Descriptive and predictive validity of somatic attributions in patients with somatoform disorders: a systematic review of quantitative research.
Research on hypochondriasis and other somatoform disorders (SFD) has provided evidence that patients with SFD tend to attribute their symptoms to organic dysfunctions or disease. However, recent studies appear to discredit this. There is no systematic evidence on whether patients with SFD predominantly rely on somatic attributions, despite calls to include somatic attributions as a positive criterion of somatic symptom disorder (SSD) in the upcoming Diagnostic and Statistical Manual of Mental Disorders (DSM-5). This study is a systematic review of quantitative studies which assess the descriptive and predictive validity of somatic attribution in SFD. The literature search was restricted to studies with patients who met the DSM-IV criteria for SFD. Somatic attribution style in SFD has acceptable descriptive but insufficient predictive validity. This confirms that the overlap between somatic and psychological attributions is often substantial. Attribution style can discriminate between SFD patients with and without comorbidity. A somatic attribution style does not qualify as a positive criterion in SSD. However, there is an urgent need for further research on causal illness perceptions in the full spectrum of medically unexplained symptoms in order to confirm this result. Given its high prevalence, research on psychological attribution style is warranted. Re-attribution does not provide a framework sophisticated enough to address the needs of patients in primary care.


Association of pretreatment serum interferon gamma inducible protein 10 levels with sustained virological response to peginterferon plus ribavirin therapy in genotype 1 infected patients with chronic hepatitis C.
Increased serum and intrahepatic interferon gamma inducible protein 10 (IP-10) levels in patients with chronic hepatitis C (CHC) have been described. To analyse the possible association of serum IP-10 levels with different outcomes to antiviral therapy. A total of 137 CHC patients treated with peginterferon plus ribavirin. Serum IP-10 levels were determined by enzyme linked immunosorbent assay before therapy, after 12 weeks of treatment, and 24 weeks after cessation of therapy. Variables significantly associated with a sustained virological response (SVR) on univariate analysis were included in a multivariate logistic regression model. Pretreatment serum IP-10 levels in patients with SVR were significantly lower than in non-responders (NR) (332.4 (222.1) v 476.8 (305.3) pg/ml, respectively; p=0.004). Serum IP-10 concentrations significantly decreased in patients with SVR (pretreatment: 332.4 (222.1) pg/ml; post-treatment: 170.2 (140.1) pg/ml; p<0.001) but not in NR (pretreatment: 476.8 (305.3) pg/ml; post treatment: 387.3 (268.1) pg/ml; p=0.06). By multivariate analysis, non-1 genotype (odds ratio (OR) 3.5 (95% confidence interval (CI) 1.1-10.4); p=0.003) and low viral load at baseline (OR 0.34 (95% CI 0.14-0.79); p=0.01) were independent predictors of SVR in all patients. When multivariate analysis was restricted to patients with genotype 1, only baseline viral load (OR 0.38 (95% CI 0.155-0.96); p=0.04) and pretreatment serum IP-10 levels (OR 0.99 (95% CI 0.996-0.999); p=0.03) were identified as predictive factors of SVR. Pretreatment serum IP-10 behaves as a predictive factor of SVR to peginterferon plus ribavirin therapy in genotype 1 infected patients.


Global Strategies for the Prevention and Control of Infectious Diseases and Non-Communicable Diseases.
This article on global health reviews the environment surrounding health strategies and plans, as well as lessons learned from the first 15 years of the 21st century, followed by a discussion on the quest for a new paradigm for disease control efforts and challenges and opportunities for Japan.


Autoimmune hemolytic anemia and venous thromboembolism: A systematic review and meta-analysis.
To investigate the risk of venous thromboembolism (VTE) among patients with autoimmune hemolytic anemia (AIHA). We conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio or standardized incidence ratio comparing the risk of VTE in patients with AIHA versus participants without AIHA. Pooled risk ratio and 95% confidence intervals were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird. Out of 592 potentially relevant articles, four studies (three cohort studies and one cross-sectional study) met our inclusion criteria and were included in the data analysis. The pooled risk ratio of VTE in patients with AIHA was 2.63 (95% CI, 1.37-5.05). The statistical heterogeneity of this study was high with an I(2) of 97%. Our study demonstrated a significantly increased risk of VTE among patients with AIHA.


Cervical-cancer screening: attendance and cost-effectiveness.
The influence of attendance on the health effects and cost-effectiveness of cervical-cancer screening was studied, both for organized screening programmes and for spontaneous screening. The asymmetric distribution of smears among the female population and the higher risk incurred by women who never or only occasionally attend screening appear crucial in determining the health effects of screening. An increase in attendance rate induces a substantial rise in health effects and a less than proportionate rise in costs, thus improving cost-effectiveness. Wider screening coverage, in order to increase the number of life-years saved, is achieved more efficiently by encouraging a greater number of women to attend than by inviting the same number of women to attend more often, i.e., with a shorter interval between successive screens. Spontaneous screening is characterized by high coverage for younger women and low coverage for middle-aged and older women. This leads to a small amount of health effects and poor cost-effectiveness as compared with organized screening.


Some physical and kinetic properties of adenylyl sulfate reductase from Desulfovibrio vulgaris.
Adenylyl sulfate reductase has been purified from the anaerobic sulfate-reducing bacterium, Desulfovibrio vulgaris, and judged to be homogenous by several criteria. Different forms of the enzyme could be visualized in polyacrylamide gels after electrophoresis and these polymeric species have been studied by a combination of absorption spectra, polyacrylamide gel electrophoresis, and sedimentation velocity experiments. A dimeric species of molecular weight 440,000 is stable in potassium phosphate buffer but can be dissociated to a 220,000 molecular weight species by either changing the buffer system to Tris-maleate or addition of AMP, DAMP, or adenylyl sulfate. Other catalytically active nucleotides are not capable of effecting this dissociation. The enzyme was determined to contain 12 non-heme irons, 12 acid-labile sulfides, and 1 FAD per molecule when calculated on the basis of a monomeric molecular weight of 220,000. ;el electrophoresis in the presence of sodium dodecyl sulfate indicated subunits of molecular weight 72,000 and 20,000. The extinction coefficient when determined in phosphate buffer at 372 nm is 108,000 M-1 cm-a. Steady state kinetic experiments employing ferricyanide, cytochrome c, and reduced methyl viologen as artificial electron transfer reagents were performed and the kinetic constants obtained under various conditions. Several nucleotide substrates were employed and compared in each assay with respect to Km and Vmax. The reduction of cytochrome c was found to be sensitive to both anaerobiosis and superoxide dismutase, suggesting the involvement of superoxide anions with this electron acceptor.


Cholinergic Neurons in Nucleus Subputaminalis in Primary Progressive Aphasia.
Primary Progressive Aphasia (PPA) is a syndrome characterized by an isolated impairment of language function at disease onset. The cholinergic system is implicated in language function and cholinergic deficits are seen in the brains of individuals with PPA. One major source of cholinergic innervation of the cerebral cortex is the nucleus basalis of Meynert (NBM) within which lies the nucleus subputaminalis (NSP). This nucleus is postulated to be involved in language function. We compared the abundance of cholinergic neurons in the NBM and NSP of controls and individuals with PPA. Also explored was whether the individuals presenting with PPA, who subsequently developed different clinical and neuropathological profiles, showed similar cholinergic deficits in the NSP. Cytoarchitecture of the basal forebrain was studied using Nissl staining in control (n = 5) and PPA (n = 5) brains. Choline acetyltransferase (ChAT) immunohistochemical staining labeled cholinergic neurons were quantified using Neurolucida software. In comparison to matched controls, PPA showed reduction of cholinergic neurons in the NBM (t(8) = 4.04, p = 0.0037; Cohen's effect size value d = 2.62) and the NSP (t(6) = 4.62, p = 0.0042; Cohen's d effect size d = 2.92). The average percent of cholinergic neuronal loss was relatively higher in the NSP (64.7%) compared to the NBM (47.7%). Regardless of underlying pathology, all cases presenting with PPA showed a marked loss of cholinergic neurons in the NSP, providing further evidence for the importance of this nucleus in language function.


[Immunochemical study of the CBA mouse kidney].
Immunoelectrophoresis and agar precipitation reaction allowed one to reveal 7 antigens in CBA mouse kidney. One of them, with a relative electrophoretic mobility--0.35, is specific for the kidney. The remaining renal antigens are common to the kidney and other organs and tissues of mice. The antigens with mobility in the albumin and alpha-globulin zones proved to be serum ones. An antigen with a mobility approximating 0 is specific for the kidney and liver. An antigen with a mobility in the alpha 2-globulin zone does not seem likely to be homogeneous and, apart from broad inter-organ specificity, bears the greatest resemblance to the lungs antigen.


Environmental scan of mental health supports across Canadian burn centers: A healthcare providers' perspective.
Early mental health care and psychosocial support after burn injury provided by a variety of specialists and non-mental health professionals is instrumental in prevention of long-term mental health sequalae such as post-traumatic stress, depressive or substance use disorders. Diversity of mental health supports available to burn survivors vary across geography, resulting in variation of long-term mental health outcomes following burn injury. A mixed-methods study utilizing a semi-structured questionnaire to explore resources available for burn survivors in Canada as an inpatient, outpatient, and more broadly in the aftercare community. Interviews were completed with 17 Canadian burn centers, with a variety of burn care professionals. In the continuum of burn care, a lack of available mental health professionals in certain regions and in the outpatient and community phases was observed. Emerging themes demonstrated the need for regular screening for mental health concerns among burn survivors and providing up to date discharge resources. In addition, increasing educational opportunities available to burn care staff with respect to burn survivor mental health was emphasized. Lastly, the importance of proactive and prolonged psychological support for burn survivors as they progress through an outpatient, rehabilitation and community setting was underlined. Identification of burn care practices and resources across Canada provides the opportunity to compare, unify and improve gaps in care that exist across the Canadian burn network.


Oxidation of liposomal membrane suppressed by flavonoids: quantitative structure-activity relationship.
Antioxidant activity of the set of 12 flavonoids in heterogeneous membrane system of dioleoyl phosphatidylcholine liposomes stressed by peroxidative damage induced by 2,2'-azobis-(2-amidinopropane)hydrochloride azoiniciator and evaluated by the thiocyanate method was assessed. Antioxidant activity (pIC(50)) was correlated with 19 molecule parameters calculated for the minimum energy conformers of the compounds tested. The linear regression analysis revealed that the parameter of hydration energy E(HYDR) (R = -0.747) was the best predictor of antioxidant activity in a liposomal system.


Hemorrhagic stroke.
Neuroimaging by CT or MR imaging is necessary for the identification of hemorrhagic stroke and provides information about its cause. The appearance of intracranial hematoma (ICH) on CT and MR imaging evolves over time and must be understood to facilitate accurate diagnosis. The cause of ICH varies by location. New evidence suggests that MR imaging alone may be adequate to identify hemorrhagic stroke in the acute setting, and that MR imaging is superior to CT for identification of chronic microbleeds and hemorrhagic conversion of infarction.


Codependence. Is it a home healthcare concern?
Professional nurses have often been labeled as codependent with the implication that this is a negative attribute that compromises patient care and weakens boundaries. This intriguing article examines this concept relative to home care nurses and provides insight on how this issue affects their practice.


Perceptual salience of global structures and the crowding effect in amblyopia.
The crowding effect refers to stronger deficits in linear acuity (e.g., letters in a line) than in single letter acuity in amblyopia. The current work investigated whether the salience of a global structure in which the target for identification is embedded influences the crowding effect in amblyopia. Compound shapes were presented to the amblyopic and fellow eyes respectively of 12 anisometropic amblyopes. The compound stimuli were presented on either a blank or a cross background so that the salience of global structures were manipulated. Reaction times (RTs) and response error rates were recorded when subjects identified global or local shapes, respectively. RTs were shorter to global than local shapes for both the amblyopic and the fellow eyes. The global RT advantage was larger for the amblyopic than the fellow eye. Interestingly, when viewing the stimuli with the amblyopic eye, subjects made more errors to local targets when the compound stimuli were presented against the blank than the cross background. The results suggest that the salience of global structures of visual stimuli contributes to the crowding effect in amblyopia.


Electrophysiologic properties of intravenous oxprenolol in man.
Electrophysiologic modifications produced by intravenous administration of 0.1 mg/Kg Oxprenolol were studied in 16 subjects with estimated normal impulse formation and conduction. Significant effects were sinus bradycardia, mild increase of sino-atrial conduction time, depression of intranodal conduction and prolongation of A-V node refractory periods. Sinus node recovery time and atrial refractory periods were unchanged. Infranodal conduction and the refractory periods of the His-Purkinje system, as well as of the bundle branches, were unchanged. These effects are compared with those observed after intravenous Propranolol and Prindolol.


Effect of prolonged exercise on oxidative damage and susceptibility to oxidants of rat tissues in severe hyperthyroidism.
We investigated effects of prolonged aerobic exercise and severe hyperthyroidism on indices of oxidative damage, susceptibility to oxidants, and respiratory capacity of homogenates from rat liver, heart and skeletal muscle. Both treatments induced increases in hydroperoxide and protein-bound carbonyl levels. Moreover, the highest increases were found when hyperthyroid animals were subjected to exercise. These changes, which were associated to reduced exercise endurance capacity, were in part due to higher susceptibility to oxidants of hyperthyroid tissues. Levels of oxidative damage indices were scarcely related to changes in antioxidant enzyme activities and lipid-soluble antioxidant concentrations. However, the finding that, following exercise the scavenger levels generally decreased in liver homogenates and increased in heart and muscles ones, suggested a net shuttle of antioxidants from liver to other tissues under need. Aerobic capacity, evaluated by cytochrome oxidase activity, was not modified by exercise, which, conversely, affected the rates of oxygen consumption of hyperthyroid preparations. These results seem to confirm the higher susceptibility of hyperthyroid tissues to oxidative challenge, because the mechanisms underlying the opposite changes in respiration rates during State 4 and State 3 likely involve oxidative modifications of components of mitochondrial respiratory chain, different from cytochrome aa3.


Identification of the HIV-1 Vif and Human APOBEC3G Protein Interface.
Human cells express natural antiviral proteins, such as APOBEC3G (A3G), that potently restrict HIV replication. As a counter-defense, HIV encodes the accessory protein Vif, which binds A3G and mediates its proteasomal degradation. Our structural knowledge on how Vif and A3G interact is limited, because a co-structure is not available. We identified specific points of contact between Vif and A3G by using functional assays with full-length A3G, patient-derived Vif variants, and HIV forced evolution. These anchor points were used to model and validate the Vif-A3G interface. The resultant co-structure model shows that the negatively charged β4-α4 A3G loop, which contains primate-specific variation, is the core Vif binding site and forms extensive interactions with a positively charged pocket in HIV Vif. Our data present a functional map of this viral-host interface and open avenues for targeted approaches to block HIV replication by obstructing the Vif-A3G interaction.


Spectroscopic studies on the interaction between carbaryl and calf thymus DNA with the use of ethidium bromide as a fluorescence probe.
The interaction between carbaryl and calf thymus DNA (ctDNA) was investigated under simulated physiological conditions (Tris-HCl buffer of pH 7.4) using ethidium bromide (EB) dye as a probe by UV-vis absorption, fluorescence and circular dichroism (CD) spectroscopy, as well as DNA melting studies and viscosity measurements. It can be concluded that carbaryl molecules could intercalate into the base pairs of DNA as evidenced by hyperchromic effect of absorption spectra, decreases in iodide fluorescence quenching effect, induced CD spectral changes, and significant increases in melting temperature and relative viscosity of DNA. The binding constants and thermodynamic parameters of carbaryl with DNA were obtained by the fluorescence quenching method. Furthermore, a chemometrics approach, parallel factor analysis (PARAFAC), was applied to resolve the measured three-way synchronous fluorescence spectral data matrix of the competitive interaction between carbaryl and EB with DNA, and the results provided simultaneously the concentration profiles and corresponding pure spectra for three reaction components (carbaryl, EB and DNA-EB complex) of the kinetic system at equilibrium. This PARAFAC analysis demonstrated the intercalation of carbaryl to the DNA helix by substituting for EB in the DNA-EB complex.


Fast and high-accuracy localization for three-dimensional single-particle tracking.
We report a non-iterative localization algorithm that utilizes the scaling of a three-dimensional (3D) image in the axial direction and focuses on evaluating the radial symmetry center of the scaled image to achieve the desired single-particle localization. Using this approach, we analyzed simulated 3D particle images by wide-field microscopy and confocal microscopy respectively, and the 3D trajectory of quantum dots (QDs)-labeled influenza virus in live cells. Both applications indicate that the method can achieve 3D single-particle localization with a sub-pixel precision and sub-millisecond computation time. The precision is almost the same as that of the iterative nonlinear least-squares 3D Gaussian fitting method, but with two orders of magnitude higher computation speed. This approach can reduce considerably the time and costs for processing the large volume data of 3D images for 3D single-particle tracking, which is especially suited for 3D high-precision single-particle tracking, 3D single-molecule imaging and even new microscopy techniques.


Supporting emergency department Nurse's self-Efficacy in victim identification through human trafficking education: A quality improvement project.
Human trafficking is a form of modern slavery, exploiting people across all cultures and ethnic groups. Human trafficking victims (HTV) are at increased risk for neglect, physical, and psychological harm. Approximately 68% of HTV report seeking medical treatments in the emergency department at some point during their captivity. Many emergency department nurses today are however not well prepared to identify potential HTV in day to day practice. The purpose of this quality improvement (QI) project was to improve emergency room nurses' self-efficacy in victim identification through education and implementation of a screening tool. Self-efficacy in victim identification was measured through a pre- and post- implementation survey. The intervention for this QI project included education delivered asynchronously online and in person across all shifts as well as a victim screening assessment. The screening assessment was imbedded in the pre-existing safety assessment of the electronic medical record. Using the mean response of pre- and post- implementation surveys, a paired t-test analysis allowed comparison indicating a significant improvement to self-reported levels of self-efficacy in nursing staff. A statistically significant change in mean practice self-efficacy scores reinforced the importance of education and screening in victim identification.


A qualitative study of physicians' and nurses' experiences of multidisciplinary collaboration with pharmacists participating at case conferences.
OBJECTIVES Previous studies have revealed a range of drug-related problems for nursing home and hospital patients. Different attempts to reduce drug-related problems have been tested. Medication reviews performed by pharmacists and subsequent presentation of findings at case conferences is one of these methods. Physicians' and nurses' experiences from multidisciplinary collaboration with pharmacists have to a lesser degree been investigated. This study aims to describe how Norwegian physicians and nurses experience collaborating with pharmacists at case conferences to reduce drug-related problems in elderly patients. METHODS This was a qualitative interview study using systematic text condensation. The setting was nursing homes (long-term care) and hospital wards (gerontology and rheumatology). Four physicians and eight nurses participated and the main outcome was physicians' and nurses' experiences of multidisciplinary collaboration with pharmacists. KEY FINDINGS Organizational problems were experienced including, among others, what professional contribution team members could expect from pharmacists and what professional role the pharmacist should have in the multidisciplinary team. Both professions reported that ambiguities as to when and if the pharmacist was supposed to attend their regular meetings resulted in some aggravation. On the other hand, the participants valued contributions from pharmacists with regard to pharmaceutical skills, and felt that this raised awareness on prescribing quality. CONCLUSIONS Physicians and nurses valued the pharmacists' services and reported that this collaboration improved patients' drug therapy. However, before implementing this service in nursing homes there is a need to make an organizational framework for this collaboration to support the professional role of the pharmacist.


NMR measurement of biomolecular translational and rotational motion for evaluating changes of protein oligomeric state in solution.
Defining protein oligomeric state and/or its changes in solution is of significant interest for many biophysical studies carried out in vitro, especially when the nature of the oligomeric state is crucial in the subsequent interpretation of experimental results and their biological relevance. Nuclear magnetic resonance (NMR) is a well-established methodology for the characterization of protein structure, dynamics, and interactions at the atomic level. As a spectroscopic method, NMR also provides a compelling means for probing both molecular translational and rotational motion, two predominant measures of effective molecular size in solution, under identical conditions as employed for structural, dynamic and interaction studies. Protein translational diffusion is readily measurable by pulse gradient spin echo (PGSE) NMR, whereas its rotational correlation time, or rotational diffusion tensor when its 3D structure is known, can also be quantified from NMR relaxation parameters, such as 15N relaxation parameters of backbone amides which are frequently employed for probing residue-specific protein backbone dynamics. In this article, we present an introductory overview to the NMR measurement of bimolecular translational and rotational motion for assessing changes of protein oligomeric state in aqueous solution, via translational diffusion coefficients measured by PGSE NMR and rotational correlation times derived from composite 15N relaxation parameters of backbone amides, without need for the protein structure being available.


Composition of blood plasma (calcium, phosphorus, magnesium, proteins) during the neonatal period in the calf. Influence of the state of health.
The changes in plasma concentrations of calcium, phosphorus, magnesium and several protein fractions, were studied from birth to the age of twenty days in 68 calves. 32 animals remained healthy while 36 animals suffered from diarrhea but survived. The day of birth the two groups differed biochemically. During the whole period studied, calcemia, phosphatemia and albuminemia of diarrheic calves were systematically lower than those of animals showing no pathologic symptoms. In addition, after intake of colostrum, the increase in total proteins and globulins was much smaller in sick calves than in those which remained healthy. The possible causes of these anomalies and their roles in the appearance of pathology are discussed.


Growth in children with chronic kidney disease: a report from the Chronic Kidney Disease in Children Study.
Growth failure is common among children with chronic kidney disease (CKD). We examined the relationship of growth parameters with glomerular filtration rate (GFR), CKD diagnosis, sex and laboratory results in children with CKD. Baseline data from 799 children (median age 11.0 years, median GFR 49.9 mL/min/1.73 m(2)) participating in the Chronic Kidney Disease in Children Study were examined. Growth was quantified by age-sex-specific height, weight, body mass index (BMI-age), and height-age-sex-specific BMI (BMI-height-age) standard deviation scores (SDS). Median height and weight SDS were -0.55 [interquartile range (IQR) -1.35 to 0.19] and 0.03 (IQR -0.82 to 0.97), respectively. Girls with non-glomerular CKD were the shortest (median height SDS -0.83; IQR -1.62 to -0.02). Compared to those with a serum bicarbonate (CO2) level of ≥ 22 mEq/L, children with CO2 of <18 mEq/L had a height SDS that was on average 0.67 lower [95 % confidence interval (CI) -0.31 to -1.03]. Only 23 % of children with a height SDS of ≤-1.88 were prescribed growth hormone therapy. Forty-six percent of children with glomerular CKD were overweight or obese (BMI-height-age ≥ 85th percentile). Growth outcomes in a contemporary cohort of children with CKD remain suboptimal. Interventions targeting metabolic acidosis and overcoming barriers to recombinant human growth hormone usage may improve growth in this population.


Identification of Polish cochineal (Porphyrophora polonica L.) in historical textiles by high-performance liquid chromatography coupled with spectrophotometric and tandem mass spectrometric detection.
The present work reports a method for identification of Polish cochineal (Porphyrophora polonica L.) in historical fabrics by the use of high-performance liquid chromatography coupled with diode array and tandem mass spectrometric detection with electrospray ionization (HPLC-DAD-ESI MS/MS). This hyphened technique allows detection and identification of 16 new minor colorants present in the discussed scale insect (including two previously observed by Wouters and Verhecken (Ann Soc Entomol Fr. 1989;25:393-410), but specified only as compounds of unknown structures) that do not occur (e.g., in American cochineal). The MS/MS experiments, complemented with UV-VIS data, enable identification of mono- and di-, C- and O-hexosides of kermesic and flavokermesic acids or their derivatives. The present paper introduces a fingerprint of color compounds present in Polish cochineal and defines them, particularly pp6 (ppI, O-hexoside of flavokermesic acid), as its markers allow distinguishing of Polish-cochineal reds from the American ones. Usefulness of the selected set of markers for identification of Polish cochineal has been demonstrated in the examination of textiles from the collection of the National Museum in Warsaw using the multiple reaction monitoring (MRM) method, originally elaborated on the basis of this study.


Extracerebral organ dysfunction in the acute stage after aneurysmal subarachnoid hemorrhage.
In patients with aneurysmal subarachnoid hemorrhage (SAH), secondary complications are an important cause of morbidity and case fatality. Delayed cerebral ischemia and hydrocephalus are important intracranial secondary complications. Potentially treatable extracranial complications are also frequently observed, and some are related to the occurrence of delayed cerebral ischemia and outcome. In addition to the occurrence of an inflammatory response and metabolic derangements, cardiac and pulmonary complications are the most common extracranial complications. This article provides an overview of the most common extracranial complications in patients with SAH and describes their effects on outcome and delayed cerebral ischemia.


Comparison of the umbilical cord Blood's anti-Mullerian hormone level in the newborns of mothers with polycystic ovary syndrome (PCOS) and healthy mothers.
Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases. At present, the cause of the disease is not fully understood, but many studies have shown that PCOS is associated with genetic and environmental factors. The present study aimed to assess the umbilical cord blood's Anti-mullerian hormone (AMH) level in the newborns of mothers suffering from PCOS comparing to healthy mothers. This prospective cohort study was conducted on 120 pregnant women with PCOS, who were selected through Rotterdam criteria, and 60 healthy pregnant women as the control group. The subjects in each group were divided into obese and non-obese mothers according to their body mass index (BMI) before pregnancy. The cord blood samples were collected from the offsprings on the time of childbirth. Finally, the circulating concentrations of AMH in both sexes of the newborns were determined by specific assays. The research results showed that the blood level of AMH was higher in the neonates of obese mothers with PCOS comparing to the controls (P < 0.001). Mean AMH level was higher in male neonates born from non-obese PCOS mothers than in the controls (P < 0.001); however, there was not a significant difference in the level of AMH in female neonates between these two groups (P = 0.264). Also the level of the above biomarker was higher in both sexes of the neonates belonging to obese PCOS mothers compared with the neonates born from non-obese PCOS mothers (P < 0.001). It can be said that the cord blood AMH level of neonates from obese women with PCOS is higher than that in the newborns of non-obese PCOS mothers. Further longitudinal studies are needed to confirm the clinical findings of the present research.


Economics of appendicitis: cost trend analysis of laparoscopic versus open appendectomy from 1998 to 2008.
Laparoscopic appendectomy (LA) has become more acceptable for the treatment of appendicitis over the last decade; however, its cost benefit compared to open appendectomy (OA) remains under debate. The purpose of this study is to evaluate the utilization of LA and its cost effectiveness based on total hospital charges stratified by complexity of disease and complications compared to OA. Nationwide Inpatient Sample data from 1998 to 2008 with the principal diagnosis of appendicitis were included. Appendicitis cases were divided by simple and complex (peritonitis or abscess) and subdivided by OA, LA, and lap converted to open (CONV). Total charges (2008 value), length of stay (LOS), and complications were assessed by disease presentation and operative approach. Between 1998 and 2008, 1,561,518 (54.3%) OA, 1,231,643 (42.8%) LA, and 84,662 (2.9%) CONV appendectomies were performed. LA had shorter LOS (2 d) than OA (3 d) and CONV (5 d) (P<0.001). CONV (7.4%) cases had more complications than OA (3.7%) and LA (2.6%). LA ($19,978) and CONV ($28,103) are costlier than OA ($15,714) based on normalized cost for simple and complex diseases (P<0.001). LA is more prevalent but its cost is higher in both simple and complex cases. Cost and complications increase if the case is converted to open. OA remains the most cost effective approach for patients with acute appendicitis.


The Associations between Evacuation Status and Lifestyle-Related Diseases in Fukushima after the Great East Japan Earthquake: The Fukushima Health Management Survey.
This study aimed to investigate the association between evacuation status and lifestyle-related disease risks among Fukushima residents following the Great East Japan earthquake. Fukushima health management survey respondents were classified into non-evacuees, returnees, evacuees in lifted areas, and evacuees in banned areas. During a seven-year follow-up, 22,234 men and 31,158 women were included. Those with a history of diabetes, hypertension, or dyslipidemia at baseline were excluded. The odds ratios of risk factors (ORs) and 95% confidence intervals (CIs) for diabetes, hypertension, and dyslipidemia were calculated using a logistic regression model. Spatial autocorrelation of the prevalence of these diseases in the Fukushima area in 2017, was calculated to detect the disease prevalence status. The risks of diabetes, hypertension, and dyslipidemia were higher in evacuees in banned areas than in non-evacuees; the multivariable ORs were 1.32 (95% CI: 1.19-1.46), 1.15 (1.06-1.25), and 1.20 (1.11-1.30) for diabetes, hypertension, and dyslipidemia, respectively. Returnees and evacuees in lifted areas had no increased risk of diseases. The area analyzed had a non-uniform spatial distribution of diabetes, hypertension, and hyperlipidemia, with clusters around Fukushima and Koriyama. Our findings imply the need for continuous support for evacuees in banned areas.


Characterizing Ryan White Part A-funded support service utilization patterns and their association with viral suppression among people with HIV in New York City.
Use of HIV-related support services has been demonstrated to improve outcomes for people living with HIV. Further exploring patterns of use could help identify how and in what settings additional HIV care and treatment adherence support could be provided. We aimed to identify support service utilization patterns and examine their association with viral load suppression (VLS). Our sample comprised 6,581 people with HIV who received Ryan White Part A support services for basic needs (food and nutrition, legal, harm reduction, housing services) in New York City from 1/2013 to 12/2016, but had not received services specifically targeting HIV care and treatment adherence. Five support service utilization classes were identified using latent class analysis, the majority of which were characterized by the predominant use of concrete services (e.g., food assistance). Compared with the low-intensity, sporadic concrete service use class, clients in all other classes had lower odds of VLS in a 365-day follow-up period, but this disadvantage disappeared with adjustment for confounding variables indicative of need. Our findings underscore the impact of need-related barriers on VLS and suggest that long-term service utilization beyond the one year period of this study may be required to diminish their negative effect on HIV outcomes.


Evaluation of patients' knowledge on warfarin in outpatient pharmacy of a tertiary care cardiac center.
Warfarin is widely used for the prevention and treatment of cardiac, thromboembolic and hypercoagulable diseases. Since warfarin is a narrow therapeutic index medicine, it requires close monitoring when used in the outpatient setting and on long term basis. Warfarin has been found to be associated with a number of complications especially bleeding. Patients' knowledge on warfarin can improve anticoagulation control with decrease in adverse drug reaction and other associated complications. The objective was to assess knowledge level of warfarin therapy among its users and to provide adequate education and counseling to the patients. In the present cross sectional study, 34 patients on warfarin were interviewed. Patients' knowledge on warfarin was assessed using a validated Anticoagulation Knowledge Assessment (AKA) questionnaire comprising 29 questions. Each correct answer scored 3.45 points whereas an incorrect answer scored zero point. Patient who answered at least 21 questions correctly or scored (21 × 3.45 = 72.4%) was considered to have adequate level of knowledge or have obtained a passing score. Association between independent variables and AKA score was assessed using Pearson Chi square test or Fisher's exact test for categorical variables. Patients were counseled regarding proper warfarin use by the researcher pharmacists at the end of each data collection schedule. Of the 34 patients, only 5.8% (n = 2) achieved a passing score whereas 94.1% (n = 32) failed to achieve the passing score. 67.6% of the patients (n = 23) achieved a score below 50%. More than 50% of the patients incorrectly answered 15 questions in the questionnaire. None of the patients scored 100%. No significant association was found between age, gender of patients and total warfarin score. A significant association (p < 0.05) was found between duration of warfarin therapy and total warfarin score. Warfarin knowledge was poor among the patients. Hence, regular counseling with timely assessment of their understanding was felt necessary.


Valacyclovir-associated acute kidney injury and encephalopathy in an elderly woman with normal kidney function: a case report.
A 72-year-old Japanese woman was treated by 3000 mg/day of valacyclovir for the herpes zoster in her left back. She had been treated as hypertension with no renal insufficiency. In two days, she visited an emergency room of a regional stroke care center with dysarthria, dexterity disorder and gait disturbance. Neither head CT nor MRI found intracranial lesions, then, laboratory tests revealed that her serum creatinine level was 4.63 mg/dL. She was transferred and admitted to our hospital on the following day and received hemodialysis under the diagnosis of AKI due to acyclovir accompanied with encephalopathy. Afterward, her serum concentration of acyclovir revealed as 44 μg/mL, which is extremely high. Her neurological symptom disappeared in parallel with the decrease of serum concentration of acyclovir. She received 3 sessions of hemodialysis and discharged on the 8th day of admission with almost normal renal function and no neurological sequela.


Effects of two models of hypercalcemia on renal acid base metabolism.
The effects of two models of chronic hypercalcemia on renal acid-base metabolism were studied in rats. In the first series of experiments, rats were rendered hyperparathyroid by the autologous grafting of 20 to 24 parathyroid glands into a single recipient. Hypercalcemia (5.48 +/- 0.03 mEq/liter in high PTH animals, 4.96 +/- 0.06 mEq/liter in pair-fed controls, P less than 0.001) occurred as did metabolic alkalosis (plasma total carbon dioxide 25.44 +/- 0.47 mEq/liter vs. 23.84 +/- 0.57 in controls, P less than 0.05). The rise in total carbon dioxide was in part a renal tubular effect since urine pH was lower (6.77 +/- 0.04 vs. 6.95 +/- 0.04, day 5, P less than 0.01) bicarbonaturia less (165 +/- 26 vs. 283 +/- 28 mumoles/24 hr, day 5, P less than 0.01) and titratable acid (TA) excretion increased (164 +/- 43.4 vs. 48.2 +/- 2.53 mEq/24 hr, day 5, P less than 0.01) in hyperparathyroid animals vs. pair-fed controls. To test the specific role of hypercalcemia versus PTH in this effect, normoparathyroid animals were treated with 1.25 (OH)2 vitamin D3 or SHAM injected, Urinary cAMP was reduced in these animals (0.030 +/- 0.004 mumoles/8 hr) compared to hyperparathyroid rats (0.055 +/- 0.01 mumoles/8 hr P less than 0.05) suggesting differences i PTH levels. Hypercalcemia occurred in 1,25(OH)2 vitamin D treated animals as did increased plasma total carbon dioxide and urinary TA while urinary bicarbonate excretion and urinary pH were reduced. Because hypercalcemia was associated with elevated total carbon dioxide in both models, it is proposed that chronic hypercalcemia stimulated renal acid excretion and in a sustained manner results in metabolic alkalosis, at least in part, on a renal basis.


Inhibition of antigen-induced contraction of guinea pig trachea by ICI 198,615.
We examined the extent of peptide leukotrienes involvement in ovalbumin-induced contraction of guinea pig trachea isolated from animals passively sensitized with antiovalbumin antibodies. Antigen challenge resulted in a concentration-dependent (EC50 = 10 +/- 3 ng/ml, X +/- S.E.M., n = 6) and prolonged (greater than 60 min) contraction of guinea pig trachea. The maximal contractile response was directly proportional to the quantity of sensitizing antibodies. The maximal response (but not EC50 for ovalbumin) was significantly (P less than 0.01) enhanced by indomethacin (20%), only slightly (10%) inhibited by the histamine H1-antagonist pyrilamine and unaffected by the platelet-activating factor (PAF) antagonist CV-3988. The potent and selective leukotriene antagonist ICI 198,615 partially (45%) inhibited the antigen-induced contraction in a concentration-related fashion (1-300 nM). Even at concentrations that abolish responses to leukotrienes, ICI 198,615 did not further inhibit the response, nor could other leukotriene antagonists (i.e. LY 171883 or FPL 55712) inhibit more than 50% of this response. In contrast, the 5-lipoxygenase inhibitors AA-861 and REV 5901, also a leukotriene antagonist, abolished the contractile response. Taken together, the results suggest that in guinea pig trachea, leukotrienes, in combination with other lipoxygenase metabolites, mediate a major part of the response to antigen. In contrast, PAF, histamine and prostaglandins appear to play only a minor role.


Serum thyroglobulin in acute and chronic liver disease.
In view of the widespread use of serum thyroglobulin determination in the follow-up of patients with differentiated thyroid carcinoma, the influence of acute and chronic liver disease on serum thyroglobulin concentration was investigated in thirty-seven consecutive patients with histologically proven alcoholic liver cirrhosis and twenty-three patients with acute non-alcoholic hepatitis. Seventy-four healthy volunteers served as controls. Serum thyroglobulin concentration was significantly elevated in cirrhosis: median 29.5 micrograms/l, (range 4.3-94.0 micrograms/l) compared to controls: median 16.0 micrograms/l, (range 4.8-89.6 micrograms/l), (P less than 0.001). Serum thyroglobulin concentration in patients with acute hepatitis: median 16.2 micrograms/l, (range 7.9-70.0 micrograms/l) was not significantly different from controls. The level of free-T3-index was significantly reduced and the level of free-T4-index was significantly elevated in both cirrhosis and hepatitis compared to controls. Serum TSH concentration was significantly elevated in cirrhosis compared to hepatitis and controls. Serum thyroglobulin levels were positively correlated to levels of free-T3-index (r = 0.35, P less than 0.05) and T3/T4-ratio (r = 0.40, P less than 0.05) but not to levels of serum TSH or free-T4-index or any of the liver function tests in any of the groups. In conclusion, our results do not clearly indicate whether the elevated serum thyroglobulin level in cirrhosis was caused by an impaired elimination and/or an increased secretion from the thyroid gland. The increase in serum thyroglobulin concentration in chronic alcoholic liver disease was not of a magnitude likely to cause misinterpretation of results obtained during the follow-up of patients with differentiated thyroid carcinoma.


Dose/dose-rate responses of shrimp larvae to UV-B radiation.
Previous work indicated dose-rate thresholds in the effects of UV-B on the near-surface larvae of three shrimp species. Additional observations suggest that the total dose response varies with dose-rate. Below 0.002 Wm-2[DNA] irradiance no significant effect is noted in activity, development, or survival. Beyond that dose-rate threshold, shrimp larvae are significantly affected if the total dose exceeds about 85 Jm-2[DNA]. Predictions cannot be made without both the dose-rate and the dose.These dose/dose-rate thresholds are compared to four-year mean dose/dose-rate solar UV-B irradiances at the experimental site, measured at the surface and calculated for 1 m depth. The probability that the shrimp larvae would receive lethal irradiance is low for the first half of the season of surface occurrence, even with a 44% increase in damaging UV radiation.


Can non-directed living liver donation help improve access to grafts and correct socioeconomic disparities in pediatric liver transplantation?
Each year, children die awaiting LT as the demand for grafts exceeds the available supply. Candidates with public health insurance are significantly less likely to undergo both deceased donor LT and D-LLD LT. ND-LLD is another option to gain access to a graft. The aim of this study was to evaluate if recipient insurance type is associated with likelihood of D-LLD versus ND-LLD LT. The SRTR/OPTN database was reviewed for pediatric LDLT performed between January 1, 2014 (Medicaid expansion era) and December 31, 2019 at centers that performed ≥1 ND-LLD LDLT during the study period. A multivariable logistic regression was performed to assess relationship between type of living donor (directed vs. non-directed) and recipient insurance. Of 299 pediatric LDLT, 46 (15%) were from ND-LLD performed at 18 transplant centers. Fifty-nine percent of ND-LLD recipients had public insurance in comparison to 40% of D-LLD recipients (p = .02). Public insurance was associated with greater odds of ND-LLD in comparison to D-LLD upon multivariable logistic regression (OR 2.37, 95% CI 1.23-4.58, p = .01). ND-LLD allows additional children to receive LTs and may help address some of the socioeconomic disparity in pediatric LDLT, but currently account for only a minority of LDLT and are only performed at a few institutions. Initiatives to improve access to both D-LLD and ND-LLD transplants are needed.


3D Cellular Architecture Modulates Tyrosine Kinase Activity, Thereby Switching CD95-Mediated Apoptosis to Survival.
The death receptor CD95 is expressed in every cancer cell, thus providing a promising tool to target cancer. Activation of CD95 can, however, lead to apoptosis or proliferation. Yet the molecular determinants of CD95's mode of action remain unclear. Here, we identify an optimal distance between CD95Ligand molecules that enables specific clustering of receptor-ligand pairs, leading to efficient CD95 activation. Surprisingly, efficient CD95 activation leads to apoptosis in cancer cells in vitro and increased tumor growth in vivo. We show that allowing a 3D aggregation of cancer cells in vitro switches the apoptotic response to proliferation. Indeed, we demonstrate that the absence or presence of cell-cell contacts dictates the cell response to CD95. Cell contacts increase global levels of phosphorylated tyrosines, including CD95's tyrosine. A tyrosine-to-alanine CD95 mutant blocks proliferation in cells in contact. Our study sheds light into the regulatory mechanism of CD95 activation that can be further explored for anti-cancer therapies.


The assessment of GFR after orthotopic liver transplantation using cystatin C and creatinine-based equations.
The measurement of kidney function after orthotopic liver transplantation (OLT) is still a clinical challenge. Cystatin C (CysC) has been proposed as a more accurate marker of renal function than serum creatinine (sCr). The aim of this study was to evaluate sCr- and CysC-based equations including the Chronic kidney disease (CKD)-EPI to determine renal function in liver transplant recipients. CysC and sCr were measured in 49 patients 24 months after OLT. The glomerular filtration rate (GFR) was calculated using the MDRD 4, the Cockroft-Gault, Hoek, Larsson, and the CKD-EPI equations based on sCr and/or CysC. As reference method, inulin clearance (IC) was estimated. Bias, precision, and accuracy of each equation were assessed and compared with respect to IC. Forty-five percent had a GFR < 60 ml/min/1.73 m(2) according to the IC. The Larsson, the Hoek and the CKD-EPI-CysC formula identified the highest percentage of patients with CKD correctly (88%, 88%, and 84%, respectively). The sCr-based equations showed less bias than CysC-based formulas with a similar precision. All CysC-based equations were superior as compared with sCr-based equations in the assessment of renal function in patients with an IC < 60 ml/min/1.73 m(2).


Rusa deer (Cervus timorensis) as a host for the cattle tick (Boophilus microplus) in Papua New Guinea.
The rusa deer (Cervus timorensis) is more resistant to the cattle tick (Boophlilus microplus) than are Britsh breed cattle in Papua New Guinea. The average yield of replete female ticks from deer was 1.6% (0.3-3.2%) as compared to 11.2% (3.4-23.1%) from calves. Ticks from deer were more slender, lighter in weight and produced fewer eggs (mean 1,800) than did ticks from calves (mean 2,200) but the deer was shown to be an effective host. A cervid population can maintain a tick population in the absence of bovine hosts thus presenting an important factor in eradication programs. Nutritional stress appears to result in a higher seasonal prevalence of infestation amongst males and non-pregnant females.


Infection prevention in a connected world: the case for a regional approach.
Results from microbiological and epidemiological investigations, as well as mathematical modelling, show that the transmission dynamics of nosocomial pathogens, especially of multiple antibiotic-resistant bacteria, is not exclusively amenable to single-hospital infection prevention measures. Crucially, their extent of spread depends on the structure of an underlying "healthcare network", as determined by inter-institutional referrals of patients. The current trend towards centralized healthcare systems favours the spread of hospital-associated pathogens, and must be addressed by coordinated regional or national approaches to infection prevention in order to maintain patient safety. Here we review recent advances that support this hypothesis, and propose a "next-generation" network-approach to hospital infection prevention and control.


YPK9 and WHI2 Negatively Interact during Oxidative Stress.
Yeast PARK9 (YPK9) shares homology with human ATP13A2, which encodes a polyamine transporter implicated in juvenile forms of Parkinson's disease. We used YPK9 to gain insight into how ATP13A2 affects cell growth and sensitivity to oxidative stress. Surprisingly, the YPK9 deletion strain from the Saccharomyces cerevisiae deletion collection (YKO) in wildtype BY4741 (mating type a) grew faster and was more resistant to hydrogen peroxide than a commercial, putative parental BY4741 wildtype strain (BY4741COM). In contrast, deleting YPK9 from BY4741COM rendered it very sensitive to hydrogen peroxide, suggesting its background is different from that of the deletion collection. Whole-genome sequencing revealed that BY4741COM and BY4741COMypk9∆ contain a novel premature stop codon near the 3' end of WHI2 (WHI2G1324T), whereas the collection's YPK9 deletion strain contains WHI2, which encodes a 486 amino acid protein, Whi2p. Replacing full-length WHI2 with the sequence coding for the predicted truncation (Whi2pE442*) rendered strains more sensitive to hydrogen peroxide, whereas the converse replacement rendered them more resistant. The sequences of WHI2 in 20 randomly chosen strains from the collection encode the full-length protein, indicating that the putative parental BY4741 WHI2G1324T strain's genetic background differs from that of the deletion collection. Examination of WHI2 sequences in several commonly used wildtype S. cerevisiae strains and isolates revealed other Whi2p truncations that might yield altered phenotypes. Together, these results demonstrate a novel premature stop codon in WHI2 that renders yeast sensitive to hydrogen peroxide; they also reveal a negative genetic interaction between WHI2 and YPK9 in the presence of hydrogen peroxide in the BY4741 background.


Locations of serial reach targets are coded in multiple reference frames.
Previous work from our lab, and elsewhere, has demonstrated that remembered target locations are stored and updated in an eye-fixed reference frame. That is, reach errors systematically vary as a function of gaze direction relative to a remembered target location, not only when the target is viewed in the periphery (Bock, 1986, known as the retinal magnification effect), but also when the target has been foveated, and the eyes subsequently move after the target has disappeared but prior to reaching (e.g., Henriques, Klier, Smith, Lowy, & Crawford, 1998; Sorrento & Henriques, 2008; Thompson & Henriques, 2008). These gaze-dependent errors, following intervening eye movements, cannot be explained by representations whose frame is fixed to the head, body or even the world. However, it is unknown whether targets presented sequentially would all be coded relative to gaze (i.e., egocentrically/absolutely), or if they would be coded relative to the previous target (i.e., allocentrically/relatively). It might be expected that the reaching movements to two targets separated by 5° would differ by that distance. But, if gaze were to shift between the first and second reaches, would the movement amplitude between the targets differ? If the target locations are coded allocentrically (i.e., the location of the second target coded relative to the first) then the movement amplitude should be about 5°. But, if the second target is coded egocentrically (i.e., relative to current gaze direction), then the reaches to this target and the distances between the subsequent movements should vary systematically with gaze as described above. We found that requiring an intervening saccade to the opposite side of 2 briefly presented targets between reaches to them resulted in a pattern of reaching error that systematically varied as a function of the distance between current gaze and target, and led to a systematic change in the distance between the sequential reach endpoints as predicted by an egocentric frame anchored to the eye. However, the amount of change in this distance was smaller than predicted by a pure eye-fixed representation, suggesting that relative positions of the targets or allocentric coding was also used in sequential reach planning. The spatial coding and updating of sequential reach target locations seems to rely on a combined weighting of multiple reference frames, with one of them centered on the eye.


Validation of the 24-hour dietary recall in preschool children.
The results of the current study indicate that data obtained by the dietary recall correlate highly with the children's weighed food intake if a parent or the primary caretaker providing the child's food responds to the interview. Meredith et al. found parents to be poor reporters of children's consumption outside the home. It is encouraging to note that parents can be reliable reporters of their children's food intake in the home environment. When errors did occur, they were errors in portion size, as 96% of foods eaten by the children were correctly identified by the parents. Parents under-reported only 4% of the time. This slight tendency to under-report is consistent with other reports of the validity of the 24-hour dietary recall. In younger children, parents appear to be reliable reporters of their children's in-home dietary intake. As children become older, they appear to be able to recall their own intake both within and outside the home. There are several possible explanations for these findings. First, several factors could have influenced the accuracy of parental reports of the child's intake during the day that we weighed foods. Because food was weighed in the homes, the parents undoubtedly attended more closely to their child's diet. Additionally, the dietary recalls were collected at the end of the day of observation. This was closer in time than most 24-hour recalls and may have reflected less memory decay than usual. Also, since our sample was primarily middle-class families who were well educated, the correspondence between actual vs. reported dietary intake may have been artificially enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of aging and acute illness on delayed hypersensitivity.
A group of standard antigens (monilia, mosquito, mumps, purified protein derivative [PPD], staphylococcus toxoid, streptokinase-streptodornase [sk-sd] and trichophyton) were applied to 321 normal volunteers, 60 patients admitted to a medical ward, and 41 patients in an intensive care unit (ICU) to evaluate their delayed hypersensitivity skin test response. Eighty-eight per cent of the normal subjects reacted with at least 5 mm. induration to one or more skin tests without any decrease in reactivity occurring with increasing age. In the hospitalized group, only 62 per cent of the ward and 63 per cent of the ICU patients reacted to the same skin tests. All (8/8) anergic ICU patients tested after discharge regained normal reactivity. Acute illness but not increasing age will impair the delayed hypersensitivity skin test response.


Does the Environment Cause Changes in Hemiparetic Lower Limb Muscle Activity and Gait Velocity During Walking in Stroke Survivors?
Stroke survivors often face difficulty in community ambulation though they attain steady-state walking in clinical setups. Compliance and unpredictability of the environment may alter the muscle activity and challenge the individual's gait. Successful reintegration into the community requires gait assessment and training in a real-life challenging environment. Little is known about the assessment and training of gait in the community environment under challenging mobility dimensions. Hence, we aimed to study the changes that real-life environmental dimensions have on the activity of selected muscles in hemiparetic lower limb and gait velocity in stroke survivors. An observational cross-sectional study was conducted on 16 ambulatory stroke survivors to assess the hemiparetic lower limb muscle activity during walking in real-life environmental dimensions. Participants were made to walk in the community on a walkway consisting of even surface, ramp, stairs, uneven terrain and obstacles. They were also made to manoeuvre through traffic and pick a load while walking for a distance in the walkway. Muscle activity of Rectus Femoris, Biceps Femoris, Gastrocnemius Medialis and Tibialis Anterior of the paretic lower limb were continuously recorded while walking using wireless surface electromyography. Gait velocity for the entire walkway and level of perceived difficulty while walking in different dimensions were also measured. Paired t-test was used to compare the percentage Maximum Voluntary Contraction (%MVC) of lower limb muscles between even surface and real-life environment dimensions while walking. One sample t-test was used to compare the gait velocity in real-life dimensions versus gait velocity in even surface measured in an earlier study. There was a significant reduction (p < 0.01) in the activity of all four hemiparetic lower limb muscles while walking under the influence of real-life environmental dimensions compared to even surface. Gait velocity (0.33 ± 0.17 m/s) was significantly lower than that is essential to be a community ambulator. The level of perceived difficulty across all dimensions was reported qualitatively with the highest difficulty reported during stair and obstacle clearance. Real-life environmental dimensions lead to the reduction of paretic lower limb muscle activities and gait velocity during walking in community-dwelling stroke survivors. Stroke survivors perceived more difficulty while walking in real-life environment dimensions particularly while negotiating stairs and obstacles. Knowledge about the influence of real-life environmental dimensions will help the clinicians to target rehabilitation methods to improve walking adaptability.


Comparative analysis of the distribution of choline acetyltransferase in the central nervous system of cyprinids.
The general organization of the cholinergic system in the central nervous system is similar among vertebrates, though fish show higher variability. Thus, in zebrafish, cholinergic cells are absent from the habenula and the rhombencephalic reticular formation, where such neurons are present in most vertebrate species analyzed. In this work, we compared the distribution of choline acetyltransferase in the central nervous system of both zebrafish and tench, in order to investigate whether these divergences in the distribution of cholinergic cells in zebrafish are species-specific, or a feature shared by members of the cyprinid family. Our data show that these two cyprinid possess in common some peculiarities in their cholinergic system that are not present in the rest of fish analyzed (e.g. absence of cholinergic cells in the habenula and their presence in the descendent octaval nucleus). Nonetheless, some cholinergic cells were observed in the dorsal thalamus and rhombencephalic reticular nuclei of the tench, which were absent in the same regions in zebrafish. The comparative analysis suggests a divergent evolution of the cholinergic system among close-related cyprinid species.


Treatment for cellulite.
Cellulite is a multifactorial condition that is present in 80% to 90% of postpubertal women and is one of the most intolerable esthetic imperfections. There are several theories on the pathophysiology of cellulite, and a number of different therapeutic regimens have been developed, from topical treatments to mechanical or energy-based devices. In this brief review, we summarize the scientific landscape to determine the clinical evidence with regard to the safety and efficacy of cellulite treatment options. Clinical protocols and the author's experience using a combination of internal and external procedures are also discussed. Studies using laser and light modalities along with radiofrequency have shown improvements in cellulite and a good safety profile, but acoustic wave therapy, subcision, and the 1440-nm Nd:YAG minimally invasive laser have demonstrated the most beneficial results in cellulite reduction. Although there is paucity of scientific evidence for treatments that improve cellulite, future emerging options and their combination may pave the way to eradicate this primarily cosmetic esthetic concern.


Impaired photosystem I oxidation induces STN7-dependent phosphorylation of the light-harvesting complex I protein Lhca4 in Arabidopsis thaliana.
Reduction of the plastoquinone (PQ) pool is known to activate phosphorylation of thylakoid proteins. In the Arabidopsis thaliana mutants psad1-1 and psae1-3, oxidation of photosystem I (PSI) is impaired, and the PQ pool is correspondingly over-reduced. We show here that, under these conditions, the antenna protein Lhca4 of PSI becomes a target for phosphorylation. Phosphorylation of the mature Lhca4 protein at Thr16 is suppressed in stn7 psad1 and stn7 psae1 double mutants. Thus, under extreme redox conditions, hyperactivation of thylakoid protein kinases and/or reorganization of thylakoid protein complex distribution increase the susceptibility of PSI to phosphorylation.


[EBF1 Promotes the Sensitivity of Cervical Cancer Cells to Cisplatin via Activating FBN1 Transcription].
Cisplatin (DDP) is widely used in the chemotherapy of cervical cancer (CC), the fourth most common female malignancy worldwide. However, some patients progress to chemotherapy resistance, which leads to chemotherapy failure, tumor recurrence, and poor prognosis. Therefore, strategies to identify the regulatory mechanisms underlying CC development and increase tumor sensitivity to DDP will help improve patient survival. This research was designed to ascertain the mechanism of EBF1-dependent regulation of FBN1 which promotes chemosensitivity of CC cells. The expression of EBF1 and FBN1 was measured in CC tissues resistant or sensitive to chemotherapy and in DDP-sensitive or -resistant cells (SiHa and SiHa-DDP cells). SiHa-DDP cells were transduced with lentiviruses encoding EBF1 or FBN1 to evaluate the influence of these two proteins on cell viability, expression of MDR1 and MRP1, and cell aggressiveness. Moreover, the interaction between EBF1 and FBN1 was predicted and demonstrated. Finally, to further verify the EBF1/FB1-dependent mechanism of DDP sensitivity regulation in CC cells a xenograft mouse model of CC was established using SiHa-DDP cells transduced with lentiviruses carrying EBF1 gene and shRNA directed to FBN1 EBF1 and FBN1 showed decreased expression in CC tissues and cells, particularly in those resistant to chemotherapy. Transduction of SiHa-DDP cells with lentiviruses encoding EBF1 or FBN1 lead to decreased viability, IC50, proliferation capacity, colony formation ability, aggressiveness, and increased cell apoptosis. We have shown that EBF1 activates FBN1 transcription by binding to FBN1 promoter region. Additionally, it was revealed that FBN1 silencing reversed the promoting effect of EBF1 overexpression on chemosensitivity of CC cells in vivo. EBF1 facilitated chemosensitivity in CC cells by activating FBN1 transcription.


The effects of a depressant and a stimulant drug on the contingent negative variation.
Three groups, each comprising eight subjects, were twice tested with an interval of one week: one group receiving 10 and 20 mg chlordiazepoxide, another group receiving 150 and 300 mg caffeine and a control group receiving placebo and 'no-drug' treatment. During each session the CNV was determined five times: one pre-drug and four post-drug measurements, each divided in a condition with and one without 'white noise'. Based on Eysenck's theory it was predicted that the CNV would increase after administering chlordiazepoxide and would decrease after administering caffeine. Furthermore it was expected that 'white noise' would attenuate the CNV of introverts and would enhance the CNV of extraverts. The first hypothesis was significantly verified comparing the chlordiazepoxide group with the caffeine group. However, making comparisons within groups, only the decrease between the measurement before taking caffeine and the first one after administering was significant. The second hypothesis could be supported for introverts only.


Maclean's rankings of health care indices in Canadian communities, 2000: comparisons and statistical contrivance.
A critical perspective is presented in regard to the 2000 regional rankings of Canadian health care indices by Maclean's magazine, June 5, 2000. This perspective is related in format to previous analyses of the Maclean's rankings of Canadian universities. Several pitfalls in the health care ranking procedures are summarized. The Maclean's data and general criteria appear conceptually reasonable, but their inconsistencies and limited range, together with problems in interpretation of rank data, do not allow them to be logically or empirically useful in the matter of health care evaluation, that is, in the manner portrayed for readers of Maclean's. Using a particular set of parameters defined as health "indicators," the rank data show gratuitously that communities better endowed with certain health services, such as those with medical schools, tend to provide higher levels of care.


Evaluation of coexposure to inorganic arsenic and titanium dioxide nanoparticles in the marine shrimp Litopenaeus vannamei.
The acute toxicity of titanium dioxide nanoparticles (nTiO2) that occur concomitantly in the aquatic environment with other contaminants such as arsenic (As) is little known in crustaceans. The objective of the present study is to evaluate whether coexposure to nTiO2 can influence the accumulation, metabolism, and oxidative stress parameters induced by arsenic exposure in the gills and hepatopancreas of the shrimp Litopenaeus vannamei. Organisms were exposed by dissolving chemicals in seawater (salinity = 30) at nominal concentrations of 10 μg/L nTiO2 or As(III), dosed alone and in combination. Results showed that there was not a significant accumulation of As in either tissue type, but the coexposure altered the pattern of the metabolism. In the hepatopancreas, no changes were observed in the biochemical response, while in the gills, an increase in the glutamate-cysteine-ligase (GCL) activity was observed upon exposure to As or nTiO2 alone, an increase in the reduced glutathione (GSH) levels was observed upon exposure to As alone, and an increase in the total antioxidant capacity was observed upon exposure to nTiO2 or nTiO2 + As. However, these modulations were not sufficient enough to prevent the lipid damage induced by nTiO2 exposure. Our results suggest that coexposure to nTiO2 and As does not alter the toxicity of this metalloid in the gills and hepatopancreas of L. vannamei but does alter its metabolism, favoring its accumulation of organic As species considered moderately toxic.


Interference of functional dual-tasks on gait in untrained people with Parkinson's disease and healthy controls: a cross-sectional study.
In Parkinson's disease (PD) population, performing secondary tasks while walking further deteriorates gait and restrict mobility in functional contexts of daily life. This study (1) analyzed the interference of functional cognitive and motor secondary task on untrained people with PD and (2) compared their walking with healthy subjects. Forty people with PD (aged 66.72 [7.5] years, Hoehn and Yahr stage I-II-III, on-medication) composed the PD group (PDG) and 43 participants (aged 66.60 [8.75] years) formed the group of healthy counterparts (HG). Gait was evaluated through spatiotemporal, kinematic and kinetic outcomes in five conditions: single task (ST) and visual, verbal, auditory and motor dual-task (DT). The velocity, stride length, and braking force performance of both groups was statistically higher in the ST condition than in verbal, auditory and motor DT (p < .05), and inferior in double support time and midstance force (p < .05). The same pattern was observed when compared the ST and visual DT condition, where participants showed a significantly higher stride length, double support time and braking force in the ST (p < .05). In addition, the PDG exhibited a significant shorter double support time and midstance force, and showed a higher braking force in the visual DT than in the verbal DT (p < .05). Similarly, the PDG showed a wider stride in the visual DT than in the motor DT condition (p < .05). PDG participants had a significantly lower performance than the HG in all the variables analyzed except for the maximum hip extension in the stance phase (p > .05). In untrained participants with PD, verbal and motor secondary tasks affect gait significantly, while auditory and visual tasks interfere to a lesser extent. Untrained people with PD have a poorer gait performance than their healthy counterparts, but in different grades according to the analyzed variables. The data in this paper are part of a single-blind, randomized, controlled trial and correspond to the evaluations performed before a physical rehabilitation program, retrospectively registered with the number at clinicaltrial.govNCT04038866.


Systematic review highlights high risk of bias of clinical prediction models for blood transfusion in patients undergoing elective surgery.
Blood transfusion can be a lifesaving intervention after perioperative blood loss. Many prediction models have been developed to identify patients most likely to require blood transfusion during elective surgery, but it is unclear whether any are suitable for clinical practice. We conducted a systematic review, searching MEDLINE, Embase, PubMed, The Cochrane Library, Transfusion Evidence Library, Scopus, and Web of Science databases for studies reporting the development or validation of a blood transfusion prediction model in elective surgery patients between January 1, 2000 and June 30, 2021. We extracted study characteristics, discrimination performance (c-statistics) of final models, and data, which we used to perform risk of bias assessment using the Prediction model risk of bias assessment tool (PROBAST). We reviewed 66 studies (72 developed and 48 externally validated models). Pooled c-statistics of externally validated models ranged from 0.67 to 0.78. Most developed and validated models were at high risk of bias due to handling of predictors, validation methods, and too small sample sizes. Most blood transfusion prediction models are at high risk of bias and suffer from poor reporting and methodological quality, which must be addressed before they can be safely used in clinical practice.


Association of Preoperative Geriatric Assessment With Length of Stay After Combined Cardiac Surgery.
For older patients undergoing cardiac surgery, geriatric factors are known to increase postoperative complications and prolong length of stay (LOS). Comprehensive geriatric assessment (CGA) is an evidence-based method for geriatric evaluation to develop an individualized-care plan to optimize physical, functional, and social issues. This study analyzed the association between preoperative CGA and hospital LOS after combined cardiac surgery. This retrospective monocentric study included all patients aged 75 years and greater who underwent combined cardiac surgery between 2014 and 2017. Hospital LOS, intensive care unit LOS, and postoperative complications were compared between patients with or without preoperative CGA before and after propensity-score matching. Mean age of the 407 patients was 79.6 years; 114 underwent a preoperative CGA (28%). For 305 patients (74.9%), coronary artery bypass was associated with aortic valve replacement. After propensity-score matching, a significant difference was found between the 2 groups (preoperative CGA versus none) for in-hospital LOS (12 versus 13 days; P = .04) and intensive care unit LOS (3 versus 4 days; P = .01). In multivariable analysis, a significant association remained between hospital LOS and CGA (P = .02), renal function (P = .02), mitral replacement (P = .001), and complications (P = .001). Our results favor the use of systematic preoperative CGA. These encouraging results need to be validated by prospective studies that assess the impact of individualized-care plan established after CGA on postoperative outcomes. With an aging population, efforts are required to determine how to implement preoperative individualized-care plans to improve postoperative outcomes for vulnerable patients undergoing cardiac surgery.


Financial Protection in Health Insurance Schemes: A Comparative Analysis of Mediclaim Policy and CHAT Scheme in India.
This article analyzes the level of financial protection to low-income people during illness in 'private health insurance' and 'people's preferred health insurance'. In a hypothetical situation of being insured with both the pro-poor version of the 'Mediclaim policy' (private health insurance) and CHAT-'Choosing Health Plans All-Together'-scheme (people's preferred health insurance), this study analyzed the out-of-pocket-spending for health care incurred by persons per reported illness episodes in four select resource-poor locations in India. Three data sources were used: (a) household survey, (b) CHAT: a field-based experiment conducted in India to reveal people's preference for health insurance benefits and (c) the specification of conditions of Mediclaim policy. The study found, first, that the Mediclaim policy covers a small proportion (eight per cent) of the total reported illness episodes but CHAT scheme covers a large proportion (90 per cent) of illness episodes and, second, that the Mediclaim policy reimburses five per cent of the total health expenditure but CHAT scheme reimburses 37 per cent. The study concludes that private health insurance provides lower level of financial protection compared to 'people's preferred health insurance' and hence recommends that health insurance packages must be comprehensive and reflect community preference to make it attractive so that health insurance penetration can be increased.


Pubertal development in thalassaemic patients after allogenic bone marrow transplantation.
To obtain further insight into gonadal function, a series of 50 prepubertal patients with beta-thalassaemia major (24 boys and 26 girls) aged from 12.6 to 18 years (mean 15 years) who had received a bone marrow transplantation (BMT) during childhood or the peripubertal period, at the age of 3.6-14.5 years (mean 10.8 years), were periodically re-evaluated at intervals of 6-12 months. The last evaluation was done 1-9 years (mean 4.2 years) after BMT. At each examination we measured height, pubertal stage, plasma gonadotrophins (LH and FSH) before and after the GnRH stimulation test (i.v.), sex steroids (total and free testosterone in males, and 17 beta-oestradiol in females), serum ferritin and bone age. Fourty percent of patients entered or passed through puberty normally despite clinical and hormonal evidence of gonadal dysfunction in most of them. A correlation was not found between the pubertal stage and age at BMT, and no statistical difference between patients who did not enter into puberty and patients with spontaneous pubertal development was found in serum ferritin levels. Our data confirm that gonads in male and female thalassaemic patients are exposed to the cytotoxic effects of the preparative transplant regime with alkylating agents. In some patients absence of pubertal development was due to gonadotrophin insufficiency, probably secondary to previous iron overload. These findings emphasize the need for a vigilant long-term follow up study of thalassaemic patients who have had BMT.


IKACh is constitutively active via PKC epsilon in aging mediated atrial fibrillation.
Atrial fibrillation (AF), the most common abnormal heart rhythm, is a major cause for stroke. Aging is a significant risk factor for AF; however, specific ionic pathways that can elucidate how aging leads to AF remain elusive. We used young and old wild-type and PKC epsilon- (PKCϵ) knockout mice, whole animal, and cellular electrophysiology, as well as whole heart, and cellular imaging to investigate how aging leads to the aberrant functioning of a potassium current, and consequently to AF facilitation. Our experiments showed that knocking out PKCϵ abrogates the effects of aging on AF by preventing the development of a constitutively active acetylcholine sensitive inward rectifier potassium current (IKACh). Moreover, blocking this abnormal current in the old heart reduces AF inducibility. Our studies demonstrate that in the aging heart, IKACh is constitutively active in a PKCϵ-dependent manner, contributing to the perpetuation of AF.


High scores on the Western Aphasia Battery correlate with good functional communication skills (as measured with the Communicative Effectiveness Index) in aphasic stroke patients.
To examine the correlation between an impairment-level and a functional-level assessment scale of aphasia. Prospective, longitudinal study. A stroke rehabilitation unit. Sixty-seven aphasic acute stroke patients who were undergoing a multi-disciplinary rehabilitation programme, including conventional speech and language therapy (SLT). Patients were assessed on study entry and 4, 8, 12 and 24 weeks after the start of SLT. The language impairment was assessed with the Western Aphasia Battery (WAB) and the communicative functional limitation associated with aphasia was measured with the Communicative Effectiveness Index (CETI).Results. There was a statistically significant correlation between the two scales for all assessment periods (Pearson's r=0.71; P<0.01). The study suggests that in the acute and subacute stages of stroke the scores of WAB and CETI can be surmised from one another.


First detection of voltage-gated sodium channel mutations in Phlebotomus argentipes collected from Bangladesh.
Phlebotomus argentipes is the main vector of visceral leishmaniasis in Bangladesh and is controlled using deltamethrin, a synthetic pyrethroid, through indoor residual spraying (IRS). A mutation at L1014 (leucine at codon 1014) of the voltage-gated sodium channel (VGSC), known as a knockdown resistance (kdr) gene, is thought to be an important pyrethroid resistance mechanism. This study detected mutations at codon 1014, and at codons 1011, 1016, and 1020, which are kdr sites in other insects. The kdr relationship with deltamethrin resistance in P. argentipes from an IRS-targeted site in Bangladesh was also evaluated. Sand flies were collected from Magurjora village, Mymensingh district, Bangladesh in November 2012. A WHO cone bioassay test using deltamethrin was conducted and specimens were grouped as 'live' or 'dead'. After morphological identification, genomic DNA was used to genotype a partial VGSC gene from P. argentipes. The kdr/ pyrethroid resistance relationship was evaluated using Fisher's exact test. Targeted codons were genotyped from 8 'live' and 63 'dead' P. argentipes. All 'live' specimens had mutant alleles (L1014F and L1014S) at codon 1014. The mutant allele rate was 94% for 'live' specimens and 55% for 'dead' specimens. The mutant allele survival odds were higher for the wild-type L1014L allele, and L1014F odds were lower for L1014S. There were no mutations at codons 1011, 1016, and 1020. The L1014 mutations suggested that pyrethroid resistance had appeared in Bangladesh. Further research on kdr mutations in P. argentipes is important for the appropriate IRS.


Quantum dot microdrop laser.
We report single-mode and multimode lasing from isolated spherical liquid microcavities containing CdSe/ZnS nanocrystal quantum dots. Lasing is observed at densities more than 2 orders of magnitude lower than previously demonstrated or theoretically predicted, assuming a uniform nanocrystal quantum dot distribution. Charged droplets, between 10 and 40 microm in size, are electrodynamically levitated and optically pumped. Substantial laser signals at low thresholds are measured from the directional emission normal to the pump beam, owing to the high Q cavity modes.


Immune response and histology of humoral rejection in kidney transplantation.
The adaptive immune response forms the basis of allograft rejection. Its weapons are direct cellular cytotoxicity, identified from the beginning of organ transplantation, and/or antibodies, limited to hyperacute rejection by preformed antibodies and not as an allogenic response. This resulted in allogenic response being thought for decades to have just a cellular origin. But the experimental studies by Gorer demonstrating tissue damage in allografts due to antibodies secreted by B lymphocytes activated against polymorphic molecules were disregarded. The special coexistence of binding and unbinding between antibodies and antigens of the endothelial cell membranes has been the cause of the delay in demonstrating the humoral allogenic response. The endothelium, the target tissue of antibodies, has a high turnover, and antigen-antibody binding is non-covalent. If endothelial cells are attacked by the humoral response, immunoglobulins are rapidly removed from their surface by shedding and/or internalization, as well as degrading the components of the complement system by the action of MCP, DAF and CD59. Thus, the presence of complement proteins in the membrane of endothelial cells is transient. In fact, the acute form of antibody-mediated rejection was not demonstrated until C4d complement fragment deposition was identified, which is the only component that binds covalently to endothelial cells. This review examines the relationship between humoral immune response and the types of acute and chronic histological lesion shown on biopsy of the transplanted organ.


Noncontiguous finished genome sequence and description of Bacillus andreraoultii strain SIT1(T) sp. nov.
Bacillus andreraoultii strain SIT1(T) (= CSUR P1162 = DSM 29078) is the type strain of B. andreraoultii sp. nov. This bacterium was isolated from the stool of a 2-year-old Nigerian boy with a severe form of kwashiorkor. Bacillus andreraoultii is an aerobic, Gram-positive rod. We describe here the features of this bacterium, together with the complete genome sequencing and annotation. The 4 092 130 bp long genome contains 3718 protein-coding and 116 RNA genes.


[Bonding strength and interface effects of different dentin surface on acetone-based adhesives bonding].
To study the influences on microstructure characteristic and bonding strength of acetone-based wet bonding systems when bonding on dry or wet dentin surface. Three acetone-based wet bonding systems, Gluma One-Bond, Bond-1 and One-Step, were used to bond Chrisma composite resin to dry or moist dentin surface, and the bonding interface was observed with HITACHI S-2700 scanning electron microscope. Microtensile strengths of different groups were measured with Instro 1195. All three bonding systems can infiltrate well into dentin bonding interface in the wet groups. A hybrid layer of about 5microm could be observed with resin tags traversing from the resin layer above into the undemineralized dentin below and the lateral branch of dentinal tubule. In the dry groups, three zones, a surface and a basal hybrid layer sandwiching a middle hybridoid region, could be observed. The hybrid layer was very thinner. Microtensile strength had significantly decreased while bonding on dry dentin surface with acetone-based wet bonding systems, with the maximum decrease of 39% in Bond-1. Incompletely infiltrated adhesive on dentin bonding interface could be observed and microtensile strength had significantly decreased while bonding on dry dentin surface with acetone-based wet bonding systems. Moist dentin surface, which can maintain collagen-rich fibrous network of demineralized dentin, is necessary when bonding with acetone-based wet bonding systems. Microtensile strength approaches to the real dentin bonding strength.


Multi-functional benefits from targeted set-aside land in a Danish catchment.
In this study, we explored how a targeted land use change in a Danish catchment (River Odense) may provide multi-functional benefits through nitrogen (N)-load reductions to obtain good ecological quality in Odense estuary, protection of N-vulnerable groundwater aquifers, protection of Natura2000 sites and carbon sequestration. An N-load model linked to GIS thematic layers of known protected areas (Natura2000 sites and N-vulnerable groundwater aquifers) was utilised targeting high N-load areas to locate set-aside land. The achieved multi-functional benefits within the catchment and estuary were assessed and cost-benefit assessment was performed by dividing the total welfare costs of the set-aside by the total multi-functional benefits gained from each strategy. The results show that obtaining multi-functional benefits at the lowest cost requires a targeted shift of set-aside from the traditional hot-spot N-load areas to designated protected areas.


Demonstration of eosinophil degranulation on the surface of opsonized schistosomules by phase-contrast cinemicrography.
Phase-contrast cinephotomicrography was used to examine eosinophil-schistosomule interaction. Eosinophil degranulation against the surface of schistosomules was observed in the presence of immune serum.


Can dicoumarol be used as a gonad-safe anticancer agent: an in vitro and in vivo experimental study.
Dicoumarol (DC) has potential for use as a gonad-safe anticancer agent. DC altered cell proliferation, decreased viability and increased apoptosis in Vero and MCF-7 cell lines but did not show any toxic effect on mouse ovarian tissues and developing oocytes in vitro and in vivo. DC suppresses cell proliferation and increases apoptosis in various cancer cells such as breast, urogenital and melanoma. DC has also been reported to alter the anticancer effects of several chemotherapeutics, including cisplatin, gemcitabine and doxorubicin in prostate, liver and uroepithelial cancer cells, respectively. Vero (African green monkey kidney epithelial cells) and MCF-7 (human cancerous breast epithelial cells) cell lines and mouse granulosa cells isolated from 21-day-old female BALB/c mice (n = 21) were used to assess the effects of DC (10, 50, 100 and 200 µm) for 24 and 48 h on cell proliferation, viability and apoptotic cell death. In vivo experiments were performed with a single i.p. injection of 32 mg/kg DC in 21-day-old female BALB/c mice (n = 12). Following 48 h, animals were sacrificed by cervical dislocation and histological sections of isolated ovaries were evaluated for apoptosis. Viability assays were based on the trypan blue dye exclusion method and an automated cell counter device was used. Terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling (TUNEL) and Annexin-V immunofluorescence were assessed by 3D confocal microscopy to address apoptotic cell death. We also assessed whether DC inhibits cell proliferation and viability through NQO1 [NAD(P)H Quinone Oxidoreductase 1], an intracellular inhibitor of reactive oxygen species (ROS). The meiotic spindle and chromosomes were studied in mouse oocytes by α-β-tubulin and 7-aminoactinomycine D (7-AAD) immunostaining in vitro and in vivo. DC does not block oocyte maturation and no significant alteration was noted in meiotic spindle or chromosome morphology in metaphase-II (M-II) stage oocytes following DC treatment in vitro or in vivo. In contrast, exposure to DC for 24 h suppressed cell proliferation (P = 0.026 at 200 µm), decreased viability (P = 0.002 at 200 µm) and increased apoptosis (P = 0.048 at 100 µm) in Vero and MCF-7 cell lines, compared with controls. These changes were not related to intracellular NQO1 levels. Mouse granulosa cells were unaffected by 50 or 100 µm DC treatment for 24 and 48 h in vitro. DC treatment in vivo did not alter the number of primordial follicles or the ratio of apoptosis in primordial, primary and secondary follicles, as well as in antral follicles, compared with the controls. DC was tested for ovarian toxicity only in isolated mouse oocytes/ovaries and healthy BALB/c mice. No cancer formation was used as an in vivo test model. The possibility that DC may potentiate ovarian toxicity when combined with traditional chemotherapeutic agents, such as mitomycin-C, cisplatin, gemcitabine and doxorubicin, must be taken into account, as DC is known to alter their effects in some cancer cells. The present study evaluated, for the first time, the effect of DC on ovarian tissue. The results suggested that DC is not toxic to ovarian tissues and developing oocytes; therefore, DC should be assessed further as a potential anticancer agent when female fertility preservation is a concern. N/A. This work includes data from dissertation thesis entitled 'Effects of dicoumarol on mitotic and meiotic cells as an anticancer agent' by DA, 2014 and was partly supported by The National Scientific and Technological Research Council of Turkey (SBAG-109S415) to AC, OC and SO. The authors confirm that this article content presents no conflicts of interest.


Timosaponin AIII induces antiplatelet and antithrombotic activity via Gq-mediated signaling by the thromboxane A2 receptor.
The thromboxane (Tx) A2 pathway is a major contributor to the amplification of initial platelet activation and is therefore a key drug target. To identify potent small-molecule inhibitors of the thromboxane prostaglandin (TP) receptor, we screened a small steroidal saponin library using U46619-induced rat platelet aggregation assays. Timosaponin AIII (TAIII) was identified as a potent inhibitor of U46619-induced rat platelet aggregation and exhibited superior selectivity for the TP receptor versus other G protein-coupled receptors and a PKC activator. TAIII inhibited U46619-induced rat platelet aggregation independent of increases in cAMP and cGMP and the inhibition of TxA2 production. Both PKC and PLC activators restored TAIII-inhibited platelet aggregation, whereas TAIII did not inhibit platelet aggregation induced by co-activation of the G12/13 and Gz pathways. Furthermore, TAIII did not affect the platelet shape change or ROCK2 phosphorylation evoked by low-dose U46619. In vivo, TAIII prolonged tail bleeding time, reduced the mortality of animals with acute pulmonary thromboembolism and significantly reduced venous thrombus weight. Our study suggests that TAIII, by preferentially targeting Gq-mediated PLC/PKC signaling from the TP receptor, induces stronger in vitro antiplatelet activity and in vivo antithrombotic effects and may be an excellent candidate for the treatment of thrombotic disorders.


Contractile and dilatory action of neuropeptides on isolated human mesenteric blood vessels.
Neuropeptide Y (NPY), substance P (SP), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), lysyl-bradykinin, somatostatin, Met- and Leu-enkephalin were tested for their smooth muscle activity in isolated human mesenteric arteries and veins. Only NPY regularly contracted both arteries and veins. Alpha-adrenergic and 5-HT2 antagonists did not affect the response. Somatostatin contracted the veins, but not the arteries, in a variable but concentration-dependent way. The other neuropeptides were without contractile effect. CGRP, bradykinin, and SP regularly dilated, in a concentration-dependent way, both arteries and veins precontracted with prostaglandin F2 alpha or uridine triphosphate. CGRP and bradykinin were the most potent dilators. VIP and somatostatin usually caused a moderate dilatation in the arteries, whereas in the veins, somatostatin was without dilatory effect and the VIP-induced dilatation was irregular. In both types of vessels Met-enkephalin seldom gave any significant dilatation, and no response occurred in the presence of Leu-enkephalin or NPY. The SP-antagonist (D-Arg, D-Trp, Leu)-SP (spantide) caused a dextal shift of the concentration-response curves for SP, in the case of the arteries also including a reduced maximum effect.


Fibrin clots from patients with acute-on-chronic liver failure are weaker than those from healthy individuals and patients with sepsis without underlying liver disease.
Previous studies identified decreased clot permeability, without differences in fibrin fiber density in clots, from patients with cirrhosis compared with those from healthy controls (HCs). Fibrinogen hypersialylation could be the reason for this discrepancy. The aim of this work was to study mechanical properties of clots and reassess clot permeability in relation to hypersialylation in patients with stable cirrhosis, acute decompensation, and acute-on-chronic liver failure (ACLF). Sepsis patients without liver disease were included to distinguish between liver-specific and inflammation-driven phenotypes. Pooled plasma was used for rheology and permeability experiments. Permeability was assessed with compression using a rheometer and by liquid permeation. Purified fibrinogen treated with neuraminidase was used to study the effects of fibrinogen hypersialylation on liquid permeation. Mechanical properties of clots from patients with stable cirrhosis and acute decompensation were similar to those of clots from HCs, but clots from patients with ACLF were softer and ruptured at lower shear stress. Clots from sepsis patients without liver disease were stiffer than those from the other groups, but this effect disappeared after adjusting for increased plasma fibrinogen concentrations. Permeability was similar between clots under compression from HCs and clots under compression from patients but decreased with increasing disease severity in liquid permeation. Removal of fibrinogen sialic acid residues increased permeability more in patients than in controls. Clots from patients with ACLF have weak mechanical properties despite unaltered fibrin fiber density. Previous liquid permeation experiments may have erroneously concluded that clots from patients with ACLF are prothrombotic as fibrinogen hypersialylation leads to underestimation of clot permeability in this setting, presumably due to enhanced water retention.