Diastereo- and Enantioselective Synthesis of β-Aminoboronate Esters by Copper(I)-Catalyzed 1,2-Addition of 1,1-Bis[(pinacolato)boryl]alkanes to Imines.
Reported herein is an efficient copper(I)-catalytic system for the diastereo- and enantioselective 1,2-addition of 1,1-bis[(pinacolato)boryl]alkanes to protected imines to afford synthetically valuable enantioenriched β-aminoboron compounds bearing contiguous stereogenic centers. The reaction exhibits a broad scope with respect to protected imines and 1,1-bis[(pinacolato)boryl]alkanes, thus providing β-aminoboronate esters with excellent diastereo- and enantioselectivity. The synthetic utility of the obtained β-aminoboronate ester was also demonstrated.


Formation of neptunium(IV)-silica colloids at near-neutral and slightly alkaline pH.
The reducing conditions in a nuclear waste repository render neptunium tetravalent. Thus, Np is often assumed to be immobile in the subsurface. However, tetravalent actinides can also become mobile if they occur as colloids. We show that Np(IV) is able to form silica-rich colloids in solutions containing silicic acid at concentrations of both the regions above and below the "mononuclear wall" of silicic acid at 2 × 10(-3) M (where silicic acid is expected to start polymerization). These Np(IV)-silica colloids have a size of only very few nanometers and can reach significantly higher concentrations than Np(IV) oxyhydroxide colloids. They can be stable in the waterborne form over longer spans of time. In the Np(IV)-silica colloids, the actinide--oxygen--actinide bonds are increasingly replaced by actinide--oxygen--silicon bonds due to structural incorporation of Si. Possible implications of the formation of such colloids for environmental scenarios are discussed.


Platelet radioligand binding and neuroendocrine challenge tests in depression.
The purpose of this work was to examine the number and function of alpha 2-adrenoceptors and the number of serotonin uptake sites in depressed patients and controls. Platelet alpha 2-adrenoceptors and platelet serotonin uptake sites were labelled with [3H]yohimbine and [3H]imipramine respectively. Central alpha 2-adrenoceptor function was assessed by growth hormone and other responses to challenge with the alpha 2-agonist clonidine. No overall difference in the binding parameters was observed between the control and depressed groups, but the results highlight the importance of drug-free interval, menopausal status and membrane protein concentration within the binding assays in the interpretation of such studies. The growth hormone response to clonidine tended to be blunted in depressed females and was significantly blunted in the subgroup of depressives who failed to suppress plasma cortisol concentrations in response to dexamethasone. Depressed subjects also showed a smaller decrease in diastolic blood pressure and a smaller increase in sedation than control subjects.


Occurrence of sympatric charr groups, Salvelinus, Salmonidae, in the lakes of Kamchatka: a legacy of the last glaciations.
Six postglacial lakes were studied along both sides of the Kamchatka central mountain range, Russia. Pairs of local morphotypes of species of Arctic charrs, Salvelinus spp., have previously been described from the southernmost lakes while the fish fauna of the four northernmost lakes was studied here for the first time. Phenotypic data support the division of Kamchatkan lacustrine charrs into two groups according to the number of gill rakers and pyloric caeca, as well as snout-dorsal and snout-ventral distances (MANOVA, P < 0·001). These groups respectively correspond to phenotypes commonly referred to as Salvelinus malma and Salvelinus taranetzi. To clarify the identity of these groups, D-loop and cytochrome b (cytb) region sequences were analysed. Haplotype network analysis of mtDNA shows the salmonids inhabiting four lakes on the south and north are phylogenetically close to either Beringian S. malma or to S. taranetzi from the Chukotka and Kolyma River basins (the mean ± s.e. pairwise per cent sequence divergence is 0·006 ± 0·001). Phenotype-genotype discordance suggests that mitochondrial introgression between species has occurred in the two smallest lakes (<0·5 km2 ) in the central part of the peninsula. Identical haplotypes of D-loop and cytb regions were found for the populations of S. taranetzi from the most distant southern and northern lakes, indicating all lakes were colonized by both species simultaneously after the last glacial maximum. Salvelinus taranetzi may have colonized the Kamchatka peninsula from one or both of two different source regions: the Arctic Beringia and the northern coast of the Okhotsk Sea.


Primary and Interval Debulking Surgery Provide Similar Survival and Platinum Sensitivity Outcomes in Advanced Ovarian Cancer: A Retrospective Study.
CHORUS and EORTC55971 trials demonstrated that neoadjuvant chemotherapy followed by interval debulking surgery (IDS) or primary debulking surgery (PDS) offered the same survival rates. These trials have since been criticised due to poor surgical complexity. We compared overall (OS), progression free (PFS), and platinum sensitivity in advanced ovarian cancer (AOC) patients undergoing IDS or PDS, who had received either intermediate or high complexity surgery to achieve complete cytoreduction. All patients with AOC treated between February 2014 and May 2019 obtaining complete cytoreduction with intermediate/high surgical complexity were included. Recurrence was defined according to GCIG criteria on radiological findings and/or CA125 levels. Seventy-one patients (38 PDS and 33 IDS) with full recurrence data were identified. No statistical difference was seen between groups in OS, PFS or platinum sensitive interval. PDS or IDS were both acceptable treatment options for AOC, showing similar survival and platinum sensitivity outcomes in patients undergoing intermediate or high complexity surgery.


Sex differences in parent and child pain ratings during an experimental child pain task.
Research in the field of pediatric pain has largely ignored the role of fathers in their children's pain experiences. The first objective of the present study was to examine the effect of the presence of mothers versus fathers on children's subjective ratings, facial expressions and physiological responses to acute pain. The second objective was to examine whether child and parent sex influence parents' proxy ratings of their children's pain. The final objective was to compare levels of agreement between mothers' and fathers' assessments of their children's pain. Participants included 73 children (37 boys, 36 girls), four to 12 years of age, along with 32 fathers and 41 mothers. Children undertook the cold pressor pain task while observed by one of their parents. During the task, the children's heart rates and facial expressions were recorded. Children provided self-reports and parents provided proxy reports of child pain intensity using the seven-point Faces Pain Scale. Neither child nor parent sex had a significant impact on children's subjective reports, facial expressions or heart rates in response to acute pain. Fathers gave their sons higher pain ratings than their daughters, whereas mothers' ratings of their sons' and daughters' pain did not differ. Kappa statistics and t tests revealed that fathers tended to be more accurate judges of their children's pain than mothers. Overall, this research highlights the importance of examining both parent and child sex differences in pediatric pain research.


Hospital daily outpatient visits forecasting using a combinatorial model based on ARIMA and SES models.
Accurate forecasting of hospital outpatient visits is beneficial for the reasonable planning and allocation of healthcare resource to meet the medical demands. In terms of the multiple attributes of daily outpatient visits, such as randomness, cyclicity and trend, time series methods, ARIMA, can be a good choice for outpatient visits forecasting. On the other hand, the hospital outpatient visits are also affected by the doctors' scheduling and the effects are not pure random. Thinking about the impure specialty, this paper presents a new forecasting model that takes cyclicity and the day of the week effect into consideration. We formulate a seasonal ARIMA (SARIMA) model on a daily time series and then a single exponential smoothing (SES) model on the day of the week time series, and finally establish a combinatorial model by modifying them. The models are applied to 1 year of daily visits data of urban outpatients in two internal medicine departments of a large hospital in Chengdu, for forecasting the daily outpatient visits about 1 week ahead. The proposed model is applied to forecast the cross-sectional data for 7 consecutive days of daily outpatient visits over an 8-weeks period based on 43 weeks of observation data during 1 year. The results show that the two single traditional models and the combinatorial model are simplicity of implementation and low computational intensiveness, whilst being appropriate for short-term forecast horizons. Furthermore, the combinatorial model can capture the comprehensive features of the time series data better. Combinatorial model can achieve better prediction performance than the single model, with lower residuals variance and small mean of residual errors which needs to be optimized deeply on the next research step.


Consonant-vowel co-occurrence patterns in Mandarin-learning infants.
Most studies on CV co-occurrence patterns in early phonetic development have been based on Indo-European languages. Data from infants learning Mandarin, which has a substantially different phonological system from Indo-European languages, can confirm or refute the findings of previous studies, thus shedding further light on the theoretical bases of CV association. Spontaneous vocalizations were recorded in 45-minute sessions for each of 24 Mandarin-learning infants aged 0;7 to 1;6. In addition, the speech production of 24 caregivers was audio-recorded during their natural daily interactions with the infants at home. Both infants' vocalizations and adults' speech were transcribed and analysed for consonant-vowel co-occurrence patterns. These patterns were similar to those in other language groups, but language-specific patterns were evident by 1;0. Combinations of alveolars+front vowels and velars+back vowels confirm Davis & MacNeilage's (1990, 1995) frame-then-content theory and Clements's (1991) model of unified features for consonants and vowels. However, our finding of a language-specific pattern (labials+back vowels) suggests the need to reexamine the 'pure frame' of Davis & MacNeilage and Clements's grouping of labials and rounded vowels.


Atraumatic Posterior Thigh Compartment Syndrome Presenting as an Acute Sciatic Nerve Palsy.A Case Report.
Atraumatic posterior thigh compartment syndrome is a rare but serious condition. We document a case of atraumatic posterior thigh compartment syndrome that presented as an acute sciatic nerve palsy and required emergent fasciotomy. Based on this case, one should keep in mind the diagnosis of posterior thigh compartment syndrome when encountering a patient presenting with an acute sciatic nerve palsy.


Ultrahigh lattice thermal conductivity in topological semimetal TaN caused by a large acoustic-optical gap.
Topological semimetals may have potential applications such as in topological qubits, spintronics and quantum computations. Efficient heat dissipation is a key factor for the reliability and stability of topological semimetal-based nano-electronics devices, which is closely related to high thermal conductivity. In this work, the elastic properties and lattice thermal conductivity of TaN are investigated using first-principles calculations and the linearized phonon Boltzmann equation within the single-mode relaxation time approximation. According to the calculated bulk modulus, shear modulus and C 44, TaN can be regarded as a potential incompressible and hard material. The room-temperature lattice thermal conductivity is predicted to be 838.62 [Formula: see text] along the a axis and 1080.40 [Formula: see text] along the c axis, showing very strong anisotropy. It is found that the lattice thermal conductivity of TaN is several tens of times higher than other topological semimetals, such as TaAs, MoP and ZrTe, which is due to the very longer phonon lifetimes for TaN than other topological semimetals. The very different atomic masses of Ta and N atoms lead to a very large acoustic-optical band gap, and then prohibit the scattering between acoustic and optical phonon modes, which gives rise to very long phonon lifetimes. Calculated results show that isotope scattering has little effect on lattice thermal conductivity, and that phonons with mean free paths larger than 20 (80) [Formula: see text] along the c direction at 300 K have little contribution to the total lattice thermal conductivity. This work implies that TaN-based nano-electronics devices may be more stable and reliable due to efficient heat dissipation, and motivates further experimental works to study lattice thermal conductivity of TaN.


Muscle-tendon arrangement and innervation pattern of the m. flexor digitorum superficialis in the common marmoset (Callithrix jacchus), squirrel monkey (Saimiri sciureus) and spider monkey (Ateles sp.).
The muscle-tendon arrangement of the m. flexor digitorum superficialis (FDS) varies among different primate groups. Recent developmental investigations revealed that the primordium of FDS emerges in the hand region first and relocates to the forearm later. The relationship between the diverse muscle-tendon arrangement and the characteristic developmental process of FDS is important for understanding the evolutionary changes of the FDS. Moreover, the innervation pattern cannot go unremarked when discussing the muscle homology and evolution. We examined the muscle-tendon arrangement and intramuscular nerve distribution of the FDS in three genera of Platyrrhini: three common marmosets (Callithrix jacchus), two squirrel monkeys (Saimiri sciureus) and two spider monkeys (Ateles sp.). We observed that the FDS consisted of multiple muscle bellies. The origin of the muscle bellies to digits II and V varied, whereas muscle bellies to digits III and IV consistently originated from the medial epicondyle. The muscle-tendon arrangement of the FDS differed among the three genera owing to the different origins of muscle bellies to digits II and V. In all the examined specimens, the muscle bellies to digits II and/or III were innervated by the direct nerve branches from the median nerve. However, the muscle bellies to digits IV and V never received direct nerve branches from the median nerve. Nerve branches within the belly to digit III extended into the belly to digit IV, and one nerve branch within the belly to digit IV extended into the belly to digit V. These consistent nerve distribution patterns suggest that different patterns of FDS muscle-tendon arrangement have changed from that of a common ancestral condition. It is plausible that the diverse origins of muscle bellies in the FDS are attributable to the difference in the destination for the relocation of the muscle bellies during developmental processes.


Reduction in Serum High-Sensitivity C-Reactive Protein Favors Kidney Outcomes in Patients with Impaired Fasting Glucose or Diabetes.
We aimed to evaluate whether the reduction in serum high-sensitivity C-reactive protein (hs-CRP) favors kidney outcomes. This study was a subanalysis including patients with impaired fasting glucose or diabetes of the Kailuan cohort study. The predictor was based on two consecutive visits of hs-CRP levels in 2006 and 2008. A total of 3924 patients with hs-CRP ≥ 3 mg/L in 2006 were divided into two groups according to whether the levels of hs-CRP were reduced in 2008: Group 1: no reduction: hs-CRP ≥ 3 mg/L in 2008; Group 2: reduction: hs-CRP < 3 mg/L in 2008. Kidney outcomes include kidney function decline and development and progression of proteinuria and were followed up until the end of 2015. There were 3905, 2049, and 493 patients included into our analysis for the outcomes of kidney function decline and the development and progression of proteinuria, respectively. A total of 398, 297, and 47 events occurred after 5 years of follow-up, respectively. Cox regression revealed that patients with reduction in hs-CRP have lower risk of kidney function decline (HR 0.71, 95% CI 0.57-0.89, and P = 0.002) and development of proteinuria (0.77, 0.61-0.99, and P = 0.038) after controlling for potential confounders as compared to those with no reduction in hs-CRP levels. Reduction in serum hs-CRP levels favors kidney outcomes in patients with impaired fasting glucose or diabetes.


Agronomic application of olive mill wastewaters with phosphate rock in a semi-arid Mediterranean soil modifies the soil properties and decreases the extractable soil phosphorus.
Olive mill wastewater (OMW), a by-product of the olive-mill industry, is produced in large amounts in Mediterranean countries. The presence of indigenous phosphate deposits in some countries like Tunisia provides an incentive for direct application or local chemical treatment at low cost to improve the solubility of low reactive phosphate rocks (PRs). The use of naturally occurring low-molecular weight organic acids (LMWOAs) that are present in OMW represents a new perspective in PR research and a possible solution for the recycling of the OMW. The present work was aimed at evaluating, under natural situations (field of olive trees), the effects of agronomic application of OMW (amounts applied: 30, 60 m(3) ha(-1)) with PR (amounts applied: 150 kg ha(-1)) on olive trees soil properties. We measured organic C, nitrogen (N), extractable phosphorus (P), exchangeable calcium (Ca), and exchangeable potassium (K), as well as other properties (pH and electrical conductivity). Our data provide evidence that agronomic application of OMW with PR has important effects on soil properties. Increases in organic C, total N, extractable P and exchangeable potassium (K) were found after the first agronomic application of OMW and PR. These increases were only temporary, following the second agronomic application of OMW and PR, significant reductions were detected in the extractable soil P (19.67 mg kg(-1) in the control soil vs. 8.99 mg kg(-1) in the amended soil). Changes in the extractable soil P could alter plant productivity and plant community structure because shifts in nutriment availability can affect the balance between limiting and non-limiting nutrients.


Preparation and Characterization of Organic-Inorganic Hybrid Macrocyclic Compounds: Cyclic Ladder-like Polyphenylsilsesquioxanes.
Organic-inorganic hybrid macrocyclic compounds, cyclic polyphenylsilsesquioxanes (cyc-PSQs), have been synthesized through hydrolysis and condensation reactions of phenyltrichlorosilane. Structural characterization has revealed that cyc-PSQs consist of a closed-ring double-chain siloxane inorganic backbone bearing organic phenyl groups. The cyc-PSQ molecules have been simulated and structurally optimized using the Forcite tool as implemented in Materials Studio. Structurally optimized cyc-PSQs are highly symmetrical and regular with high stereoregularity, consistent with the dimensions of their experimentally derived structures. Thermogravimetric analysis showed that these macrocyclic compounds have excellent thermal stability. In addition to these perfectly structured compounds, macrocyclic compounds with the same ring ladder structure but bearing an additional Si-OH group, cyc-PSQs-OH, have also been synthesized. A possible mechanism for the formation of the closed-ring molecular structures of cyc-PSQs and cyc-PSQs-OH is proposed.


Thymosin beta 4 binds actin in an extended conformation and contacts both the barbed and pointed ends.
The beta-thymosins are a family of highly polar peptides which serve in vivo to maintain a reservoir of unpolymerized actin monomers. In vitro, beta-thymosins form 1:1 complexes with actin monomers and inhibit both polymerization and exchange of the bound nucleotide. Circular dichroism data indicate that free thymosin beta 4 is predominantly unstructured, containing at most six residues of alpha-helix, and that up to six additional residues may adopt an alpha-helical conformation upon binding actin. NMR data indicate that many parts of thymosin beta 4 are not in tight contact with actin. Contacts between specific residues in actin and thymosin beta 4 were identified by zero-length cross-linking followed by isolation and sequencing of cross-linked peptides. After carbodiimide-mediated cross-linking, Lys-3 of thymosin beta 4 was cross-linked to Glu-167 of actin, and Lys-18 of thymosin beta 4 was cross-linked to one of the the N-terminal acidic residues of actin (Asp-1-Glu-4); the cross-linked actin residues lie within subdomains 3 and 1, respectively. These two contacts flank the alpha-helical region of thymosin beta 4 and place it on the barbed end; thymosin beta 4 can thus block actin polymerization sterically. After transglutaminase-mediated cross-linking, Lys-38 of thymosin beta 4 was cross-linked to Gln-41 of actin, placing the C-terminal region of thymosin beta 4 in contact with subdomain 2 on the pointed end; thymosin beta 4 may sterically block actin polymerization at the pointed end as well as the barbed end of the monomer. The distance between the pointed-end and barbed-end contacts requires that the C-terminal half of thymosin beta 4 be in a predominantly extended conformation.


Enzyme replacement therapy for Farber disease: Proof-of-concept studies in cells and mice.
A series of studies were carried out in Farber disease (OMIM #228000) cells and mice to evaluate the feasibility of enzyme replacement therapy (ERT) for this disorder. Media from Chinese hamster ovary (CHO) cells overexpressing human recombinant acid ceramidase (rhAC) was used to treat fibroblasts from a Farber disease patient, leading to significantly reduced ceramide. We also found that chondrocytes from Farber disease mice had a markedly abnormal chondrogenic phenotype, and this was corrected by rhAC as well. Acute dosing of rhAC in Farber mice confirmed the enzyme's bioactivity in vivo, and showed that it could be safely administered at doses up to 50 mg/kg. These studies also revealed little or no re-accumulation of ceramide in tissues for at least 7 days after enzyme administration. Once weekly administration of rhAC moderately improved survival of the mice, which could be enhanced by starting enzyme administration at an earlier age (3 days vs. 3 weeks). Repeat administration of the enzyme also led to normalization of spleen size, significantly reduced plasma levels of monocyte chemoattractant protein 1 (MCP-1), reduced infiltration of macrophages into liver and spleen, and significantly reduced ceramide and sphingosine in tissues. Overall, we conclude that ERT should be further developed for this debilitating and life-threatening disorder.


Metal and Metalloid Contaminants in Atmospheric Aerosols from Mining Operations.
Mining operations are potential sources of airborne metal and metalloid contaminants through both direct smelter emissions and wind erosion of mine tailings. The warmer, drier conditions predicted for the Southwestern US by climate models may make contaminated atmospheric dust and aerosols increasingly important, with potential deleterious effects on human health and ecology. Fine particulates such as those resulting from smelting operations may disperse more readily into the environment than coarser tailings dust. Fine particles also penetrate more deeply into the human respiratory system, and may become more bioavailable due to their high specific surface area. In this work, we report the size-fractionated chemical characterization of atmospheric aerosols sampled over a period of a year near an active mining and smelting site in Arizona. Aerosols were characterized with a 10-stage (0.054 to 18 μm aerodynamic diameter) multiple orifice uniform deposit impactor (MOUDI), a scanning mobility particle sizer (SMPS), and a total suspended particulate (TSP) collector. The MOUDI results show that arsenic and lead concentrations follow a bimodal distribution, with maxima centered at approximately 0.3 and 7.0 μm diameter. We hypothesize that the sub-micron arsenic and lead are the product of condensation and coagulation of smelting vapors. In the coarse size, contaminants are thought to originate as aeolian dust from mine tailings and other sources. Observation of ultrafine particle number concentration (SMPS) show the highest readings when the wind comes from the general direction of the smelting operations site.


Physical performance and muscle strength rather than muscle mass are predictor of all-cause mortality in hemodialysis patients.
Patients undergoing maintenance hemodialysis usually suffer a high burden of poor functional status. The aim of this study was to investigate the association between muscle mass, muscle strength as well as physical performance with all-cause mortality in hemodialysis patients. 923 hemodialysis patients (565 men, mean aged 61.3 ± 12.7 years) were included from eight facilities in Tianjin and Shanghai of China from 2019 to 2021. Muscle mass was evaluated by skeletal muscle index (SMI) and muscle strength was assessed by handgrip strength. Different measures of physical performance were measured via gait speed, Timed Up and Go Test (TUGT) and short physical performance battery (SPPB). Cox proportional hazards regression models were used to determine the adjusted hazard ratios (HRs) of mortality with 95% confidence intervals (95% CIs) for baseline muscle mass, muscle strength and different measures of physical performance. Additionally, the area under the Receiver Operating Characteristic (ROC) curves were constructed to determine which index is a better predictor of mortality. During a median follow-up of 14 (12-17 months), 79 (8.6%) patients died. Using the Cox regression analysis, we founded that muscle strength and physical performance rather than muscle mass were significantly negatively associated with mortality. The C-index for different measures of physical performance in predicting mortality were 0.709 for SPPB, 0.7 for TUGT and 0.678 for gait speed, respectively. The C-index for muscle strength was 0.635, and the ability of prediction was significantly lower than the physical performance. Physical performance seems to a better indicator of mortality than muscle mass and strength in hemodialysis patients. Simple measures of physical performance may be appropriately used as a screening tool targeting high-risk hemodialysis patients for the prevention of mortality.


Post Hepatitis B vaccination sero-conversion among health care workers in the Cape Coast Metropolis of Ghana.
HBV vaccine is known to offer protection against transmission of HBV infection. Health care workers are mandated to have this vaccination as part of their occupational health safety measures. Post vaccination response data for HCWs in our setting is not available. This study therefore aimed to evaluate the anti-HBs titre levels after Hepatitis B vaccination among HCWs from selected heath facilities in the Cape Coast Metropolis, Ghana. A multicenter (3 selected sites) analytical cross-sectional study involving 711 HCWs was conducted. Five (5mls) of blood samples were collected from each study participant and the serum used for HBV immunological profile testing anti-HBs quantification by ELISA test (Fortress Diagnostics Limited, Northern Ireland, United Kingdom). Data analyses were performed using Stata version 14.0 software (STATA Corp, Texas USA). The median age of participants was 29 years (IQR = 26-35 years). Majority (80.9%, n = 575) took their vaccination from Government health facilities compared with 19.1% (n = 136) from private vaccination sources. A total of 7 (3 males and 4 females) were found to be HBsAg positive giving prevalence of 1%. In all, 8.2% (n = 58) of the HCWs had anti-HBs titre levels <10IU/ml giving a sero-protection rate of 91.8%. HCWs who received 3 doses of HBV vaccine were more likely to be sero-protected as compared to those who received only one dose in multivariate analysis (aOR = 3.39, 95%CI: 1.08-10.67), p<0.037). Gender, cigarette smoking and alcohol consumption were not found to be associated with sero-protection. There is a high HBV vaccine efficacy among HCWs in the Cape Coast Metropolis of Ghana with higher prevalence of anti-HBs titre level associated with full vaccine dose adherence. Post vaccination antibody titre determination could be an integral part of HBV vaccination protocol for HCWs in Ghana.


The thyroid and the gut.
Thyroid disease is common, and its effects on the gastrointestinal system are protean, affecting most hollow organs. Hashimoto disease, the most common cause of hypothyroidism, may be associated with an esophageal motility disorder presenting as dysphagia or heartburn. Dyspepsia, nausea, or vomiting may be due to delayed gastric emptying. Abdominal discomfort, flatulence, and bloating occur in those with bacterial overgrowth and improve with antibiotics. Reduced acid production may be due to autoimmune gastritis or low gastrin levels. Constipation may result from diminished motility, leading to an ileus, megacolon, or rarely pseudoobstruction. Ascites in myxedema is characterized by a high protein concentration. Graves' disease accounts for 60% to 80% of thyrotoxicosis. Hyperthyroidism is accompanied by normal gastric emptying with low acid production, partly due to an autoimmune gastritis with hypergastrinemia. Transit time from mouth to cecum is accelerated, resulting in diarrhea. Steatorrhea is due to hyperphagia and stimulation of the adrenergic system. Diarrhea in medullary carcinoma of the thyroid (MCT) may be due to elevated calcitonin, prostaglandins, or 5-hydroxyindoleacetic acid. Ileal or colonic function may be abnormal. The esophagus may be compressed by benign processes, but more often by malignancies. MRI and CT scans are the best diagnostic modalities. The gastrointestinal manifestations of thyroid disease are generally due to reduced motility in hypothyroidism, increased motility in hyperthyroidism, autoimmune gastritis, or esophageal compression by a thyroid process. Symptoms usually resolve with treatment of the thyroid disease.


O-GlcNAcylated p53 in the liver modulates hepatic glucose production.
p53 regulates several signaling pathways to maintain the metabolic homeostasis of cells and modulates the cellular response to stress. Deficiency or excess of nutrients causes cellular metabolic stress, and we hypothesized that p53 could be linked to glucose maintenance. We show here that upon starvation hepatic p53 is stabilized by O-GlcNAcylation and plays an essential role in the physiological regulation of glucose homeostasis. More specifically, p53 binds to PCK1 promoter and regulates its transcriptional activation, thereby controlling hepatic glucose production. Mice lacking p53 in the liver show a reduced gluconeogenic response during calorie restriction. Glucagon, adrenaline and glucocorticoids augment protein levels of p53, and administration of these hormones to p53 deficient human hepatocytes and to liver-specific p53 deficient mice fails to increase glucose levels. Moreover, insulin decreases p53 levels, and over-expression of p53 impairs insulin sensitivity. Finally, protein levels of p53, as well as genes responsible of O-GlcNAcylation are elevated in the liver of type 2 diabetic patients and positively correlate with glucose and HOMA-IR. Overall these results indicate that the O-GlcNAcylation of p53 plays an unsuspected key role regulating in vivo glucose homeostasis.


Treatment Recruitment and Retention of Geriatric Participants With Hoarding Disorder.
This study describes the initial contact of 255 potential participants, recruitment of 63 participants, and retention of 57 participants from three geriatric Hoarding Disorder (HD) studies. Patients with HD were easily recruited from the community, primarily through the use of clinician referrals and posted flyers, as evidenced by steady patient flow despite lack of compensation for participation. Contrary to treatment outcomes of late life mood and anxiety disorders, geriatric HD patients are largely retained in clinical research treatment studies. Results demonstrate that older adults with HD can be engaged in treatment. Participants often needed the study staff to provide substantial support, including informal motivational interviewing and problem solving, in scheduling and attending the initial visit.


Construction of a redox-responsive drug delivery system utilizing the volume of AS1411 spatial configuration gating mesoporous silica pores.
In recent years, diverse redox-responsive drug delivery systems have emerged to prevent premature drug release and reduce drug toxicity in the human body in cancer treatment. In this paper, we put forward a view of directly utilizing the spatial structure size of the AS1411 aptamer as the nano-gatekeeper on the pore openings of MCM-41 type mesoporous silica and thus constructed a redox-responsive drug delivery system named MCM-41-SS-AS1411. The particles obtained at each step were characterized by TEM, FTIR, SXRD, TGA and zeta potential measurement. The characterization data confirmed that the particles were successfully prepared. The binding amount of the aptamer was ca. 3.1 × 103 for each carrier particle averagely. The anticancer drug Dox was regarded as a drug model to investigate the redox-controlled drug release behavior by fluorescence measurements. The investigation results demonstrate that the spatial volume of aptamer AS1411 can block the mesopore, and this drug-carrier can realize controlled drug release by GSH. We hope this idea can play a prompt role in relevant research. Meanwhile, the preparation steps of this DDS are simplified.


Binding Protein-Dependent Uptake of Maltose into Cells via an ATP-Binding Cassette Transporter.
Maltose and maltodextrins are actively transported across the cytoplasmic membrane of Escherichia coli and Salmonella by a periplasmic binding protein (BP)- dependent transport system. Since 1996, there have been many advances in the understanding of the structure and mechanism of the maltose transporter, in the assembly of the membrane-associated transporter complex, and in the mechanism of regulation of transport both at the DNA and the protein level. The transporter has been studied in detergent and reconstituted in liposome vesicles, and while many features, including the ability of maltose-binding protein (MBP) to stimulate ATPase activity, are retained in detergent, it has been noted that the basal ATPase activity of the transporter is elevated in detergent compared with liposomes. This review focuses on these recent developments, which have culminated in a high resolution structure of MBP in a complex with the MalFGK2 transporter. While this review focuses on the maltose system, complementary work has been carried out on many different ATP binding cassette (ABC) transporters, all of which has contributed in important ways to the understanding of the maltose transport system. The regulation of the maltose transport system, at the DNA level, is implemented by the synergistic action of MalT and cAMP/CAP complex and, at the protein level, by interactions of MalK with unphosphorylated EIIAglc, a signal-transducing component of the phosphoenolpyruvate-glucose phosphotransferase system.


[Revascularization of the penis].
Revascularization of the penis is indicated in those patients in whom peripheral arterial occlusion of the internal pudendal artery alone or in combination with the venous incompetence of the penis, was detected to be the cause of erectile dysfunction. The authors present the results of penile revascularization in 12 patients impotent after crushing pelvic fracture associated with urethral rupture. Revascularization of the dorsal artery of the penis by the inferior epigastric artery was used as the method of surgical treatment. Satisfactory functional results were achieved in 58% of patients. In other 8 patients with combined arteriogenic and venogenic impotence, arterialization of the venous system of the penis was utilized. In 6 patients the method of "triple" anastomosis of the inferior epigastric artery, dorsal artery of the penis, and penile deep dorsal vein was used. In 2 cases the deep dorsal vein of the penis was arterialized by the inferior epigastric artery. The cumulative success rate of venous arterialization of the penis was 62.5%. (Fig. 5, Ref. 15.)


Prehospital-initiated vs hospital-initiated thrombolytic therapy. The Myocardial Infarction Triage and Intervention Trial.
To determine the effect of prehospital-initiated vs hospital-initiated treatment of myocardial infarction on clinical outcome. Randomized, controlled clinical trial. Multicenter study involving 19 hospitals and all paramedic systems in the Seattle, Wash, metropolitan area. A total of 360 patients with symptoms for 6 hours or less, no risk factors for serious bleeding, and ST-segment elevation were selected by paramedics and a remote physician for inclusion into the trial. They represented 4% of patients with chest pain who were screened and 21% of those with acute infarction. Patients were allocated to have aspirin and alteplase treatment initiated before or after hospital arrival. Intravenous sodium heparin was administered to both groups in the hospital. The primary endpoint was a ranked composite score (combining death, stroke, serious bleeding, and infarct size). The relation between time to treatment and outcome (composite score, infarct size, ejection fraction, and mortality) was also assessed. Initiating treatment before hospital arrival decreased the interval from symptom onset to treatment from 110 to 77 minutes (P < .001). Although more patients whose therapy was initiated before hospital arrival had resolution of pain by admission (23% vs 7%; P < .001), there were no significant differences in the composite score (P = .64), mortality (5.7% vs 8.1%), ejection fraction (53% vs 54%), or infarct size (6.1% vs 6.5%). A secondary analysis of time to treatment and outcome showed that treatment initiated within 70 minutes of symptom onset was associated with better outcome (composite score, P = .009; mortality, 1.2% vs 8.7%, P = .04; infarct size, 4.9% vs 11.2%, P < .001; and ejection fraction, 53% vs 49%, P = .03) than later treatment. Identification of patients eligible for thrombolysis by paramedics reduced the hospital treatment time from 60 minutes (for patients not in the study) to 20 minutes (for study patients allocated to begin treatment in the hospital). There was no improvement in outcome associated with initiating treatment before hospital arrival; however, treatment within 70 minutes of symptom onset--whether in the hospital or in the field--minimized the infarct process and its complications.


Evolving role of positron emission tomography (PET) in urological malignancy.
We present a review on the increasing indications for the use of positron emission tomography (PET) in uro-oncology. In this review we describe the details of the different types of PET scans, indications for requesting PET scans in specific urological malignancy and the interpretation of the results.


Regulation of Dendrobium Polysaccharides on Proliferation and Oxidative Stress of Human Umbilical Vein Endothelial Cells in the High Glucose Environment.
Polysaccharides of Dendrobium candidum (PDC) showed a strong antioxidant effect on islet cells while the effects of PDC on human umbilical vein endothelial cells (HUVECs) under the high glucose condition remain unclear. Material and Method. HUVECs were incubated with high glucose (33.3 mmol/L) for 48 hours to induce injury, and cells were treated with PDC (100, 200, and 400 μg/mL) for 48 hours. The tetrazolium blue colorimetric (MTT) assay was used to detect cell proliferation, superoxide dismutase (SOD), and nitric oxide (NO) content in cell supernatants. Flow cytometry was used to detect reactive oxygen species (ROS) and calcium levels. (1) Compared with the control group, the proliferation of HUVECs cells in the high glucose (33.3 mmol/L) group decreased (P < 0.05). The intracellular calcium ion concentration and the intracellular ROS level increased (P < 0.01 and P < 0.05). SOD activity and the level of NO in the culture medium were reduced (P <0.05). (2) Compared with the control group, PDC (50, 100, 200, 400, and 800 μg/mL) did not significantly affect the cell proliferation of HUVECs (P > 0.05). (3) Compared with the high glucose group, the HUVEC cell viability of the high glucose + PDC (100, 200, and 400 μg/mL) group increased while the intracellular calcium ion concentration decreased in a concentration-dependent manner (P < 0.05). Intracellular ROS levels were reduced, while SOD activity and the level of NO in culture fluids increased (P < 0.05). PDC can promote the proliferation of HUVECs in the high glucose environment by reducing oxidative stress injury of HUVECs induced by high glucose.


Pleomorphism of Premature Ventricular Complexes originating from Papillary Muscles and their Myocardial Connections.
Patients with arrhythmias originating from papillary muscles (PAP) often have pleomorphic ventricular arrhythmias (PVA) that can result in failed ablations. The mechanism of PVAs is unknown. The purpose of this study was to assess the prevalence, mechanisms of PVAs and impact on outcomes in patients with focal left ventricular (LV) PAP VAs. The sites of origin (SOO) of VAs in 43 consecutive patients referred for ablation of focal LV PAP VAs were determined by activation and pace-mapping. SOOs were classified as 1. unifocal generating a single VA morphology, 2. unifocal from a deeper-seated origin generating multiple VA morphologies, 3. unifocal located on a PAP branching site, 4. multifocal from a single or multiple PAPs generating multiple VA morphologies, and 5. multifocal from a PAP and a different anatomic source. Most patients had multiple morphologies (n=34,79%) and multiple mechanisms (79%) generating the different VA morphologies. Most of the patients with PVAs had multiple SOOs from a single or different PAPs (n=23, 68%) followed by patients with SOOs from PAP and non-PAP sites (n=19, 56%). In 13 patients (38%) single SOOs accounted for the observed PVAs. The frequent observation (n=20) of changing QRS morphologies after RF delivery targeting a single VA suggests the presence of a deeper focus with changing sites of preferential conduction. VA pleomorphism in patients with PAP arrhythmias is most often due to PVCs originating from different SOOs. The second most common cause is preferential conduction from a single SOO via PAP branching sites.


Personal attitudes toward time: The relationship between temporal focus, space-time mappings and real life experiences.
What influences how people implicitly associate "past" and "future" with "front" and "back?" Whereas previous research has shown that cultural attitudes toward time play a role in modulating space-time mappings in people's mental models (de la Fuente, Santiago, Román, Dumitrache & Casasanto, 2014), we investigated real life experiences as potential additional influences on these implicit associations. Participants within the same single culture, who are engaged in different intermediate-term educational experiences (Study 1), long-term living experiences (Study 2), and short-term visiting experiences (Study 3), showed their distinct differences in temporal focus, thereby influencing their implicit spatializations of time. Results across samples suggest that personal attitudes toward time related to real life experiences may influence people's space-time mappings. The findings we report on shed further light on the high flexibility of human conceptualization system. While culture may exert an important influence on temporal focus, a person's conceptualization of time may be attributed to a culmination of factors.


Omphalocele and gastroschisis: an 18-year review study.
Using data from a single University Genetics Division practice, the authors sought to determine if gastroschisis is increasing in occurrence compared to omphalocele. Associated abnormalities were also examined. In addition, prenatal exposure to teratogens and other parameters were compared. All fetal and infant cases of omphalocele and gastroschisis seen in the University of South Florida Division of Genetics between January 2, 1982 and December 31, 1999 were retrieved through the database and analyzed through chart review. There were 127 cases of omphalocele and 121 cases of gastroschisis. Ninety-three of the 127 probands with omphalocele had karyotype determinations and 20% were abnormal; for gastroschisis, 37 had cytogenetic studies and none had chromosomal anomalies. Seventy-six percent of the probands with omphalocele had associated abnormalities; twenty-three percent of the probands with gastroschisis, none of which were syndromic, had associated anomalies. The prematurity rate for omphalocele was 42% and mortality was 22%; for gastroschisis, the figures were 57% and 9%, respectively. There were no significant differences in teratogen exposure between the two groups. Familial cases of both defects occurred in < 4%, and the prevalence of dizygous twinning was increased in both groups. Mean maternal age was 21.8 years for the gastroschisis group, 27.2 years for the omphalocele group. In this study, the number of cases of omphalocele and gastroschisis were similar, compared to the expected 3:2 ratio, suggesting an increase in the occurrence of gastroschisis. Cases with omphalocele had more syndromic and nonsyndromic anomalies, more chromosomal anomalies, a higher mortality rate, and older mothers.


Thromboangiitis obliterans with cryoglobulinemia.
Thromboangiitis obliterans (TAO), or Buerger's disease, is a vascular occlusive disease associated with cigarette smoking. It typically affects medium sized vessels of extremities. Basic pathology of TAO is described to be endothelial activation with highly inflammatory intraluminal thrombosis preserving internal elastic membrane. Cryoglobulins are immunoglobulins that precipitate in the cold and dissolve on re-warming. Cryoglobulinemic vasculitis is a typical small vessel disease associated with cryoglobulinemia commonly bearing typical purpuric skin lesions. An association of TAO with cryoglobulinemia is not reported yet. We report a 34-year-old male heavy cigarette smoker seen for extremity pain and cyanosis of left little finger along with skin rashes characteristic of small vessel disease. Initial presentation of his symptoms at winter and unusual purpuric skin lesions led to search for cold-agglutinating globulins in his plasma. He had severe cryoglobulinemia while the other laboratory tests were normal. TAO associated with cryoglobulinemia merges as a possibility.


Seed limitation restricts population growth in shaded populations of a perennial woodland orchid.
Seed production and seedling recruitment are thought to be of minor importance in determining population dynamics and long-term viability in long-lived perennial plants. Seed addition experiments, on the other hand, have amply shown that supplemental addition of seeds almost always, irrespective of longevity, results in increased seedling recruitment. Any change in the environment that affects fruit and seed production can thus be expected to affect seedling recruitment, but the extent to which increased fruit and seed production affect overall population dynamics remains relatively unknown. In this paper, we present demographic data of six populations of the long-lived woodland orchid Orchis purpurea that were monitored for seven consecutive years (2002-2008) occurring in two contrasting light environments. We use a nested life table response experiment (LTRE) at the vital rate level to disentangle the relative contributions of each of six annual transitions, six sites, and two light environments on the population dynamics of this species and to determine vital rate variations that contributed most to variation in population growth rate. Population growth rates (lamda) were significantly higher in the light environment than in the shaded environment (average lamda = 0.9930 and 1.0492 in the shaded and light environment, respectively). The LTRE analysis showed that variation in fecundity and, to a lesser extent, variation in growth made the largest total contributions to variation in lamda, whereas the contributions of variation in survival were almost negligible. Fruit production was two times larger and the net reproductive rate (R0) was approximately six times higher in the light environment than in shaded areas, suggesting that variables related to reproduction are the key drivers of population dynamics of this long-lived orchid species in different light environments. Our results indicate that light is an important factor affecting population dynamics of Orchis purpurea and illustrate that, even in long-lived species, flower and seed production can have important effects on the population dynamics.


Upregulation of microRNA-125b-5p alleviates acute liver failure by regulating the Keap1/Nrf2/HO-1 pathway.
Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are the two most common subtypes of liver failure. They are both life-threatening clinical problems with high short-term mortality. Although liver transplantation is an effective therapeutic, its application is limited due to the shortage of donor organs. Given that both ACLF and ALF are driven by excessive inflammation in the initial stage, molecules targeting inflammation may benefit the two conditions. MicroRNAs (miRNAs) are a group of small endogenous noncoding interfering RNA molecules. Regulation of miRNAs related to inflammation may serve as promising interventions for the treatment of liver failure. To explore the role and mechanism of miR-125b-5p in the development of liver failure. Six human liver tissues were categorized into HBV-non-ACLF and HBV-ACLF groups. Differentially expressed miRNAs (DE-miRNAs) were screened and identified through high-throughput sequencing analysis. Among these DE-miRNAs, miR-125b-5p was selected for further study of its role and mechanism in lipopolysaccharide (LPS)/D-galactosamine (D-GalN) -challenged Huh7 cells and mice in vitro and in vivo. A total of 75 DE-miRNAs were obtained. Of these DE-miRNAs, miR-125b-5p was the focus of further investigation based on our previous findings and preliminary results. We preliminarily observed that the levels of miR-125b-5p were lower in the HBV-ACLF group than in the HBV-non-ACLF group. Meanwhile, LPS/D-GalN-challenged mice and Huh7 cells both showed decreased miR-125b-5p levels when compared to their untreated control group, suggesting that miR-125b-5p may have a protective role against liver injury, regardless of ACLF or ALF. Subsequent results revealed that miR-125b-5p not only inhibited Huh7 cell apoptosis in vitro but also relieved mouse ALF in vivo with evidence of improved liver histology, decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and reduced tumor necrosis factor-α (TNF-α) and IL-1β levels. Based on the results of a biological prediction website, microRNA.org, Kelch-like ECH-associated protein 1 (Keap1) was predicted to be one of the target genes of miR-125b-5p, which was verified by a dual-luciferase reporter gene assay. Western blot results in vitro and in vivo showed that miR-125b-5p could decrease the expression of Keap1 and cleaved caspase-3 while upregulating the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1(HO-1). Upregulation of miR-125b-5p can alleviate acute liver failure by regulating the Keap1/Nrf2/HO-1 pathway, and regulation of miR-125b-5p may serve as an alternative intervention for liver failure.


High-power thermally guiding index-antiguiding-core fibers.
We investigate high-power operation of a very-large-mode-area (VLMA) fiber concept based on an index-antiguiding, thermally guiding core in which an ytterbium-doped region is completely surrounded by silica with a slightly higher refractive index. Experimentally, regimes of antiguidance, single-mode operation, and mode instabilities predominantly with radially symmetric higher-order modes are observed. Fundamental limitations for conventional VLMA step-index fibers are discussed.


Synaptic mechanisms of associative memory in the amygdala.
Do associative learning and synaptic long-term potentiation (LTP) depend on the same cellular mechanisms? Recent work in the amygdala reveals that LTP and Pavlovian fear conditioning induce similar changes in postsynaptic AMPA-type glutamate receptors and that occluding these changes by viral-mediated overexpression of a dominant-negative GluR1 construct attenuates both LTP and fear memory in rats. Novel forms of presynaptic plasticity in the lateral nucleus may also contribute to fear memory formation, bolstering the connection between synaptic plasticity mechanisms and associative learning and memory.


Hepatic portal vein gas following endoscopic retrograde cholangiography with sphincterotomy. Case report.
In a 60-year-old woman, endoscopic retrograde choledochography with sphincterotomy was followed by appearance of gas in the portal venous system. Venous bleeding was seen immediately after completion of sphincterotomy. The patient recovered well. Even in the absence of duodenal perforation, sphincterotomy may be complicated by hepatic portal venous gas.


A rare case of portal vein gas: accidental hydrogen peroxide ingestion.
Hydrogen peroxide (H(2)O(2)) is a colourless and odourless liquid with oxidant characteristics used for various purposes. Whereas in lower concentrations (3%), H(2)O(2) is used as a disinfectant in home cleaning products and wound care, in higher concentrations (35%) it is used in textile and paper industry as a bleaching agent and is diluted for use in lightening hair dyes. Like other caustic substances, direct injuries may develop if H(2)O(2) is swallowed and systemic air embolisms may occur due to the resultant gaseous oxygen. This study discusses a patient who was detected with the presence of gas in the portal venous system due to H(2)O(2) intoxication and was treated conservatively.


Hamstring muscle fibre typology is not associated with hamstring strain injury history or performance in amateur male soccer players: a retrospective magnetic resonance spectroscopy study.
Hamstring strain injuries (HSI) are still the most common injuries in soccer. Recent research has been focusing on the role of hamstring muscle morphology and architecture. The hamstring's fibre type composition might play a role as well, but this has never been investigated in the light of HSI risk in an athletic population. The purpose of this study was to investigate the association between hamstring muscle fibre type, hamstring strain injury history (HSIH), performance and isokinetic strength in a population of amateur male soccer players. In this cross-sectional observational study, 44 male soccer players (22 with and 22 without HSIH) participated. The research consisted of a non-invasive fibre composition evaluation using proton magnetic resonance spectroscopy (1H-MRS), functional performance (evaluated by means of maximal jumping height, maximal sprinting speed and hamstring muscle strength endurance (single leg hamstring bridge testing)), and isokinetic strength testing. The results revealed that hamstring carnosine concentration demonstrated a high inter-individual variability within this soccer population and was not significantly associated with either HSIH or with any of the functional performance parameters. The only secondary outcome measure presenting a significant association with the intramuscular carnosine content was the hamstrings' explosive strength production capacity, objectified by means of the time to peak torque (TPT), measured concentrically at an angular velocity of 240 degrees/second (°/s) during isokinetic strength testing. This TPT was significantly shorter in players presenting higher carnosine concentrations (p = 0.044). The findings indicate that in male amateur soccer players (1) the hamstrings have no distinct fibre type dominance and (2) fibre typology in this population does not relate to HSIH or performance.


Structure, dynamics, and electronic properties of lithium disilicate melt and glass.
Ab initio molecular dynamics simulations within the framework of density functional theory have been performed to study the structural, dynamic, and electronic properties of lithium disilicate melt and the glass derived from quenching the melt. It is found that lithium ions have a much higher diffusion coefficient and show different diffusion mechanisms than the network forming silicon and oxygen ions in the melt. The simulated lithium disilicate glass structure has 100% four coordinated silicon, close to theoretical nonbridging oxygen to bridging oxygen ratio (2:3), and Q(n) distributions of 20.8%, 58.4%, and 20.8% for n=2,3,4, respectively. In the melt there are considerable amounts (10%-15%) of silicon coordination defects; however, the average silicon coordination number remains about 4, similar to that in the glass. The lithium ion coordination number increases from 3.7 in the glass to 4.4 in the melt mainly due to the increase of bridging oxygen in the first coordination shell. The bond length and bond angle distributions, vibrational density of states, and static structure factors of the simulated glass were determined where the latter was found to be in good agreement with experimental measurement. Atomic charges were obtained based on Bader and Hirshfeld population analyses [Atoms in Molecule: A Quantum Theory (Oxford University Press, Oxford, 1990); Theor. Chim. Acta 44, 129 (1977)]. The average Bader charges found in lithium disilicate glass were -1.729, 3.419, and 0.915 for oxygen, silicon, and lithium, respectively. The corresponding Hirshfeld charges were -0.307, 0.550, and 0.229. The electronic densities of states of the melt and glass were calculated and compared with those of crystalline lithium disilicate.


Antibacterial Efficacy of Green Synthesized Silver Nanoparticles Using Salvia nubicola Extract against Ralstonia solanacearum, the Causal Agent of Vascular Wilt of Tomato.
Ralstonia solanacearum is a phytopathogen causing bacterial wilt diseases of tomato and affecting its productivity, which leads to prominent economic losses annually. As an alternative to conventional pesticides, green synthesized nanoparticles are believed to possess strong antibacterial activities besides being cheap and ecofriendly. Here, we present the synthesis of silver nanoparticles (Sn-AgNPs) from medicinally important aqueous plant extracts of Salvia nubicola. Characterization of biologically synthesized nanoparticles was performed through UV-vis spectrophotometry, Fourier transform infrared spectroscopy (FTIR), energy-dispersive X-ray spectroscopy, X-ray diffraction, scanning electron microscopy, transmission electron microscopy (TEM), and thermogravimetric analysis. The antibacterial activity of the biosynthesized silver nanoparticles was tested against the phytopathogen R. solanacearum through in vitro experiments. Preliminary phytochemical analysis of the plant extracts revealed the presence of substantial amounts of flavonoids (57.08 mg GAE/g), phenolics (42.30 mg GAE/g), tannins, and terpenoids. The HPLC phenolic profile indicated the presence of 25 possible bioactive compounds. Results regarding green synthesized silver nanoparticles revealed the conformation of different functional groups through FTIR analysis, which could be responsible for the bioreduction and capping of Ag ions into silver NPs. TEM results revealed the spherical, crystalline shape of nanoparticles with the size in the range of 23-63 nm, which validates SEM results. Different concentrations of Sn-AgNPs (T1 (500 μg/mL) to T7 (78.1 μg/mL)) with a combination of plant extracts (PE-Sn-AgNPs) and plant extracts alone exhibited an efficient inhibition of R. solanacearum. These findings could be used as an effective alternative preparation against the bacterial wilt of tomato.


Comparison of partial excision with simple section of the transverse carpal ligament in the treatment of carpal tunnel syndrome.
In the surgical treatment of carpal tunnel syndrome, debate has commonly focused on whether decompression should be performed by open or blind techniques. Contrarily, the goal of the present study was to determine whether instead of simple section, partial excision of the transverse carpal ligament has contributed to better results. Because complete healing of the transverse carpal ligament observed during reoperations has been reported elsewhere, the charts of 75 carpal tunnel syndrome patients who had been treated with open technique at Dokuz Eylül University were reviewed. Statistical analysis was performed using the Fisher's exact test and Student's t test when appropriate. Thirty-five patients had been treated with simple section of the transverse carpal ligament, whereas 40 had been treated with partial excision. Internal neurolysis was also performed in 19 of the patients, 11 of whom were treated with partial excision. The average follow-up time was 3.8 years. The comparisons regarding the overall operative outcomes did not show any significant difference between the two different techniques of releasing the transverse carpal ligament. In patients treated without neurolysis, results of partial excision of the transverse carpal ligament improved when compared with those of simple section, but this superiority was not statistically significant. There seemed to be statistically higher reoperation rates and worse outcomes after neurolysis (p < 0.05). Reoperation was required in eight patients (11 percent). Five of the patients who underwent reoperation had initially been treated with partial excision and neurolysis, whereas two had been treated with simple section and neurolysis. Another patient who had undergone reoperation had initially undergone only simple section. The mean time to return to work or daily activities did not differ between the types of applied technique for releasing the transverse carpal ligament. However, neurolysis lengthened these periods significantly when performed (p < 0.05). In the present study, partial excision of the transverse carpal ligament without adding neurolysis offered relatively better results than simple section. Verification of this finding endoscopically, if applicable, may improve the success rate of surgical therapy in patients with carpal tunnel syndrome.


Quercetine attenuates the gentamicin-induced ototoxicity in a rat model.
The aim of this study is to evaluate the protective role of quercetin in gentamicin-induced ototoxicity through an auditory brainstem response (ABR) test and a histopathological evaluation of the cochlea. In this study, 48 female adult Sprague-Dawley rats aged 20-22 weeks and weighing 200-250g were used. An ABR test was carried out on all rats prior to drug administration, after which, the rats were divided into four groups of 12 animals each. Drug administration was gentamicin 120mg/kg plus ethanol in group one; gentamicin 120mg/kg plus quercetin 15mg/kg in group two; quercetin 15mg/kg in group three; and ethanol in group four. The drugs were administered intraperitoneally once a day for two weeks, and the ABR test was repeated after drug administration. Subsequently, the rats were sacrificed and their cochleae were dissected and examined histopathologically. There was no significant difference between the pre-treatment ABR measurement values of the groups. However, a significant increase was detected in the ABR values in the group of rats that were administered gentamicin plus ethanol, while no statistically significant increase was found in the ABR values in the groups administered with gentamicin plus quercetin; quercetin alone; and ethanol alone. The number of TUNEL positive cells in the inner and outer hair cells in the Corti organ was found to be fewer, and Caspase 3 and 9 expressions were found to be weaker in the group receiving gentamicin plus quercetin than in the group receiving gentamicin plus ethanol. Auditory function was detected to be significantly protected and apoptotic cells were found to be decreased when quercetin was administered together with gentamicin. From these results it was concluded that quercetin, a powerful antioxidant, attenuates ABR thresholds and histopathological lesions in the cochlea in gentamicin-induced ototoxicity in rats.


Interdisciplinary Citizen Science and Design Projects for Hazard and Disaster Education.
Disaster science is increasingly incorporating interdisciplinary methods and participatory research techniques. Yet, traditional higher education programs remain focused on lecture. More examples of educational efforts that meet these need of future researchers and practitioners to foster collaborate across disciplines and with communities are needed. This paper describes one such effort that included three projects co-designed and co-led by university students, faculty, and community residents to address flooding challenges in socially vulnerable neighborhoods. This paper overviews the educational program, the three projects, provides feedback from graduate and undergraduate students who helped initiated these efforts, and discusses benefits and challenges for similar interdisciplinary and participatory educational programs. Benefits for students include increased interdiciplinary dialogue, improved science communication, increased research participation, real-world research experience, and awareness of resident perspectives and knowledge. Challenges, though, are a lack of cultural competency among students, time needed to earn resident trust, and mismatched community, academic, and student schedules.


A tracer study with systemically and locally administered dinitrophenylated osteopontin.
Osteopontin (OPN), a major non-collagenous matrix protein of bone, is also found in tissue fluids and in the circulation. It is still not clear whether circulating OPN contributes to bone formation. To elucidate this question, rat OPN was tagged with dinitrophenol groups and administered to rats either intravenously or by infusion with an osmotic minipump through a "surgical window" in the bone of the hemimandible. Dinitrophenylated rat albumin (ALB) was used as a control. The presence and distribution of tagged proteins were revealed by immunogold labeling on sections of tibia and alveolar bone. Tagged molecules of OPN were found in mineralization foci, surfaces and interfaces, and matrix accumulations among calcified collagen fibrils. Even though dinitrophenylated ALB was administered at several-fold higher concentrations, it did not accumulate in these sites. These results show that circulating OPN can be incorporated into specific compartments of forming bone and suggest that such molecules may play a more important role than previously suspected.


[Access to health care for destitute persons at Public Assistance Hospitals in Paris].
All legal French residents are entitled to health care. The 1992 regulatory measures, which create a contractual agreement between the government and public medical institutions, aim at facilitating access to health care by resolving the financial obstacles to accessing health care. The Assistance Publique-Hôpitaux de Paris (AP-HP) has set up a medical reception center in several hospitals since 1993. This system is integrated in the general structure of each hospital: in some cases, there is a single and centralized unit; in other cases, all departments of the hospital, including the emergency room, are involved in caring for destitute patients. Whatever the type of the structure may be, social workers are a key element to helping the patients recover their social rights. Thirty to seventy-percent of patients visiting these centers regain access to social and health care coverage. The epidemiological survey of the active file of patients revealed that 70% are male, more than 50% are non-French nationals, half of which do not have legal immigration status in France. Homeless people represent 40 to 80% of the population. The average age is around 35. The number of medical visits varies greatly from one hospital to another and range from 20 to 60 per month. The reasons for visiting the center and the identified medical disorders are strongly related to the patients' life conditions and vary significantly with the risk factors related to the social and economic situation. The frequency of some diseases (psychiatric disorders, tuberculosis, infections by the HIV and HCV) is higher in this population than in general population. Delayed visits to the medical center represents a severity factor. The hospitals' mission statement is not only to ensure that patients facing a precarious social and professional situation have equal access to health care, but also to help such patients recover their social rights, facilitate their integration in the society and fight against social exclusion.


Suppressed diluting segment reabsorption in Bartter's syndrome: studies in 1 patient and synthesis of literature data.
We analyzed renal sodium handling in a patient with Bartter's syndrome after equilibration on diets containing 200 and 700 mmol NaCl/day. No potassium supplements were given. Clearance studies were performed during maximal water diuresis, maximal free water clearance was taken as measure of diluting segment sodium reabsorption. A normal reference frame of diluting segment NaCl reabsorption at varying delivery rates to that segment was drawn from data collected in similarly studied normal subjects after equilibration on low (20 and 200 mmol/day) or very high (916-1,224 mmol/day) sodium intakes. The results were compatible with a defect in diluting segment reabsorption in the patient, which appeared more pronounced during the high sodium intake. Recent reports do not agree with the existence of such a defect in Bartter's syndrome. One of the reasons of this difference may be the lack of a proper reference frame in previously published studies. We, therefore, compared clearance data in adults with Bartter's syndrome published by others with our studies in normals. Our analysis showed that in Bartter's syndrome (1) a moderate diluting segment NaCl reabsorption defect is often present, and (2) the proximal reabsorption is frequently elevated relative to sodium intake. Severely suppressed diluting segment reabsorption and relatively low proximal reabsorption may also occur, particularly in association with salt loading or reduced glomerular filtration. It seems, therefore, that much of the continuing controversy on renal sodium handling in Bartter's syndrome may be solved by using the proper frame of reference.


Brain-specific homeobox Bsx specifies identity of pineal gland between serially homologous photoreceptive organs in zebrafish.
The pineal gland functioning as a photoreceptive organ in non-mammalian species is a serial homolog of the retina. Here we found that Brain-specific homeobox (Bsx) is a key regulator conferring individuality on the pineal gland between the two serially homologous photoreceptive organs in zebrafish. Bsx knock-down impaired the pineal development with reduced expression of exorh, the pineal-specific gene responsible for the photoreception, whereas it induced ectopic expression of rho, a retina-specific gene, in the pineal gland. Bsx remarkably transactivated the exorh promoter in combination with Otx5, but not with Crx, through its binding to distinct subtypes of PIRE, a DNA cis-element driving Crx/Otx-dependent pineal-specific gene expression. These results demonstrate that the identity of pineal photoreceptive neurons is determined by the combinatorial code of Bsx and Otx5, the former confers the pineal specificity at the tissue level and the latter determines the photoreceptor specificity at the cellular level.


Advertising and prescription drugs: promotion, education, and the public's health.
The data presented by Joel Weissman and colleagues and by Robert Dubois do not justify the conclusions that the effects of pharmaceutical promotion are beneficial. Among consumers of direct-to-consumer advertising (Weissman and colleagues), those heavily influenced by such promotion were no more likely than others were to have new conditions diagnosed or confirmed and were much less likely to have laboratory studies ordered or lifestyle changes recommended. A second study (Dubois) arguing that drug advertising improves the appropriateness of prescribing relies on unconvincing ecological arguments. A greater presence of noncommercial, public health-oriented communication would make a more useful and cost-effective impact on the nation's health.


Advances in the pathogenesis representing definite outcomes in chronic urticaria.
We reviewed in this article, the recent advances in CSU physiopathology and potential clinical and laboratory biomarkers in CSU. In addition to the central role of mast cells in urticaria physiopathology, increased interest in basophils has arisen. Recent data corroborate the autoimmunity pathway as one of the main pathways in mast cell activation. The association of inflammatory cytokines, heat shock proteins and staphylococcal infection with CSU are also reviewed. C-reactive protein, D-dimers, autologous serum skin test, IgE levels and FcεRI expression in basophils have shown their potential as biomarkers for disease duration, activity, severity and/or response to treatment. A comprehensive understanding of chronic spontaneous urticaria mechanisms is essential to find novel biomarkers and treatments. The use of these biomarkers in clinical practice will guide us in choosing the best treatment option for our patients.


Observation of density-induced tunneling.
We study the dynamics of bosonic atoms in a tilted one-dimensional optical lattice and report on the first direct observation of density-induced tunneling. We show that the interaction affects the time evolution of the doublon oscillation via density-induced tunneling and pinpoint its density and interaction dependence. The experimental data for different lattice depths are in good agreement with our theoretical model. Furthermore, resonances caused by second-order tunneling processes are studied, where the density-induced tunneling breaks the symmetric behavior for attractive and repulsive interactions predicted by the Hubbard model.


Role of surgical resection for non-colorectal non-neuroendocrine liver metastases.
It is widely accepted that the indications for hepatectomy in colorectal cancer liver metastases and liver metastases of neuro-endocrine tumors result in relatively better prognoses, whereas, the indications and prognoses of hepatectomy for non-colorectal non-neuroendocrine liver metastases (NCNNLM) remain controversial owing to the limited number of cases and the heterogeneity of the primary diseases. There have been many publications on NCNNLM; however, its background heterogeneity makes it difficult to reach a specific conclusion. This heterogeneous disease group should be discussed in the order from its general to specific aspect. The present review paper describes the general prognosis and risk factors associated with NCNNLM while specifically focusing on the liver metastases of each primary disease. A multidisciplinary approach that takes into consideration appropriate timing for hepatectomy combined with chemotherapy may prolong survival and/or contribute to the improvement of the quality of life while giving respite from systemic chemotherapy.


Pre-equating: a simulation study based on a large scale assessment model.
Although post-equating (PE) has proven to be an acceptable method in the scaling and equating of items and forms, there are times when the turn-around period for equating and converting raw scores to scale scores is so small that PE cannot be undertaken within the prescribed time frame. In such cases, pre-equating (PrE) could be considered as an acceptable alternative. Assessing the feasibility of using item calibrations from the item bank (as in PrE) is conditioned on the equivalency of the calibrations and the errors associated with it vis a vis the results obtained via PE. This paper creates item banks over three periods of item introduction into the banks and uses the Rasch model in examining data with respect to the recovery of item parameters, the measurement error, and the effect cut-points have on examinee placement in both the PrE and PE situations. Results indicate that PrE is a viable solution to PE provided the stability of the item calibrations are enhanced by using large sample sizes (perhaps as large as full-population) in populating the item bank.


[Development and Application of Ontology of Cancer Hallmarks].
Objective To develop a traceable cancer hallmark ontology with terminology including gene mutation,cancer hallmark,and cell line for knowledge integration,standardization,correlation,and discovery.Methods The Ontology Development 101 and the current ontology development methods were employed to determine the content coverage,structural layers,reusable terms,and new terms of the cancer hallmark ontology.Taking colorectal cancer as a study case,we extracted the knowledge related with colorectal cancer hallmarks using text mining and text classification technology from PubMed,and then formalized the extracted knowledge into the cancer hallmark ontology.Moreover,we made use of existing cancer hallmark evidence in Catalogue of Somatic Mutations in Cancer and further semantic retrieval to discover new knowledge.Results The established cancer hallmark ontology comprised 9910 classes and 6138 instances,which realized the semantic representation of 2310 article abstracts about colorectal cancer and 26 pieces of evidence about genes and their cancer hallmarks.Compared with the Catalogue of Somatic Mutations in Cancer,new evidence for more genes associated with colorectal cancer hallmarks was found based on cancer hallmark ontology.Conclusion This study is of great significance to the research on the cancer pathogenesis at the molecular level,the revealing of specific roles of genes and mutations in the occurrence of cancer,and the rapid knowledge discovery of cancer hallmarks.


Study protocol of a phase II clinical trial evaluating the efficacy of neoadjuvant intraperitoneal and systemic albumin-bound paclitaxel combined with camrelizumab and S-1 in the treatment of patients with exfoliative cell-positive gastric cancer.
Currently, gastric cancer with positive lavage cytology without gross peritoneal dissemination (GC-CY1) is a special type of metastatic form with poor prognosis. Consensus guidelines on treatment strategies for patients with GC-CY1 have not been established. This study involves a single-arm, prospective, phase II clinical trial to examine the efficacy and safety of neoadjuvant intraperitoneal and systemic (NIPS) albumin-bound paclitaxel combined with Camrelizumab and S-1 in the treatment of GC-CY1 patients. This is a prospective single-center exploratory study, and the primary endpoints of the trial are R0 resection rate and conversion rate of abdominal free cancer cells (FCCs), with secondary endpoints of 3-year progression-free survival (PFS); 3-year overall survival (OS); objective remission rate (ORR); disease control rate (DCR); safety and TRG classification. This study is the first to apply NIPS albumin-bound paclitaxel combined with Camrelizumab and S-1 to the conversion therapy of GC-CY1 patients. It is speculated that this combination of regimens will increase the negative conversion rate of FCCs by 20%, which will provide innovative insights into conversion treatment ideas for GC-CY1 patients to be managed in a more comprehensive and optimized manner. http://clinicaltrials.gov/, identifier NCT05410847.


Constructing protein-protein interaction network of hypertension with blood stasis syndrome via digital gene expression sequencing and database mining.
To construct a protein-protein interaction (PPI) network in hypertension patients with blood-stasis syndrome (BSS) by using digital gene expression (DGE) sequencing and database mining techniques. DGE analysis based on the Solexa Genome Analyzer platform was performed on vascular endothelial cells incubated with serum of hypertension patients with BSS. The differentially expressed genes were filtered by comparing the expression levels between the different experimental groups. Then functional categories and enriched pathways of the unique genes for BSS were analyzed using Database for Annotation, Visualization and Integrated Discovery (DAVID) to select those in the enrichment pathways. Interologous Interaction Database (I2D) was used to construct PPI networks with the selected genes for hypertension patients with BSS. The potential candidate genes related to BSS were identified by comparing the number of relationships among genes. Confirmed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), gene ontology (GO) analysis was used to infer the functional annotations of the potential candidate genes for BSS. With gene enrichment analysis using DAVID, a list of 58 genes was chosen from the unique genes. The selected 58 genes were analyzed using I2D, and a PPI network was constructed. Based on the network analysis results, candidate genes for BSS were identified: DDIT3, JUN, HSPA8, NFIL3, HSPA5, HIST2H2BE, H3F3B, CEBPB, SAT1 and GADD45A. Verified through qRT-PCR and analyzed by GO, the functional annotations of the potential candidate genes were explored. Compared with previous methodologies reported in the literature, the present DGE analysis and data mining method have shown a great improvement in analyzing BSS.


Diagnosis and reality: a noun is a terrible thing to waste.
The use of a diagnosis for identifying disease processes has been crucial in the field of medicine. But it is essential that the diagnostic noun represent real processes. In psychiatry, to meet the important criterion of reliability we have focused on objective phenomena. But since psychiatric disorders are human processes and a major aspect of being human is our subjectivity, we also need to pay far more attention to subjective phenomena, even those difficult to define reliably. The arts have much to teach us about the nature of those processes. It is essential that we learn from these and other sources to focus more effectively on subjectivity, and thereby understand the factors that underlie and define psychiatric disorders.


MicroRNAs in the oriental fruit fly, Bactrocera dorsalis: extending Drosophilid miRNA conservation to the Tephritidae.
The oriental fruit fly, Bactrocera dorsalis, is an important plant pest species in the family Tephritidae. It is a phytophagous species with broad host range, and while not established in the mainland United States, is a species of great concern for introduction. Despite the vast amount of information available from the closely related model organism Drosophila melanogaster, information at the genome and transcriptome level is still very limited for this species. Small RNAs act as regulatory molecules capable of determining transcript levels in the cells. The most studied small RNAs are micro RNAs, which may impact as much as 30 % of all protein coding genes in animals. We have sequenced small RNAs (sRNAs) from the Tephritid fruit fly, B. dorsalis (oriental fruit fly), specifically sRNAs corresponding to the 17 to 28 nucleotides long fraction of total RNA. Sequencing yielded more than 16 million reads in total. Seventy five miRNAs orthologous to known miRNAs were identified, as well as five additional novel miRNAs that might be specific to the genera, or to the Tephritid family. We constructed a gene expression profile for the identified miRNAs, and used comparative analysis with D. melanogaster to support our expression data. In addition, several miRNA clusters were identified in the genome that show conservancy with D. melanogaster. Potential targets for the identified miRNAs were also searched. The data presented here adds to our growing pool of information concerning the genome structure and characteristics of true fruit flies. It provides a basis for comparative studies with other Dipteran and within Tephritid species, and can be used for applied research such as in the development of new control strategies based on gene silencing and transgenesis.


Live performance of male broilers subjected to constant or increasing air velocities at moderate temperatures with a high dew point.
This study examined the effects of varying air velocities vs. a constant air velocity with a cyclic temperature curve of 25-30-25 degrees C and a dew point of 23 degrees C on broilers from 28 to 49 d of age. Four replicate trials were conducted. In each trial, 742 male broilers were randomly allocated to 6 floor pens or 2 air velocity tunnels, with each tunnel consisting of 4 pens. Bird density, feeder, and waterer space were similar across all pens (53 birds/ pen; 0.07 m2/bird). The treatments were control (still air), constant air velocity of 120 m/min, and increasing air velocity (90 m/min from 28 to 35 d, 120 m/min from 36 to 42 d, and 180 m/min from 43 to 49 d). Birds grown in a still air environment gained less weight, consumed less feed, and converted feed less efficiently between 28 and 49 d than birds subjected to moving air (constant or increasing). Growth responses between the air velocity treatments were similar from 28 to 35 and 36 to 42 d of age. Increasing air velocity to 180 m/min improved (P < or = 0.02) the growth rate of broilers from 43 to 49 d of age over birds receiving an air velocity of 120 m/min, but the incidence of mortality was not affected. These results provide evidence that increasing air velocity from 120 to 180 m/min is beneficial to broilers weighing 2.5 kg or greater when exposed to moderate temperatures.


Aromatase and its inhibitors: significance for breast cancer therapy.
Endocrine adjuvant therapy for breast cancer in recent years has focussed primarily on the use of tamoxifen to inhibit the action of estrogen in the breast. The use of aromatase inhibitors has found much less favor due to poor efficacy and unsustainable side effects. Now, however, the situation is changing rapidly with the introduction of the so-called phase III inhibitors, which display high affinity and specificity towards aromatase. These compounds have been tested in a number of clinical settings and, almost without exception, are proving to be more effective than tamoxifen. They are being approved as first-line therapy for elderly women with advanced disease. In the future, they may well be used not only to treat young, postmenopausal women with early-onset disease but also in the chemoprevention setting. However, since these compounds inhibit the catalytic activity of aromatase, in principle, they will inhibit estrogen biosynthesis in every tissue location of aromatase, leading to fears of bone loss and possibly loss of cognitive function in these younger women. The concept of tissue-specific inhibition of aromatase expression is made possible by the fact that, in postmenopausal women when the ovaries cease to produce estrogen, estrogen functions primarily as a local paracrine and intracrine factor. Furthermore, due to the unique organization of tissue-specific promoters, regulation in each tissue site of expression is controlled by a unique set of regulatory factors. These factors are potential targets for the design of selective aromatase modulators, which could selectively inhibit aromatase expression in breast with the same efficacy as the phase III inhibitors of activity but leave expression in other local sites such as bone and brain untouched.


[Severity of coronary artery disease in patients with acute coronary syndrome without ST segment elevation].
Risk stratification of patients presenting to the hospital with acute coronary syndrome (ACS) is usually based on ECG assessment, and several clinical and biochemical criteria, which are all intended to identify subjects with more severe disease, who might benefit from aggressive medical or interventional treatment. However, no one widely accepted jeopardy score is available. Our aim was to determine whether the initial ECG, biochemical data and past medical history correlate with the extent of coronary artery disease in patients with ACS thus identifying subjects with severe coronary artery disease (CAD) who may benefit from the early invasive strategy. Patients' data was prospectively collected and retrospectively analysed according to the result of angiography examination. Our cohort consisted of 220 consecutive patients hospitalised due to typical chest pain (> 5 min.) occurring at rest within the last 24 hours. Study group comprised of 115 patients, who were subsequently subjected to coronary angiography Blood for qualitative troponin I test (Cardiac STATus, Spectral Inc., NJ, USA), and other routine biochemistry tests was drawn and ECG was done on admission. Chi-square and Pearson correlation tests were used for statistical analysis, p < 0.05 being considered statistically significant. Stepwise forward regression analysis was used to identify variables predictive of significant coronary artery stenosis. We have identified 65 patients with significant and 5 patients with insignificant multivessel stenosis, 33 patients with significant and 7 patients with insignificant single vessel disease. Five patients had normal coronary arteries. Male sex was significantly more prevalent among patients with coronary artery disease than with normal arteries (71% vs. 40%, p = 0.02). No differences in biochemistry values were seen among the groups. There was a significant difference in the prevalence in ST segment depression (p = 0.03) among these patients and in the incidence of plasma fibrinogen levels of >380 mg% (p = 0.02), those findings being most frequently encountered in significant multi- and single-vessel disease subjects. Hypertension, myocardial infarction more than 10 days ago, history of smoking, hypercholesterolemia and diabetes were independent predictors of the presence of significant stenosis. Assessment of admitting ECG and troponin I together with patients medical history may allow for identification of ACS patients with significant CAD that may benefit from early invasive treatment.


The Anti-Inflammatory Effects of Glucagon-Like Peptide Receptor Agonist Lixisenatide on the Retinal Nuclear and Nerve Fiber Layers in an Animal Model of Early Type 2 Diabetes.
This study explored the anti-inflammatory effects of a glucagon-like peptide-1 receptor agonist (GLP-1RA), known as lixisenatide, on the eyes of early type 2 diabetic mice. Diabetic (db/db) mice were divided into three groups: GLP-1RA [lixisenatide (LIX)], insulin (INS) with controlled hyperglycemia based on the glucose concentration of lixisenatide, and diabetic control (D-CON). Nondiabetic control mice (db/dm) were also characterized for comparison. After 8 weeks of treatment, mRNA levels of inflammatory markers, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, immunohistochemical staining; Western blot of glial fibrillary acidic protein (GFAP) and thioredoxin-interacting protein; and retinal thickness were assessed in the central and peripheral neurosensory retina. LIX showed decreased immunohistochemical staining for both thioredoxin-interacting protein and GFAP in the central and peripheral neurosensory retina compared with D-CON and INS, and decreased expression of these proteins in the neurosensory retina and immunohistochemical staining in the optic nerve head for GFAP compared with D-CON. The inner nuclear layer in the peripheral retina in LIX was only thinner than those of D-CON and INS. In an early type 2 diabetic mouse model, lixisenatide treatment showed superior anti-inflammatory effects on the retina and optic nerve head independent of hyperglycemia. Thus, the neuroprotective effects of lixisenatide treatment in the peripheral inner nuclear layer should be evaluated in early type 2 diabetic retinopathy.


Small bowel ulcerative lesions are common in elderly NSAIDs users with peptic ulcer bleeding.
To determine the frequency of small bowel ulcerative lesions in patients with peptic ulcer and define the significance of those lesions. In our prospective study, 60 consecutive elderly patients with upper gastrointestinal bleeding from a peptic ulceration (cases) and 60 matched patients with a non-bleeding peptic ulcer (controls) underwent small bowel capsule endoscopy, after a negative colonoscopy (compulsory in our institution). Controls were evaluated for non-bleeding indications. Known or suspected chronic inflammatory conditions and medication that could harm the gut were excluded. During capsule endoscopy, small bowel ulcerative lesions were counted thoroughly and classified according to Graham classification. Other small bowel lesions were also recorded. Peptic ulcer bleeding was controlled endoscopically, when adequate, proton pump inhibitors were started in both cases and controls, and Helicobacter pylori eradicated whenever present. Both cases and controls were followed up for a year. In case of bleeding recurrence upper gastrointestinal endoscopy was repeated and whenever it remained unexplained it was followed by repeat colonoscopy and capsule endoscopy. Forty (67%) cases and 18 (30%) controls presented small bowel erosions (P = 0.0001), while 22 (37%) cases and 4 (8%) controls presented small bowel ulcers (P < 0.0001). Among non-steroidal anti-inflammatory drug (NSAID) consumers, 39 (95%) cases and 17 (33%) controls presented small bowel erosions (P < 0.0001), while 22 (55%) cases and 4 (10%) controls presented small bowel ulcers (P < 0.0001). Small bowel ulcerative lesions were infrequent among patients not consuming NSAIDs. Mean entry hemoglobin was 9.3 (SD = 1.4) g/dL in cases with small bowel ulcerative lesions and 10.5 (SD = 1.3) g/dL in those without (P = 0.002). Cases with small bowel ulcers necessitate more units of packed red blood cells. During their hospitalization, 6 (27%) cases with small bowel ulcers presented bleeding recurrence most possibly attributed to small bowel ulcers, nevertheless 30-d mortality was zero. Presence of chronic obstructive lung disease and diabetes was related with unexplained recurrence of hemorrhage in logistic regression analysis, while absence of small bowel ulcers was protective (relative risk 0.13, P = 0.05). Among NSAID consumers, more bleeders than non-bleeders with peptic ulcers present small bowel ulcers; lesions related to more severe bleeding and unexplained episodes of bleeding recurrence.


Computational analysis of Rho GTPase cycling.
The Rho family of GTPases control actin organization during diverse cellular responses (migration, cytokinesis and endocytosis). Although the primary members of this family (RhoA, Rac and Cdc42) have different downstream effects on actin remodeling, the basic mechanism involves targeting to the plasma membrane and activation by GTP binding. Our hypothesis is that the details of GTPase cycling between membrane and cytosol are key to the differential upstream regulation of these biochemical switches. Accordingly, we developed a modeling framework to analyze experimental data for these systems. This analysis can reveal details of GDI-mediated cycling and help distinguish between GDI-dependent and -independent mechanisms, including vesicle trafficking and direct association-dissociation of GTPase with membrane molecules. Analysis of experimental data for Rac membrane cycling reveals that the lower apparent affinity of GDI for RacGTP compared to RacGDP can be fully explained by the faster dissociation of the latter from the membrane. Non-dimensional steady-state solutions for membrane fraction of GTPase are presented in multidimensional charts. This methodology is then used to analyze glucose stimulated Rac cycling in pancreatic β-cells. The charts are used to illustrate the effects of GEFs/GAPs and regulated affinities between GTPases and membrane and/or GDI on the amount of membrane bound GTPase. In a similar fashion, the charts can be used as a guide in assessing how targeted modifications may compensate for altered GTPase-GDI balance in disease scenarios.


[Hepatic tuberculosis: case report of pseudotumoral form].
Inflammatory pseudo-tumors of the liver are rare and difficult to diagnose, mimicking malignant tumors. We report a patient, 42 year old with hepatic pseudo-tumor who was suspected to have pseudotumoral hepatic tuberculosis without immunodepression and treated by major hepatic surgery because no sure diagnosis. Therapeutic approach of hepatic inflammatory pseudotumors is often medical and surgical and may need major hepatic surgery in case of sure etiologic diagnosis.


Effects of different delayed exercise regimens on cognitive performance in fimbria‑fornix transected rats.
Studies have shown that exercise can positively influence cognitive performance after brain injury. This study investigated the effects of different exercise regimens on allocentric place learning after fimbria‑fornix (FF) transection. One hundred and sixteen pre‑shaped rats were subjected either to a mechanical transection of the FF or control sham surgery and divided into following groups: i) no exercise (NE), ii) voluntary exercise in a running wheel (RW), iii) forced swimming exercise administered as interval training of short (3x5 min) duration (FS‑SI), iv) forced swimming exercise administered as interval training of long (3x15 min) duration (FS‑LI), v) forced swimming exercise administered as one session of short (5 min) duration (FS‑SS), and vi) forced swimming exercise administered as one session of long (15 min) duration (FS‑LS). The exercise was initiated 21 days post‑surgery. Subsequently, all animals were administered 28 acquisition sessions in an 8‑arm radial maze. Both sham operated and lesioned animals showed a significant learning response, however, the lesion induced a marked and lasting impairment, which was not alleviated neither by voluntary nor forced (spaced or one‑session only) exercise regimens. Exercise regimens had no effect on the place learning of control sham animals. We conclude that the lesion location as well as factors related to the exercise‑ and cognitive testing protocols can profoundly influence the potential of exercise as a general recovery‑promoting method.