Identification and characterization of Cu(2)O- and ZnO-binding polypeptides by Escherichia coli cell surface display: toward an understanding of metal oxide binding.
We have used the FliTrx cell surface display system to identify disulfide-constrained dodecapeptides binding to the semiconducting metal oxides Cu(2)O and ZnO. Sequence analysis of the inserts revealed that the two populations exhibit similar, yet subtly different patterns of amino acid usage. Both sets of binders were enriched in arginine, tryptophan, and glycine with a higher degree of positional preference in the case of Cu(2)O binders. Tyrosine, proline, and serine were underrepresented in both populations. Peptides binding electrodeposited Cu(2)O or ZnO with high avidity could be subdivided into two classes based on pI and hydrophilicity. In the hydrophilic and positively charged Class I binders, the Arg-X-X-Arg tetrapeptide appears to be implicated in metal oxide binding, whereas Arg-Arg and Arg-Lys pairs allow for discrimination between Cu(2)O and ZnO. Molecular dynamics simulations of the disulfide-constrained peptides suggest that the aforementioned motifs are important to properly orient two basic residues that are likely to contact the metal oxides. The implications of our results in understanding the rules governing the interaction between peptides and inorganic compounds and in their use for the design of hybrid nanoarchitectures are discussed.


Are Drinking Cognitions Associated with Marijuana and Concurrent Alcohol and Marijuana Use among Adolescents and Young Adults?
Concurrent use of alcohol and marijuana (i.e., CAM use) is the most common poly-drug use pattern among adolescents and young adults and is associated with negative outcomes. Research indicates that Prototype Willingness Model (PWM) drinking cognitions are associated with alcohol use. This secondary analysis was conducted to explore cross-sectional associations between PWM drinking cognitions, alcohol, marijuana, and CAM use. Adolescents and young adults between 15-25 years (N = 124, M age = 18.7) completed a baseline assessment as part of a larger study, including questions on alcohol and marijuana use, and PWM drinking cognitions. In the social reaction pathway, descriptive norms, perceived vulnerability, and prototype favorability, but not willingness were associated with greater alcohol use, whereas in the reasoned pathway attitudes and intentions were associated with frequency of drinking whereas injunctive norms were not. Both willingness and intention to drink were related to marijuana and CAM use when controlling for alcohol use frequency. Greater willingness to drink was the only significant predictor of marijuana use, and only descriptive norms predicted CAM use. However, of the cognitions within the reasoned pathway, greater attitudes toward drinking and drinking intention were related to greater marijuana and CAM use. Results also indicated that CAM users displayed higher levels of certain risk cognitions than non-users or single substance users. Findings support and extend the utility of the PWM by indicating that specific alcohol cognitions are associated with alcohol, marijuana, and CAM use in adolescents and young adults.


Novelty in Impact of Neurorehabilitation in a Classic Case of Syringomyelia.
A fluid-filled hole inside the parenchyma or central canal of the spinal cord causes syringomyelia, a neurological condition. It is most frequently linked to type 1 Chiari malformations. Syringomyelia can be caused by tumors in the spinal cord, trauma, and post-traumatic or infectious adhesive arachnoiditis. Syringomyelia is shown to have a prevalence of 8.4/100,000 to 0.9/10,000 in certain studies, making it one of the few unusual cases. A large proportion of patients are between 20 and 50 years of age. In our case, the patient is a 17-year-old boy who complained of tingling and weakness in both lower extremities, as well as loss of sensation in both hands. MRI of his spine revealed a Chiari I malformation involving evidence of medulla, fourth ventricle, and cerebellar vermis displacement into the foramen magnum. Arnold Chiari's malformation with cord syringomyelia and tonsillar herniation was diagnosed based on the symptoms and investigation findings. The goal of this case is to highlight the benefits of exercise treatment in improving the patient's quality of life, as physiotherapy protocol instillation is not practiced on a daily basis for such conditions.


Chemical Characterization and Biological Activity of the Mastic Gum Essential Oils of Pistacia lentiscus Var. Chia from Turkey.
The essential oils (EOs) were isolated by hydrodistillation from wild and cultivated Pistacia lentiscus L. var. chia-mastic gum tree (Anacardiaceae) from two natural habitats, namely from Cesme-Uzunkoy (1) and Mordogan (2), and one cultivated source, Cesme-Germiyan (3), in Izmir, Turkey. This comparative study evaluated the chemical composition and biological activity of mastic gum essential oils (MGEOs). For this purpose, MGEOs 1-3 were analyzed by gas chromatography-flame ionization detection (GC-FID), gas chromatography-mass spectrometry (GC-MS), and chiral GC for α-pinene. Laboratory assays were conducted to assess for potential in vitro cytotoxicity (multiple in vitro cancer cell lines), antimicrobial properties (five bacterial species and yeast), anti-inflammatory activity (inhibition of inducible nitric oxide synthase, iNOS), and the attraction of Ceratitis capitata (Mediterranean fruit fly, medfly), respectively. Chemical analysis indicated that MGEOs 1 and 2 were rich in α-pinene (56.2% and 51.9%), myrcene (20.1% and 18.6%), and β-pinene (2.7% and 3.1%), respectively; whereas MGEO-3 was characterized by a high level of α-pinene (70.8%), followed by β-pinene (5.7%) and myrcene (2.5%). Chiral GC analyses showed that concentration ratios between (-)/(+)-α-pinene and (-)-α-pinene/myrcene allowed for differentiation between wild and cultivated MGEO sources. In biological assays, MGEOs 1-3 did not exhibit significant antimicrobial effects against the pathogens evaluated and were not strong attractants of male medflies; however, all three MGEOs displayed a dose-dependent inhibition of iNOS, and MGEOs 1 and 2 exhibited selective in vitro cytotoxicity against human cancer cells. These results suggest that wild-type mastic gum oils from Cesme and Mordogan (MGEOs 1 and 2) are potential sources of beneficial products and warrant further investigation.


AP-1 activity rises by stimulation-dependent c-Fos expression in auditory neurons.
Acoustical or intracochlear stimulation may induce expression of the immediate early gene product c-Fos in neurons throughout the auditory brainstem. Attempting to estimate its consequences, we sought to determine if c-Fos expression occurs in neurons that also contain c-Jun p39 with which it could form the heterodimeric transcription factor AP-1 to activate a large number of genes, among them several involved in neuroplastic remodeling. Following intracochlear stimulation, c-Fos and c-Jun were found to be colocalized in nuclei of many neurons at all levels of the subcortical auditory system. We conclude that stimulation triggers Fos-Jun dimerization, causing cascades of gene expression that potentially culminate in structural changes of neurons affected by the specific pattern of activity imposed on the neuronal system.


[A novel oncogene from a human hepatocellular carcinoma].
Primary human hepatocellular carcinomas (HCC) were surveyed for oncogenes by transformation assays using NIH3T3 cells and the calcium phosphate coprecipitation method. High-molecular-weight DNA obtained from the HCC tissues was employed for this purpose. One new transforming DNA, named lca (for liver cancer) was obtained, and its properties were studied in detail. This transforming DNA had a linkage to the Alu sequence and was cloned in lambda phage. Restriction enzyme analyses showed that the minimum size of the lca DNA is about 10.5 kilobase pairs and that its nucleotide sequence is different from that of any known human gene or retroviral oncogene. Southern blot analyses of DNAs from flow-sorted human chromosomes and human-mouse somatic cell hybrids indicated that the lca DNA is located on human chromosome 2. It showed identical restriction enzyme cleavage profiles with its counterpart DNA obtained from normal tissue, indicating that there is no extensive DNA rearrangement associated with the activation process of the lca DNA. The normal counterpart DNA shows no transforming activity. An independently obtained transforming DNA from another HCC exhibited identical restriction enzyme cleavage profiles. Thus, lca DNA is likely to represent a commonly encountered transforming DNA in HCC.


[Effects of salmon calcitonin in treatment of osteoporosis in patients undergoing dialysis].
To investigate the prevalence of osteoporosis in patients undergoing maintenance dialysis and explore the safety and efficacy of salmon calcitonin in maintenance dialysis patients underwent with osteoporosis. Double-energy X-ray bone density meter was used on 256 patients undergoing maintenance dialysis, 126 males and 130 females, aged 60 +/- 14 (22 -79), to measure the bone mineral density (BMD) at the lumbar spine and femoral neck. 108 of them with the T values < -2.5 s were diagnosed as with osteoporosis, and then were randomly divided into 2 equal groups matched in baseline age, sex, mode of dialysis, and levels of iPTH, ALP, and BMD: control group receiving oral administration of calcium carbonate 1500 mg tid and rocaltrol 0.25 microg qn for 18 months, and experimental group, received subcutaneous injection of salmon calcitonin (50 U) three times a week in addition. The BMD levels of lumbar spine and femoral neck, and serum intact parathyroid hormone (iPTH), calcium, phosphorus, and alkaline phosphatase (ALP) were assessed before treatment and 3, 6, 12, and 18 months after treatment. (1) The osteoporosis rate of the 256 maintenance dialysis patients was 42.19%. (2) The osteoporosis rate of the 201 patients undergoing maintenance hemodialysis (MHD) was 47.76%, significantly higher than that of the 55 patients undergoing maintenance peritoneal dialysis (21.82%, P < 0.01). (3) At the end of the trial, there was a significant increase of BMD of lumbar spine and femoral neck in the experiment group compared with the control group. (4) Compared with the control group, the serum ALP, iPTH, and BGP levels 3, 6, 12, and 18 months after treatment were all significantly lower than the baseline level and those of the corresponding control groups (all P < 0.01). The serum calcium of the control group at the end of experiment increased significantly in comparison with baseline level (P < 0.05). (5) No adverse events were found after the treatment of salmon calcitonin. Salmon calcitonin effectively increases the BMD of the maintenance dialysis patients and is well tolerated.


Chest pain associated with moderator band pacing.
A 65-year-old man was evaluated for chronic chest pain that had been present for 8 years after placement of a dual-chamber implantable cardioverter-defibrillator to treat inducible ventricular tachycardia. Previous coronary angiography had revealed nonobstructive coronary artery disease and a left ventricular ejection fraction of 0.45 to 0.50, consistent with mild idiopathic nonischemic cardiomyopathy. Evaluation with chest radiography and transthoracic echocardiography showed the implantable cardioverter-defibrillator lead to be embedded within the right ventricle at the moderator band, which had mild calcification. Treatment included extraction of the dual-coil lead and placement of a new single-coil right ventricular lead at the mid septum. The patient had complete relief of symptoms after the procedure. This case shows that chest pain can be associated with the placement of a right ventricular implantable cardioverter-defibrillator lead in the moderator band and that symptomatic relief can occur after percutaneous lead extraction and the implantation of a new right ventricular lead to the mid septal region.


Regulation of EGFR protein stability by the HECT-type ubiquitin ligase SMURF2.
Epidermal growth factor receptor (EGFR) is overexpressed in a variety of epithelial tumors and is considered to be an important therapeutic target. Although gene amplification is responsible for EGFR overexpression in certain human malignancies including lung and head and neck cancers, additional molecular mechanisms are likely. Here, we report a novel interaction of EGFR with an HECT-type ubiquitin ligase SMURF2, which can ubiquitinate, but stabilize EGFR by protecting it from c-Cbl-mediated degradation. Conversely, small interfering RNA (siRNA)-mediated knockdown of SMURF2 destabilized EGFR, induced an autophagic response and reduced the clonogenic survival of EGFR-expressing cancer cell lines, with minimal effects on EGFR-negative cancer cells, normal fibroblasts, and normal epithelial cells. UMSCC74B head and neck squamous cancer cells, which form aggressive tumors in nude mice, significantly lost in vivo tumor-forming ability on siRNA-mediated SMURF2 knockdown. Gene expression microarray data from 443 lung adenocarcinoma patients, and tissue microarray data from 67 such patients, showed a strong correlation of expression between EGFR and SMURF2 at the messenger RNA and protein levels, respectively. Our findings suggest that SMURF2-mediated protective ubiquitination of EGFR may be responsible for EGFR overexpression in certain tumors and support targeting SMURF2-EGFR interaction as a novel therapeutic approach in treating EGFR-addicted tumors.


Assessing Resilience to Sleep Loss Among the Italian Population: A 13-Item Model of the Iowa Resistance to Sleeplessness Test (iREST).
The present study aimed to validate the Italian version of the Iowa Resistance to Sleeplessness Test (iREST), a 16-item self-report assessing resilience to sleep debt in the affective, cognitive, and somatic domains. We examined its factor structure, assessed internal consistency and criterion validity, and established test-retest reliability on 768 Italian native speakers (65.8% of women) with a mean age of 25.98 years old. Confirmatory factor analysis (CFA) revealed a new 13-item structure for the Italian iREST (iREST-13), demonstrating more satisfactory goodness-of-fit values, and exhibiting good internal consistency (Cronbach's α ranging from 0.73 to 0.89), relative to the 16-item original version. Results supported the iREST convergent validity, showing significant independence from established measures of sleep; low correlations with conceptually unrelated measures supported divergent validity, indicating that the iREST effectively measures resistance to sleeplessness without confounding with other constructs. Lastly, test-retest reliability was evaluated by administering the iREST to the same sample with a 2-week interval: the significant correlations supported its temporal stability. Further studies are needed to evaluate the applicability of the iREST in diverse populations and explore its relationship with objective sleep measures. Nevertheless, the Italian iREST provides a valuable tool for assessing resistance to sleep loss, offering insights into individual differences in resilience. Additionally, the iREST can assist in identifying individuals who require interventions to enhance resilience to sleep debt, as well as help clinicians evaluate the impact of chronic sleep disruption and deliver targeted interventions.


[Aspergillus infection in skin transplantation and its therapy].
In a 10 years old girl sustaining a corrosive injury of the lower leg from sulphuric acid, in the region of a skin transplantation colonization with Aspergillus fumigatus (Fresenium) and Aspergillus niger (van Tieghem) took place. This infection endangered the attempt of transplantation and the saving of the foot. Treatment by medication with nystatin (moronal) and canesten (clotrimazol) were ineffective. Pimaricin (pimafucin, natamycin) quickly erradicated the mycotic infection and secured an undisturbed progress for the transplantation. Additionally the epidemiology of infections by Aspergillus is briefly discussed.


Emotional deficit in subjects with psychopathic tendencies as assessed by the Minnesota Multiphasic Personality Inventory-2: an event-related potentials study.
On the basis of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), 20 male students were separated in low (LP) versus high (HP) subjects with psychopathic tendencies. Pictures from the Ekman and Friesen series were used in an event-related potentials study to investigate the neurophysiological correlates of the emotional deficit described in psychopathy. Subjects were confronted with a visual oddball design, in which they had to detect, as quickly as possible, deviant happy, sad or fearful faces amongst a train of standard stimuli (neutral faces). Behavioral results suggest that LP subjects are more efficient in the detection of emotional deviant faces. This emotional deficit was neurophysiologically indexed, in HP subjects, by a decreased N300 component, which is supposed to be particularly sensitive to affective features of stimuli rather than to physical characteristics. Moreover, independently of the nature of the deviant faces, the P3a component shows an earlier latency in the HP group as compared to the LP group, whereas the reversed pattern was shown for the P3b component. Implications of these results were discussed.


Root Adaptation to H2O2-Induced Oxidative Stress by ARF-GEF BEN1- and Cytoskeleton-Mediated PIN2 Trafficking.
Abiotic stress poses constant challenges for plant survival and is a serious problem for global agricultural productivity. On a molecular level, stress conditions result in elevation of reactive oxygen species (ROS) production causing oxidative stress associated with oxidation of proteins and nucleic acids as well as impairment of membrane functions. Adaptation of root growth to ROS accumulation is facilitated through modification of auxin and cytokinin hormone homeostasis. Here, we report that in Arabidopsis root meristem, ROS-induced changes of auxin levels correspond to decreased abundance of PIN auxin efflux carriers at the plasma membrane (PM). Specifically, increase in H2O2 levels affects PIN2 endocytic recycling. We show that the PIN2 intracellular trafficking during adaptation to oxidative stress requires the function of the ADP-ribosylation factor (ARF)-guanine-nucleotide exchange factor (GEF) BEN1, an actin-associated regulator of the trafficking from the PM to early endosomes and, presumably, indirectly, trafficking to the vacuoles. We propose that H2O2 levels affect the actin dynamics thus modulating ARF-GEF-dependent trafficking of PIN2. This mechanism provides a way how root growth acclimates to stress and adapts to a changing environment.


Investigating the Qn site of the cytochrome bc1 complex in Saccharomyces cerevisiae with mutants resistant to ilicicolin H, a novel Qn site inhibitor.
The cytochrome bc1 complex resides in the inner membrane of mitochondria and transfers electrons from ubiquinol to cytochrome c. This electron transfer is coupled to the translocation of protons across the membrane by the protonmotive Q cycle mechanism. This mechanism topographically separates reduction of quinone and reoxidation of quinol at sites on opposite sites of the membrane, referred to as center N (Qn site) and center P (Qp site), respectively. Both are located on cytochrome b, a transmembrane protein of the bc1 complex that is encoded on the mitochondrial genome. To better understand the parameters that affect ligand binding at the Qn site, we applied the Qn site inhibitor ilicicolin H to select for mutations conferring resistance in Saccharomyces cerevisiae. The screen resulted in seven different single amino acid substitutions in cytochrome b rendering the yeast resistant to the inhibitor. Six of the seven mutations have not been previously linked to inhibitor resistance. Ubiquinol-cytochrome c reductase activities of mitochondrial membranes isolated from the mutants confirmed that the differences in sensitivity toward ilicicolin H originated in the cytochrome bc1 complex. Comparative in vivo studies using the known Qn site inhibitors antimycin and funiculosin showed little cross-resistance, indicating different modes of binding of these inhibitors at center N of the bc1 complex.


Reprint of "Biological motion perception links diverse facets of theory of mind during middle childhood".
Two cornerstones of social development-social perception and theory of mind-undergo brain and behavioral changes during middle childhood, but the link between these developing domains is unclear. One theoretical perspective argues that these skills represent domain-specific areas of social development, whereas other perspectives suggest that both skills may reflect a more integrated social system. Given recent evidence from adults that these superficially different domains may be related, the current study examined the developmental relation between these social processes in 52 children aged 7 to 12years. Controlling for age and IQ, social perception (perception of biological motion in noise) was significantly correlated with two measures of theory of mind: one in which children made mental state inferences based on photographs of the eye region of the face and another in which children made mental state inferences based on stories. Social perception, however, was not correlated with children's ability to make physical inferences from stories about people. Furthermore, the mental state inference tasks were not correlated with each other, suggesting a role for social perception in linking various facets of theory of mind.


Identification of novel antioxidant peptide from porcine plasma hydrolysate and its effect in in vitro digestion/HepG2 cells model.
A novel antioxidant peptide EDEQKFWGK from porcine plasma hydrolysate (PPH) was separated by chromatography, HPLC, and identified by LC-MS/MS. Results showed that EDEQKFWGK had better antioxidant ability (Hydroxyl RAS 32.19%, ABTS RAS 92.93% and DPPH RAS 26.76%) compared with glutathione (30.11%, 82.01%, 26.44%) due to the presence of hydrophobic, aromatic acids (F, W) and acidic amino acids (E, D), decreasing ROS by providing hydrogen atom and chelating metal ions. Furthermore, the antioxidant properties of synthetic EDEQKFWGK still significant despite in vitro digestion because of the production of smaller active peptide. Additionally, it could increase SOD, CAT, GSH-Px to resist oxidative damage in HepG2 cells by inhibiting ROS (O2- , OH·), forming complexes to prevent OH· from destroying DNA and binding to ARE to promote antioxidase expression. Thereby, the novel peptide EDEQKFWGK from porcine plasma had much stable antioxidant properties and hade great potential in formulating functional foods. PRACTICAL APPLICATIONS: This research isolated a novel antioxidant peptide. Moreover, the antioxidant effects of peptide were confirmed under the in vitro digestion model and oxidative damage HepG2 cells model. The results showed the antioxidant peptide could play better effect after digestion and protect the cells from oxidative damage. These data could expand the sequence data of antioxidant peptides and promote the high-value utilization of PPH.


Victorian era esthetic and restorative dentistry: an advertising trade card gallery.
A chief means of print advertising in the Victorian era was the "trade card." Innumerable products, companies, and services were highlighted on colorful chromolithographic trade cards, and these became desirable collectible objects which were pasted into scrapbooks and enjoyed by many families. Dentistry- and oral health-related subjects were often depicted on Victorian trade cards, and esthetic and restorative dentistry themes were featured. This review describes the history of advertising trade cards and offers a photographic gallery of dentistry-related cards of the era.


Direct and indirect patient costs of dermatology clinic visits and their impact on access to care and provider preference.
The direct and indirect costs of dermatology clinic visits are infrequently quantified. Indirect costs, such as the time spent traveling to and from appointments and the value of lost earnings from time away from work, are substantial costs that often are not included in economic analyses but may pose barriers to receiving care. Due to the national shortage of dermatologists, patients may have to wait longer for appointments or travel further to see dermatologists outside of their local community, resulting in high time and travel costs for patients. Patients' lost time and earnings comprise the opportunity cost of obtaining care. A monetary value for this opportunity cost can be calculated by multiplying a patient's hourly wage by the number of hours that the patient dedicated to attending the dermatology appointment. Using a single institution survey, this study quantified the direct and indirect patient costs, including opportunity costs and time burden, associated with dermatology clinic visits to better appreciate the impact of these factors on health care access and dermatologic provider preference.


Moving beyond the national lung screening trial: discussing strategies for implementation of lung cancer screening programs.
The National Lung Screening Trial (NLST) has sparked new interest in the adoption of lung cancer screening using low-dose computed tomography (LDCT). If adopted at a national level, LDCT screening may prevent approximately 18,000 lung cancer deaths per year, potentially constituting a high-value public health intervention. Before incorporating LDCT screening into practice, health care institutions need to consider the risks associated with LDCT screening and the impact of LDCT screening on health care costs, as well as other remaining areas of uncertainty, including the unknown cost-effectiveness of LDCT screening. This article will review the benefits and risks of LDCT screening in light of the results of the NLST and other randomized trials, it will discuss the additional health care costs associated with LDCT screening from the perspective of health care payers, and it will examine the published cost-effectiveness analyses of LDCT screening. A subsequent discussion highlights guideline recommendations for implementation strategies, the goals of which are to ensure that those eligible for LDCT screening derive the benefits while minimizing the risks of screening and avoiding an unnecessary escalation in screening-related costs. The article concludes by endorsing the use of LDCT screening in institutions capable of responsible implementation of screening in both medical and economic terms. The key elements of responsible implementation include the development of standardized screening practices, careful selection of screening candidates, and the creation of prospective registries that will mitigate current areas of uncertainty regarding LDCT screening.


Economic injury levels and economic thresholds for Leptoglossus zonatus (Dallas) (Hemiptera: Coreidae) infesting seed maize.
Although Leptoglossus zonatus is considered a secondary pest of maize grown for grain, when grown for seed, this pest can cause significant economic damage. There are no records of management recommendations for this pest. The objectives of this work were to quantify losses caused by L. zonatus to different genotypes used for seed maize production and to estimate the acute toxicity of selected insecticides to L. zonatus using different application technologies. The ultimate goal was to calculate economic injury levels (EILs) and develop economic thresholds (ETs) for L. zonatus infesting seed maize. EILs and ETs varied, respectively, from 3 to 8 and from 2 to 6 adults per 1000 plants, depending on the genotype, insecticide and application technology. Effective control was obtained by using aerial or ground application of λ-cyhalothrin (10.6%) + thiametoxan (14.1%) or permethrin (38.4%) at the rates of 1.48 mL ha-1 and 27.10 mL ha-1 , respectively, or ground application of methomyl (21.5%) at the rate of 244.06 mL ha-1 . Maize grown for seed is susceptible to L. zonatus damage during reproductive stages, and the pest densities requiring management vary with genotype, insecticide, and application technology. These results contribute significantly to integrated pest management (IPM) for seed maize. © 2017 Society of Chemical Industry.


[A retrospective analysis of clinical characteristics and outcomes of heart failure patients with different left ventricular ejection fractions].
Objective: To compare the clinical characteristics, and outcomes of patients with heart failure with different left ventricular ejection fractions (LVEF). Methods: A total of 1 182 hospitalized patients with heart failure (HF) were enrolled and retrospectively studied in the present study. The patients were stratified by LVEF as reduced (HFrEF, LVEF<40%, n=313), mid-range (HFmrEF, 40% ≤LVEF <50%, n=287) and preserved (HFpEF, LVEF≥50%, n=582) ejection fraction groups. Among the 1 182 cases, 941 of them (81.3%, 84.9%, and 84.0% inHFrEF, HFmrEF and HFpEF groups, respectively) were followed up for an median duration of 27.3 months. Results: (1) Among the study patients, 26.5% were in HFrEF, 24.3% in HFmrEF, and 49.2% in HFpEF groups. (2) Ischemic heart disease with HFmrEF was more frequent than that in patients with HFrEF. The average age, percentage of female subjects, systolic blood pressure, uric acid, N terminal B-type natriuretic peptide precursor (NT-proBNP), hemoglobin, and the incidence of hypertensive heart disease, anemia, atrial fibrillation in patients with HFmrEF were higher than those in patients with HFrEF, but lower than those in patients with HFpEF (all P<0.01). (3) The all-cause cumulative mortality was 10.8% at 1 year, 20.6% at 2 years and 35.9% at 5 years. No difference was observed in the all-cause cumulative mortality at 1 year, 2 years, 5 years among the three groups (all P>0.05). Conclusions: The HFmrEF patients, as a new and distinct group, were with many intermediate characteristics compared with HFrEF and HFpEF subjects. However, the all-cause mortality was not significantly different among HF patients with different LVEF.


Bioethics in artificial reproduction in the Muslim world.
In Islam infertility and its remedy with the unforbidden is allowed and encouraged. It is essential if it involves preservation of procreation and treatment of infertility in one partner of the married couples. This is applicable to artificial reproduction which is one line of treatment of infertility.... The prevention and treatment of infertility are of particular significance in the Muslim World. The social status of the Muslim woman, her dignity and self-esteem are closely related to her procreation potential in the family and in the society as a whole. Childbirth and rearing are regarded as family commitments and not just biological and social functions.


Diverse accumulation and distribution of nutrient elements in developing wheat grain studied by laser ablation inductively coupled plasma mass spectrometry imaging.
The present study focused on the elemental distribution in the developing wheat grain by using the laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging technique. Our studies show that the embryo accumulated high concentrations of nutrient elements, such as Fe, K, Cu, and Zn, while Ca was accumulated in the bran of the wheat grain which might be attributed to its function of structural maintenance. In the endosperm the majority of the nutrients were located in the aleurone layer. Within the grain, the embryo could be considered as a nutrient pool for macro- and micro-elements essential for the development of the seedling. Elemental images showed that considerable amounts of nutrients were stored in the scutellum of the embryo, which might be related to the high gene expression of element transporters in the scutellum. Root primordia and leaf primordia were enriched in particular elements, such as Mn and Zn respectively. In total 34 cross sections were analyzed and used for generation of a sequence of elemental distribution images to demonstrate elemental changes along the perpendicular axis of the wheat grain embryo. Further development of three-dimensional modeling will be combined with physiological studies to better understand the mechanisms of elemental distribution and storage in the wheat grain. These studies will provide fundamental knowledge on improving the nutritional value and agronomic practices.


Genomic alterations related to HPV infection status in a cohort of Chinese prostate cancer patients.
Human papillomavirus (HPV) has been proposed as a potential pathogenetic organism involved in prostate cancer (PCa), but the association between HPV infection and relevant genomic changes in PCa is poorly understood. To evaluate the relationship between HPV genotypes and genomic alterations in PCa, HPV capture sequencing of DNA isolated from 59 Han Chinese PCa patients was performed using an Illumina HiSeq2500. Additionally, whole-exome sequencing of DNA from these 59 PCa tissue samples and matched normal tissues was carried out using the BGI DNBSEQ platform. HPV infection status and genotyping were determined, and the genetic disparities between HPV-positive and HPV-negative PCa were evaluated. The presence of the high-risk HPV genome was identified in 16.9% of our cohort, and HPV16 was the most frequent genotype detected. The overall mutational burden in HPV-positive and HPV-negative PCa was similar, with an average of 2.68/Mb versus 2.58/Mb, respectively, in the targeted whole-exome region. HPV-negative tumors showed a mutational spectrum concordant with published PCa analyses with enrichment for mutations in SPOP, FOXA1, and MED12. HPV-positive tumors showed more mutations in KMT2C, KMT2D and ERCC2. Copy number alterations per sample were comparable between the two groups. However, the significantly amplified or deleted regions of the two groups only partially overlapped. We identified amplifications in oncogenes, including FCGR2B and CCND1, and deletions of tumor suppressors, such as CCNC and RB1, only in HPV-negative tumors. HPV-positive tumors showed unique deletions of tumor suppressors such as NTRK1 and JAK1. The genomic mutational landscape of PCa differs based on HPV infection status. This work adds evidence for the direct involvement of HPV in PCa etiology. Different genomic features render HPV-positive PCa a unique subpopulation that might benefit from virus-targeted therapy.


Improved cleaning of hydrophilic protein-coated surfaces using the combination of Nanobubbles and SDS.
The use of nanobubbles, the common surfactant sodium dodecyl sulfate (SDS), and nanobubbles in combination with SDS as cleaning agents to remove lysozyme from the solid-liquid interface has been investigated using a quartz crystal microbalance on both hydrophobic and hydrophilic surfaces. On the hydrophobic surface, significant amounts of protein remained on the surface after 10 cycles of nanobubble treatment for 10 s periods in phosphate buffer. The cleaning efficiency of SDS was far superior and was shown to remove approximately 90% of the protein. The use of nanobubbles in combination with SDS failed to improve the cleaning efficiency further. On the other hand, lysozyme on the hydrophilic surface cannot be removed effectively by either 10 cycles of cleaning with nanobubbles or 10 cycles of cleaning with SDS. Nevertheless, the protein can be removed completely after 6 cycles of cleaning with nanobubbles in combination with SDS.


Quality-of-life: a many-splendored thing? Belgian population norms and 34 potential determinants explored by beta regression.
To identify determinants of health-related quality-of-life in the Belgian population and to provide age-specific population norms of health-related quality-of-life. Between September 2010 and February 2011, a representative sample of 1774 persons (age 0-99) was surveyed using the standard Euroqol questionnaire (EQ-5D-3L) with a Visual Analogue Scale (VAS). Significant determinants were identified using multivariate beta (VAS) and one-inflated beta (EQ-5D) regression, the latter modelling the probability to be in perfect health separately from the average EQ-5D score if not in perfect health. Health-related quality-of-life depends largely on age and experience with severe disease. The probability to be in perfect health is highest for children. For 0-2 years children who are not in perfect health, proxies report EQ-5D and VAS scores as low as that of the elderly. Also smoking behaviour, educational attainment, pet ownership, working or having worked in health care, and potentially household size and 60+ living on their own (yes/no) are associated with health-related quality-of-life, whereas no association was found with gender, living in a single-parent home, educational attainment of mothers, alcohol consumption of 60+, having (grand-) children and the frequency of seeing them. The same determinants are significant for VAS and the probability to be in perfect health, but not for the average EQ-5D score if not in perfect health. The population norms provided can be used directly as input in health economic evaluations. Estimating health-related quality-of-life in children and developing statistical tools capturing the particular features of health-related quality-of-life measures are important areas for future research.


Stable nano-sized emulsions produced from soy protein and soy polysaccharide complexes.
In this research, a simple, green and effective strategy was developed to produce long-term stable oil in water emulsion from soy protein and soy polysaccharide. Soy protein and soy polysaccharide formed dispersible complexes at pH around 3.25 aqueous solution through electrostatic and hydrophobic interactions. A high pressure homogenization produced the protein/polysaccharide complex emulsion having a droplet size about 250 nm. A heat treatment of the emulsion resulted in the protein denaturation, forming irreversible oil-water interfacial films composed of soy protein/soy polysaccharide complexes. The droplets of the emulsion were characterized by dynamic light scattering, ζ-potential, transmission electron microscopy, polysaccharide digestion via pectinase, and confocal laser scanning microscopy observation via dual fluorescence probes. As a result of the polysaccharide being fixed on the droplet surface, the emulsions exhibited long-term stability in the media containing pH values of 2-8 and 0.2 mol/L NaCl. The stable soy protein/soy polysaccharide complex emulsion is a suitable food-grade delivery system in which lipophilic bioactive compounds can be encapsulated.


Does Remote and/or Virtual Learning Prepare First-Year Physician Assistant Students for Clinical Rotations as Effectively as In-Person Learning?
The coronavirus disease 2019 pandemic has profoundly affected many lives, and the aftermath is still uncertain. Many aspects of life have been affected, including physician assistant (PA) education. The collective efforts of students and faculty, perseverance, and optimism have allowed the uninterrupted preparation of the next generation of PAs. The objective of this study was to understand PA students' perceptions of the effectiveness of remote and/or virtual learning in preparing PA students for clinical rotations. This pilot study was a mixed-methods survey with quantitative and qualitative data involving 3 accredited PA programs in the United States. Statistics were analyzed using SAS 9.4. Ninety-four individuals responded to the survey with a response rate of 46.8%. Response distributions, standard deviations, and means were calculated. Likert scale response means for each survey item were used to estimate the overall perspective of the participants. Most participants highlighted the advantages of flexibility and an opportunity to balance school and family life, but the participants did not favor remote and/or virtual learning platforms for effectively preparing students for their clinical phase. More research on a larger scale is warranted. Including students' hands-on skills performance measures in addition to perceptions could provide objective evidence for the efficacy of remote and/or virtual learning in preparing students for clinical rotations.


Determination of common parameters fo iodothyronine metabolism and distribution in man by noncompartmental analysis.
A noncompartmental method is proposed for the calculation of the total distribution volume of exchangeable iodothyronine, the fractional irreversible removal rate from the exchangeable pool, and the metabolic clearance rate of labeled triiodothyronine (T3) and thyroxine (T4). The method depends on a graphic analysis and does not require the use of computers. The results of noncompartmental analysis of T3 and T4 distribution and metabolism are compared to single compartmental calculations in 12 subjects. Single compartmental analysis appeared to overestimate the distribution volume of T3 by a factor of 2.9, the metabolic clearance rate by a factor of 1.4, and underestimate the fractional removal rate by a factor of 0.48. Whereas single compartmental analysis did not introduce a significant error into the calculation of the metabolic clearance rate of T4, the distribution volume appeared to be overestimated by a factor of 1.4 and the fractional removal rate underestimated by a factor of 0.9.


Ca2+ calmodulin regulates basal gallbladder absorption.
Gallbladder absorption is altered during gallstone formation, a phenomenon that may be partly the result of elevated biliary Ca2+ levels. Recent studies suggest that changes in gallbladder absorption are mediated by intracellular Ca2+ ([Ca2+]ic). However, the mechanisms by which [Ca2+]ic regulates gallbladder ion transport are not known. Calmodulin is a Ca2+ receptor protein in the Ca2+ messenger system that modulates ion transport in the small intestine. We hypothesized that Ca(2+)-calmodulin mediates the effects of [Ca2+]ic on gallbladder absorption. Prairie dog gallbladders were mounted in Ussing chambers, and standard electrophysiologic parameters were recorded. Unidirectional Na+, Cl-, and water fluxes were measured before and after mucosal exposure to 5 x 10(-5) mol/L trifluoperazine, a potent calmodulin antagonist. In addition, the ion transport effects of increased extracellular calcium and theophylline were determined in the presence of calmodulin inhibition. Inhibition of calmodulin resulted in an increase in net Na+ and water absorption and converted the gallbladder from a Cl- absorptive state. Similar results were obtained during exposure to two other calmodulin antagonists that differ only in their affinity for calmodulin but not in their hydrophobicity, suggesting that the observed changes were caused by specific calmodulin inhibition. Effects of trifluoperazine were reversed by increasing luminal [Ca2+] or theophylline exposure. The effects of calmodulin inhibition are directly opposite of the effects of the Ca2+ ionophore. We conclude that Ca(2+)-calmodulin regulates gallbladder absorption at basal [Ca2+]ic. Further studies are needed to determine whether altered calmodulin activity is responsible for increased gallbladder absorption during gallstone formation.


[Intervention of mobile palliative care team on nursing homes: retrospective study].
Interventions of mobile palliative care teams in nursing homes have been the subject special consideration, however very little data are available on this subject. To determine the proportion of patients followed and consultations conducted in nursing homes for the dependent elderly by a mobile palliative care team, to describe the patients followed and to analyze the various aspects of this intervention. Retrospective study on the interventions carried out by a mobile palliative care team in nursing homes between January 1st and December 31st, 2012. The interventions in nursing homes targeted, 7.2% of the followed patients and represented 8.7% of the total activity of the mobile team. Intervention requests were made primarily by the family physician. The followed patients were mostly women (63%), with a mean age of 84 years, presenting non-cancerous diseases (78.2%), and had an average of 4.4 consultations. Half of the patients died during follow-up. Three quarters of the patients presented pain, neuro-psychological symptoms and verbal communication disorders. Four out of ten patients met with the occupational therapist and one of ten, the psychologist. The activity of mobile palliative care teams remains marginal, although steadily (on the rise. The collected data illustrate the specificity of geriatric palliative care, while certain characteristics inherent to nursing homes require establishing appropriate therapy proposals. Although quantitatively limited, the activity of mobile palliative care teams in nursing homes appears important as these interventions are likely meet the needs of both patients and staff in addition to enabling patients in palliative care to remain at their current place of residence.


The opposite effect of a low and a high dose of serotonin-1A agonist on behavior induced by MK-801.
The purpose of the present study was to investigate the opposite effect of the pre- and postsynaptic serotonin-1A (5-HT(1A)) receptors on the psychotic-like behavior induced by a non-competitive antagonist of the NMDA receptor, dizocilpine (MK-801). Male Wistar rats received two doses (0.025mg/kg and 1mg/kg) of 5-HT(1A) receptor agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin) and/or MK-801 in two different doses, 0.1mg/kg or 0.3mg/kg. We measured sensorimotor gating by testing prepulse inhibition of acoustic startle response (PPI) and locomotor activity of rats. We found an opposite effect of the low and high 5-HT(1A) receptor agonist doses on MK-801 induced deficit in PPI and hyperlocomotion in habituated rats. The low dose of 8-OH-DPAT, which preferentially acts on presynaptic 5-HT(1A) receptors, restored the deficit in PPI and hyperlocomotion in MK-801 (0.1mg/kg)-treated habituated rats. However, the high dose of 8-OH-DPAT, which activates both pre- and postsynaptic 5-HT(1A) receptors, decreased PPI and increased locomotor activity after administration of the low dose of MK-801. Administration of 8-OH-DPAT itself dose-dependently decreased PPI. However, only the high dose of 8-OH-DPAT increased spontaneous locomotor activity of rats. Our results indicate that there is an interaction between the NMDA and 5-HT(1A) receptors. In addition, these findings could indicate that activation of the 5-HT(1A) autoreceptor could be effective as a treatment in schizophrenia, but full potent agonism of the receptor could worsen the psychotic symptoms.


Founder effect and genetic disease in Sottunga, Finland.
Pedigree data are analyzed in order to determine the factors responsible for the high frequencies of certain genetic disorders in an isolated Swedish-speaking population of Finland's A land archipelago. The founders of Sottunga are identified, and the genetic contributions of each founder to descending birth cohorts are estimated. Founders born before 1700 have far more descendants in the contemporary gene pool than do more recent founders. However, because of migration and depopulation since 1900, the expected genetic contributions of the early founders to the present-day population are similar to those of later founders. A descendant in the contemporary population has a 2% chance of having inherited a particular gene from the founder who makes the largest single contribution to the gene pool. This corresponds approximately to a 2% probability of inheriting an autosomal dominant disease gene from this founder. Given an average inbreeding coefficient of 0.0016, the probability of inheriting two recessive disease genes from this founder is 0.000032. The incidence of autosomal dominant von Willebrand disease in Sottunga is greater than 10% while that of autosomal recessive tapetoretinal disease is 1.5%. We conclude, therefore, that the high frequencies of these diseases are not due to the disproportionate genetic contribution of one or a few particular founders. It is more likely that these disease genes occurred in high frequency in the initial population or were introduced repeatedly through time.


The effect of a G:T mispair on the dynamics of DNA.
Distortions in the DNA sequence such as damages or mispairs are specifically recognized and processed by DNA repair enzymes. A particular challenge for the enzymatic specificity is the recognition of a wrongly-placed native nucleotide such as thymine in T:G mispairs. An important step of substrate binding which is observed in many repair proteins is the flipping of the target base out of the DNA helix into the enzyme's active site. In this work we investigate how much the intrinsic dynamics of mispaired DNA is changed compared to canonical DNA. Our molecular dynamics simulations of DNA with and without T:G mispairs show significant differences in the conformation of paired and mispaired DNA. The wobble pair T:G shows local distortions such as twist, shear and stretch which deviate from canonical B form values. Moreover, the T:G mispair is found to be kinetically less stable, exhibiting two states with respect to base opening: a closed state comparable to the canonical base pairs, and a more open state, indicating a proneness for base flip. In addition, we observe that the thymine base in a T:G mispair is significantly more probable to be flipped than thymine in a T:A pair or cytosine in a C:G pair. Such local deformations and in particular the existence of a second, more-open state can be speculated to help the target-site recognition by repair enzymes.


The economics of alternative payment models for pharmaceuticals.
Pharmaceuticals are priced uniformly by convention, but vary in their degree of effectiveness for different disease indications. As more high-cost therapies have launched, the demand for alternative payment models (APMs) has been increasing in many advanced markets, despite their well-documented limitations and challenges to implementation. Among policy justifications for such contracts is the maximization of value given scarce resources. We show that while uniform pricing rules can handle variable effectiveness in efficient markets, market inefficiencies of other kinds create a role for different value-based pricing structures. We first present a stylized theoretical model of efficient interaction among drug manufacturers, payers, and beneficiaries. In this stylized setting, uniform pricing works well, even when treatment effects are variable. We then use this framework to define market failures that result in obstacles to uniform pricing. The market failures we identify include: (1) uncertainty of patient distribution, (2) asymmetric beliefs, (3) agency imperfection by payer, (4) agency imperfection by provider, and (5) patient behavior and treatment adherence. We then apply our insights to real-world examples of alternative payment models, and highlight challenges related to contract implementation.


Biological activities and chemical components of Potentilla kleiniana Wight & Arn.
In this study, we investigated the antimicrobial, antioxidant, and cytoprotective activities of ethanol extract and the ethyl acetate (EtOAc) fraction of P. kleiniana Wight & Arn. The EtOAc fraction exhibited antimicrobial effects against most of the microorganisms that were tested, including Staphylococcus aureus, Candida albicans, Pseudomonas aeruginosa, and, Escherichia coli, but not Aspergillus niger. In addition to its excellent antioxidant activity, the EtOAc fraction attenuated the UVB-induced cell death via upregulation of caspase-3 expression in human keratinocytes. The HPLC/ESI-MS/MS analysis allowed identification of the components in the EtOAc fraction. Overall, our results suggest that P. kleiniana is a valuable source of bioactive compounds for the development of pharmaceuticals and cosmetics.


The Live Well, Be Well study: a community-based, translational lifestyle program to lower diabetes risk factors in ethnic minority and lower-socioeconomic status adults.
We evaluated a community-based, translational lifestyle program to reduce diabetes risk in lower-socioeconomic status (SES) and ethnic minority adults. Through an academic-public health department partnership, community-dwelling adults at risk for diabetes were randomly assigned to individualized lifestyle counseling delivered primarily via telephone by health department counselors or a wait-list control group. Primary outcomes (6 and 12 months) were fasting glucose level, triglycerides, high- and low-density lipoprotein cholesterol, weight, waist circumference, and systolic blood pressure. Secondary outcomes included diet, physical activity, and health-related quality of life. Of the 230 participants, study retention was 92%. The 6-month group differences for weight and triglycerides were significant. The intervention group lost 2 pounds more than did the control group (P=.03) and had decreased triglyceride levels (difference in change, 23 mg/dL; P=.02). At 6 months, the intervention group consumed 7.7 fewer grams per day of fat (P=.05) and more fruits and vegetables (P=.02) than did control participants. Despite challenges designing effective translational interventions for lower-SES and minority communities, this program modestly improved some diabetes risk factors. Thus, individualized, telephone-based models may be a promising alternative to group-based interventions.


INVESTIGATING DIFFERENCES IN BRAIN FUNCTIONAL NETWORKS USING HIERARCHICAL COVARIATE-ADJUSTED INDEPENDENT COMPONENT ANALYSIS.
Human brains perform tasks via complex functional networks consisting of separated brain regions. A popular approach to characterize brain functional networks in fMRI studies is independent component analysis (ICA), which is a powerful method to reconstruct latent source signals from their linear mixtures. In many fMRI studies, an important goal is to investigate how brain functional networks change according to specific clinical and demographic variabilities. Existing ICA methods, however, cannot directly incorporate covariate effects in ICA decomposition. Heuristic post-ICA analysis to address this need can be inaccurate and inefficient. In this paper, we propose a hierarchical covariate-adjusted ICA (hc-ICA) model that provides a formal statistical framework for estimating covariate effects and testing differences between brain functional networks. Our method provides a more reliable and powerful statistical tool for evaluating group differences in brain functional networks while appropriately controlling for potential confounding factors. We present an analytically tractable EM algorithm to obtain maximum likelihood estimates of our model. We also develop a subspace-based approximate EM that runs significantly faster while retaining high accuracy. To test the differences in functional networks, we introduce a voxel-wise approximate inference procedure which eliminates the need of computationally expensive covariance matrix estimation and inversion. We demonstrate the advantages of our methods over the existing method via simulation studies. We apply our method to an fMRI study to investigate differences in brain functional networks associated with post-traumatic stress disorder (PTSD).


A multi-label CNN model for the automatic detection and segmentation of gliomas using [18F]FET PET imaging.
The aim of this study was to develop a convolutional neural network (CNN) for the automatic detection and segmentation of gliomas using [18F]fluoroethyl-L-tyrosine ([18F]FET) PET. Ninety-three patients (84 in-house/7 external) who underwent a 20-40-min static [18F]FET PET scan were retrospectively included. Lesions and background regions were defined by two nuclear medicine physicians using the MIM software, such that delineations by one expert reader served as ground truth for training and testing the CNN model, while delineations by the second expert reader were used to evaluate inter-reader agreement. A multi-label CNN was developed to segment the lesion and background region while a single-label CNN was implemented for a lesion-only segmentation. Lesion detectability was evaluated by classifying [18F]FET PET scans as negative when no tumor was segmented and vice versa, while segmentation performance was assessed using the dice similarity coefficient (DSC) and segmented tumor volume. The quantitative accuracy was evaluated using the maximal and mean tumor to mean background uptake ratio (TBRmax/TBRmean). CNN models were trained and tested by a threefold cross-validation (CV) using the in-house data, while the external data was used for an independent evaluation to assess the generalizability of the two CNN models. Based on the threefold CV, the multi-label CNN model achieved 88.9% sensitivity and 96.5% precision for discriminating between positive and negative [18F]FET PET scans compared to a 35.3% sensitivity and 83.1% precision obtained with the single-label CNN model. In addition, the multi-label CNN allowed an accurate estimation of the maximal/mean lesion and mean background uptake, resulting in an accurate TBRmax/TBRmean estimation compared to a semi-automatic approach. In terms of lesion segmentation, the multi-label CNN model (DSC = 74.6 ± 23.1%) demonstrated equal performance as the single-label CNN model (DSC = 73.7 ± 23.2%) with tumor volumes estimated by the single-label and multi-label model (22.9 ± 23.6 ml and 23.1 ± 24.3 ml, respectively) closely approximating the tumor volumes estimated by the expert reader (24.1 ± 24.4 ml). DSCs of both CNN models were in line with the DSCs by the second expert reader compared with the lesion segmentations by the first expert reader, while detection and segmentation performance of both CNN models as determined with the in-house data were confirmed by the independent evaluation using external data. The proposed multi-label CNN model detected positive [18F]FET PET scans with high sensitivity and precision. Once detected, an accurate tumor segmentation and estimation of background activity was achieved resulting in an automatic and accurate TBRmax/TBRmean estimation, such that user interaction and potential inter-reader variability can be minimized.


Neuroendocrine changes in patients undergoing whole body hyperthermia.
A phase I study of whole body hyperthermia (WBH) (52 treatments/12 patients) utilizing a radiant heat device has been completed. This study incorporated a temperature escalation scheme from 39.5 to 41.8 degrees C for up to 150 min. Pain relief or a sense of well being was observed post-WBH in the first three patients entered in this study. We postulated that WBH might result in increases in the opiate peptide beta-endorphin. Therefore we elected to study prospectively the next six patients entered in this study to test the hypothesis that WBH stimulates the neuroendocrine axis. Results are reported which show thermal-induced increases in plasma levels of beta-endorphin as well as prolactin, ACTH and cortisol.


Injuries, sequelae, and treatment of lightning-induced injuries: 10 years of experience at a swiss trauma center.
Principals. Lightning is one of the most powerful and spectacular natural phenomena. Lightning strikes to humans are uncommon but can cause devastating injuries. We analyzed lightning-related admissions to our emergency department from January 2000 to December 2010 to review and highlight the main features of lightning-related injuries. Methods. All data were collected prospectively and entered in the emergency department' database (Qualicare Switzerland) and retrospectively analyzed. Results. Nine patients with lightning-related injuries presented to our emergency department. Four were female, and five were male. The most common site of injury was the nervous system (6 out of 9 patients) followed by the cardiovascular system (5 out of 9 patients). The third most common injuries occurred to the skin (3 out of 9 patients). Four of the patients had to be hospitalized for further observation. Conclusion. Reports of lightning strikes and related injuries are scarce. The establishment of an international register would therefore benefit the understanding of their injury patterns and facilitate specific treatment.


Geographic distance and pH drive bacterial distribution in alkaline lake sediments across Tibetan Plateau.
Continent-scale biogeography has been extensively studied in soils and marine systems, but little is known about biogeographical patterns in non-marine sediments. We used barcode pyrosequencing to quantify the effects of local geochemical properties and geographic distance for bacterial community structure and membership, using sediment samples from 15 lakes on the Tibetan Plateau (4-1670 km apart). Bacterial communities were surprisingly diverse, and distinct from soil communities. Four of 26 phyla detected were dominant: Proteobacteria, Bacteroidetes, Firmicutes and Actinobacteria, albeit 20.2% of sequences were unclassified at the phylum level. As previously observed in acidic soil, pH was the dominant factor influencing alkaline sediment community structure, phylotype richness and phylogenetic diversity. In contrast, archaeal communities were less affected by pH. More geographically distant sites had more dissimilar communities (r=0.443, P=0.030). Variance partitioning analysis showed that geographic distance (historical contingencies) contributed more to bacterial community variation (12.2%) than any other factor, although the environmental factors explained more variance when combined (28.9%). Together, our results show that pH is the best predictor of bacterial community structure in alkaline sediments, and confirm that both geographic distance and chemical factors govern bacterial biogeography in lake sediments.


Quality improvement in New Zealand pediatric anesthesia: National quality direction, patient experience, equity, and collaboration.
The current priorities of the quality and safety of patient care in New Zealand at a central government level are described, with a focus on equity and patient experience. Priorities between stakeholders differ. We report the current quality activities of New Zealand pediatric anesthetists in relation to these governance aims, seeking gaps and suggesting future directions to align governance priorities and local activities. International relevance is also outlined. New Zealand Māori experience health inequity. Complex systemic factors including those of systemic racism and prejudice contribute to the inequity. The specific contributions to health inequity from pediatric anesthetists are unknown but could include aspects of cultural safety, delays in treatment and treatment deficits. Patient experience is correlated positively with other quality domains. Peri-operative patient experience tools require outcomes of interest that matter to patients, including relevant cultural safety domains. Risk identification and critical event review contribute to local learnings in departments and institutions, and more widely to national and binational (with Australia) learnings. Several collaborative projects in Australia and New Zealand, whilst not primarily quality improvement projects, may improve pediatric anesthesia. These collaborations include a pediatric anesthesia professional network, a curriculum for a pediatric anesthetic fellowship, contributions to a document on standards for pediatric anesthesia, and a national quality group researching key performance indicators across New Zealand.


Comparison of Non-Contrast Cardiovascular Magnetic Resonance Imaging to Computed Tomography Angiography for Aortic Annular Sizing Before Transcatheter Aortic Valve Replacement.
Accurate measurement of aortic annulus is crucial before transcatheter aortic valve replacement (TAVR). Computed tomography (CT) angiography is the most commonly utilized method, but requires contrast administration. Cardiovascular magnetic resonance (CMR) imaging is a promising alternative modality to provide aortic annulus measurements. Few studies have compared the clinical feasibility and accuracy of non-contrast CMR to contrast-enhanced computed tomography (CT) angiography in order to provide a non-contrast alternative to CT annular sizing. Twenty-one consecutive patients (mean age, 85.7 ± 5.2 years) with severe aortic stenosis (mean aortic valve area, 0.6 ± 0.1 cm²) underwent pre-TAVR CT angiography and a non-contrast CMR at 1.5 T. CT measurements were performed during systole as the clinical non-invasive standard. CMR measurements were performed during systole and diastole and included three-dimensional (3D) and two-dimensional (2D) methods. Interobserver differences were assessed using intraclass correlation. We recorded scan time in each patient. The mean systolic annular area was not significantly different between CT and 3D-CMR (480.0 ± 77.9 mm² vs 479.4 ± 66.2 mm²; P=.98) in systole. There was no clinically relevant systematic difference between area measurements [mean difference, 0.6 mm²; limits of agreement -38.2 mm²; 39.3 mm²] using Bland-Altman analyses. Interobserver correlation was excellent. The diagnostic systolic 3D-CMR annular sizing scan was achieved in 4.4 ± 2.7 min. Non-contrast CMR protocol for the measurement of aortic annulus area is feasible and accurate. 3D-CMR could provide an alternative for annular sizing pre-TAVR assessment in patients who cannot undergo contrast-enhanced CT studies.


Patent ductus arteriosus in Murrah buffalos.
Two cases of patent ductus arteriosus are described in 2 Murrah buffalos, a 7.5-month-old heifer calf and a 5-month-old bull calf. The main clinical signs consisted of exercise intolerance, dyspnea, and tachycardia. At necropsy, lesions were consistent with congestive heart failure as indicated by dependent subcutaneous edema, body cavity effusions, and nutmeg liver. The lungs were extensively atelectatic. The heart was enlarged and had a globous shape. The ductus arteriosus, measuring 0.8 cm in length and 0.4 cm in caliber, was patent. The proximal pulmonary artery had an approximately 50-mm-long aneurysm. Eccentric cardiac hypertrophy was evident primarily in the right but to a lesser degree also in the left ventricle. Additionally, there was diffuse subendocardial fibrosis in the left and right ventricle. To the best of the authors' knowledge, patent ductus arteriosus was not previously described in buffalos. Since both calves were sired by the same bull, it is possible that this cardiac anomaly has a hereditary basis.


What Do We Do When We "Do" Clinical Ethics? A Primer.
AbstractThis article presents a model for doing clinical ethics consultations. It describes four phases of a consultation: investigation, assessment, action, and review. The consultant must identify the problem and determine whether it is a nonmoral problem (e.g., lack of information) or a moral problem involving uncertainty or conflict. The consultant must be able to identify the types of moral arguments that are used by participants to the situation. A simplified taxonomy of moral arguments is presented. The consultant must then assess the arguments for their cogency and identify where they align and where they conflict. The action phase of the consultation involves finding ways for the arguments to be presented and hopefully reconciled. The normative limitations to the role of the consultant are described.


[Induction effect of platelet-activating factor on Src-suppressed C kinase substrate gene expression in rat pulmonary microvascular endothelial cells].
To investigate the effect of platelet-activating factor (PAF) on the production of Src-suppressed C kinase substrate (SSeCKS) mRNA in rat pulmonary microvascular endothelial cell (RPMVEC) and its signal transduction pathways. Cellular in situ hybridization was performed to reveal changes in SSeCKS mRNA expression in the cultured RPMVECs after giving PAF stimulation. Normal RPMVECs expressed SSeCKS mRNA at a low level, which appeared throughout the cytoplasm with specific hybridization signals. 1.5 hours of 10(-10), 10(-9), 10(-8), 10(-7) mol/L PAF incubation induced a progressive increase in SSeCKS mRNA expression. When compared to the normal control group each difference had statistical significance (0.054 9 + or - 0.000 7, 0.059 9 + or - 0.001 8, 0.069 0 + or - 0.001 8, 0.075 4 + or - 0.001 9 vs. 0.036 8 + or - 0.003 7, respectively, all P<0.05). Within 0.5, 1.5, 3, 6, 12, 24 hours of 10(-7) mol/L PAF challenge, the level of SSeCKS mRNA expression raised at 0.5 hour markedly (0.071 0 + or - 0.001 5), peaked at 1.5 hours (0.075 6 + or - 0.001 7), then began to decline gradually, and still persisted at a higher level than the normal control group until 24 hours (0.043 9 + or - 0.001 0 vs. 0.038 2 + or - 0.004 1, all P<0.05). Pre-incubation of 10 micromol/L pyrrolidine dithiocarbamate (PDTC) that inhibits activity of nuclear factor-KappaB (NF-KappaB) in RPMVECs caused a conspicuous attenuation of PAF-induced SSeCKS mRNA expression (0.049 7 + or - 0.003 2 vs. 0.071 9 + or - 0.001 9, P<0.05), whereas no change of PAF-induced effect was found by pretreatment of protein kinase C (PKC) inhibitor bis-indolylmaleimide (BIM, 0.069 7 + or - 0.002 1 vs. 0.071 9 + or - 0.001 9, P>0.05). PAF can up regulate the expression of SSeCKS mRNA in a dose- and time-dependent manner in RPMVECs. It is NF-KappaB rather than PKC signal pathway that is involved in modulation of the intracellular signaling process.


Role of nanotechnology in development of artificial organs.
Improvements in our understanding of the interactions between implants and cells have directed attention towards nanoscale technologies. To date, nanotechnology has played a helping hand in the development of synthetic artificial organs and regenerative medicine. This includes the production of smart nanocomposite materials; fluorescent nanoparticles like Quantum Dots (QD) and magnetic nano particles (MNP) for stem cell tracking; and carbon nanotubes (CNT) and graphene for enhancement of material properties. The scope of this paper includes the role of nanoparticles in the development of nanomaterials; the chemical surface modifications possible to improve implant function and an overview of the performance of nano-engineered organs thus far. This includes implants developed for aesthetic purposes like nasal and auricular scaffolds, plastic and reconstructive surgical constructs (i.e. dermal grafts), hollow organs for cardiothoracic applications; and last but not least, orthopedic implants. The five-year outlook for nano-enhanced artificial organs is also discussed, highlighting the key research and development areas, available funds and the hurdles we face in accomplishing progression from prototypes on the laboratory bench to off-the-shelf products for the consumer market. Ultimately, this review aims to delineate the advantages of incorporating nanotechnology, as an individual entity or as a part of a construct for the development of tissue engineering scaffolds and/or artificial organs, and unravel the mechanisms of tissue cell-biomaterial interactions at the nanoscale, allowing for better progress in the development and optimization of unique nanoscale surface features for a wide range of applications.


Growth hormone deficiency in the Rothmund-Thomson syndrome.
We describe the first proven occurrence of growth hormone deficiency in an individual with the Rothmund-Thomson syndrome. This was suspected because of the patient's severely retarded growth and bone age and her failure to respond normally to growth hormone stimulation testing with l-DOPA, arginine, and growth hormone releasing factor. In addition, we have briefly reviewed other genetic and malformation syndromes that have been found associated with growth hormone deficiency. We recommend that growth hormone deficiency be considered in these syndromes, especially when the growth failure is more marked than expected.


Resistance of spontaneously transformed Syrian hamster embryo cells and their malignant variants to cytotoxic activity of recombinant tumor necrosis factor-alpha.
To study the possible role of the host macrophages in the selection of tumor cells and tumor progression, a series of Syrian hamster tumor cell lines all originating from a single spontaneously transformed Syrian hamster embryo cell line (STHE strain) have been established. These STHE tumor cell variants, selected either in vitro with resident and lipopolysaccharide-activated macrophages or in vivo, differ in tumorigenic and metastatic activity. The selected malignant STHE cells become resistant to cytotoxic activity of activated peritoneal macrophages and of exogenous hydrogen peroxide (H2O2). Since activated macrophages are a known source for both cytotoxic agents H2O2 and tumor necrosis factor (TNF), the purpose of the present study was to define the sensitivity of the STHE tumor cell lines to a direct cytotoxic activity mediated by recombinant TNF-alpha in an attempt to understand the role of the cytokine in in vitro selection of a malignant STHE cells by activated macrophages. The spontaneously transformed STHE cells (selected in vivo and in vitro) as well as the hamster embryo cells transformed in vitro by a tumorigenic Rous sarcoma virus (Schmidt-Ruppin strain) were used as targets. TNF-alpha-sensitive mouse L929 cells were included in the study as a positive control. Sensitivity of actinomycin D-pretreated target cells studied for cytotoxic activity of a recombinant TNF-alpha was examined over 21 h with a crystal violet dye assay. It was found that, in contrast to L929 cells, the spontaneously transformed STHE cells as well as tumorigenic Rous sarcoma virus hamster embryo transformants, were all significantly resistant to the TNF-alpha-mediated cytolysis. This indicates that TNF-alpha is not the single factor responsible in in vitro selection of malignant STHE cell variants by activated macrophages. It appears that H2O2 is involved in the selection of the hamster macrophage-resistant STHE tumor cells.


A method of purifying feline T lymphocytes from peripheral blood using the plant lectin from Pisum sativum.
The binding properties of several plant lectins on feline peripheral blood lymphocytes (PBL) were examined by flow cytometry to reveal if any could serve as probes for identifying specific lymphocyte subclasses. Most of the lectins bound > or = 90% of PBL in a uniform manner. The exceptions were the lectins from Glycine max, Phaseolus limensis, and Dolichos biflorus, which bound only a proportion of the PBL. The differential binding of the lectins to lymphocyte subclasses was examined by comparing the staining of control PBL to T cell-depleted PBL. The lectins from Pisum sativum, Lens culinaris, succinylated Triticum vulgaris, and Dolichos biflorus stained T-depleted PBL more brightly than control PBL. Extensive cytofluorometric analyses of the binding properties of Pisum sativum agglutinin (PSA) on feline PBL and mesenteric lymph node cells indicated that feline B lymphocytes express more higher affinity surface receptors for PSA than do T lymphocytes. The higher affinity binding of PSA to B lymphocytes was further demonstrated by PSA-mediated cellular affinity chromatography. With this procedure it was possible to deplete PBL of B lymphocytes and to obtain pure populations of feline T lymphocytes.


A Biologically Plausible Neural Network for Multichannel Canonical Correlation Analysis.
Cortical pyramidal neurons receive inputs from multiple distinct neural populations and integrate these inputs in separate dendritic compartments. We explore the possibility that cortical microcircuits implement canonical correlation analysis (CCA), an unsupervised learning method that projects the inputs onto a common subspace so as to maximize the correlations between the projections. To this end, we seek a multichannel CCA algorithm that can be implemented in a biologically plausible neural network. For biological plausibility, we require that the network operates in the online setting and its synaptic update rules are local. Starting from a novel CCA objective function, we derive an online optimization algorithm whose optimization steps can be implemented in a single-layer neural network with multicompartmental neurons and local non-Hebbian learning rules. We also derive an extension of our online CCA algorithm with adaptive output rank and output whitening. Interestingly, the extension maps onto a neural network whose neural architecture and synaptic updates resemble neural circuitry and non-Hebbian plasticity observed in the cortex.


Divergent Evolutionary Patterns of NAC Transcription Factors Are Associated with Diversification and Gene Duplications in Angiosperm.
NAC (NAM/ATAF/CUC) proteins constitute one of the biggest plant-specific transcription factor (TF) families and have crucial roles in diverse developmental programs during plant growth. Phylogenetic analyses have revealed both conserved and lineage-specific NAC subfamilies, among which various origins and distinct features were observed. It is reasonable to hypothesize that there should be divergent evolutionary patterns of NAC TFs both between dicots and monocots, and among NAC subfamilies. In this study, we compared the gene duplication and loss, evolutionary rate, and selective pattern among non-lineage specific NAC subfamilies, as well as those between dicots and monocots, through genome-wide analyses of sequence and functional data in six dicot and five grass lineages. The number of genes gained in the dicot lineages was much larger than that in the grass lineages, while fewer gene losses were observed in the grass than that in the dicots. We revealed (1) uneven constitution of Clusters of Orthologous Groups (COGs) and contrasting birth/death rates among subfamilies, and (2) two distinct evolutionary scenarios of NAC TFs between dicots and grasses. Our results demonstrated that relaxed selection, resulting from concerted gene duplications, may have permitted substitutions responsible for functional divergence of NAC genes into new lineages. The underlying mechanism of distinct evolutionary fates of NAC TFs shed lights on how evolutionary divergence contributes to differences in establishing NAC gene subfamilies and thus impacts the distinct features between dicots and grasses.


Engineering organic macrocycles and cages: versatile bonding approaches.
The emergence of supramolecular chemistry has led to the discovery of a rising number of macrocycles and cages with a range of functionalities. Most of these supramolecular aggregates are metal coordination networks, whereas pure organic assemblies are less developed. Organic macrocycles and cages have the advantages of chemical robustness, processability in organic solvents, and suitability for pilot-scale applications. They are constructed primarily from covalent bonds, with irreversible and reversible bond types. We herein highlight the use of different versatile bonding approaches in engineering these soft materials, as well as their emerging applications, such as gas storage, thin films, liquid crystals, and catalysis.


Sex and estrous cycle differences in the behavioral effects of high-strength static magnetic fields: role of ovarian steroids.
Advances in magnetic resonance imaging are driving the development of higher-resolution machines equipped with high-strength static magnetic fields (MFs). The behavioral effects of high-strength MFs are largely uncharacterized, although in male rats, exposure to 7 T or above induces locomotor circling and leads to a conditioned taste avoidance (CTA) if paired with a novel taste. Here, the effects of MFs on male and female rats were compared to determine whether there are sex differences in behavioral responses and whether these can be explained by ovarian steroid status. Rats were given 10-min access to a novel saccharin solution and then restrained within a 14-T magnet for 30 min. Locomotor activity after exposure was scored for circling and rearing. CTA extinction was measured with two-bottle preference tests. In experiment 1, males were compared with females across the estrous cycle after a single MF exposure. Females circled more and acquired a more persistent CTA than males; circling was highest on the day of estrus. In experiment 2, the effects of three MF exposures were compared among intact rats, ovariectomized females, and ovariectomized females with steroid replacement. Compared with intact rats, ovariectomy increased circling; estrogen replacement blocked the increase. Males acquired a stronger initial CTA but extinguished faster than intact or ovariectomized females. Thus the locomotor circling induced by MF exposure was increased in females and modulated by ovarian steroids across the estrous cycle and by hormone replacement. Furthermore, female rats acquired a more persistent CTA than male rats, which was not dependent on estrous phase or endogenous ovarian steroids.


Cross-Saharan transport of water vapor via recycled cold pool outflows from moist convection.
Very sparse data have previously limited observational studies of meteorological processes in the Sahara. We present an observed case of convectively driven water vapor transport crossing the Sahara over 2.5 days in June 2012, from the Sahel in the south to the Atlas in the north. A daily cycle is observed, with deep convection in the evening generating moist cold pools that fed the next day's convection; the convection then generated new cold pools, providing a vertical recycling of moisture. Trajectories driven by analyses were able to capture the direction of the transport but not its full extent, particularly at night when cold pools are most active, and analyses missed much of the water content of cold pools. The results highlight the importance of cold pools for moisture transport, dust and clouds, and demonstrate the need to include these processes in models in order to improve the representation of Saharan atmosphere.


Bicycle-riding circumstances and injuries in school-aged children. A case-control study.
To identify bicycle-riding circumstances associated with bicycle-related injury among school-aged children. Case-control. One metropolitan emergency department and 3 suburban emergency departments. Consecutive sample of children aged 7 through 18 years who experienced bicycle-related trauma and control children seen for non-bicycle-related trauma (matched for age within 1 year, sex, and area of residence [urban vs suburban]). Parents and case children were interviewed by telephone about the bicycle ride resulting in their visit to the emergency department. Parents and control children were interviewed about their most recent bicycle ride. The survey instrument addressed the following potential risk factors: helmet use, bicycle speed, road conditions, riding location, bicycle condition, an adult presence, riding destination, bicycle style, and stunt riding. Interviews were completed with 47 (73%) of 64 eligible case children and 42 (69%) of 61 control children with the following age distribution: 27 (30%) of the interviews were completed with children aged 7 to 9 years, 40 (45%) of the interviews were completed with children aged 10 to 14 years, and 22 (25%) of the interviews were completed with children aged 15 to 18 years. Fourteen children (16%) were wearing helmets. There was a high degree of agreement between parent and child responses, higher for case children than for control children. In univariate analyses, injury was associated with riding with other children (vs riding alone or with adults), riding fast or slow (vs normal speed), riding a BMX-style (motocross) bicycle (vs another standard or multispeed style bicycle), playing on the bicycle (vs going to school or other purposeful or nonpurposeful trip), and riding only on the sidewalk (vs in the street). More case children than control children were farther than 3/4 mile (> 1.2 km) from home (38% vs 19%, P = .05). Multiple logistic regression identified' slow riding speed (odds ratio, 10.3;95% confidence interval, 1.6-66.8), distance from home farther than 3/4 mile (> 1.2 km) (odds ratio, 3.7;95% confidence interval, 1.1-12.5), and riding on the sidewalk (odds ratio, 6.1;95% confidence interval, 1.8-20.5) as independent risk factors for injury. This study identifies 3 counterintuitive but apparently strong behavioral risk factors for bicycle injuries treated in an emergency department in children aged 7 through 18 years in the Chicago (III) area. These findings will need to be confirmed in larger samples from a wider range of locales. In addition to stressing the importance of wearing a helmet when riding a bicycle, it may be desirable to include the findings of this study in anticipatory guidance discussions with school-aged children.


[Therapy of elderly patients with colorectal carcinoma].
Treating elderly patients with colorectal cancer is a challenging task for which many aspects have to be taken into account. Almost 70% of patients with colorectal cancer are 65 years or older and the number of elderly patients is expected to increase. As elderly patients frequently exhibit adverse physical or socio-economic conditions, a thorough geriatric assessment of the patient's suitability for therapy is essential before making a decision. The first line treatment for colorectal cancer is surgery. Complete resection of the tumor should also be attempted in elderly patients, as there are little differences in cancer--specific survival in selected elderly patients compared to younger patients. Surgery with palliative intention can be attempted for symptom control or to prevent later local complications caused by the primary tumor. At present, adjuvant 5-FU based chemotherapy (in colon cancer) and adjuvant radio-chemotherapy (in rectal cancer) in the elderly is recommended for locally advanced or node positive tumor after tumor resection, since the benefit seems to be comparable to that achieved in younger patients. There is also enough data to support the use of 5-FU based chemotherapy in elderly patients in the palliative setting. New drugs have recently been added to the armentarium for the treatment of metastatic colorectal cancer. However, there is as yet not sufficient data to guide the use of these new drugs (such as oxaliplatin or irinotecan) in elderly patients. However, first clinical studies seem to indicate a comparable efficacy and toxicity in elderly patients to that observed in younger patients. Further clinical trials of chemotherapy in elderly patients with colorectal cancer are necessary to gain information about treatment recommendations. It is the aim of this manuscript to summarize the current knowledge about the management of colorectal cancer in elderly patients.


Brazilin Inhibits Prostatic Acidic Phosphatase Fibrillogenesis and Decreases its Cytotoxicity.
A 39-amino acid peptide fragment that is derived from prostatic acidic phosphatase (PAP), PAP248-286 , is secreted in large amounts in human semen and forms amyloid fibrils. These fibrils can capture HIV virions and increase the attachment of virions to target cells; as such, they are called a "semen-derived enhancer of virus infection" (SEVI). Therefore, the inhibition of the formation of PAP248-286 amyloid fibrils is of great significance. Herein, we demonstrate that brazilin effectively inhibits PAP248-286 aggregation. The inhibitory effect increases with increasing brazilin concentration. Thioflavin T fluorescence assays and TEM observations confirmed that a few fibrils formed when brazilin was present with PAP248-286 in an equimolar concentration. Circular dichroism spectroscopy indicated that brazilin inhibited the secondary structural transitions from α-helices and random coils into β-sheets. Cytotoxicity assays showed that brazilin significantly decreased the cytotoxicity of the fibrils at 0.01 mmol L-1 . Isothermal titration calorimetry revealed that hydrophobic interactions were the main driving force for the binding of brazilin to the PAP248-286 monomer (dissociation constant, 4.03 μmol L-1 ), and that the binding affinity of brazilin for the fibrils was at least three orders of magnitude lower than that for the monomer. These results indicate that brazilin holds great potential as a small-molecule agent against SEVIs.


Risk assessment at the primary health care level in Moshi, Tanzania: limits in predicting sexually transmitted infections among women.
To identify risk factors for sexually transmitted infections (STI) and to evaluate the accuracy of using risk assessment for identifying infected women in Moshi, Tanzania. A cross sectional study. Three primary health care clinics in Moshi. 382 consenting women attending the clinics for routine reproductive health care were interviewed followed by a pelvic examination between September and December 1999. Blood and genital specimens were collected for STI diagnosis. Prevalent STIs, risk factors and accuracy of using risk factors to identify infected women. Among 382 women, 118 (31%) had at least one STI diagnosed clinically or by a laboratory test; (T. vaginalis 21%, syphilis 4.2%, chlamydia and/or gonococcal cervicitis 3.2%, genital ulcer 4.5% and warts 2%). The risk of CT/GC cervicitis was greater among women aged < 20 years (p = 0.04), with cervical friability (p = 0.01) and with > 10 cervical leucocytes (p < 0.001), while having more than one partner in the past three months (p = 0.008) predicted syphilis infection. Trichomoniasis was associated with the presence of vaginal discharge (p = 0.001) and pH > 4.5 (p < 0.001). However, using these risk factors as a screening tool for various STIs achieved a low sensitivity and a low positive predictive value, hence a low utility for case detection. STIs were prevalent in this setting. However, risk factors were not a good tool for identifying infected women. While there is an urgent need to develop low cost microbiological tests for case detection, efforts should be made to maximise the available control strategies, such as proper treatment of symptomatic patients and their partners.


Survey on the presence of non-dioxine-like PCBs (NDL-PCBs) in loggerhead turtles (Caretta caretta) stranded in south Mediterranean coasts (Sicily, Southern Italy).
A total of 71 loggerhead turtles (Caretta caretta) stranded along the coasts of Sicily (Southern Italy) were examined for non-dioxine like polychlorinated biphenyl (NDL-PCB) levels in muscle and adipose tissue by a gas chromatography-mass spectrometry/mass spectrometry (GC-MS/MS) method. The results revealed 6 high-indicator congener (∑6 PCBIND ) levels in 45% of the loggerhead turtles examined, with mean values of 980.39 ± 2508.39 ng/g wet weight in adipose tissue and 102.53 ± 238.58 ng/g wet weight in muscle tissue. The hexachloro and heptachloro PCB congeners were the most abundant in both the sample types. The highest NDL-PCB levels were reached in an adipose tissue sample of a loggerhead turtle of 80 kg stranded along the coasts of Termini Imerese (14 183.85 ng/g wet wt). No significant correlation was found between modified Fulton's K values of the loggerhead turtles and PCB contents (S = 47 151, p > 0.05). Furthermore, no significant differences were found between sexes (W = 365, p > 0.05). The PCB levels found in the present study were much higher than those found in the literature. The present study is the first report on the existence of NDL-PCBs in loggerhead turtles stranded in Sicilian coasts confirming C. caretta as a valuable indicator of contaminant exposure in the marine environment because of their specific biological and ecological characteristics. Environ Toxicol Chem 2017;36:2997-3002. © 2017 SETAC.


Selectivity of compounds isolated from the leaves of Nerium indicum Mill. on various human cancer cell lines.
The leaves of Nerium indicum Mill. have been utilized traditionally to cure cancer. By Bioassay (BST) guided isolation method, six compounds were isolated from the CHCl3 extract of the leaves. Selectivity of these compounds (in 0.6-12,500 ng/ml) was tested on various human cancer (MCF7, EVSA-T, T47D, H226, IGROV, A498, WIDR, M19, HeLa) and normal (Vero) cells in vitro. Doxorubicin and cysplatin were used as positive controls. The result indicated that NiO2D (5alpha-oleandrin) possessed the best cytotoxic effect on HeLa cells (IC50, 8.38 x10(-6) mM) and NiO2C (16, 17-dehidrodeasetil-5alpha-oleandrin) on A498 cells (IC50, 1.43 x 10(-6) mM). Those two compounds were not cytotoxic to normal cell.


Prolactin in man: a tale of two promoters.
The pituitary hormone prolactin (PRL) is best known for its role in the regulation of lactation. Recent evidence furthermore indicates PRL is required for normal reproduction in rodents. Here, we report on the insertion of two transposon-like DNA sequences in the human prolactin gene, which together function as an alternative promoter directing extrapituitary PRL expression. Indeed, the transposable elements contain transcription factor binding sites that have been shown to mediate PRL transcription in human uterine decidualised endometrial cells and lymphocytes. We hypothesize that the transposon insertion event has resulted in divergent (pituitary versus extrapituitary) expression of prolactin in primates, and in differential actions of pituitary versus extrapituitary prolactin in lactation versus pregnancy respectively. Importantly, the TE insertion might provide a context for some of the conflicting results obtained in studies of PRL function in mice and man.


Blood concentrations of lidocaine, mepivacaine and bupivacaine during caudal analgesia in children.
The venous blood concentrations of lidocaine, mepivacaine and bupivacaine were measured in children following the caudal epidural administration of these local anaesthetic solutions with adrenaline. The mean maximum concentrations of lidocaine and mepivacaine were 2.20 micrograms/ml and 2.53 micrograms/ml, respectively, which occurred at 45 min after injection of lidocaine or mepivacaine 11 mg/kg. By combined administration of 5.5 mg/kg equally of lidocaine and mepivacaine, the blood concentration of mepivacaine was significantly higher than that of lidocaine. The mean maximum concentration of bupivacaine was 0.67 micrograms/ml and occurred at 45 min after injection of bupivacaine 3.7 mg/kg. The blood concentration of bupivacaine was consistently significantly lower than that of lidocaine or mepivacaine. These results demonstrate that the blood concentrations of the three local anaesthetics following caudal administration are all below the toxic levels in spite of application of the maximum dosage recommended for adults.


Sirolimus-related pulmonary toxicity mimicking 'asthma like' symptoms.
Sirolimus is an immunosuppressant with expanding use in pediatric organ transplantation, dermatology and rheumatology. We report two cases of children who developed asthma like symptoms and were diagnosed with interstitial lung disease, which responded to discontinuation of sirolimus. Pediatricians should be aware about the pulmonary side effects of sirolimus.


[HCV-PCR-Hybrid.ELISA for the detection of HCV RNA in serum samples from hepatitis patients].
To detect HCV RNA in serum samples from hepatitis patients by using the methods of HCV-Reverse transcription polymerase chain reaction and hybrid ELISA. HCV RNA in serum samples was amplified by RT-PCR with one of the primer labeled with biotin. PCR amplified products were detected with microtiter plate hybridization with HCV specific probe, then determined with steptavidin-HRP assay. Anti-HCV in these samples was also detected with ELISA simultaneously. The positive rates of HCV RNA were 81.8% (72/88) in anti-HCV positive group and 57.9% (88/152) in the whole patients group. Serum HCV RNA and anti-HCV positive rates were compared and the consistent rate was 78.9% (120/152, P>0.05). The positive rate of HCV RNA was higher in H.ELISA (57.9%, 88/152) than that in electrophoresis (35.5%, 54/152)(P<0.01). The HCV-PCR-H.ELISA was a sensitive, specific, stable, semi-quantitative and easy to operate method. This HCV RNA detection was especially beneficial to early diagnosis during viramia period and was helpful for the evaluation of anti-HCV therapy.


Theories of truth and teaching clinical reasoning and problem solving.
In this paper, we will first discuss two current meta-theories dealing with different, aspects of "truth". The first metatheory conceives of truth in terms of coherence (rationality, consistency): a body of knowledge is true when it contains no inconsistencies and has at least some credibility. The second metatheory conceives of truth as correspondence, i.e., empirical accuracy. The two metatheories supplement each other, but are also incommensurable, i.e., they cannot be expressed in each other's terms, for they employ completely different criteria to establish truth (Englebretsen in Bare facts and naked truths: a new correspondence theory of truth, Routledge, London, 2005). We will discuss both the role of both metatheories in medicine, in particular in medical education in a clinical context. In line with Hammond's view (Med Decis Mak 16(3):281-287, 1996a; Human judgment and social policy: irreducible uncertainty, inevitable error, unavoidable injustice, Oxford University Press, New York, 1996b), we will extend the two metatheories to two forms of competence: coherence competence and correspondence competence, and demonstrate that distinguishing these two forms of competence increases our insights as to the best way to teach undergraduate students clinical problem solving.