Vibratory perception in patients with generalized scleroderma.
The vibratory perception threshold (VPT) was measured on eight different test-spots in 13 patients suffering from generalized scleroderma of the acrosclerosis type without clinical evidence of peripheral neuropathy. VPT was significantly elevated in skin areas severely involved in the sclerodermic process, whereas normal on test-spots with less affected skin. The pattern of impaired vibratory perception differs from that usually seen in peripheral neuropathy and it is concluded that the pattern most probably reflects the viscous-elastic properties of the test-spots, indicating that cutaneous sclerosis exerts a damping effect on external vibrations. It is suggested that this phenomenon could be utilized as an objective gauge for the severity of the sclerosis.


A four-day subrenal capsule assay for testing the effectiveness of anticancer drugs against human tumors.
The subrenal capsule assay may predict to which anticancer drug a given patient's tumor is sensitive and may also be used to screen new anticancer drugs. The present study documents that the use of this model requires a histological assessment of both the exploitability of a subrenal capsule assay and the extent of drug-induced antitumor lesions. Thirty-five tumors from 34 patients with solid tumor were submitted to a subrenal capsule assay in a total of 1130 male B6D2F1 mice. After being biopsied, each tumor was dissected by a pathologist and cut into 50 pieces (1.5 X 1.5 X 1.5 cu mm), and one piece was implanted under the renal capsule of 35 mice; the mean tumor diameter was measured on Day 0. Mice were randomized into groups of 6 to 10 animals each. On Days 1, 2, and 3, mice were treated either with placebo (control group) or with various anticancer agents. On Days 4 or 6, mice were sacrificed, the mean tumor diameter measured, and the tumor-bearing kidney fixed in Bouin's picroformol solution and processed for histological analysis after staining with hematein -eosin. Seven histological parameters were blindly rated in a semiquantitative fashion yielding a compound score ( PAPAN ) which estimated the overall quality of each xenograft between -3 and +11. On Day 4, as opposed to Day 6, mean lymphocytic infiltration was 3-fold lower (p less than 0.01), and the rate of xenografts containing well-preserved cancer cells was 2-fold larger (p less than 0.01) in three different tumor specimens. Twenty-two of 31 (71%) assays were evaluable, as defined by a histological quality control test. In those, drug effects were demonstrable by statistically significant differences among groups in 2 assays (9%) by using the relative variation in tumor size as an index of drug effectiveness and in 12 assays (54%) by PAPAN histological score. This suggests the higher sensitivity of histological scoring over tumor size measurements. Moreover, no correlation between relative variation in tumor size and PAPAN was demonstrable with statistical significance indicating the poor reliability of tumor size measurements as an index of the antitumor effectiveness of cytostatic drugs.


Synergistic abiotic and biotic stressors explain widespread decline of Pinus pinaster in a mixed forest.
Global change potentially increases forest vulnerability. Different abiotic and biotic factors may interact to cause forest decline and accelerated tree mortality. We studied a mixed Mediterranean continental forest where Pinus pinaster Ait. (maritime pine) shows widespread decline to analyse the role of different abiotic and biotic factors on health status and growth dynamics both at the individual and plot levels. We also analysed stand composition and regeneration of tree species to check whether there is a change in species dominance. Fungal pathogens were seldom present and we detected no pervasive fungi or insect infestation and no presence of pathogens like Heterobasidion or Phytophthora. Infection of hemiparasite plants like Viscum album L. (mistletoe) can reduce leaf area and its abundance is generally considered an expression of host decline. Yet, the existence among declining trees of high defoliation levels without mistletoe, but not vice versa, suggests that defoliation in response to some abiotic stressor could be a predisposing factor preceding mistletoe infection. Compared to healthy trees, declining and dead trees exhibited higher defoliation rates, smaller needles and lower recent growth with steeper negative trends. Dead and declining trees showed similar negative growth trends since the early 1990s droughts, which we interpreted as early warning signals anticipating mortality of currently declining trees in the near future. Mortality of maritime pine extending across all size classes, the lower presence of this species in the smallest size classes and its lack of regeneration suggest it is potentially losing its current dominance and being replaced by other co-occurring, more drought-tolerant species. Our results unravelled that maritime pine decline seems to be mainly driven by a combination of predisposing and inciting abiotic factors (microenvironment and drought stress) and biotic factors (mistletoe). The absence of widespread fungal pathogens suggests that they may have a minor role on pine decline acting only eventually as contributing factors. Although there could be other interrelations among factors or other biotic agents at play, our results strongly suggest that water stress plays a major role in the decline process of the dominant species on an ecosystem with strong land-use legacies.


Labour and non-labour market productivity in Chinese patients with systemic lupus erythematosus.
A cross-sectional study was performed to assess the self-reported loss of labour and non-labour market productivity, as well as to characterize the risk factors of loss of productivity in patients with SLE. A consecutive sample of 125 Chinese patients with a diagnosis of SLE and within working age was recruited. Work disability, daily activity limitations and receipt of social help, along with demographic information and health status, were collected from a self-reported questionnaire. Disease characteristics were collected by clinical examination and chart review. Univariate and multivariate logistic analyses were used to describe the relationships between labour/non-labour productivity and demographic/clinical variables. Twenty (16%) patients reported complete work disability as a result of SLE after a median duration of 9 years since disease onset. A total of 46 (36.8%) patients reported difficulty in performing their daily activities, including household work, studying and leisure activities, among which 28% received social help from families or friends. Risk of work disability was strongly predicted by low education level, long disease duration and history of having pleurisy. Patients' global well-being, physical health status and functional status were factors independently associated with impaired non-labour market productivity. SLE has a profound impact on individuals' labour and non-labour market productivity. Vocational education programmes may be useful in lowering the work disability rate in SLE. Preserving patients' physical and mental functioning or improving patients' quality of life may help in restoring both labour and non-labour productivity.


A Comparative Study of Hemorrhagic Conversion Patterns After Stroke Thrombolysis With Alteplase Versus Tenecteplase.
Tenecteplase is the thrombolytic drug of choice for acute ischemic stroke (AIS) as it has unique pharmacologic properties, along with results demonstrating its non-inferiority compared to alteplase. However, there are contradictory data concerning the risk of intracranial hemorrhage. The purpose of the study was to report the rate and patterns of symptomatic intracranial hemorrhage (sICH) in AIS patients after thrombolysis with tenecteplase compared to alteplase. This is a retrospective cohort study with data collected 90 days before and after the change from alteplase to tenecteplase from 15 Texas stroke centers. The primary endpoint is the incidence of sICH according to the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) and European Cooperative Acute Stroke Study III (ECASS-3) criteria. The secondary endpoints are the radiographic pattern of hemorrhagic conversion according to the Heidelberg bleeding classification (HBC). A total of 431 patients were eligible for thrombolytic therapy. Half of the cohort received alteplase (n=216), and the other half received tenecteplase (n=215). The average age of the alteplase group was 62.94 years old (SD=15.12) and 64.45 years old (SD=14.51) for the tenecteplase group. Seven patients in the alteplase group (3.2%) and 14 (6.5%) in the tenecteplase group had sICH, with an odds ratio of 1.44 (95% CI 0.60-3.43; P=0.41). An increased National Institutes of Health Stroke Scale (NIHSS) score on arrival (1.06; 95% CI 1.0004-1.131; P=0.04) was a statistically significant predictor of sICH. Tenecteplase was associated with a statistically significant increase in HBC-3 (P=0.040) over alteplase. Compared with alteplase, our study revealed a higher rate of sICH with tenecteplase that was not statistically significant and a higher rate of HBC-3 hemorrhages that was statistically significant. The proposed mechanism of bleeding is hemorrhagic conversion in clinically silent infarcts and contusions underlying the lesions. Further studies are needed to confirm our findings and determine predictive risk factors.


Mediterranean Diet, Sustainability, and Tourism-A Study of the Market's Demand and Knowledge.
Globalization intensified competitiveness among agribusinesses worldwide in recent years. The European Commission focused on enhancing sustainable agriculture and food products' territorial uniqueness for competing in the international market. The Mediterranean diet (MD) is a model of feeding and lifestyle belonging to the ancient Mediterranean culture, which also embodies a sustainable food system. Therefore, in 2010, UNESCO recognized the MD as Intangible Cultural Heritage of Humanity, and Sicily (southern Italy) is its official physical site. Despite its worldwide fame, the notion of the MD runs the risk of being mystified because it is described most often as something that does not correspond to what it is holistically. The aim of this study is to know the market demand of the MD by Italian people and foreign tourists in Sicily and the level of knowledge of the MD by users, both consumers and experts. A survey at top Sicilian traditional restaurants with owners/chefs and their clients was carried out. The study provided an in-depth understanding of the current lack of knowledge about the holistic meaning of the MD. The study highlights the desirability of integrated science-policy actions (also for communication) and proposes a vertical communication system to revive and direct the MD demand toward its holistic model.


In vitro hemotoxic, α-neurotoxic and vasculotoxic effects of the Mexican black-tailed rattlesnake (Crotalus molossus nigrescens) venom.
The Mexican black-tailed rattlesnake Crotalus molossus nigrescens is distributed in the Mexican plateau. Its venom is known to cause hemolysis and presents fibrinogen coagulase, collagenase and fibrinolytic activities. These activities may be associated with hemostatic alterations, such as platelet aggregation, hemolysis and fibrinolysis, often described in ophidic accidents. However, the mechanisms of action of the C. m. nigrescens venom remain unclear. In this study we investigated the in vitro hemotoxic, neurotoxic, and vasculotoxic effects of the venom. We found that this venom produces two types of hemolytic responses, Oxyhemoglobin release and Methemoglobin formation. As a result of the cytotoxicity to endothelial cells produces morphological biphasic toxicity. The first step in this process is characterized by morphological changes, as well as the loss of cellular adhesion and reduction in thickness. The second phase is characterized by massive cellular aggregation and death. It also induced laminin, type IV collagen, perlecan and nidogen degradation. However, the venom did not modulate the muscular fetal and neuronal nicotinic acetylcholine receptors activity. Thus, we concluded that the C. m. nigrescens venom produced hemolysis and hemorrhages via degradation of the basement membrane components and endothelial cell cytotoxicity, but not by neurotoxicity at the receptor level in nicotinic acetylcholine receptors.


Propofol sedation Quality and safety. Failure mode and effects analysis.
Sedation is a key component of digestive endoscopy. While ensuring procedural safety and quality represents a primary goal, a detailed assessment of patient-focused risks and improvements is lacking on most occasions. Failure mode and effect analysis (FMEA) is a useful tool in this context as a means of raising barriers and defense mechanisms to prevent adverse events from developing.


The Benefits of Using Case Study Focussed, Problem Based Learning Approaches to Unit Design for Biomedical Science Students.
As part of the Biomedical Sciences undergraduate degree course students are required to apply biological principles to the interpretation of clinical case studies and the diagnosis of patients. Case study-based learning, i.e., application of knowledge to patient diagnosis, is new to most students as case studies do not form part of non-applied A level courses in biological sciences. This approach is an example of Problem Based Learning (PBL) which has been shown to support higher levels of student learning, encouraging critical thinking and analysis. PBL approaches have also been shown to increase academic satisfaction and student engagement. In recent years we have observed a downwards trend in student engagement and historically student performance in applied case study-based assessments to be lower than that observed for assessments based on detailing fundamental biological principles. We hypothesised that PBL teaching delivery would support students in preparing for case study-based assessments, helping them to demonstrate their critical evaluation and problem-solving skills, and hence, improve student performance. We also hypothesised that the student learning experience would be enhanced by a PBL teaching delivery approach which would improve overall engagement. We therefore redesigned a second year Biomedical Sciences degree haematology and clinical biochemistry unit: "Blood Science," with a stronger focus on PBL, including case study focussed activities throughout the unit. We subsequently analysed whether this PBL-focussed unit design improved student experience and feedback, student engagement and student confidence for biomedical science undergraduate students. We present here, our teaching strategy and the impact our changes had on student feedback for the 21/22 and 22/23 academic years. Our findings demonstrate that case study-based activities and tutorial PBL exercises, when incorporated into the curriculum design, can improve student experience in the Biomedical Sciences and other biological science undergraduate degree courses.


Estimating prevalence of avian haemosporidians in natural populations: a comparative study on screening protocols.
Birds harbour an astonishing diversity of haemosporidian parasites. Renewed interest in avian haemosporidians as a model system has placed a greater emphasis on the development of screening protocols to estimate parasite prevalence and diversity. Prevalence estimates are often based on the molecular or blood-smear microscopy techniques. However, variation in diagnostic sensitivity among screening methodologies represents a potential source of bias that may lead to erroneous inference in comparisons of prevalence across studies. Here, we analyzed a suite of blood samples for the presence of parasites using four diagnostic tools and compared method-specific estimates of detection probability to assess the relative performance of screening strategies. We screened a total of 394 bird blood samples collected in India (n = 203) and Sweden (n = 191) for the combined presence of Plasmodium, Haemoproteus and Leucocytozoon with three PCR assays: (i) qPCR; (ii) restriction enzyme-based assay; and (iii) nested protocol. In addition, we examined blood smears for estimates of parasite intensity which was further screened using qPCR method to evaluate if parasite intensity shows a relationship with qPCR (Ct values). Furthermore, we used single infected samples from parasite intensities: low, medium, high, very high to establish the reproducibility in qPCR. For the combined data sets from India and Sweden, detection probability for submicroscopic and low intensity infections was highest for the qPCR method, followed by the nested protocol and the restriction enzyme-based assay. For high parasite intensities, the qPCR had high PCR reproducibility, with three out of three PCR replicates being positive and with consistent Ct values across all tenfold dilution series. For parasite intensities at very low and submicroscopic samples, the qPCR was reproducible in one out of the three replicates. The intensity of parasitemia estimated from smears showed inverse relationship with Ct values in both the Indian and Swedish data sets. Our study highlights the importance of accounting for methodological issues to better estimate infection in parasitological studies and illustrates how a wider deployment of diagnostic tools combined with statistical approaches is needed for each study, in order to provide adequate insight into the most appropriate approach to avoid erroneous inferences.


Affinity identification of delta-opioid receptors using latex nanoparticles.
Three types of latex nanoparticles carrying naltrindole (NTI) derivatives were synthesized as probes for the affinity isolation of their binding proteins including the delta-opioid receptor. The effect of the attachment of NTI to different positions on the linker was investigated. Only latex nanoparticles in which the NTI derivative was linked through the phenol group were useful for isolating the recombinant delta-opioid receptor solubilized from CHO cell membrane. These latex nanoparticles could be a useful tool for investigations of the pharmacological activity of NTI.


Discrete determinants in transfer RNA for editing and aminoacylation.
During translation errors of aminoacylation are corrected in editing reactions which ensure that an amino acid is stably attached to its corresponding transfer RNA (tRNA). Previous studies have not shown whether the tRNA nucleotides needed for effecting translational editing are the same as or distinct from those required for aminoacylation, but several considerations have suggested that they are the same. Here, designed tRNAs that are highly active for aminoacylation but are not active in translational editing are presented. The editing reaction can be controlled by manipulation of nucleotides at the corner of the L-shaped tRNA. In contrast, these manipulations do not affect aminoacylation. These results demonstrate the segregation of nucleotide determinants for the editing and aminoacylation functions of tRNA.


Unplanned Readmission to the Pediatric Cardiac Intensive Care Unit: Prevalence, Outcomes, and Risk Factors.
Factors leading to cardiac intensive care unit (CICU) readmission and the impact on mortality have yet to be well delineated. We sought to define the prevalence and outcome for unscheduled CICU readmission. Secondary objectives were to identify indications and risk factors for unscheduled CICU readmission. Retrospective analysis of prospectively collected registry data at a tertiary care children's hospital. Pediatric and adult patients with congenital and acquired heart disease who survived to initial CICU discharge were included. Patients with unexpected return to the CICU for acute change in clinical status were defined as unscheduled readmissions. Of the 645 discharges that met inclusion criteria, 37 resulted in unplanned readmission to the CICU. Patients requiring unscheduled readmission had higher mortality rates (16.2% vs 0.5%, P < .0001). Cardiac symptoms were the most common reason for readmission. On multivariate analysis, genetic anomaly (P = .001) and longer length of stay (LOS) during the index CICU admission (P = .01) were independently associated with readmission. For surgical patients, genetic anomaly (P = .001), single-ventricle anatomy (P = .05), and longer surgical support time (P < .001) were independently associated with readmission. Unscheduled readmission to the CICU within the same hospitalization was uncommon but associated with a higher mortality rate. Genetic anomaly and longer initial LOS were important risk factors for the entire cohort. Single-ventricle anatomy and longer intraoperative course were risk factors for surgical readmissions.


Aspirin-triggered resolvin D1 attenuates PDGF-induced vascular smooth muscle cell migration via the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) pathway.
Resolvin D1 (RvD1) is a specialized pro-resolving lipid mediator that has been previously shown to attenuate vascular smooth muscle cell (VSMC) migration, a key process in the development of intimal hyperplasia. We sought to investigate the role of the cAMP/PKA pathway in mediating the effects of the aspirin-triggered epimer 17R-RvD1 (AT-RvD1) on VSMC migration. VSMCs were harvested from human saphenous veins. VSMCs were analyzed for intracellular cAMP levels and PKA activity after exposure to AT-RvD1. Platelet-derived growth factor (PDGF)-induced migration and cytoskeletal changes in VSMCs were observed through scratch, Transwell, and cell shape assays in the presence or absence of a PKA inhibitor (Rp-8-Br-cAMP). Further investigation of the pathways involved in AT-RvD1 signaling was performed by measuring Rac1 activity, vasodilator stimulated phosphoprotein (VASP) phosphorylation and paxillin translocation. Finally, we examined the role of RvD1 receptors (GPR32 and ALX/FPR2) in AT-RvD1 induced effects on VSMC migration and PKA activity. Treatment with AT-RvD1 induced a significant increase in cAMP levels and PKA activity in VSMCs at 5 minutes and 30 minutes, respectively. AT-RvD1 attenuated PDGF-induced VSMC migration and cytoskeletal rearrangements. These effects were attenuated by the PKA inhibitor Rp-8-Br-cAMP, suggesting cAMP/PKA involvement. Treatment of VSMC with AT-RvD1 inhibited PDGF-stimulated Rac1 activity, increased VASP phosphorylation, and attenuated paxillin localization to focal adhesions; these effects were negated by the addition of Rp-8-Br-cAMP. The effects of AT-RvD1 on VSMC migration and PKA activity were attenuated by blocking ALX/FPR2, suggesting an important role of this G-protein coupled receptor. Our results suggest that AT-RvD1 attenuates PDGF-induced VSMC migration via ALX/FPR2 and cAMP/PKA. Interference with Rac1, VASP and paxillin function appear to mediate the downstream effects of AT-RvD1 on VSMC migration.


Evaluation of equine papillomas, aural plaques, and sarcoids for the presence of Equine papillomavirus DNA and Papillomavirus antigen.
Immunohistochemical (IHC) testing and electron microscopy have implicated Papillomavirus (PV) as the etiologic agent for equine papillomas and aural plaques, but Equine papillomavirus (EPV) DNA has yet to be demonstrated in these lesions by polymerase chain reaction (PCR). The purpose of this study was to evaluate formalin-fixed, paraffin-embedded tissues from naturally occurring cases of equine papillomas, aural plaques, and sarcoids for the presence of EPV DNA by means of PCR and for the presence of PV antigen by means of IHC testing. We used EPV-specific primers that amplified a region of 384 base pairs (bp) spanning the E4 and L2 genes of the EPV genome and consensus PV primers that amplified a 102-bp region of the L1 gene. Group-specific PV structural antigens were detected with the use of a streptavidin-biotin-alkaline phosphatase IHC stain. With IHC testing, 23 of 38 papillomas, 4 of 9 aural plaques, and 0 of 10 sarcoids were positive for PV antigen; EPV DNA was found in 20 of the 38 papillomas and 1 of the 10 sarcoids but 0 of the 9 aural plaques. The consensus primers did not amplify novel PV DNA in any of the tissues. Nucleotide sequencing of viral DNA from 7 papillomas amplified with EPV-specific primers revealed DNA fragments that were 96% to 99% identical to known EPV sequences. Some samples had nucleotide substitutions in common, which suggests infection with related strains. Together, EPV DNA or PV antigen (or both) was demonstrated in 26 (68%) of the 38 equine papillomas. Although aural plaques contained PV antigen, they were negative for EPV DNA; therefore, we hypothesize that aural plaques contain a PV distinct from EPV.


Biodegradation of aliphatic-aromatic copolyesters by Thermomonospora fusca and other thermophilic compost isolates.
Random aliphatic-aromatic copolyesters synthesized from 1,4-butanediol, adipic acid, and terephthalic acid (BTA) have excellent thermal and mechanical properties and are biodegradable by mixed cultures (e.g., in compost). Over 20 BTA-degrading strains were isolated by using compost as a microbial source. Among these microorganisms, thermophilic actinomycetes obviously play an outstanding role and appear to dominate the initial degradation step. Two actinomycete strains exhibited about 20-fold higher BTA degradation rates than usually observed in a common compost test. These isolates were identified as Thermomonospora fusca strains. They appeared to be particularly suitable for establishment of rapid degradation tests and were used in comparative studies on the biodegradation of various polyesters.


Petroleum Carcinogenicity and Aerodigestive Tract: In Context of Developing Nations.
Head and neck cancers from a diverse group of neoplasms, the occurrence of which can be attributed to habitual tobacco use, race, alcohol consumption, ultraviolet (UV) exposure, occupational exposure, viruses, and diet. The surging incidence rates reflect the prevalence of risk factors such as tobacco use (smoked and smokeless), betel nut chewing, urbanization and issues relating to urban air quality. Urbanization and development have catalyzed a multifold rise in levels of pollution in metropolitan cities. Ever-increasing consumption of fuels to meet demands of the growing population coupled with industrial activity has adversely affected the air quality, especially in developing countries. The cause most neglected in risk assessment of aerodigestive tract cancer research is that from petroleum exposure. The global issue of petroleum carcinogenicity has assumed high proportions. Polycyclic aromatic hydrocarbons and heavy metals are essential constituents of total petroleum hydrocarbons which infiltrate into the environment and are recognized worldwide as priority pollutants because of their toxicity and carcinogenicity. High levels of sulfur dioxide, nitrogen dioxide, ozone, carbon monoxide, ammonia and particulate matter PM10 has skyrocketed aerodigestive tract diseases especially carcinomas. The identification of specific biomarkers and role of metal ions in aerodigestive tract cancers will indicate the molecular basis of disease to provide quality care for patients confronting new threats from climate-sensitive pathologies. There is an urgent need to evaluate existing public health infrastructure so as to take ameliorative and adaptive measures.


Clinical Application of Phase Angle and BIVA Z-Score Analyses in Patients Admitted to an Emergency Department with Acute Heart Failure.
Acute heart failure is characterized by neurohormonal activation, which leads to sodium and water retention and causes alterations in body composition, such as increased body fluid congestion or systemic congestion. This condition is one of the most common reasons for hospital admission and has been associated with poor outcomes. The phase angle indirectly measures intracellular status, cellular integrity, vitality, and the distribution of spaces between intracellular and extracellular body water. This parameter has been found to be a predictor of health status and an indicator of survival and other clinical outcomes. In addition, phase angle values of <4.8° upon admission were associated with higher mortality in patients with acute heart failure. However, low phase angle values may be due to alterations-such as the shifting of fluids from an intracellular body water (ICW) compartment to an ECW (extracellular body water) compartment and a concurrent decrease in body-cell mass (which can reflect malnutrition)-that are present in heart failure. Thus, a low phase angle may be due to overhydration and/or malnutrition. BIVA provides additional information about the body-cell mass and congestion status with a graphical vector (R-Xc graph). In addition, a BIVA Z-score analysis (the number of standard deviations from the mean value of the reference group) that has the same pattern as that of the ellipses for the percentiles on the original R-Xc graph can be used to detect changes in soft-tissue mass or tissue hydration and can help researchers compare changes in different study populations. This protocol explains how to obtain and interpret phase angle values and BIVA Z-score analyses, their clinical applicability, and their usefulness as a predictive marker for the prognosis of a 90-day event in patients admitted to an emergency department with acute heart failure.


Effect of the sulphur atom on geometry and spectra of the biomolecule 2-thiouracil and in the WC base pair 2-thiouridine-adenosine. Influence of water in the first hydration shell.
The effect of the sulphur atom on 2-thiouracil (2TU) and 2-thiouridine molecules, as compared with uracil and uridine molecules, respectively, was carried out in several environments. The predicted IR spectrum of 2TU in the isolated state was compared with that obtained for uracil molecule and with those reported experimentally in matrix isolation. Its crystal unit cell in the solid state was simulated through a tetramer form using DFT methods for the first time. The calculated Raman spectrum was compared to the experimental ones in the solid state. A linear scaling procedure was used for this task. The first hydration shell was simulated by explicit number of water molecules surrounding 2TU up to 30 and was compared with that obtained in uracil molecule. Water molecules 'distributed' around 2TU was preferred over that 'clustering', because it can better reproduce the hydration and their effects on different parameters of the molecular structure of 2TU and uracil. The total atomic charges and several calculated thermodynamic parameters were discussed. The effect of the sulphur atom on the Watson-Crick (WC) and reverse WC base pair uridine-adenosine was estimated, and the CP corrected interaction energies were calculated. 2-thiouridine has a weaker WC pair than that with uridine, although its slight higher dipole moment (μ) facilitates the interaction with the water molecules. Several helical parameters were determined.


Derivation of a germline competent transgenic Fischer 344 embryonic stem cell line.
Embryonic stem (ES) cell-based gene manipulation is an effective method for the generation of mutant animal models in mice and rats. Availability of germline-competent ES cell lines from inbred rat strains would allow for creation of new genetically modified models in the desired genetic background. Fischer344 (F344) males carrying an enhanced green fluorescence protein (EGFP) transgene were used as the founder animals for the derivation of ES cell lines. After establishment of ES cell lines, rigorous quality control testing that included assessment of pluripotency factor expression, karyotype analysis, and pathogen/sterility testing was conducted in selected ES cell lines. One male ES cell line, F344-Tg.EC4011, was further evaluated for germline competence by injection into Dark Agouti (DA) X Sprague Dawley (SD) blastocysts. Resulting chimeric animals were bred with wild-type SD mates and germline transmissibility of the ES cell line was confirmed by identification of pups carrying the ES cell line-derived EGFP transgene. This is the first report of a germline competent F344 ES cell line. The availability of a new germline competent ES cell line with a stable fluorescence reporter from an inbred transgenic rat strain provides an important new resource for genetic manipulations to create new rat models.


Long-term third-party assessment of results after continent cutaneous diversion with Lundiana pouch.
To investigate the long-term functional outcomes and complications after continent cutaneous diversion with the Lundiana pouch. Complications, re-operations, renal function, and continence were ascertained from patient charts. Outcome variables were validated by a second and independent review of the patient files. A complication of Clavien-Dindo grade ≥III, including unscheduled re-admissions, occurred in 45/193 patients (23%) at ≤90 days of surgery. At a median follow-up of 13 years, 105/193 patients (54%) had undergone at least one re-operation, with uretero-intestinal stricture being the most prevalent cause [28 patients (15%)]. Re-operations were more prevalent in patients operated during the first half of the study period than during the second half (2000-2007; 62% vs 47%; P = 0.03), and they were also more frequent in patients who underwent surgery for benign causes than in patients who underwent surgery for malignancy (60% vs 51%; P = 0.04). Continence was achieved in 172/188 patients (91%). In all, 16% of all patients required revisional surgery of the outlet to remain continent with an easily catheterisable pouch or to address stomal stenosis. The mean decrease in estimated glomerular filtration rate was more pronounced in patients with benign indications for urinary diversion than in those with malignancies, even after adjusting for younger age at surgery and longer follow-up in the former group (22 vs 11 mL/min/1.73 m2 ; P < 0.006). A disinterested third-party assessment revealed 10 postoperative complications, 17 re-operations during follow-up, and seven occasions of hospitalisation due to pyelonephritis (included in data above) not recorded at the primary data review. The Lundiana pouch is associated with a high risk of re-operation, although the functional results are good. Independent review by a third party increased the validity of the outcome data.


Intrahepatic splenosis mimics hepatocellular carcinoma in a patient with chronic hepatitis B: A case report and literature review.
Splenosis is a benign and relatively uncommon condition caused by trauma or splenectomy or other procedures involving splenic tissue. It is usually asymptomatic, and often diagnosed accidentally, especially misdiagnosed as malignant tumor. A 54-year-old man with prior history of chronic hepatitis B virus infection and underwent splenectomy for traumatic splenic rupture following a traffic accident 23 years previously was admitted to our hospital and found a hepatic mass in the right upper quadrant during an imaging examination. The diagnosis of his was not clear and finally he agreed to receive a surgical treatment. During the operation, we found a mass in the right posterior lobe of the liver and a hard nodule on the right side of the diaphragm, both were completely resected, and postoperative histopathologic examination revealed that all excised tissues were proved to have histological structure typical for the spleen. The occurrence of intrahepatic splenosis is rare with only few cases previously reported in the literature. It is a benign disease and sometimes difficult to distinguish from diseases of the liver. The need for positive surgical resection of splenosis is still controversial.


Characterization of peritoneal transport in patients with failed renal allografts receiving CAPD.
Many patients with failed renal transplants elect to receive continuous ambulatory peritoneal dialysis (CAPD) as their modality of dialysis. For others, cardiovascular considerations or access difficulties make CAPD a necessary option when these patients return to dialysis. It is unclear what effects renal transplantation, chronic immunosuppressive therapy and graft rejection might have on the integrity of the peritoneal membrane. We report on thirteen patients receiving CAPD who had peritoneal equilibration test (PET) studies after a failed renal transplant. Three of these patients had studies done pre and post transplantation. Our solute equilibration studies demonstrated that for 10 patients studied with the older 4.25% technique the mean post transplantation D/P creatinine was 0.688 (SE:0.039) on the border of high and low average, and the mean D/Do glucose was 0.228 (SE:0.024) in the high transporter range. Three patients tested pre and post transplantation (upon their return to CAPD after graft failure) had no change in these values. From the above data, 13 patients with peritoneal equilibration testing post transplantation have well-functioning peritoneal membranes allowing for adequate dialysis and flexibility in dialysis prescription. We conclude that renal transplantation does not adversely affect peritoneal membrane function if these patients return to CAPD after graft failure.


Docetaxel in prostate cancer: a familiar face as the new standard in a hormone-sensitive setting.
The increasing knowledge of prostate cancer is leading to many questions about its natural history and to reconsider conventional therapeutic strategies. Androgen ablation therapy has been the standard therapy in the advanced setting. Although docetaxel has demonstrated increased survival in patients with metastatic prostate cancer who had progressed to hormone treatments, due to its potential toxicity the role of chemotherapy has been relegated to patients who were symptomatic or who had high tumor burden. Several studies have assessed whether docetaxel could have a role in hormone-sensitive disease or even in earlier stages with no distant metastases. In the CHAARTED and STAMPEDE studies, docetaxel provides an unprecedented increase in overall survival (OS). This review summarizes the evidence behind the paradigm shift to strengthening docetaxel as a new standard of treatment that prolongs survival in earlier stages of prostate cancer.


Data analytics identify glycated haemoglobin co-markers for type 2 diabetes mellitus diagnosis.
Glycated haemoglobin (HbA1c) is being more commonly used as an alternative test for the identification of type 2 diabetes mellitus (T2DM) or to add to fasting blood glucose level and oral glucose tolerance test results, because it is easily obtained using point-of-care technology and represents long-term blood sugar levels. HbA1c cut-off values of 6.5% or above have been recommended for clinical use based on the presence of diabetic comorbidities from population studies. However, outcomes of large trials with a HbA1c of 6.5% as a cut-off have been inconsistent for a diagnosis of T2DM. This suggests that a HbA1c cut-off of 6.5% as a single marker may not be sensitive enough or be too simple and miss individuals at risk or with already overt, undiagnosed diabetes. In this study, data mining algorithms have been applied on a large clinical dataset to identify an optimal cut-off value for HbA1c and to identify whether additional biomarkers can be used together with HbA1c to enhance diagnostic accuracy of T2DM. T2DM classification accuracy increased if 8-hydroxy-2-deoxyguanosine (8-OhdG), an oxidative stress marker, was included in the algorithm from 78.71% for HbA1c at 6.5% to 86.64%. A similar result was obtained when interleukin-6 (IL-6) was included (accuracy=85.63%) but with a lower optimal HbA1c range between 5.73 and 6.22%. The application of data analytics to medical records from the Diabetes Screening programme demonstrates that data analytics, combined with large clinical datasets can be used to identify clinically appropriate cut-off values and identify novel biomarkers that when included improve the accuracy of T2DM diagnosis even when HbA1c levels are below or equal to the current cut-off of 6.5%.


Drosophila rasiRNA pathway mutations disrupt embryonic axis specification through activation of an ATR/Chk2 DNA damage response.
Small repeat-associated siRNAs (rasiRNAs) mediate silencing of retrotransposons and the Stellate locus. Mutations in the Drosophila rasiRNA pathway genes armitage and aubergine disrupt embryonic axis specification, triggering defects in microtubule polarization as well as asymmetric localization of mRNA and protein determinants in the developing oocyte. Mutations in the ATR/Chk2 DNA damage signal transduction pathway dramatically suppress these axis specification defects, but do not restore retrotransposon or Stellate silencing. Furthermore, rasiRNA pathway mutations lead to germline-specific accumulation of gamma-H2Av foci characteristic of DNA damage. We conclude that rasiRNA-based gene silencing is not required for axis specification, and that the critical developmental function for this pathway is to suppress DNA damage signaling in the germline.


Childhood leprosy in eastern Nepal: a hospital-based study.
A hospital-based retrospective study on childhood leprosy was carried out at B.R. Koirala Institute of Health Sciences, Dharan, covering the period April 1998-April 2002. 20 (4.45%) leprosy patients were detected in children aged 6-14 years. The male:female ratio was 4:1. History of contact was found in 10% of the patients. The commonest type of leprosy was borderline tuberculoid leprosy (550%), followed by borderline lepromatous leprosy (301%). Most of the patients had more than one lesion. Nerve involvement and grade 2 deformity were noted in 55% and 20% of the patients respectively. Slit skin smear was positive in 30% of patients.


Enlargement of laser iridotomies over time.
We reviewed the photographs of our patients who have undergone laser iridotomies since 1975. We were able to examine photographs of 21 eyes of 13 patients to determine whether their iridotomies had enlarged over time. We detected an appreciable increase in the size of the iridotomy in seven of the 21. We attempted to determine whether there was any relation between an increase in iridotomy size and several ocular as well as systemic factors, but no such relations could be identified.


Magnetic resonance imaging in foetuses with bilateral moderate ventriculomegaly and suspected anomaly of the corpus callosum on ultrasound scan.
The diagnosis of anomalies of the corpus callosum (ACC) in foetuses with bilateral moderate ventriculomegaly (BMV) is difficult by means of ultrasound scan. The aim of this study was to examine the value of the additional investigation with magnetic resonance imaging (MRI) in foetuses with BMV and suspected ACC on ultrasound scan. Pathogenesis and clinical presentation of BMV and ACC are discussed. 41 foetuses with central nervous system (CNS) anomalies on ultrasound scan were assessed by ultrasonography and MRI from 1999 to 2001. Eight of these 41 foetuses presented with BMV and suspected ACC on ultrasound scan and were prospectively included in the study. Foetal investigations with sonography and MRI were analysed with regard to diagnostic confidence; results were correlated with post partum findings. Six of these 41 foetuses presented with BMV without suspected ACC on ultrasound scan and were retrospectively analysed. Ultrasonography suspected ACC in 8 foetuses with BMV. MRI confirmed the presence of ACC in 4 of these 8 cases. MRI additionally showed ACC in two of the six retrospectively analysed foetuses with BMV without suspected ACC on ultrasound scan. Prenatal MRI diagnosis was confirmed after delivery in all cases. MRI is more sensitive than ultrasonography in the evaluation of ACC in foetuses with BMV. For prenatal screening ultrasound still remains the investigation of choice.


Microgravity protein crystallization.
Over the past 20 years a variety of technological advances in X-ray crystallography have shortened the time required to determine the structures of large macromolecules (i.e., proteins and nucleic acids) from several years to several weeks or days. However, one of the remaining challenges is the ability to produce diffraction-quality crystals suitable for a detailed structural analysis. Although the development of automated crystallization systems combined with protein engineering (site-directed mutagenesis to enhance protein solubility and crystallization) have improved crystallization success rates, there remain hundreds of proteins that either cannot be crystallized or yield crystals of insufficient quality to support X-ray structure determination. In an attempt to address this bottleneck, an international group of scientists has explored use of a microgravity environment to crystallize macromolecules. This paper summarizes the history of this international initiative along with a description of some of the flight hardware systems and crystallization results.


Locate the Lesion: A Project-Based Learning Case that Stimulates Comprehension and Application of Neuroanatomy.
A fictitious patient, Mr. Challenge, is admitted to the emergency room and displays symptoms consistent with damage to the central nervous system. In this problem-based learning case, students are challenged to determine the location of a lesion that is consistent with Mr. Challenge's symptoms. Students discover details about Mr. Challenge's symptoms while exploring three anatomical pathways: corticospinal tract, spinothalamic tract and medial lemniscal pathway. Students make predictions as to which of these pathways may be damaged in Mr. Challenge and defend their predictions based on their research of the function and anatomical location of these tracts. This ultimately leads the student to identifying a single lesion site that can account for Mr. Challenge's symptoms. This case is executed in an undergraduate neuroscience course and would be useful in anatomy and physiology course, as well as other courses that serve students interested in health science related careers.


A Finite Element Investigation on Material and Design Parameters of Ventricular Septal Defect Occluder Devices.
Ventricular septal defects (VSDs) are the most common form of congenital heart defects. The incidence of VSD accounts for 40% of all congenital heart defects (CHDs). With the development of interventional therapy technology, transcatheter VSD closure was introduced as an alternative to open heart surgery. Clinical trials of VSD occluders have yielded promising results, and with the development of new material technologies, biodegradable materials have been introduced into the application of occluders. At present, the research on the mechanical properties of occluders is focused on experimental and clinical trials, and numerical simulation is still a considerable challenge due to the braided nature of the VSD occluder. Finite element analysis (FEA) has proven to be a valid and efficient method to virtually investigate and optimize the mechanical behavior of minimally invasive devices. The objective of this study is to explore the axial resistive performance through experimental and computational testing, and to present the systematic evaluation of the effect of various material and braid parameters by FEA. In this study, an experimental test was used to investigate the axial resistive force (ARF) of VSD Nitinol occluders under axial displacement loading (ADL), then the corresponding numerical simulation was developed and compared with the experimental results to verify the effectiveness. Based on the above validation, numerical simulations of VSD occluders with different materials (polydioxanone (PDO) and Nitinol with different austenite moduli) and braid parameters (wire density, wire diameter, and angle between left and right discs) provided a clear presentation of mechanical behaviors that included the maximal axial resistive force (MARF), maximal axial displacement (MAD) and initial axial stiffness (IAS), the stress distribution and the maximum principal strain distribution of the device under ADL. The results showed that: (1) In the experimental testing, the axial resistive force (ARF) of the tested occluder, caused by axial displacement loading (ADL), was recorded and it increased linearly from 0 to 4.91 N before reducing. Subsequent computational testing showed that a similar performance in the ARF was experienced, albeit that the peak value of ARF was smaller. (2) The investigated design parameters of wire density, wire diameter and the angle between the left and right discs demonstrated an effective improvement (7.59%, 9.48%, 1.28%, respectively, for MARF, and 1.28%, 1.80%, 3.07%, respectively, for IAS) for the mechanical performance for Nitinol occluders. (3) The most influencing factor was the material; the performance rose by 30% as the Nitinol austenite modulus (EA) increased by 10,000 MPa. The performance of Nitinol was better than that of PDO for certain wire diameters, and the performance improved more obviously (1.80% for Nitinol and 0.64% for PDO in IAS, 9.48% for Nitinol and 2.00% for PDO in MARF) with the increase in wire diameter. (4) For all of the models, the maximum stresses under ADL were distributed at the edge of the disc on the loaded side of the occluders. The experimental testing presented in the study showed that the mechanical performance of the Nitinol occluder and the MARF prove that it has sufficient ability to resist falling out from its intended placement. This study also represents the first experimentally validated computational model of braided occluders, and provides a perception of the influence of geometrical and material parameters in these systems. The results could further provide meaningful suggestions for the design of biodegradable VSD closure devices and to realize a series of applications for biodegradable materials in VSD.


Coping Flexibility and Alcohol-Related Outcomes: Examining Coping Motives as Mediators.
Background: Coping has been implicated in the etiology and treatment of problem drinking. Traditional, static measurement of coping styles (e.g., approach, avoidance, social support) may fail to capture how adaptive a given coping style may be. Coping flexibility is an emerging construct, associated with psychological health, and one that may shed light on coping's role in drinking risk. Coping flexibility includes (1) discontinuation of an ineffective coping strategy ("Discontinuation") and (2) production of an alternative strategy ("Implementation"). This study is the first to our knowledge to examine its association to drinking outcomes. Further, because coping deficits are theorized to lead to drinking through coping motives, we also examined mediated pathways from coping flexibility to alcohol outcomes via coping motives. Methods: College students (N = 528) completed an online assessment. Data were analyzed using path analysis. Control variables included sex and coping styles. Results: In path analytic models, Implementation was negatively associated with alcohol use and, indirectly via coping motives, negatively associated with alcohol consequences. The direct effect on alcohol use remained when controlling for coping styles and sex, but the mediational pathway was no longer significant. Conclusions: This study provides some evidence for the protective role of coping flexibility in alcohol use behavior, which may have implications for how best to address coping skills in alcohol interventions. The direct effect of Implementation on drinking suggests that there may be utility in teaching clients a flexible approach to coping in treatment. Replication, particularly with longitudinal designs, is needed.


Ready biodegradability of trifluoromethylated phenothiazine drugs, structural elucidation of their aquatic transformation products, and identification of environmental risks studied by LC-MS( n ) and QSAR.
The environmental fate of transformation products from organic pollutants such as drugs has become a new research area of increasing interest over the last few years. Whereas in the past mainly parent compounds or their major human metabolites were studied, new questions have arisen what compounds could be formed during incomplete degradation in the aquatic environment and what effects the resulting transformation products might have on nature and mankind. Psychiatric drugs are among the most important prescription drugs worldwide, but so far only little data is provided upon their degradation behavior. This especially accounts for tricyclic antipsychotic drugs of the phenothiazine class. Therefore, the degradation of such drugs was investigated in this study. In this study the aerobic Closed Bottle test (The Organisation for Economic Co-operation and Development (OECD) 301D) was used to assess the ready biodegradability of three trifluoromethylated phenothiazine drugs: fluphenazine, triflupromazine, and trifluoperazine. As it is known from literature that phenothiazine drugs can easily form various photolytic transformation products under light exposure, photochemical transformation was also investigated. Since transformation products are usually not available commercially, the calculation of environmental parameters with the aid of quantitative structure activity relationship (QSAR) software was used for first evaluation of these compounds. According to the OECD test guideline, all trifluoromethylated phenothiazines had to be classified as not readily biodegradable. Chromatographic data revealed the formation of some transformation products. Comparing retention time and mass spectrometric data with the analytical results of the light exposure experiments, we found peaks with the same retention time and mass spectra. So these transformation products were not of bacterial, but photolytic, origin and are formed very quickly even under low light doses. A special chromatographic column and solvent gradient along with multiple stage mass spectrometric fragmentation experiments uncovered the presence of, in total, nine photolytic transformation products and allowed for their structural elucidation. Typical modifications of the molecules were sulfoxidation, exocyclic N-oxidation, and transformation of the trifluoromethyl to a carboxylic moiety. The obtained results of the QSAR calculations show that all transformation products are highly mobile in the aquatic environment and elimination through biotic or abiotic pathways cannot be expected. Transformation products of trifluoromethylated phenothiazine drugs have to be expected in the aquatic environment, yet nothing is known about their toxicological properties. Therefore, further risk assessment upon these drugs and their fate is strongly recommended.


The use of R-roscovitine to fit the 'time frame' on in vitro porcine embryo production by intracytoplasmic sperm injection.
Micromanipulation of oocytes is time consuming during ICSI experiments; however the 'time frame' to manipulate oocytes without a drop in efficiency is not very wide due to the use of not completely matured and/or aged MII oocytes. Therefore, the aim of this work was to study the effect of a short roscovitine pretreatment for 5 h and two different IVM periods (5R + 40IVM or 5R + 45IVM) and a prolonged IVM time from 45 h (45IVM) to 50 h (50IVM) on parthenogenetic and ICSI embryo development, in order to fit the time frame to manipulate pig oocytes to the whole labour day session. In the first experiment, oocytes, pretreated with roscovitine and IVM cultured for 5 h, showed a similar nuclear stage as non-cultured oocytes and a significantly higher percentage of GVI-GVII oocytes compared with non-roscovitine treated oocytes cultured for 5 h in IVM conditions. When COC were cultured under the 5R + 40IVM system, nuclear maturation and cleavage rates after electrical activation were significantly lower than when COC were cultured under the 45IVM, 50IVM and 5R + 45IVM culture systems (54.2% vs. 72.6-76.8% and 58.8% vs. 81.4-88.3%, respectively). However, this difference was not statistically significant for parthenogenote blastocyst rate. No differences were observed in MII and in parthenogenote and ICSI embryo development among 45IVM, 50IVM and 5R + 45IVM experimental groups. In conclusion, under our conditions and using parthenogenetic and ICSI embryos, we observed that it is feasible to prolong the pig oocyte manipulation 'time frame' by at least 5 h with no significant drop in blastocyst rate.


Initial investigation of the effects of an experimentally learned schema on spatial associative memory in humans.
Networks of interconnected neocortical representations of prior knowledge, "schemas," facilitate memory for congruent information. This facilitation is thought to be mediated by augmented encoding and accelerated consolidation. However, it is less clear how schema affects retrieval. Rodent and human studies to date suggest that schema-related memories are differently retrieved. However, these studies differ substantially as most human studies implement pre-experimental world-knowledge as schemas and tested item or nonspatial associative memory, whereas animal studies have used intraexperimental schemas based on item-location associations within a complex spatial layout that, in humans, could engage more strategic retrieval processes. Here, we developed a paradigm conceptually linked to rodent studies to examine the effects of an experimentally learned spatial associative schema on learning and retrieval of new object-location associations and to investigate the neural mechanisms underlying schema-related retrieval. Extending previous findings, we show that retrieval of schema-defining associations is related to activity along anterior and posterior midline structures and angular gyrus. The existence of such spatial associative schema resulted in more accurate learning and retrieval of new, related associations, and increased time allocated to retrieve these associations. This retrieval was associated with right dorsolateral prefrontal and lateral parietal activity, as well as interactions between the right dorsolateral prefrontal cortex and medial and lateral parietal regions, and between the medial prefrontal cortex and posterior midline regions, supporting the hypothesis that retrieval of new, schema-related object-location associations in humans also involves augmented monitoring and systematic search processes.


Chitosan-Based Biomaterials for Hemostatic Applications: A Review of Recent Advances.
Hemorrhage is a detrimental event present in traumatic injury, surgery, and disorders of bleeding that can become life-threatening if not properly managed. Moreover, uncontrolled bleeding can complicate surgical interventions, altering the outcome of surgical procedures. Therefore, to reduce the risk of complications and decrease the risk of morbidity and mortality associated with hemorrhage, it is necessary to use an effective hemostatic agent that ensures the immediate control of bleeding. In recent years, there have been increasingly rapid advances in developing a novel generation of biomaterials with hemostatic properties. Nowadays, a wide array of topical hemostatic agents is available, including chitosan-based biomaterials that have shown outstanding properties such as antibacterial, antifungal, hemostatic, and analgesic activity in addition to their biocompatibility, biodegradability, and wound-healing effects. This review provides an analysis of chitosan-based hemostatic biomaterials and discusses the progress made in their performance, mechanism of action, efficacy, cost, and safety in recent years.


[Expression of IFN-alpha/beta receptor in the PBMCs and liver of patients with hepatitis B and its clinical significance].
To explore the role of interferon (IFN)-alpha/beta receptor beta subunit (IFNAR2) in the patients' response to IFN-alpha therapy as influenced by the grade of chronic hepatic inflammation, and understand the relation of IFNAR2 expression in the peripheral blood mononuclear cells (PBMCs) with HBV infection. Liver tissue specimens were obtained from 21 patients with chronic hepatitis B for examination of the hepatic inflammation, and PBMCs were isolated from another 16 patients with chronic hepatitis B and 15 health control subjects. Both the hepatic tissues and PBMCs were examined for IFNAR2 expression using immunohistochemistry. The 21 patients with chronic hepatitis B were divided into 3 groups according to the severity of hepatic inflammation, namely G(1) (n=3), G(2) (n=7) and G(3) (n=11) groups. The patients in G(3) group showed had significantly higher IFNAR2 expressions in liver (25.1307-/+7.0700) than those of the G(1) (5.6913-/+1.8422) and G(2) (7.4706-/+5.3572) groups (P=0.000). The IFNAR2 levels in the PBMCs, however, did not show significant difference between patients with chronic hepatitis B and the healthy control subjects. In patients with chronic hepatitis B, IFNAR2 expression level is positively correlated to the severity of hepatic inflammation, and increased IFNAR2 expression in severe hepatic inflammation is therefore likely to result in increased response rate to INF-alpha therapy. The expression of IFNAR2 in the PBMCs is not associated with HBV infection.


Assessing Quality of Life among Radiation-Induced Hypopituitary Patients.
Introduction Radiation-induced hypopituitarism (RIH) has long been recognized as one of the deleterious side effects of skull base radiation. This study aims to assess the quality of life (QoL) among patients with RIH compared with radiated patients who did not develop hypopituitarism using the validated Anterior Skull Base Questionnaire (ASBQ). Methods This was a single-institution retrospective cohort study. Included patients had a history of anterior skull base tumor, underwent at least one round of radiation to the skull base, and had filled out at least one ASBQ survey after their radiation treatment. Three statistical models were used to determine the effect of hypopituitarism and treatment on QoL scores. Results A total of 145 patients met inclusion criteria, and 330 ASBQ surveys were analyzed. Thirty-five percent (51/145) had evidence of RIH at some point after their radiation treatment. Those with hypopituitarism had significantly lower overall ASBQ scores across all three models even after adjusting for potential confounders and intraperson correlation (average decrease of 0.24-0.45 on a 5-point Likert scale; p -values ranging from 0.0004 to 0.018). The increase in QoL with hormonal replacement was modulated by time out from radiation, with long-term survivors (5+ years out from radiation) gaining the most benefit from treatment (increase of 0.89 on a 5-point Likert scale, p 0.0412), especially in the vitality domain. Conclusion This data demonstrates that hypopituitarism is an independent predictor of lower QoL. Early detection and appropriate treatment are essential to avoid the negative impact of hypopituitarism on QoL.


Chlorophyllin supplementation modulates hyperglycemia-induced oxidative stress and apoptosis in liver of streptozotocin-administered mice.
Chlorophyllin is a water-soluble mixture of sodium-copper salts of chlorophyll with antioxidant and antimutagen properties. In this study, an attempt has been made to evaluate the effect of chlorophyllin on hyperglycemia-induced oxidative stress and apoptosis in liver of streptozotocin (STZ)-administered mice. In STZ-induced diabetes, two causative factors for pancreatic β-cell deaths are DNA alkylation and profound reactive oxygen species (ROS) generation. In this study, chlorophyllin treatment was found to be able to modulate oxidative stress and apoptosis in liver of diabetic mice. Diabetic mice exhibited a significant reduction of ROS, malondialdehyde (MDA), and protein carbonyl levels upon treatment with the chlorophyllin. However, antioxidant enzymes, such as copper-zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD), and catalase (CAT) showed enhanced activity as well as expression in chlorophyllin-administered diabetic mice. The hepatoprotective effect of chlorophyllin was confirmed from the decreased activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). The histological and ultrastructural studies revealed the ability of chlorophyllin to restore morphological and cellular alterations as observed in STZ-induced diabetic mice. The effect of chlorophyllin on apoptosis showed the downregulation of cysteine-dependent aspartate-specific protease (caspase) 3 and caspase 9, whereas upregulation of B-cell lymphoma-2 (Bcl-2) protein, and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) assay demonstrated a few apoptotic cells. In conclusion, it can be stated that chlorophyllin treatment can exert hepatoprotective effect via modulating hyperglycemia-induced oxidative stress and apoptosis in STZ-administered diabetic mice. © 2018 BioFactors, 44(5):418-430, 2018.


Drinking and smoking patterns amongst women attending an antenatal clinic--II. During pregnancy.
This paper describes smoking and drinking patterns during pregnancy amongst a cohort of 2266 women who enrolled at a London antenatal clinic 1982-1983. Only 12% of mothers were non-drinkers before pregnancy, but 44% abstained in the first trimester, 38% in the second and 50% in the third. Before pregnancy 20% of mothers were drinking more than the recommended 10 units of alcohol per week. This dropped to 6% during pregnancy. Mean consumption at each of the three stages of pregnancy was highest amongst those mothers who were the heaviest drinkers before pregnancy. The heaviest pre-pregnancy drinkers were also the least likely to abstain at any point in pregnancy. Of those mothers who were drinking less than 10 units of alcohol per week before pregnancy, 3% increased during pregnancy. Wine was the most popular beverage choice but heavier drinkers were more likely to drink beers and spirits in addition. Before pregnancy 29% of mothers smoked. This dropped to 23% in pregnancy. Consumption levels fell amongst those who continued smoking. The heaviest pre-pregnancy smokers were the most likely to reduce but the least likely to stop. Smoking was positively associated with the level of both pre-pregnancy and pregnancy drinking. The most commonly cited reasons for changes in drinking and smoking habits in pregnancy were concern for the child, concern for self or concern for both. Feeling sick or ill was a more commonly stated reason for reduction of drinking than smoking. Social pressures were important in reducing smoking, but the mass media were quoted as a more important influence in reducing drinking. Mothers who drank more than 10 units of alcohol per week during pregnancy were more likely to be older, of higher social status and primiparous. In contrast those who smoked in pregnancy were more likely to be younger, of lower social status and multiparous. This has important implications for planning antenatal health education.


Direct spectroscopic evidence of hyperconjugation unveils the conformational landscape of hydrazides.
The stereochemistry of hydrazides makes them especially interesting as building blocks for molecular design. An exhaustive conformational analysis of three model hydrazides was conducted in a conformer-selective approach by using a combination of high-level quantum chemistry calculations and vibrational spectroscopy in the gas phase and in solution. The NH stretch frequency was found to be highly sensitive to hyperconjugation, thus making it an efficient probe of the conformation of the neighboring nitrogen atom. This property greatly assisted the identification of the isomers observed experimentally in the conformer pool. A rationalization of the hydrazide conformational landscape is proposed, therefore paving the way for a better characterization of secondary structures in larger systems.


Involvement of Lipids in Alzheimer's Disease Pathology and Potential Therapies.
Lipids constitute the bulk of the dry mass of the brain and have been associated with healthy function as well as the most common pathological conditions of the brain. Demographic factors, genetics, and lifestyles are the major factors that influence lipid metabolism and are also the key components of lipid disruption in Alzheimer's disease (AD). Additionally, the most common genetic risk factor of AD, APOE ϵ4 genotype, is involved in lipid transport and metabolism. We propose that lipids are at the center of Alzheimer's disease pathology based on their involvement in the blood-brain barrier function, amyloid precursor protein (APP) processing, myelination, membrane remodeling, receptor signaling, inflammation, oxidation, and energy balance. Under healthy conditions, lipid homeostasis bestows a balanced cellular environment that enables the proper functioning of brain cells. However, under pathological conditions, dyshomeostasis of brain lipid composition can result in disturbed BBB, abnormal processing of APP, dysfunction in endocytosis/exocytosis/autophagocytosis, altered myelination, disturbed signaling, unbalanced energy metabolism, and enhanced inflammation. These lipid disturbances may contribute to abnormalities in brain function that are the hallmark of AD. The wide variance of lipid disturbances associated with brain function suggest that AD pathology may present as a complex interaction between several metabolic pathways that are augmented by risk factors such as age, genetics, and lifestyles. Herewith, we examine factors that influence brain lipid composition, review the association of lipids with all known facets of AD pathology, and offer pointers for potential therapies that target lipid pathways.


[Mild brain injury: forensic sciences and indemnification].
Victims of mild trauma brain injury may develop post-concussive symptoms in an inverse proportion to the organic damages leading to difficulties in their social, occupational and family activities. Proving the link which exists between the trauma and its consequences is a difficult task and insufficient methods for evaluating post-concussive symptoms make it very difficult to demonstrate the cause and effect relationship. The judge's assessment is essential to avoid the nearly systematic but wrong diagnosis of pathological predispositions of the patient. It is particularly important to improve the nomenclature of the different kinds of injuries to reach a better indemnification for those patients who suffer from their trauma their entire life.


Hepatitis B and breastfeeding in Hangzhou, Zhejiang Province, People's Republic of China.
This study examined infant feeding methods in hepatitis B-positive mothers in Zhejiang Province, People's Republic of China. A cohort study was undertaken in Hangzhou in Zhejiang Province. A sample of 638 mothers was recruited at birth from the city of Hangzhou and was followed up until their infants were 6 months of age. Chronic hepatitis B is a continuing public health issue in pregnant women. Breastfeeding is the foundation of infant nutrition, sets the scene for lifetime health, and is important for all mothers. In the Hangzhou cohort of 638 mothers, 38 were identified as hepatitis B positive, a rate of 6.0%. All of the infants of the hepatitis B-positive mothers were fed on formula immediately after birth while their breastmilk was tested for virus transmission and their infants were vaccinated. At 1 month of age 61.8% of the hepatitis B-positive mothers were breastfeeding compared to 92% of the remainder of the cohort. The rates at 3 months were 60.6% and 89% and at 6 months were 45.5% and 64%, respectively. The hazard ratio for hepatitis B-positive mothers discontinuing breastfeeding before 6 months was 3.69 (95% confidence interval, 2.28, 5.98). The World Health Organization recommends that all mothers who are hepatitis B positive breastfeed their infants and that their infants be immunized at birth. In this study breastfeeding rates of hepatitis B-positive mothers were substantially less than those of the other mothers.


Expression of CXCR3 on Adaptive and Innate Immune Cells Contributes Oviduct Pathology throughout Chlamydia muridarum Infection.
CXCR3 is a chemokine receptor expressed on a wide range of leukocytes, and it is involved in leukocyte migration throughout the blood and lymphatics. Specifically, CXCR3 is required for lymphocyte homing to the genital mucosa. When compared to wild type (WT) mice, CXCR3 deficiency (CXCR3-/-) mice infected with Chlamydia muridarum (C. muridarum) did not display impaired clearance and resolution of infection. However, they possessed significantly higher bacterial burden and lower levels of IFN-γ-producing TH1 cells. The knockouts also demonstrated a significant decrease in the level of activated conventional dendritic cells in the GT, ultimately leading to the decrease in activated TH1 cells. In addition, few activated plasmacytoid dendritic cells, which possess an inflammatory phenotype, were found in the lymph node of infected mice. This reduction in pDCs may be responsible for the decrease in neutrophils, which are acute inflammatory cells, in the CXCR3-/- mice. Due to the significantly reduced level of acute inflammation, these mice also possess a decrease in dilation and pathology in the oviduct. This demonstrates that the CXCR3-/- mice possess the ability to clear C. muridarum infections, but they do so without the increased inflammation and pathology in the GT.


Ocular surface microbiome in meibomian gland dysfunction.
To investigate the ocular microbiome in meibomian gland dysfunction in Auckland, New Zealand. Prospective, cross-sectional, observational, university-based study. Participants resident in New Zealand for ≥2 years (n = 157) were classified as normal (n = 66), mild (n = 41) or moderate-to-severe meibomian gland dysfunction (n = 50). Contact lens wear and anterior blepharitis status were recorded, as well as symptoms and clinical features. Bacteria collected from lid margin swabs, before and after gland expression, were isolated and identified by conventional microbiological culture techniques. Aerobic isolates were identified in all 157 participants, and both aerobic and anaerobic bacteria isolated in a subset of 87 subjects. Bacterial incidence according to meibomian gland dysfunction status RESULTS: Symptoms, bulbar hyperaemia, conjunctival staining, lipid layer grade and tear film stability, but not corneal staining, showed moderate association with meibomian gland dysfunction severity. Participants with and without meibomian gland dysfunction showed a similar microbiome, unaffected by gland expression. Anterior blepharitis, a common co-morbidity, was not an independent predictor of the microbiome. Sterile cultures were more common in contact lens wearers than non-wearers. The incidence of Staphylococcus aureus was higher than anticipated across all severity groups, and that of coagulase-negative Staphylococcus, Corynebacterium and streptococci was lower. Modest differences in relative proportions of bacteria compared with other studies support climatic variations in the ocular surface microbiome. Similarity in microbiome profile, irrespective of meibomian gland dysfunction severity, anterior blepharitis presence or contact lens wear, suggests potential for commonality in treatment.


Social factors, allergen, endotoxin, and dust mass in mattress.
Indoor environment has been associated with allergic disease. Further, it has been observed that the prevalences of allergic sensitization are different in different social groups. We therefore investigated the association between socioeconomic status (SES) and indoor bio-contaminants. House dust samples were collected from parents' and infants' mattress from 2166 families in Munich (62.2%) and Leipzig (37.8%), Germany. Major mite allergen Der p 1 and Der f 1, cat allergen Fel d 1, and endotoxin were extracted and quantified. Parental educational level and family equivalent income were used independently as socioeconomic indicators. Indoor endotoxin, mite allergen Der p 1, and the amount of sampled dust were not associated with the social factors. Mite allergen Der f 1 was slightly associated by family SES but without a consistent pattern. In families who are not cat owners, however, a negative association between the amount of cat allergen and family SES were observed. The observed negative association between cat allergen loads and concentrations in mattress and family SES in non-cat owners' homes indicated that community is an important source of cat allergen exposure. The study indicated that community is a major source of cat allergen exposure especially in communities of low SES.


Acromioclavicular joint disorders.
The acromioclavicular (AC) joint is a highly used, versatile, and complex joint that provides stability and increases function. Acute and chronic dysfunction at the AC joint can have debilitating effects that should be treated appropriately and expediently to preserve function. The historical, physical examination, and radiographic findings are generally very consistent and lead to both diagnosis and well-established treatment protocols. With few exceptions, injuries can be treated nonoperatively with a high degree of success. When indicated, surgical outcomes are also successful but have an overall higher rate of complications. A physician should be well versed in both acute and chronic conditions to ensure the patient has the best opportunity to reclaim function, return to sport, and avoid pain, restriction in range of motion, and need for further surgery.


Treatment of non-union of the forearm using distraction-compression osteogenesis.
The goal of the study is presentation broad abilities like gives Ilizarov method in the treatment of posttraumatic nonunion the of forearm with concomitant shortening and axis deformity, in minimally invasive technique, with contemporary axis correction and lengthening . . Authors present 6 patient operated on with the use of Ilizarov method, in years 2001-2005 , suffer from vital nonunion of the forearm - 6 cases radius; 1 case ulna and radius. In all cases with nonunion concomitant shortening of the radius from 2 to 3 cm and valgosity of radius with deformity in sagittal plane in 4 patients (2antecurvation, 2 retrocurvation). All patients had restricted rotation ROM of forearm and restriction of wrist motion . Author's modification of Ilizarov apparatus (with mini-Schanz's half-pins, which permitted rotation of forearm) was used in most of patients. In 3 cases monofocal slow correction with lengthening within nonunion was performed. In 2 cases bifocal, one-step slow correction of deformity and compression within nonunion with lengthening was performed. In 1 remaining case compression of ulna nonunion and compression with deformity correction of radius nonunion were performed. Distraction and correction start in 7 postoperative day in rate from 0,25 to 1 mm/day and correspondingly from1 to 2o/day. Time of correction and distraction was average 63,3 days (40 - 90 days) . Total time of stabilization was average 25,4 weeks (20 - 35 weeks). Bone union was obtained in all patients. In all cases considerable recovery of limb function was achieved. All patients had superficial pin-tract infection . One patient had staphylococcal pin-tract infection of soft tissues, which retreat after 3-weeks guided antibiotic therapy. The Ilizarov method permit for contemporary axis correction and/or distraction or compression. There is the method of choice in the treatment of nonunion of forearm with concomitant shortening and axis deformity.


Haemophagocytosis in typhoid fever.
This report deals with a young man who developed features of haemophogocytosis during the course of typhoid fever. The pertinent clinical and laboratory features of typhoid-associated haemophagocytosis are discussed. The need for blood component replacement therapy in addition to specific anti-microbials to treat haemophagocytosis complicating typhoid fever is stressed.


A photo-stable chalcogenide glass.
Photo-darkening and photo-bleaching are well known phenomena in As-Se and Ge-Se chalcogenide glasses, respectively. Consequently, a systematic dependence of photo-induced optical changes in Ge(x)As(45-x)Se(55) glass series on x is expected between these two extremes. This prediction of photosensitivity on Ge/As ratio has been exploited to demonstrate the first intrinsically photo-stable chalcogenide glass at x approximately 10, which would be suitable for fabricating photo-insensitive optical components for various applications.


Enhancement of water solubility and mobility of phenanthrene by natural soil nanoparticles.
Nanoparticles (NPs) in soils may participate in essential ecological services, since they have special characteristics arising from their nanoscale sizes and large surface areas. We did aqueous solubility enhancement experiments to derive the partition coefficients of phenanthrene between water and six natural soil NPs. The coefficients were approximately exponentially reduced with increasing concentrations of NPs, low concentrations of NPs (50 mg L(-1)) had significant high adsorption capacities for phenanthrene. Further experiments based on dynamic light scattering technique and column tests were performed to examine the aggregation and mobility of soil NPs and how they influence phenanthrene mobility in porous media. NPs have high and reversible adsorption on surfaces of porous media with aggregation taking place during their transport and they largely control the mobility of phenanthrene in sand columns.


Color duplex sonography in post-therapeutic neck evaluation.
Assessment of the clinical utility of color duplex sonography for post-therapeutic evaluation of the neck. Eighty neck sides were evaluated in a prospective nonrandomized study during the post-therapeutic course. Of these, 74 previously had undergone surgery, and 60 subsequently had additional radiotherapy. The diagnostic procedures applied were clinical examination, computed tomography, positron emission tomography, and color duplex sonography. The mean observation period was 18.6 months. Seven of 80 (8.75%) neck sides exhibited recurrent disease, and 76.2% of the lymph nodes resected during the postoperative observation period showed malignancy. Color duplex echography could detect all lymph nodes. Sensitivity was 100%, and the specificity was 95.8%. The sensitivity and specificity of computed tomography and positron emission tomography were found to be 85.7% and 97.2%, respectively. Palpation had a sufficient specificity (95.8%) but only a very poor 14.2% sensitivity in the post-therapeutic neck. In complex tissue alterations of the post-therapeutic neck, color duplex echography is a highly sensitive and easily applied diagnostic procedure for the detection of recurrent disease. It allows a high-resolution depiction of intranodal vascularization and adjacent structures. Problems may occur in the evaluation of vessels in nodes with a diameter of 6 millimeters and below. This may impair specificity in some cases.


Solvent effects on isotactic poly(methyl methacrylate) crystallization and syndiotactic poly(methacrylic acid) incorporation in porous thin films prepared by stepwise stereocomplex assembly.
The solvent effects on the crystallization of porous isotactic (it) poly(methyl methacrylate) (PMMA) thin films as well as the incorporation behavior of syndiotactic (st) poly(methacrylic acid) (PMAA) into the porous films were investigated. The porous it-PMMA thin films were prepared by the extraction of st-PMAA from a stepwise layer-by-layer (LbL) assembly composed of it-PMMA and st-PMAA. The X-ray diffraction pattern of the it-PMMA thin films after immersion in acetonitrile/water (4/6, v/v) showed two characteristic peaks of a crystalline it-PMMA double-stranded helix (2theta = 9 degrees and 14 degrees , d = 0.96 and 0.62 nm). This suggested that acetonitrile promoted the crystallization of the thin films, because water is a nonsolvent for PMMA. The surface structural change of the it-PMMA films was also analyzed by atomic force microscopy. The it-PMMA conformation was maintained after crystallization as observed by infrared spectroscopy. The incorporation percentages of st-PMAA into the porous it-PMMA thin films under various solvent conditions were estimated using a quartz crystal microbalance. The incorporation of st-PMAA decreased as the it-PMMA films crystallized or with growing thickness of the porous it-PMMA films. This suggested that the polymer-polymer interactions and the entanglement of the it-PMMA chains played an important role. The incorporation was promoted as the acetonitrile content in the st-PMAA solution increased, indicating that it was necessary for st-PMAA incorporation to solvate it-PMMA.


Effects of miR-224-5p-enhanced downregulation of pannexin-1 on docetaxel-induced apoptosis in amoeboid-like CD44high oral cancer cells.
We previously found that microRNAs play major roles in the maintenance of amoeboid-like oral squamous cell carcinoma (OSCC) cells with high expression of CD44 (CD44high ). However, the roles of microRNAs in chemotherapeutic resistance exhibited by CD44high amoeboid-like OSCC cells are unclear. Here, docetaxel-induced apoptosis was examined in CD44high OSCC cells (CD44high OM-1 cells) cultured on laminin-coated silicone gel. Amoeboid-like CD44high OSCC cells exhibited robust resistance to docetaxel-induced apoptosis and significant upregulation of miR-224-5p expression compared with epithelial-like CD44high OSCC cells and mesenchymal-like CD44high OSCC cells. The expression of pannexin-1 (PANX1), a channel-forming protein that regulates the release of ATP, was significantly upregulated following transfection of amoeboid-like CD44high OSCC cells with an miR-224-5p inhibitor. These results suggest that miR-224-5p inhibits PANX1 expression. Furthermore, miR-224-5p inhibitor-transfected amoeboid-like CD44high OSCC cells exhibited significant enhancement of the proportion of apoptotic cells; however, this effect was significantly inhibited by knockdown of PANX1 with PANX1 small interfering RNA. Additionally, the miR-224-5p inhibitor-enhanced extracellular ATP levels were significantly reduced by PANX1 knockdown. These findings imply that miR-224-5p plays a vital role in the resistance to docetaxel-induced apoptosis by attenuating PANX1-induced ATP discharge. Moreover, amoeboid-like CD44high OSCC cells may be involved in chemotherapeutic resistance of OSCC.


A plant basal in vitro system supporting accurate transcription of both RNA polymerase II- and III-dependent genes: supplement of green leaf component(s) drives accurate transcription of a light-responsive rbcS gene.
An in vitro transcription initiation system has been developed from nuclei of rapidly growing, non-green tobacco (Nicotiana tabacum) cultured (BY-2) cells. Conditions for nuclear extraction and in vitro transcription reaction have been optimized with a tobacco beta-1,3-glucanase gene, a constitutively expressed gene in BY-2 cells. The in vitro system supports accurate transcription of RNA polymerase II-dependent promoters from not only plant genes (tobacco beta-1,3-glucanase gene, cauliflower mosaic virus 35S promoter) but also animal genes (adenovirus 2 major late promoter, simian virus 40 early major promoter). In addition, this system drives accurate transcription of an RNA polymerase III-dependent Arabidopsis thaliana U6 snRNA gene. As BY-2 cells do not differentiate in response to light or any other stimuli, they would provide a basal transcription system which lacks tissue-specific and light-responsive nuclear signals as well as chloroplast-derived signals. Consequently, the BY-2 cell-free system is unable to transcribe the tomato gene encoding the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (rbcS3C) whose expression is tissue-specific and light-inducible. However, the transcription of rbcS3C was obtained by supplementing the BY-2 system with a nuclear extract of light-grown tomato seedlings. The promoter regions necessary for rbcS transcription was mapped in vitro using a series of 5' deletion mutants. The 351 bp upstream sequence is essential and the further upstream region from -351 to -441 enhances its transcription. The in vitro basal system will be useful to identify specific signals from both the nucleus and chloroplast in green leaves and other organs/tissues.


Hepatoprotective effects of bioactive compounds from traditional herb Tulsi (Ocimum sanctum Linn) against galactosamine-induced hepatotoxicity in rats.
Ocimum sanctum L. (Tulsi; Family: libiaceae), also known as "The Queen of herbs" or "Holy Basil," is an omnipresent, multipurpose plant that has been used in folk medicine of many countries as a remedy against several pathological conditions, including anticancer, antidiabetic, cardio-protective, antispasmodic, diaphoretic, and adaptogenic actions. This study aims to assess O. sanctum L.'s hepatoprotective potential against galactosamine-induced toxicity, as well as investigate bioactive compounds in each extract and identify serum metabolites. The extraction of O. sanctum L as per Ayurveda was simultaneously standardized and quantified for biochemical markers: rutin, ellagic acid, kaempferol, caffeic acid, quercetin, and epicatechin by HPTLC. Hepatotoxicity was induced albino adult rats by intra-peritoneal injection of galactosamine (400 mg/kg). The quantified hydroalcoholic and alcoholic extract of O. sanctum L (100 and 200 mg/kg body weight/day) were compared for evaluation of hepatoprotective potential, which were assessed in terms of reduction in histological damage, change in serum enzymes such as AST, ALT, ALP and increase TBARS. Twenty chemical constituents of serum metabolites of O. sanctum were identified and characterized based on matching recorded mass spectra by GC-MS with those obtained from the library-Wiley/NIST. We evaluated the hepatoprotective activity of various fractions of hydroalcoholic extracts based on the polarity and investigated the activity at each phase (hexane, chloroform, and ethyl acetate) in vitro to determine how they affected the toxicity of CCL4 (40 mM) toward Chang liver cells. The ethyl acetate fraction of the selected plants had a higher hepatoprotective activity than the other fractions, so it was used in vacuum liquid chromatography (VLC). The ethyl acetate fraction contains high amounts of rutin (0.34% w/w), ellagic acid (2.32% w/w), kaempferol (0.017% w/w), caffeic acid (0.005% w/w), quercetin (0.038% w/w), and epicatechin (0.057% w/w) which are responsible for hepatoprotection. In comparison to standard silymarin, isolated bioactive molecules displayed the most significant hepatoprotective activity in Chang liver cells treated to CCl4 toxicity. The significant high hepatoprotection provided by standard silymarin ranged from 77.6% at 100 μg/ml to 83.95% at 200 μg/ml, purified ellagic acid ranged from 70% at 100 μg/ml to 81.33% at 200 μg/ml, purified rutin ranged from 63.4% at 100 μg/ml to 76.34% at 200 μg/ml purified quercetin ranged from 54.33% at 100 μg/ml to 60.64% at 200 μg/ml, purified epicatechin ranged from 53.22% at 100 μg/ml to 65.6% at 200 μg/ml, and purified kaempferol ranged from 52.17% at 100 μg/ml to 60.34% at 200 μg/ml. These findings suggest that the bioactive compounds in O. sanctum L. have significant protective effects against galactosamine-induced hepatotoxicity.


Making sense of microarray data distributions.
Typical analysis of microarray data has focused on spot by spot comparisons within a single organism. Less analysis has been done on the comparison of the entire distribution of spot intensities between experiments and between organisms. Here we show that mRNA transcription data from a wide range of organisms and measured with a range of experimental platforms show close agreement with Benford's law (Benford, PROC: Am. Phil. Soc., 78, 551-572, 1938) and Zipf's law (Zipf, The Psycho-biology of Language: an Introduction to Dynamic Philology, 1936 and Human Behaviour and the Principle of Least Effort, 1949). The distribution of the bulk of microarray spot intensities is well approximated by a log-normal with the tail of the distribution being closer to power law. The variance, sigma(2), of log spot intensity shows a positive correlation with genome size (in terms of number of genes) and is therefore relatively fixed within some range for a given organism. The measured value of sigma(2) can be significantly smaller than the expected value if the mRNA is extracted from a sample of mixed cell types. Our research demonstrates that useful biological findings may result from analyzing microarray data at the level of entire intensity distributions.


Mechanical Ventilation in Pediatric and Neonatal Patients.
Pediatric acute respiratory distress syndrome (PARDS) remains a significant cause of morbidity and mortality, with mortality rates as high as 50% in children with severe PARDS. Despite this, pediatric lung injury and mechanical ventilation has been poorly studied, with the majority of investigations being observational or retrospective and with only a few randomized controlled trials to guide intensivists. The most recent and universally accepted guidelines for pediatric lung injury are based on consensus opinion rather than objective data. Therefore, most neonatal and pediatric mechanical ventilation practices have been arbitrarily adapted from adult protocols, neglecting the differences in lung pathophysiology, response to injury, and co-morbidities among the three groups. Low tidal volume ventilation has been generally accepted for pediatric patients, even in the absence of supporting evidence. No target tidal volume range has consistently been associated with outcomes, and compliance with delivering specific tidal volume ranges has been poor. Similarly, optimal PEEP has not been well-studied, with a general acceptance of higher levels of F i O2 and less aggressive PEEP titration as compared with adults. Other modes of ventilation including airway pressure release ventilation and high frequency ventilation have not been studied in a systematic fashion and there is too little evidence to recommend supporting or refraining from their use. There have been no consistent outcomes among studies in determining optimal modes or methods of setting them. In this review, the studies performed to date on mechanical ventilation strategies in neonatal and pediatric populations will be analyzed. There may not be a single optimal mechanical ventilation approach, where the best method may simply be one that allows for a personalized approach with settings adapted to the individual patient and disease pathophysiology. The challenges and barriers to conducting well-powered and robust multi-institutional studies will also be addressed, as well as reconsidering outcome measures and study design.


Phylogenetic analysis of Shewanella spp. isolated from fish.
Different species of Shewanella spp. widely inhabit freshwater and marine environments. Some of them are opportunistic fish pathogens. The application of high-throughput sequencing enabled the characterization and taxonomic reclassification of many Shewanella spp. species. Still, some strains collected from fish need to be better recognized. The aim of the present study was to classify and determine the phylogenetic relationships of Shewanella spp. collected from fish. The complete genomes of 94 strains of Shewanella spp. from different fish species were sequenced using Illumina platform (MiSeq). The 16S rRNA gene, genomic features and whole-genome relationships of those bacteria were comprehensively analysed in comparison to reference strains. Whole-genome analysis showed that the tested Shewanella spp. strains were clustered into six groups similar to reference strains of S. xiamenensis, S. oneidensis, S. glacialipiscicola, S. hafniensis, S. baltica and S. oncorhynchi. Our study indicates that the whole-genome sequence analysis enabled taxonomic classification and assessment of the diversity of the Shewanella spp. strains, as opposed to recently the gold standard method of 16S rRNA amplicon sequencing. The high genetic diversity and low similarity to the reference genome of S. oneidensis indicate that the group of strains may be a subspecies or even new species. Furthermore, we showed that the most frequent Shewanella spp. species occurring in freshwater fish in our study is the recently described species S. oncorhynchi.


Acrodermatitis enteropathica-like eruption associated with combined nutritional deficiency.
We present here a case of acrodermatitis enteropathica-like eruption associated with essential free fatty acid and protein deficiencies as well as borderline zinc deficiency that occurred after Whipple's operation in a 31-yr-old woman. Her eruptions were improved not by zinc supplements alone, but her condition was improved by total parenteral nutrition including amino acids, albumin, lipid and zinc. Although we could not exactly decide which of the nutrients contributed the most to her manifestations, we inferred that all three elements in concert caused her dermatoses. This case shows that even though the patient's skin manifestations and laboratory results are suggestive of acrodermatitis enteropathica, the physicians should keep in mind the possibility that this disease can be associated with other nutritional deficiencies such as free fatty acid or protein deficiency.


Studies on the accessory reproductive organs in the drake. 1. Addition to semen on the fluid from the ejaculatory groove region.
This study was performed to clarify whether the semen from the vasa deferentia is diluted with a fluid before ejaculation and to locate the ejecting region of the fluid. Vas deferens semen, ejaculated semen and the fluid ejected from the ejaculatory groove region were obtained from the drake and their characteristics were determined. The mean concentration of ejaculated semen, 9.46 millions/mm.3, was nearly half as much as that of ampulla semen (semen contained in the dilated portion of the vasa deferentia; 20.40 millions/mm.3), and the former had positive aldose color reaction in contrast with complete negative reaction in the latter, suggesting that ampulla semen might be diluted twofold with a fluid containing aldose before ejaculation. The aldose positive fluid was observed to be ejected from the ejaculatory grove region of the cloaca and it could be collected from the vasectomized drake using an artificial vagina. Thus, the ejaculated semen of the drake, about 0.4 ml. in volume, was considered to be a mixture of the semen ejected from the vasa deferentia (estimated to be about 0.2 ml.) and the fluid ejected from the ejaculatory groove region (about 0.2 ml.). The pH value, glucose content and electrophoretic pattern of protein of the ejecting fluid were similar to that of blood plasma, and it was assumed that the fluid might be a fluid of blood origin.