Relative risk of pulmonary embolism in the very elderly compared with the elderly.
Pulmonary embolism (PE) can be an acute, life-threatening emergency, and studies suggest that advanced age is a risk factor for this condition. However, the literature is scarce regarding PE in patients above the age of 90 years. This study examined the relative risk for PE in the very elderly (>90 years) compared with that in the elderly (80-89 years). A retrospective study was performed examining very elderly patients diagnosed with PE in the Department of Internal Medicine at the University Hospital Homburg/Saar in Germany between 2004 and 2012. Elderly patients (aged 80-89 years) diagnosed with PE served as controls. PE was confirmed by contrast-enhanced chest computed tomography or ventilation perfusion scintigraphy in both groups. A total of 2230 patients were examined for PE in this study. Of these, 15 (0.67%) in the study group and 197 (8.83%) in the control group underwent further evaluation for PE. After performing a radiological examination, 11 (73.3%, including six [54.55%] women) of the 15 study patients (mean age 91.6 ± 1.67 years) and 148 (75.1%, including 93 [62.84%] women) of the 197 controls (mean age 84.0 ± 2.59 years) were confirmed to have PE. There was a significantly lower proportion of the very elderly enrolled in the study (P < 0.001). There were no significant differences in clinical presentation, cardiovascular risk factors, electrocardiograms, blood gas analyses, radiological diagnoses, or acute comorbidities between the groups. However, the very elderly were more likely to experience minor bleeding in the extremities (P = 0.016) and to have more chronic diseases (P < 0.001). An increased relative risk of PE was not detected in the very elderly (relative risk 0.98, P = 0.88). Furthermore, D-dimer, troponin T, and high-sensitive troponin T levels had limited predictive value for PE in the very elderly. There were no significant differences in the number of hospital admissions, intensive care or ward treatments, or duration of hospitalization. The relative risk for PE in the very elderly is not higher than that in the elderly.


Ileocolonoscopic findings in seronegative spondylarthropathies.
Ileocolonoscopy with biopsy of caecum, ileocaecal valve and terminal ileum were performed on 232 patients with seronegative spondylarthropathies and on 65 control patients. Inflammatory gut lesions were found in 65% of the patients with reactive arthritis (ReA) and in 57% of the patients with ankylosing spondylitis (AS), especially in those with peripheral arthritis. The controls had a normal gut. This finding would suggest that exogenous factors causing inflammation of the gut lead to a disturbed permeability of the gut wall or to a deficient local immunological defence mechanism permitting antigens to enter the circulation, inducing the joint and tendon inflammation. Support for this hypothesis was provided by the results of a repeat ileocolonoscopy, disclosing a strong association between the presence of gut inflammation on biopsy and the persistence of joint inflammation. Patients presenting some of the histological lesions found on biopsy (especially active chronic lesions) and patients with proven Crohn's disease were found to share a genetic marker (HLA-BW62). This would suggest that some of the patients with seronegative spondylarthropathies suffer from a subclinical form of Crohn's disease of which the joint symptoms are the unique clinical manifestation.


Phase II study of capecitabine and mitomycin C as first-line treatment in patients with advanced colorectal cancer.
This study was designed to assess the safety and efficacy of capecitabine and mitomycin C (MMC) in previously untreated patients with advanced colorectal cancer (CRC). Patients received capecitabine 2500 mg m(2) day 1, orally divided in two doses of 1250 mg m(-2) in the morning and evening for 14 days every 21 days and MMC 7 mg m(-2) (maximum total dose 14 mg) as an intravenous bolus every 6 weeks for a total of four courses. The median age was 70 years (range 24-85) and the majority of patients (86.9%) were of performance status 1/2. The most common metastatic site was liver. In all, 84 patients were assessable for response. The overall response rate was 38% (95% CI: 27.7-49.3) and a further 33.3% of patients achieved stable disease over 12 weeks. There was good symptom resolution ranging from 64 to 86%. Grade 3/4 toxicity was as follows: hand-foot syndrome 19.7%; diarrhoea 10%; neutropenia 2.4%; infection 2.3%. Capecitabine and MMC have shown encouraging activity with a favourable toxicity profile, a convenient administration schedule, and could be considered for patients deemed unsuitable for oxaliplatin and irinotecan combinations.


Sensitivity analysis of respiratory parameter estimates in the constant-phase model.
The constant-phase model is increasingly used to fit low-frequency respiratory input impedance (Zrs), highlighting the need for a better understanding of the use of the model. Of particular interest is the extent to which Zrs would be affected by changes in parameters of the model, and conversely, how reliable are parameters estimated from model fits to the measured Zrs. We performed sensitivity analysis on respiratory data from 6 adult mice, at functional residual capacity (FRC), total lung capacity (TLC), and during bronchoconstriction, obtained using a 1-25 Hz oscillatory signal. The partial derivatives of Zrs with respect to each parameter were first examined. The limits of the 95% confidence intervals, 2-dimensional pairwise and p-dimensional joint confidence regions were then calculated. It was found that airway resistance was better estimated at FRC, as determined by the confidence region limits, whereas tissue damping and elastance were better estimated at TLC. Airway inertance was poorly estimated at this frequency range, as expected. During methacholine-evoked pulmonary constriction, there was an increase in the uncertainty of airway resistance and tissue damping, but this can be compensated for by using the relative (weighted residuals) in preference over the absolute (unweighted residuals) fitting criterion. These results are consistent with experimental observation and physiological understanding.


[Undesirable pharmacokinetic drug-to-drug interactions affecting the effectiveness and safety of anti-infectious pharmacotherapy].
The occurence of pharmacokinetic drug-to-drug interactions is the serious clinical problem in the course of pharmacotherapy of infections. Its essential part is the influence of such interactions on the effectiveness and safety of antimicrobial therapy. The aim of study was to present, the most significant on clinical hand, examples of interactions and their mechanisms between antimicrobial agents and other drugs on stages of absorption, distribution, biotransformation and elimination, leading to the decreased antimicrobial activity and ineffective pharmacotherapy or to the increased antimicrobial activity and to the increased risk of adverse effects due to agents used for anti-infectious pharmacotherapy.


Gonadotropin response to LH-RH in anorexia nervosa.
The gonadotropin-ovary axis of patients with anorexia nervosa was assessed with the aim of distinguishing between an intrinsically hypophysial deficiency and pituitary malfunction secondary to hypothalamic impairment. The most consistent endocrine abnormality was low serum luteinizing and follicle stimulating hormone (LH and FSH) levels associated with depressed serum estradiol levels. Gonadotropin levels responded to luteinizing hormone-releasing hormone (LH-RH), thus indicating a primarily hypothalamic dysfunction. The increase in serum FSH was at least as great as that of LH. The LH levels were additionally depressed and their increase after LH-RH injection somewhat blunted by three-day treatment with ethinyl estradiol.


[Maternal serum AFP determination in the 2d trimester: a suitable screening method for detection of fetuses with Down's syndrome in young females?].
The frequency distributions of maternal serum alpha-fetoprotein levels in pregnancies with fetal Down syndrome (n = 84) and in unaffected pregnancies (n = 9982) were fitted to extreme value distributions. The risk of an individual woman having a pregnancy associated with Down's syndrome was estimated depending on age and serum AFP level (MOM). A risk of Down's syndrome greater than 1:384 corresponding to the risk of a greater than or equal to 35-year-old woman was chosen to the lowest risk indicating referral for amniocentesis. The retrospective analysis of our data showed an age depending sensitivity of the maternal serum AFP screening. Only five of twenty-one cases in younger women (less than 35-year-old) but all of the thirteen cases in older women (38-40 years old) could have been detected based on low AFP levels. By calculating the sensitivity of the AFP Screening it seems to be impossible to reduce clearly the risk of Down's syndrome in young women.


Diagnosis and treatment of antibody-mediated kidney allograft rejection.
Evidence of a significant pathogenetic role of donor-reactive antibodies (DRA) in kidney allograft rejection is accumulating. At least, partially owing to the recent discovery of the complement split product C4d as a valuable rejection marker, antibody-mediated rejection (AMR) has regained increasing attention. We review here the value of various diagnostic criteria, including immunohistochemistry (C4d staining), histomorphology and posttransplant serology, for the diagnosis of AMR. Furthermore, the mechanisms underlying alloantibody/complement-mediated allograft injury are discussed in detail. Finally, a thorough discussion of recently proposed "anti-humoral" therapeutic strategies is provided.


Green fluorescent protein fused to peptide agonists of two dissimilar G protein-coupled receptors: novel ligands of the bradykinin B2 (rhodopsin family) receptor and parathyroid hormone PTH1 (secretin family) receptor.
We hypothesized that peptide hormone sequences that stimulate and internalize G protein-coupled receptors (GPCRs) could be prolonged with a functional protein cargo. To verify this, we have selected two widely different pairs of peptide hormones and GPCRs that nevertheless share agonist-induced arrestin-mediated internalization. For the parathyroid hormone (PTH) PTH1 receptor (PTH1R) and the bradykinin (BK) B2 receptor (B2R), we have designed fusion proteins of the agonists PTH1-34 and maximakinin (MK, a BK homologue) with the enhanced green fluorescent protein (EGFP), thus producing candidate high molecular weight ligands. According to docking models of each hormone to its receptor, EGFP was fused either at the N-terminus (MK) or C-terminus (PTH1-34) of the ligand; the last construction is also secretable due to inclusion of the preproinsulin signal peptide and has been produced as a conditioned medium. EGFP-MK has been produced as a lysate of transfected cells. Using an enzyme-linked immunosorbent assay (ELISA) for GFP, average concentrations of 1.5 and 1670 nmol/L, respectively, of ligand were found in these preparations. The functional properties and potential of these analogs for imaging receptor-expressing cells were examined. Microscopic and cytofluorometric evidence of specific binding and internalization of both fusion proteins was obtained using recipient HEK 293a cells that expressed the cognate recombinant receptor. Endosomal colocalization studies were conducted (Rab5, Rab7, β-arrestin1). Evidence of agonist signaling was obtained (expression of c-Fos, cyclic AMP responsive element (CRE) reporter gene for PTH1-34-EGFP). The constructs PTH1-34-EGFP and EGFP-MK represent bona fide agonists that support the feasibility of transporting protein cargoes inside cells using GPCRs.


Experiences of women referred for urgent assessment of postmenopausal bleeding (PMB).
Women with postmenopausal bleeding (PMB) are referred for specialist assessment within 2 weeks of presentation to their GP. No research has previously examined women's experiences of expedited referral. This was investigated in the present study using questionnaires (6-item State Anxiety Inventory (6-STAI)) and focus groups. A total of 55 women completed questionnaires. Results showed high levels of anxiety at first hospital visit (mean 47.0 (SD 14.27); 95% CI 43.14-50.93). Scores declined by 90 days, but were higher in those not undergoing hysteroscopy. Fifteen women who underwent hysteroscopy attended focus groups. Women recalled fear of cancer from symptom onset until receipt of results. Anxiety was exacerbated by poor knowledge of PMB and lack of awareness of expedited referral. Post-discharge, those with unexplained or recurrent symptoms expressed frustration and upset. Effective strategies to raise awareness of PMB and its causes are needed, including reasons for expedited referral. Women without cancer may also need more support.


Two cases of the same family with the unusual elevation of CA19-9 levels.
Serum carbohydrate associated antigen (CA19-9) is widely used marker in clinical practice and shows small increases in a few benign diseases. Here we report two cases, a mother and her daughter with slightly elevated CA19-9 levels not accompanied by any clinical pathology. The mother with elevated CA19-9 level (89.90 U/mL; upper limit of normal range (ULNR) < 37 U/mL) was referred to our department for evaluation. Similar increase was determined in her daughter incidentally. Daughter's CA19-9 level was 123.92 U/mL. Extensive laboratory data, imaging procedures and clinical evaluations were within the normal ranges except elevated CA19- 9 levels for both. Also, any pathology compatible with the elevated CA19-9 level couldn't be determined. In order to avoid laboratory errors and interferences, we measured the samples at four different immunoassay platforms twice. Healthy people can be in excess of the ULNR. Therefore, clinicians need to be aware of these rare situations without missing the malignant disorders.


Antifreeze poisoning: A case report.
The current study reported the case of a 35-year-old male that presented with antifreeze poisoning. The clinical manifestations, laboratory investigations and treatments were analyzed, and the obtained results were compared with those in previous reports. Subsequent to consuming antifreeze, the patient mainly presented nausea and agitation, without disturbance of consciousness. Laboratory investigations indicated severe metabolic acidosis, renal dysfunction and hyperkalemia. The patient underwent hemodialysis and his condition was significantly improved on the day of admission. Renal function gradually deteriorated, but was eventually improved due to treatment, including hemodialysis, mannitol for catharsis, furosemide for diuresis, Xuebijing for the removal of blood stasis and detoxication, and reduced glutathione for the protection of major organs. The patient was discharged 1 month after hospital admission. In conclusion, the significance and clinical manifestations of antifreeze poisoning should be identified in clinical practice, and active hemodialysis should be provided. The aim of the current study was to summarize the clinical manifestations and treatments of patients with antifreeze poisoning, and to advance the recognition of antifreeze poisoning.


Induced Folding Under Membrane Mimetic and Acidic Conditions Implies Undiscovered Biological Roles of Prokaryotic Ubiquitin-Like Protein Pup.
Ubiquitin-like proteins play important roles in diverse biological processes. In Mycobacterium tuberculosis, Pup (prokaryotic ubiquitin-like protein), a functional homologue of eukaryotic ubiquitin, interacts with the proteasome ATPase subunit Mpa to recognize and unfold substrates, and then translocate them into the proteasome core for degradation. Previous studies revealed that, Pup, an intrinsically disordered protein (IDP), adopts a helical structure upon binding to the N-terminal coiled-coil domain of Mpa, at its disordered C-terminal region. In the present study, using circular dichroism (CD), surface plasmon resonance (SPR) and nuclear magnetic resonance (NMR), we show that membrane mimetic and acidic conditions also induce Pup to adopt helical conformations. Moreover, at low pH, Pup, via both of its N- and C-terminal regions, binds to Mpa on sites from the N-terminal region in addition to the C-terminal region of the coiled-coil domain. Our results imply Pup may play undiscovered roles in some biological processes e.g. those involve in membrane.


Two complex, adenovirus-based vaccines that together induce immune responses to all four dengue virus serotypes.
Dengue virus infections can cause hemorrhagic fever, shock, encephalitis, and even death. Worldwide, approximately 2.5 billion people live in dengue-infested regions with about 100 million new cases each year, although many of these infections are believed to be silent. There are four antigenically distinct serotypes of dengue virus; thus, immunity from one serotype will not cross-protect from infection with the other three. The difficulties that hamper vaccine development include requirements of the natural conformation of the envelope glycoprotein to induce neutralizing immune responses and the necessity of presenting antigens of all four serotypes. Currently, the only way to meet these requirements is to use a mixture of four serotypes of live attenuated dengue viruses, but safety remains a major problem. In this study, we have developed the basis for a tetravalent dengue vaccine using a novel complex adenovirus platform that is capable of expressing multiple antigens de novo. This dengue vaccine is constructed as a pair of vectors that each expresses the premembrane and envelope genes of two different dengue virus serotypes. Upon vaccination, the vaccine expressed high levels of the dengue virus antigens in cells to mimic a natural infection and induced both humoral and cellular immune responses against multiple serotypes of dengue virus in an animal model. Further analyses show the humoral responses were indeed neutralizing against all four serotypes. Our studies demonstrate the concept of mimicking infections to induce immune responses by synthesizing dengue virus membrane antigens de novo and the feasibility of developing an effective tetravalent dengue vaccine by vector-mediated expression of glycoproteins of the four serotypes.


[Analysis of Oxidative Damage to Components Removed from Beznoska/Poldi Total Hip Replacements].
PURPOSE OF THE STUDY Ultrahigh molecular weight polyethylene (UHMWPE) is today the most frequently used bearing surface in total joint replacements (TJR) because of its properties, i.e., excellent biocompatibility, good mechanical and tribological performance and high wear resistance. UHMWPE liners are the most loaded TJR components and, therefore, their properties are decisive for TJR longevity. This study had three objectives: 1) to evaluate the oxidative degradation of explanted UHMWPE components; 2) to look for a statistically significant relationship between the extent of oxidative degradation and the durability of joint replacements; and 3) to investigate whether the durability of a TJR was related to the type of sterilisation used in manufacture. MATERIAL AND METHODS The study included 26 acetabular components obtained at revision arthroplasty between 2004 and 2013 from patients in whom a Beznoska/Poldi total hip replacement was used in the period from 1977 to 2002. The average age of the patients at the time of primary implantation was 57.9 years, the average longevity of the components removed was 18.63 years (range, 6.9 to 27.9 years). Samples of worn out and unworn areas from explanted components were processed in a three-step procedure in order to finally obtain 2-mm microtome sections. These were studied by infrared microspectroscopy. Oxidative damage to UHMWPE was determined as the oxidation index (OI); radiation damage to UHMWPE during sterilization was evaluated as the transvinylene index (VI); oxidation-induced changes in the polymer structure and its properties were characterised as the crystallinity index (CI); and local changes in mechanical properties due to oxidative degradation were assessed as microhardness (MH). Spearman's correlation coefficient and the Wilcoxon two-sample test were used for statistical analysis. RESULTS The OI values (average and maximum) in both worn out and unworn surface areas were related to component longevity. The difference between the oxidation index of ruptured components and that of the other components was statistically significant. Significant differences were also found between the average and maximum OI values of worn out areas and those of unworn surfaces. The relationship between the average oxidation index in both the unworn and worn out areas of UHMWPE components and the longevity of cracked components was statistically significant. DISCUSSION Our results show that the OI values obtained by microspectroscopy correlated with both the microscopic damage and the longevity of UHMWPE liners and the correlation was statistically significant also in relation to the longevity of total replacements. Relationships amongst OI, VI, CI and MH values as well as their relation to failure and longevity of total replacements are discussed. CONCLUSIONS It can be concluded that infrared microspectroscopic measurement of OI values is a simple and fast method to characterise UHMWPE liners. In addition, the IR spectra also show other supplementary characteristics, such as VI and CI indices. These values provide information on the quality of various UHMWPE types currently used in TJR surgery. The types of UHMWPE which exhibit high oxidative degradation should be avoided in clinical practice due to increased risk of early TJR failure. Responsible orthopedic surgeons should be aware of this fact and, if possible, collaborate with an independent, noncommercial laboratory in order to evaluate the quality of various UHMWPE liners used in their hospitals. UHMWPE, oxidation, total joint replacement, infrared spectroscopy, microhardness.


Reciprocal Effects of Self-Regulation, Semantic Knowledge, and Reading Comprehension in Early Elementary School.
Many assume that cognitive and linguistic processes, such as semantic knowledge (SK) and self-regulation (SR), subserve learned skills like reading. However, complex models of interacting and bootstrapping effects of SK, SR, instruction, and reading hypothesize reciprocal effects. Testing this "lattice" model with children (n = 852) followed from first to second grade (5.9-10.4 years of age) revealed reciprocal effects for reading and SR, and reading and SK, but not SR and SK. More effective literacy instruction reduced reading stability over time. Findings elucidate the synergistic and reciprocal effects of learning to read on other important linguistic, self-regulatory, and cognitive processes; the value of using complex models of development to inform intervention design; and how learned skills may influence development during middle childhood.


Risk factors associated with the onset and progression of Alzheimer's disease: A systematic review of the evidence.
A systematic review was conducted to identify risk factors associated with the onset and progression of Alzheimer's disease (AD). Moderate and high quality systematic reviews were eligible for inclusion. Primary studies reporting on non-genetic risk factors associated with neuropathologically or clinically confirmed AD were considered. Eighty one systematic reviews reporting on AD onset and 12 reporting on progression satisfied the eligibility criteria. Four hundred and thirty-two relevant primary studies reporting on onset were identified; however, only those published between 2010 and 2012 (n=65) were included in the qualitative synthesis. Several factors including statins, light-to-moderate alcohol consumption, compliance with a Mediterranean diet, higher educational attainment, physically and cognitively stimulating activities, and APOE ε2 appeared to be associated with a decreased risk of AD onset. The evidence was suggestive of an increased risk of AD associated with head injury in males, age, diabetes mellitus, conjugated equine estrogen use with medroxyprogesterone acetate, current smoking, and lower social engagement. With respect to genetic factors, APOE ε4 remained the strongest predictor of AD. Physical and cognitive activities were associated with a beneficial effect on cognitive function and other indicators of dementia progression while higher educational attainment was associated with faster cognitive decline. Although suggestive of an association, the current evidence for a majority of the identified putative factors for AD onset and progression was weak, at best due to conflicting findings across studies or inadequate evidence. Further research is required to confirm the etiological or protective role of a number of risk factors.


Relational themes in the inpatient community meeting.
The authors present a model of psychiatric inpatient community meetings run as large group interpretive psychotherapy. They developed this model in part from Gill's notion that patients attach plausible meanings to therapist behavior based on the patient's characteristic and stereotypical ways of experiencing relationships. The model provides a framework for the description of 11 clinically derived "unconscious relational configurations" that can frequently be detected as organizing "relational themes" of community meetings. The authors present two clinical vignettes in which staff detect these themes and interpret them together with the defenses against them. They then discuss the prominent negative affective valence that characterizes the "unconscious relational configurations."


Assessment of abdominal muscle function during a simulated unilateral weight-bearing task using ultrasound imaging.
Cross-sectional study. To investigate the function of the transversus abdominis (TrA) and internal oblique (10) muscles bilaterally during a simulated weight-bearing task using ultrasound imaging. An important aspect of neuromuscular control at the lumbopelvic region is stabilization. Biomechanical models have predicted that activation of transversely oriented muscles, such as the TrA and 10 muscles, can stiffen the sacroiliac joints and actively stabilize the pelvis for weight bearing. Nineteen healthy subjects were positioned in supine lying with their right heel against a footplate linked to a force transducer. Each subject performed a static simulated weight-bearing task of the right lower extremity. Ultrasound imaging was used to assess resultant changes in thickness of the 10 and TrA muscles, as well as the lateral slide of the anterior abdominal fascia on each side of the abdomen alternately. Muscle thickness and slide of the fascia were assessed at standardized force levels (0% and 25% of body weight). Substantial increases (P < .0001) in mean (+/- SD) thickness of the 10 (18.5% +/- 9.7%) and TrA (24.7% +/- 175%) muscles during the weight-bearing task were measured. Lateral movement (slide) of the anterior abdominal fascia of the TrA muscle also occurred (mean +/- SD, 1.3 +/- 2.0 mm; P = .014) with weight bearing. Changes in muscle thickness and amount of slide were similar for the left and right side of the abdomen (P > or = .11). The findings are consistent with biomechanical models that predicted symmetrical activation of the deep transversely oriented lumbopelvic muscles in healthy subjects in response to a unilateral functional weight-bearing task. Ultrasound imaging as a measurement tool represents a noninvasive method for measuring abdominal muscle function in functional axial loading.


Effect of eTansiyon smartphone application on hypertension control.
To investigate the effectiveness of eTansiyon smartphone application in blood pressure control in patients with hypertension. Global prevalence of hypertension and the burden of chronic illness care, especially in primary care, are increasing in world. We have developed eTansiyon to ensure the continuity of patient-physician relationship, so it may help to improve the lifestyle of patients with hypertension, increase their adherence to treatment and achieve the target blood pressure. This study was a non-randomized controlled study. The sample was selected by random sampling method among the patients registered in 6 Family Health Units (FHUs). Randomization was performed at the FHU level; the units were randomized to 4 control group (CG) and 2 intervention group (IG), so that randomization in this study was 2:1. Both groups were followed up for at least four months. In addition to CG, IG were provided to use eTansiyon. Obtained data were analysed to evaluate differences between groups at the beginning and end of the study, intra-group changes after follow-up and interaction between groups and follow-up period. The study was performed with 124 patients in CG and 61 patients in IG. At the end of the study, the average systolic blood pressure/diastolic blood pressure (SBP/DBP) of office and home was significantly lower in IG compared to CG (P < 0.001, MD 9.5 mmHg; P = 0.007, MD 3.8 mmHg; P < 0.001, MD 10.6 mmHg; P < 0.001, MD 4.8 mmHg, respectively), and it was found that the proportion of people with target blood pressure in IG was significantly higher than CG (P < 0.001, 49.2%(n = 30) and 22.6%(n = 28), respectively). Repeated measures ANOVA and generalized estimating equations results showed that follow-up period and interaction between groups were significant in terms of office and home SBP/DBP and target blood pressure level during follow-up period (P < 0.001, P < 0.001, P < 0.001, P < 0.001, P < 0.024, respectively).


The Relationship between Muscle Fiber Composition and Pork Taste-traits Assessed by Electronic Tongue System.
To investigate relationships of electronic taste-traits with muscle fiber type composition (FTC) and contents of nucleotides, porcine longissimus lumborum (LL), psoas major (PM), and infra spinam (IS) muscles were obtained from eight castrated LYD pigs. FTC and taste-traits in these three porcine muscles were measured by histochemical analysis and electronic tongue system, respectively. IS had significantly higher proportion of type I fibers while LL had significantly higher proportion of type IIB than other muscles (p<0.05). IS had the highest inosine monophosphate (IMP) content while LL had the lowest IMP content (p<0.05). In contrast, LL had significantly higher hypoxanthine content compared to PM and IS (both p<0.05). For taste-traits, IS had significantly higher umami and richness values but lower sourness value than LL and PM (p<0.05). Sourness and astringency values of LL were significantly higher than those of IS (p<0.05). The proportion of type IIB fiber was positively correlated with sourness and astringency but negatively correlated with saltiness. These results suggest that sourness and astringency tastes are increased with increasing proportions of type IIB fibers in porcine muscles due to increase of hypoxanthine content. These results also imply that umami and richness tastes are increased with increasing contents of type I and IIA fibers because of increased IMP content in porcine muscles.


DNA polymerases from RNA tumor viruses and human cells: inhibition by polyuridylic acid.
Polyuridylic acid inhibited DNA polymerases purified from three species of oncornaviruses as well as three out of seven DNA polymerases purified from cells. Viral and cellular DNA polymerases could not be distinguished by polyuridylic acid inhibition, but were easily distinguished by their template preferences in the presence of magnesium.


A Synergy Cropland of China by Fusing Multiple Existing Maps and Statistics.
Accurate information on cropland extent is critical for scientific research and resource management. Several cropland products from remotely sensed datasets are available. Nevertheless, significant inconsistency exists among these products and the cropland areas estimated from these products differ considerably from statistics. In this study, we propose a hierarchical optimization synergy approach (HOSA) to develop a hybrid cropland map of China, circa 2010, by fusing five existing cropland products, i.e., GlobeLand30, Climate Change Initiative Land Cover (CCI-LC), GlobCover 2009, MODIS Collection 5 (MODIS C5), and MODIS Cropland, and sub-national statistics of cropland area. HOSA simplifies the widely used method of score assignment into two steps, including determination of optimal agreement level and identification of the best product combination. The accuracy assessment indicates that the synergy map has higher accuracy of spatial locations and better consistency with statistics than the five existing datasets individually. This suggests that the synergy approach can improve the accuracy of cropland mapping and enhance consistency with statistics.


Segmental morphometrics of the olive baboon (Papio anubis): a longitudinal study from birth to adulthood.
The linear dimensions and inertial characteristics of the body are important in locomotion and they change considerably during the ontogeny of animals, including humans. This longitudinal and ontogenetic study has produced the largest dataset to date of segmental morphometrics in a Catarrhini species, the olive baboon. The objectives of the study were to quantify the changes in body linear and inertial dimensions and to explore their (theoretical) mechanical significance for locomotion. We took full-body measurements of captive individuals at regular intervals. Altogether, 14 females and 16 males were followed over a 7-year period, i.e. from infancy to adulthood. Our results show that individual patterns of growth are very consistent and follow the general growth pattern previously described in olive baboons. Furthermore, we obtained similar growth curve structures for segment lengths and masses, although the respective time scales were slightly different. The most significant changes in body morphometrics occurred during the first 2 years of life and concerned the distal parts of the body. Females and males were similar in size and shape at birth. The rate and duration of growth produced substantial size-related differences throughout ontogeny, while body shapes remained very similar between the sexes. We also observed significant age-related variations in limb composition, with a proximal shift of the centre of mass within the limbs, mainly due to changes in mass distribution and in the length of distal segments. Finally, we observed what we hypothesize to be 'early biomechanical optimization' of the limbs for quadrupedal walking. This is due to a high degree of convergence between the limbs' natural pendular periods in infants, which may facilitate the onset of quadrupedal walking. Furthermore, the mechanical significance of the morphological changes observed in growing baboons may be related to changing functional demands with the onset of autonomous (quadrupedal) locomotion. From a wider perspective, these data provide unique insights into questions surrounding both the processes of locomotor development in primates and how these processes might evolve.


IgE production in allergic asthmatic patients with different asthma control status.
Although much is known about the fact that IgE-mediated allergic inflammatory response contributes to airway inflammation, bronchial hyperresponsiveness, and asthma severity, little is known about the degree of IgE response in allergic asthmatics during treatment. To determine the amount of total serum IgE among allergic asthmatic patients with various asthma controls. A total of 190 non-smoking patients with allergic asthma were divided into three groups by using the asthma control definition according to the GINA 2006 criteria. There were 64 well-controlled, 88 partly-controlled, and 38 uncontrolled. After study entry, patients underwent lung function test, methacholine challenge and skin prick test to establish allergic status. Peripheral venous blood specimens were collected to measure total IgE and absolute eosinophil numbers. The data are expressed as mean +/- SD. The logarithm of total serum IgE was significantly higher in subjects with uncontrolled allergic asthma than in those with well-controlled disease (p < .0001). IgE response in uncontrolled asthmatics was still high despite having been treated with ICS at a dose which was significantly high when compared with well-controlled subjects (1075.4 +/- 420 vs. 703.5 +/- 355, p < .0001). The logarithm of total serum IgE was associated with increased blood eosinophil counts (r = 0.25, p .0007) among three asthmatic groups and with decreased prebronchodilator FEV1 (r = -0.42, p = .0075) and PC20 (r = -0.36, p = .04) only in uncontrolled group. In allergic asthmatic patients with various disease control stages, there are differences in IgE immune response. Both high and non-suppressible total serum IgE response may be involved in the development of uncontrolled asthma.


Expressive Language Intratest Scatter of Preschool-Age Children Who Stutter.
The purpose of this study was to assess intratest scatter (variability) on standardized tests of expressive language by preschool-age children who do (CWS) and do not stutter (CWNS). Participants were 40 preschool-age CWS and 46 CWNS. Between-group comparisons of intratest scatter were made based on participant responses to the Expressive subtest of the Test of Early Language Development - 3 (TELD-Exp; Hresko, Reid, & Hamill, 1999) and the Expressive Vocabulary Test 2 (EVT-2; Williams, 2007). Within-group correlational analyses between intratest scatter and stuttering frequency and severity were also conducted for CWS. Findings indicated that, for CWS, categorical scatter on the EVT-2 was positively correlated with their stuttering frequency. No significant between-group differences in intratest scatter were found on the TELD-Exp or the EVT-2. Consistent with earlier findings, variability in speech-language performance appears to be related to CWS' stuttering, a finding taken to suggest an underlying cognitive-linguistic variable (e.g., cognitive load) may be common to both variables.


Association of alginate from Pseudomonas aeruginosa with two forms of heparin-binding lectin isolated from rat lung.
An endogenous heparin-binding lectin activity isolated from rat lung was separated into two distinct isolectin forms which showed subtle changes in carbohydrate specificity. The two lectin forms displayed different specificities toward alginic acid-purified cystic fibrosis isolates of Pseudomonas aeruginosa when assayed by inhibition of both hemagglutination and [3H]heparin binding. This ability of isolectin forms to show higher affinity toward alginic acid from certain P. aeruginosa strains may suggest that there is a selective mechanism in the colonization of patients with cystic fibrosis.


Metals and Metalloids in Feathers of Neotropic Cormorants (Phalacrocorax brasilianus) Nesting in Lake Livingston and Richland Creek, Texas, USA.
Breast feathers of Neotropic Cormorants (Phalacrocorax brasilianus) from two nesting colonies in Lake Livingston (LALIV) and Richland Creek, Texas, were collected during 2014 and were analyzed for metals and metalloids. Mean concentrations of Al, As, Cr, Cu, Fe, Pb, Sb, and Se were not significantly different in breast feathers of cormorants from the two locations or between sexes. However, mean concentrations of Co, Mn, Ni, and V were significantly greater in feathers of cormorants from Richland Creek than in those from LALIV; and Zn concentrations were greater in cormorants from LALIV than in those from Richland Creek (p < 0.05). Overall, except for a few outliers for Pb, concentrations of heavy metals and metalloids in feathers were similar or lower than those reported in other species of cormorants from all over the world and were below levels of concern for lethal or sublethal effects on the species.


Harnessing Brightness in Naphthalene Diimides.
The development of brightly emissive compounds is of great research and commercial interest, with established and emerging applications across chemistry, biology, physics, medicine and engineering. Among the many types of molecules available, naphthalene diimides have been widely used for both fundamental photophysical studies and in practical applications that utilise fluorescence as an information readout. The monomeric naphthalene diimide is weakly fluorescent, however through various methods of core-derivatisation, it can be developed to be highly fluorescent and further functionalised to add utility. In this review, we highlight recent advances made in naphthalene diimide chemistry that have led to development of molecules with improved optical properties, and the design strategies utilised to produce bright fluorescence emission as small molecules or in supramolecular architectures.


Effect of loading rate and HRT on the removal of cephalosporin and their intermediates during the operation of a membrane bioreactor treating pharmaceutical wastewater.
The viability of treating high-concentration antibiotic wastewater by a membrane bioreactor (MBR) was studied using submerged flat sheet membrane. The major problems for these modules are concentration polarization and subsequent fouling. By using gas-liquid two-phase flow, these problems can be ameliorated. A case study has been identified and the current issues in one of the major pharmaceutical industry (manufacturing cephalosporin drugs) located in Chennai, India, has been discussed for the possible removal of anaerobically transformed intermediates of antibiotic pharmaceutical wastewater. The objective of the study was to determine the effect of organic loading rate and hydraulic retention time on the removal of cephalosporin derivative, viz., cephalexin (C(16)H(17)N(3)O(4)S.H(2)O) and the intermediates [7-amino-3-deacetoxycephalosporanic acid (7-ADCA) and acyl group (Phenyl acetic acid)] in the MBR with enhanced biodegradation using bioaugmentation technique. Based on the critical examination of results, the industry is looking for the alternatives of either direct disposal of 7-ADCA and phenyl acetic acid or for further degradation and disposal, which will essentially require additional cost and maintenance. The present regulatory standard implemented at a global level, (meaning the intermediates which are transformed during its course of travel within the industry and in the treatments plants, i.e., in the present study it is, 7-ADCA and phenyl acetic acid are not allowed to discharge on water bodies), does not envisage such disposal alternatives and hence the present study was aimed at the complete removal of intermediates (7-ADCA) and phenyl acetic acid prior to discharge.


Listening to paediatric primary care nurses: a qualitative study of the potential for interprofessional oral health practice in six federally qualified health centres in Massachusetts and Maryland.
To explore the opportunities for interprofessional collaboration (IPC) to improve paediatric oral health in federally qualified health centres (FQHCs), to identify challenges to IPC-led integration of oral health prevention into the well-child visit and to suggest strategies to overcome barriers. Nurse managers (NMs), nurse practitioners (NPs), paediatric clinical staff and administrators in six FQHCs in two states were interviewed using a semistructured format. Grounded theory research. Topics included feasibility of integration, perceived barriers and strategies for incorporating oral health into paediatric primary care. Qualitative data were coded and analysed using NVivo 10 to generate themes iteratively. Nurses in diverse roles recognised the importance of oral health prevention but were unaware of professional guidelines for incorporating oral health into paediatric encounters. They valued collaborative care, specifically internal communication, joint initiatives and training and partnering with dental schools or community dental practices. Barriers to IPC included inadequate training, few opportunities for cross-communication and absence of charting templates in electronic health records. NMs, NPs and paediatric nursing staff all value IPC to improve patients' oral health, yet are constrained by lack of oral health training and supportive charting and referral systems. With supports, they are willing to take on responsibility for introducing oral health preventive measures into the well-child visit, but will require IPC approaches to training and systems changes. IPC teams in the health centre setting can work together, if policy and administrative supports are in place, to provide oral health assessments, education, fluoride varnish application and dental referrals, decrease the prevalence of early childhood caries and increase access to a dental home for low-income children.


Leg regeneration in the cockroach, Blatella germanica. II. Regeneration from a non-congruent tibial graft/host junction.
The interactions occurring between host and graft leg epidermis at a non-congruent junction were studied in the cockroach, Blatella germanica. Graft and host tibia were cut perpendicular to the proximal-distal axis and two heteropleural combinations were used to reverse separately the two transverse axes of the graft relative to the host. Use of dark and light cuticle colour mutants gave a good indication of the graft or host origin of regenerated structures. Graft/host junctions regenerated segmented structures in various spatial arrangements, always comprising two copies of all structures distal to the level of the junction. It is concluded that the categories--two separate laterals, double lateral, completely and partially autonomous regeneration--reflect two processes. (i) If the graft tarsus is removed, graft and host may not heal together and interact, but form autonomous regenerates lying in mirror-image symmetry separating original graft and host levels. (ii) If interaction occurs between graft and host (or their developing autonomous regenerates) two laterals of dual origin are produced, one from each point of transverse axis incongruity. These laterals may secondarily fuse together to form a double structure originating from a point of congruity. The orientation and composition of the component tarsi of the double structure depend on the site of origin and the extent to which the two laterals fuse. It is argued that the four 'faces' and two 'transverse axes' of the leg are merely descriptive terms. A new model is developed whereby lateral regeneration arises directly from the circumferential organisation of the leg epidermis. Previous work has shown that position is specified continuously around the circumference, and that intercalary regeneration occurs by the shortest route between confronted positions. After reversal of one 'transverse axis' the shortest route between confronted graft and host positions is different on the two sides of each of the two points of 'axis' incongruity, and at these points the two halves of a complete circumference are formed. These lateral circumferences, like the terminal circumference exposed by amputation, cannot heal over by intercalary regeneration, and this leads to regeneration of distal structures. The model accounts for lateral regeneration after reversal of both 'transverse axes' by 180 degrees rotation of a homopleural graft. The possibility is discussed that there may be clonal restrictions on the circumferential positions which the progeny of a cell may occupy.


Clinical Implementation of a Free-Breathing, Motion-Robust Dynamic Contrast-Enhanced MRI Protocol to Evaluate Pleural Tumors.
OBJECTIVE. The purpose of this study was to develop a motion insensitive clinical dynamic contrast-enhanced MRI (DCE-MRI) protocol to assess the response of pleural tumors in clinical trials. MATERIALS AND METHODS. Thirty-two patients with pleura-based lesions were administered contrast material and imaged with gradient-recalled echo DCE-MRI sequence variants: either a traditional cartesian k-space acquisition (FLASH), a time-resolved imaging with stochastic trajectories acquisition (TWIST), or a radial stack-of-stars acquisition (radial) sequence in addition to other standard-of-care imaging sequences. Each image acquisition's sensitivity to motion was evaluated by comparing the motion of the thoracic border in 3D throughout the acquisition. One-way ANOVA was used to compare the image quality between different acquisitions. The 95% CIs were calculated for mean thoracic border displacement. The effects of motion on kinetic parameter estimation were explored with simulations according to clinically acquired data. RESULTS. Radial was the most motion-robust sequence with subvoxel mean displacement in the superior-inferior direction (0.4 ± 1.2 [SD] mm). FLASH showed intermediate displacement (4.6 ± 2.0 mm), whereas TWIST was most sensitive to motion (6.4 ± 3.4 mm). Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the images acquired with the radial sequence were on par or better than the FLASH and TWIST sequences when reconstructed with an improved density compensation algorithm. Simulations showed that motion on scans showing pleural-based lesions can lead to markedly inaccurate kinetic parameter estimation and inappropriate kinetic model convergence within a nested model analysis. CONCLUSION. A practical radial k-space trajectory sequence that provides motion-insensitive pharmacokinetic parameters was incorporated as part of the DCE-MRI protocol of pleural tumors. Validation and usefulness in clinical trials assessing response to therapy is needed.


Chlamydial ocular infection: efficacy of partner notification by patient referral.
Records on 254 patients with chlamydial ocular infection observed over a period of 67 months at the Moorfield's Eye Hospital were reviewed retrospectively in relation to sexual partners in the 6 months prior to diagnosis. Contactable partners were given an appointment through index patients to attend our clinic. Those unable to attend were issued contact slips, as used by the sexually transmitted disease (STD) clinics in the United Kingdom, to attend elsewhere: 175/328 (53%) of all partners were seen in our clinic: 161/218 (74%) of current regular partners compared to only 7/57 (12%) of ex-regular and 7/53 (13%) of casual partners. However, of those given appointments 175/201 (87%) attended: 161/179 (90%) of current regular, 7/14 (50%) of ex-regular and 7/8 (88%) of casual partners. Seventy of 328 (21%) of all partners were issued contact slips, of whom 47/70 (67%) were reported to have attended elsewhere. No contact slips were returned by other clinics, indicating a failure in the contact slip system. Thirty-five of 53 (66%) of casual, 22/57 (39%) of ex-regular and none of the current regular partners were untraceable. One hundred and five of 196 (54%) female partners were examined, of whom 59/105 (56%) had chlamydial genital infection, 45/105 (43%) had other genital infections and 35/105 (33%) had multiple genital infections. Seventy of 132 (53%) male partners were examined, of whom 58/70 (83%) had chlamydial or non-specific urethritis, 5/70 (7%) had other genital infections and 4/70 (6%) had multiple genital infections. Partner notification is important to interrupt chlamydia transmission.(ABSTRACT TRUNCATED AT 250 WORDS)


COVID-19 aerosol transmission modeling in support of company HVAC guideline.
A company COVID-19 Heating, Ventilation, and Air Conditioning Guideline was implemented globally, as part of a larger control measure toolset, to minimize the potential for SARS-CoV-2 aerosol transmission. The COVID-19 Heating, Ventilation, and Air Conditioning Guideline informed and provided the process to optimize existing ventilation systems, set occupancy duration limits, and set clearance periods for a given space. Aerosol transmission modeling was used extensively to determine space limitations to reduce the potential for aerosol transmission in various manufacturing, lab, warehouse, aircraft, and administrative workspaces. This paper focuses on the modeling completed for administrative spaces (e.g., offices, conference rooms, restrooms, elevators) due to their lower ventilation rates, higher occupant densities, and greater vocalization levels. A detailed description of how the Guideline was implemented, with examples showing the evaluation and determinations made for specific spaces, is provided. World-wide implementation of this Guideline, as one of the layers of protection, was a key component in the overall strategy to reduce aerosol transmission of the SARS-CoV-2 virus.


Preparation of highly purified C-phycoerythrin from marine cyanobacterium Pseudanabaena sp.
C-phycoerythrin was isolated and purified from marine Pseudanabaena sp. using two step chromatographic methods. Phycobiliproteins in the marine Pseudanabaena was extracted in 100 mM phosphate buffer (pH 7.2) and precipitated by salting out. The precipitated C-phycoerythrin was purified by gel filtration with Sephadex G-150, and then it was purified by ion exchange chromatography on DEAE cellulose, which was developed by linear ionic strength gradients. Purified phycoerythrin showed absorption maxima at 568 and 541 nm, and displayed a fluorescence maximum at 578 nm. The absorbance ratio A₅₆₈/A₂₈₀, a criterion for purity (purity ratio) achieved was 6.86. It showed a single band on examination by polyacrylamide gel electrophoresis (PAGE). The polypeptide analysis of the purified C-phycoerythrin by SDS-PAGE demonstrated that it contained two chromophore-carrying subunits. The yield of purified C-phycoerythrin obtained was 13.6 mg/g of the cell dry weight with 47% of yield. Obtaining highly pure C-phycoerythrin allows one to evaluate its fluorescence properties for future applications in biochemical and biomedical research.


Synthesis, Photophysics, and Self-Assembly of Furan-Embedded Heteroarenes.
A series of pyrene/phenanthrene-fused furan derivatives (1-8) were synthesized by a simple condensation reaction between pyrene-4,5-diketone/phenanthrenequinone and substituted phenol/naphthol in the presence of trifluoromethanesulfonic acid in 1,2-dichlorobenzene heated at reflux. The formed compounds can emit strong blue light in organic solvents. Additionally, the self-assembly behaviors of two of the compounds (3 and 5) were studied through re-precipitation method and the resulting nanostructures were characterized by UV/Vis, fluorescence spectra, and field-emission scanning electron microscopy (FESEM). The findings showed that the shape and size of compounds 3 and 5 could be tuned by the ratio of THF and hexadecyl trimethyl ammonium bromide (CTAB) solution in water.


Prevalence of vasospastic ischaemia induced by the cold pressor test or hyperventilation in patients with severe angina.
We performed coronary artery spasm provocation, using the cold pressor test (CPT) and hyperventilation (HVT) in 105 patients (87 males, 18 females) with mean age 51.9 years (range 25-69) consecutively admitted for coronary angiography due to attacks of chest pain. A positive response to spasm provocation (ST segment elevation or depression greater than or equal to 0.1 mV or pseudonormalization of negative T-waves) was seen in 25 patients (23.9%) (group A), with 8 patients responding to CPT and 23 to HVT. In the remaining patients (group B) a negative response was found. Of 80 patients with coronary artery stenosis (diameter reduction greater than 50%), 22 (27.5%) showed a positive response. During CPT and HVT the rate pressure product increased 25% and 16%, respectively in group A versus an increase of 139% during exercise testing in the same patients. This suggests that ischaemia induced by CPT or HVT is not caused by increased myocardial oxygen demand. Repeat spasm provocation was performed during coronary angiography in 14 patients from group A and 14 from group B. The induced reduction in the diameters of the ischaemia related vessels was on average 48.3% in group A versus a 9.9% reduction of the left anterior descending artery in the patients from group B (P less than 0.01). In group A 88% had a history of nocturnal angina versus 38.8% in group B (P less than 0.001). A positive exercise test was found in 87% and 35.6% in group's A and B respectively (P less than 0.0005).


Causal conclusions are most sensitive to unobserved binary covariates.
There is a rich literature that considers whether an observed relation between treatment and response is due to an unobserved covariate. In order to quantify this unmeasured bias, an assumption is made about the distribution of this unobserved covariate; typically that it is either binary or at least confined to the unit interval. In this paper, this assumption is relaxed in the context of matched pairs with binary treatment and response. One might think that a long-tailed unobserved covariate could do more damage. Remarkably that is not the case: the most harm is done by a binary covariate, so the case commonly considered in the literature is most conservative. This has two practical consequences: (i) it is always safe to assume that an unobserved covariate is binary, if one is content to make a conservative statement; (ii) when another assumption seems more appropriate, say normal covariate, there will be less sensitivity than with a binary covariate. This assumption implies that it is possible that a relation between treatment and response that is sensitive to unmeasured bias (if the unobserved covariate is dichotomous), ceases to be sensitive if the unobserved covariate is normally distributed. These ideas are illustrated by three examples. It is important to note that the claim in this paper applies to our specific setting of matched pairs with binary treatment and response. Whether the same conclusion holds in other settings is an open question.


Lisfranc joint injuries: diagnosis and treatment.
Injuries to the tarsometatarsal or Lisfranc joint, though rare, are often undiagnosed or inadequately treated, resulting in poor long-term outcomes. Clinical and radiographic data are needed to recognize and treat these injuries for optimal outcomes. In this article, we review the anatomy, biomechanics, injury mechanisms, clinical presentation, radiographic evaluation, injury classification, treatment, outcome, and complications of Lisfranc joint injuries.


Centenary of Insulin Discovery (1921-2021): Nicolae Paulescu's Original Contributions.
Nicolae Paulescu (1869-1930) was born in Bucharest in an aristocratic family. His education from childhood to maturity (Paris University of Medicine) was marked by illustrious professors, even pioneers of their field. After completing his medical and scientific education in Paris under his mentor, Etienne Lancereaux, considered the founder of modern physiology, he returned to Romania where he founded the first Department of Physiology at "Carol Davila" University of Medicine and Pharmacy. His scientific career is marked by the publishing of 88 original research articles in renown international medical journals of the time and two Treatise on Physiology (comprising in total 8 volumes and 5976 pages). His activity as an endocrinologist reaches the peak with the discovery of insulin with the article Recherche sur le rôle du pancréas dans l'assimilation nutritive published in the Archives Internationales de Physiologie (Liege, Belgium) on August 31st, 1921. While he was not internationally or even nationally acclaimed for the discovery of insulin, his contribution to the reformation of the national education and medical system and the recommendation of his students to pioneers of their fields of interest still have reverberations even today.


Urothelial Tight Junction Barrier Dysfunction Sensitizes Bladder Afferents.
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic voiding disorder that presents with pain in the urinary bladder and surrounding pelvic region. A growing body of evidence suggests that an increase in the permeability of the urothelium, the epithelial barrier that lines the interior of the bladder, contributes to the symptoms of IC/BPS. To examine the consequence of increased urothelial permeability on pelvic pain and afferent excitability, we overexpressed in the urothelium claudin 2 (Cldn2), a tight junction (TJ)-associated protein whose message is significantly upregulated in biopsies of IC/BPS patients. Consistent with the presence of bladder-derived pain, rats overexpressing Cldn2 showed hypersensitivity to von Frey filaments applied to the pelvic region. Overexpression of Cldn2 increased the expression of c-Fos and promoted the activation of ERK1/2 in spinal cord segments receiving bladder input, which we conceive is the result of noxious stimulation of afferent pathways. To determine whether the mechanical allodynia observed in rats with reduced urothelial barrier function results from altered afferent activity, we examined the firing of acutely isolated bladder sensory neurons. In patch-clamp recordings, about 30% of the bladder sensory neurons from rats transduced with Cldn2, but not controls transduced with GFP, displayed spontaneous activity. Furthermore, bladder sensory neurons with tetrodotoxin-sensitive (TTX-S) action potentials from rats transduced with Cldn2 showed hyperexcitability in response to suprathreshold electrical stimulation. These findings suggest that as a result of a leaky urothelium, the diffusion of urinary solutes through the urothelial barrier sensitizes bladders afferents, promoting voiding at low filling volumes and pain.


Prevalence of delirium among outpatients with dementia.
Delirium and dementia are highly interrelated. However, few comprehensive epidemiological studies have examined this altered state of consciousness superimposed on dementia. We investigated the frequency of delirium in patients with dementia, its prevalence in patients with each dementia type, and its association with cerebrovascular disease (CVD) in patients with neurodegenerative dementias. We studied 261 consecutive outpatients in the memory clinic of a psychiatric hospital between April 2010 and September 2011. All patients underwent routine laboratory tests and computed tomography (CT), and their Mini-Mental State Examination, Neuropsychiatric Inventory (NPI), Physical Self-Maintenance Scale (PSMS), and Delirium Rating Scale - Revised 98 scores were recorded. The diagnosis of delirium was based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision. CVD was detected by CT. Among the 206 patients with dementia, delirium was present in 40 (19.4%). The proportion of patients who experienced episodes of delirium was 14.7% in the Alzheimer's disease, 34.4% in the vascular dementia, 31.8% in the dementia with Lewy bodies, and none in frontotemporal lobar degeneration. Delirium was frequently observed in patients with dementia and CVD. The NPI total and agitation subscale scores were significantly higher in dementia patients with delirium than in those without delirium. PSMS scores were significantly lower for patients with delirium than for patients without delirium. The frequency of delirium varies with each dementia type. In addition, delirium decreases activities of daily living, exaggerates behavioral and psychological symptoms dementia, and is associated with CVD in patients with neurodegenerative dementias.


[The missed care in Nursing Homes: a pilot study].
. The missed care in Nursing Homes: a pilot study. To date missed care have been described mostly in hospitals and data on nursing homes (NH) are missing. To describe missed care in NH residents identifying their perceived impact and seriousness. A pilot study was conducted in 10 Piedmont NHs. For each omitted or delayed care on 20 residents observed for 3 consecutive days, the nurses provided information on the type of care, and information on the residents and on the organization were collected. Twenty-three nurses reported 57 missed care for 44/200 residents (22%; median 5 for each NH, range 0-13). Twenty-five missed/omitted care on 20 residents were considered of medium/high severity: 14 (56%) involved drug therapies and 5 (20%) the monitoring of vital signs. The level of severity derived from the distress caused to the resident, the risk of deterioration of residents'conditions and the repeated omissions on the same resident. Of the 32 missed care on 25 residents, judged of limited impact, the more frequent were dressing changes (12, 37.5%), and drugs administration (10, 31.3%). The most frequent reasons for delay/omission were unplanned events (16, 28.1%), shortage of nurses (12, 21.1%), and residents' clinical conditions (9, 15.7%). Missed care occur also in NHs. If staff shortage play a key role among potentially modifiable factors, a sizeable number of omission is associated to unlikely forseeable or avoidable events.


Uncertainty of Standardized Track Insulation Measurement Methods for Stray Current Assessment.
Stray current is a relevant phenomenon in particular for DC electrified transportation systems, affecting track and infrastructure within the right of way and other structures and installations nearby. It worsens with time and the level of protection depends on timely maintenance, as well as correct design choices. The assessment of track insulation is the starting point for both stray current monitoring systems and at commissioning or upon major changes. Standardized methods (ref. EN 50122-2 or IEC 62128-2) have been almost unchanged in the last 20 years but suffer from accuracy issues and variability due to parameters and conditions not under the operator's control. The uncertainty of test methods is increasingly important now that contractual specifications require a high level of insulation for new systems. A critical discussion and analysis of the sources of variability and practical constraints is proposed, followed by an evaluation of uncertainty, with the objective not only to assess the accuracy of the provided results, but also to foster research on innovative, more flexible and accurate methods.


Lipoprotein lipase increases lipoprotein binding to the artery wall and increases endothelial layer permeability by formation of lipolysis products.
Mechanisms responsible for the accumulation of low-density lipoprotein (LDL) were investigated in a new model, the perfused hamster aorta. To do this, we developed a method to study LDL flux in real time in individually perfused arteries; each artery served as its own control. Using quantitative fluorescence microscopy, the rates of LDL accumulation and efflux were separately determined. Perfusion of arteries with buffer plus lipoprotein lipase (LpL) increased LDL accumulation 5-fold (0.1 +/- 0.03 mV/min [control] versus 0.5 +/- 0.05 mV/min [LpL]) by increasing LDL retention in the artery wall. This effect was blocked by heparin and monoclonal antibodies directed against the amino-terminal region of apolipoprotein B (apo B). This suggests that specific regions of apo B are involved in LDL accumulation within arteries. Also, the effect of hydrolysis of triglyceride-rich lipoproteins on endothelial barrier function was studied. We compared endothelial layer permeability using a water-soluble reference molecule, fluorescently labeled dextran. When LpL was added to hypertriglyceridemic plasma, dextran accumulation within the artery wall increased > 4-fold (0.024 +/- 0.01 mV/min [control] versus 0.098 +/- 0.05 mV/min [LpL]). Under the same conditions, LpL increased LDL accumulation approximately 3-fold (0.016 +/- 0.003 mV/min [control] versus 0.047 +/- 0.013 mV/min [LpL]). Rapid efflux of LDL from the artery wall indicated that increased endothelial layer permeability was the primary mechanism during periods of increased lipolysis. Our data demonstrate two LpL-mediated effects that may increase the amount of LDL in the artery wall. These findings may pertain to the observed relationship between increased postprandial lipemia and atherosclerosis.


Animal experiments on an absorbable synthetic thread made of polyglycolic acid (PGA) in corneal surgery.
Monofilaments of the absorbable synthetic thread Dexon made from PGA have properties similar to nylon 10-0. Experiments with intra-lamellar implantation of the monofilament in rabbit corneas showed the same good material tolerance as nylon 10-0. Perforating corneal wounds were closed with interrupted and running sutures from PGA monofilaments, respectively. One week post-operatively, increased intraocular pressure caused a wound rupture but not a thread rupture. Two weeks post-operatively an increased intraocular pressure of more than 300 mm Hg could no longer rupture the wound. Slit lamp and histological examinations revealed symptoms of absorption after the second week. According to our findings, PGA monofilaments may be suitable for corneal surgery in patients.


Suppression of Lamb wave excitation via aperture control of a transducer array for ultrasonic clamp-on flow metering.
During ultrasonic clamp-on flow metering, Lamb waves propagating in the pipe wall may limit the measurement accuracy by introducing absolute errors in the flow estimates. Upon reception, these waves can interfere with the up and downstream waves refracting from the liquid, and disturb the measurement of the transit time difference that is used to obtain the flow speed. Thus, suppression of the generation of Lamb waves might directly increase the accuracy of a clamp-on flow meter. Existing techniques apply to flow meters with single element transducers. This paper considers the application of transducer arrays and presents a method to achieve a predefined amount of suppression of these spurious Lamb waves based on appropriate amplitude weightings of the transducer elements. Finite element simulations of an ultrasonic clamp-on flow measurement setting will be presented to show the effect of array aperture control on the suppression of the Lamb waves in a 1-mm-thick stainless steel pipe wall. Furthermore, a proof-of-principle experiment will be shown that demonstrates a good agreement with the simulations.


Nausea and vomiting in pregnancy.
Prospective data on 86 pregnant women were analysed to investigate the relationship between the pregnancy symptoms of nausea and vomiting and various demographic, social and psychological factors. In contrast to previous research findings no significant differences were discovered along demographic or social dimensions between women reporting no nausea, mild nausea and severe nausea during the first trimester of pregnancy. Not surprisingly, those women experiencing severe nausea reported significantly more sleep disturbances, fatigue and irritability. Women having both nausea and vomiting during the first trimester, reported significantly more unplanned, undesired pregnancies and negative relationships with their own mothers, than first trimester groups experiencing nausea only or no symptoms. Finally, those with continuing nausea and vomiting in the third trimester, when compared with those having no symptoms, tended to have reported significantly more psychological/psychiatric problems in the first trimester and were significantly more negative in their assessment of their own maternal relationship.


[Bronchospasm during extracorporeal circulation].
Six cases of bronchospasm are reported, which occurred at the end of cardiopulmonary bypass (CPB). One patient developed this condition twice within one year. This was a rare occurrence (6 cases for 3714 CPB). Symptoms were the same every time: increased inflation pressures, impossible deflation, and low left atrial pressures. Adrenaline given by way of the bypass was the quickest and most effective treatment. The favourable outcome in all 5 patients was due to the continuing of circulatory assistance by the CPB. Although the prevention of anaphylactoid accidents in atopic patients has been well documented, the cause of the bronchospasm in our patients has not been recognized, and it may well not have been due to a particular drug.


Higher plasma homocysteine is associated with increased risk of developing colorectal polyps.
Colorectal adenomas are considered to be precursors of colorectal cancer. B-vitamins (i.e., folate, vitamin B(6) and B(12)) are involved in homocysteine metabolism and play an important role as coenzymes in 1-carbon metabolism, which is thought to have a critical role in the progression of colorectal polyps. The purpose of this study was to examine the effects of B-vitamins and homocysteine on the risk of developing colorectal polyps. Forty-eight participants with colorectal polyps [29 adenomatous polyps (AP), 19 hyperplastic polyps (HP)], and 96 age- and sex-matched healthy controls were recruited. Fasting blood was drawn from each participant to measure hematological parameters, plasma pyridoxal 5'-phosphate (PLP), serum folate and vitamin B(12), and plasma homocysteine. Participants with AP and HP had significantly higher plasma homocysteine levels than did healthy controls. There was no significant difference in serum folate and vitamin B(12) and plasma PLP among the 3 groups. B-vitamins had no significant effect on the risk of colorectal polyps. However, participants with higher plasma homocysteine [odds ratio (OR) = 1.87, 95% confidence interval (CI) = 1.13, 3.08) level exhibited significantly increased risk of colorectal polyps after adjusting for potential confounders. Plasma homocysteine was a strong predictor of the risk of colorectal polyps in participants with adequate B-vitamins status.


Cloning and nucleotide sequence analysis of a Brucella abortus gene encoding an 18 kDa immunoreactive protein.
A DNA fragment encoding an approximately 18 kDa protein from Brucella abortus strain 2308 was cloned and expressed in Escherichia coli. This recombinant protein, designated BA18K, reacted in Western blot analysis with sera obtained from experimentally and naturally infected animals including mice, goats, dogs and humans. Restriction enzyme analysis of the plasmid (pBA28) encoding BA18K revealed the presence of an approximately 8.7 kbp Sau3A genomic DNA fragment within the vector and subsequent subcloning and Western blot analysis limited the region encoding BA18K to an approximately 3.0 kbp Pst 1 DNA fragment. DNA sequence analysis of this region identified an open reading frame capable of encoding a protein of 177 amino acids with a predicted relative molecular mass of 17529. Comparison of the deduced amino acid sequence of BA18K with those in the protein sequence databases yielded no homology with previously described proteins from other bacterial genera. These searches did, however, indicate that BA18K is identical to the previously described outer membrane protein (OMP) from B. abortus strain 544 designated Omp 19.


Genome-Wide Association Mapping of Crown Rust Resistance in Oat Elite Germplasm.
Oat crown rust, caused by f. sp. , is a major constraint to oat ( L.) production in many parts of the world. In this first comprehensive multienvironment genome-wide association map of oat crown rust, we used 2972 single-nucleotide polymorphisms (SNPs) genotyped on 631 oat lines for association mapping of quantitative trait loci (QTL). Seedling reaction to crown rust in these lines was assessed as infection type (IT) with each of 10 crown rust isolates. Adult plant reaction was assessed in the field in a total of 10 location-years as percentage severity (SV) and as infection reaction (IR) in a 0-to-1 scale. Overall, 29 SNPs on 12 linkage groups were predictive of crown rust reaction in at least one experiment at a genome-wide level of statistical significance. The QTL identified here include those in regions previously shown to be linked with seedling resistance genes , , , , , and and also with adult-plant resistance and adaptation-related QTL. In addition, QTL on linkage groups Mrg03, Mrg08, and Mrg23 were identified in regions not previously associated with crown rust resistance. Evaluation of marker genotypes in a set of crown rust differential lines supported as the identity of . The SNPs with rare alleles associated with lower disease scores may be suitable for use in marker-assisted selection of oat lines for crown rust resistance.


DMG-α--a computational geometry library for multimolecular systems.
The DMG-α library grants researchers in the field of computational biology, chemistry, and biophysics access to an open-sourced, easy to use, and intuitive software for performing fine-grained geometric analysis of molecular systems. The library is capable of computing power diagrams (weighted Voronoi diagrams) in three dimensions with 3D periodic boundary conditions, computing approximate projective 2D Voronoi diagrams on arbitrarily defined surfaces, performing shape properties recognition using α-shape theory and can do exact Solvent Accessible Surface Area (SASA) computation. The software is written mainly as a template-based C++ library for greater performance, but a rich Python interface (pydmga) is provided as a convenient way to manipulate the DMG-α routines. To illustrate possible applications of the DMG-α library, we present results of sample analyses which allowed to determine nontrivial geometric properties of two Escherichia coli-specific lipids as emerging from molecular dynamics simulations of relevant model bilayers.


Influence of crystal structure and oxygen vacancies on optical properties of nanostructured multi-stoichiometric tungsten suboxides.
Four distinct tungsten suboxide (WO3-x) nanomaterials were synthesized via chemical vapour transport reaction and the role of their crystal structures on the optical properties was studied. These materials grow either as thin, quasi-2D crystals with the WnO3n-1formula (in shape of platelets or nanotiles), or as nanowires (W5O14, W18O49). For the quasi-2D materials, the appearance of defect states gives rise to two indirect absorption edges. One is assigned to the regular bandgap occurring between the valence and the conduction band, while the second is a defect-induced band. While the bandgap values of platelets and nanotiles are in the upper range of the reported values for the suboxides, the nanowires' bandgaps are lower due to the higher number of free charge carriers. Both types of nanowires sustain localized surface plasmon resonances, as evidenced from the extinction measurements, whereas the quasi-2D materials exhibit excitonic transitions. All four materials have photoluminescence emission peaks in the UV region. The interplay of the crystal structure, oxygen vacancies and shape can result in changes in optical behaviour, and the understanding of these effects could enable intentional tuning of selected properties.


Study of cryptosporidiosis in a rural area of Maharashtra.
Human cryptosporidiosis has been reported world wide, both from developed and developing countries and from urban and rural areas. Present study is undertaken to assess the occurrence of cryptosporidiosis in human and cattle population (cows and calves) in and around the rural areas of Loni, district Ahmednagar, Maharashtra State. Human stool samples were collected from 220 patients of age ranging between newborn to 85 years, attending the Pravara Rural Hospital, Loni. The samples were examined using modified Ziehl-Neelsen staining technique. Drug samples were also examined from 101 asymptomatic (apparently healthy and non-diarrhoeic) cows and calves from the same area, to detect Cryptosporidium. Three positive cases (1.36%) in human and 11 positive cases (10.89%) in cattle (cows and calves) were detected. It is assumed that in rural areas the most likely source of human infection is cattle. This is the first report of human infection by Cryptosporidium from rural Maharashtra and also the first report of occurrence in cattle from India.


Clerodane diterpenoids from Salvia splendens.
Four new clerodane diterpenoids, salvisplendins A-D (1-4), have been isolated from an acetone extract of the flowers of Salvia splendens, together with an artifact (5), arising from salvisplendin D (4) by addition of diazomethane, and the already known clerodane olearin (6). The structures of the new compounds (1-5) were established mainly by 1D and 2D NMR spectroscopic studies and, in the case of salvisplendin A (1), by chemical correlation with splenolide B (7). Complete 1H and 13C NMR assignments for olearin (6), not published hitherto, are also reported.


[Influence of Precipitation Change on Soil Respiration in Desert Grassland].
Global climate change has significantly changed precipitation patterns. Soil respiration (SR), as an important pathway through which CO2 is released from the soil carbon pool into the atmosphere, may affect the carbon cycle process of terrestrial ecosystems and have a feedback effect on global climate change in response to precipitation change. However, at present there is limited understanding of how SR is affected by precipitation change. Field precipitation control experiments were conducted (with -40%, -20%, natural, 20%, and 40% precipitation) on desert grassland in the west of the Loess Plateau, to investigate the influence of precipitation change on SR dynamics and its relationship with soil water content, soil temperature, aboveground biomass, soil organic carbon, microbial biomass carbon, carbon-nitrogen ratio, and other factors. The results show that the diurnal variations of SR under different precipitation treatments were consistent in unimodal and bimodal models over three years. SR showed an increasing trend with added precipitation, relative to the control, and significant differences were observed between the second year (wetter) and the third year (drier) of the precipitation-manipulation experiment, indicating that precipitation changes had a legacy effect on SR. At the same time, SR was lowest under the -40% treatment and highest under the 40% treatment during the wetter year. The negative response of SR to precipitation exclusion treatments was stronger than the positive response to precipitation addition treatments. SR in drier years was significantly higher under precipitation addition treatments than the control, and the positive response of SR to increased precipitation treatment was significantly stronger than that under decreased precipitation treatment. In addition, soil water content, aboveground biomass, soil organic carbon, and carbon-nitrogen ratio were the environmental factors that obviously affected SR and increased with additional precipitation. SR increased with increases in soil water content, aboveground biomass, soil organic carbon, and carbon-nitrogen ratio, but decreased with increases in microbial biomass carbon. Among these factors, soil water content had the highest interpretation rate for SR, indicating that soil water content was the main environmental factor controlling SR in desert grassland. In both wetter and drier years, the amplitude of plant biomass input was lower than the amplitude of SR output under precipitation change, indicating that precipitation change may be unfavorable to soil carbon sequestration, especially in drier years, when precipitation change has a stronger influence on carbon pool output. Therefore, precipitation changes on SR in desert grassland in various dry and wet years may have different influences on the carbon cycle process of ecosystems, thus providing a reference for regional carbon budget assessment.


Effectiveness of Large-Scale Chagas Disease Vector Control Program in Nicaragua by Residual Insecticide Spraying Against Triatoma dimidiata.
Chagas disease is one of the most serious health problems in Latin America. Because the disease is transmitted mainly by triatomine vectors, a three-phase vector control strategy was used to reduce its vector-borne transmission. In Nicaragua, we implemented an indoor insecticide spraying program in five northern departments to reduce house infestation by Triatoma dimidiata. The spraying program was performed in two rounds. After each round, we conducted entomological evaluation to compare the vector infestation level before and after spraying. A total of 66,200 and 44,683 houses were sprayed in the first and second spraying rounds, respectively. The entomological evaluation showed that the proportion of houses infested by T. dimidiata was reduced from 17.0% to 3.0% after the first spraying, which was statistically significant (P < 0.0001). However, the second spraying round did not demonstrate clear effectiveness. Space-time analysis revealed that reinfestation of T. dimidiata is more likely to occur in clusters where the pre-spray infestation level is high. Here we discuss how large-scale insecticide spraying is neither effective nor affordable when T. dimidiata is widely distributed at low infestation levels. Further challenges involve research on T. dimidiata reinfestation, diversification of vector control strategies, and implementation of sustainable vector surveillance.


Radiation doses to local populations near nuclear weapons test sites worldwide.
Nuclear weapons testing was conducted in the atmosphere at numerous sites worldwide between 1946 and 1980, which resulted in exposures to local populations as a consequence of fallout of radioactive debris. The nuclear tests were conducted by five nations (United States, Soviet Union, United Kingdom, France, and China) primarily at 16 sites. The 16 testing sites, located in nine different countries on five continents (plus Oceania) contributed nearly all of the radioactive materials released to the environment by atmospheric testing; only small amounts were released at a fewother minor testing sites. The 16 sites discussed here are Nevada Test Site, USA (North American continent), Bikini and Enewetak, Marshall Islands (Oceania); Johnston Island, USA (Oceania), Christmas and Malden Island, Kiribati (Oceania); Emu Field, Maralinga, and Monte Bello Islands, Australia (Australian continent); Mururoa and Fangataufa, French Polynesia (Oceania), Reggane, Algeria (Africa), Novaya Zemlya and Kapustin Yar, Russia (Europe), Semipalatinsk, Kazakhstan (Asia), and Lop Nor, China (Asia). There were large differences in the numbers of tests conducted at each location and in the total explosive yields. Those factors, as well as differences in population density, lifestyle, environment, and climate at each site, led to large differences in the doses received by local populations. In general, the tests conducted earliest led to the highest individual and population exposures, although the amount of information available for a few of these sites is insufficient to provide any detailed evaluation of radiation exposures. The most comprehensive information for any site is for the Nevada Test Site. The disparities in available information add difficulty to determining the radiation exposures of local populations at each site. It is the goal of this paper to summarize the available information on external and internal doses received by the public living in the regions near each of the mentioned nuclear test sites as a consequence of local fallout deposition.


The natural history of the multicystic dysplastic kidney in children.
The objective of this study was to examine the natural history of the multicystic dysplastic kidney and the use of sonography for follow-up studies. A retrospective study was performed on 66 children with a radiological diagnosis of multicystic kidney. The change in size demonstrated on sonograms was examined. Adequate follow-up was available on 55 children over a period of 32 months (range 2-69 months). 40/55 of the kidneys underwent a reduction in size, including 22 which were no longer detectable by ultrasound. 10/55 kidneys showed an increase in size and 5/55 showed no change. Reduction in size occurred at a mean age of 84 weeks (range 20-120 weeks). In conclusion, most multicystic kidneys undergo partial or complete involution over the first 2 years of life. The mean size of the multicystic kidney at diagnosis is a poor predictor of eventual outcome.


Protein kinase CK2α catalytic subunit is overexpressed and serves as an unfavorable prognostic marker in primary hepatocellular carcinoma.
Protein kinase CK2 alpha (CK2α), one isoform of the catalytic subunit of serine/threonine kinase CK2, has been indicated to participate in tumorigenesis of various malignancies. We conducted this study to investigate the biological significances of CK2α expression in hepatocellular carcinoma (HCC) development. Real-time quantitative polymerase and western blotting analyses revealed that CK2α expression was significantly increased at mRNA and protein levels in HCC tissues. Immunohistochemical analyses indicated that amplified expression of CK2α was highly correlated with poor prognosis. And functional analyses (cell proliferation and colony formation assays, cell migration and invasion assays, cell cycle and apoptosis assays) found that CK2α promoted cell proliferation, colony formation, migration and invasion, as well as inhibited apoptosis in hepatoma cell lines in vitro. CK2α-silenced resulted in significant apoptosis in cells that was demonstrated been associated with downregulation of expression of Bcl-2, p-AKT (ser473) and upregulation of expression of total P53, p-P53, Bax, caspase3 and cleaved-caspase3 in HCC cells. In addition, experiments with a mouse model revealed that the stimulative effect of CK2α on tumorigenesis in nude mice. Our results suggest that CK2α might play an oncogenic role in HCC, and therefore it could serve as a biomarker for prognostic and therapeutic applications in HCC.


LncRNA TP53TG1 plays an anti-oncogenic role in cervical cancer by synthetically regulating transcriptome profile in HeLa cells.
Long non-coding RNAs (lncRNAs) have been extensively studied as important regulators of tumor development in various cancers. Tumor protein 53 target gene 1 (TP53TG1) is a newly identified lncRNA in recent years, and several studies have shown that TP53TG1 may play oncogenic or anti-oncogenic roles in different cancers. Nevertheless, the role of TP53TG1 in the development of cervical cancer is unclear. In our study, pan-cancer analysis showed that high expression of TP53TG1 was significantly associated with a better prognosis. We then constructed a TP53TG1 overexpression model in HeLa cell line to explore its functions and molecular targets. We found that TP53TG1 overexpression significantly inhibited cell proliferation and induced apoptosis, demonstrating that TP53TG1 may be a novel anti-oncogenic factor in cervical cancer. Furthermore, overexpression of TP53TG1 could activate type I interferon signaling pathways and inhibit the expression of genes involved in DNA damage responses. Meanwhile, TP53TG1 could affect alternative splicing of genes involved in cell proliferation or apoptosis by regulating the expression of many RNA-binding protein genes. Competing endogenous RNA (ceRNA) network analysis demonstrated that TP53TG1 could act as the sponge of several miRNAs to regulate the expression level of target genes. In conclusion, our study highlights the essential role of lncRNA TP53TG1 in the development of cervical cancer and suggests the potential regulatory mechanisms.


Drug-induced liver injury: the role of drug metabolism and transport.
Many studies have pinpointed the significant contribution of liver-mediated drug metabolism and transport to the complexity of drug-induced liver injury (DILI). Phase I cytochrome P450 (CYP450) enzymes can lead to altered drug metabolism and formation of toxic metabolites, whilst Phase II enzymes are also associated with DILI. The emerging role of hepatic transporters in regulating the movement of endogenous and exogenous chemicals (e.g., bile acids and drugs) across cellular and tissue membranes is critical in determining the pathophysiology of liver disease as well as drug toxicity and efficacy. Genetic and environmental factors can have a significant impact on drug metabolism and transporter proteins, consequently increasing the risk of DILI in susceptible individuals. The assessment of these factors therefore represents an important approach for predicting and preventing DILI, by better understanding the pharmacological profile of a specific drug. This review focuses on the mechanisms of DILI associated with drug metabolism and hepatic transport, and how they can be influenced by underlying factors.


Childless Canadian men's and women's childbearing intentions, attitudes towards and willingness to use assisted human reproduction.
What are the childbearing intentions of currently childless men and women? What is their attitude towards, and willingness to use, assisted human reproduction (AHR) treatments and family-building options should they be faced with fertility challenges in the future? Men and women expect to become parents significantly later in life than they believe is ideal. If faced with future fertility challenges, respondents were open to using IVF, but were not positively predisposed to third-party family-building options. Delayed childbearing is an increasing worldwide phenomenon that has considerable health and fertility-related implications. Research to date has focused primarily on women, and indicates a lack of knowledge about the fertility life span and the limitations of AHR in fully compensating for age-related fertility declines. Cross-sectional study of 2000 childless women and 599 childless men, conducted between April 2010 and May 2011. A total of 2599 childless, presumed fertile individuals between the ages of 20 and 50 years. An online questionnaire assessed fertility beliefs and intentions and willingness to use AHR. The findings indicate that men and women expect to become parents significantly later in life than they believe is ideal. If faced with fertility challenges in the future, both men and women were open to using IVF. Men were significantly more willing to consider using donated eggs and embryos, gestational surrogacy and fertility preservation. Women were significantly more willing to consider using home fertility testing, IVF, ICSI and donor sperm. Overall, the childless respondents were not positively predisposed to third party-family-building options. The geographic specificity of the sample, the online format and recruitment methods may limit the generalizability of these findings. Given the worldwide trend towards delayed childbearing, and the widespread availability of AHR, it is likely that these findings could extend to the wider North American, European and Australasia populations of English- and French-speaking childless men and women. However, it should be noted that international differences exist, especially concerning regulations governing the funding of AHR and payment for gametes and surrogacy. It is significant that women and men in this study indicated a lack of willingness to consider the use of third third-party treatments--the very options they may need to use in building their families, if the increasing trend towards delayed childbearing continues. This research was funded by a grant from the Canadian Institutes of Health Research and Assisted Human Reproduction Canada #PAH-103594, 2009/10. No competing interests.


Increased atrial natriuretic factor receptor density in cultured vascular smooth muscle cells of the spontaneously hypertensive rat.
To explore the role of the atrial natriuretic factor (ANF) system in the pathophysiology of hypertension we examined the binding kinetics of synthetic ANF to cultured vascular smooth muscle cells (VSMCs) derived from the spontaneously hypertensive rat (SHR) and two normotensive controls-the Wistar Kyoto (WKY) and American Wistar (W). The number of maximal binding sites (Bmax) per cell (mean +/- SEM; X10(3] were: SHR = 278.0 +/- 33.0, WKY = 28.3 +/- 7.1 and W = 26.6 +/- 4.2. The differences between the SHR and normotensive strains were significant at p less than 0.001. The equilibrium dissociation constant (Kd; X 10(-9)M) was higher in SHR VSMCs (0.94 +/- 0.14) than in WKY (0.22 +/- 0.09; p less than 0.01) and W (0.39 +/- 0.14; p less than 0.02) cells. The plasma levels of the immunoreactive ANF were higher in SHR than the normotensive controls. We suggest that the relatively greater ANF receptor density in cultured VSMCs of the SHR represents a response to the in vitro environment which is relatively more deficient in ANF for VSMCs of the SHR as compared with the normotensive rats. Thus, the capacity of the SHR VSMC to regulate ANF receptor density appears to be independent of the blood pressure level.


The meningeal lymphatic vasculature in neuroinflammation.
The lymphatic vasculature is a unidirectional network of lymphatic endothelial cells, whose main role is to maintain fluid homeostasis along with the absorption of dietary fat in the gastrointestinal organs and management and coordination of immune cell trafficking into lymph nodes during homeostasis and under inflammatory conditions. In homeostatic conditions, immune cells, such as dendritic cells, macrophages, or T cells can enter into the lymphatic vasculature and move easily through the lymph reaching secondary lymph nodes where immune cell activation or peripheral tolerance can be modulated. However, under inflammatory conditions such as pathogen infection, increased permeabilization of lymphatic vessels allows faster immune cell migration into inflamed tissues following a chemokine gradient, facilitating pathogen clearance and the resolution of inflammation. Interestingly, since the re-discovery of lymphatic vasculature in the central nervous system, known as the meningeal lymphatic vasculature, the role of these lymphatics as a key player in several neurological disorders has been described, with emphasis on the neurodegenerative process. Alternatively, less has been discussed about meningeal lymphatics and its role in neuroinflammation. In this review, we discuss current knowledge about the anatomy and function of the meningeal lymphatic vasculature and specifically analyze its contribution to different neuroinflammatory processes, highlighting the potential therapeutic target of meningeal lymphatic vasculature in these pathological conditions.