparations of Shiau-feng-saan and Dang-guei-nian-tong-tang. The calibration curves for the five marker compounds were linear over the concentration range 50-2500 ng/mL (R2>0.9971). The matrix effect was minimized and the recoveries of the five marker compounds were >90% at a concentration of 1 microg/mL. Our experimental data reveal that significant differences exist between samples obtained from different sources.


Modulation of luminescence by subtle anion-cation and anion-π interactions in a trigonal Au(I)···Cu(I) complex.
The trigonally coordinated [AuCu(PPh(2)py)(3)](BF(4))(2) (1) crystallizes in two polymorphs and a pseudopolymorph, each of which contains a trigonally coordinated cation with short Au(I)-Cu(I) separations of ∼2.7 Å. Under UV illumination, these crystals luminesce different colors ranging from blue to yellow. The structures of these cations are nearly superimposable, and the primary difference resides in the relative placement of the anions and solvate molecules. As confirmed by time-dependent density functional theory calculations, it is these interactions that are responsible for the differential emission properties.


Pintomyia evansi (Diptera: Psychodidae) larvae susceptibility to hydrated lime under laboratory conditions.
This study evaluated the effect of Calcium hydroxide (Ca(OH)2 Mg(OH)2) on third stages Pi. evansi larvae mortality under experimental laboratory conditions. Three treatments containing a mixture of phlebotomine natural breeding soil (substrate) and Calcium hydroxide at different concentrations were used: Treatment 1 (T1), 1 kg of substrate mixed with 56.2 g of lime; Treatment 2 (T2), 1 kg of substrate mixed with 62.5 g of lime; and Treatment 3 (T3), 1 kg of substrate mixed with 70 g of lime. in addition, a sample of substrate without lime was used as a control for each treatment. The mortality in T1 was 1% at 24 h and 12% at 48 h, reaching a maximum of 56% at 72 h of exposure. For T2, mortality was progressive, starting with 12% at 12 h, 36% at 24 h, 52% at 48 h, and 100% at 72 h; while T3 showed mortality percentages of 94% and 100% between 12 and 24 h of exposure. Therefore, T3 was the most effective to according to the Kaplan-Meier survival analysis. This study showed that treatments over 62 g of Calcium hydroxide per 1 kg of substrate offer a starting point for immature stage control under laboratory conditions. With these results, we propose to evaluate the cost-effectiveness and feasibility of the application, of the latter concentration, under field conditions in urban environments for its application in vector control programs.


Hypofractionated irradiation for gliomas with 45.5Gy in 13 fractions: a retrospective study.
The aim of the present retrospective study was to evaluate the efficacy and toxicity of a hypofractionated radiotherapy (HFRT) schedule for grade IV glioblastoma multiforme (GBM). Fourteen elderly patients with KPS less than 70, received 13 fractions of 350cGy with 3D-conformal technique (3DCRT) and non-coplanar fields. Acute and late skin and CNS toxicity was graded according to EORTC/RTOG criteria. The median follow-up was 9 months. All patients completed the irradiation without interruptions due to toxicity and received temozolomide (TMZ) after the completion of 3DCRT. The KPS during RT and at follow-up was not significantly changed (P=0.108). The median overall survival was 7 months. No severe skin acute or late toxicity was noted. In terms of CNS toxicity, only one patient presented grade III toxicity requiring hospitalization for two days. The irradiation schedule of 45.5Gy in 13 fractions seems effective and without moderate or severe toxicity. The suggested HFRT schedule might be an alternative one, for elderly patients with dismal prognosis, unfit for six weeks of daily irradiation. Prospective studies are needed for further validation of our results, especially with the use of TMZ.


Distinct heparin binding sites on VEGF165 and its receptors revealed by their interaction with a non sulfated glycoaminoglycan (NaPaC).
We previously demonstrated that a non sulfated analogue of heparin, phenylacetate carboxymethyl benzylamide dextran (NaPaC) inhibited angiogenesis. Here, we observed that NaPaC inhibited the VEGF165 binding to both VEGFR2 and NRP-1 and abolished VEGFR2 activity. Further, we explored the effects of NaPaC on VEGF165 interactions with its receptors, VEGFR2 and NRP-1, co-receptor of VEGFR2. Surface plasmon resonance and affinity gel electrophoresis showed that NaPaC interacted directly with VEGF165, VEGFR2 and NRP-1 but not with heparin-independent factor such as VEGF121. NaPaC completely inhibited the heparin binding to VEGF165, NRP-1 and VEGFR2. We found that NaPaC bound to all three molecules, VEGF165, VEGFR2 and NRP-1, but was more effective in inhibiting heparin binding to VEGF165. These results suggested that heparin binding sites of VEGFR2 and NRP-1 were different from those of VEGF165.


Childhood Obesity and Depression: Connection between these Growing Problems in Growing Children.
Depression and obesity have been recognized as major public health issues in youths. Although they have traditionally been compartmentalized as separate physical and emotional health conditions, evidence suggests interactions and common pathways between them, implying that successful treatment should ideally target shared underlying mechanisms. The purpose of the present article is to review the pediatric diagnostic criteria for depression and obesity, highlight similarities in their clinical presentation, identify common pathways and underlying mechanisms, describe their developmental trajectories, and suggest areas for future study to guide development of innovative prevention and treatment initiatives.


Quantitation of the interaction between citrate synthase and malate dehydrogenase.
Formation of a bienzyme complex of pig heart mitochondrial malate dehydrogenase and citrate synthase in a buffered system is demonstrated by means of a covalently attached fluorescent probe to citrate synthase. Assuming 1:1 stoichiometry of the enzymes in the complex, an apparent dissociation constant of 10(-6) M was calculated from fluorescence anisotropy measurements. The effect of various metabolites on the interaction was tested. NAD+, oxalacetate, citrate, ATP, and L(-)- or D(+)-malate had no effect on the association of the two enzymes, whereas alpha-ketoglutarate increased and NADH decreased it. The interaction of mitochondrial citrate synthase with cytosolic malate dehydrogenase was found to be much weaker, whereas interaction of citrate synthase with another cytosolic enzyme, aldolase, could not be detected. In kinetic experiments, the activation of malate dehydrogenase by citrate synthase was observed. The effect of pyridine nucleotides and alpha-ketoglutarate is discussed in relation to the direction of the metabolic flow of oxalacetate.


The Associations of Genetically Predicted Plasma Alanine with Coronary Artery Disease and its Risk Factors: A Mendelian Randomization Study.
Alanine is an amino acid commonly used as a nutritional supplement and plays a key role in the glucose-alanine cycle. Plasma alanine has been associated in observational studies with a higher risk of coronary artery disease (CAD) and unhealthier lipid profiles. However, evidence from large randomized controlled trials is lacking. Using Mendelian randomization (MR), we assessed the unconfounded associations of plasma alanine with CAD and CAD risk factors. We applied single nucleotide polymorphisms that were strongly (P < 5 ×10-8) associated with plasma alanine as genetic instruments to large genome-wide association studies of CAD (63,108 cases; 296,901 controls), diabetes (90,612 cases; 583,493 controls), glucose (515,538 participants), lipids (low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol, triglycerides, total cholesterol, and apolipoprotein B) (>1.1 million participants), blood pressure (BP) (757,601 participants), and body mass index (682,137 participants). Given the potential sex disparity, we also conducted sex-specific analyses. MR estimates per standard deviation increase in alanine concentrations were obtained using inverse variance weighting followed by sensitivity analyses using weighted median, MR-Egger, MR-Pleiotropy RESidual Sum and Outlier, and MR-Robust Adjusted Profile Score. Genetically predicted plasma alanine was not associated with CAD but with a higher risk of diabetes (odds ratio [OR]: 1.35; 95% confidence interval [CI]: 1.06, 1.72), higher glucose (β: 0.11; 95% CI: 0.02, 0.19), LDL cholesterol (β: 0.08; 95% CI: 0.04, 0.12), triglycerides (β: 0.25; 95% CI: 0.13, 0.38), total cholesterol (β: 0.14; 95% CI: 0.08, 0.20), apolipoprotein B (β: 0.12; 95% CI: 0.03, 0.21), and BP (β: 1.17; 95% CI: 0.31, 2.04 for systolic BP: β: 0.97; 95% CI: 0.49, 1.45 for diastolic BP) overall. The positive associations of serum alanine with LDL cholesterol and triglycerides were more notable in women than in men. Alanine or factors affecting alanine may have causal effects on diabetes, blood glucose, lipid profiles, and BP but not on CAD. Further studies are needed to clarify possible mechanisms.


Linear estimates of rates of disease progression as predictors of survival in patients with ALS entering clinical trials.
Maximal voluntary isometric grip and foot dorsiflexion (FD) strength and forced vital capacity (FVC) were obtained in 62 patients with ALS at or close to enrollment into two clinical trials. The agents tested did not slow disease progression. Isometric strength data were standardized, and the worse side was taken. FVC was expressed as a percentage of the predicted value (FVC%). We derived linear estimates of rates of disease progression based on the isometric myometry and FVC measures and on disease duration. Forty one patients were known to have died or to have undergone tracheostomy for ventilatory support. Probability of tracheostomy-free survival was calculated using the Kaplan-Meier method. The measured values, the linear estimates for rates of decline of these values, gender, age at onset, bulbar vs. spinal onset, height and weight were tested as risk factors within the Cox proportional hazards model, using regression techniques. When tested individually, estimates of rates of decline based on all three measures (FD, grip and FVC%) were the only statistically significant risk factors (P<0.005). Multivariate analysis resulted in a 3-variable model (chi-square=75.3, P<0.00001) in which estimated rates of decline of FD strength and of FVC%, and bulbar onset were independently significant (P<0.0001, P<0.0007 and P<0.05, respectively). We conclude that linear estimates of the rate of disease progression till enrollment into a clinical trial may be better predictors of patient survival than demographic data or discrete biologic measures.


HLA shared epitope and ACPA: just a marker or an active player?
Autoantibody production is genetically controlled and anti-citrullinated protein/peptide antibodies (ACPA) are not an exception to the rule. ACPA are highly specific markers of rheumatoid arthritis (RA) and are also associated with a more severe disease course. The production of ACPA is almost invariably observed in HLA-shared epitope (SE) positive patients. The DRB1 alleles sharing SE are those conferring susceptibility to RA. SE alleles behave like immune response genes, controlling both the specificity and the amount of ACPA produced. These data suggest a role of SE in the presentation of citrullinated antigens. The ability of SE alleles to bind selectively to citrullinated sequences as compared to the native counterparts has been demonstrated in the case of peptides derived from several joint associated proteins (vimentin, fibrinogen and cartilage intermediate-layer protein). On the contrary, EBV-derived citrullinated peptides do not display a biologically relevant binding to SE alleles even if the immune response to VCPs is under the genetic control of these alleles (namely *0401 and *0404). Thus, the presentation of citrullinated epitopes does not represent the only molecular mechanisms underlying the HLA-DRB1 effect on ACPA production.


Depiction of the vitreous pocket by optical coherence tomography.
The reported shape and size of the vitreous pocket vary depending on the method of visualization. We used spectral domain optical coherence tomography (SD-OCT) to clarify the structure of the normal vitreous pocket. The macular retina of 20 consecutive non-highly myopic eyes of 10 healthy young adults (aged 22-27 years) was examined using spectral SD-OCT. The premacular vitreous pocket and the pre-papillary Cloquet's canal were observed in a scan area 9 mm in transverse diameter and 6 mm in longitudinal diameter. On SD-OCT, the vitreous pocket was observed in all the eyes, anterior to the macula as a flat dish-like structure measuring 7.5 ± 0.6 mm in transverse diameter, 5.2 ± 0.3 mm in longitudinal diameter, and 0.3 ± 0.5 mm in thickness. The boundary of the vitreous pocket was clear, the central portion was thin, and the peripheral portion protruded anteriorly. The posterior wall of the vitreous pocket which can be observed at the macular region was a thin layer of vitreous cortex. Mildly reflective dots were observed inside the vitreous pocket. A thin wall was observed between the vitreous pocket and the pre-papillary Cloquet's canal. On SD-OCT, the vitreous pocket of healthy young adults was visualized as a liquefied lacuna with a clear boundary measuring approximately 7.5 × 5.2 × 0.3 mm, with the posterior wall composed of a layer of vitreous cortex and separated from the pre-papillary Cloquet's canal by a thin wall.


Planning CT Identifies Patients at Risk of High Prostate Intrafraction Motion.
Prostate motion (standard deviation, range of motion, and diffusion coefficient) was calculated from 4D ultrasound data of 1791 fractions of radiation therapy in N = 100 patients. The inner diameter of the lesser pelvis was obtained from transversal slices through the pubic symphysis in planning CTs. On the lateral and craniocaudal axes, motility increases significantly (t-test, p < 0.005) with the inner diameter of the lesser pelvis. A diameter of >106 mm (ca. 6th decile) is a good predictor for high prostate intrafraction motion (ca. 9th decile). The corresponding area under the receiver operator curve (AUROC) is 80% in the lateral direction, 68% to 80% in the craniocaudal direction, and 62% to 70% in the vertical direction. On the lateral x-axis, the proposed test is 100% sensitive and has a 100% negative predictive value for all three characteristics (standard deviation, range of motion, and diffusion coefficient). On the craniocaudal z-axis, the proposed test is 79% to 100% sensitive and reaches 95% to 100% negative predictive value. On the vertical axis, the proposed test still delivers 98% negative predictive value but is not particularly sensitive. Overall, the proposed predictor is able to help identify patients at risk of high prostate motion based on a single planning CT.


A case report: Community-acquired Pseudomonas aeruginosa necrotizing fasciitis in a morbidly obese diabetic young man can be fatal.
We present a case study of a 26-year-old morbidly obese man with a three-day history of right leg pain and swelling. The swelling was associated with low grade fever. He was alert and conscious upon presentation to the hospital. His physical examination showed gross swelling of the entire right lower limb with no systemic manifestations. There was no discharge and bullae from the swelling area of the leg. He had high blood sugar and was newly diagnosed with type 2 diabetes mellitus. He was diagnosed with necrotizing fasciitis. An intravenous imipenem-cilastatin 500 mg every 6 h together with clindamycin 900 mg every 8 h was started empirically. Extensive wound debridement was performed. The swab culture obtained intraoperatively grew Pseudomonas aeruginosa. He required an above knee amputation due to worsening infection despite wound debridement. Post-operatively, he developed acute kidney injury with severe metabolic acidosis, which required daily hemodialysis. However, the patient deteriorated due to septic shock with multi-organ failure, resulting in his death.


Expression of aromatase and oestrogen receptors in reproductive tissues of the stallion and a single cryptorchid visualised by means of immunohistochemistry.
Androgen metabolism may proceed to amplify the action of testosterone by its aromatisation to oestradiol. Recently, a growing body of evidence suggests a role of oestrogens in the male reproductive tract via their specific oestrogen receptors (ERs). In order to check whether androgens are converted to oestrogens in the testis, epididymis and prostate of the stallion, the expression of aromatase was visualised by means of immunohistochemistry. Moreover, to show the cellular targets for oestrogens the presence of oestrogen receptor alpha (ERalpha) and oestrogen receptor beta (ERbeta) was demonstrated in these tissues. Finally, to show whether naturally occurring cryptorchidism has any influence on the localisation of aromatase and distribution of ERs, the reproductive tissues of a single horse, bilaterally cryptorchid, were also taken for this study. The results demonstrated that aromatase and ERs are ubiquitously distributed throughout the male reproductive tract, what indicates a putative role of oestrogens in modulating the function of the reproductive tissues of the stallion. In the cryptorchid horse the increase in conversion of androgen to oestrogen was observed as manifested by aromatase overexpression. This is the first report showing the cellular site of oestrogen biosynthesis not only in the testis but also in the epididymis and prostate of sexually mature stallion and a single, adult cryptorchid.


Optimizing an 18F-NaF and 18F-FDG cocktail for PET assessment of metastatic castration-resistant prostate cancer.
PET/computed tomography (CT) imaging with the sodium-(F)-fluoride/2-(F)-fluoro-2-deoxy-D-glucose (F-NaF/F-FDG) cocktail has been proposed for patients with osseous metastases. This work aimed to optimize the cocktail composition for patients with metastatic castration-resistant prostate cancer (mCRPC). The study was carried out on six patients with mCRPC, with a total of 26 analyzed lesions. The patients were injected with F-NaF and F-FDG at separate time points. Dynamic PET/CT imaging recorded the uptake time course for both the tracers into osseous metastases. F-NaF and F-FDG uptakes were decoupled by kinetic analysis, which enabled calculation of F-NaF and F-FDG standardized uptake values (SUVs) images. Peak, mean, and total SUVs were evaluated for both tracers and all visible lesions. The F-NaF/F-FDG cocktail was optimized under the assumption that the contribution of both tracers to image formation is equal. SUV images from PET/CT imaging with a combination of F-NaF and F-FDG were generated for cocktail compositions with an F-NaF : F-FDG ratio varying from 1 : 8 to 1 : 2. The F-NaF peak and mean SUVs were on average four to five times higher than the F-FDG peak and mean SUVs, with an interlesion coefficient of variations of 20%. The total SUV for F-NaF was on average seven times higher than that for F-FDG. When the F-NaF : F-FDG ratio changed from 1 : 8 to 1 : 2, the typical SUV on the generated PET images increased by 50%, whereas the change in the uptake visual pattern was hardly noticeable. F-NaF and F-FDG in the cocktail contribute equally to image formation when the F-NaF : F-FDG ratio is 1 : 5. Therefore, we propose this ratio as the optimal cocktail composition for mCRPC patients. We also urge to strictly control the cocktail composition during any F-NaF/F-FDG cocktail PET/CT examination.


Cardiovascular and pulmonary complications of epidemic typhus.
A case of typhus fever associated with cardiac and pulmonary complications is reported. The patient was a 24-year-old Egyptian female with characteristic clinical presentation of rickettsial infection, though no rash was present throughout the course of the disease. We could not find a report of such complications in the English medical literature.


Cumulative Effects of Exposure to Continuous and Intermittent Sounds on Temporary Hearing Threshold Shifts Induced in a Harbor Porpoise (Phocoena phocoena).
The effects of exposure to continuous and intermittent anthropogenic sounds on temporary hearing threshold shifts (TTSs) in a harbor porpoise were investigated by testing hearing before and after exposure to 1- to 2-kHz downsweeps of 1 s, without harmonics, presented as paired-intermittent and continuous-exposure combinations with identical cumulative sound exposure levels (SEL(cum)). Exposure to intermittent sounds resulted in lower TTSs than exposure to continuous sounds with the same SEL(cum). Therefore, the hearing of marine mammals is at less risk from intermittent anthropogenic noises than from continuous ones at the same received sound pressure level and duration.


Sperm shape abnormality and urine mutagenicity in mice treated with niclosamide.
Niclosamide, a widely used anthelmintic drug in underdeveloped countries, is known to be mutagenic in the Salmonella typhimurium microsomal test system. The urine obtained from mice treated with niclosamide is mutagenic in the TA98 and TA1538 strains. Its effects on mouse-sperm morphology were evaluated in CD1 and (BALB/cJ x DBA/2J) F1 mice after 5 daily oral niclosamide doses of either 60, 80, 100 or 120 mg/kg. A statistically significant increase in abnormal sperm morphology was detected in both CD1 and (BALB/cJ x DBA/2J) F1 mice. No drug-related effects on testis weight nor on sperm count were observed in either genotype. Urine samples obtained from niclosamide-treated F1 mice were assayed with the Salmonella typhimurium strain TA1538 both in the absence and presence of beta-glucuronidase. In the absence of glucuronidase, urine mutagenicity increased with increasing dose and the highest doses were toxic. In the presence of glucuronidase, urine mutagenicity and toxicity also increased. Only at the highest dose (120 mg/kg), however, was there a positive correlation between the urine mutagenic activity and an increase in the number of abnormal sperm. The results of this study suggest that the increase in abnormal sperm depends on the systemic presence of non-conjugated niclosamide metabolites.


Gradual withdrawal of remifentanil infusion may prevent opioid-induced hyperalgesia.
The aim of this study was to examine if gradual withdrawal of remifentanil infusion prevented opioid-induced hyperalgesia (OIH) as opposed to abrupt withdrawal. OIH duration was also evaluated. Nineteen volunteers were enrolled in this randomized, double-blinded, placebo-controlled, crossover study. All went through three sessions: abrupt or gradual withdrawal of remifentanil infusion and placebo. Remifentanil was administered at 2.5 ng ml(-1) for 30 min before abrupt withdrawal or gradual withdrawal by 0.6 ng ml(-1) every five min. Pain was assessed at baseline, during infusion, 45-50 min and 105-110 min after end of infusions using the heat pain test (HPT) and the cold pressor test (CPT). The HPT 45 min after infusion indicated OIH development in the abrupt withdrawal session with higher pain scores compared with the gradual withdrawal and placebo sessions (both P<0.01. Marginal mean scores: placebo 2.90; abrupt 3.39; gradual 2.88), but no OIH after gradual withdrawal compared with placebo (P=0.93). In the CPT 50 min after end of infusion there was OIH in both remifentanil sessions compared with placebo (gradual P=0.01, abrupt P<0.01. Marginal mean scores: placebo 4.56; abrupt 5.25; gradual 5.04). There were no differences between the three sessions 105-110 min after infusion. We found no development of OIH after gradual withdrawal of remifentanil infusion in the HPT. After abrupt withdrawal OIH was present in the HPT. In the CPT there was OIH after both gradual and abrupt withdrawal of infusion. The duration of OIH was less than 105 min for both pain modalities. NCT 01702389. EudraCT number 2011-002734-39.


The effects of hyperuricemia on endothelial cells are mediated via GLUT9 and the JAK2/STAT3 pathway.
Uric acid (UA) transporters mediate the uptake and outflow of UA, and are greatly involved in the control of UA concentrations. Glucose transporter 9 (GLUT9), one of the UA transporters, has been confirmed to be expressed in human umbilical vein endothelial cells (HUVECs). This study aimed to characterize GLUT9's effect on intracellular UA accumulation in HUVECs in a high-UA environment and to explore the mechanism of cellular dysfunction. HUVECs were treated with UA to establish a model of cellular dysfunction. Then, UA uptake, GLUT9 expression and endothelial nitric oxide synthase (eNOS) and reactive oxygen species (ROS) amounts were measured. UA uptake was concentration- and time-dependent, and UA treatment significantly reduced nitric oxide (NO) levels and eNOS activity. UA also upregulated pro-inflammatory molecules and GLUT9, and increased intracellular ROS amounts in HUVECs. GLUT9 knockdown reduced UA uptake and ROS content, but antioxidant treatment did not reduce GLUT9 expression. To assess the function of JAK2/STAT3 signaling, HUVECs were treated with UA, and the phosphorylation levels of JAK2, STAT3, IL-6 and SOCS3 were increased by a high concentration of UA. In addition, GLUT9 knockdown reduced the phosphorylation of JAK2/STAT3 intermediates and increased p-eNOS amounts. GLUT9 mediated the effects of high UA levels on HUVECs by increasing the cellular uptake of UA, activating JAK2/STAT3 signaling, and reduced the production of active eNOS and NO in HUVECs.


Colony size and parasitoid load in two species of colonial Metepeira spiders from Mexico (Araneae: Araneidae).
While a number of advantages may result from group living, it may also lead to increased levels of attack by parasites because groups may be easier to find. This leads to the prediction that levels of parasitism should increase with colony size. We test this prediction by comparing colony size and parasitoid load for two species of colonial orb-weaving spiders from Mexico, Metepeira (undesc. sp., tentatively named atascadero) and Metepeira incrassata, which exhibit contrasting levels of social organization and utilize different habitats. For M. atascadero, which occurs solitarily or in small groups in desert/mesquite grassland habitat, rates of egg-sac parasitism fluctuate widely from year to year, and are closely tied to spider egg output. There is no relationship between colony size and rate of parasitism. For colonial M. incrassata, which occur in tropical rain forest/agricultural habitat, rates of parasitism are relatively constant from year to year. However, there is a positive relationship between colony size and rate of parasitism in this species. These differences are discussed with regard to the stability of the two habitats, prey availability, and the foraging behavior of the respective parasitoids.


Hydrocortisone administration alters glial reaction to entorhinal lesion in the rat dentate gyrus.
Young adult male rats received subcutaneous implants of Alzet osmotic minipumps which delivered 400 micrograms hydrocortisone per day. Untreated rats received no pumps or pumps containing the vehicle. Five days after receiving the implantation, both groups of rats were subjected to unilateral entorhinal lesion. Seven days after surgery, brains were analyzed quantitatively for glial changes in the denervated dentate outer molecular layer. Numerical densities of astrocytes and nonastrocytic glia were calculated by cell counting using 1.0-micron toluidine blue-stained sections. Glial acid phosphatase staining was quantitated using computer-assisted cytophotometric measurement of individual glial cells. Hydrocortisone-treated animals demonstrated 31% more astrocytes and 22.4% less nonastrocytes in the dentate outer molecular layer compared with untreated animals. Glia in the treated animals also showed a 33% decrease in average optical density of cytoplasmic acid phosphatase staining. These findings suggest that hydrocortisone treatment prior to and following an entorhinal lesion accelerates lesion-induced migration of astrocytes to the outer molecular layer, and reduces the increase in microglial number resulting from the lesion. The observed effect on microglia may result from a direct hormonal inhibition of local proliferation of microglia or from the well known systemic anti-inflammatory action of glucocorticoids on monocytes, the putative precursors of brain microglia. Our findings suggest that glucocorticoid hormones significantly alter the response of non-neuronal cells to neural tissue damage.


Characteristics of the nuclear translocation of progesterone receptor in fetal guinea pig uterus "in vivo", "in vitro" and in organ culture.
The translocation of progesterone receptor from the cytosol into the nucleus was studied under "in vivo" and "in vitro" conditions in the uteri of guinea pig fetuses exposed to progesterone or a synthetic progestin, R5020. Progesterone treatment of estrogen-primed fetuses leads to a rapid (before 1h) transfer of cytosol progesterone receptor into the nucleus which is, however, short-lived (less than 3h). A rapid decrease in the retention of the estrogen receptor in the nucleus also occurs. In the "in vitro" incubations of whole fetal uteri, translocation of progesterone receptor is temperature-dependent and specific for progesterone and R5020; estradiol and cortisol have no effect. Putative progesterone receptors can also be induced in explants of fetal guinea pig uteri in organ culture which translocate from the cytosol into the nucleus under the same "in vitro" conditions as in whole uteri. Fetal uterine progesterone receptor, either stimulated "in vivo" by estrogen-priming or induced in organ culture, translocates from the cytosol into the nucleus and this process seems to be accompanied by a decrease in retention of the estrogen receptor in the nucleus which appears to be the mechanism by which progesterone antagonises estrogen action in fetal guinea pig uterus.


Harnessing dielectric forces for separations of cells, fine particles and macromolecules.
A review of conventional dielectrophoresis on a microchip platform is presented. The benefits of miniaturization, some device geometries used to accomplish on-chip separations, and applications of these devices are discussed.


Growth characteristics and immunogenicity of the R-3327 rat prostate carcinoma.
The transplantable R-3327 prostate adenocarcinoma (Dunning tumor) has been studied in the Copenhagen rat. We present information about androgen-dependent and hormone-independent tumors in regard to metastasis, growth rate, extrapolated cell kinetics, and response to treatment.


Evaluation of an educational program for nurses providing cancer symptom management: The pan-Canadian Oncology Symptom Triage and Remote Support Online Tutorial.
To evaluate the acceptability of the pan-Canadian Oncology Symptom Triage and Remote Support (COSTaRS) open-access online tutorial and its impact on nurses' knowledge and perceived confidence in symptom management. Retrospective pre-/post-test evaluation of nurses who completed the tutorial knowledge test and/or acceptability survey. The tutorial was modeled after the previously evaluated in-person workshop to prepare nurses providing cancer symptom management using COSTaRS practice guides. From 2017-2021, 743 nurses completed the knowledge test, and 749 nurses evaluated the tutorial. Mean knowledge score was 4.4/6 and 83% of participants achieved passing scores. Compared to pre-tutorial, nurses improved their perceived confidence in assessing, triaging, guiding patients in self-care (p<0.001), and ability to use the COSTaRS guides (p<0.001). Nurses rated the tutorial as easy to understand (95%), just the right amount of information (92%), providing new information (75%), overall good to excellent (89%), and would recommend it to others (83%). More than 700 nurses accessed the tutorial. After completion, nurses demonstrated good knowledge and improved perceived confidence in cancer symptom management.


Association of Handgrip Strength and Muscle Mass with Dependency in (Instrumental) Activities of Daily Living in Hospitalized Older Adults -The EMPOWER Study.
Handgrip strength (HGS) and muscle mass are strong predictors for dependency in Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) in community dwelling older adults. Whether this also applies to older hospitalized patients is yet unknown. We studied the association between HGS and muscle mass with ADL and IADL dependency at admission and change of ADL and IADL dependency at three months after discharge in older hospitalized patients. Observational longitudinal inception cohort (EMPOWER) including 378 patients aged 70 years and older. Four different clinical wards of a university teaching hospital, The Netherlands. HGS and muscle mass were measured within 48 hours after admission using hand dynamometry and Bio-electrical Impedance Analysis respectively. ADL dependency was assessed using the Katz score (0-6 points) and IADL dependency using the Lawton and Brody score (0-8 points) within 48 hours after admission and three months after discharge. At admission, lower HGS was associated with ADL dependency in both males and females. Lower muscle mass was associated with ADL dependency in males. Lower HGS was associated with IADL dependency, but only in males. Lower HGS at admission in males was associated with an increase in ADL dependency three months after discharge. In hospitalized older patients, HGS is associated with ADL and IADL and muscle mass measures with ADL in male patients only. HGS should be explored as predictive marker for outcome of hospitalized older patients after discharge.


Symptom patterns in children and adolescents with obsessive-compulsive disorder (OCD).
Obsessive-compulsive disorder (OCD) defined at the diagnostic level encompasses divergent symptoms. The present study examines symptom patterns in OCD in children and adolescents in order to search for the presence of diagnostic heterogeneity. Two hundred and thirteen outpatients with primary OCD participated. The patients' and primary caretakers' responses on the Children's Yale-Brown Obsessive-Compulsive Scale were used to generate severity ratings for 61 OCD symptoms, and cluster analysed them. A five cluster solution was judged to be the most clinically and theoretically relevant model. The clusters were named: (1) "Mental Rituals, Touching & Ordering", (2) "Contamination & Cleaning", (3) "Superstitions", (4) "Obsessions/Checking & Confessing" and (5) "Somatic Concerns". The symptom patterns of the groups differed, and three groups were particularly homogeneous. In addition, there were differences in severity, number of symptoms and age. OCD in children and adolescents is a heterogeneous disorder and discrepancies vis-à-vis adult studies indicate that childhood OCD may have developmentally specific traits. The sub-groups obtained are likely to have implications for the assessment of OCD symptoms in children, their prognosis and outcome in treatment research.


Fever.
Fever is caused by a resetting of the thermoregulatory center in the hypothalamus, most often by viral or bacterial infections. The specific etiologic diagnoses vary, depending on the child's age and height and duration of fever. Fever lasting 7 days or more is termed an FUO. When evaluating children who have fever, the most critical diagnostic maneuver is the carefully performed clinical evaluation, observation, history, and physical examination. Laboratory studies may be ordered based on the results of the clinical evaluation as well as the child's age and height and duration of the fever. Recent studies have outlined the manner in which data from the clinical evaluation and laboratory test results may be integrated to formulate an effective plan of management and follow-up.


Some actions of catechol on synaptic transmission in the isolated spinal cord of the frog.
The isolated frog spinal cord was used to investigate the synaptic effects of the convulsant agent catechol. Addition of the compound to the superfusate consistently enhanced orthodromic reflex activity recorded from ventral roots and augmented primary afferent depolarization. Concomitantly catechol altered the polarization changes produced in ventral and dorsal roots by putative neurotransmitter amino acids when these compounds were applied in Mg2+-containing Ringer. Catechol reduced the hyperpolarizations induced in motoneurons by the neutral amino acids, GABA, beta-alanine, taurine and glycine, but did not affect the depolarizations produced by the dicarboxylic amino acids, L-glutamate and L-aspartate. In contrast, catechol increased the dorsal root depolarizations elicited by both neutral and dicarboxylic amino acids and also the depolarizations produced by elevated potassium concentrations. Catechol did not bring about significant changes in the passive electrical properties of motoneurons or dorsal root fibers. In addition, it did not alter either the high affinity uptake or the depolarization-evoked release of tritiated GABA, glycine, L-glutamate and L-aspartate. It appears that the postsynaptic actions of catechol explain its ability to enhance spinal reflexes.


Safety and efficacy of the supraclavicular approach to thoracic outlet decompression.
Thoracic outlet syndrome (TOS) is a clinical diagnosis encountered by both thoracic and vascular surgeons. The goal of surgical therapy involves relieving compression of the neurovascular structures at the superior thoracic aperture. The traditional approach to thoracic outlet decompression has been transaxillary; however more centers are moving toward a more tailored approach through a supraclavicular incision. The medical records of 67 patients who underwent surgical decompression between 1993 and 2001 for TOS were retrospectively reviewed. Patient demographics and early outcome were assessed through clinic follow-up. Seventy-two thoracic outlet decompressions were performed on 67 patients with the diagnosis of TOS. Five patients underwent bilateral thoracic outlet decompression. All operations in this time period were safely accomplished through a supraclavicular approach. The syndromes associated with thoracic outlet compression were neurogenic (n = 59), venous (n = 10), and arterial (n = 3). Forty-six of 72 (63.9%) operations resulted in complete resolution of symptoms, 17 cases (23.6%) had partial resolution, and 9 patients (12.5%) had no resolution. There were no deaths and morbidity was minimal with 6 complications (8.3%). The supraclavicular approach is a safe and effective technique in managing all forms of thoracic outlet compression.