Metabolomic profiling reveals potential biomarkers in esophageal cancer progression using liquid chromatography-mass spectrometry platform.
Esophageal cancer (EC) is one of the most common malignancies with poor prognosis. Metabolomics has been shown to be a powerful approach to discover the potential biomarkers for cancer diagnosis and prognosis. The goal of this study is to screen potential biomarkers for early diagnosis and prognosis. In this study, 40 tissue samples and the corresponding control samples from the same esophageal squamous cell carcinoma (ESCC) patients were analyzed by liquid chromatography-mass spectrometry (LC-MS)-based metabolomics. 20 potential diagnostic biomarkers were selected. Moreover, 9 metabolites were found to be closely correlated with the pathological feature such as local invasion, lymphatic metastasis and postoperative survival time. Glutamate was correlated with local invasion of tumor, and oleic acid, LysoPC(15:0), uracil, inosine and choline were closely related with the lymphatic metastasis, while glutamine, kynurenine, serine and uracil were related with postoperative survival time. The results indicated that the potential biomarkers discovered by metabolomics could reflect the metabolic characterization of ESCC, and offers a novel approach for early diagnosis, assessment and prognosis of the disease.


Binding properties of aromatic carbon-bound fluorine.
A systematic computational analysis of the ability of aromatic carbon-bound fluorine to participate in hydrogen bonding and electrostatic interactions has been completed. The interaction energies between the most common fluoroaromatics used in medicinal chemistry and both water, the prototypical hydrogen bond donor, and several cations have been calculated at different levels of theory (HF, MP2, DFT). Our results show that aromatic fluorine can participate in significant hydrogen bonds and can also interact with charged molecules.


[Cognitive function and factors related to cognitive function in hospitalized patients with chronic heart failure].
To explore the cognitive function status and potential influence factors on cognitive function in hospitalized patients with chronic heart failure. Using a cross-sectional research design, CHF patients (n = 267, mean age (63.8 ± 9.4) years) were recruited from two care units-Heart Failure Care Unit and Intensive Care Unit of our hospital. Cognitive function status was evaluated by the Montreal Cognitive Assessment (MoCA) screen test. Based on the MoCA score, 37.8% (101/267) patients suffered from cognitive impairment (score<26), especially on the three specific cognitive functions-memory, langue and executive capability. Multifactorial analysis showed that after controlling for other factors, there was a downward trend on cognitive function with aging (OR = 1.09, 95%CI:1.05-1.14) while higher left ventricular ejection fraction (LVEF) was related to better cognitive function (OR = 0.97, 95%CI:0.95-0.99); patients who took medicine regularly also had better cognitive function (OR = 3.71, 95%CI:1.40-10.91); cognitive function was better in patients with high level of social support compared those with low social support (OR = 0.92, 95%CI:0.88-0.96). Incidence of cognitive impairment is high in hospitalized patients with chronic heart failure. Age, LVEF, whether taking medication regularly and social support are factors related to cognitive function in CHF patients.


The impact of COVID-19 on cancer care of outpatients with low socioeconomic status.
Patients with low socioeconomic status (SES) are among the most underserved groups of people regarding cancer care. Analyzing the impact of the coronavirus-induced disease 2019 (COVID-19) pandemic on health care disparities and calling attention to inequalities in cancer care is crucial to justify and initiate adequate countermeasures. We aimed to determine whether the COVID-19 pandemic aggravated health care disparities of cancer outpatients related to their SES and analyzed patient data of the largest university center providing services for patients with hematologic and oncologic disorders in Austria from 2018 to 2021. SES was assessed using three indicators: monthly net household income, level of education and occupational prestige. In total, 1217 cancer outpatients (51.1% female) with a mean age of 59.4 years (SD = 14.2) participated. In the first year of the pandemic, the relative proportion of individuals with low income, low education level and low occupational prestige seeking cancer care at our outpatient center decreased significantly (P ≤ .015). The strongest indicator was income, with a consistent effect throughout the first pandemic year. Countermeasures and specific interventions to support cancer patients with low SES in their access to health care should be initiated and prioritized.


Polymer-supported bimetallic Ag@AgAu nanocomposites: synthesis and catalytic properties.
Supported noble bimetallic nanomaterials have attracted great interest owing to their applications in catalysis. Herein, polystyrene-supported Ag@AgAu bimetallic nanocomposites were synthesized by using a seed-growth route. The size and degree of coverage of the Ag@AgAu NPs could be controlled by changing the experimental parameters. SEM, TEM, STEM, EDS, and XPS analysis was used to characterize the morphology, structure, and composition of these nanocomposites. We found that the bimetallic nanoparticles on the polystyrene beads had a core-shell structure that was comprised of a Ag core and a AgAu alloy shell. The optical properties of the nanocomposites were also studied by UV/Vis/NIR spectroscopy, which indicated that the localized surface plasmon resonance (LSPR) absorptions of the nanocomposites could be tailored over a large scale from 450 nm to 950 nm. The catalytic properties of the nanocomposites were studied by using the reduction of 4-nitrophenol (4-NP) by NaBH(4) as a model system. The results showed that the catalytic activity of the polystyrene-supported Ag@AgAu bimetallic nanocomposites was remarkably superior to that of polystyrene-supported monometallic Ag and Au nanocomposites with the same nanoparticle size. In addition, an investigation of the recycling catalytic activity of the PS-Ag@AgAu nanocomposites revealed that the catalyst possessed good stability. The enhancement of the catalytic activity was proposed to be due to the ligand and strain effects between Ag and Au.


Membrane trafficking as an active regulator of constitutively secreted cytokines.
Immune-cell activation by inflammatory stimuli triggers the transcription and translation of large amounts of cytokines. The transport of newly synthesized cytokines to the plasma membrane by vesicular trafficking can be rate-limiting for the production of these cytokines, and immune cells upregulate their exocytic machinery concomitantly with increased cytokine expression in order to cope with the increasing demand for trafficking. Whereas it is logical that trafficking is rate-limiting for regulated secretion where an intracellular pool of molecules is waiting to be released, the reason for this is not obvious for constitutively secreted cytokines, such as interleukin-6 (IL-6), interleukin-12 (IL-12) and tumor necrosis factor-α (TNF-α). These constitutively secreted cytokines are primarily regulated at the transcriptional and/or translational level but mounting evidence presented here shows that cells might also increase or decrease the rate of post-Golgi cytokine trafficking to modulate their production. Therefore, in this Hypothesis, we ask the question: why is there a need to limit the trafficking of constitutively secreted cytokines? We propose a model where cells monitor and adjust their production rate of cytokines by sensing the intracellular level of cytokines while they are in transit to the plasma membrane. This self-regulation of cytokine production could prevent an overshooting response of acute-phase cytokines, such as IL-6, IL-12 and TNF-α, upon acute infection.


Proper reprogramming of imprinted and non-imprinted genes in cloned cattle gametogenesis.
Epigenetic abnormalities in cloned animals are caused by incomplete reprogramming of the donor nucleus during the nuclear transfer step (first reprogramming). However, during the second reprogramming step that occurs only in the germline cells, epigenetic errors not corrected during the first step are repaired. Consequently, epigenetic abnormalities in the somatic cells of cloned animals should be erased in their spermatozoa or oocytes. This is supported by the fact that offspring from cloned animals do not exhibit defects at birth or during postnatal development. To test this hypothesis in cloned cattle, we compared the DNA methylation level of two imprinted genes (H19 and PEG3) and three non-imprinted genes (XIST, OCT4 and NANOG) and two repetitive elements (Satellite I and Satellite II) in blood and sperm DNAs from cloned and non-cloned bulls. We found no differences between cloned and non-cloned bulls. We also analyzed the DNA methylation levels of four repetitive elements (Satellite I, Satellite II, Alpha-satellite and Art2) in oocytes recovered from cloned and non-cloned cows. Again, no significant differences were observed between clones and non-clones. These results suggested that imprinted and non-imprinted genes and repetitive elements were properly reprogramed during gametogenesis in cloned cattle; therefore, they contributed to the soundness of cloned cattle offspring.


Reversal of relative thresholds for synaptic facilitation and increased excitability induced by serotonin and tail nerve stimulation in Aplysia sensory neurons.
Tail shock induces reflex sensitization in Aplysia and, in parallel, induces a number of modulatory effects in central neurons, such as increased excitability in tail sensory neurons (SNs) and facilitation of synaptic transmission from SNs to motor neurons. Both of these modulatory effects are mimicked by exogenous application of serotonin (5HT) or electrical stimulation of the tail nerve P9. In the present study we examined the activation thresholds for increased excitability and synaptic facilitation induced by either 5HT or P9 stimulation. We found that the concentration of 5HT sufficient to produce a significant increase in excitability produced no significant synaptic facilitation and, conversely, that the intensity of nerve stimulation sufficient to produce significant synaptic facilitation produced no excitability changes. This reversal of relative thresholds for these modulatory effects may reflect the differential access of exogenous 5HT and endogenous 5HT (released by tail nerve stimulation) to the SN cell body and synaptic terminals, respectively.


3-Amino-5,5-dimethylhexanoic acid. Synthesis, resolution, and effects on carnitine acyltransferases.
The selective inhibition of individual carnitine acyltransferases may be useful in the therapy of diabetes and heart disease. Aminocarnitine (3) is a weak competitive inhibitor (K(i) = 4.0 mM) for carnitine acetyltransferase (CAT), although the N-acetyl derivative 4 is about 165 times more potent (K(i) = 0.024 mM) than 3. Compound 3 is also a potent competitive inhibitor for carnitine palmitoyltransferases 1 and 2 (CPT-1 and CPT-2) (IC50 for CPT-2 = 805 nM). We synthesized 3-amino-5,5-dimethylhexanoic acid (7) and its N-acetyl derivative (8) as isosteric analogs of 3 and 4 that lack the quaternary ammonium positive charge. Like 3 and 4, compounds 7 and 8 were competitive inhibitors of CAT with significantly different potencies, but in this case, 8 (K(i) = 25 mM) was 10 times less potent than 7 (K(i) = 2.5 mM). R-(-)-7 and S-(+)-7 were stereoselective inhibitors of CAT (K(i) = 1.9 and 9.2 mM, respectively). Racemic 7 was a weak competitive inhibitor of CPT-2 (K(i) = 20 mM) and had no effect on CPT-1. These results are consistent with differences among the carnitine-binding sites on carnitine acyl-transferases that may be useful in selective inhibitor design. Furthermore, the data suggest that the quaternary ammonium positive charge of carnitine may be important for the proper orientation of carnitine and its analogs in the binding site.


Pathophysiological role of prostaglandin E2-induced up-regulation of the EP2 receptor in motor neuron-like NSC-34 cells and lumbar motor neurons in ALS model mice.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective degeneration of motor neurons. The primary triggers for motor neuronal death are still unknown, but inflammation is considered to be an important factor contributing to the pathophysiology of ALS both clinically and in ALS models. Prostaglandin E2 (PGE2) and its corresponding four E-prostanoid receptors play a pivotal role in the degeneration of motor neurons in human and transgenic models of ALS. It has also been shown that PGE2-EP2 signaling in glial cells (astrocytes or microglia) promotes motor neuronal death in G93A mice. The present study was designed to investigate the levels of expression of EP receptors in the spinal motor neurons of ALS model mice and to examine whether PGE2 alters the expression of EP receptors in differentiated NSC-34 cells, a motor neuron-like cell line. Immunohistochemical staining demonstrated that EP2 and EP3 immunoreactivity was localized in NeuN-positive large cells showing the typical morphology of motor neurons in mice. Semi-quantitative analysis showed that the immunoreactivity of EP2 in motor neurons was significantly increased in the early symptomatic stage in ALS model mice. In contrast, the level of EP3 expression remained constant, irrespective of age. In differentiated NSC-34 cells, bath application of PGE2 resulted in a concentration-dependent decrease of MTT reduction. Although PGE2 had no effect on cell survival at concentrations of less than 10 μM, pretreatment with 10 μM PGE2 significantly up-regulated EP2 and concomitantly potentiated cell death induced by 30 μM PGE2. These results suggest that PGE2 is an important effector for induction of the EP2 subtype in differentiated NSC-34 cells, and that not only EP2 up-regulation in glial cells but also EP2 up-regulation in motor neurons plays a pivotal role in the vulnerability of motor neurons in ALS model mice.


Signal recognition and hearing protectors with normal and impaired hearing.
Recognition of acoustic signals when perception is subject to interference from noise has already been extensively studied. In this study the influence of hearing protectors (HP) (plugs, muffs) and hearing loss on signal recognition is examined. Different spectrums and levels of the noise are also included. The test results are shown as the masked threshold for the signals heard and identified. In the case of normally hearing subjects a frequency-independent HP (plug) improves hearing performance, while frequency-dependent HP (muffs) tends to worsen it, especially with low-frequency noise. Hearing losses even worsen hearing performance when plugs are worn. Design suggestions are made to optimise signal recognition. Minimum signal-to-noise ratio and the use of HP are discussed.


Placental drug transfer in near-term ewes: acetylsalicylic and salicylic acid.
Radiolabelled acetylsalicylic acid (ASA) and salicylic acid (SA) were given intravenously to four near-term ewes and their occurrence in both maternal and fetal plasma was ascertained using a specific thin-layer chromatographic analysis procedure. Findings proved that ASA and SA cross the placental barrier and reach distribution equilibrium about 40 min after salicylate administration. The equilibrium plasma fetal/maternal ratio for both salicylates averaged 0.4. Plasma concentrations of the two compounds in the mother and the fetus accorded with a two-compartment model having unusually large mean estimates (54 and 39 L) for the tissue distribution space of ASA and SA, respectively. Furthermore, the mean SA clearance in the ewe (358 mL X min-1) was much greater than that reported in man, while the mean ASA clearance (764 mL X min-1) was similar. Since ASA is an irreversible inhibitor of arachidonate cyclooxygenase, our findings reassert the need for caution in the use of the drug during pregnancy.


Orthodontic treatment need for Brazilian schoolchildren: a study using the Dental Aesthetic Index.
To determine the normative orthodontic treatment need among 12-year-old Brazilian schoolchildren, in the municipality of Juiz de Fora, Minas Gerais, Brazil, and compare with the need as perceived by the children themselves and their parents or caregivers, assessing putative associated sociodemographic factors. Four hundred and fifty one children without a previous history of orthodontic treatment were randomly selected from a population of 7,993 schoolchildren regularly attending the public and private educational sectors of the municipality of Juiz de Fora, Minas Gerais, Brazil. The prevalence of normative orthodontic treatment need in 12-year-old children, assessed with the Dental Aesthetic Index (DAI) was 65.6% (n = 155). The need perceived by the caregivers was 85.6%, and by the children was 83.8%. Only the perception by the caregivers maintained a significant correlation with the normative need of treatment when adjusted to the parents' schooling and economical level (p = 0.023). There is a high prevalence (65.6%) of malocclusion requiring orthodontic treatment in 12-year-old Brazilian schoolchildren. The most prevalent malocclusions in the study were: Crowding, Class II molar relationship and increased overjet. There was no significant correlation between the Index of Orthodontic Treatment Need - Aesthetic Component (IOTN-AC) related to dental aesthetic perception and the normative treatment need assessed with the DAI.


A Type Ib ParB protein involved in plasmid partitioning in a gram-positive bacterium.
Our current understanding of segregation of prokaryotic plasmids has been derived mainly from the study of the gram-negative bacterial plasmids. We previously reported a replicon of the cryptic plasmid from a gram-positive bacterium, Leifsonia xyli subsp. cynodontis. The replicon contains a putative plasmid partition cassette including a Walker-type ATPase followed by open reading frame 4 without sequence homologue. Here we reported that the orf4 gene was essential for maintaining the plasmid stability in L. xyli subsp. cynodontis. Furthermore, the purified orf4 protein specifically and cooperatively bound to direct repeat sequences located upstream of the parA gene in vitro, indicating that orf4 is a parB gene and that the direct repeat DNA sequences constitute a partition site, parS. The location of parS and the features of ParA and ParB proteins suggest that this plasmid partition cassette belongs to type Ib, representing the first type Ib cassette identified from a gram-positive bacterial plasmid.


Therapeutic impact of methoxyamine: blocking repair of abasic sites in the base excision repair pathway.
A major obstacle to effective treatment with alkylating agents in cancer is the presence of elaborate mechanisms of DNA repair. For instance, the methylating therapeutic agent, temozolomide forms O6-methylguanine (O6mG), 7-methylguanine (N7mG) and 3-methyladenine (N3mA) DNA adducts that are repaired by at least two mechanisms. The O6mG DNA adduct, a cytotoxic and genotoxic lesion, is repaired by O6-methylguanine DNA-methyltransferase (MGMT). Thus, MGMT is a major mechanism of resistance to methylating agents. Meanwhile, cell death caused by O6mG adducts is promoted by mismatch repair (MMR) system, such that deficiency in MMR is associated with pronounced resistance to methylating agents. N7mG, the dominant lesions formed by methylating therapeutic agents, and N3mA DNA adducts are removed by the base excision repair (BER) pathway. Efficient BER repair minimizes the impact of these lesions in normal and tumor cells. Thus, only when BER is disrupted, do these abundant N-methylated DNA adducts become highly cytotoxic. Most importantly, BER disruption is able to bypass other resistance factors such as MMR defects and high MGMT activity. BER, in fact, is an important drug-resistant factor because of its variety of substrates and the ability to rapidly and efficiently repair these DNA lesions. However, the impact of both active BER and inactive BER on anticancer therapy has yet to be fully studied. This review will establish the premise that targeting abasic sites formed during BER will disrupt this pathway and enhance the therapeutic efficacy of alkylating agents.


Male-male contests for mates, sexual size dimorphism, and sex ratio in a natural population of a solitary parasitoid.
Understanding how different behavioural and life history traits interact is fundamental to developing ethological theory. Here we study the interaction of male-male competition for mates and sexual size dimorphism in a solitary wasp, with implications for sex allocation. In Hymenoptera, females are normally larger than males suggesting that males do not benefit as much as females from larger size. However, in our focal species, a solitary Eurytoma wasp, males compete for mates by pairwise contests at female emergence sites, suggesting that male size may strongly affect fitness. In contests observed in the field, larger males were more likely to win fights, and males fighting at female emergence sites were much larger than average males. Males showed higher variance in body size than females, such that all the smallest individuals were males, a majority of medium-to-large individuals were female, but the majority of largest individuals were male. Our data suggest that sexual size dimorphism in this species has been affected by intra-sexual selection for male size, which may have implications for sex allocation.


Styraxoside A isolated from the stem bark of Styrax japonica inhibits lipopolysaccharide-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 in RAW 264.7 cells by suppressing nuclear factor-kappa B activation.
In the present study, the effects of terpenes (styraxosides A and B) and lignans (egonol, masutakeside I, and styraxlignolide A) isolated from the stem bark of Styrax japonica Sieb. et Zucc. (styracaceae) were evaluated on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production by the RAW 264.7 macrophage cell line. Of the tested compounds, styraxoside A was found to most potently inhibit the productions of NO and PGE2, and also significantly reduced the release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta). Consistent with these observations, the protein expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and the mRNA expression levels of iNOS, COX-2, TNF-alpha and IL-1beta were found to be inhibited by styraxoside A in a concentration-dependent manner. Furthermore, styraxoside A inhibited the LPS-induced DNA binding activity of nuclear factor-kappaB (NF-kappaB). Taken together, our data indicate that styraxoside A inhibits LPS-induced iNOS, COX-2, TNF-alpha, and IL-1beta expressions through the down-regulation of NF-kappaB-DNA binding activity.


Does the endometrial gene expression of fertile women vary within and between cycles?
Does gene expression of putative endometrial implantation markers vary in expression between menstrual cycles? In fertile women the expression of certain genes exhibits a pattern of stable regulation.which is not affected even when sampled twice in one cycle. Successful implantation occurs in a minority of IVF embryo transfers. In contrast to knowledge regarding the ovulatory process, there is a sparse understanding of endometrial genes critical to implantation. This lack of knowledge hinders progress in this field. Endometrial pipelle samples were collected based on blood endocrinological markers at 2 and 7 days post initial LH surge. Five samples were collected over four cycles where the interval between collections ranged from sequential months to three years. Six fertile women attending an IVF clinic for male factor infertility, had samples collected. Global gene expression profiles were obtained from laser-microdissected, endometrial glands and stroma. Nineteen potential proliferation, cytokine and adhesion markers based on previous validated reports were studied. There was a significant modification between LH+2 and LH+7 of expression for 23 genes-11 in 8 in glands and stroma, 4 in stroma only and 3 in glands only suggesting stable, controlled regulation. Nevertheless, genes exhibited individual characteristics, e.g MKI67 exhibited lower expression at LH+7 than LH+2 and CCL4 higher, whereas TRO expressed limited difference in both cell types. Stability between cycles was demonstrated for gene expression at both LH+2-more than 60% of genes had <25% variation and at LH+7-60% had <30% variation. Further, effects of prior collection of an LH+2 sample on gene expression at LH+7 were not detected. The range of mRNA expression suggested that a clinical/diagnostic sample at LH+2 and LH+7 is likely to be a better index of endometrial function than a single sample. The possibility of redundancy suggests a panel would be more informative than a single marker. Raw and normalized microarray data have been deposited with the EMBL's European Genome-Phenome Archive for collaborative analysis, reference ega-box-815 (Lappalainen I, Almeida-King J, Kumanduri V, Senf A, Spalding JD, Ur-Rehman S, Saunders G, Kandasamy J, Caccamo M, Leinonen R et al. The European Genome-phenome Archive of human data consented for biomedical research. Nat Genet 2015;47:692-695.) [https://www.ebi.ac.uk/ega/home]. This type of research has difficulties of recruitment of fertile women for multiple blood testing and repeat endometrial biopsies. Therefore, these data had decreased statistical power due to the overall participant numbers. However, the inclusion of four cycles for each participant permitted the aim of obtaining information on intercycle and intracycle variability to be achieved. Our results support the feasibility of a clinical means of identification of a functional receptive endometrium. The robustness of data from individual women suggests that samples from one cycle can generally be applied to subsequent cycles. Funding was granted from the Tertiary Education Commission of New Zealand, Contract I.D.:UOOX06007. There are no competing interests.


Perspectives in gene therapy for MS.
The blood-brain barrier limits the therapeutic efficacy of systemic administration of anti-inflammatory and/or neuroprotective molecules to patients affected by immune-mediated inflammatory demyelinating diseases of the central nervous system (CNS) such as multiple sclerosis. Drug delivery to the CNS using non-replicative viral vectors may represent a valid alternative therapeutic strategy. Gene therapy for multiple sclerosis might include different "human-grade" vectors, which could be used to deliver anti-inflammatory molecules as well as neuroprotective agents into the CNS in a flexible and useful way. These potential "therapeutic" vectors would have different life spans, tissue tropism and infectivity rates.


Evaluation of Bunch Protectors for Preventing Insect Infestation and Preserving Yield and Fruit Quality of Dates, Phoenix dactylifera L.
In experiments comparing conventional date paper wraps with polyester mesh bags, date bunches enclosed in polyester mesh bags had lower insect infestations than dates covered by paper wraps. Carob moth, Ectomyelois ceratoniae (Zeller), infestations of marketable fruit were significantly lower for mesh bags (0.6-3.1%) compared with paper wraps (8.5-15.5%). Other fruit pests [raisin moth, Cadra figulilella (Gregson), and beetles in the family Nitidulidae] were less common than carob moth, and infestation by these insects was consistently lower in fruit protected by mesh bags. Date bunches in mesh bag treatments had a 21-46% net increase in marketable date fruit owing to the fact that the bags prevented marketable dates from falling to the garden floor. The number of abscised kimri fruit was higher in the mesh bag treatment than the paper wrap treatment, yet there were no differences in the incidences of other fruit maladies (black nose, fruit with fungi, shriveled fruit, abscised khalal fruit, infertile fruit, and nonripe fruit). Bunch sanitation, used just prior to bagging and wrapping dates, successfully removed abscised kimri fruit from bunches, which resulted in a significantly lower number of cull dates from one garden, but this response was not present at a second garden. These studies show that mesh bags should be included in an integrated pest management program on dates.


Breast reconstruction: options post-mastectomy.
Breast cancer is the most common cancer affecting women in the UK. Breast reconstruction after resection of breast cancers increases patients' quality of life and psychosocial functioning. This article introduces this field and explores the options available to patients with breast cancer.


Prophylactic antiemetic therapy with droperidol in patients undergoing laparoscopic cholecystectomy.
The incidence of postoperative nausea and vomiting (PONV) following laparoscopic cholecystectomy (LC) is relatively high when no prophylactic antiemetic is given. We have studied the efficacy of a commonly used and well-established antiemetic, droperidol, for the prevention of PONV in patients undergoing LC. In a randomized, double-blind, placebo-controlled study, 60 patients received placebo (saline) or droperidol 50 microg.kg(-1) (maximum dose, 2.5 mg) intravenously immediately before the induction of anesthesia (n = 30 of each). A standard general anesthetic technique was employed throughout. A complete response, defined as no PONV and no need for another rescue antiemetic medication during the first 24 h after anesthesia, was 57% and 83% in patients who had received placebo and droperidol 50 microg.kg(-1), respectively ( P < 0.05). No clinically serious adverse events were observed in any of the groups. Prophylactic antiemetic therapy with droperidol 50 microg.kg(-1) (maximum dose, 2.5 mg) is highly effective for preventing PONV after LC.


[A case of organized chronic subdural hematoma presented with transient neurologic deficits].
A 59-year-old diabetic male presented with transient motor aphasia and monoparesis of the right upper limb. Brain CT scan showed a low density area in the left subdural space with a mild midline shift. Magnetic resonance (MR) T2-weighted and fluid-attenuated inversion recovery (FLAIR) imagings revealed homogenous hyperintensity with a hypointense web-like structure in the subdural hematoma. Cervical MR angiography showed no abnormal lesion at the bifurcation of the bilateral common carotid arteries. Conventional cerebral angiography showed an avascular, crescent, space-occupying mass over the left hemisphere without an etiologic lesion of cerebral ischemia. CT perfusion imagings indicated reduced cerebral blood flow (CBF) and prolonged mean transit time (MTT) in the left middle cerebral artery territory underneath the subdural hematoma. No epileptic discharge was found in electroencephalogram. Operative findings indicated that the hematoma was encapsulated with thickened outer and inner membranes including paste-like materials, and the brain surface was intact. Postoperative CT perfusion imagings revealed normal CBF and MTT. The pathophysiological mechanism which the chronic subdural hematoma produces the transient neurological deficit is still uncertain. The mechanical pressure of the hematoma on the neighboring cerebral vessels may cause impairment of blood flow leading to cerebral ischemia and paralysis of function. Our case indicated the transient neurological deficits attributed to a decreased CBF around the subdural hematoma and a change in pressure exerted by the hematoma during changes of head position and increased blood viscosity.


Thresholds for epidemic outbreaks in finite scale-free networks.
We numerically investigate the existence of a threshold for epidemic outbreaks in a class of scale-free networks characterized by a parametri- cal dependence of the scaling exponent, influencing the convergence of fluctuations in the degree distribution. In finite-size networks, finite thresholds for the spreading of an epidemic are always found. However, both the thresholds and the behavior of the epidemic prevalence are quite diferent with respect to the type of network considered and the system size. We also discuss agreements and diferences with some analytical claims previously reported.


Variability of anti-human transglutaminase testing in celiac disease across Mediterranean countries.
To verify the precision and accuracy of transglutaminase antibodies (TGA) assays across Mediterranean countries. This study involved 8 referral centres for celiac disease (CD) in 7 Mediterranean countries. A central laboratory prepared 8 kits of 7 blinded and randomized serum samples, with a titrated amount of Human TGA IgA. Each sample was analysed three times on three different days, with each centre running a total of 21 tests. The results were included in a blindly coded report form, which was sent to the coordinator centre. The coordinator estimated the mean coefficient of Variation (CoVar = σ/μ), the mean accuracy (Accur = Vobserved - Vreal) and the mean percent variation (Var% = [(Vobserved - Vreal)/Vreal] × 100). The analysis showed that 79.17% of the mean variation fell between -25% and +25% of the expected value, with the accuracy and precision progressively increasing with higher titres of TGA. From values 1.25 times greater than the normal cut-off, the measurements were highly reliable. TGA estimation is a crucial step for the diagnosis of CD; given its accuracy and precision, clinicians could be confident in establishing a diagnosis.


Short stature: new challenges in growth hormone therapy.
Until recently, the limited supplies of pituitary derived growth hormone (GH) enabled us to treat only those patients who were classical GH deficient. With the unlimited supplies of recombinant GH available, there is no limitation to the number of patients we can treat. It becomes necessary, however, to select those patients who will most benefit from GH therapy. Our preliminary results demonstrate that the short-term growth response to growth hormone is not an all-or-none phenomenon. The lower the growth velocity and the growth hormone reserve, the better the growth response to therapy. On the other hand we do not recommend institution of GH therapy for children with a normal growth rate and a normal GH spontaneous secretion. In children with classical GH deficiency (GHD) and in children with a subnormal spontaneous secretion of GH (NSD) adult height prediction decreases when GH therapy is started at an age older than 12. We have found that GHD and NSD boys differ in their growth pattern. Pubertal maturation and bone age maturation progress more rapidly in NSD patients. Therefore special caution is needed in NSD patients older than 12 years. The older the patient and the longer the treatment period, the faster the pubertal process can advance. Further studies are needed before recommendations for therapy in non-classical GHD patients can be made. Until patients involved in clinical trials reach final height, recommendations for new indications cannot be made.


Master of Primary Health Care degree: who wants it and why?
INTRODUCTION The Department of General Practice and Primary Health Care at the University of Auckland is considering developing a Master of Primary Health Care (MPHC) programme. Masters level study entails considerable investment of both university and student time and money. AIM To explore the views of potential students and possible employers of future graduates to discover whether there is a market for such a programme and to inform the development of the programme. METHODS Semi-structured interviews were conducted with 30 primary health care stakeholders. Interviews were digitally recorded, transcribed and analysed using a general inductive approach to identify themes. FINDINGS Primary care practitioners might embark on MPHC studies to develop health management and leadership skills, to develop and/or enhance clinical skills, to enhance teaching and research skills, or for reasons of personal interest. Barriers to MPHC study were identified as cost and a lack of funding, time constraints and clinical workload. Study participants favoured inter-professional learning and a flexible delivery format. Pre-existing courses may already satisfy the post-graduate educational needs of primary care practitioners. Masters level study may be superfluous to the needs of the primary care workforce. CONCLUSIONS Any successful MPHC programme would need to provide value for PHC practitioner students and be unique. The postgraduate educational needs of New Zealand primary care practitioners may be already catered for. The international market for a MPHC programme is yet to be explored.


[Professor LI Rui's mind regulation theory in the clinical application of acupuncture and moxibustion].
The experience in the clinical application of Professor LI Rui's "mind regulation" theory is introduced in the paper. The substantial foundation of mind and the brief understanding of "mind derangement" are explained and the content of the theory of mind regulation in acupuncture and moxibustion is explained in detail. It is important to emphasize the mind regulation in the heart, brain and spleen as well as the promotion of qi activity.


Serpentinization as the source of energy, electrons, organics, catalysts, nutrients and pH gradients for the origin of LUCA and life.
Serpentinization in hydrothermal vents is central to some autotrophic theories for the origin of life because it generates compartments, reductants, catalysts and gradients. During the process of serpentinization, water circulates through hydrothermal systems in the crust where it oxidizes Fe (II) in ultramafic minerals to generate Fe (III) minerals and H2. Molecular hydrogen can, in turn, serve as a freely diffusible source of electrons for the reduction of CO2 to organic compounds, provided that suitable catalysts are present. Using catalysts that are naturally synthesized in hydrothermal vents during serpentinization H2 reduces CO2 to formate, acetate, pyruvate, and methane. These compounds represent the backbone of microbial carbon and energy metabolism in acetogens and methanogens, strictly anaerobic chemolithoautotrophs that use the acetyl-CoA pathway of CO2 fixation and that inhabit serpentinizing environments today. Serpentinization generates reduced carbon, nitrogen and - as newer findings suggest - reduced phosphorous compounds that were likely conducive to the origins process. In addition, it gives rise to inorganic microcompartments and proton gradients of the right polarity and of sufficient magnitude to support chemiosmotic ATP synthesis by the rotor-stator ATP synthase. This would help to explain why the principle of chemiosmotic energy harnessing is more conserved (older) than the machinery to generate ion gradients via pumping coupled to exergonic chemical reactions, which in the case of acetogens and methanogens involve H2-dependent CO2 reduction. Serpentinizing systems exist in terrestrial and deep ocean environments. On the early Earth they were probably more abundant than today. There is evidence that serpentinization once occurred on Mars and is likely still occurring on Saturn's icy moon Enceladus, providing a perspective on serpentinization as a source of reductants, catalysts and chemical disequilibrium for life on other worlds.


Mediterranean spotted fever in Spain, 1997-2014: Epidemiological situation based on hospitalization records.
Mediterranean spotted fever (MSF) is a zoonotic disease caused by Rickettsia conorii. In Spain, deficiencies in the official reporting result in misreporting of this disease. This study aims to describe the clinical and temporal-spatial characteristics of MSF hospitalizations between 1997 and 2014. We performed a retrospective descriptive study using the Hospitalization Minimum Data Set (CMBD). All CMBD's hospital discharges with ICD-9 CM code 082.1 were analyzed. Hospitalization rates were calculated and clinical characteristics were described. Spatial distribution of cases and their temporal behavior were also assessed. A total of 4,735 hospitalizations with MSF diagnosis were recorded during the study period, out of which 62.2% were male, mean age of 48. Diabetes mellitus, alcohol dependence syndrome, and chronic liver disease occurred in 10.8%, 2.4% and 2.8% hospitalizations, respectively. The median annual hospitalization rate showed a decreasing trend from a maximum of 12.9 in 1997 to a minimum rate of 3.1 in 2014. Most admissions occurred during the summer, showing a significant annual seasonal behavior. Important regional differences were found. Although MSF hospitalization rates have decreased considerably, it remains a public health problem due to its severity and economic impact. Therefore, it would be desirable to improve its oversight and surveillance.


Growth development and its relationship to intellectual functioning of children with phenylketonuria.
Growth measurements, including weight, height, and head circumference, of 67 early treated children with phenylketonuria (PKU) were compared to normal standards from infancy up to six years of age. Children with PKU, both girls and boys, achieved growth parameters that were similar to those of normals. Head circumference of the boys at six years of age and of the girls at three and four years of age correlated positively with IQ scores. Weight/height (W/H) ratios at one year of age correlated positively with IQ scores for boys. Similar correlations between IQs and weight/height ratios were found for girls at one, two, and three years of age.


Broad-spectrum chemokine inhibition reduces vascular macrophage accumulation and collagenolysis consistent with plaque stabilization in mice.
A major determinant of the risk of myocardial infarction is the stability of the atherosclerotic plaque. Macrophage-rich plaques are more vulnerable to rupture, since macrophages excrete an excess of matrix-degrading enzymes over their inhibitors, reducing collagen content and thinning the fibrous cap. Several genetic studies have shown that disruption of signalling by the chemokine monocyte chemoattractant protein 1 reduced the lipid lesion area and macrophage accumulation in the vessel wall. We have tested whether a similar reduction in macrophage accumulation could be achieved pharmacologically by treating apolipoprotein-E-deficient mice with the chemokine inhibitor NR58-3.14.3. Mice treated for various periods of time (from several days to 6 months) with NR58-3.14.3 (approximately 30 mg/kg/day) consistently had 30-40% fewer macrophages in vascular lesions, compared with mice treated with the inactive control NR58-3.14.4 or PBS vehicle. Similarly, cleaved collagen staining was lower in mice treated for up to 7 days, although this effect was not maintained when treatment time was extended to 12 weeks. The vascular lipid lesion area was unaffected by treatment, but total collagen I staining and smooth muscle cell number were both increased, suggesting that a shift to a more stable plaque phenotype had been achieved. Strategies, such as chemokine inhibition, to attenuate macrophage accumulation may therefore be useful to promote stabilization of atherosclerotic plaques.


Transgrediens et progrediens palmoplantar keratoderma (Greither disease) and confluent and reticulated papillomatosis of Gougerot and Carteaud in the same patient: a coincidental finding?
A 13-year-old patient with typical findings of transgrediens et progrediens palmoplantar keratoderma that developed confluent and reticulated papillomatosis of Gougerot and Carteaud is presented. Although coexistence of the two disorders might be coincidental, the possibility of common pathogenetic pathways resulting in alterations of keratinization could be of investigational interest.


The wellbeing of women and men with and without disabilities: evidence from cross-sectional national surveys in 27 low- and middle-income countries.
Little is known about disability-related inequities in personal wellbeing (PWB) in low- and middle-income countries (LMICs). Secondary analysis of data collected in Round 6 of UNICEF's Multiple Indicator Cluster Surveys (MICS) undertaken in 27 LMICs (n = 296,693 women, 66,557 men). Data were aggregated across countries by mixed effects multi-level modelling and meta-analysis. Women and men with disabilities were less likely than their non-disabled peers to report being happy and to be satisfied with their life. These differences were evident in all countries for women and in 18 of 22 countries for men. Aggregated data indicated that: (1) women with disabilities were 14-15% less likely to be happy and 17% less likely to be satisfied with their lives; (2) men with disabilities were 15-17% less likely to be happy and 17-19% less likely to be satisfied with their lives; (3) disability-related inequalities in personal wellbeing were reduced by 22-26% for women and 11-22% for men by adjusting for differences in living conditions. Future releases of MICS data could prove a valuable resource in monitoring country-level progress to realising Sustainable Development Goal 3 and the extent to which progress is equitable between women and men and between people with/without disabilities. Results also suggest that a significant proportion of the disability-related inequities in wellbeing may be accounted for by modifiable differences in their living conditions and life experiences.


Bone growth into porous high-density polyethylene.
The purpose of this study was to delineate the process by which bone comes to fill the pores of porous high-density polyethylene (PHDPE) implants. PHDPE (450 mu pore size) pellets 4 mm in diameter and 1 cm long were implanted into the femurs of dogs. A bone biopsy procedure was utilized to obtain PHDPE pellets implanted for periods of 3 days through 8 weeks. A one-year biopsy specimen taken from the PHDPE coating on the stem of a canine total-hip prosthesis was also studied. The results demonstrated that significant amounts of bone formed within the PHDPE pellets as early as 14 days after implantation. Bone was identified throughout the specimens after 4 weeks. After 6 weeks, the tissue in hematopoietic marrow. Scanning electron microscopy was utilized in conjunction with light microscopy and microradiography to study the ultrastructural features of the bone ingrowth process.


[Cancer Therapy Targeting Fusion Genes in Lung Cancer].
Therapeutic landscape of lung cancer has undergone a dramatic shift due to the better understandings of disease biology and the identification of oncogenic driver alterations. Consequently, the new classification paradigm of non-small-cell lung cancer is further characterized by molecularly defined subsets, and making the therapeutic landscape increasingly complex. Driver gene mutations have been found in approximately 75% of Japanese non-squamous, non-small-cell lung cancers. Among these, the gene mutations for which molecularly-targeted therapies are being developed include EGFR mutations, ALK fusion gene, ROS1 fusion gene, BRAF V600E mutation, MET exon 14 skipping mutation, KRAS G12C mutation, RET fusion gene, and NTRK fusion gene. When limited to fusion genes, as of June 2022, crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib are approved for the ALK fusion gene; crizotinib and entrectinib for the ROS1 fusion gene; selpercatinib for the RET fusion gene; entrectinib and larotrectinib for the NTRK fusion gene have been approved in Japan. This article summarizes the therapeutic development of each fusion gene mutation, as well as the therapeutic outcomes and adverse events of the approved drugs.


Causal association between sleep traits and the risk of coronary artery disease in patients with diabetes.
The association between sleep traits and coronary artery disease (CAD) in patients with diabetes has been reported in previous observational studies. However, whether these potential relationships are causal remains unclear. We aim to assess the causal relationship between sleep traits and CAD in diabetic. Genetic instrumental variables associated with five sleep-related traits (insomnia, sleep duration, ease of getting up, morningness and snoring) were extracted from corresponding genome-wide association studies (GWAS). The associations of genetic variants with CAD were based on 15,666 individuals with diabetes (3,968 CAD cases and 11,696 controls). The primary analysis was derived using the inverse variance weighting method. Further sensitivity analysis was conducted to confirm the robustness and consistency of the main results. Genetic liability to insomnia was significantly related to the increased risk of CAD in individuals with diabetes [odds ratio (OR): 1.163; 95% CI: 1.072-1.254; p = 0.001]. Suggestive evidence was found for the borderline associations between both sleep duration (OR: 0.629; 95% CI: 0.380-1.042, p = 0.072) and snoring (OR: 1.010, 95% CI: 1.000-1.020, p = 0.050) with CAD risk. However, no consistent evidence was found for the association between ease of getting up and morningness with the risk of CAD in diabetic. Similar results can be verified in most sensitivity analyses. We provide consistent evidence for the causal effect of insomnia on the increased risk of CAD in individuals with diabetes. The management of sleep health should be emphasized to prevent CAD in diabetic patients.


Demographic and Clinical Characteristics of COPD Patients at Different Blood Eosinophil Levels in the UK Clinical Practice Research Datalink.
Blood eosinophil count may be a useful biomarker for predicting response to inhaled corticosteroids and exacerbation risk in chronic obstructive pulmonary disease (COPD) patients. The optimal cut point for categorizing blood eosinophil counts in these contexts remains unclear. We aimed to determine the distribution of blood eosinophil count in COPD patients and matched non-COPD controls, and to describe demographic and clinical characteristics at different cut points. We identified COPD patients within the UK Clinical Practice Research Database aged ≥40 years with a FEV1/FVC <0.7, and ≥1 blood eosinophil count recorded during stable disease between January 1, 2010 and December 31, 2012. COPD patients were matched on age, sex, and smoking status to non-COPD controls. Using all blood eosinophil counts recorded during a 12-month period, COPD patients were categorized as "always above," "fluctuating above and below," and "never above" cut points of 100, 150, and 300 cells/μL. The geometric mean blood eosinophil count was statistically significantly higher in COPD patients versus matched controls (196.6 cells/µL vs. 182.1 cells/µL; mean difference 8%, 95% CI: 6.8, 9.2), and in COPD patients with versus without a history of asthma (205.0 cells/µL vs. 192.2 cells/µL; mean difference 6.7%, 95%, CI: 4.9, 8.5). About half of COPD patients had all blood eosinophil counts above 150 cells/μL; this persistent higher eosinophil phenotype was associated with being male, higher body mass index, and history of asthma. In conclusion, COPD patients demonstrated higher blood eosinophil count than non-COPD controls, although there was substantial overlap in the distributions. COPD patients with a history of asthma had significantly higher blood eosinophil count versus those without.


Papillary urothelial carcinoma of the urinary bladder demonstrating prominent signet-ring cells in a smear. A case report.
The appearance of numerous signetring cells (SRCs) without any other type of adenocarcinoma cells originating in papillary transitional cell carcinoma (TCC) in a urine smear is rare. The cytology from mucus-urine that was initially obtained by washing from a 69-year-old female revealed three different types of cells: (1) numerous single SRC carcinoma-type cells, (2) low grade TCC-type cells arranged in sheets, and (3) intermediate (transitional)-type cells with both aspects of TCC and adenocarcinoma (SRC carcinoma) and mucus in the background. The latter two cell populations were retrospectively confirmed after histologic diagnosis of a primary papillary TCC with glandular differentiation. One should keep in mind that even a low grade papillary TCC with glandular differentiation of the bladder can exhibit excessive SRC-type cells in urine.


Two-Dimensional Unipolar Memristors with Logic and Memory Functions.
Two-dimensional materials have been widely used in electronics due to their electrical properties that are not accessible in traditional materials. Here, we present the first demonstration of logic functions of unipolar memristors made of functionalized HfSe2-xOx flakes and memtransistors made of MoS2/graphene/HfSe2-xOx van der Waals heterostructures. The two-terminal memristors exhibit stable unipolar switching behavior with high switching ratio (>106), high operating temperature (106 °C), long-term endurance (>104 s), and multibit data storage and can operate as memory latches and logic gates. Benefiting from these superior memristive properties, the three-terminal heterostructure memtransistors show wide tunability in electrical switching behaviors, which can simultaneously implement logic operation and data storage. Finally, we investigate their application prospect in logical units with memory capability, such as D-type flip-flop. These results demonstrate the potential of two-dimensional materials for resistive switching applications and open up an avenue for future in-memory computing.


Brief Report: Intestinal Dysbiosis in Ankylosing Spondylitis.
Ankylosing spondylitis (AS) is a common, highly heritable immune-mediated arthropathy that occurs in genetically susceptible individuals exposed to an unknown but likely ubiquitous environmental trigger. There is a close relationship between the gut and spondyloarthritis, as exemplified in patients with reactive arthritis, in whom a typically self-limiting arthropathy follows either a gastrointestinal or urogenital infection. Microbial involvement in AS has been suggested; however, no definitive link has been established. The aim of this study was to determine whether the gut in patients with AS carries a distinct microbial signature compared with that in the gut of healthy control subjects. Microbial profiles for terminal ileum biopsy specimens obtained from patients with recent-onset tumor necrosis factor antagonist-naive AS and from healthy control subjects were generated using culture-independent 16S ribosomal RNA gene sequencing and analysis techniques. Our results showed that the terminal ileum microbial communities in patients with AS differ significantly (P < 0.001) from those in healthy control subjects, driven by a higher abundance of 5 families of bacteria (Lachnospiraceae [P = 0.001], Ruminococcaceae [P = 0.012], Rikenellaceae [P = 0.004], Porphyromonadaceae [P = 0.001], and Bacteroidaceae [P = 0.001]) and a decrease in the abundance of 2 families of bacteria (Veillonellaceae [P = 0.01] and Prevotellaceae [P = 0.004]). We show evidence for a discrete microbial signature in the terminal ileum of patients with AS compared with healthy control subjects. The microbial composition was demonstrated to correlate with disease status, and greater differences were observed between disease groups than within disease groups. These results are consistent with the hypothesis that genes associated with AS act, at least in part, through effects on the gut microbiome.


Single step affinity chromatographic purification of human alpha-amylase from aspirated duodenal juice and its application in the measurement of pancreatic alpha-amylase synthesis rates in man.
Human alpha-amylase was purified from aspirated duodenal juice to electrophoretic homogeneity in a single step by affinity chromatography with the competitive inhibitor acarbose (IC50 = 1.22 mumol/l) as ligand. Duodenal juice was applied to an agarose resin to which acarbose had been coupled covalently via a 1.9 nm spacer group. Pure alpha-amylase, eluted with free acarbose, had a molecular mass of 55,000, and isoelectrofocusing revealed the presence of six isozymes with pI values of 7.3, 6.8, 6.7, 6.5, 6.4 and 6.3, all of which possessed amylase activity based on positive starch/iodine staining. The potential usefulness of this one-step purification procedure in the measurement of pancreatic alpha-amylase synthesis rates was evaluated in two control patients with non-pancreatic disease. Aspirated duodenal juice was obtained during a pulse/continuous intravenous 4 h infusion of [14C]leucine together with secretin and pancreozymin, and alpha-amylase purified using our protocol. Pancreatic alpha-amylase synthesis rates were determined from the rate of incorporation of [14C]leucine into alpha-amylase; values of 4.4 and 5.1 h were obtained for the two control patients.


Subchronic toxicity of photomirex in the female rat: results of 28- and 90-day feeding studies.
Photomirex (8-monohydromirex) was administered to female Sprague-Dawley rats at dietary levels of 0.2, 1.0, 5.0, 25.0 and 125 ppm. Food intake and body weight gain were significantly depressed at the 125 ppm level in the 28- but not in the 90-day study. Significant alterations were observed in some hematological and biochemical parameters at the highest dietary level in the 90-day study. Photomirex residues accumulated in a dose-dependent manner in perirenal fat, liver, brain, kidney, and spleen. Dose-dependent histotoxic effects were observed in liver and thyroid at and above 1 ppm; hepatomegaly was observed at 25.0 and 125 ppm. These results indicate that photomirex was approximately five times more toxic than mirex in terms of liver histology. When these results are compared with those observed in an earlier study in the male rat, it is evident that the female is less susceptible to photomirex than the male.


[Affect regularity of medicinal species and heating time on flavonoids contents in Epimedium cut crude drug].
To study the affect regularity of medicinal species and heating time on flavonoids contents in Epimedium cut crude drug. Setting processing temperature at 170 degrees C, 39 batches Epimedium cut crude drug of different species were heated for 0, 5, 10 minutes. The contents of epimedin A, B, C, icariin, Baohuoside I in different species of Epimedium were determined by HPLC. The variance analysis was used to study the effect of medicinal species and heating time on the contents change of five major flavonoids. The contents of Epimedin A, B, C were significantly impacted by medicinal species (P < 0.01), and Baohuoside I was also impacted (P < 0. 05). The contents of Epimedin A, B, icariin and Baohuoside I were significantly impacted by heating time (P < 0.01). But the flavonoids contents in Epimedium were not impacted by the interaction effect of heating time and species (P > 0.05). The medicinal species and heat processed time are two important influence factors on the flavonoids contents in Epimedium. The contents of Epimedin A, C are abundant in Epimedium pubescens, and the contents of Epimedin B, Baohuoside I are higher in Epimedium brevicornu. After heating, the contents of Epimedin A, B, C are decreased, and icariin, Baohuoside I are increased. This study provides scientific evidences for variety certification, optimizing processing technology, exploring processing mechanism and clinical rational administration.


Does Implementing an Enhanced Recovery After Surgery Protocol Increase Hospital Charges? Comparisons From a Radical Cystectomy Program at a Specialty Cancer Center.
To compare perioperative charges induced at the initial phase of a standardized enhanced recovery after surgery (ERAS) program from a tertiary referral center. A multidisciplinary ERAS protocol was implemented in our department on July 2015. During the subsequent year, all patients were treated according to this protocol (ERAS group). The patients were compared in terms of real in-hospital charges per surgical episode with a control group consisting of consecutive patients before the start of ERAS. Individual charges were analyzed per sample population and compared with the Wilcoxon rank-sum test or t test. Additionally, cost variances for each group were evaluated. A total of 257 consecutive patients were evaluated of which the last 112 were ERAS patients. The median length of stay for each group was 6 days (P = .748). ERAS patients incurred higher medication charges ($1939 vs $1729, P = .036). Control patients incurred higher supplies ($861 vs $692), treatment ($90 vs $72), and miscellaneous charges ($537 vs $388) (all, P < .001). The median total charges per patient were $59,539 for the control group and $60,655 for the ERAS group (P = .175). ERAS adoption significantly reduced variance in billed charges (P < .001). ERAS implementation did not significantly increase expenditure for cystectomy patients. ERAS showed decreased variance in charges likely due to standardization of care while eliciting savings in supplies, treatment, and miscellaneous costs.


Five-year follow-up study of hearing loss at several locations within a large automobile company.
This longitudinal epidemiologic study was designed to investigate hearing loss over a 5-year period among noise-exposed employees of a large automobile company and to assess effectiveness of hearing conservation programs at locations representing the spectrum of operations (assembly, light manufacturing, heavy manufacturing and machining, metal fabrication, and founding). Based on computerized audiometric test data, the study summarizes methodology developed for measuring occupational hearing loss and its application in evaluating programs at these locations, which had maximal 8-hr time-weighted average (TWA) noise exposures ranging from 104 to 110 dB(A). Methods presented here provide for consideration of age and hearing level of study subjects at baseline audiogram and clearly demonstrate the extent of hearing loss during the study period. Among five study locations, the average hearing loss at 2,000-4,000 Hz in the worst-loss ear ranged from 3.4 to 6.2 dB over the follow-up period; after adjustment for presbycusis, the loss was less than 2 dB at all but one location, which showed a loss of nearly 4 dB. In comparison to a control group of nonnoise-exposed employees, hearing conservation programs at four of the five locations were judged to be effective. One location, a metal fabrication plant with a large percentage of employees having an 8-hr TWA noise exposure over 90 dB(A), was particularly noted for the effectiveness of its program.


Importance of comorbidities in comatose survivors of shockable and non-shockable out-of-hospital cardiac arrest treated with target temperature management.
Comorbidity prior to out-of-hospital cardiac arrest (OHCA) and primary rhythm in relation to survival is not well established. We aimed to assess the prognostic importance of comorbidity in relation to primary rhythm in OHCA-patients treated with Target Temperature Management (TTM). Consecutive comatose survivors of OHCA treated with TTM in hospitals in the Copenhagen area between 2002-2011 were included. Utstein-based pre- and in-hospital data collection was performed. Data on comorbidity was obtained from The Danish National Patient Register and patient charts, assessed by the Charlson Comorbidity Index (CCI). A total of 666 patients were included. A third (n = 233, 35%) presented with non-shockable rhythm, and they were less often male (64% vs. 82%, p < .001), and OHCA in public, witnessed OHCA, and bystander cardiopulmonary resuscitation (CPR) were less common compared to patients with a shockable primary rhythm (public: 27% vs. 48%, p < .001, witnessed: 79% vs. 90%, p < .001, bystander CPR: 47% vs. 63%, p < .001). 30-day mortality was 62% compared to 28% in patients with non-shockable and shockable rhythm, respectively. By Cox-regression analyses, any comorbidity (CCI ≥1) was the only factor independently associated with 30-day mortality in patients with non-shockable rhythm (HR =1.9 (95% CI: 1.2-2.9), p < .01), whereas in patients with shockable rhythm comorbidity was not associated with outcome after adjustment for prognostic factors (HR = 0.82 (0.55-1.2), p = .34). No significant interaction between primary rhythm and comorbidity in terms of mortality was present. A higher comorbidity burden was independently associated with a higher 30-day mortality rate in patients presenting with non-shockable primary rhythm but not in patients with shockable rhythm.


Identification of USP29 as a key regulator of nucleotide biosynthesis in neuroblastoma through integrative analysis of multi-omics data.
Cancer cells show enhanced nucleotide biosynthesis, which is essential for their unlimited proliferation, but the underlying mechanisms are not entirely clear. Ubiquitin specific peptidase 29 (USP29) was reported to sustain neuroblastoma progression by promoting glycolysis and glutamine catabolism; however, its potential role in regulating nucleotide biosynthesis in tumor cells remains unknown. In this study, we depleted endogenous USP29 in MYCN-amplified neuroblastoma SK-N-BE2 cells by sgRNAs and conducted metabolomic analysis in cells with or without USP29 depletion, we found that USP29 deficiency caused a disorder of intermediates involved in glycolysis and nucleotide biosynthesis. De novo nucleotide biosynthesis was analyzed using 13C6 glucose as a tracer under normoxia and hypoxia. The results indicated that USP29-depleted cells showed inhibition of nucleotide anabolic intermediates derived from glucose, and this inhibition was more significant under hypoxic conditions. Analysis of RNA sequencing data in SK-N-BE2 cells demonstrated that USP29 promoted the gene expression of metabolic enzymes involved in nucleotide anabolism, probably by regulating MYC and E2F downstream pathways. These findings indicated that USP29 is a key regulator of nucleotide biosynthesis in tumor cells.


[A case report of left renal cell carcinoma with tumor thrombus extending into the right atrium].
A case report of left renal cell carcinoma with tumor thrombus extending into the right atrium is reported. A 76-year-old woman was found to have a left renal tumor with tumor thrombus extending into the inferior vena cava and right atrium by computed tomographic-scanning. Left nephrectomy and removal of an intra-atrial tumor thrombus were performed under a cardiopulmonary bypass. The post-operative course was uneventful and the patient was discharged from the hospital 22 days postoperatively. The pathological diagnosis was clear cell carcinoma. After surgery, the patient received interferon-gamma. However, the patient developed lung metastases 26 months after the operation and is currently being observed while receiving interferon-alpha.


Effect of Quercetin on Cell Cycle and Cyclin Expression in Ovarian Carcinoma and Osteosarcoma Cell Lines.
Resistance to chemotherapeutic drugs is a major problem in cancer treatment. The search for new interventions able to overcome this resistance may involve compounds of natural origin, such as flavonoids, ubiquitously present in many foods. In the present study, the cytotoxic effects and cell cycle modulation of the flavonoid quercetin were investigated in ovarian carcinoma (SKOV3) and osteosarcoma (U2OS) human cell lines and in their cisplatin (CDDP)-resistant counterparts (SKOV3/CDDP and U2OSPt cells, respectively). Quercetin (10-50 μM) caused evident changes in the distribution of cell cycle phases in the CDDP-resistant SKOV3/CDDP ovarian cell line. The levels of cyclin D1 and cyclin B1 were determined by means of Western blot in all cell lines incubated with quercetin (50 μM) for 48 hours. The cyclin D1 expression was significantly decreased following the treatment with quercetin in SKOV3 and U2OSPt cells, but not in SKOV3/CDDP and U2OS cells. The reduction of cyclin D1 level could be linked to the G1/S phase alteration found in quercetin-treated cells. Although cyclin B1 is required for G2/M phase, and despite our observation that quercetin influenced the G2/M phase of cell cycle, the flavonoid did not affect cyclin B1 levels in all cell lines, indicating the involvement of other possible mechanisms. These results suggest that quercetin, exceeding the resistance to CDDP, might become an interesting tool to evaluate cytotoxic activity in combination with chemotherapy drugs.


Immunoglobulins of the chicken antibody to Newcastle disease virus (Mukteswar and F strain).
The qualitative and quantitative development of chicken immunoglobulins in response to R2B (Mukteswar) and F strain of Newcastle disease virus was studied. One primary (R2B) and two secondary (R2B - R2B, F - R2B) vaccination trials were conducted. Sera was collected at weekly intervals and analyzed. There was an increase in total serum protein content in parallel to an increase in serum neutralizing (SN), hemagglutination inhibition (HI), and precipitating antibodies. The SN, HI and precipitating activities were detected both in IgM and IgG immunoglobulins when sera were treated with mercapto-ethanol. However, Sephadex G-200 fractionated sera showed only SN activity in the IgM fraction, whereas the IgG fraction showed both HI and SN activity. Serum IgM antibodies appeared during the first week following vaccination, then diminished, then rose again following secondary vaccination. Apparently, immunoglobulin induction and serological activities were not significantly influenced by the age of the chickens.


Copy number alteration is an independent prognostic biomarker in triple-negative breast cancer patients.
Next-generation sequencing (NGS) has enabled comprehensive genomic profiling to identify gene alterations that play important roles in cancer biology. However, the clinical significance of these genomic alterations in triple-negative breast cancer (TNBC) patients has not yet been fully elucidated. The aim of this study was to clarify the clinical significance of genomic profiling data, including copy number alterations (CNA) and tumor mutation burden (TMB), in TNBC patients. A total of 47 patients with Stage I-III TNBC with genomic profiling of 435 known cancer genes by NGS were enrolled in this study. Disease-free survival (DFS) and overall survival (OS) were evaluated for their association to gene profiling data. CNA-high patients showed significantly worse DFS and OS than CNA-low patients (p = 0.0009, p = 0.0041, respectively). TMB was not associated with DFS or OS in TNBC patients. Patients with TP53 alterations showed a tendency of worse DFS (p = 0.0953) and significantly worse OS (p = 0.0338) compared with patients without TP53 alterations. Multivariable analysis including CNA and other clinicopathological parameters revealed that CNA was an independent prognostic factor for DFS (p = 0.0104) and OS (p = 0.0306). Finally, multivariable analysis also revealed the combination of CNA-high and TP53 alterations is an independent prognostic factor for DFS (p = 0.0005) and OS (p = 0.0023). We revealed that CNA, but not TMB, is significantly associated with DFS and OS in TNBC patients. The combination of CNA-high and TP53 alterations may be a promising biomarker that can inform beyond standard clinicopathologic factors to identify a subgroup of TNBC patients with significantly worse prognosis.


Kaempferol and Its Glycoside, Kaempferol 7-O-Rhamnoside, Inhibit PD-1/PD-L1 Interaction In Vitro.
Kaempferol (KO) and kaempferol 7-O-rhamnoside (KR) are natural products from various oriental herbs such as Geranii Herba. Previous studies have reported some biological activities of KO and KR; however, their effects on PD-1/PD-L1 interaction have not been reported yet. To elucidate their inhibitory activities on PD-1/PD-L1 protein-protein interaction (PPI), biochemical assays including competitive ELISA and biolayer interferometry (BLI) systems were performed. Cellular PD-1/PD-L1 blocking activity was measured in a co-culture system with PD-1 Jurkat and PD-L1/aAPC CHO-K1 cells by T-cell receptor (TCR) activation-induced nuclear factor of activated T cells (NFAT)-luciferase reporter assay. The detailed binding mode of action was simulated by an in silico docking study and pharmacophore analysis. Competitive ELISA revealed that KO and its glycoside KR significantly inhibited PD-1/PD-L1 interaction. Cellular PD-1/PD-L1 blocking activity was monitored by KO and KR at non-cytotoxic concentration. Surface plasmon resonance (SPR) and biolayer interferometry (BLI) analysis suggested the binding affinity and direct inhibition of KR against PD-1/PD-L1. An in silico docking simulation determined the detailed mode of binding of KR to PD-1/PD-L1. Collectively, these results suggest that KR could be developed as a potent small molecule inhibitor for PD-1/PD-L1 blockade.


Overaugmentation to compensate for postextraction ridge atrophy using a putty-type porcine bone substitute material with recombinant bone morphogenetic protein-2: 4 weeks of healing in a canine model.
The aims of the present study were (i) to determine the short-term effects of putty-type porcine bone substitute material (PB) with recombinant bone morphogenetic protein-2 (rhBMP-2) for alveolar ridge preservation (ARP) and (ii) evaluate the early healing of labial overaugmentation. Two groups were randomly assigned to the extraction sockets in mandibular incisors of eight dogs: labial overaugmentation with (i) PB (control) or (ii) rhBMP-2-loaded PB (BMP). Microcomputed tomography (micro-CT), and histologic and histomorphometric analyses were performed after 4 weeks. Micro-CT revealed that some of the overaugmented PB was dispersed in both groups. The new bone volume was significantly larger in the BMP group than in the control group (18.4 ± 3.3 vs. 15.5 ± 3.0 mm3, mean ± SD, P < 0.05). Labial bone resorption was generally found histologically. No signs of mineralization were observed in the overaugmented area despite significantly increased ridge width, as compared to the adjacent tooth area. The area of new bone formation was larger in the BMP group than in the control group overall (23.7 ± 18.8 vs. 18.3 ± 21.2 mm2) and in three parts (apical, middle, and coronal), although the difference was statistically significant only in the coronal part (7.7 ± 7.9 vs. 4.6 ± 6.4 mm2, P < 0.05). The addition of rhBMP-2 enhanced ossification in the coronal part of the extraction socket relative to using PB alone. Overaugmentation increased the ridge dimension with no evidence of ossification in situ at 4 weeks. In early healing following ARP, rhBMP-2 enhances bone formation within the socket, but ossification in the overaugmented area needs to be studied further.


Cotransfection of ICAM-1 and HLA-DR reconstitutes human antigen-presenting cell function in mouse L cells.
The initiation of a specific immune response is believed to require not only activation through antigen-specific receptors on T cells and B cells but also antigen-independent interactions between accessory molecules. One such molecule is LFA-1, which enhances the avidity of interactions between T cells and antigen-presenting cells, and is possibly involved in signal transduction across the T-cell membrane. Intercellular adhesion molecule-1 (ICAM-1), a surface glycoprotein of relative molecular mass (Mr) 80,000-110,000, has been defined as a ligand for LFA-1, and has been shown to participate in the interaction between T cells and monocytes. The determination of the precise contribution of such accessory molecules to antigen presentation, however, is complicated by the need to analyse against a background of multiple molecular interactions. We have investigated the role of LFA-1/ICAM-1 interactions in antigen presentation directly by quantifying the contribution of ICAM-1 expression to T-cell stimulation using L-cell transfectants that co-express ICAM-1 and HLA-DR. In the case of transfectants expressing modest levels of HLA-DR, co-expression of ICAM-1 is critical for effective HLA class II-restricted and allospecific T-cell activation, pointing to an important role for ICAM-1 in the induction of T-cell responses.


Organic Hydroperoxide Resistance Gene ohr (VPA1681) Confers Protection against Organic Peroxides in the Presence of Alkyl Hydroperoxide Reductase Genes in Vibrio parahaemolyticus.
The marine foodborne enteropathogen Vibrio parahaemolyticus contains the chief organic peroxide reductases AphC1-AhpC2 and a putative organic hydroperoxide resistance enzyme (Ohr; VPA1681) against different peroxides. This study investigated the function of the Ohr under the presence of AhpC1-AhpC2 in this pathogen by gene mutation. Experimental results demonstrated that the ohr gene product was a weak scavenger of H2O2 only in the mutant strains that lacked the peroxide sensor/regulator oxyR and ahpC1-ahpC2 genes. The Ohr of V. parahaemolyticus was highly effective at scavenging organic peroxide, as demonstrated by assaying the defective changes in the Δohr mutant strain and determining the detoxifying activity of the purified recombinant V. parahaemolyticus Ohrvp protein in the reduced form. The Ohr and AhpC1-AhpC2 exhibited similar functions against organic peroxides; however, only the ΔahpC1ΔahpC2 mutant strain showed a significant increase in susceptibility to several disinfectants, organic acids, and antibiotics compared with the wild-type strain. The transcription of the ohr gene depended on exogenous cumene hydroperoxide (cumene) stress and was markedly enhanced in the ΔohrR (VPA1682) mutant strains. This study revealed the organic hydroperoxide reductase activity of the Ohr in V. parahaemolyticus, and its role probably depends on sophisticated regulation by OhrR. IMPORTANCE Vibrio parahaemolyticus is the most prevalent foodborne pathogen in Taiwan and some other coastal Asian countries, and its antioxidative activity contributes to the tolerance of this bacterium to different environmental stresses. This study reports on the function of the organic hydroperoxide resistance gene (ohr; VPA1681) and its gene regulator, ohrR (VPA1682), in this pathogen. The strain with the ohr gene had effective protection against organic peroxide, and the recombinant Ohrvp was active in its reduced form. The function of Ohr was significant mostly in strains in which the function of AhpC1-AhpC2 was limited. The ohrR repressor of the ohr gene was effective at low concentrations of organic peroxide. Other common Vibrio species that contain homologous ohr, ohrR, ahpC1, and ahpC2 genes, which are phylogenetically close to those of V. parahaemolyticus, may share similar functions to those revealed in this study.


Taste preferences of infants for sweetened or unsweetened foods.
This is a report of research on whether or not the addition of sugar to foods consumed by babies early in their feeding significantly alters later preference for sweetened or unsweetened foods. Twenty control babies were fed regular baby food (which already has additional sugar) for the first 3 months of their solid-food feeding experience; 20 experimental babies were fed a diet with no added sugar for a similar time period. The two groups were then studied during a 4-week period in which they were randomly assigned to four different sequences of sweetened and unsweetened food. Their reactions to sweetened and unsweetened food were scored according to parental interpretation of their preferences and according to how much food they consumed. Neither group was found to prefer sweetened or unsweetened food. This finding is in contradiction of other studies and common lay and clinical views that infants prefer sweetened foods. It would seem that if babies do not prefer sweet foods, there is certainly no reason to add sugar to commercial products.


The alteration of temoporfin distribution in multicellular tumor spheroids by β-cyclodextrins.
To be effective anticancer drugs must penetrate tissue efficiently, reaching all target population of cancer cells in a concentration sufficient to exert a therapeutic effect. This study aimed to investigate the ability of methyl-β-cyclodextrin (Me-β-CD) and 2-hydroxypropyl-β-cyclodextrin (Hp-β-CD) to alter the penetration and diffusion of temoporfin (mTHPC) in HT29 multicellular tumor spheroids. mTHPC had а nonhomogenous distribution only on the periphery of spheroids. The presence of β-CDs significantly altered the distribution of mTHPC consisting in the increase of both the depth of photosensitizer penetration and accumulation in HT29 spheroids. We suggest that this improvement is related to the nanoshuttle mechanism of β-CD action, when β-CDs facilitate mTHPC transportation to the cells in the inner layers of spheroids. As a result of mTHPC distribution improvement, β-CDs enhance mTHPC photosensitizing activity towards HT29 multicellular tumor spheroids. The observed effects strongly depend on the type of β-CD. Thus, varying the type of β-CD we can finely tune the possibility of using mTHPC for diagnostic (delimitation of tumor margins) or therapeutic purposes.


Self-reported expression and consequences of embarrassment in portugal and the u.k.
Data was collected by questionnaire from Portuguese and U.K. college students in order to compare self-reports of the physiological/behavioural response associated with embarrassment, coping attempts and observer reactions to the actor's embarrassment in the two cultures. Blushing/increased temperature, increased heart rate and smiling/grinning characterised embarrassment in both cultures, although blushing was referred to with less frequency by the Portuguese sample; gaze aversion was a response specific to the U.K. sample. Smiling/grinning as a method of coping with embarrassment and as a reported reaction from an observer was reported with similar frequency by both samples; gaze aversion as a method of coping with embarrassment was referred to with greater frequency by the U.K sample; staring by observers was mentioned with greater frequency by the Portuguese sample. More intense experiences of embarrassment were reported by the Portuguese sample who also reported being more successful in attempts to control their embarrassment. The results are discussed in relation to national stereotypes.


Aortic diameter remodelling after the frozen elephant trunk technique in aortic dissection: results from an international multicentre registry.
The frozen elephant trunk (FET) technique allows one-stage hybrid repair approach in aortic dissection (AoD). Even if the effect of the FET technique on promoting false lumen (FL) thrombosis has been proved in the past, the relative importance of FL thrombosis on aortic remodelling at different levels of the distal aorta and the magnitude of this effect is not well known. The aim of the study was to evaluate aortic remodelling following a FET technique for AoD. A multicentre international registry database was searched to identify all patients who underwent a FET procedure for an AoD. A total of 383 patients with AoD were operated on between January 2005 and March 2014 with the FET technique; 137 patients (65 acute AoD and 72 chronic AoD) who survived the initial repair with at least a 1-year follow-up CT scan were included in the study. The rate of FL thrombosis was higher in the mid-descending thoracic aorta (99.3%) and lower in the distal abdominal aorta (13.9%) but similar between acute and chronic AoDs. The negative remodelling rate was similar between acute and chronic AoDs in the abdominal aorta, but chronic AoD exhibited a higher rate of negative remodelling in the descending thoracic aorta (33% vs 17.5%, P = 0.040). The FET technique provides an effective treatment for AoD, promoting FL thrombosis and remodelling in the descending thoracic aorta. Changes in the diameter of the aortic lumen depend mainly on the status of the FL and are similar between acute and chronic AoD. Changes in the diameter of true lumen are affected by both the FL status and the timing of the presentation. However, increased FL thrombosis and positive remodelling rates are not maintained at the level of the abdominal aorta, and strict follow-up is mandatory to detect early changes in the aortic dimensions, which may warrant further interventions.


Neuromeningeal Cryptococcosis and Tuberculosis Coinfection in Bamako: A One-Year Case Series.
Cryptococcosis and tuberculosis are life-threatening opportunistic infections that occur in apparently immunocompetent or severely immunocompromised individuals worldwide. As both infections are strongly linked to HIV infection, they may share certain clinical manifestations, and the interaction of their treatments should be considered. However, despite their similarity, concurrent tuberculosis and cryptococcal infections have rarely been reported in West Africa. Herein, we present 3 cases of neuromeningeal cryptococcosis and lung tuberculosis coinfection collected prospectively over a year at the Department of Infectious Diseases of the Point G Teaching Hospital in Bamako. Two patients had HIV disease, and the third patient had no underlying immunosuppressive illnesses. Thus, active screening for tuberculosis and cryptococcosis, particularly in individuals with HIV, can reduce misdiagnosis and ensure appropriate coinfection management. Moreover, this may reduce mortality due to AIDS-related opportunistic infections in resource-limited settings.


A patient with mixed type Evans syndrome: efficacy of rituximab treatment.
Mixed type Evans syndrome is a very rare hematologic disease. Although mixed type Evans syndrome may initially respond well to steroids, this disease usually runs a chronic course with intermittent exacerbations. We describe here a 46-yr-old female with the steroid-refractory, mixed type Evans syndrome, and she had a prompt response to rituximab. She was diagnosed as having the mixed type Evans syndrome with the clinical features of symptomatic anemia, jaundice and thrombocytopenia. Prednisone therapy was commenced and her hemoglobin and platelet level returned to the normal. However, after 15 weeks, she relapsed with hemolytic anemia and thrombocytopenia. We started rituximab at the dose of 375 mg/m(2) once weekly for a total of 4 doses, which was well-tolerated and this induced the normalization of hemoglobin, bilirubin and lactic dehydrogenase, and there was also a significant increase of the platelet count.


Type 4 pili are dispensable for biofilm development in the cyanobacterium Synechococcus elongatus.
The hair-like cell appendages denoted as type IV pili are crucial for biofilm formation in diverse eubacteria. The protein complex responsible for type IV pilus assembly is homologous with the type II protein secretion complex. In the cyanobacterium Synechococcus elongatus PCC 7942, the gene Synpcc7942_2071 encodes an ATPase homologue of type II/type IV systems. Here, we report that inactivation of Synpcc7942_2071 strongly affected the suite of proteins present in the extracellular milieu (exo-proteome) and eliminated pili observable by electron microscopy. These results support a role for this gene product in protein secretion as well as in pili formation. As we previously reported, inactivation of Synpcc7942_2071 enables biofilm formation and suppresses the planktonic growth of S. elongatus. Thus, pili are dispensable for biofilm development in this cyanobacterium, in contrast to their biofilm-promoting function in type IV pili-producing heterotrophic bacteria. Nevertheless, pili removal is not required for biofilm formation as evident by a piliated mutant of S. elongatus that develops biofilms. We show that adhesion and timing of biofilm development differ between the piliated and non-piliated strains. The study demonstrates key differences in the process of biofilm formation between cyanobacteria and well-studied type IV pili-producing heterotrophic bacteria.


Survey results of currently used techniques and materials by dentists for fabrication of complete removable dental prostheses.
The present study was based on the screening of procedures and materials used by dentists in constructing complete removable dental prostheses, considering their professional background and years of experience. Questions arose regarding differences and similarities within the local dental society, of which approximately 75% were trained in Europeans countries with differences in academic background, and compared to international dentistry. A questionnaire web site was used in order to anonymously collect answers to the survey by general practicing and specialist dentists. The survey contained 28 multiple choice questions that were based on 5 parameters: years of experience, location of dental studies, specialization, location and field of specialization. One hundred one survey sheets were collected. The results show statistical significance (p less than 0.05) for the following comparisons: practicing time had an impact on practitioner-technician interaction, while the level of qualification had an effect on articulator and face-bow usage. Location of dental studies, specialization and residency had impact on final impression materials, teeth set-up as well as tooth shape and color selection. The differences found between dentists' working techniques set the ground for future research that should focus on rating the success of the different methods towards a goal of creating recommendations for an ideal set of working techniques.


Combinatorial signalling controls Neurogenin2 expression at the onset of spinal neurogenesis.
A central issue during embryonic development is to define how different signals cooperate in generating unique cell types. To address this issue, we focused on the function and the regulation of the proneural gene Neurogenin2 (Neurog2) during early mouse spinal neurogenesis. We showed that Neurog2 is first expressed in cells within the neural plate anterior to the node from the 5 somite-stage. The analysis of Neurog2 mutants established a role for this gene in triggering neural differentiation during spinal cord elongation. We identified a 798 base pair enhancer element (Neurog2-798) upstream of the Neurog2 coding sequence that directs the early caudal expression of Neurog2. Embryo culture experiments showed that Retinoic Acid (RA), Sonic hedgehog (Shh) and Fibroblast Growth Factor signals act in concert on this enhancer to control the spatial and temporal induction of Neurog2. We further demonstrated by transgenesis that two RA response elements and a Gli binding site within the Neurog2-798 element are absolutely required for its activity, strongly suggesting that the regulation of Neurog2 early expression by RA and Shh signals is direct. Our data thus support a model where signal integration at the level of a single enhancer constitutes a key mechanism to control the onset of neurogenesis.


Goiter in rural area of Aligarh district.
The survey of iodine deficiency disorder (IDD) and an inquiry about intake of goitrogenic items in two villages of the Aligarh District with a population of 1819 was done. Out of 1152 subjects examined, 348 had goiters but no other abnormality related to the IDD could be found in these subjects. The goiter positivity was 30.2% with visible goiter (grade II & III) rate 8.5%. Six of the subjects had multi nodular goiter of grade III. Urinary iodine levels in 316 of the goitrous subjects were lower (4.939 +/- 1.593 micrograms/dL, M +/- SD, P < 0.001, Median 4.9 micrograms/dL) than 50 urban inhabitants (6.638 +/- 1.372 micrograms/dL). Through in most of the cases (83.9%) T3, T4 and TSH were within normal range, in 35% of the 69 from whom the blood samples were drawn, T3 levels > 150 ng/dL and in 41% of the cases TSH levels > 3.5 mU/L was seen. As in most of the goitrous subjects T3, T4, TSH levels were within normal limits, only iodine deficiency could not be the causative factor for the goiter in 30.2% (severe endemia) of the total population of these two villages. Consumption of millets by the villagers, known to contain goitrogens along with the iodine deficiency in the food and drinking water appears to be responsible for the higher goiter rate in these villagers.


Polymer microfiber meshes facilitate cardiac differentiation of c-kit(+) human cardiac stem cells.
Electrospun microfiber meshes have been shown to support the proliferation and differentiation of many types of stem cells, but the phenotypic fate of c-kit(+) human cardiac stem cells (hCSCs) have not been explored. To this end, we utilized thin (~5µm) elastomeric meshes consisting of aligned 1.7µm diameter poly (ester-urethane urea) microfibers as substrates to examine their effect on hCSC viability, morphology, proliferation, and differentiation relative to cells cultured on tissue culture polystyrene (TCPS). The results showed that cells on microfiber meshes displayed an elongated morphology aligned in the direction of fiber orientation, lower proliferation rates, but increased expressions of genes and proteins majorly associated with cardiomyocyte phenotype. The early (NK2 homeobox 5, Nkx2.5) and late (cardiac troponin I, cTnI) cardiomyocyte genes were significantly increased on meshes (Nkx=2.5 56.2±13.0, cTnl=2.9±0.56,) over TCPS (Nkx2.5=4.2±0.9, cTnl=1.6±0.5, n=9, p<0.05 for both groups) after differentiation. In contrast, expressions of smooth muscle markers, Gata6 and myosin heavy chain (SM-MHC), were decreased on meshes. Immunocytochemical analysis with cardiac antibody exhibited the similar pattern of above cardiac differentiation. We conclude that aligned microfiber meshes are suitable for guiding cardiac differentiation of hCSCs and may facilitate stem cell-based therapies for treatment of cardiac diseases.


A primer on meta-analysis of correlation coefficients: the relationship between patient-reported therapeutic alliance and adult attachment style as an illustration.
The aim of this article is twofold: to offer an introduction to meta-analysis using correlation coefficients to facilitate greater understanding of meta-analytic findings and to guide those interested in conducting meta-analyses. The authors review calculations for a weighted average effect size, the statistical significance of this effect, a test of homogeneity, confidence intervals, and file drawer analysis. They provide a running example of the relationship between patient-reported therapeutic alliance and adult attachment style. Results (k = 12, N = 581.17, weighted average r = .17, p < .0001, 95% confidence interval=.13-.21) indicated a positive, statistically significant relationship, suggesting that greater attachment security is associated with stronger therapeutic alliances, whereas greater attachment insecurity is associated with weaker therapeutic alliances. File drawer results suggested that some caution is warranted in terms of the size of the effect.


Treatment Rate of Schizophrenia in China: a Meta-Analysis of Epidemiological Studies.
Effective and prompt medication treatment is essential for schizophrenia patients to alleviate psychotic symptoms and improve prognosis. The treatment rate of schizophrenia usually varies greatly across studies. This is a meta-analysis that examined the overall treatment rate of schizophrenia in China. Both international (PubMed, EMBASE, PsycINFO, Web of Science) and Chinese (CNKI, WanFang and Sinomed) databases were searched. The random effects model was used to analyze the data. Fifteen studies with 1,219,472 patients were included. This meta-analysis found that 73% (95%CI: 66%, 80%) of schizophrenia patients received treatment in any type of medical institutions, while 31.0% (95%CI = 21.0%, 41.0%) received treatment in psychiatric institutions. Studies conducted in middle region of China (76.8% for any type of medical institutions; 42.6% for psychiatric institutions) and those published before 2007 (74.6% for any type of medical institutions; 31.3% for psychiatric institutions) reported significantly higher treatment rates. Studies using combined diagnostic instruments had a higher treatment rate of schizophrenia (72.0%) in any type of medical institutions, while using the Chinese classification of Mental Disorders (47.7%) and including both rural and urban areas (35.7%) had higher treatment rates of schizophrenia in psychiatric institutions. The treatment rate of schizophrenia was relatively high in China, but most treatments were delivered in non-psychiatric medical institutions. Greater efforts should be made to improve the provision of accessible mental health services for schizophrenia patients in this part of the world.


Local spread of metamitron resistant Chenopodium album L. patches.
Molecular markers can provide valuable information on the spread of resistant weed biotypes. In particular, tracing local spread of resistant weed patches will give details on the importance of seed migration with machinery, manure, wind or birds. This study investigated the local spread of metamitron resistant Chenopodium album L. patches in the southwest region of the province West-Flanders (Belgium). During the summer of 2009, leaf and seed samples were harvested in 27 patches, distributed over 10 sugar beet fields and 1 maize field. The fields were grouped in four local clusters. Each cluster corresponded with the farmer who cultivated these fields. A cleaved amplified polymorphic sequence (CAPS) procedure identified the Ser264 to Gly mutation in the D1 protein, endowing resistance to metamitron, a key herbicide applied in sugar beet. The majority of the sampled plants within a patch (97% on average) carried this mutation. Amplified fragment length polymorphism (AFLP) analysis was performed with 4 primer pairs and yielded 270 molecular markers, polymorphic for the whole dataset (303 samples). Analysis of molecular variance revealed that a significant part of the genetic variability was attributed to variation among the four farmer locations (12 %) and variation among Chenopodium album patches within the farmer locations (14%). In addition, Mantel tests revealed a positive correlation between genetic distances (linearised phipt between pairs of patches) and geographic distances (Mantel-coefficient significant at p = 0.002), suggesting isolation-by-distance. In one field, a decreased genetic diversity and strong genetic relationships between all the patches in this field supported the hypothesis of a recent introduction of resistant biotypes. Furthermore, genetic similarity between patches from different fields from the same farmer and from different farmers indicated that seed transport between neighbouring fields is likely to have an important impact on the spread of metamitron resistant biotypes.