Preliminary report: neural firing patterns specific for Meniere's disease.
To describe the application of a new, objective diagnostic test for Meniere's disease. Electrovestibulography (EVestG) is a complex, newly-developed test paradigm that searches for neural firing patterns that may be diagnostic for particular neural disorders. EVestG system was previously "trained" to distinguish Meniere's disease from other patients on a set of training data. In this paper we illustrate its diagnostic application in a new group of unknown subjects. Collaborative Academic Bioengineering Research Centre. Prospective, blinded human Clinical Trial. In an attempt to understand the specific neural firing patterns that may objectively characterize latent Meniere's disease, two hundred fifty-six consecutive patients who presented for electronystagmography testing were asked to undergo EVestG testing. Ten subjects actually completed testing but data were too noisy to permit analysis for one patient. Complete data were available for nine patients with either a clinical diagnosis of either Meniere's disease (4 patients) or some other vestibular disorder (2 vestibular neuritis, 2 benign positional vertigo and 1 non-specific dizziness). None of the patients were experiencing attacks of vertigo within a week of EVestG testing. Ten normal control subjects with no history or symptoms of ear disease were also tested. EVestG was performed in a separate engineering research facility by investigators who were unaware of their clinical diagnosis. If EVestG suggested that the probability of Meniere's disease was 0.5 or greater Meniere's disease was considered present by the objective testing. The objective and clinical diagnoses were compared. EVestG testing correctly identified three of four Meniere's disease patients and rejected the diagnosis in 9 of the 10 controls. Two of the 5 dizzy, non-Meniere's patients were incorrectly identified as Meniere's disease. The sensitivity and specificity of EvestG testing were 75% and 80%, respectively. EVestG results were statistically significantly different for Meniere's patients versus the other dizzy patients and controls (Univariate ANOVA difference contrasts p = 0.0340) even in this small sample. The EVestG protocol appeared to show promise as an objective, diagnostic test for Meniere's disease, but our sample size is too small to generalize widely. N.A. Prospective Human clinical trial.


The impact of oral disease and nonsurgical treatment on bacteremia in children.
The authors examine the role of dental disease and nonsurgical dental procedures in the incidence and duration of bacteremia in children. The authors randomized a group of children to receive amoxicillin or a placebo before dental rehabilitation in an operating room setting. They collected eight blood draws at the following times: two minutes after intubation (draw 1); after dental restorations, pulp therapy and cleaning (draw 2); 10 minutes later (draw 3); and five draws during and after dental extractions (draws 4-8). The authors compared dental disease parameters and the type of dental procedures performed with the incidence and duration of bacteremia. The authors enrolled 100 children (aged 1-8 years) in the study. The incidence of bacteremia from draw 2 was 20 percent in the placebo group and 6 percent in the amoxicillin group (P = .07), and the incidence from draw 3 was 16 percent in the placebo group and zero percent in the amoxicillin group (P = .03). Subjects with higher gingival scores were more likely to have a bacteremia for draw 2 (P = .01). The authors found that subjects in the group with bacteremia for draw 3 had undergone more pulpotomies than did subjects in the group without bacteremia for draw 3 (3 +/- 2.5 standard deviation [SD] versus 1.5 +/- 1.6 SD, P = .04), while they found almost no differences for draw 2. This study suggests that gingival disease has an impact on bacteremia after dental restorations and prophylaxis. Although antibiotics have an impact, they do not eliminate bacteremia altogether.


Noncancer palliative care: the lost pieces in an acute care setting in Taiwan.
Little is known about the picture of patients receiving palliative care in the acute care setting. The study was conducted in a medical center in Taiwan. Cancer palliative care (CPC) was performed for terminal do-not-resuscitate (DNR) patients with advanced cancers. Noncancer palliative care (NCPC) was performed for DNR patients who did not fulfill the criteria of CPC. Of the 1379 consecutive admissions, 258 patients were identified, with 193 (74.8%) requiring NCPC and 65 (25.2%) requiring CPC. The NCPC patients were older and had lower Charlson comorbidity index (2.6 vs 8.6, P < .001) than CPC patients and had poorer consciousness and more organ failure than CPC patients when recognized. Many noncancer patients without access to specialist palliative care services were treated in the acute care setting with delayed recognition.


High temperature effects on Pi54 conferred resistance to Magnaporthe oryzae in two genetic backgrounds of Oryza sativa.
The global temperatures are predicted to rise due to climate change. However, knowledge on the mechanisms underlying the effect of high temperature (HT) on plant pathogen interaction is limited. We investigated the effect of elevated temperature on host phenotypic, biochemical and gene expression patterns in the rice-Magnaporthe oryzae (Mo) pathosystem using two genetic backgrounds, Co39 (Oryzae sativa-indica) and LTH (O. sativa-japonica) with (CO and LT) and without (Co39 and LTH) R gene (Pi54). After exposure to 28°C and 35°C the two genetic backgrounds showed contrasting responses to Mo. At 28°C, CO, Co39 and LTH displayed a more severe disease phenotype than LT. Surprisingly, CO became resistant to Mo after exposure to 35°C. CO and LT were used for further analysis to determine the defence related biochemical and transcriptome changes associated with HT induced resistance. Pre-exposure to 35°C triggered intense callose deposits and cell wall fluorescence of the attacked epidermal cells, as well as, increased hydrogen peroxide (H2O2) and salicylic acid (SA) levels. Transcriptional changes due to combined stress (35°C+Mo) were largely overridden by pathogen infection in both backgrounds, suggesting that the plants tended to shift their response to the pathogen. However, significant differences in global gene expression patterns occurred between CO and LT in response to both single (35°C and Mo) and double stress (35°C+Mo). Collectively, our results suggest that rice lines carrying Pi54 respond to Mo by rapid induction of callose and H2O2, and that these resistance mechanisms are amplified at HT. The relative difference in disease severity between CO and LT at 28°C suggests that the genetic background of japonica rice facilitates the function of Pi54 more than the background of indica rice. The phenotypic plasticity and gene expression differences between CO and LT reveal the presence of intricate background specific molecular signatures that may potentially influence adaptation to plant stresses.


A graph-theoretic approach to the identification of three-dimensional patterns of amino acid side-chains in protein structures.
This paper discusses the use of graph-theoretic methods for the representation and searching of three-dimensional patterns of side-chains in protein structures. The position of a side-chain is represented by pseudo-atoms, and the relative positions of pairs of side-chains by the distances between them. This description of the geometry can be represented by a labelled graph in which the nodes and the edges of the graph represent the pseudo-atoms and the sets of inter-pseudo-atomic distances, respectively. Given such a representation, a protein can be searched for the presence of a user-defined query pattern of side-chains by means of a subgraph-isomorphism algorithm which is implemented in the program ASSAM. Experiments with one such algorithm, that due to Ullmann, show that it provides both an effective and a highly efficient way of searching for patterns of side-chains. The method is illustrated by searches for the serine protease catalytic triad, for residues involved in the catalytic activity of staphyloccocal nuclease, and for the zinc-binding side-chains of thermolysin. The catalytic triad pattern search revealed the existence of a second Asp-His-Ser triad-like arrangement of residues in trypsinogen and chymotrypsinogen, in addition to the catalytic residues. In addition the program can be used to search for hypothetical patterns, as is shown for a pattern of three tryptophan side-chains. These searches demonstrate that the search algorithm can successfully retrieve the great majority of the expected proteins, as well as other, previously unreported proteins that contain the pattern of interest.


Synthesis of L-hexoses and their related biomolecules.
Carbohydrates either conjugated or as free entities are major players in numerous biological processes. The desire to comprehend the nature of their functions and further develop therapeutic and diagnostic applications has fuelled the recent upsurge in the glycoscience field. Mainly accessed through chemical synthesis, homogeneous and well-defined sugar constructs are on high demand for structure-activity evaluation. Although the d-sugars, particularly the d-hexoses, have dominated the carbohydrate landscape, L-hexoses also attracted attention because they are known components of important polysaccharides, antibiotics, and other natural products. Nonetheless, the L-hexose-based materials needed for making building blocks for sugar assemblies are rare and are usually expensive if commercially available. Thus, intense efforts were focused on the development of innovative and reliable methods for the acquisition of L-hexoses and their derivatives. This review outlines several efficient and cost-effective routes for the chemical syntheses of L-hexoses, particularly focusing on approaches that utilize commercially abundant sugars as starting materials. A sampling of the applications of the generated L-hexoses in preparing biologically relevant compounds is also provided.


Accidental BTX drops into the conjunctival sac: is this a cause for concern?
Any injector can accidentally spill a few drops of BTX into the eye. It might very well be a harrowing experience to the uninformed: the good news is that the patient is at no risk of untoward sequelae. Although the BTX that diffuses into the orbit from these injections might well cause adverse effects, the same neurotoxin dropped into the eye is no more than a matter of wasting expensive material. We present herein our experience with such an accident, and support it with theoretical considerations.


Update on the Role of Neuropeptide Y and Other Related Factors in Breast Cancer and Osteoporosis.
Breast cancer and osteoporosis are common diseases that affect the survival and quality of life in postmenopausal women. Women with breast cancer are more likely to develop osteoporosis than women without breast cancer due to certain factors that can affect both diseases simultaneously. For instance, estrogen and the receptor activator of nuclear factor-κB ligand (RANKL) play important roles in the occurrence and development of these two diseases. Moreover, chemotherapy and hormone therapy administered to breast cancer patients also increase the incidence of osteoporosis, and in recent years, neuropeptide Y (NPY) has also been found to impact breast cancer and osteoporosis.Y1 and Y5 receptors are highly expressed in breast cancer, and Y1 and Y2 receptors affect osteogenic response, thus potentially highlighting a potential new direction for treatment strategies. In this paper, the relationship between breast cancer and osteoporosis, the influence of NPY on both diseases, and the recent progress in the research and treatment of these diseases are reviewed.


Geographic variation and trade-offs in parasitoid virulence.
Host-parasitoid systems are characterized by a continuous development of new defence strategies in hosts and counter-defence mechanisms in parasitoids. This co-evolutionary arms race makes host-parasitoid systems excellent for understanding trade-offs in host use caused by evolutionary changes in host immune responses and parasitoid virulence. However, knowledge obtained from natural host-parasitoid systems on such trade-offs is still limited. In this study, the aim was to examine trade-offs in parasitoid virulence in Asecodes parviclava (Hymenoptera: Eulophidae) when attacking three closely related beetles: Galerucella pusilla, Galerucella calmariensis and Galerucella tenella (Coleoptera: Chrysomelidae). A second aim was to examine whether geographic variation in parasitoid infectivity or host immune response could explain differences in parasitism rate between northern and southern sites. More specifically, we wanted to examine whether the capacity to infect host larvae differed depending on the previous host species of the parasitoids and if such differences were connected to differences in the induction of host immune systems. This was achieved by combining controlled parasitism experiments with cytological studies of infected larvae. Our results reveal that parasitism success in A. parviclava differs both depending on previous and current host species, with a higher virulence when attacking larvae of the same species as the previous host. Virulence was in general high for parasitoids from G. pusilla and low for parasitoids from G. calmariensis. At the same time, G. pusilla larvae had the strongest immune response and G. calmariensis the weakest. These observations were linked to changes in the larval hemocyte composition, showing changes in cell types important for the encapsulation process in individuals infected by more or less virulent parasitoids. These findings suggest ongoing evolution in parasitoid virulence and host immune response, making the system a strong candidate for further studies on host race formation and speciation.


[The role of node-picking lymphadenectomy in the treatment of differentiated carcinoma of the thyroid].
A retrospective analysis of the treatment of spreading of differentiated thyroid carcinoma to regional lymph nodes was performed in 201 patients observed in 1973-1991. In 183 patients with no clinical metastatic involvement (A group), no lymph node excision was performed. In 36 patients with limited metastatic lymph node involvement (B group), a node-picking lymphadenectomy was performed. After 1977, all patients were treated also with metabolic radiotherapy postoperatively. Actuarial 15-year survival was 98.28% in A group and 87.50% in B group (n.s. difference). In 15 patients with lymph nodal relapse, actuarial 10-year survival was 83.4%. The survival figures are not different from those obtained after more radical operations. So, in limited metastatic involvement of neck lymph nodes by differentiated thyroid carcinoma, in the opinion of the Authors, node-picking lymphadenectomy is equally effective as more radical surgical procedures.


Protein Chips Compatible with MALDI Mass Spectrometry Prepared by Ambient Ion Landing.
We present a technology that allows the preparation of matrix-assisted laser desorption/ionization (MALDI)-compatible protein chips by ambient ion landing of proteins and successive utilization of the resulting protein chips for the development of bioanalytical assays. These assays are based on the interaction between the immobilized protein and the sampled analyte directly on the protein chip and subsequent in situ analysis by MALDI mass spectrometry. The electrosprayed proteins are immobilized on dry metal and metal oxide surfaces, which are nonreactive under normal conditions. The ion landing of electrosprayed protein molecules is performed under atmospheric pressure by an automated ion landing apparatus that can manufacture protein chips with a predefined array of sample positions or any other geometry of choice. The protein chips prepared by this technique are fully compatible with MALDI ionization because the metal-based substrates are conductive and durable enough to be used directly as MALDI plates. Compared to other materials, the nonreactive surfaces show minimal nonspecific interactions with chemical species in the investigated sample and are thus an ideal substrate for selective protein chips. Three types of protein chips were used in this report to demonstrate the bioanalytical applications of ambient ion landing. The protein chips with immobilized proteolytic enzymes showed the usefulness for fast in situ peptide MALDI sequencing; the lectin-based protein chips showed the ability to enrich glycopeptides from complex mixtures with subsequent MALDI analysis, and the protein chips with immobilized antibodies were used for a novel immunoMALDI workflow that allowed the enrichment of antigens from the serum followed by highly specific MALDI detection.


Regulation of bradykinin action at the receptor level.
Intact cultured human foreskin fibroblasts can be used as an in vitro system to study the regulatory events related to kinin receptor function. Specific bradykinin (BK) receptor sites (B2 subtype) were measured by direct binding study and correlated with BK-induced biological effects such as the release of inositol phosphates, formation of prostacyclin (PGI2), and accumulation of cyclic 3'5' adenosine monophosphate (cAMP). Depending on the ambient concentration of BK in the culture medium, homologous receptor downregulation accompanied by a reduction in BK-stimulated PGI2 release occurred. These events were transient and followed by the recovery of both BK binding sites and BK responsiveness that was related to destruction of BK by highly active degradation systems. The fate of receptor-bound [3H]BK was studied by the acetic acid "stripping technique" that completely removes surface-bound [3H]BK while leaving internalized material with the remaining cells. Kinetic analysis of inside/surface ratios of 3H radioactivity revealed data consistent with the hypothesis of internalization of BK-receptor complexes. High-performance liquid chromatography (HPLC) analysis of internalized 3H counts showed significant quantities of intact [3H]BK occurring in an intracellular compartment. Compounds or drugs that enhance intracellular cAMP levels or inhibit generation of eicosanoids were shown to modify the BK response by indirect means. BK-receptor binding sites appear to be under tight regulatory control by both the mechanisms influencing the ambient concentration of BK and the interaction between multiple mediators.


Temperature Preference and Sex Differentiation in African Catfish, Clarias gariepinus.
The African catfish Clarias gariepinus has a genetic sex determination system in which high temperature induces masculinization. The thermosensitive period for sex differentiation is short and occurs very early (from 6 to 8 days posthatching [dph]). As young juveniles can encounter high masculinizing temperature (36.5°C) in African water points, we aimed to determine the thermal preference of sexually undifferentiated juveniles and investigate if they spontaneously move toward high masculinizing temperature. Experiments were carried out in an environmental continuum (28-28-28°C and 28-32-36.5°C) made up of three 50-L aquariums connected together. Four hundred larvae from 10 different full-sib progenies were reared successively from 2 to 14 dph in these facilities. Before and after thermal treatments, fish were reared at 28°C until sex ratio determination at 70 dph. In the control continuum, fish were nearly equally distributed in the three compartments. Conversely, in the thermal continuum, compartment occupation significantly differed with progeny and period. During the highly thermosensitive period, two of five progenies significantly preferred (54.7% and 39.8% occupation) the 36.5°C compartment. All tested progenies reared in thermal continuum and separated 36.5°C aquarium showed a skewed sex ratio toward the male phenotype (78-100%). Nevertheless, no correlation was found between 36.5°C compartment occupation and sex ratio in thermal continuum groups. As masculinization temperature could be encountered in African water points during the spawning season, we discussed the adaptive advantage for the African catfish to display a sex differentiation process controlled by a temperature effect.


Tubal endometriosis diagnosed within one month after menarche: a case report.
A 13-year-old nulligravida girl, 158.5 cm in height and 76.0 kg in body weight, came to our department complaining of continuous right lower abdominal pain. One month earlier, an ovarian cyst in the right ovary, about 3 cm in diameter, was found when she underwent appendectomy at another hospital, but was left untreated. Menarche occurred at the age of 13 years and 1 month, which was after the appendectomy and 24 days before the present operation. Right hematosalpinx with peripheral obstruction and a para-ovarian serous cyst on the same side were diagnosed, and therefore right salpingectomy with para-ovarian cyst resection was performed. The bilateral ovaries and uterus were completely normal by inspection. The post operative histological examination confirmed hematosalpinx and revealed tubal endometriosis.


Barriers preventing Palestinian women from having a mammogram: a qualitative study.
The mammogram is considered a life-saving breast cancer screening procedure for women aged 40 years and older, yet uptake of mammography services by Palestinian women is very low. Breast cancer is the most common cancer, comprising 17% of all reported cancer cases, and the second leading cause of death in women in the occupied Palestinian territory. The aim of this study was to understand the barriers to mammography uptake through an exploratory qualitative study in Ramallah and Salfeet. The qualitative approach of the study consisted of 24 semi-structured, in-person interviews and seven focus-group discussions with women from different settings and backgrounds through a purposive sampling approach. The interviews and discussions focused on women's knowledge of mammograms, reasons behind their decision to use the service or not, and whether they encouraged the service. Interviews were recorded after informed consent was received. Interviews and focus-group discussions were then transcribed and analysed thematically. Women mentioned a variety of barriers, including their psychological, social, and religious beliefs as well as disease-related, health system-related, political, and financial factors. Women expressed psychosocial issues such as shyness, fear from being diagnosed, losing femininity, losing financial and emotional support, losing independence and control of their lives, suffering pain besides low self-prioritising, being busy with children and house keeping, and having low knowledge of mammography. Only one woman expressed political concerns about access to screening services. Interviewees raised cultural factors, and lack of health insurance was a primary barrier to mammography for uninsured, widowed, and divorced women. More women had financial concerns with the treatment process and access if they were found to have cancer. Others had concerns about test efficacy, safety, and importance. Participants also raised issues related to social stigma: many women had concerns about family norms and values with respect to a possible second marriage of their husband if they were diagnosed with cancer as well as the potential negative effect of a cancer diagnosis on their daughters' marriage prospects. Health-seeking behaviours by women are controversial and affect their decision to participate in mammography for screening or diagnoses. Given the sensitivity of the topic and the importance of early detection, health policies need to take those behaviours and barriers into account. None.


Head-to-Head Comparison of 68Ga-PSMA-11 with 68Ga-P137 in Patients with Suspected Prostate Cancer.
P137 is a novel oxalyldiaminopropionic acid-urea-based prostate-specific membrane antigen (PSMA) targeting agent. This study compared the uptake patterns of 68Ga-P137 and the FDA-approved PET tracer 68Ga-PSMA-11 for diagnosing prostate cancer (PCa). Sixteen patients suspected of PCa were scanned by 68Ga-PSMA-11 and 68Ga-P137 PET/CT, respectively, followed by prospective analysis. The tumor-to-background ratio was calculated using normal prostate tissue, blood pool, muscle, and urine as backgrounds. Pathology or follow-up results were used to analyze uptake patterns of benign/malignant lesions and various organs. Thirteen patients were diagnosed with PCa and three with benign prostate diseases (BPD). The number and location of primary lesions, lymph node metastasis (LNM) (n = 25), bone metastasis (n = 30), and liver metastasis (n = 3) detected by the two tracers were identical. Maximum standardized uptake value (SUVmax), tumor/normal prostate ratio, as well as semiquantitative miPSMA-ES and PRIMARY diagnostic scores (P all >0.05) showed similar uptake levels of primary lesions between 68Ga-P137 and 68Ga-PSMA-11. Compared to 68Ga-P137, the SUVmax of 68Ga-PSMA-11 was significantly higher for bone metastasis, LNM, and liver metastasis (14.9 ± 7.2 vs 9.1 ± 4.4, 14.4 ± 5.0 vs 7.5 ± 2.4, 13.9 ± 2.0 vs 8.8 ± 2.4, P all <0.05). One-hour postinjection, SUVmax of the duodenum (9.4 ± 2.1 vs 16.2 ± 6.1), kidney (19.4 ± 4.3 vs 45.6 ± 20.9), and urine (14.1 ± 7.1 vs 42.1 ± 25.9) were significantly lower for 68Ga-P137 than for 68Ga-PSMA-11 (P all <0.05), whereas the radioactivity accumulation of blood pool and muscle (3.9 ± 0.5 vs 1.6 ± 0.4, 1.0 ± 0.1 vs 0.6 ± 0.1, P all <0.05) of 68Ga-P137 was significantly higher than 68Ga-PSMA-11. The uptake level of 68Ga-P137 has no significant difference from that of 68Ga-PSMA-11 in prostate primary lesions, and their imaging performances are visually equivalent for both primary and metastatic lesions, despite a higher blood pool and muscle background and a lower uptake in metastatic lesions. Due to the lower urine excretion of 68Ga-P137, primary prostate lesions near the urine can potentially be displayed clearer than 68Ga-PSMA-11.


Child protective services: research for the future.
The legal context of child protective services provides the framework for all inquiries and knowledge-building in the field. From this foundation, it is possible to analyze the definition of a child protective services case, describe who is served by the system, evaluate current system functioning, and identify outcome measures. Future research should address formative questions such as the development of consistent definitions of maltreatment and evaluation of service delivery. Evaluation should include measuring treatment outcomes as well as examining the functioning and management of the system.


Retinal nerve fiber layer measures in high- and normal-tension glaucoma.
To use optical coherence tomography (OCT) to investigate the qualitative and quantitative differences in the defects of the retinal nerve fiber layer (RNFL) in subjects with high tension primary open angle glaucoma and subjects with normal tension glaucoma. RNFL was assessed with OCT in 21 eyes with high-tension glaucoma (HTG) and 20 eyes with normal-tension glaucoma (NTG). Regression analyses were performed to investigate the interaction of disease group and location for localized RNFL loss, and to predict diffuse and localized RNFL loss as a function of age, mean defect, spherical equivalent, disease group, and location. Local RNFL thicknesses for superior clock-hour regions were estimated after adjustment for the thicknesses of symmetrically opposed locations. There were no differences in mean age, visual field defect mean deviation, and refractive error between subjects in HTG and NTG groups. Diffuse RNFL thickness was not significantly different between the two groups [mean RNFL for NTG > HTG by 3.48 mum, 95% confidence interval (CI) -3.9 to 10.9 microm, p = 0.092]. There was no significant interaction of group and location for localized RNFL loss (p = 0.916). Local RNFL thickness at superior regions was not significantly different in the two groups, after adjustment for RNFL thickness at corresponding inferior locations (mean RNFL for NTG > HTG by 6.30 microm, 95% CI -1.08 to 13.7 microm, p = 0.34). RNFL thickness decreased, on average (1.88 microm/dB mean deviation, 95% CI 1.21 to 2.55 microm, p < 0.0001) and locally (1.37 microm/dB mean deviation, 95% CI 0.79 to 1.96 microm, p < 0.0001), with increasing severity of glaucoma. There is no difference in the spatial pattern of RNFL defects, as assessed by the OCT, between HTG and NTG.


Predicting atrial fibrillation after cardiac surgery: a scoping review of associated factors and systematic review of existing prediction models.
Postoperative atrial fibrillation (POAF) is common after cardiac surgery and associated with increased hospital length of stay, patient morbidity and mortality. We aimed to identify factors associated with POAF and evaluate the accuracy of available POAF prediction models. We screened articles from Ovid MEDLINE® and PubMed Central® (PMC) and included studies that evaluated risk factors associated with POAF or studies that designed or validated POAF prediction models. We only included studies in cardiac surgical patients with sample size n ⩾ 50 and a POAF outcome group ⩾20. We summarised factors that were associated with POAF and assessed prediction model performance by reviewing reported calibration and discriminative ability. We reviewed 232 studies. Of these, 142 fulfilled the inclusion criteria. Age was frequently found to be associated with POAF, while most other variables showed contradictory findings, or were assessed in few studies. Overall, 15 studies specifically developed and/or validated 12 prediction models. Of these, all showed poor discrimination or absent calibration in predicting POAF in externally validated cohorts. Except for age, reporting of factors associated with POAF is inconsistent and often contradictory. Prediction models have low discrimination, missing calibration statistics, are at risk of bias and show limited clinical applicability. This suggests the need for studies that prospectively collect AF relevant data in large cohorts and then proceed to validate findings in external data sets.


Medicaid incentive programs to encourage healthy behavior show mixed results to date and should be studied and improved.
In September 2011 the Centers for Medicare and Medicaid Services awarded $85 million in grants to ten states to test financial incentive programs to encourage healthy behavior among Medicaid enrollees with chronic diseases. There is little published evidence about the effectiveness of such incentives within the Medicaid program. We evaluated the available research from three earlier Medicaid incentive programs and found mixed results. On the one hand, in Florida only about half of the $41.3 million in available credits was "claimed" by enrollees between 2006 and 2011. On the other, Idaho's incentive program was credited with improving the proportion of children who were up-to-date on well-child visits. Our findings suggest that Medicaid incentive programs should be designed so that enrollees can understand them and so that the incentives are attractive enough to motivate participation. Medicaid incentive programs also should be subject to rigorous evaluation to more clearly establish their effectiveness.


The specificity of schizophrenic thought disorder: a replication and extension of previous findings.
Eight thought-disordered schizophrenics, eight non-thought-disordered schizophrenics and eight normal subjects each completed four repertory grids, formed by combinations of two types of construct, psychological and physical, and two types of element, photographs and known people. The finding of McPherson & Buckley (1970) that thought-disordered schizophrenics are relatively less disordered when using physical constructs than when using psychological constructs was replicated. Further, this specificity of schizophrenic thought disorder was extended from grids employing photographs of strangers to grids employing known people, thus disconfirming an explanation of schizophrenic grid performance (Williams, 1971) in terms of 'cue insensitivity'.


Pediatric Stroke: A Single-Center Experience.
The aim of this study was to evaluate the clinical characteristics, risk factors, treatment, and outcomes of pediatric stroke cases. A total of 118 patients diagnosed with arterial ischemic stroke (AIS), hemorrhagic stroke, and sinovenous thrombosis (SVT) between January 2000 and December 2011 were included. Neonatal cases were excluded. Demographic and clinical findings were retrospectively examined from medical records. We identified 118 patients with stroke. The age of the patients ranged from 1 to 215 months (17.92 y), with a mean age of 5.19±5.25 years. AIS accounted for the majority of cases (n=69, 58.5%), and the major etiology was cardiac disease (17%). Hemorrhagic stroke accounted for 19.5% (n=23) of the cases, and late hemorrhagic disease of the newborn was the major etiology (43%, n=10). SVT accounted for 22% (n=26) of the cases, and the major etiology was otitis media-mastoiditis (27%, n=7). Hemiplegia and headache were the most frequent symptoms for AIS and SVT, respectively. Stroke is rare in children compared with adults; however, it is detected more frequently with better imaging techniques and increased awareness. We found that children with AIS presented more commonly with hemiplegia and children with SVT with headache and strabismus. We did not find an association between thrombophilia and stroke.


Effect of ultrasound-activated microbubbles on the cell electrophysiological properties.
New clinical applications of ultrasound contrast microbubbles extend beyond imaging and diagnosis toward therapeutic applications. Cell membrane permeability and the uptake of substances have been shown to be enhanced by microbubbles under ultrasound stimulation. However, the mechanisms of action of ultrasound-activated microbubbles are still unknown. The aim of our study was to examine how microbubbles and ultrasound interact with cells in an attempt to understand the sonoporation mechanism. The ruptured-patch-clamp whole-cell technique was used to measure membrane potential variations of a single cell. SonoVue microbubbles and mammary breast cancer cell line MDA-MB-231 were used. Ultrasound was applied using single-element transducers of 1 MHz. Microbubbles and cells were simultaneously video monitored during ultrasound exposure. Our results showed that, during sonoporation, a marked cell membrane hyperpolarization occurs (n = 6 cells) at negative pressures above 150 kPa, indicating the activation of specific ion channels while the cell and the microbubbles remain viable. The hyperpolarization was sustained for as long as the microbubbles are in a direct contact with the cell and the ultrasound waves are transmitted. Smaller acoustic amplitudes induced only mild hyperpolarization, whereas shutting off the ultrasound brings the cell membrane potential to its resting value. However, ultrasound alone did not affect the cell membrane potential. A similar hyperpolarization of the cell membrane was observed when a mechanical pressure was applied on the cell through a glass probe. In conclusion, the results demonstrate that microbubbles' oscillations under ultrasound activation entail modifications of the electrophysiologic cell activities by triggering the modulation of ionic transports through the plasmic cell membrane. However, only cells in direct contact with the microbubbles are impacted. The mechanisms involved are likely related to activation of specific channels sensitive to mechanical stresses (stretch-activated channels) and possibly nonspecific ion channels.


Evaluation of intestinal absorption after longitudinal intestinal lengthening for short bowel syndrome.
The aim of this study was to answer if the longitudinal intestinal lengthening and tailoring (LILT) by Bianchi, modified by Aigrain, can allow the child to be weaned from parenteral nutrition (PN) and if the length of the bowel after the procedure can influence the results of the absorption test such as Schilling or D-xylose test. We reviewed the files of 7 children who have had LILT from 1980 to 2003. We performed to explore 2 intestinal function tests: the D-xylose and the Schilling tests. Both were performed early (during the first year after the procedure) and late (during the second year) after the LILT. We used the chi2 and Bartlett's correlation tests for statistical analysis. There were 6 boys and 1 girl. The surgical indication was short bowel syndrome with parenteral nutrition owing to multiple intestinal atresia (2 cases), severe necrotizing enterocolitis with volvulus (1 case), necrotizing enterocolitis (1 case), intestinal atresia with gastroschisis (2 cases), and volvulus owing to malrotation (1 case). The length of the bowel was significantly different before and after LILT (P < .0001). After LILT, the length of the bowel was significantly correlated with the percentage of PN on energy at 6 months (P = .02) and at 12 months (P = .001). Moreover, the length of the bowel after the procedure was significantly correlated with the results of the D-xylose test during the first year (P = .002) but not with the results after the second year. The length after lengthening influenced neither the results of the Schilling test during the first nor those of the second year after. Four patients were weaned from the PN 21 months in average after the LILT (57%); 1 was not because we had only a 2-month follow-up. The average follow-up was 111 (5 months; range, 4-206). Longitudinal intestinal lengthening and tailoring for short bowel syndrome is a good option to allow children to be weaned from the PN. The length of the bowel after the procedure can influence the absorption test such as D-xylose during the first postoperative year but not during the second and does not influence the Schilling test. We think it is not necessary to perform these tests during the follow-up of these patients.


The fate of the unexpected positive intraoperative cultures after revision total knee arthroplasty.
Of a consecutive series of 692 revision total knees at 3 centers, intraoperative cultures were unexpectedly found to be positive in 41 cases (5.9%). Of the 41, 29 (71%) cases had a single positive intraoperative culture and were determined to be a probable false positive based on absence of any other evidence of infection, of which 5 were treated with extended course of intravenous antibiotics after hospital discharge and the remaining 24 received no further treatment. None of these 24 patients manifested any sign of infection at follow-up, averaging 46 months (range, 24-74 months). Twelve patients were determined to have probable type 1 periprosthetic infection, 11 of which were treated with a course of antibiotics. Two of these patients became reinfected within a year. A single positive intraoperative culture after revision total knee arthroplasty does not mandate further treatment in the absence of any other signs of infection.


Coelenterazine Indicators for the Specific Imaging of Human and Bovine Serum Albumins.
Albumin assays in serum are important for the prognostic assessment of many life-threatening diseases, such as heart failure, liver disease, malnutrition, inflammatory bowel disease, infections, and kidney disease. In this study, synthetic coelenterazine (CTZ) indicators are developed to quantitatively illuminate human and bovine serum albumins (HSA and BSA) with high specificity. Their functional groups were chemically modified to specifically emit luminescence with HSA and BSA. The CTZ indicators were characterized by assaying the most abundant serum proteins and found that the CTZ indicators S6 and S6h were highly specific to HSA and BSA, respectively. Their colors were dramatically converted from blue, peaked at 480 nm, to yellowish green, peaked at 535 nm, according to the HSA-BSA mixing ratios, wherein the origins and mixing levels of the albumins can be easily determined by their colors and peak positions. The kinetic properties of HSA and BSA were investigated in detail, confirming that the serum albumins catalyze the CTZ indicators, which act as pseudo-luciferases. The catalytic reactions were efficiently inhibited by specific inhibitors, blocking the drug-binding sites I and II of HSA and BSA. Finally, the utility of the CTZ indicators was demonstrated through a quantitative imaging of the real fetal bovine serum (FBS). This study is the first example to show that the CTZ indicators specify HSA and BSA with different colors. This study contributes to the expansion of the toolbox of optical indicators, which efficiently assays serum proteins in physiological samples. Considering that these CTZ indicators immediately report quantitative optical signals with high specificity, they provide solutions to conventional technical hurdles on point-of-care assays of serum albumins.


[Sex hormones in chronic renal failure of the diabetic].
Renal failure per se complicates the study of the hypothalamo-hypophyso-gonadal axis. Impotence in the male and amenorrhoea in the female are virtually constant in advanced renal failure. In men, there is probably a double hypophysogonadal involvement and, hypothetically, in women, a hypothalamic involvement. Although the functional disorders were major in our group of haemodialysed diabetic patients, the laboratory abnormalities were only moderate. These abnormalities were absent in men and women with moderate renal failure. As the pathogenesis of the abnormalities is unknown, preventative treatment cannot be proposed. The clinical and biochemical status of the patients remains unchanged regardless of the dialysis procedure, but transplantation corrects the majority of the abnormalities, including the functional disorders.


Helminth parasitism in two closely related South African rodents: abundance, prevalence, species richness and impinging factors.
We investigated patterns of helminth infection in two closely related rodents (social Rhabdomys pumilio occurring mainly in xeric habitats and solitary R. dilectus occurring mainly in mesic habitats) at 20 localities in different biomes of South Africa and asked if between-species differences were mainly caused by difference in sociality or difference in environmental conditions of their respective habitats. Helminths recovered from the gastrointestinal tract totalled 11 nematode and 5 cestode species from R. pumilio and 19 nematode and 7 cestode species from R. dilectus. In both hosts, mean abundance and prevalence of nematodes were higher compared to cestodes. Cestode infection as well as nematode abundance, species richness or prevalence did not differ between the two rodents. However, incidence of nematode infection was significantly higher in R. dilectus than in R. pumilio. Moreover, nematode numbers and species richness in infracommunities of R. pumilio inhabiting the relatively more xeric Karoo biome were significantly lower than in those inhabiting the relatively less xeric Fynbos biome. Although we could not unequivocally distinguish between effects of host sociality and environmental factors on the number of individuals and species of helminths in the two hosts, differences in the incidence of nematode infection between R. pumilio and R. dilectus as well as differences in the number of nematode individuals and species between R. pumilio from the Fynbos and the Karoo suggested the effect of environmental conditions on helminth infection to be more important than that of sociality.


Hemorheological disorders in the microcirculation following hemorrhage.
We analysed hemorheological disorders in the microcirculation of intestinal mesenterium of adult laboratory rats following massive exsanguinations when the mean arterial pressure dropped and then the hemorrhagic shock developed in the animals. The mesenteric microcirculation was analysed by the Texture Analysis System (Leitz, Wetzlar): (a) diameters of the afferent arterioles, capillaries, and efferent venules; (b) the blood flow velocity; (c) microvascular blood flow changes (during the RBC aggregation); (d) local microvascular hematocrit; and (e) the transformation of capillaries into plasmatic microvessels. During development of the hemorrhagic shock we found that the blood flow velocity decreased in all microvessels, there was an increased RBC aggregation which gradually enhanced in the mesenteric microvessels' lumen causing blood flow slowing down till appearance of stases. A part of the capillaries transformed into plasmatic vessels. Therefore the microcirculation demonstrated a significant decrease, this being related both to the lowered pressure gradient and to specific hemorheological disorders in the capillary networks.


Mechanisms and efficacy of heat and cold therapies for musculoskeletal injury.
Nonpharmacological treatment strategies for acute musculoskeletal injury revolve around pain reduction and promotion of healing in order to facilitate a return to normal function and activity. Heat and cold therapy modalities are often used to facilitate this outcome despite prevalent confusion about which modality (heat vs cold) to use and when to use it. Most recommendations for the use of heat and cold therapy are based on empirical experience, with limited evidence to support the efficacy of specific modalities. This literature review provides information for practitioners on the use of heat and cold therapies based on the mechanisms of action, physiological effects, and the medical evidence to support their clinical use. The physiological effects of cold therapy include reductions in pain, blood flow, edema, inflammation, muscle spasm, and metabolic demand. There is limited evidence from randomized clinical trials (RCTs) supporting the use of cold therapy following acute musculoskeletal injury and delayed-onset muscle soreness (DOMS). The physiological effects of heat therapy include pain relief and increases in blood flow, metabolism, and elasticity of connective tissues. There is limited overall evidence to support the use of topical heat in general; however, RCTs have shown that heat-wrap therapy provides short-term reductions in pain and disability in patients with acute low back pain and provides significantly greater pain relief of DOMS than does cold therapy. There remains an ongoing need for more sufficiently powered high-quality RCTs on the effects of cold and heat therapy on recovery from acute musculoskeletal injury and DOMS.


Acrylamide-induced alterations in lungs of mice in relation to oxidative stress indicators.
The aim of the experiment was to study the influence of acrylamide (ACR) on major antioxidants in the lungs of Swiss mice. The experiment was conducted on male mice that were 8 weeks old. The mice were exposed to ACR at a single dose of 26 µg per animal, which was administered orally. Mice were anesthetized 3, 24, and 48 h after the ACR gavage. Next, histopathological and biochemical analyses of GSH concentration and the activities of SOD, GPx, and CAT were performed in the lungs. Animals exposed to ACR showed demonstrated symptoms of inflammation in lungs, hypertrophy of bronchiolar epithelium, and hyperplasia of alveolar epithelium. GSH concentration was significantly decreased 3 h after ACR gavage, which was followed by a significant increase 48 h after ACR gavage. Similarly, SOD and GPx demonstrated decreased activities 3 h after exposure to ACR, followed by increased activities 48 h after exposure to ACR. CAT activity was significantly increased 24 and 48 h after exposure to ACR. We conclude that oral exposure of mice to ACR results in alterations of lung microstructure, accompanied by the symptoms of redox imbalance.


First report of plasmid-mediated colistin resistance mcr-8.1 gene from a clinical Klebsiella pneumoniae isolate from Lebanon.
Colistin is considered as a last resort treatment for infections caused by multidrug-resistant Enterobacteriaceae. Plasmid-mediated mobile colistin resistance (mcr) genes contributed to the global spread of colistin resistance. This is the first report of plasmid-mediated colistin resistance mcr-8 gene from a clinical Klebsiella pneumoniae K9 isolate recovered from Lebanon. The isolate was characterized phenotypically and genotypically through both short and long read whole-genome sequencing, plasmid typing and conjugation assays. k9 belonged to sequence type 15 and harbored 31 antimicrobial resistance genes. The mcr-8.1 variant was carried on a novel ~ 300 kb multireplicon plasmid having IncFIA, IncR and IncHI1B. The plasmid was conjugative and carried a plethora of antimicrobial resistance determinants. The introduction of novel mcr variants in Lebanon poses an alarming health concern. Surveillance and screening for colistin resistant Enterobacteriaceae and mcr in livestock, animal farms, imported meat and poultry is highly recommended along with monitoring antibiotic use.


Alcohol misuse and posttraumatic stress disorder: a response to Lacoursiere and Coyne.
The criticisms in Lacoursiere and Coyne's comment are refuted point by point. The criticisms of Roy's statistical methods are judged irrelevant because statistical significance related to what was only a tangential issue in Roy's study. The clinical implications of the relationship between posttraumatic stress disorder and alcohol misuse are also discussed.


Cyclodextrin-Assisted Synthesis of Pd/Co/C Nanopolyhedra by ZIF-67 as a Highly Acid Tolerant Catalyst for Hexavalent Chromium Reduction.
The palladium/cobalt/carbon (Pd/Co/C) nanopolyhedra were synthesized by calcinating the precursor prepared by a cyclodextrin (CD) modified palladium acetylacetonate loaded on ZIF-67, hydroxypropyl-β-cyclodextrin (HP-β-CD)-[Pd(acac)2]/ZIF-67. On one hand, the HP-β-CD was used to increase the solubility of Pd(acac)2 by supramolecular interactions, and on the other hand, ZIF-67 was employed to provide the Co/C as the magnetic support. The Pd/Co/C nanopolyhedra obtained with the assistance of HP-β-CD have high activity and reusability for the reduction of the dichromate ion in the presence of formic acid without using any buffer solution, and no significant leaching of metallic Co of the catalyst was observed. This could be ascribed to the fact that the presence of HP-β-CD could lead to a more homogeneous distribution of metallic Pd in the Pd/Co/C nanopolyhedra, which could prevent the dissolution of metallic Co by formic acid.


Microwave-mediated heterocyclization to benzimidazo[2,1-b]quinazolin-12(5H)-ones.
An effective route to benzimidazo[2,1-b]quinazolin-12(5H)-ones from commercially available o-aryl isothiocyanate esters and o-phenylenediamines is reported. This method accommodates a variety of substituents on either starting material and proceeds under microwave irradiation in the presence of barium hydroxide, conditions that do not hydrolyze methyl ester substituents. The pharmacologically pertinent benzimidazoquinazolinone heterocycle is delivered in excellent yield and purity via both solution- and solid-phase protocols, the latter involving traceless release from the resin.


Thermography Improves Clinical Assessment in Patients with Systemic Sclerosis Treated with Ozone Therapy.
Objective. Treatment of scleroderma is challenging and limited. The aim of our study was to evaluate the usefulness of thermography in assessment of the clinical condition (joints movability and skin thickness) in clinically advanced patients with systemic sclerosis before and after ozone therapy. Method. The study included 42 patients aged 32 to 73 years with advanced systemic sclerosis hospitalized in the university clinic between 2003 and 2006. Thermography and clinical examinations were conducted at baseline and after two series of bath in water with ozone. Results. The comparison of results showed significant increase in skin temperature by 2.5°C, significant increase in interphalangeal joints movability by 18 degrees, and significant decrease in skin score by 14.7 points. The skin temperature was correlated with skin score (r = -0.59) and joints movability (r = +0.8). Conclusions. Ozone therapy shows positive effect on clinical parameters and skin temperature as measured with thermography. The study indicated possibility of introducing ozonotherapy as an independent therapy in cases with low level of progression or during remission periods and as additional treatment in patients with advanced disease requiring immunosuppressive treatment. Thermography is useful in assessment of skin condition showing strong correlation between skin temperature and clinical parameters.


[Diagnosis and non-invasive evaluation of a patient with obliterating arteriopathy of the lower limbs].
Obliterating arteriopathy of the lower limbs (OALL) is a pathology that manifests itself late in the natural history of an atheromatous patient. It is largely a localised pathology but should be considered as a marker for more generalised disease, for which the prognosis is modified by cardiac and cerebrovascular complications. Measurement of the systolic blood pressure index at the ankles is indispensable for initial management, with measures inferior to 0.90 correlating with an arterial stenosis of more than 50%, even in the absence of symptoms. Although the diagnosis is above-all clinical, further investigations complete the initial management by estimating the severity of the lesions, identifying the threatening lesions, allowing an overview of the general disease and a follow-up of the patient. Undoubtedly, the Doppler ultrasound remains the first-line investigation of choice. Helical computerised tomography and angiography by magnetic resonance imaging complete the initial investigation when a revascularisation procedure is envisaged, their respective indications depending on the protocols of each Vascular Centre. The walking-on-a-rolling-carpet test allows evaluation of residual functional capacity of the patient at the stage of claudication. The discovery of OALL calls for at least coronary screening, whatever be the stage of severity, with one patient in four dying of a coronary complication in 5 years. Other vascular localisations should be screened for depending on the clinical symptomatology. The medico-economic value of an extensive systematic vascular work-up is, in effect, still only demonstrated for the stage of claudication.


P-glycoprotein polymorphism in hypo- and hyper-thyroidism patients.
P-glycoprotein (Pgp) is encoded by the multidrug resistance gene (MDR1) in humans and is the product of MDR1. It is expressed in various tissues and is related to drug distribution in intestinal erythrocytes, capillary endotel of brain, proximal tubules cells of kidneys and liver canalicular cells. Expression of Pgp is affected by Pgp polymorphism, and exon 26 C3435T polymorphism is the most common one. It has been thought that expression of Pgp is high in C-allele subjects and this situation is responsible for the resistance against some drugs and substances. Pgp may have a role in the distribution of thyroid hormones, drugs used for hypo- and hyperthyroidism and the resistance occurred. For this purpose possible relationship between T and C alleles and frequency of Pgp polymorphism as well as thyroid hormone distribution in patients with hypo- and hyperthyroidism was investigated. Thirty five hyperthyroidism patients diagnosed as Graves' disease, 78 hypothyroidism patients diagnosed as Hashimoto's thyroiditis and 100 healthy volunteers were included in the study. According to the results obtained no statistically significant difference was found in Pgp C3435T polymorphism between hypo- and hyperthyroidism patients. In addition, the serum free T3 levels of hyperthyroidism patients with C alleles was higher than those of subjects with T alleles. No statistically significant difference was seen in the CC, CT and TT genotype frequencies between the patients and control groups. In conclusion, it seems that Pgp polymorphism is not a predictor factor for the occurrence of hypo- and hyperthyroidism. There is a significant relationship between Pgp and the elevated serum free T3 levels of hyperthyroidism patients, and further research will help understand this situation.


[The proper use of carbapenem examined by Monte Carlo simulation].
Monte Carlo simulation was employed for this comparative study to determine the optimal Carbapenem and its dosing strategy to cure the infections by Escherichia coli and Pseudomonas aeruginosa and to consider how the difference of each Carbapenems in dosing regimens and antibiotic activity influenced to maximize % T > MIC. This result revealed that it was important to increase a dose and a number of doses a day, in addition to great antibiotic activity for maximizing % T > MIC.


Mortality from non-malignant respiratory disease in the fibreglass manufacturing industry.
To investigate the question of whether there is an association between workplace exposures and sociodemographic factors and mortality from non-malignant respiratory disease excluding influenza and pneumonia (NMRDxIP) among workers in a fibreglass wool manufacturing facility. A case-control study with cases and controls derived from deaths recorded from the Kansas City plant in the Owens Corning mortality surveillance system. The cases are defined as decedents with NMRDxIP as the underlying cause of death. Matched, unadjusted odds ratios (ORs) were used to assess any association between NMRDxIP and cumulative exposure history and sociodemographic factors individually. Matched, adjusted ORs were obtained by conditional logistic regression to estimate the effect of any one variable while controlling for the effect of all the others. Results of the unadjusted analysis, considering variables one at a time, yielded no significant associations between NMRDxIP and any of the exposure or sociodemographic variables. The smoking OR was substantially increased (OR 5.09; 95%CI 0.65 to undeterimed). Also, there were no significant variables in a conditional logistic regression analysis in which all variables were simultaneously adjusted. ORs for respirable glass fibres were below unity at all concentrations of exposure in the adjusted analysis. For respirable silica there was no consistent relation across all exposure levels. The ORs increased through the first three exposure concentrations but decreased for the highest exposure. However, ORs although not significant, are greater than unity for all respirable concentrations of silica exposure. The findings for Kansas City show no association between respirable glass fibres and NMRDxIP. The adjusted ORs for all exposures to respirable fibres were less than unity. On the other hand, the ORs for silica exposures were all above unity although there was no clear dose-response relation and none of the ORs were significant. Exposures for all substances considered were very low. Further, given the number of cases and controls, the statistical power to detect relatively small increases in risk, if any increase truly exited, was relatively low. The ORs for exposures to silica were all above unity although there was no clear dose-response relation and none of the ORs were significant. These raised ORs for silica suggest that continued surveillance would be prudent.


A novel method for plastic particle sizing in suspension based on acoustic impedance spectrum.
The objective of this paper is to explore the relationship between the characteristics of plastic particles in suspension and acoustic impedance spectrum and to present a novel non-invasive methodology for both spherical and non-spherical particle sizing. By modifying the ultrasonic attenuation spectral model, theories relating acoustic impedance spectrum to particle characteristics have been established to implement quite a few numerical simulations for the first time, revealing that the acoustic impedance of plastic particles is sensitive to changes in particle concentration and size. Afterwards, experiments were carried out on polystyrene suspensions made by particles with different sizes. On the basis of the theoretical analysis, different transducers were employed over a frequency varied from 10MHz to 100MHz for different particle sizes respectively. Not only were spherical particles chosen for the experiment, but also non-spherical particles with three different size distributions considering the fact that practical particles have irregular shapes. All the samples were verified by optical microscope technique and their comparisons with the experimental results show that the plastic particles with different sizes are distinguishable by using acoustic impedance spectrum.


ff14IDPs force field improving the conformation sampling of intrinsically disordered proteins.
Intrinsically disordered proteins are proteins which lack of specific tertiary structure and unable to fold spontaneously without the partner binding. These intrinsically disordered proteins are found to associate with various diseases, such as diabetes, cancer, and neurodegenerative diseases. However, current widely used force fields, such as ff99SB, ff14SB, OPLS/AA, and Charmm27, are insufficient in sampling the conformational characters of intrinsically disordered proteins. In this study, the CMAP method was used to correct the φ/ψ distributions of disorder-promoting amino acids. The simulation results show that the force filed parameters (ff14IDPs) can improve the φ/ψ distributions of the disorder-promoting amino acids, with RMSD less than 0.10% relative to the benchmark data of intrinsically disordered proteins. Further test suggests that the calculated secondary chemical shifts under ff14IDPs are in quantitative agreement with the data of NMR experiment for five tested systems. In addition, the simulation results show that ff14IDPs can still be used to model structural proteins, such as tested lysozyme and ubiquitin, with better performance in coil regions than the original general Amber force field ff14SB. These findings confirm that the newly developed Amber ff14IDPs is a robust model for improving the conformation sampling of intrinsically disordered proteins.


Rituximab therapy in nephrotic syndrome: implications for patients' management.
Rituximab offers an alternative to current immunosuppressive therapies for difficult-to-treat nephrotic syndrome. The best outcomes are seen in patients with steroid-dependent nephrotic syndrome who have failed to respond to multiple therapies. By contrast, the benefits of rituximab therapy are limited in patients with steroid-resistant nephrotic syndrome, particularly those with focal segmental glomerulosclerosis (FSGS). Therapy with plasma exchange and one or two doses of rituximab has shown success in patients with recurrent FSGS. Young patients and those with normal serum albumin at recurrence of nephrotic syndrome are most likely to respond to rituximab therapy. A substantial proportion of rituximab-treated patients with idiopathic membranous nephropathy show complete or partial remission of proteinuria, and reduced levels of phospholipase A(2) receptor autoantibodies, which are implicated in the pathogenesis of this disorder. Successful rituximab therapy induces prolonged remission and enables discontinuation of other medications without substantially increasing the risk of infections and other serious adverse events. However, the available evidence of efficacy of rituximab therapy is derived chiefly from small case series and requires confirmation in prospective, randomized, controlled studies that define the indications for use and predictors of response to this therapy.


Aspirin as a COX inhibitor and anti-inflammatory drug in human skeletal muscle.
Although aspirin is one of the most common anti-inflammatory drugs in the world, the effect of aspirin on human skeletal muscle inflammation is almost completely unknown. This study examined the potential effects and related time course of an orally consumed aspirin dose on the inflammatory prostaglandin E2 (PGE2)/cyclooxygenase (COX) pathway in human skeletal muscle. Skeletal muscle biopsies were taken from the vastus lateralis of 10 healthy adults (5 male and 5 female, 25 ± 2 yr old) before (Pre) and 2, 4, and 24 h after (Post) a standard dose (975mg) of aspirin and partitioned for analysis of 1) in vivo PGE2 levels in resting skeletal muscle and 2) ex vivo skeletal muscle PGE2 production when stimulated with the COX substrate arachidonic acid (5 μM). PGE2 levels in vivo and PGE2 production ex vivo were generally unchanged at each time point after aspirin consumption. However, most individuals clearly showed suppression of PGE2, but at varying time points after aspirin consumption. When the maximum suppression after aspirin consumption was examined for each individual, independent of time, PGE2 levels in vivo (184 ± 17 and 104 ± 23pg/g wet wt at Pre and Post, respectively) and PGE2 production ex vivo (2.74 ± 0.17 and 2.09 ± 0.11pg·mg wet wt-1·min-1 at Pre and Post, respectively) were reduced ( P < 0.05) by 44% and 24%, respectively. These results provide evidence that orally consumed aspirin can inhibit the COX pathway and reduce the inflammatory mediator PGE2 in human skeletal muscle. Findings from this study highlight the need to expand our knowledge regarding the potential role for aspirin regulation of the deleterious influence of inflammation on skeletal muscle health in aging and exercising individuals. NEW & NOTEWORTHY This study demonstrated that orally consumed aspirin can target the prostaglandin/cyclooxygenase pathway in human skeletal muscle. This pathway has been shown to regulate skeletal muscle metabolism and inflammation in aging and exercising individuals. Given the prevalence of aspirin consumption, these findings may have implications for skeletal muscle health in a large segment of the population.


Characterization of Candidate probionts isolated from human breast milk.
This study was designed to isolate and identify the potential probionts present in 32 healthy mothers' breast milk. Microbial culture media and 16SrRNA sequencing were used to isolate and identify the bacteria and all isolates were analyzed for their antagonistic potential, resistance to acidic pH, bile salts and survival under simulated gastric and intestinal conditions. The colonization potential was further assessed based on adherence to human enterocyte-like Caco-2 cell lines. The breast milk samples harbored significant numbers of Gram positive and catalase negative (85%) bacteria. Based on 16SrRNA sequencing, these isolates were identified as Lactobacillus casei, L.gasseri, L.fermentum, L.plantarum, Pediococcus acidilactici, and Enterococcus facieum. Among the isolates, P. acidilactici was the most frequent species (71%) present in these samples. Few Gram and catalase positive isolates, Staphylococcus aureus and S.hominiis were also observed. The isolates were viable and unviable in pH 3 and 1.5, respectively, while all isolates survived in 1.0% bile salt. As putative probionts, P.acidilactici 1C showed a significantly higher percentage of adhesion to Caco-2 cells (p< 0.05)than the other two isolates L.plantarum 7A and E.facieum 2C. Bacterial strains isolated from human breast milk were shown to have probiotic properties including anti-infective protection and may be considered as future therapeutics for infants.


Management of myocardial infarction in the elderly. Insights from Spanish Minimum Basic Data Set.
We aimed to assess the impact of implementation of reperfusion networks, the type of hospital and specialty of the treating physician on the management and outcomes of ST segment elevation myocardial infarction in patients aged ⩾75 years. We analysed data from the Minimum Basic Data Set of the Spanish public health system, assessing hospital discharges between 2004 and 2013. Discharges were distributed in three groups depending on the clinical management: percutaneous coronary intervention, thrombolysis or no reperfusion. Primary outcome measure was all cause in-hospital mortality. For risk adjustment, patient comorbidities were identified for each index hospitalization. We identified 299,929 discharges, of whom 107,890 (36%) were in-patients aged ⩾75 years. Older patients had higher prevalence of comorbidities, were less often treated in high complexity hospitals and were less frequently managed by cardiologists ( p<0.001). Both percutaneous coronary intervention and fibrinolysis were less often performed in elderly patients ( p<0.001). A progressive increase in the rate of percutaneous coronary intervention was observed in the elderly across the study period (from 17% in 2004 to 45% in 2013, p<0.001), with a progressive reduction of crude mortality (from 23% in 2004 to 19% in 2013, p<0.001). Adjusted analysis showed an association between being treated in high complexity hospitals, being treated by cardiologists and lower in-hospital mortality ( p <0.001). Elderly patients with ST segment elevation myocardial infarction are less often managed in high complexity hospitals and less often treated by cardiologists. Both factors are associated with higher in-hospital mortality.


[Off-pump coronary artery bypass: analysis of 1080 patients].
A consecutive cohort including 1080 patients undergoing "off-pump" myocardial revascularization was reviewed. An average of 2.22 bypass/patients was performed. The death-rate during the first 30 days after surgery was 0.65%. Four cases needed cross-over to on-pump. The postoperative events were: need of inotropic drugs (2.7%), atrial fibrillation (12.4%), myocardial infarction (6.6%). The extubation was performed before the first postoperative 24 h in 91.9% of cases. The majority of patients was discharged from hospital before 8 days after surgery. Off pump coronary artery bypass surgery exhibit good results for most of the patients even if they present multiple vessel disease and high operating risk.


[Immunodiagnosis of cancer: requirements and results (author's transl)].
Theoretical aspects are considered on the requirements of immunological cancer tests. The criteria of clinical applicability are: Specificity, sensitivity, information with respect to tumour localisation. Immunodiagnostic tests cover the following areas: Early diagnosis on the basis of screening of the whole population or of risk groups, differential diagnosis, detection of relapse or metastases, prognosis. Experimental results are presented on a test for tumour detection. In a blind test study patients with clinically manifest tumours were recognized in about 80--90%, when using human fetal extract as antigen in the macrophage-electro-phoretic-mobility technique.


Socioeconomic variations in responses to chest pain: qualitative study.
To explore and explain socioeconomic variations in perceptions of and behavioural responses to chest pain. Qualitative interviews. Community based study in Glasgow, Scotland. 30 respondents (15 men and 15 women) from a socioeconomically deprived area of Glasgow and 30 respondents (15 men and 15 women) from an affluent area of Glasgow. Participants' reports of their perceptions of and actions in response to chest pain. Residents of the deprived area reported greater perceived vulnerability to heart disease, stemming from greater exposure to heart disease in family members and greater identification with high risk groups and stereotypes of cardiac patients. This greater perceived vulnerability was not associated with more frequent reporting of presenting to a general practitioner. People from the deprived area reported greater exposure to ill health, which allowed them to normalise their chest pain, led to confusion with other conditions, and gave rise to a belief that they were overusing medical services. These factors were associated with a reported tendency not to present with chest pain. Anxiety about presenting among respondents in the deprived area was heightened by self blame and fear that they would be chastised by their general practitioner for their risk behaviours. Important socioeconomic variations in responses to chest pain may contribute to the known inequities in uptake of secondary cardiology services. Primary care professionals and health promoters should be aware of the ways in which perceptions of symptoms and illness behaviour are shaped by social and cultural factors.


The Interrelationship between Refractive Error, Blood Vessel Anatomy, and Glaucomatous Visual Field Loss.
We quantified the interrelationship between retinal blood vessel (BV) anatomical variation, spherical equivalent (SE) of refractive error, and functional diagnostic parameters in glaucoma to identify optimal parameters for the improvement of optical coherence tomography (OCT) retinal nerve fiber layer thickness (RNFLT) norms. A trained observer marked the intersections of the main superior/inferior temporal arteries and veins with concentric circles around the optic nerve head (ONH) center on fundus images. The interrelationship of BV, SE, and visual field global parameters was analyzed by multivariate regression and model comparison. A total of 445 eyes of 445 patients in a large glaucoma practice were selected. Of all investigated BV parameters, interartery angles (IAA) between superior and inferior arteries at a radius of 1.73 mm around the ONH center demonstrated the strongest relationship to SE (Bayesian information criterion difference to null model, 11.9). SE and BV parameters are unrelated to functional parameters, including mean deviation (MD), pattern standard deviation, and glaucoma hemifield test results. BV locations outside the ONH are sufficiently stable over glaucoma severity to represent individual eye anatomy, and the IAA at 1.73 mm eccentricity is the optimal parameter to be considered for novel OCT RNFLT norms. Among a large set of BV location parameters, considering IAA may improve RNFLT norms optimally and thereby increase the accuracy of clinical glaucoma diagnosis.


Nisin-induced changes in Bacillus morphology suggest a paradigm of antibiotic action.
Nisin is a small cationic lanthionine antibiotic produced by Lactococcus lactis. During its antimicrobial action, it targets intermediates in the bacterial cell-wall biosynthesis, lipid II, and undecaprenyl pyrophosphate. Here, we report results from electron microscopic investigations of the effects of lethal nisin doses on Bacillus subtilis cell morphology. Bacterial membranes were permeabilized shortly after B. subtilis was incubated with nisin, but this did not lead to immediate cell death. Cell division, as well as other life functions, persisted over at least half an hour after nisin was added. Slower bacterial elongation, consistent with cell envelope inhibition and accelerated division, resulted in cell-length reduction. Abnormal morphogenesis near the division site suggests this to be the primary site of nisin action. Morphological changes are characteristic of deregulation of a filamentous cell envelope protein, Mbl, and the division-inhibiting Min system. We propose a previously undescribed model, in which the lethal action of nisin against B. subtilis starts with membrane permeabilization and is followed by accelerated cell division, cell envelope inhibition, and aberrant cell morphogenesis.


Plate presetting and arthroscopic reduction technique (PART) for treatment of distal radius fractures.
Arthroscopy has been reported to be an efficient adjunct for the surgical treatment for distal radius fractures (DRF). However, performing wrist arthroscopy during palmar locking plate fixation seems to be troublesome. We have developed a surgical technique involving presetting of a palmar locking plate and an arthroscopic reduction technique (PART) of the fracture that can facilitate the procedure. This study is aimed to investigate the effectiveness of our technique in the treatment of DRF. 249 fractures of the distal radius were treated by PART. 205 fractures in 200 patients were followed-up on average for 15 (12-60) months. There were 46 men and 154 women with an average age of 62 (16-85) years. According to the AO/ASIF fracture classification system there were 51 extra-articular fractures, and 154 intra-articular fractures. Scapholunate interosseous ligament injuries were classified according to Geissler and tears of the triangular fibrocartilage complex according to Abe. On arthroscopic inspection, residual intra-articular fragment dislocation after reduction under fluoroscopy was evaluated. Final evaluation included a radiological examination, measurements of wrist and forearm motion, grip strength, the Mayo modified wrist score (MMWS), and the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. On arthroscopic inspection, intraarticular dislocations were found to be residual in 22.7%, even if reduction seemed to have been achieved when viewed by fluoroscopy. Scapholunate interosseous ligament tears were recognized in 29.8%, and triangular fibrocartilage complex tears in 62.4%. The mean palmar tilt was 5.7 (-10 to 16)°, radial inclination 26.0 (18-31)°, and ulnar variance 0.1 (-2 to 5) mm. The mean extension of the wrist was 71 (50-85)°, and the mean flexion was 62 (40-79)°. The mean pronation of the forearm was 87.5 (70-90)°, and the mean supination was 89.1 (75-95)°. The mean grip strength was 90.0% (31-133%) of the opposite side. According to the MMWS there were 156 excellent, 47 good, and 2 fair results. The mean DASH score was 3.9. The palmar locking plate in combination with arthroscopic reduction technique (PART) leads to good and excellent results. It can be recommended for all fractures of the distal radius needing operative treatment. Arthroscopic reduction of intra-articular fragments is superior to reduction under fluoroscopy. PART allows also the detection of intra-articular soft tissue lesions such as scapholunate ligament tears and injuries of the triangular fibrocartilage complex.


Chemical composition of an aqueous oxalato-/citrato-VO(2+) solution as determinant for vanadium oxide phase formation.
Aqueous solutions of oxalato- and citrato-VO(2+) complexes are prepared, and their ligand exchange reaction is investigated as a function of the amount of citrate present in the aqueous solution via continuous-wave electron paramagnetic resonance (CW EPR) and hyperfine sublevel correlation (HYSCORE) spectroscopy. With a low amount of citrate, monomeric cis-oxalato-VO(2+) complexes occur with a distorted square-pyramidal geometry. As the amount of citrate increases, oxalate is gradually exchanged for citrate. This leads to (i) an intermediate situation of monomeric VO(2+) complexes with a mix of oxalate/citrate ligands and (ii) a final situation of both monomeric and dimeric complexes with exclusively citrato ligands. The monomeric citrato-VO(2+) complexes dominate (abundance > 80%) and are characterized by a 6-fold chelation of the vanadium(IV) ion by 4 RCO2(-) ligands at the equatorial positions and a H2O/R-OH ligand at the axial position. The different redox stabilities of these complexes, relative to that of dissolved O2 in the aqueous solution, is analyzed via (51)V NMR. It is shown that the oxidation rate is the highest for the oxalato-VO(2+) complexes. In addition, the stability of the VO(2+) complexes can be drastically improved by evacuation of the dissolved O2 from the solution and subsequent storage in a N2 ambient atmosphere. The vanadium oxide phase formation process, starting with the chemical solution deposition of the aqueous solutions and continuing with subsequent processing in an ambient 0.1% O2 atmosphere, differs for the two complexes. The oxalato-VO(2+) complexes turn into the oxygen-deficient crystalline VO2 B at 400 °C, which then turns into crystalline V6O13 at 500 °C. In contrast, the citrato-VO(2+) complexes form an amorphous film at 400 °C that crystallizes into VO2 M1 and V6O13 at 500 °C.


Does sexual dimorphism vary by population? Laryngeal and ear anatomy in cricket frogs.
Acoustic communication in many anuran species can show the effects of both natural and sexual selection. This is reflected in the sexually dimorphic anatomy of the larynx and ear structures, as well as the allometric relationship of these morphological traits to head or body size. In this study, we examined laryngeal and ear structures of cricket frogs Acris crepitans not only as sexually dimorphic characteristics, but also as they differ across populations in environmentally different habitats. We used 2-way ANOVA to determine whether the volumetric or linear measurements of these structures differed by sex and population. Females have significantly larger body, head, and ear sizes, but significantly smaller larynges than males. Furthermore, females as well as males show larger body and head sizes, ears, and larynges in a dryer open habitat. An ANCOVA analysis shows that males, but not females, differ in laryngeal size across populations beyond the allometric changes attributable to head size alone indicating that males have a greater degree of laryngeal population variation. In contrast, our covariate analysis found that in both sexes many of the ear differences are non-significant once head size is accounted for, suggesting that most of the population-level ear variation is due to allometric effects of body size. We conclude that although both sexes show size differences in the larynx related to selection for larger body size in dry, open habitats, selection on males for larger larynx size related to the production of lower frequency calls in those habitats does not result in correlated changes in the female larynx. The results suggest that in anurans, selection for changes in body and head size affects both sexes equally, male calls and the vocal structures responsible for them can further diversify without concordant changes in females.


In vitro mineralization and bone osteogenesis in poly(ε-caprolactone)/gelatin nanofibers.
The implementation of bio-inspired strategies in developing scaffolds for the reconstruction of oral, craniofacial and bone skeletal tissues after injury or resection remains a challenge. Currently, advanced scaffolds comprising nanofibers endowed with biochemical/biophysical signaling capability offer great advantages in bone regeneration, because of their faithful mimesis of the characteristic size scales encountered in the fibrous network of the native extracellular matrix (ECM). In this study, we investigate the biological potential of nanofibers made of polycaprolactone and gelatin on guiding the regenerative mechanisms of bone. Contact angle measurements and environmental SEM investigations indicate a weak linkage of gelatin molecules to PCL chains, facilitating an efficient adhesion signal to cells up to 3 days of culture. In vitro studies performed on human mesenchymal stem cells (hMSC) until 3 weeks in culture medium with osteogenic supplementation, clearly showing the effectiveness of PCL/Gelatin electrospun scaffolds in promoting bone osteogenesis and mineralization. The increase of alkaline phosphatase activity (ALP) and gene expression of bone-related molecules (bone sialoprotein, osteopontin and osteocalcin), indicated by immunodetection and upregulation level of mRNA, confirm that proposed nanofibers promote the osteogenic differentiation of hMSC, preferentially in osteogenic medium. Moreover, the evidence of newly formed collagen fibers synthesis by SIRCOL and their mineralization evaluated by Alizarin Red staining and EDS mapping of the elements Ca, P and Mg corroborate the idea that native osteoid matrix is ultimately deposited. All these data suggest that PCL and gelatin electrospun nanofibers have great potential as osteogenesis promoting scaffolds for successful application in bone surgery.


TIME OF ORIGIN AND BIOGEOGRAPHICAL HISTORY OF SPECIALIZED RELATIONSHIPS BETWEEN NORTHERN MARINE PLANTS AND HERBIVOROUS MOLLUSCS.
A survey of cool-temperate North Pacific and North Atlantic marine plants and herbivorous molluscs and their descendants was undertaken to determine the time of origin and the biogeographical history of specialized host-guest relationships between plants and herbivores. Of 12 such associations, 6 (50%) were established no earlier than the Pliocene. These six associations resulted from the invasion of either the plant (three cases) or the herbivore (three cases) from geographical regions other than the one in which the association was forged. These results are contrary to the widely held view that specialized ("coevolved") relationships tend to be ancient, and highlight the importance of biotic interchange as a biogeographical process influencing the opportunity for trophic specialization.


One-year safety of ibuprofen/famotidine fixed combination versus ibuprofen alone: pooled analyses of two 24-week randomized, double-blind trials and a follow-on extension.
To evaluate the safety of the fixed combination of ibuprofen and famotidine compared with ibuprofen alone from two 24-week, multicenter, double-blind trials designed to evaluate the comparative incidence of endoscopically documented upper gastrointestinal ulcers and a 28-week double-blind extension study. Safety was analyzed by pooling data from the two double-blind trials and the follow-on study. Safety was assessed by monitoring the incidence, causality, and severity of adverse events (AEs). In the pivotal efficacy and safety trials, discontinuation rates due to any cause and dyspepsia were significantly lower for the ibuprofen/famotidine combination versus ibuprofen alone. Other than dyspepsia, gastrointestinal and cardiovascular AEs of special interest were similar. Events judged to be treatment related were significantly lower with the ibuprofen/famotidine combination (20.6% vs. 25%). In the safety extension population, there were no differences in the discontinuation rates and the reporting of AEs or serious AEs (SAEs) between the two groups. Gastrointestinal-related events were similar between the groups. Incidence of cardiovascular-related AEs of special interest were 11% (ibuprofen/famotidine) and 2% (ibuprofen) (p=0.06), possibly due to a higher number of rheumatoid arthritis patients in the combination group. Of these, 80% were reports of hypertension (8% ibuprofen/famotidine vs. 2% ibuprofen). Three cases of hypertension in the ibuprofen/famotidine group were considered treatment related. The probability of a cardiovascular event decreased during days 112-167 of treatment and remained low with continued treatment. One-year safety data from two pivotal trials and a long-term extension study indicate that the ibuprofen/famotidine combination demonstrates a favorable gastrointestinal safety profile and more patients continued on therapy compared to ibuprofen alone. No new safety signals have been identified. These data offer additional evidence supporting a new therapeutic option to improve gastrointestinal safety and adherence for patients who require long-term ibuprofen.


Pharmacological comparison of UTP- and thapsigargin-induced arachidonic acid release in mouse RAW 264.7 macrophages.
1. Although stimulation of mouse RAW 264.7 macrophages by UTP elicits a rapid increase in intracellular free Ca2+ ([Ca2+]i), phosphoinositide (PI) turnover, and arachidonic acid (AA) release, the causal relationship between these signalling pathways is still unclear. In the present study, we investigated the involvement of phosphoinositide-dependent phospholipase C (PI-PLC) activation, Ca2+ increase and protein kinase activation in UTP-induced AA release. The effects of stimulating RAW 264.7 cells with thapsigargin, which cannot activate the inositol phosphate (IP) cascade, but results in the release of sequestered Ca2+ and an influx of extracellular Ca2+, was compared with the effects of UTP stimulation to elucidate the multiple regulatory pathways for cPLA2 activation. 2. In RAW 264.7 cells UTP (100 microM) and thapsigargin (1 microM) caused 2 and 1.2 fold increases, respectively, in [3H]-AA release. The release of [3H]-AA following treatment with UTP and thapsigargin were non-additive, totally abolished in the Ca2+-free buffer, BAPTA (30 microM)-containing buffer or in the presence of the cPLA2 inhibitor MAFP (50 microM), and inhibited by pretreatment of cells with pertussis toxin (100 ng ml(-1)) or 4-bromophenacyl bromide (100 microM). By contrast, aristolochic acid (an inhibitor of sPLA2) had no effect on UTP and thapsigargin responses. 3. U73122 (10 microM) and neomycin (3 mM), inhibitors of PI-PLC, inhibited UTP-induced IP formation (88% and 83% inhibition, respectively) and AA release (76% and 58%, respectively), accompanied by a decrease in the [Ca2+]i rise. 4. Wortmannin attenuated the IP response of UTP in a concentration-dependent manner (over the range 10 nM-3 microM), and reduced the UTP-induced AA release in parallel. RHC 80267 (30 microM), a specific diacylglycerol lipase inhibitor, had no effect on UTP-induced AA release. 5. Short-term treatment with PMA (1 microM) inhibited the UTP-stimulated accumulation of IP and increase in [Ca2+]i, but had no effect on the release of AA. In contrast, the AA release caused by thapsigargin was increased by PMA. 6. The role of PKC in UTP- and thapsigargin-mediated AA release was shown by the blockade of these effects by staurosporine (1 microM), Ro 31-8220 (10 microM), Go 6976 (1 microM) and the down-regulation of PKC. 7. Following treatment of cells with SK&F 96365 (30 microM), thapsigargin-, but not UTP-, induced Ca2+ influx, and the accompanying AA release, were down-regulated. 8. Neither PD 98059 (100 microM), MEK a inhibitor, nor genistein (100 microM), a tyrosine kinase inhibitor, had any effect on the AA responses induced by UTP and thapsigargin. 9. We conclude that UTP-induced cPLA2 activity depends on the activation of PI-PLC and the sustained elevation of intracellular Ca2+, which is essential for the activation of cPLA2 by UTP and thapsigargin. The [Ca2+]i-dependent AA release that follows treatment with both stimuli was potentiated by the activity of protein kinase C (PKC). A pertussis toxin-sensitive pathway downstream of the increase in [Ca2+]i was also shown to be involved in AA release.


Experimental demonstration of deterministic quantum search for multiple marked states without adjusting the oracle.
Grover's search algorithm is a well-known quantum algorithm that has been extensively studied and improved to increase its success rate and enhance its flexibility. However, most improved search algorithms require an adjustment of the oracle, which may not be feasible in practical problem-solving scenarios. In this work, we report an experimental demonstration of a deterministic quantum search for multiple marked states without adjusting the oracle. A linear optical setup is designed to search for two marked states, one in a 16-state database with an initial equal-superposition state and the other in an 8-state database with different initial nonequal-superposition states. The evolution of the probability of finding each state in the database is also measured and displayed. Our experimental results agree well with the theoretical predictions, thereby proving the feasibility of the search protocol and the implementation scheme. This work is a pioneering experimental demonstration of deterministic quantum search for multiple marked states without adjusting the oracle.


A brief overview of the most common histiocytic disorders.
Histiocytosis refers to a diverse collection of disorders unified by a proliferation and accumulation of histiocytes into a variety of organs. The following review article will discuss and briefly describe the clinical and histological findings of some of the more common histiocytic disorders. The article is divided into sections according to the current classification system and prevalence of the condition.


Aedes mosquito in Aswan Governorate, Egypt.
Mosquitoes play the most serious role in transmission of many zoonotic diseases over the world, particularly in the Tropic and Sub-tropic countries. This paper surveyed Aswan Governorate for the immature and matures stages of the tiger mosquito, Aedes aegypti.


Prevalence of antibody to group B (atypical) rotavirus in humans and animals.
Enzyme-linked immunosorbent assays were developed for the detection of group B rotavirus antigen and antibody. The specificities of both assays were evaluated for antigens and serum specific for rotavirus groups A to D. Serum collected in the United Kingdom from different animal species exhibited the following high prevalence of group B rotavirus-specific antibody: pigs, 97%; cattle, 71%; sheep, 91%; and goats, 91%. In human serum, a lower prevalence of group B-specific antibody was detected; serum from blood donors showed 10% prevalence, and serum from veterinarians showed 4% prevalence.


Enkephalins and Endorphins. Clinical, pharmacological and therapeutic implications.
During the past 8 years there has been substantial progress in our understanding of the structure, distribution and action of endogenous opioid peptides. Currently, there appear to be 2 groups of peptides; those derived from beta-lipotropin and an enkephalin-related group. Some of these peptides have been shown to be distributed widely in the central nervous system and in endocrine tissues. The activity of the peptides probably occurs at several receptors but only 1 relatively specific (mu-receptor) antagonist, naloxone, is well studies. Although there have been many clinical studies of the action of opioids in man, no novel therapeutic applications have yet been established in clinical practice. Of the many areas of involvement attributed to opioids, those of analgesia, reproductive endocrinology, opiate dependence, and certain as yet undefined subtypes of major psychoses seem reasonably promising. Speculation surround opioid involvement in other disorders such as spinal trauma, septic shock, alcohol dependence, "functional' gastrointestinal disease, diabetes and asthma is of considerable interest but is supported by less clinical evidence. It seems that as research in opioids advances, the putative physiological opioid "spheres of influence' widen. At the same time, opioid mechanisms of action are being revealed to be more subtle and complex than previously thought. As a consequence, the expectations of rapid therapeutic application of opioid peptides and their antagonists are being modified and refined and realistic research strategies applied. In view of the work reviewed in this paper it seems reasonable to expect that such work will pay dividends in the not too distant future.


Importance of chirality and reduced flexibility of protein side chains: a study with square and tetrahedral lattice models.
Side chains of amino acid residues are the determining factor that distinguishes proteins from other unstable chain polymers. In simple models they are often represented implicitly (e.g., by spin states) or simplified as one atom. Here we study side chain effects using two-dimensional square lattice and three-dimensional tetrahedral lattice models, with explicitly constructed side chains formed by two atoms of different chirality and flexibility. We distinguish effects due to chirality and effects due to side chain flexibilities, since residues in proteins are L residues, and their side chains adopt different rotameric states. For short chains, we enumerate exhaustively all possible conformations. For long chains, we sample effectively rare events such as compact conformations and obtain complete pictures of ensemble properties of conformations of these models at all compactness region. This is made possible by using sequential Monte Carlo techniques based on chain growth method. Our results show that both chirality and reduced side chain flexibility lower the folding entropy significantly for globally compact conformations, suggesting that they are important properties of residues to ensure fast folding and stable native structure. This corresponds well with our finding that natural amino acid residues have reduced effective flexibility, as evidenced by statistical analysis of rotamer libraries and side chain rotatable bonds. We further develop a method calculating the exact side chain entropy for a given backbone structure. We show that simple rotamer counting underestimates side chain entropy significantly for both extended and near maximally compact conformations. We find that side chain entropy does not always correlate well with main chain packing. With explicit side chains, extended backbones do not have the largest side chain entropy. Among compact backbones with maximum side chain entropy, helical structures emerge as the dominating configurations. Our results suggest that side chain entropy may be an important factor contributing to the formation of alpha helices for compact conformations.


Diagnostic and therapeutic approach of systemic amyloidosis.
Amyloidosis is a group of diseases, all characterised by deposition of protein fibrils with a beta-sheet structure. This structure generates affinity of amyloid for Congo red dye and is resistant to proteolysis. Three types of systemic amyloidosis are important for the clinician: AA (related to underlying chronic inflammation), AL (related to underlying monoclonal light chain production) and ATTR amyloidosis (related to old age or underlying hereditary mutations of transthyretin). Signs and symptoms vary considerably among the three types and the choice of treatment differs completely. A stepwise approach in diagnosis and therapy is presented. When amyloidosis is suspected the first step is histological proof of amyloid and the second is proof of systemic involvement. The next two steps are determination of the type of amyloid followed by detection of the precursor protein. The fifth step is a thoughtful clinical evaluation, necessary for assessment of prognosis and therapy. Subsequently, the choice of therapy is based on the 'precursor-product' concept. In the final step, the effects of therapy on the underlying disease as well as on the amyloidosis are assessed during follow-up. In this evaluation serum amyloid P component (SAP) scintigraphy helps to show organ involvement and therapy response.


T cell development in the chicken.
This review summarizes our current view of gamma delta and alpha beta T cell development in the chicken. In it we emphasize the functional interplay between the gamma delta and alpha beta T cell subpopulations.