Aeromedical Decision Making in Internal Jugular Phlebectasia.
BACKGROUND: Internal jugular phlebectasia (IJP) is an uncommon entity with only about 100 reported cases and with very few available cases in the literature. The current case study is about a male trainee fighter pilot incidentally diagnosed to have IJP. With limited literary evidence, it was a complex task to predict the prognosis of IJP and its implications on fighter flying.CASE REPORT: In order to confirm the diagnosis, a preliminary study was carried out to find out the normal and expanded area of the internal jugular vein (IJV) of 30 volunteers. The expanded area of the right IJV of the trainee pilot fell beyond 1 SD of the study population, confirming the diagnosis of IJP in the trainee pilot.DISCUSSION: Aeromedical concerns were the anti-G straining maneuver, positive pressure breathing for G, negative Gz, modified Valsalva maneuver, and rapid decompression. Considering the potential progression of IJP by repeated exposure to aviation stresses, the trainee pilot was re-assigned to helicopters.Khatua SS, Sannigrahi P, Dahiya M, Rastogi P, Raheem A. Aeromedical decision making in internal jugular phlebectasia. Aerosp Med Hum Perform. 2019; 90(2):132-134.


Deficiency of PDK1 in liver results in glucose intolerance, impairment of insulin-regulated gene expression and liver failure.
The liver plays an important role in insulin-regulated glucose homoeostasis. To study the function of the PDK1 (3-phosphoinositide-dependent protein kinase-1) signalling pathway in mediating insulin's actions in the liver, we employed CRE recombinase/loxP technology to generate L(liver)-PDK1-/- mice, which lack expression of PDK1 in hepatocytes and in which insulin failed to induce activation of PKB in liver. The L-PDK1-/- mice were not insulin-intolerant, possessed normal levels of blood glucose and insulin under normal feeding conditions, but were markedly glucose-intolerant when injected with glucose. The L-PDK1-/- mice also possessed 10-fold lower levels of hepatic glycogen compared with control littermates, and were unable to normalize their blood glucose levels within 2 h after injection of insulin. The glucose intolerance of the L-PDK1-/- mice may be due to an inability of glucose to suppress hepatic glucose output through the gluconeogenic pathway, since the mRNA encoding hepatic PEPCK (phosphoenolpyruvate carboxykinase), G6Pase (glucose-6-phosphatase) and SREBP1 (sterol-regulatory-element-binding protein 1), which regulate gluconeogenesis, are no longer controlled by feeding. Furthermore, three other insulin-controlled genes, namely IGFBP1 (insulin-like-growth-factor-binding protein-1), IRS2 (insulin receptor substrate 2) and glucokinase, were regulated abnormally by feeding in the liver of PDK1-deficient mice. Finally, the L-PDK1-/- mice died between 4-16 weeks of age due to liver failure. These results establish that the PDK1 signalling pathway plays an important role in regulating glucose homoeostasis and controlling expression of insulin-regulated genes. They suggest that a deficiency of the PDK1 pathway in the liver could contribute to development of diabetes, as well as to liver failure.


Feasibility of MRI based oxygenation imaging for the assessment of acute limb ischemia.
Acute limb ischemia (ALI) can lead to death and amputation. Evaluating the severity of ischemia is important but difficult, through current methods of examination. The purpose of this research was to demonstrate the feasibility of magnetic resonance imaging (MRI) susceptibility-based imaging techniques for use in assessing muscle oxygenation alterations in ALI. ALI animal models were established in 11 rabbits. Their left iliac arteries were embolized by microspheres. MRI scans were conducted 24 hours before (Pre) and 1 hour (Post 1) and 3 hours (Post 2) after the procedure. A susceptibility model was used to calculate skeletal muscle oxygenation extraction fraction (SMOEF) and relaxation rate (R2'). T2 weighted (T2w) imaging and diffusion-weighted (DW) imaging were performed. The average calf muscle SMOEF in the embolized hindlimbs increased from 0.43±0.02 (Pre) to 0.48±0.02 (Post 1) and 0.50±0.02 (Post 2), both P<0.05. The R2' value increased from 13.01±2.31 s-1 (Pre) to 16.78±2.28 s-1 (Post 1) and 17.90±3.29 s-1 (Post 2), both P<0.05. No significant changes of SMOEF and R2' were found after embolization in the contralateral hindlimbs. Apparent diffusion coefficient (ADC) values derived from DW imaging remained unchanged at different stages compared to before the procedures (all P>0.05). No abnormal signals were observed in the anatomical T2w images at Post 1 and Post 2. This study demonstrates the feasibility of using SMOEF for the assessment of oxygenation alterations in ALI models. SMOEF is more sensitive than T2w and DW imaging in detecting acute muscle ischemia at an early stage.


Patterns of Autofluorescence in Common Genotypes of Retinitis Pigmentosa.
To investigate whether different forms of retinitis pigmentosa (RP) could be distinguished from one another using fundus autofluorescence (FAF) imaging. The National Institutes of Health EyeGene database was used to gather FAF images from 31 patients with RP, which were separated into 11 groups based on the RP-associated gene that was mutated. Investigators reviewed the images for patterns of autofluorescence (AF) and recorded qualitative observations. Four patterns of AF were noted within the macula, including central foveal hyper AF, a perifoveal hyper AF ring, a macular hyper AF ring, and a bull's-eye pattern of AF. Four patterns of AF were noted outside of the macula, including a mid-peripheral hyper AF ring, extramacular spots of hyper AF, patches of hypo AF, and diffuse hypo AF in the periphery. Double hyper AF rings were present in RHO, RPGR, USH2A, and NR2E3-linked RP. Similar patterns of AF were seen in different forms of RP, and AF failed to distinguish different genotypes. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:426-431.].


An adenosinetriphosphate-activated hemolytic system. II. Utilization of adenosinetriphosphate in the reaction.
Failure to demonstrate ATP(1) utilization in an ATP-activated hemolytic system had been previously reported. In the present study ATP utilization is shown to be associated with the hemolytic reaction and also with the ATP-dependent inactivation of the hemolytic factor of the system by crude, washed, human red cell stroma. Using crude stroma, relatively large ATP utilization occurs and continues, but at a decreasing rate, after inactivation of the hemolytic factor is complete. With purified stroma there is very slight uptake of ATP by the stroma in the presence of hemolytic factor and Mg(++). This uptake can only be demonstrated by radioactive ATP. Both C(14)- and P(32)-labelled nucleotide were used for this purpose. In the presence of an excess of stroma the uptake seems to be dependent on the amount of hemolytic factor used. Evidence is given contraindicating the possibility that this uptake is non-specific.


Role for Fes/Fps tyrosine kinase in microtubule nucleation through is Fes/CIP4 homology domain.
We have previously demonstrated that Fes/Fps (Fes) tyrosine kinase is involved in Semaphorin3A-mediated signaling. Here we report a role for Fes tyrosine kinase in microtubule dynamics. A fibrous formation of Fes was observed in a kinase-dependent manner, which associated with microtubules and functionally correlated with microtubule bundling. Microtubule regeneration assays revealed that Fes aggregates colocalized with gamma-tubulin at microtubule nucleation sites in a Fes/CIP4 homology (FCH) domain-dependent manner and that expression of FCH domain-deleted Fes mutants blocked normal centrosome formation. In support of these observations, mouse embryonic fibroblasts derived from Fes-deficient mice displayed an aberrant structure of nucleation and centrosome with unbundling and disoriented filaments of microtubules. Our findings suggest that Fes plays a critical role in microtubule dynamics including microtubule nucleation and bundling through its FCH domain.


Prediction of the potential geographical distribution of Betula platyphylla Suk. in China under climate change scenarios.
Climate is a dominant factor affecting the potential geographical distribution of species. Understanding the impact of climate change on the potential geographic distribution of species, which is of great significance to the exploitation, utilization, and protection of resources, as well as ecologically sustainable development. Betula platyphylla Suk. is one of the most widely distributed temperate deciduous tree species in East Asia and has important economic and ecological value. Based on 231 species distribution data points of Betula platyphylla Suk. in China and 37 bioclimatic, soil, and topography variables (with correlation coefficients < 0.75), the potential geographical distribution pattern of Betula platyphylla Suk. under Representative Concentration Pathway (RCP) climate change scenarios at present and in the 2050s and 2070s was predicted using the MaxEnt model. We analyzed the main environmental variables affecting the distribution and change of suitable areas and compared the scope and change of suitable areas under different climate scenarios. This study found: (1) At present, the main suitable area for Betula platyphylla Suk. extends from northeastern to southwestern China, with the periphery area showing fragmented distribution. (2) Annual precipitation, precipitation of the warmest quarter, mean temperature of the warmest quarter, annual mean temperature, and precipitation of the driest month are the dominant environmental variables that affect the potential geographical distribution of Betula platyphylla Suk. (3) The suitable area for Betula platyphylla Suk. is expected to expand under global warming scenarios. In recent years, due to the impact of diseases and insect infestation, and environmental damage, the natural Betula platyphylla Suk. forest in China has gradually narrowed. This study accurately predicted the potential geographical distribution of Betula platyphylla Suk. under current and future climate change scenarios, which can provide the scientific basis for the cultivation, management, and sustainable utilization of Betula platyphylla Suk. resources.


Functional analysis of novel variants identified in cis in the PCCB gene in a patient with propionic acidemia.
Next-generation sequencing has improved the diagnosis of inborn errors of metabolism, allowing rapid confirmation of cases detected by clinical/biochemical studies or newborn screening. The challenge, however, remains for establishing the pathogenicity of the identified variants, especially for novel missense changes or small in-frame deletions. In this work we report a propionic acidemia patient exhibiting a severe neonatal form with coma and hyperammonaemia. Genetic analysis identified the previously described pathogenic PCCB variant p.R512C in the maternal allele and two novel PCCB variants in cis in the paternal allele, p.G246del and p.S322F. Expression analysis in a eukaryotic system confirmed the deleterious effect of the novel missense variant and of the one amino acid deletion, as they both exhibited reduced protein levels and reduced or null PCC activity compared to the wild-type construct. Accordingly, the double mutant resulted in no residual activity. This study increases the knowledge of the genotype-phenotype correlations in the rare disease propionic acidemia and highlights the necessity of functional analysis of novel variants to understand their contribution to disease severity and to accurately classify their pathogenic status. In conclusion, two novel PCCB pathogenic variants have been identified, expanding the current mutational spectrum of propionic acidemia.


CD27 instructs CD4+ T cells to provide help for the memory CD8+ T cell response after protein immunization.
For optimal quality, memory CD8(+) T cells require CD4(+) T cell help. We have examined whether CD4(+) T cells require CD27 to deliver this help, in a model of intranasal OVA protein immunization. CD27 deficiency reduced the capacity of CD4(+) T cells to support Ag-specific CD8(+) T cell accumulation at the tissue site after primary and secondary immunization. CD27-dependent CD4(+) T cell help for the memory CD8(+) T cell response was delivered during priming. It did not detectably affect formation of CD8(+) memory T cells, but promoted their secondary expansion. CD27 improved survival of primed CD4(+) T cells, but its contribution to the memory CD8(+) T cell response relied on altered CD4(+) T cell quality rather than quantity. CD27 induced a Th1-diagnostic gene expression profile in CD4(+) T cells, which included the membrane molecule MS4A4B. Accordingly, CD27 increased the frequency of IFN-gamma- and IL-2-producing CD4(+) T cells. It did not affect CD40L expression. Strikingly, MS4A4B was also identified as a unique marker of CD8(+) memory T cells that had received CD27-proficient CD4(+) T cell help during the primary response. This apparent imprinting effect suggests a role for MS4A4B as a downstream effector in CD27-dependent help for CD8(+) T cell memory.


Practical development of genetically engineered animals as human disease models.
Since transgenic (Tg) mice were first produced in 1980, the technology to produce genetically engineered animals, such as Tg and knock-out mice, has advanced exponentially. These animals have contributed greatly to basic research at the molecular level and have proven to be powerful tools for elucidating complex biological processes. The effort that is required to develop and establish genetically engineered animals as models for human diseases or toxicologic studies is not always appreciated by researchers and laboratory animal scientists. Genetically engineered animals remain only candidates of defined animal models until they are developed for practical use, in accordance with their objectives, through cooperation between the researchers performing the experiments and laboratory animal scientists. The practical development of these animals consists of three steps: establishment as standardized laboratory animals through the setting of quality standards and the establishment of a production and supply system; establishment as defined animal models through confirmation of the usefulness and limitations of the animal in the purpose of use; and establishment of an in vivo experimentation system (an animal experimentation system), using the defined animal models. This report serves as an introduction to those that follow and describes our concept of how best to establish genetically engineered animals as valid animal models. The development of Tg mice carrying the poliovirus receptor gene (PVR) will be used as an example. The TgPVR mice were produced by the introduction of the human poliovirus receptor gene into the mouse genome, mainly to study the molecular mechanisms of pathogenesis of the virus. The value of these mice is that they mimic human and nonhuman primate susceptibility to poliovirus infection and thus serve as a model for the study of the disease and for the assessment of poliovirus vaccines. They are being touted as a replacement for nonhuman primates in the neurovirulence testing of oral poliovirus vaccine.


Improving oral health through dental fluoride varnish application in a primary care paediatric practice.
Dental caries affect 97% of people during their lifetime. A total of 59% of children aged 12-19 will have at least one documented cavity. The American Academy of Pediatrics recommends fluoridated toothpaste to all children starting at tooth eruption, regardless of caries risk. Besides, fluoride varnish is recommended for all children every 3-6 months from tooth emergence until they have a permanent dental home. This project aimed to increase oral fluoride varnish application for children starting at 6 months or the time of tooth eruption up to 3 years of age by at least 50% over 18 months. The stakeholders identified were physicians, nurses, medical assistants and the health information team. We obtained baseline data about oral health screening and fluoride varnish from both the clinic sites. The quality improvement (QI) project was based on Plan-Do-Study-Act (PDSA) cycles with a 6-month gap in-between the three cycles. For the first cycle, all medical staff members participated in 2-hour knowledge and skills training on dental caries and current recommendations on fluoride varnish. PDSA cycle 2 involved having automatic reminders for providers in electronic medical records. PDSA cycle 3 planned to have automatic fluoride orders for the recommended age groups. The QI team analysed the results after every 6 months, and improvements were made based on the input from data and medical staff. The number of patients who had fluoride varnish applied increased from 14% (n=50) to 55% at the end of PDSA cycle 3. Administration of the varnish did not affect the flow of the patients in busy primary care practice. The rate of improvement was across all the age groups, providers and in both clinical sites. It is possible to adhere to the oral fluoride varnish guidelines in a busy primary care practice, which may help benefit young children who are at risk for caries.


A case of junctional epidermolysis bullosa (Herlitz-Pearson) with corneal bullae.
A proven case of junctional epidermolysis bullosa is presented in which there have been recurrent right and left corneal lesions. The corneal changes arose either spontaneously or after minor trauma. We have no histological findings of the cornea at present, but the clinical features are similar to those reported in epidermolysis bullosa dystrophica-recessive. We believe that this is the first detailed case report of corneal involvement in proven junctional epidermolysis bullosa. The literature is reviewed.


Use of hepatitis B core antibody-positive donors in orthotopic liver transplantation.
Hepatic allografts from donors positive for antibody to hepatitis B core antigen (anti-HBc) frequently transmit hepatitis B virus (HBV) infection to recipients. Therefore, most transplantation centers will not use these organs for orthotopic liver transplantation (OLT). Although it is expensive and not always efficacious, hepatitis B immune globulin (HBIG) has been used routinely for indefinite periods to prevent HBV infection in liver allograft recipients. We assessed the effectiveness of long-term use of a nucleoside analog, lamivudine, in preventing HBV transmission by anti-HBc-positive allografts. Retrospective study. A tertiary care center. Twelve patients received hepatic allografts from anti-HBc-positive donors at Loyola University Medical Center, Chicago, between February 23, 1998, and March 13, 2001. All patients received 10 000 U/d of intravenous HBIG for 7 days. In addition, they received 300 mg/d of lamivudine in divided doses. Their liver biopsy specimens were tested for HBV DNA, hepatitis B surface antigen (HBsAg), and hepatitis B core antibody (HBcAb). Serum samples from the donor and recipient were tested for HBcAb, HBV DNA, and hepatitis B surface antibody (HBsAb). The incidence of HBV infection in recipients who received HBcAb-positive donor livers and lamivudine prophylaxis. All recipients were anti-HBc negative before OLT. Five of the recipients had HBsAb titers greater than 150 U at the time of OLT. Three of the donor livers were HBV DNA positive and 2 were hepatitis B core antigen positive at the time of OLT. Donor serum was HBcAb positive in all 12 donors. None of the recipients have become infected with HBV with a follow-up of 2 to 38 months. Perioperative use of HBIG combined with long-term use of lamivudine can prevent HBV infection in recipients who receive hepatic allografts from HBcAb-positive donors.


Ophiopogonin D inhibits cell proliferation and induces apoptosis of human laryngocarcinoma through downregulation of cyclin B1 and MMP-9 and upregulation of p38-MAPK signaling.
The pharmacological actions of Ophiopogonin D include resistance to cardiovascular and cerebrovascular diseases, anti-aging effects, improvement in learning deficit and dysmnesia, anti-tumor, anti-radiation and anti-inflammatory effects, immunoregulation, and the relief of cough and hepatopulmonary pathological lesions. However, the efficacy of Ophiopogonin D on human laryngocarcinoma remains to be elucidated. The present study therefore investigated whether the anti-cancer effect of Ophiopogonin D inhibits cell proliferation and induces apoptosis of human laryngocarcinoma. In the present study, it was found that Ophiopogonin D inhibited cell proliferation, promoted cytotoxicity, induced apoptosis and increased caspase-3/9 activity in human laryngocarcinoma cells. Ophiopogonin D significantly suppressed cyclin B1 and matrix metalloproteinase-9 (MMP-9) protein expression, and upregulated p-p38 MAPK protein expression in human laryngocarcinoma cells. Together, these results suggest Ophiopogonin D inhibits cell proliferation and induced apoptosis in human laryngocarcinoma cells through downregulation of cyclin B1 and MMP-9 and upregulation of the p38 MAPK signaling pathway. Therefore, Ophiopogonin D may be a potential therapy for the treatment of human laryngocarcinoma.


Recycling soil nitrate nitrogen by amending agricultural lands with oily food waste.
With current agricultural practices the amounts of fertilizer N applied are frequently more than the amounts removed by the crop. Excessive N application may result in short-term accumulation of nitrate nitrogen (NO3-N) in soil, which can easily be leached from the root zone and into the ground water. A management practice suggested for conserving accumulated NO3-N is the application of oily food waste (FOG; fat + oil + greases) to agricultural soils. A two-year field study (1995-1996 and 1996-1997) was conducted at Elora Research Center (43 degrees 38' N, 80 degrees W; 346 m above mean sea level), University of Guelph, Ontario, Canada to determine the effect of FOG application in fall and spring on soil NO3-N contents and apparent N immobilization-mineralization of soil N in the 0- to 60-cm soil layer. The experiment was planned under a randomized complete block design with four replications. An unamended control and a reference treatment [winter wheat (Triticum aestivum L.) cover crop] were included in the experiment to compare the effects of fall and spring treatment of oily food waste on soil NO3-N contents and apparent N immobilization-mineralization. Oily food waste application at 10 Mg ha(-1) in the fall decreased soil NO3-N by immobilization and conserved 47 to 56 kg NO3-N ha(-1), which would otherwise be subject to leaching. Nitrogen immobilized due to FOG application in the fall was subsequently remineralized by the time of fertilizer N sidedress, whereas no net mineralization was observed in spring-amended plots at the same time.


[Hemorrhoidal disease. Current surgical treatment and the place of Whitehead's operation].
In the presented material a review of the current data and comprehensions of the anatomy and physiology of the hemorrhoids is made, as like of the ethiology and pathogenesis of the disease. The new conceptions of the surgical treatment of the disease are pointed out. An attempt was made to differentiate the operative methods in patogenetical principal. The operative results of the General Surgery Clinic by the University Hospital "St. Ann", Sofia for the period 1991-2000 of 157 treated patients with hemorrhoidal disease are presented. Based on these results the authors come to a conclusion, that the Whitehead's operation remains "the golden standard" as a choice of an operative method for the treatment of the hemorrhoidal disease in advanced stages (III-d or IV-th).


A fully adjusted two-stage procedure for rank-normalization in genetic association studies.
When testing genotype-phenotype associations using linear regression, departure of the trait distribution from normality can impact both Type I error rate control and statistical power, with worse consequences for rarer variants. Because genotypes are expected to have small effects (if any) investigators now routinely use a two-stage method, in which they first regress the trait on covariates, obtain residuals, rank-normalize them, and then use the rank-normalized residuals in association analysis with the genotypes. Potential confounding signals are assumed to be removed at the first stage, so in practice, no further adjustment is done in the second stage. Here, we show that this widely used approach can lead to tests with undesirable statistical properties, due to both combination of a mis-specified mean-variance relationship and remaining covariate associations between the rank-normalized residuals and genotypes. We demonstrate these properties theoretically, and also in applications to genome-wide and whole-genome sequencing association studies. We further propose and evaluate an alternative fully adjusted two-stage approach that adjusts for covariates both when residuals are obtained and in the subsequent association test. This method can reduce excess Type I errors and improve statistical power.


The "Ethics" Expertise in Clinical Ethics Consultation.
The nature, possibility, and implications of ethics expertise (or moral expertise) in general and of bioethics expertise in particular has been the focus of extensive debate for over thirty years. What is ethics expertise and what does it enable experts to do? Knowing what ethics expertise is can help answer another important question: What, if anything, makes a claim of expertise legitimate? In other words, how does someone earn the appellation "ethics expert?" There remains deep disagreement on whether ethics expertise is possible, and if so, what constitutes such expertise and what it entails and legitimates. Discussion of bioethics expertise has become particularly important given the growing presence of bioethicists in the clinical setting as well as efforts to professionalize bioethics through codes of ethics and certification (or quasi-certification) efforts. Unlike in the law or in engineering, where there may be a body of knowledge that professional organizations or others have articulated as important for education and training of experts, ethics expertise admits of no such body of knowledge or required experience. Nor is there an entity seen as having the authority to articulate the necessary scope of knowledge. Questions about whether there is such a body of knowledge for particular areas within bioethics have emerged and played a central role in professionalization efforts in recent years, especially in the area of clinical ethics.


Quantifying the Ligand-Induced Triplet Energy Transfer Barrier in a Quantum Dot-Based Upconversion System.
During photon upconversion, quantum dots (QDs) transfer energy to molecules in solution through a long ligand shell. This insulating ligand shell imparts colloidal stability at the expense of efficient photosensitization. For the first time, we quantify the barrier these aliphatic ligands pose for triplet energy transfer in solution. Using transient absorption spectroscopy, we experimentally measure a small damping coefficient of 0.027 Å-1 for a ligand exceeding 10 carbons in length. The dynamic nature of ligands in solution lowers the barrier to charge or energy transfer compared to organic thin films. In addition, we show that surface ligands shorter than 8 carbons in length allow direct energy transfer from the QD, bypassing the need for a transmitter ligand to mediate energy transfer, leading to a 6.9% upconversion quantum yield compared with 0.01% for ligands with 18 carbons. This experimentally derived insight will enable the design of efficient QD-based photosensitizers for catalysis and energy conversion.


Effects of arterial load variations on dynamic arterial elastance: an experimental study.
Dynamic arterial elastance (Ea dyn ), the relationship between pulse pressure variation (PPV) and stroke volume variation (SVV), has been suggested as a functional assessment of arterial load. The aim of this study was to evaluate the impact of arterial load changes during acute pharmacological changes, fluid administration, and haemorrhage on Ea dyn . Eighteen anaesthetized, mechanically ventilated New Zealand rabbits were studied. Arterial load changes were induced by phenylephrine ( n =9) or nitroprusside ( n =9). Thereafter, animals received a fluid bolus (10 ml kg -1 ), followed by stepwise bleeding (blood loss: 15 ml kg -1 ). The influence of arterial load and cardiac variables on PPV, SVV, and Ea dyn was analysed using a linear mixed-effects model analysis. After phenylephrine infusion, mean ( sd ) Ea dyn decreased from 0.89 (0.14) to 0.49 (0.12), P <0.001; whereas after administration of nitroprusside, Ea dyn increased from 0.80 (0.23) to 1.28 (0.21), P <0.0001. Overall, the fluid bolus decreased Ea dyn [from 0.89 (0.44) to 0.73 (0.35); P <0.01], and haemorrhage increased it [from 0.78 (0.23) to 0.95 (0.26), P =0.03]. Both PPV and SVV were associated with similar arterial factors (effective arterial elastance, arterial compliance, and resistance) and heart rate. Furthermore, PPV was also related to the acceleration and peak velocity of aortic blood flow. Both arterial and cardiac factors contributed to the evolution of Ea dyn throughout the experiment. Acute modifications of arterial load induced significant changes on Ea dyn ; vasodilatation increased Ea dyn , whereas vasoconstriction decreased it. The Ea dyn was associated with both arterial load and cardiac factors, suggesting that Ea dyn should be more properly considered as a ventriculo-arterial coupling index.


Protein Oxidation in the Lungs of C57BL/6J Mice Following X-Irradiation.
Damage to normal lung tissue is a limiting factor when ionizing radiation is used in clinical applications. In addition, radiation pneumonitis and fibrosis are a major cause of mortality following accidental radiation exposure in humans. Although clinical symptoms may not develop for months after radiation exposure, immediate events induced by radiation are believed to generate molecular and cellular cascades that proceed during a clinical latent period. Oxidative damage to DNA is considered a primary cause of radiation injury to cells. DNA can be repaired by highly efficient mechanisms while repair of oxidized proteins is limited. Oxidized proteins are often destined for degradation. We examined protein oxidation following 17 Gy (0.6 Gy/min) thoracic X-irradiation in C57BL/6J mice. Seventeen Gy thoracic irradiation resulted in 100% mortality of mice within 127-189 days postirradiation. Necropsy findings indicated that pneumonitis and pulmonary fibrosis were the leading cause of mortality. We investigated the oxidation of lung proteins at 24 h postirradiation following 17 Gy thoracic irradiation using 2-D gel electrophoresis and OxyBlot for the detection of protein carbonylation. Seven carbonylated proteins were identified using mass spectrometry: serum albumin, selenium binding protein-1, alpha antitrypsin, cytoplasmic actin-1, carbonic anhydrase-2, peroxiredoxin-6, and apolipoprotein A1. The carbonylation status of carbonic anhydrase-2, selenium binding protein, and peroxiredoxin-6 was higher in control lung tissue. Apolipoprotein A1 and serum albumin carbonylation were increased following X-irradiation, as confirmed by OxyBlot immunoprecipitation and Western blotting. Our findings indicate that the profile of specific protein oxidation in the lung is altered following radiation exposure.


Art and emotion in psychoanalysis.
Freud's view that art satisfies psychic needs has been taken to mean that art has its source in the unconscious and that it unifies pleasure and reality. The author argues that there is a third point that Freud repeatedly emphasizes, which should not be overlooked, that art influences our emotions. The author examines what Freud means by this claim, in particular, his reading of Michelangelo's Moses. Freud's focus here on emotions as fundamental to subjective experience, as subject to regulation and as potentially healthy forms of communication serves to supplement and even challenge what he says in his theory of affect. The author concludes by making inferences about a contemporary psychoanalytic theory of affects: that it ought to be inclusive of science (more receptive to neurobiology and less bound to Freud) as well as art (preserving the focus on subjective experience, especially the processing of complex emotions), which is illustrated with the concept of mentalized affectivity.


Children's Sleep and Academic Achievement: The Moderating Role of Effortful Control.
Poor sleep is thought to interfere with children's learning and academic achievement (AA). However, existing research and theory indicate there are factors that may mitigate the academic risk associated with poor sleep. The purpose of this study was to examine the moderating role of children's effortful control (EC) on the relation between sleep and AA in young children. One hundred and three 4.5- to 7-year-olds (M = 5.98 years, SD = 0.61) wore a wrist-based actigraph for five continuous weekday nights. Teachers and coders reported on children's EC. EC was also assessed with a computer-based task at school. Additionally, we obtained a standardized measure of children's AA. There was a positive main effect of sleep efficiency to AA. Several relations between sleep and AA were moderated by EC and examination of the simple slopes indicated that the negative relation between sleep and AA was only significant at low levels of EC.


Silencing quorum sensing through extracts of Melicope lunu-ankenda.
Quorum sensing regulates bacterial virulence determinants, therefore making it an interesting target to attenuate pathogens. In this work, we screened edible, endemic plants in Malaysia for anti-quorum sensing properties. Extracts from Melicope lunu-ankenda (Gaertn.) T. G. Hartley, a Malay garden salad, inhibited response of Chromobacterium violaceum CV026 to N-hexanoylhomoserine lactone, thus interfering with violacein production; reduced bioluminescence expression of E. coli [pSB401], disrupted pyocyanin synthesis, swarming motility and expression of lecA::lux of Pseudomonas aeruginosa PAO1. Although the chemical nature of the anti-QS compounds from M. lunu-ankenda is currently unknown, this study proves that endemic Malaysian plants could serve as leads in the search for anti-quorum sensing compounds.


Gene expression profile of the synovium and cartilage in a chronic arthritis rat model.
Primary osteoarthritis (OA) is a polygenic disease. To investigate the gene expression profile of cartilage and synovium from osteoarthritis and healthy rats using cDNA microarray is beneficial to recognize the pathogenesis of osteoarthritis and provide evidence for gene therapy of osteoarthritis. The present study aimed to investigate the gene expression profile of the cartilage and synovium of chronic arthritis and healthy rats through cDNA microarray assay, and identify the differentially expressed genes. This study may be helpful for understanding the role of differentially expressed genes in osteoarthritis and the gene polymorphism of osteoarthritis. A total of 24 male Wistar rats were randomly divided into control group and osteoarthritis group (n = 12 per group). The synovial and cartilage were obtained and total RNA was extracted. cDNA microarray assay was performed to identify the differentially expressed genes, and cluster analysis was conducted. A total of 82 differentially expressed genes were identified, among which 27 were up-regulated and 55 down-regulated. Gene microarray assay is effective to identify differentially expressed genes and may find out novel osteoarthritis associated genes. Multiple genes are involved in the pathogenesis of osteoarthritis. The differentially expressed genes provide important information for further studies on the pathogenesis of osteoarthritis and gene therapy of osteoarthritis.


Quality indicators for colonoscopy: Current insights and caveats.
Colonoscopy is the diagnostic modality of choice for investigation of symptoms suspected to be related to the colon and for the detection of polyps and colorectal cancer (CRC). Colonoscopy with removal of detected polyps has been shown to reduce the incidence and mortality of subsequent CRC. In many countries, population screening programs for CRC have been initiated, either by selection of patients for colonoscopy with fecal occult blood testing or by offering colonoscopy directly to average-risk individuals. Several endoscopy societies have formulated quality indicators for colonoscopy. These quality indicators are almost always incorporated as process indicators, rather than outcome measures. This review focuses on the quality indicators bowel preparation, cecal intubation rate, withdrawal time, adenoma detection rate, patient comfort, sedation and complication rate, and discusses the scientific evidence supporting them, as well as their potential shortcomings and issues that need to be addressed. For instance, there is still no clear and generally accepted definition of adequate bowel preparation, no robust scientific evidence is available supporting a cecal intubation rate ≥ 90% and the association between withdrawal time and occurrence of interval cancers has not been clarified. Adenoma detection rate is currently the only quality indicator that has been shown to be associated with interval colorectal cancer, but as an indicator it does not differentiate between subjects with one or more adenoma detected.


[Computer-assisted coronary surgery].
Routine totally endoscopic, beating heart, coronary surgery should be made possible by the use of computer enhanced surgical techniques. It includes a totally endoscopic mammary artery harvesting, a correct exposure and an adequate stabilization of the coronary artery at the anastomotic site, a perfect anastomosis of the mammary artery on the left anterior descending coronary artery using a microsurgical suture technique. This complex surgical protocol will be reached by a step by step approach. The first 20 patients who accepted to be operated with tele-manipulated instruments make the substance of this first report. In 19 cases, the dissection of the internal mammary artery could be performed with an optimal result: the lack of bleeding during the dissection emphasizes the excellent visualization of the operative field and the precision of the dissection. The satisfactory blood flow in the mammary artery at the time of the coronary anastomosis suggests the lack of spasm and confirms the atraumatic dissection. The distal anastomosis of the coronary bypass has been performed through a mid line sternotomy to avoid an excessive prolongation of the operative time. The anatomic conditions and the quality of the vessel wall allowed to perform the coronary anastomosis with the tele-manipulated instruments in nine cases only: in six patients, the mammary artery has been implanted on the descending artery, in three, a venous autograft on the diagonal branch. Our initial clinical experience with this new technique suggests that a very precise and fine surgery can be performed with an acceptable prolongation of the operative time. More experience and further developments in the instrumentation are nevertheless required to allow completion of the entire procedure totally closed chest, on a beating heart.


Retrospectively Assessed Early Motor and Current Pragmatic Language Skills in Autistic and Neurotypical Children.
Autistic individuals often struggle developmentally, even in areas that are not explicit diagnostic criteria, such as motor skills. This study explored the relation between early motor skills, assessed retrospectively, and current pragmatic language skills. Caregivers of neurotypical and autistic children, matched on gender and age, completed assessments of their child's early motor development and current language abilities. Early motor skills were correlated with later pragmatic language skills, and autistic children exhibited fewer motor skills than neurotypical children. In fact, motor skills were a better predictor of an autism spectrum diagnosis than were scores on a measure of current pragmatic language. These results highlight the important role of motor skills in autism spectrum disorders.


[Stanford Type B Acute Aortic Dissection Associated with Transcatheter Aortic Valve Implantation:Report of a Case].
Transcatheter aortic valve implantation (TAVI)-related Stanford type B aortic dissection is an extremely rare but potentially fatal complication. Here, we present a case of 82-year-old man who developed acute type B aortic dissection during transfemoral TAVI. During successful TAVI procedure, dissection in the descending aorta was demonstrated by transesophageal echocardiography. Computed tomography( CT) clearly showed Stanford type B aortic dissection and an intimal tear in severely tortuous part of the descending aorta. Cause of aortic dissection was supposed to be related to the guidewire or the device that passed across affected position. The patient showed no complication associated with aortic dissection, such as rupture or malperfusion. Therefore, he was treated conservatively, and follow-up CT confirmed progressive clotting of the false lumen. Although the indication for TAVI has got broaden recently, physicians should be always aware of possible aortic dissection.


Colon Ischemia After Weight-Loss Medication in a 36-Year-Old Woman.
Weight-loss medications have been associated with many conditions, including valvular heart disease, ischemic colitis, and pulmonary hypertension. There is a constant increase in the use of these drugs, especially new medications with better efficacy. Phentermine is one such drug, approved for short-term use to lose weight. We report a case of ischemic colitis in a female patient linked to inappropriate phentermine intake. The patient presented with symptoms of severe abdominal pain and repeated bowel movement associated with rectal bleeding for two weeks. Initial blood work was unremarkable for infectious and inflammatory causes. A CT scan was performed which revealed findings of ischemic colitis extending from transverse to descending colon. A biopsy study confirmed the same. Upon further questioning, the patient admitted to taking 37.5 mg of phentermine for two years beyond her prescribed period of 12 weeks. Hence, we propose that inappropriate use of phentermine caused ischemic colitis. With the widespread use of these medications, there is a need for heightened awareness among clinicians regarding adverse effects of phentermine.


[Immunomorphologic characteristics of the tonsils and their lymph nodes in human fetuses].
This study was carried out having in view our inadequate knowledge of immunological parameters of human normal tonsils. The purpose of the study was to investigate the development of basic morphological and immunological parameters of organs constituting the functional complex, i. e. palatine, pharyngeal, lingual tonsils and neck lymph nodes that drain them, in human fetuses. Altogether 50 palatine, 31 pharyngeal, 16 lingual tonsils and neck lymph nodes of human fetuses (14 to 32 weeks) were examined. The development and morphology of tonsils as well as the time of lymphocyte settlement were investigated. The pattern of lymphocyte differentiation was studied immunologically. In terms of expression of surface markers, the heterogeneity of T- and B-cell immunity systems and their kinetics in the course of embryogenesis typical of each organ under study were identified. In the complex of organs combined by immune functions, neck lymph nodes can be identified as the pool of T-cells the amount of which makes the total number of the cells in all tonsils. As to B-cells, tonsils contained predominantly EAC-RFC. When compared to tonsils, lymph nodes contained the least quantities of B-lymphocytes.


[Treatment of non-Hodgkin's lymphomas in adults, stages III and IV with favorable histology : abstention or therapeutic aggressiveness?].
Within the inhomogeneous group of non Hodgkin's lymphomas, the natural history of lymphomas with favorable histologies, stages III and IV is uncommon; survival can be long, but the relapse rate is high, and finally the ten-year survival rate is poor. In order to improve these results, various proposals have been made. Presently, two main attitudes can be defined. The first one is based on data showing a better survival rate when a complete remission has been obtained; consequently, a very aggressive treatment scheme (for example an association of chemotherapy--including Adriamycin--and total body irradiation) is proposed. The second attitude is based on favorable results obtained by a "deferred treatment", the patients being treated only when the disease is symptomatic. Actually, the review of the literature shows that these two attitudes are complementary rather than antagonistic. For a young adult patient, essentially if histology is more "intermediate" than really "favorable" and if the patient presents with bulky tumoral masses, aggressive treatment must be proposed, because it is the only attitude able to achieve complete remission and therefore able to provide chances of long term survival. For an older patient, essentially with a very favorable histology and without any symptoms such an aggressive therapy appears too risky. "Light" treatments and occasionally "deferred treatment" can be proposed in these cases.


Common Fibril Structures Imply Systemically Conserved Protein Misfolding Pathways In Vivo.
Systemic amyloidosis is caused by the misfolding of a circulating amyloid precursor protein and the deposition of amyloid fibrils in multiple organs. Chemical and biophysical analysis of amyloid fibrils from human AL and murine AA amyloidosis reveal the same fibril morphologies in different tissues or organs of one patient or diseased animal. The observed structural similarities concerned the fibril morphology, the fibril protein primary and secondary structures, the presence of post-translational modifications and, in case of the AL fibrils, the partially folded characteristics of the polypeptide chain within the fibril. Our data imply for both analyzed forms of amyloidosis that the pathways of protein misfolding are systemically conserved; that is, they follow the same rules irrespective of where inside one body fibrils are formed or accumulated.


Episodic Future Thinking about the Ideal Self Induces Lower Discounting, Leading to a Decreased Tendency toward Cheating.
Delay discounting refers to a pervasive tendency toward preferring smaller immediate gains over larger future gains. Recent empirical research has shown that episodic future thinking (EFT; i.e., projecting oneself into the future to pre-experience forthcoming events) can reduce the tendency toward discounting. A common tenet of psychological theories of crime is that delinquency results from focusing on short-term gains while failing to consider adequately the longer-term consequences of delinquent behavior. We investigated whether an EFT intervention involving the ideal self could induce lower discounting rates and, as a consequence, reduced delinquency. The results showed that, compared with control participants, participants engaging in EFT, that is, envisaging life events that would be experienced by their ideal selves, exhibited a lower discounting rate in a monetary choice task (Experiments 1 and 2), as well as a decreased tendency to make delinquent choices in imaginary scenarios (Experiment 1) and cheat in a matrix task (Experiment 2). The discounting tendency mediated the relationship between engaging in EFT pertaining to the ideal self and the tendency toward morally questionable behavior (Experiments 1 and 2). The findings of the two experiments indicate that engagement in EFT with a focus on the ideal self is sufficient to induce lower discounting rates, by promoting consideration of distant costs and thus increasing resistance to delinquent involvement and cheating (given the temptation of the immediate benefits that may accrue from such behavior). The current research constitutes an innovative approach to delinquency prevention and the promotion of morality.


Tertiary syphilis mimicking hepatic metastases of underlying primary peritoneal serous carcinoma.
Tertiary syphilis, especially in cases involving visceral gummatous disease, can be confused with cancer of the solid organs. We report a case of tertiary hepatic syphilis that manifested with intrahepatic masses in a patient who had an underlying primary peritoneal serous carcinoma (PPSC). The patient was diagnosed with PPSC and achieved a complete remission of PPSC following six cycles of platinum-based chemotherapy. Two hepatic nodules developed during the follow-up period and were initially labeled as hepatic metastases from the underlying PPSC, based on radiological findings. A resection of hepatic nodules was performed for therapeutic and diagnostic purposes, because there were no other metastatic foci except in the liver. Unexpectedly, serology and histology confirmed tertiary syphilis. This rare case emphasizes the importance of including tertiary syphilis in the differential diagnosis of a space-occupying lesion, even with an existing diagnosis of underlying cancer.


Phospholipid Membrane Formation Templated by Coacervate Droplets.
We report the formation of coacervate-supported phospholipid membranes by hydrating a dried lipid film in the presence of coacervate droplets. Coacervate-supported membranes were characterized by fluorescence imaging, polarization, fluorescence recovery after photobleaching of labeled lipids, lipid quenching experiments, and solute uptake experiments. Our findings are consistent with the presence of lipid membranes around the coacervates, with many droplets fully coated by what appear to be continuous lipid bilayers. In contrast to traditional giant lipid vesicles formed by gentle hydration in the absence of coacervates, the coacervate-templated membrane vesicles are more uniform in size, shape, and apparent lamellarity. Due to their fully coacervate model cytoplasm, these simple artificial cells are macromolecularly crowded and can be easily pre-loaded with high concentrations of proteins or nucleic acids. Within the same population, in addition to coacervate droplets having intact lipid membrane coatings, other coacervate droplets are coated with membranes having defects or pores that permit solute entry, and some are coated with multilayered membranes. Membranes surrounding protein-based coacervate droplets provided protection from a protease added to the external solution. The simplicity of producing artificial cells having a coacervate model cytoplasm surrounded by a model membrane is at the same time interesting as a potential mechanism for prebiotic protocell formation and appealing for biotechnology. We anticipate that such structures could serve as a new type of model system for understanding interactions between intracellular phases and cell or organelle membranes, which are implicated in a growing number of processes ranging from neurotransmission to signaling.


In vitro and in vivo pharmacology of kratom.
Kratom products have been historically and anecdotally used in south Asian countries for centuries to manage pain and opioid withdrawal. The use of kratom products has dramatically increased in the United States. More than 45 kratom alkaloids have been isolated, yet the overall pharmacology of the individual alkaloids is still not well characterized. The purpose of this chapter is to summarize in vitro and in vivo opioid activities of the primary kratom alkaloid mitragynine and its more potent metabolite 7-hydroxymitragynine. Following are experimental procedures described to characterize opioid receptor activity; receptor binding and functional assays, antinociceptive assays, operant conditioning assays, and respiratory plethysmography. The capacity of kratom alkaloids to confer tolerance and physical dependence as well as their pharmacokinetic properties are also summarized. The data reviewed here suggest that kratom products and mitragynine possess low efficacy agonist activity at the mu-opioid receptor in vivo. In addition, kratom products and mitragynine have been demonstrated to antagonize the effects of high efficacy mu-opioid agonists. The data further suggest that 7-hydroxymitragynine formed in vivo by metabolism of mitragynine may be minimally involved in the overall behavioral profile of mitragynine and kratom, whereas 7-hydroxymitragynine itself, at sufficiently high doses administered exogenously, shares many of the same abuse- and dependence-related behavioral effects associated with traditional opioid agonists. The apparent low efficacy of kratom products and mitragynine at mu-opioid receptors supports the development of these ligands as effective and potentially safe medications for opioid use disorder.


Evaluation of postoperative complications according to treatment of third molars in mandibular angle fracture.
The aim of this study was to evaluate the implication of third molars in postoperative complications of mandibular angle fracture with open reduction and internal fixation (ORIF). Data were collected on patients who presented with mandibular angle fracture at our Department of Oral and Maxillofacial Surgery between January 2011 and December 2015. Of the 63 total patients who underwent ORIF and perioperative intermaxillary fixation (IMF) with an arch bar, 49 patients were identified as having third molars in the fracture line and were followed up with until plate removal. The complications of postoperative infection, postoperative nerve injury, bone healing, and changes in occlusion and temporomandibular joint were evaluated and analyzed using statistical methods. In total, 49 patients had third molars in the fracture line and underwent ORIF surgery and perioperative IMF with an arch bar. The third molar in the fracture line was retained during ORIF in 39 patients. Several patients complained of nerve injury, temporomandibular disorder (TMD), change of occlusion, and postoperative infection around the retained third molar. The third molars were removed during ORIF surgery in 10 patients. Some of these patients complained of nerve injury, but no other complications, such as TMD, change in occlusion, or postoperative infection, were observed. There was no delayed union or nonunion in either of the groups. No statistically significant difference was found between the non-extraction group and the retained teeth group regarding complications after ORIF. If the third molar is partially impacted or completely nonfunctional, likely to be involved in pathologic conditions later in life, or possible to remove with the plate simultaneously, extraction of the third molar in the fracture line should be considered during ORIF surgery of the mandible angle fracture.


Peroxiredoxin 1 promotes pancreatic cancer cell invasion by modulating p38 MAPK activity.
The aim of this study was to investigate the role of peroxiredoxin 1 (Prdx1) in the invasiveness of pancreatic ductal adenocarcinoma (PDAC) cells. Immunohistochemistry was used to determine overexpression of Prdx1 in human PDAC tissues. Immunoprecipitation and immunocytochemistry were used to determine the interaction and intracellular distribution of Prdx1 and a member of the mitogen-activated protein kinase (MAPK) family protein, p38 MAPK, in PDAC cells. Finally, immunocytochemistry and Matrigel invasion assay were used to examine the effects of Prdx1 and p38 MAPK on the formation of cell protrusions and PDAC cell invasion. Prdx1 is overexpressed in human PDAC tissues. Peroxiredoxin 1 interacts with active forms of p38 MAPK, and complexes of Prdx1 and phosphorylated p38 MAPK localize at the leading edges of migrating PDAC cells. Suppression of Prdx1 decreases active p38 MAPK localized in cell protrusions and inhibits the invasiveness of PDAC cells. Consequently, suppression of Prdx1 inhibits membrane ruffling and protrusions. The p38 MAPK inhibitor SB203580 also decreases the formation of membrane protrusions and inhibits invasiveness. Prdx1 associates with the formation of membrane protrusions through modulation of the activity of p38 MAPK, which in turn promotes PDAC cell invasion.


Pre-pregnancy high-risk factors at first antenatal visit: how predictive are these of pregnancy outcomes?
To determine relationships between pre-pregnancy risk factors at first antenatal visit booking and pregnancy outcomes. This was a multicenter, cross-sectional study involving women admitted for singleton delivery from July 1 until October 31 (3 months), 2013, at nine major maternity clinics in Kinshasa, Democratic Republic of Congo. All women were checked for hereditary, community, and personal medical/surgical risk situations and mother/infant problems in previous pregnancies. Maternal and perinatal complications related to current/just-terminated pregnancy were analyzed according to pre-pregnancy risk factors in order to establish their prediction concerning maternal and perinatal complications related to current/just-terminated pregnancy (odds ratios). Results are given with 95% confidence intervals, and P<0.05 was considered significant. The study sample comprised 2,086 women. Primiparity (36.5%), single relationship status (26.4%), and maternal age ≥35 years (18.3%) were the most important non-pathologic risk factors, while arterial hypertension in family (34.3%), previous miscarriage (33.2%), overweight/obesity (21.9%), diabetes in family (21.1%), previous cesarean section (15.7%), previous postpartum hemorrhage (13.1%), low birth weight (10%), previous macrosomia (10%), and previous premature rupture of membranes (6.2%) predominated among pathologic risk factors. Major adverse outcomes recurred in some women, with recurrence rates of 21/37 (57%), 111/208 (53%), 74/208 (36%), 191/598 (32%), 132/466 (28%), 24/130 (18%), and 4/65 (6%) for prematurity, low birth weight, macrosomia, preeclampsia/eclampsia, cesarean section, premature rupture of membranes, and stillbirth, respectively. Outcomes that were significantly influenced by non-pathologic risk factors were also significantly influenced by pathologic risk factors. Pregnancy adverse outcomes are strongly influenced by either non-pathologic or pathologic pre-pregnancy risk factors at first antenatal visit booking. The recurrence potential of complications is one reason to establish the predictability and preventability of morbidity such that the most appropriate referrals and best options throughout the pregnancy can be determined.


Seasonal variation on the ectoparasitic communities of Nile tilapia cultured in three regions in southern Brazil.
A total of 240 Nile tilapia were examined between April 2007 and March 2008, gathered from three different fish farms, 20 fish in each fish farm, in the four seasons of the year. Fish ponds were located in Joinville, Blumenau and Ituporanga, Santa Catarina state, Brazil and each pond had a different culture system. Prevalence, mean intensity, mean abundance and mean relative dominance were compared among fish ponds and seasons. During this period, the water quality was kept in normal values. Piscinoodinium pillulare (Dinoflagellida) was the most dominant parasite followed by Trichodina magna e T. compacta (Ciliophora), Cichlydogyrus sclerosus, C halli, C. thurstonae, Scutogyrus longicornis (Monogenoidea), copepodids Lernaeidae gen. sp. The highest prevalence, mean intensity and mean abundance of ectoparasites were found on the body surface in fish from Joinville followed by Blumenau and Ituporanga. In the gills, the highest mean intensity and mean abundance were found in fish from Blumenau and Ituporanga in the winter. Piscinoodinium pillulare showed prevalence 100% during autumn in Blumenau and Ituporanga. In winter P. pillulare occurred in all study facilities. Fish from Joinville showed 100% prevalence of Monogenoidea during all seasons, as well as the highest mean intensity and abundance. The results showed that the majority of examined fish had higher infestations by protozoan during autumn and winter and higher infestations by metazoan have occurred in spring and summer.


Alendronate-induced chemical laryngitis.
Alendronate is a bisphosphonate used in treating osteoporosis. Its recognized side-effects include oesophageal irritation and ulceration. The authors describe a case of laryngitis induced by transient contact of this medication with the laryngeal mucosa. Successful management of this case is also detailed.


Sophisticated Cloning, Fermentation, and Purification Technologies for an Enhanced Therapeutic Protein Production: A Review.
The protein productions strategies are crucial towards the development of application based research and elucidating the novel purification strategies for industrial production. Currently, there are few innovative avenues are studies for cloning, upstream, and purification through efficient bioprocess development. Such strategies are beneficial for industries as well as proven to be vital for effectual therapeutic protein development. Though, these techniques are well documented, but, there is scope of addition to current knowledge with novel and new approaches and it will pave new avenues in production of recombinant microbial and non-microbial proteins including secondary metabolites. In this review, we have focussed on the recent development in clone selection, various modern fermentation and purification technologies and future directions in these emerging areas. Moreover, we have also highlighted notable perspectives and challenges involved in the bioengineering of such proteins, including quality by design, gene editing and pioneering ideas. The biopharmaceutical industries continue to shift towards more flexible, automated platforms and economical product development, which in turn can help in developing the cost effective processes and affordable drug development for a large community.


Enhanced expression of urokinase-type plasminogen activator in the rat endometrium following induction of decidualisation.
Urokinase-type plasminogen activator(uPA) assayed in uteri of cycling and deciduoma bearing rats shows detectable levels of this enzyme in endometrium. Zymographic analysis confirms uPA of decidual tissue and, following artificial induction of decidualisation, uPA activity constantly increases in the decidualising endometrium reaching a peak on day 9 of pseudopregnancy. Endometrial uPA of nonpregnant rats does not show any significant change during estrous cycle. Results are discussed in relation to expression of this activator in endometrium of rats during morphogenesis of decidual cells.


Catalytic Hydrothiolation: Regio- and Enantioselective Coupling of Thiols and Dienes.
We report a Rh-catalyzed hydrothiolation of 1,3-dienes, including petroleum feedstocks. Either secondary or tertiary allylic sulfides can be generated from the selective addition of a thiol to the more substituted double bond of a diene. The catalyst tolerates a wide range of functional groups, and the loading can be as low as 0.1 mol %.


Breast cancer: missed interval and screening-detected cancer at full-field digital mammography and screen-film mammography-- results from a retrospective review.
To compare the percentages and mammographic features of cancers missed at full-field digital mammography (FFDM) and screen-film mammography (SFM) in women who participated in the Norwegian Breast Cancer Screening Program in 2002-2008. Social Science Data Services approval was obtained; the requirement for informed consent was waived. Cases were all the interval and screening-detected cancers from 35 127 FFDM and 52 444 SFM examinations in two Norwegian counties. Prior and diagnostic FFDM examinations of 49 interval and 86 screening-detected breast cancers were reviewed by four breast radiologists and compared with a review of SFM examinations of 81 interval and 123 screening-detected cancers. Cancers were classified as missed or true, mammographic features were described, percentages were compared by using the χ(2) or Fisher exact test, and 95% confidence intervals (CIs) were calculated. The percentages of interval and screening-detected cancers missed at FFDM and SFM did not differ significantly. (interval cancers missed: 33% [16 of 49] at FFDM vs 30% [24 of 81] at SFM [P = .868]; screening-detected cancers missed: 20% [17 of 86] at FFDM vs 21% [26 of 123] at SFM [P = .946]). Asymmetry was present in 27% (95% CI: 13.3%, 45.5%) of prior mammograms of cancers missed at FFDM and 10% (95% CI: 3.3%, 21.8%) of those missed at SFM (P = .070). Calcifications were observed in 18% (95% CI: 7.0%, 35.5%) of the cancers missed at FFDM and 34% (95% CI: 21.2%, 48.8%) of those missed at SFM (P = .185). Average mammographic tumor size of missed cancers manifesting as masses was 10.4 mm at FFDM and 13.6 mm at SFM (P = .036). The use of FFDM has not reduced the challenge of missed cancers. Cancers missed at FFDM tend to have different mammographic features than those missed at SFM.


Alpha-2,6-sialylation of L-PHA reactive oligosaccharides and expression of N-acetylglucosaminyltransferase V in human diffuse large B cell lymphoma.
Cell surface sialylation and beta1-6 branching of L-PHA reactive oligosaccharides play an important role in metastatic capacities of various tumor cell lines. We analyzed the expression and sialylation of L-PHA reactive oligosaccharides in human diffuse large B cell lymphoma (DLBCL). DLBCL was grouped into three types; i). Group A, non-reactive type with no expression of L-PHA reactive oligosaccharides, ii). Group B, sialylated type with expression of sialylated L-PHA reactive oligosaccharides and iii). Group C, non-sialylated type with expression of non-sialylated L-PHA reactive oligosaccharides. To clarify the linkage of sialic acid residues in L-PHA reactive oligosaccharides of Group B cases, L-PHA lectin histochemistry after treatment with two different neuraminidases was performed. In all Group B cases, L-PHA binding reactivity was found after treatment with Vibrio cholerae neuraminidase. But not after treatment with Newcastle disease virus neuraminidase. These data indicate that alpha2,6-linked sialic acid residues were predominantly involved in sialylation of L-PHA reactive oligosaccharides of Group B. To clarify the relationship between expression of N-acetylglucosaminyltransferase V (GnT-V), which catalyzes beta1-6 branching of L-PHA reactive oligosaccharides, and L-PHA reactivities in DLBCL, we investigated the expression of GnT-V using immunohistochemical methods. Most of the Group B and C cases expressed GnT-V while 33% of Group A cases showed no expression of GnT-V. These data suggest that expression of GnT-V is not always correlated with the expression of L-PHA reactive glycoconjugates. Furthermore, survival of patients in Group A which showed no expression of GnT-V was significantly shorter than that of patients in Group C which expressed GnT-V. Therefore, loss of non-sialylated L-PHA reactive oligosaccharides due to lack of expression of GnT-V in lymphoma cells may be associated with aggressiveness of DLBCL.


Assessment of kininases in rheumatic diseases and the effect of therapeutic agents.
Bradykinin is degraded in human plasma by a carboxypeptidase to yield desArg9-bradykinin (DBK) which is then digested by angiotensin-converting enzyme (ACE) to the pentapeptide Arg-Pro-Pro-Gly-Phe and the tripeptide Ser-Pro-Phe. We have studied the rate of kinin degradation by each of these enzymes in patients with rheumatoid arthritis (RA) and with systemic lupus erythematosus (SLE), compared with the degradation rate in degenerative joint disease and normal subjects. Carboxypeptidase activity was the same in all individuals, but ACE activity was increased in the RA and SLE patients. We examined the effects of aspirin, sodium salicylate, auranofin, penicillamine, and corticosteroids on kinin metabolism, and all of these were marked inhibitors of ACE; however, only penicillamine had any demonstrable inhibition of carboxypeptidase. These observations suggest rapid degradation of DBK in patients with untreated RA and SLE, whereas drugs utilized in therapy have the opposite effects. Studies to examine the role of DBK in disease manifestations are in progress.


The ongoing impact of the COVID-19 pandemic on physical activity and screen time among Canadian youth.
The COVID-19 pandemic has caused changes in health behaviours, including participation in physical activity and screen time. The purpose of this paper is to examine trends in physical activity and screen time among Canadian youth from January 2018 to February 2022. The Canadian Community Health Survey asks Canadian youth (aged 12 to 17 years) to report the time they spend active by domain: recreation, transportation, school and household. Survey respondents are also asked to report their screen time on school days and non-school days. The present analysis compares the physical activity from four cross-sectional samples collected during 2018 (January to December; n=3,952), January to March 2020 (n=911), September to December 2020 (n=1,573), and January 2021 to February 2022 (n=3,501). Screen time is compared between 2018 and 2021/2022. Sub-annual descriptive analyses examine how physical activity and screen time varied within and between these years. Before the COVID-19 pandemic, half of Canadian youth met the physical activity recommendation (2018: 49.6%; January to March 2020: 53.7%). The percentage meeting the recommendation dropped in the first year of the pandemic (September to December 2020: 37.3%) and recovered slightly in 2021 (43.8%). From 2018 to 2021, total physical activity dropped by 8.3 minutes per day (58.1 minutes per week) among girls and by 2.1 minutes per day (14.7 minutes per week) among boys. The percentage of youth meeting the screen time recommendation on school days dropped from 40.7% in 2018 to 29.1% in 2021 and from 21.4% in 2018 to 13.2% in 2021 on non-school days. The COVID-19 pandemic had a detrimental impact on the physical activity and screen time of youth, in particular among girls. This analysis provides an update on how the pandemic has continued to affect the physical activity and screen habits of youth in 2020, 2021, and early 2022.


Lipoprotein particle distribution and skeletal muscle lipoprotein lipase activity after acute exercise.
Many of the metabolic effects of exercise are due to the most recent exercise session. With recent advances in nuclear magnetic resonance spectroscopy (NMRS), it is possible to gain insight about which lipoprotein particles are responsible for mediating exercise effects. Using a randomized cross-over design, very low density lipoprotein (VLDL) responses were evaluated in eight men on the morning after i) an inactive control trial (CON), ii) exercising vigorously on the prior evening for 100 min followed by fasting overnight to maintain an energy and carbohydrate deficit (EX-DEF), and iii) after the same exercise session followed by carbohydrate intake to restore muscle glycogen and carbohydrate balance (EX-BAL). The intermediate, low and high density lipoprotein particle concentrations did not differ between trials. Fasting triglyceride (TG) determined biochemically, and mean VLDL size were lower in EX-DEF but not in EX-BAL compared to CON, primarily due to a reduction in VLDL-TG in the 70-120 nm (large) particle range. In contrast, VLDL-TG was lower in both EX-DEF and EX-BAL compared to CON in the 43-55 nm (medium) particle range. VLDL-TG in smaller particles (29-43 nm) was unaffected by exercise. Because the majority of VLDL particles were in this smallest size range and resistant to change, total VLDL particle concentration was not different between any of these conditions. Skeletal muscle lipoprotein lipase (LPL) activity was also not different across these 3 trials. However, in CON only, the inter-individual differences in LPL activity were inversely correlated with fasting TG, VLDL-TG, total, large and small VLDL particle concentration and VLDL size, indicating a regulatory role for LPL in the non-exercised state. These findings reveal a high level of differential regulation between different sized triglyceride-rich lipoproteins following exercise and feeding, in the absence of changes in LPL activity.


Clinically relevant biology of hereditary breast cancer.
The identification of the two major breast cancer susceptibility genes BRCA1 and BRCA2 has led to an explosion of work covering the biology and epidemiology of these genes. Clinically, much is known about the risks associated with mutations in these genes, but less is certain with regards to their impact on treatment. This review will touch upon several important aspects of the biology of BRCA1 and BRCA2, but comments regarding these areas will be restricted to those most relevant to the clinician. The three main sections are molecular pathology, DNA repair, and finally other functions of the BRCA1 and BRCA2 proteins.


Modeling the lifecycle of Ebola virus under biosafety level 2 conditions with virus-like particles containing tetracistronic minigenomes.
Ebola viruses cause severe hemorrhagic fevers in humans and non-human primates, with case fatality rates as high as 90%. There are no approved vaccines or specific treatments for the disease caused by these viruses, and work with infectious Ebola viruses is restricted to biosafety level 4 laboratories, significantly limiting the research on these viruses. Lifecycle modeling systems model the virus lifecycle under biosafety level 2 conditions; however, until recently such systems have been limited to either individual aspects of the virus lifecycle, or a single infectious cycle. Tetracistronic minigenomes, which consist of Ebola virus non-coding regions, a reporter gene, and three Ebola virus genes involved in morphogenesis, budding, and entry (VP40, GP1,2, and VP24), can be used to produce replication and transcription-competent virus-like particles (trVLPs) containing these minigenomes. These trVLPs can continuously infect cells expressing the Ebola virus proteins responsible for genome replication and transcription, allowing us to safely model multiple infectious cycles under biosafety level 2 conditions. Importantly, the viral components of this systems are solely derived from Ebola virus and not from other viruses (as is, for example, the case in systems using pseudotyped viruses), and VP40, GP1,2 and VP24 are not overexpressed in this system, making it ideally suited for studying morphogenesis, budding and entry, although other aspects of the virus lifecycle such as genome replication and transcription can also be modeled with this system. Therefore, the tetracistronic trVLP assay represents the most comprehensive lifecycle modeling system available for Ebola viruses, and has tremendous potential for use in investigating the biology of Ebola viruses in future. Here, we provide detailed information on the use of this system, as well as on expected results.


Effect of Total Laparoscopic Hysterectomy vs Total Abdominal Hysterectomy on Disease-Free Survival Among Women With Stage I Endometrial Cancer: A Randomized Clinical Trial.
Standard treatment for endometrial cancer involves removal of the uterus, tubes, ovaries, and lymph nodes. Few randomized trials have compared disease-free survival outcomes for surgical approaches. To investigate whether total laparoscopic hysterectomy (TLH) is equivalent to total abdominal hysterectomy (TAH) in women with treatment-naive endometrial cancer. The Laparoscopic Approach to Cancer of the Endometrium (LACE) trial was a multinational, randomized equivalence trial conducted between October 7, 2005, and June 30, 2010, in which 27 surgeons from 20 tertiary gynecological cancer centers in Australia, New Zealand, and Hong Kong randomized 760 women with stage I endometrioid endometrial cancer to either TLH or TAH. Follow-up ended on March 3, 2016. Patients were randomly assigned to undergo TAH (n = 353) or TLH (n = 407). The primary outcome was disease-free survival, which was measured as the interval between surgery and the date of first recurrence, including disease progression or the development of a new primary cancer or death assessed at 4.5 years after randomization. The prespecified equivalence margin was 7% or less. Secondary outcomes included recurrence of endometrial cancer and overall survival. Patients were followed up for a median of 4.5 years. Of 760 patients who were randomized (mean age, 63 years), 679 (89%) completed the trial. At 4.5 years of follow-up, disease-free survival was 81.3% in the TAH group and 81.6% in the TLH group. The disease-free survival rate difference was 0.3% (favoring TLH; 95% CI, -5.5% to 6.1%; P = .007), meeting criteria for equivalence. There was no statistically significant between-group difference in recurrence of endometrial cancer (28/353 in TAH group [7.9%] vs 33/407 in TLH group [8.1%]; risk difference, 0.2% [95% CI, -3.7% to 4.0%]; P = .93) or in overall survival (24/353 in TAH group [6.8%] vs 30/407 in TLH group [7.4%]; risk difference, 0.6% [95% CI, -3.0% to 4.2%]; P = .76). Among women with stage I endometrial cancer, the use of total abdominal hysterectomy compared with total laparoscopic hysterectomy resulted in equivalent disease-free survival at 4.5 years and no difference in overall survival. These findings support the use of laparoscopic hysterectomy for women with stage I endometrial cancer. clinicaltrials.gov Identifier: NCT00096408; Australian New Zealand Clinical Trials Registry: CTRN12606000261516.


Spheroid formation and modulation of tenocyte-specific gene expression under simulated microgravity.
For tendon tissue engineering, tenocyte-seeded scaffolds are a promising approach. Under conventional 2D culture however, tenocytes show rapid senescene and phenotype loss. We hypothesized that phenotype loss could be counteracted by simulated microgravity conditions. Human tenocytes were exposed to microgravity for 9 days on a Random Positioning Machine (RPM). Formation of 3D-structures (spheroids) was observed under light microscopy, gene expression was measured by real-time PCR. Cells under conventional 2D-culture served as control group. Simulated microgravity reached a value of as low as 0.003g. Spheroid formation was observed after 4 days, and spheroids showed stable existance to the end of the observation period. After 9 days, spheroids showed a significantly higher gene expression of collagen 1 (Col1A1) compared to adherent cells under microgravity (4.4x, p=0.04) and compared to the control group (5.6x, p=0.02). Gene expression of collagen 3 (COL3A1) was significantly increased in spheroids compared to the control group (2.3x, p=0.03). Gene expressions of the extracellular matrix genes Tenascin C und Fibronectin (TNC and FN) were increased in adherent cells under microgravity compared to the 1g-control group, not reaching statistical significance (p=0.1 and p=0.3). For the gene expression of vimentin, no significant alteration was observed both in the adherent cells and in the spheroids compared to the 1g control group. Gene expression of the tenocyte-specific transcription factor scleraxis (SCX) was significantly increased in spheroids compared to the control group (3.7x, p=0.03). Simulated microgravity could counteract tenocyte senescence in vitro and serve as a promising model for scaffold-free 3D cell culturing and tissue engineering. V (laboratory study).


Genetic correlations with floral display lead to sexual dimorphism in the cost of reproduction.
In dioecious plants, females typically invest more biomass in reproduction than males and consequently experience stronger life-history trade-offs. Sexual dimorphism in life history runs counter to this pattern in Silene latifolia: females acquire less carbon and invest more biomass in reproduction, but males pay a higher cost of reproduction. The species is sexually dimorphic for many traits, especially flower number, with males producing many, small flowers compared to females. We tested whether the cost of reproduction is higher in males because flower number, which we presume to be under sexual selection in males, is genetically correlated with traits that would affect life-history trade-offs. We performed artificial selection to reduce the sexual dimorphism in flower size and looked at correlated responses in ecophysiological traits. We found significant correlated responses in total vegetative mass, leaf mass, leaf thickness, and measures of CO(2) exchange. Individuals in the many-and-small-flowered selection lines did not grow as large or invest as much biomass in leaves, and their leaves exhibited an up-regulated physiology that shortened leaf life span. Our results are consistent with the hypothesis that genetic correlations between floral display and ecophysiological traits lead to a higher cost of reproduction for males.


Renegotiating formal and informal care while ageing abroad: Older Pakistani women's healthcare access, preferences and expectations in Norway.
This study explores older Pakistani women's preferences and expectations of formal and informal care while ageing in Norway. Our study is based on qualitative interviews with older Pakistani women living in Oslo municipality, Norway. The participants were aged between 48 and 81 years and had been living in Norway for 26 to 46 years. Our analyses resulted in five themes: 1) renegotiating the expectations of informal care in light of the 'nazaam' (or social system and practices) of Norway, 2) fear of being left behind in residential care homes, 3) disloyalty and shame of being cared for by outsiders, 4) perceptions about the quality of formal care and 5) concerns about mixing with other cultures and genders. Our findings point to potential barriers beyond culture that influence older Pakistani women's preferences for, expectations of and access to formal care services. The study further highlights the structural barriers that older Pakistani women perceive and experience in accessing formal care services in a majority society.


Tumor-altered dendritic cell function: implications for anti-tumor immunity.
Dendritic cells (DC) are key regulators of both innate and adaptive immunity, and the array of immunoregulatory functions exhibited by these cells is dictated by their differentiation, maturation, and activation status. Although a major role for these cells in the induction of immunity to pathogens has long been appreciated, data accumulated over the last several years has demonstrated that DC are also critical regulators of anti-tumor immune responses. However, despite the potential for stimulation of robust anti-tumor immunity by DC, tumor-altered DC function has been observed in many cancer patients and tumor-bearing animals and is often associated with tumor immune escape. Such dysfunction has significant implications for both the induction of natural anti-tumor immune responses as well as the efficacy of immunotherapeutic strategies that target endogenous DC in situ or that employ exogenous DC as part of anti-cancer immunization maneuvers. In this review, the major types of tumor-altered DC function will be described, with emphasis on recent insights into the mechanistic bases for the inhibition of DC differentiation from hematopoietic precursors, the altered programing of DC precursors to differentiate into myeloid-derived suppressor cells or tumor-associated macrophages, the suppression of DC maturation and activation, and the induction of immunoregulatory DC by tumors, tumor-derived factors, and tumor-associated cells within the milieu of the tumor microenvironment. The impact of these tumor-altered cells on the quality of the overall anti-tumor immune response will also be discussed. Finally, this review will also highlight questions concerning tumor-altered DC function that remain unanswered, and it will address factors that have limited advances in the study of this phenomenon in order to focus future research efforts in the field on identifying strategies for interfering with tumor-associated DC dysfunction and improving DC-mediated anti-tumor immunity.


Bioactivity-Guided Isolation of Cytotoxic Phenanthrenes from Spiranthes sinensis.
Bioactivity-guided separation led to the isolation of six novel phenanthrenes, spiranthesphenanthrenes A-F (1-6), together with 19 known compounds, including seven phenanthrenes (7-13), one bibenzyl compound (14), five flavonoids (15-16 and 20-22), and six simple phenolic compounds (17-19 and 23-25), from the petroleum ether (PE) and ethyl acetate (EtOAc) extracts of Spiranthes sinensis (Pers.) Ames, an edible medicinal plant named "panlongshen" in Chinese that is popularly used in medicinal foods and herbal teas. The structures of the obtained compounds were identified on the basis of extensive NMR spectroscopy and HR-ESI-MS analyses. The cytotoxicities of the phenanthrenes (1-13), the bibenzyl compound (14) , and the flavonoids (15-16 and 20-22) toward SGC-7901, HepG2, and B16-F10 cell lines were examined in vitro. Compounds 1 and 7 exhibited moderate cytotoxic activities toward all of the selected cancer cell lines, and their IC50 values ranged from 19.0 ± 7.3 to 30.2 ± 5.6 μM. Spiranthesphenanthrene A (1) exhibited higher cytotoxic activity than the positive control cisplatin toward the B16-F10 cell line (IC50 = 19.0 ± 7.3 μM). A wound healing assay revealed the inhibition of the migration of B16-F10 cancer cells in a time- and dose-dependent pattern by treatment with 2.5, 5, and 10 μM solutions of compound 1 for 24 and 48 h, respectively. Western blots revealed that compound 1 obviously increased the level of the E-cadherin protein (an epithelial marker) and decreased the levels of the vimentin and N-cadherin proteins (mesenchymal markers). Furthermore, the level of the transcription factor Snail was also obviously decreased by compound 1 in a dose-dependent manner. Taken together, compound 1 inhibits the migration of B16-F10 cancer cells, which may be closely related to the inhibition of the epithelial-mesenchymal transition. Compound 1 represents a promising drug candidate for the prevention of tumor metastasis.


Is the binary hard-sphere mixture a good reference system for sterically stabilized colloids?
The relevance of the hard-sphere mixture model as a starting point for the study of sterically stabilized colloids is discussed. Two physical situations are distinguished: true molecular solvent-colloid mixtures, and pseudobinary mixtures of two supramolecular objects. For the former, the limitation of the hard-sphere mixture model are recalled. Its potential use as a reference system for perturbation treatments is then analyzed. The accuracy of the latter is tested numerically. This study shows that the hard-sphere mixture is, in general, not a good reference system for sterically stabilized colloids in molecular solvents. For pseudobinary mixtures, the potential of mean force between the bigger solutes induced by the smaller ones is considered. The influence of a very short-range heteroattraction is discussed.


Molecular and organismal changes in offspring of male mice treated with chemical stressors.
Both gene methylation changes and genetic instability have been noted in offspring of male rodents exposed to radiation or chemicals, but few specific gene targets have been established. Previously, we identified the gene for ribosomal RNA, rDNA, as showing methylation change in sperm of mice treated with the preconceptional carcinogen, chromium(III) chloride. rDNA is a critical cell growth regulator. Here, we investigated the effects of paternal treatments on rDNA in offspring tissue. A total of 93 litters and 758 offspring were obtained, permitting rigorous mixed-effects models statistical analysis of the results. We show that the offspring of male mice treated with Cr(III) presented increased methylation in a promoter sequence of the rDNA gene, specifically in lung. Furthermore polymorphic variants of the multi-copy rDNA genes displayed altered frequencies indicative of structural changes, as a function of both tissue type and paternal treatments. Organismal effects also occurred: some groups of offspring of male mice treated with either Cr(III) or its vehicle, acidic saline, compared with those of untreated mice, had altered average body and liver weights and levels of serum glucose and leptin. Males treated directly with Cr(III) or acidic saline presented serum hormone changes consistent with a stress response. These results establish for the first time epigenetic and genetic instability effects in a gene of central physiological importance, in offspring of male mice exposed preconceptionally to chemicals, possibly related to a stress response in these males.


A reappraisal of the monoclonal rheumatoid factor test for circulating immune complexes: a comparison of two monoclonal rheumatoid factor reagents.
Assays involving monoclonal rheumatoid factor (mRF) reagents are frequently used for the detection of circulating immune complexes, particularly in the rheumatic diseases. A study has been performed to investigate the interaction of two purified mRF reagents with normal sera, sera and synovial fluid from patients with rheumatic diseases and with heat-aggregated human IgG used as a model of immune complexes. Interaction has been measured by a simple laser nephelometric technique and a sensitive radiolabelled mRF precipitation assay. Both mRF reagents showed little reactivity with normal sera but reacted strongly with many of the pathological specimens. Similarly both mRFs reacted with large molecular sized heat aggregates of IgG while a variable reactivity was found with uncomplexed or monomeric IgG. However in pathological sera, both mRFs reacted predominantly with monomeric IgG and a significant correlation was found between the two reagents. This reactivity with monomeric IgG remained after separation of pathological sera in low pH sucrose gradients suggesting it was not due to the presence of small immune complexes of the classical type. In addition no reactivity was found with either reagent with IgG-RF intermediate complexes. It is concluded that mRF reagents are not specific for IgG containing immune complexes. They also react with monomeric IgG and this reactivity is particularly prominent in certain pathological sera. The possible nature of this reactive monomeric IgG is discussed.


Effects of firing frequency on length-dependent myofascial force transmission between antagonistic and synergistic muscle groups.
Effects of stimulation frequency on myofascial force transmission between rat peroneal and triceps surae and antagonistic anterior crural muscles, and between extensor digitorum longus (EDL) and tibialis anterior and extensor hallucis longus (TA + EHL) muscles were investigated for lengthening of all anterior crural muscles. Muscles contracted isometrically at firing rates of 10, 20, 30 and 100 Hz. EDL and TA + EHL were distally lengthened. Peroneal and triceps surae muscles attained a constant muscle-tendon complex length. Peroneal and triceps surae distal active force decreased significantly as a function of anterior crural muscle length, also at submaximal activation. The absolute decrease was highest for 100 Hz (peroneal muscles -0.87 N; triceps surae muscles -0.92 N), but the highest normalized decrease occurred at 10 Hz stimulation (peroneal muscles -34%; triceps surae muscles -18%). At all muscle lengths, a negative proximo-distal difference in EDL active force was present which decreased with lower firing frequencies (from -0.4 N at 100 Hz to -0.03 N at 10 Hz). The passive proximo-distal force difference attained positive values. EDL and TA + EHL length-force characteristics agree with effects of firing frequency, except for 10 Hz stimulation, where active force was higher than expected and optimum length shifted to lower muscle lengths. It is concluded that also at submaximal stimulation frequencies, extramuscular myofascial force transmission between peroneal and triceps surae muscles and antagonistic anterior crural muscles is substantial. Although lengthening of submaximally active anterior crural muscles decreases the net myofascially transmitted load on EDL, myofascial force transmission significantly alters effects of firing frequency on length-force characteristics.


Association of decreased spermatozoa omega-3 fatty acid levels and increased oxidative DNA damage with varicocele in infertile men: a case control study.
Varicocele is commonly associated with male infertility because it impairs normal sperm morphology and activity. Polyunsaturated fatty acids (PUFA) are important determinants of sperm cell structure and function, but their relationship with varicocele remains unclear. The aim of the present study was to investigate the PUFA composition in spermatozoa of infertile men with varicocele and to evaluate the potential relationship between PUFA and varicocele. This case control study recruited 92 infertile men with varicocele, 99 infertile men without varicocele and 95 fertile male control subjects. Semen morphology and activity parameters were assessed and seminal plasma 8-hydroxy-2-deoxyguanosine (8-OHdG) content was determined by ELISA. Sperm concentrations of omega-3 and omega-6 fatty acids were measured by gas chromatography. Infertile men with varicocele had lower concentrations of omega-3 PUFA, higher omega-6:omega-3 PUFA ratios and greater oxidative DNA damage in spermatozoa compared with infertile men without varicocele and normal subjects. The degree of varicocele and DNA damage was associated with decreased omega-3 PUFA concentrations and semen quality in infertile men with varicocele. The findings suggest that omega-3 PUFA deficiency could be implicated in varicocele-associated infertility, and highlight the need for intervention trials to test the usefulness of omega-3 supplementation in reducing sperm abnormalities in infertile men with varicocele.


Antibacterial activity of bladder surface mucin duplicated in the rabbit bladder by exogenous glycosaminoglycan (sodium pentosanpolysulfate).
Previous data from our laboratory suggest that the transitional epithelium of the urinary bladder secretes and binds to its surface a glycosaminoglycan. The presence of this substance at the bladder surface markedly reduces the ability of microorganisms to adhere to the mucosa. Furthermore, this glycosaminoglycan can be removed (with acid) and replaced by intravesical instillation of a synthetic sulfonated glycosaminoglycan (heparin), whose presence is as effective as that of the natural glycosaminoglycan in reducing adherence. We conducted the current study with a different sulfonated glycosaminoglycan to determine whether the antiadherence activity is generalized to heparin congeners and whether the antiadherence effect of heparin is independent of its known anticoagulant activity. In this study we examined the sulfonated glycosaminoglycan, sodium pentosanpolysulfate, which lacks significant anticoagulant activity, and found it to have a mechanism of antiadherence analogous to that of heparin and almost equally as active on a weight basis.


The nurse as a sex object in motion pictures, 1930 to 1980.
A content analysis of 191 motion pictures featuring 211 nurses as significant characters was conducted to determine the nature and extent of the motion picture industry's depiction of the nurse as a sex object and to identify changes in that portrayal from 1930 to 1980. Seventy-three percent of the nurse roles characterized nurses as sex objects. The frequency and intensity of stereotypes of nurses as sex objects rose significantly during the 1960s and 1970s (p less than .0001). Exploitation of the nurse as a sex object was more common in the larger nurse roles. However, in films with a strong emphasis on professional nursing in either the story or in character development, sexual stereotyping of nurses was uncommon. It was concluded that the image of the nurse as a professional care giver was incompatible with that of the nurse as sex object, and that the motion picture industry has opted primarily to present the latter image. The extremely negative sexual stereotype of nursing promulgated during the past 20 years is cause for concern. Actions that the nursing profession can employ to counter the unfavorable portrayal of nurses in 1980s motion pictures are suggested.


Analysis of the sex-specific variability of blood parameters in data sets of the Mouse Phenome Database.
The use of mice as animal models in biomedical research allows the standardization of genetic background and environmental conditions, which both affect phenotypic variability. As the use of both sexes in experiments is strongly recommended, sex-specific phenotypic variability is discussed with regard to putative consequences on the group size which is necessary for achieving valid and reproducible results. In this study, the sex-specific variability of 25 clinical chemical and hematological parameters which represent a comprehensive blood screen of laboratory mice, was analyzed in data sets which have been submitted to the Mouse Phenome Database. The overall analysis comprising all 25 clinical chemical and hematological parameters showed no evidence for substantial and robust general sex-specific variability. A large range of the ratio of the female and male coefficient of variation (CV) was found for every parameter among the respective strain data sets. This clearly demonstrated the appearance of unpredictable major interactions between genotype and environment regarding the sex-specific variability of the blood parameters analyzed.


[Effect of the aerosol inhalations of some antibacterial preparations on the cocco bacterial flora of the respiratory tract in pulmonary tuberculosis].
As a result of the experiments it was found the negativation of the sputum was 2 times higher in patients treated in addtion with inhalation of antibacterial drugs as compared to that in patients using no aerosol therapy. The rate of isolation of pathogenic staphylococci to the end of the treatment course was statistically insignificant though there was some tendency to an increase. No significant difference was observed in the antibiotic resistance development in the coccal and bacterial flora of the patients treated and not treated with streptomycin in the form of inhalation.