[ARTERIAL STIFFNESS AND BONE MINERAL DENSITY IN WOMEN WITH CORONARY HEART DISEASE AND CONCOMITANT SEVERE OSTEOPOROSIS].
The aim of the study was to estimate arterial stiffness and bone mineral density (BMD) in women with coronary heart disease (CHD) and concomitant osteoporosis. It included 120 patients (mean age 68.5 ± 8.7 years) divided into 2 groups matched for age and CHD duration. Group I was comprised of 74 women with CHD and severe osteoporosis, group 2 consisted of 46 women with isolated CHD. Carotid-femoral pulse wave velocity and central pulse wave were subjected to contour analysis by applanation tonometry using a SphygmoCor AtCor Medical apparatus (Australia). BMD was measured in lumbar vertebrae and proximal part of the femur by X-ray densitometer (XRD). Statistical treatment of the data obtained was performed with the use of Statistica 6.0 package, Wald-Wolfovitz criterion, and multifactorial regressive analysis; differences were considered statistically significant when the calculated P value was less than 0.05. Women with CHD and osteoporosis had higher arterial (diastolic/systolic) pressure, mean aortic pressure, and pulse wave velocity than patients with isolated CHD. The independent determinants of carotid-femoral segment stffness were age (β = 0.3, 95% CI 0.08-0.11, p = 0.027), BMD in the proximal part of the femur based on Z criterion (β = 5.02, 95% CI 8.4-10.6, p = 0.0059), BMD in the Wards area based on T criterion β = 5.07, 95% CI 6.0-8.1, p = 0.005). It is concluded that women with CHD and osteoporosis have elevated parameters of arterial stiffness including carotid-femoral pulse wave velocity, augmentation index, central pulse pressure, BMD in lumbar vertebrae and proximal part of the femur. Age and BMD in the proximal part of the femur are independent factors affecting arterial stiffness.


Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1beta in the substantia nigra.
The functional role of the long-lasting inflammation found in the substantia nigra (SN) of Parkinson's disease (PD) patients and animal models is unclear. Proinflammatory cytokines such as interleukin-1beta (IL-1beta) could be involved in mediating neuronal demise. However, it is unknown whether the chronic expression of cytokines such as IL-1beta in the SN can alter neuronal vitality. The aim of this study was to investigate the effects of the chronic expression of IL-1beta in the adult rat SN using a recombinant adenovirus expressing IL-1beta. The chronic expression of IL-1beta for 60 days induced dopaminergic cell death in the SN and unilateral akinesia starting only at 21 days post-injection. Microglial cell activation and inflammatory cell infiltrate were associated with dopaminergic cell death and motor disabilities. Astrocytic activation was delayed and associated with scar formation. The chronic expression of a single proinflammatory cytokine as IL-1beta in the SN elicited most of the characteristics of PD, including progressive dopaminergic cell death, akinesia and glial activation. Our data suggest that IL-1beta per se is able to mediate inflammatory-mediated toxic effects in the SN if its expression is sustained. This model will be helpful to identify possible therapeutic targets related to inflammation-derived neurodegeneration in the SN.


Bodily distress syndrome after receiving vaccines: A case report.
A 48-year-old woman presented with various symptoms, including widespread body pains, insomnia, palpitations, and shortness of breath, after receiving tetanus toxoid. After going through multiple visits to clinicians of various subspecialties, she was referred to our infectious diseases clinic. She was diagnosed with bodily distress syndrome (BDS), possibly triggered by tetanus toxoid injection. Her symptoms improved shortly after reassurance and medical management. Functional disorders such as BDS can occur after vaccinations, and one must be aware of this possibility in patients with multiple symptoms after receiving vaccines.


[Mechanism of hematopoietic stem/progenitor cell aging induced by radiation damage].
To explore the mechanism underlying the aging of hematopoietic stem/progenitor cells (HSC/HPC) induced by radiation stress. Male C57BL/6J mice were divided randomly into radiation group and control group. The radiation group were treated with total 6.5 Gy X-ray radiation for 24 h; the control group received the same treatment except radiation. Thereafter, Sca-1(+);HSC/HPC were isolated by magnetic-activated cell sorting (MACS) from bone marrow of all the mice. The distributions of cell cycle were tested by flow cytometry. The percentage of aging cells was detected by SA-β-Gal staining. The potentials of self-renewal and multi-differentiation were measured by CFU-Mix assay. DNA damages of Sca-1(+);HSC/HPC were analyzed by single cell gel electrophoresis technique (SCGE). The expressions of senescence-associated genes p16(INK4a);, p19(Arf);, p53, p21(Cip1/Waf1); mRNA were detected by RT-PCR. Western blotting was performed to analyze the expressions of p16(INK4a); and p21(Cip1/Waf1); proteins. The purity of Sca-1(+);HSC/HPC reached 94% after MACS. Compared with control group cells, after radiation, the number of Sca-1(+);HSC/HPC per femur and CFU-Mix sharply decreased (P<0.05), Sca-1(+);HSC/HPC apparently showed G1 arrest and elevated percentage of SA-β-Gal positive cells (P<0.05), cell trailing had a prolonged time, and the expressions of senescence-associated genes (p16(INK4a);, p19(Arf);, p53, p21(Cip1/Waf1);) and relevant proteins (p16(INK4a);, p21(Cip1/Waf1);) were up-regulated significantly (P<0.05). DNA damage and senescence-associated biological changes of Sca-1(+);HSC/HPC can be achieved by X-ray radiation, which may be involved in p16(INK4a);-Rb and p19(Arf);-p53-p21(Cip1/Waf1); signal pathways.


Brachytherapy for clinically localized prostate cancer.
Prostate brachytherapy is an effective treatment option for clinically organ-confined prostate carcinoma. Observed 5- and 10-year follow-up have documented prostate-specific antigen (PSA) levels that were comparable to published radical prostatectomy series and were better than several published external-beam radiation series. Between January 1987 and June 1988, a total of 152 consecutive patients with Stage T1 to T3 low to high Gleason grade prostate cancer were studied at Northwest Hospital in Seattle, Washington. Patients' median age was 70 years (range, 53 to 92 years). All patients received Iodine-125 prostate brachytherapy with or without a 45 Gy dose of external-beam radiation. The average preoperative PSA, clinical stage, and prostate needle biopsy Gleason sum were 11 ng/ml, T2, and (5), respectively, and were known in all but five patients. PSA follow-up, clinical examination, and biopsy results judged disease-free survival at 5 and 10 postoperative years. Elevation of PSA above 0.5 ng/ml or a positive biopsy or a positive bone scan was considered treatment failure. The authors provide an historical review of prostate brachytherapy in conjunction with up-to-date implant techniques and long-term outcome results.


Characterization of partially purified 8 kDa antigenic protein of Clonorchis sinensis.
The 8 kDa antigenic protein of Clonorchis sinensis was partially purified by ammonium sulfate precipitation and subsequently by a column chromatographic steps. The purified protein was separated into 7 and 8 kDa protein bands through SDS-tricine gel electrophoresis, while the protein was found to migrate to a 8 kDa band in 7.5-15% SDS-PAGE. The molecular weight of the antigen was estimated to be 110 kDa by Superose 6 HR 10/30 gel filtration. The purified antigen strongly reacted with the human sera of clonorchiasis. The hyperimmune sera of BALB/c mice immunized against the 8 kDa protein were reacted with both the crude extract and the excretory-secretory product of adult worms, but not with the metacercarial extract. Immunohistochemical staining demonstrated that the protein was distributed to the tegument and subtegumental cells and also to the seminal receptacle. The present findings suggest that the 8 kDa protein is a partition of the multicomplex protein originating from various organs of adult C. sinensis, and that it is composed of several 7 and 8 kDa proteins.


Impact of Exercise on Gut Microbiota in Obesity.
Physical activity, exercise, or physical fitness are being studied as helpful nonpharmacological therapies to reduce signaling pathways related to inflammation. Studies describing changes in intestinal microbiota have stated that physical activity could increase the microbial variance and enhance the ratio of Firmicutes/Bacteroidetes, and both actions could neutralize the obesity progression and diminish body weight. The aim of this review is to provide an overview of the literature describing the relationship between physical activity profiles and gut microbiota and in obesity and some associated comorbidities. Promoting physical activity could support as a treatment to maintain the gut microbiota composition or to restore the balance toward an improvement of dysbiosis in obesity; however, these mechanisms need to be studied in more detail. The opportunity to control the microbiota by physical activity to improve health results and decrease obesity and related comorbidities is very attractive. Nevertheless, several incompletely answered questions need to be addressed before this strategy can be implemented.


[Demonstration and biological significance of viral and cellular oncogenes in uterine carcinomas].
Premalignant and malignant lesions of the cervix uteri and endometrium were analyzed for the presence of human papillomavirus (HPV) DNA and c-myc or c-erbB2/neu oncogene expression. HPV DNA was detected by PCR in 100% of the cervical carcinomas and CIN lesions, but also in endometrial lesions (3/8 adenocarcinomas, two hyperplasias and one adenomyosis uteri). Myc-overexpression was found in 25-30% of the cervical carcinomas and severe dysplasias, but not in endometrial lesions. C-erbB2 was overexpressed in 4/11 endometrial carcinomas and 3/19 CIN3 lesions. The implications of these results are discussed.


Stepwise approach to myopathy in systemic disease.
Muscle diseases can constitute a large variety of both acquired and hereditary disorders. Myopathies in systemic disease results from several different disease processes including endocrine, inflammatory, paraneoplastic, infectious, drug- and toxin-induced, critical illness myopathy, metabolic, and myopathies with other systemic disorders. Patients with systemic myopathies often present acutely or sub acutely. On the other hand, familial myopathies or dystrophies generally present in a chronic fashion with exceptions of metabolic myopathies where symptoms on occasion can be precipitated acutely. Most of the inflammatory myopathies can have a chance association with malignant lesions; the incidence appears to be specifically increased only in patients with dermatomyositis. In dealing with myopathies associated with systemic illnesses, the focus will be on the acquired causes. Management is beyond the scope of this chapter. Prognosis is based upon the underlying cause and, most of the time, carries a good prognosis. In order to approach a patient with suspected myopathy from systemic disease, a stepwise approach is utilized.


Updates in technology-based interventions for attention deficit hyperactivity disorder.
Technological advancement has led to the development of novel treatment approaches for attention deficit hyperactivity disorder (ADHD). This review aims to review recent studies which employ the use of technology to treat ADHD, with particular focus on studies published during a 1-year period from February 2019 to February 2020. Most recent studies involved children aged 12 years and below. Interventions included cognitive training through games, neurofeedback and a combination of several approaches. More novel approaches included trigeminal nerve stimulation and brain-computer interface, and studies had utilized technology such as X-box Kinect and eye tracker. There was a shift towards delivering intervention at home and in school, enabled by technology. The study outcomes were variable and mainly included executive functioning measures and clinical ratings. These interventions were generally safe with few reported adverse events. Technology has enabled interventions to be delivered outside of the clinic setting and presented an opportunity for increased access to care and early intervention. Better quality studies are needed to inform on the efficacy of these interventions.


[Blood vessels of the myocardial microcirculatory bed after radical correction of tetralogy of Fallot].
The intraoperative right ventricular myocardial biopsy specimens taken from 54 patients during radical correction of Fallot's tetrad were used to examine the microcirculatory vessels during combined pharmacological ice-chip cardioplegia (PICC) and reperfusion. The combined PICC was shown to fail to exclude myocardial microcirculatory vessel lesions, namely: ultrastructural evidence for edema and destructive changes in the membrane structures of endothelial cells, expanded interendothelial contacts, basal membrane stratification. The lesions were more marked in patients with cyanotic heart disease in cardioplegia lasting more than 65 min. Coronary blood flow recovery was accompanied by evolving endotheliocytic cytoplasmic edema, phenomena of microclasmatosis, microvascular obstruction with cell fragments and membrane structures. This impaired microcirculation, promoted interstitial edema and dystrophic cardiomyocytic changes and might be followed by acute heart failure in the postoperative period.


Surface quinone-induced formation of aqueous reactive sulfur species controls pine wood biochar-mediated reductive dechlorination of hexachloroethane by sulfide.
Understanding the mechanisms controlling the redox transformation of organic contaminants mediated by biochar is of great significance for application of biochar in remediation of contaminated soils and sediments. Here we investigated the mediation effect of a pine wood-derived biochar (P-char) in comparison with multiwalled carbon nanotubes (MCNTs) and graphite on the reductive dechlorination of hexachloroethane by sulfide. Upon normalization of the mediator's surface area, the reduction rate of hexachloroethane follows an order of P-char < MCNTs < graphite. Aqueous polysulfides and polysulfide free radicals were readily produced by reacting sulfide only with P-char, and the supernatant separated from the reaction system could account for 83.4% of the pseudo-kinetic rate constant of hexachloroethane mediated by P-char. In contrast, MCNTs and graphite had weak abilities to produce reactive sulfur species, and the supernatant exhibited very low reduction capability (<20.7%) of hexachloroethane. Electron paramagnetic resonance (EPR) analysis demonstrated that the surface quinone moieties on P-char induced the formation of polysulfides and polysulfide free radicals from sulfide by serving as one-electron acceptors. Consistently, polysulfides prepared by reacting elemental sulfur with sulfide showed much stronger reducing capability compared to sulfide. Thus, the mediation effect of P-char was dominantly attributed to the surface quinone-induced formation of reactive reducing sulfur species, whereas the mediation effect of MCNTs and graphite mainly stemmed from the enhanced electron transfer by the graphitized carbon. These results showed for the first time that surface quinone-induced formation of aqueous reactive sulfur species could control biochar-mediated reductive dechlorination of chloroorganic contaminants by sulfides.


The history of varicocele: from antiquity to the modern ERA.
Men have most likely been affected by varicocele since the assumption of the upright position. In De Medicina, written during the first century AD, Celsus credits the Greeks with the first description of a varicocele, and he recorded his own acute observation: "The veins are swollen and twisted over the testicle, which becomes smaller". Celsus himself is credited with the distinction between varicocele (dilation of surface veins) and "cirsocele" (dilation of deep veins). There has been a long history of treatment attempts and failures, some of which are remarkably strange, that have sometimes culminated in tragedy, as in the case of French professor Jacques-Mathieu Delpech (1772- 1832). Although some questions regarding the etiopathology and treatment of varicocele remain unanswered, a succession of more or less conservative attempts involving all medical cultures has been performed throughout history. The report by W.S. Tulloch in 1952 brought varicocele into the era of modern evidence-based medicine, and varicocele surgery finally progressed beyond the aim of merely relieving scrotal pain and swelling. From 1970 to 2000, varicocelectomies gained worldwide attention for the treatment of male infertility. Several innovative procedures to correct varicoceles began to appear in the world's literature as interventional radiology, microsurgery, laparoscopy, and robotics, while comprehensive review articles were also published on the subject of varicocelectomies. Microsurgery is nowadays used worldwide and it can be considered to be the gold standard for correcting infertility linked to varicocele.


Increased therapeutic index of antineoplastic drugs in combination with intracellular histamine antagonists.
L-Histidinol, a protein synthesis inhibitor and structural analogue of L-histidine, has been demonstrated in chemotherapy-treated mice to be cytoprotective to normal stem cells but to enhance cytotoxicity to tumor cells. N,N-Diethyl-2-[4-(phenylmethyl) phenoxy]ethanamine.HCl (DPPE) is an antagonist of recently described microsomal and nuclear intracellular histamine receptors implicated in the mediation of proliferation and modulation of prostaglandin synthesis. DPPE is cytotoxic to tumor cells in vitro and cytoprotective to the gut in vivo. Noting the similar pharmacologic profiles for histidinol and DPPE and the structural resemblance between histidinol and histamine, we tested 1) whether binding to intracellular histamine receptors may be important to the action of histidinol, 2) whether there exists a differential effect of DPPE and histidinol on proliferating normal and transformed or malignant cells, and 3) whether DPPE, like histidinol, protects host cells from the effects of chemotherapy while augmenting tumor cell kill in vivo. It was observed that histidinol does compete at intracellular histamine receptors in isolated microsomes and nuclei, but with significantly lower affinity than DPPE. Nevertheless, for each agent, potency at intracellular histamine receptors correlates with potency to inhibit DNA and protein synthesis, without cytotoxicity, in normal mitogen-stimulated murine lymphocytes and to kill transformed mouse lymphocytes or MCF-7 human breast cancer cells. As demonstrated previously for histidinol (1-2 g/kg), DPPE (4 mg/kg) protected murine bone marrow progenitors from doxorubicin or fluorouracil, while doses of 4-50 mg/kg significantly enhanced the antitumor activity of doxorubicin and daunorubicin in murine models of early cancer. One postulate to explain the effects of intracellular histamine receptor ligands is that intracellular histamine mediates DNA and protein synthesis, possibly through a downward modulation of growth-inhibitory prostaglandin levels. Antagonism of the intracellular action of histamine at intracellular histamine receptors by DPPE or histidinol may result in differential perturbations of growth/eicosanoid metabolism in normal and malignant cells, thus forming the basis of a new approach to chemotherapy.


JMM Profile: Actinobacillus pleuropneumoniae: a major cause of lung disease in pigs but difficult to control and eradicate.
The Gram-negative bacterium Actinobacillus pleuropneumoniae is the causative agent of pleuropneumonia in pigs, its only known natural host. Typical symptoms of peracute disease include fever, apathy and anorexia, and time from infection to death may only be 6 h. Severe lung lesions result from presence of one or two of the ApxI-III toxins. Control is through good husbandry practice, vaccines and antibiotic use. Culture and presence of the species-specific apxIV gene by PCR confirms diagnosis, and identification of serovar, of which 19 are known, informs on appropriate vaccine use and epidemiology.


The roots of modern oncology: from discovery of new antitumor anthracyclines to their clinical use.
In May 1960, the Farmitalia CEO Dr. Bertini and the director of the Istituto Nazionale dei Tumori of Milan Prof. Bucalossi (talent scout and city's Mayor) signed a research agreement for the discovery and development up to clinical trials of new natural antitumor agents. This agreement can be considered as a pioneering and fruitful example of a translational discovery program with relevant transatlantic connections. Owing to an eclectic Streptomyces, found near Castel del Monte (Apulia), and to the skilled and motivated participants of both institutions, a new natural antitumor drug, daunomycin, was ready for clinical trials within 3 years. Patent interference by the Farmitalia French partner was overcome by the good quality of the Italian drug and by the cooperation between Prof. Di Marco, director of the Istituto Ricerche Farmitalia Research Laboratories for Microbiology and Chemotherapy, and Prof. Karnofsky, head of the Sloan-Kettering Cancer Institute of New York, leading to the first transatlantic clinical trials. The search for daunomycin's sister anthracyclines led to the discovery and development of adriamycin, one of the best drugs born in Milan. This was the second act prologue of the history of Italian antitumor discovery and clinical oncology, which started in July 1969 when Prof. Di Marco sent Prof. Bonadonna the first vials of adriamycin (doxorubicin) to be tested in clinical trials. This article reviews the Milan scene in the 1960s, a city admired and noted for the outstanding scientific achievements of its private and public institutions in drugs and industrial product discovery.


Concentration of glycerol in aqueous microdroplets by selective removal of water.
A major roadblock to the vitrification of cells is the requirement of high concentrations of cryoprotectant (CPA) chemicals and the damage caused by prolonged exposure of cells to these high concentrations above the glass transition temperature. These effects are minimized with controlled CPA loading. Certain organic oils, such as soybean oil, are made of triacylglycerols and are capable of dissolving small amounts of water, a property which is enhanced significantly as temperature is increased. This phenomenon was exploited here to accomplish temperature-controlled concentration of glycerol in single water droplets dispersed in the organic phase. Emulsions of aqueous solutions of glycerol in soybean oil were made and subjected to a temperature increase of 10 degrees C from room temperature. Upon increasing temperature, water dissolved into the oil, rendering the 15-20 microm droplets concentrated an average of 3.6 times and 2.6 times for 1 and 2 M starting concentrations, respectively, with the oil-insoluble glycerol in 90-110 s. This phenomenon could be used to dynamically concentrate CPAs within cell-containing droplets which may then be vitrified before being exposed to high temperatures for fatally long times.


Mucus clearance from peripheral airways.
Mucociliary clearance data obtained with 5 microns radioaerosol particles have been analyzed for asymptomatic young cigarette smokes and non-smokers. The rate and the amount of peripheral zone clearance were both considered in relationship to the overall depth of radioaerosol lung penetration. In the smokers, but not in the non-smokers, the forms of relationship found appeared compatible with prediction based on simple mathematical modelling of aerosol deposition sites within the lung. We suggest that the results found in the non-smokers are attributable to poor mucociliary defence (which is rarely required) of their more distal peripheral airways--due presumably to low levels of cross-linked glycoprotein mucus in these airways--whilst those in the smokers functionally reflect the presence of an increased supply of mucus appropriate for mucociliary transport.


Genetics of irritable bowel syndrome.
Irritable bowel syndrome (IBS) is one of the most common diagnoses made by gastroenterologists and primary care providers alike, and yet the underlying mechanism remains poorly understood. Family and twin studies suggest that IBS may have a genetic basis. Several candidate gene association studies have been performed, but thus far, they have failed to clearly identify an "IBS gene." Epidemiological studies are needed to facilitate phenotype definition and identify relevant environment risk factors that will need to factor in gene and environment interactions in all future genetic studies. As genetic research in IBS is relatively nascent, much opportunity, as well as many challenges, exists in identifying the genes responsible for IBS.


Protein Supplementation and Grazing Behavior for Cows on Differing Late-Season Rangeland Grazing Systems.
The objective was to determine if low- or high-residual feed intake (LRFI or HRFI, n = 24 for each) Hereford × Angus cows on continuously or rotationally grazed rangeland altered their grazing behavior when provided a protein supplement in late autumn. Treatments included continuously grazed, control (CCON, n = 12); continuously grazed, supplemented (CTRT, n = 12); rotationally grazed, control (RCON, n = 12); and rotationally grazed, supplemented pastures (RTRT, n = 12). Cows in each treatment had grazing time (GT), resting time (RT), and walking time (WLK) measured for 2 years with accelerometers. Bite rate (BR) was also measured. Time distributions of GT and RT differed by year (p < 0.05), being influenced by colder temperatures in 2016. Cattle in 2016 spent more time grazing during early morning and late evening (p < 0.05) and rested more during the day (p < 0.05). In 2017, cattle in the CCON treatment walked more (p < 0.05) during early morning time periods than did the CTRT cattle, indicative of search grazing. All supplemented cattle had greater BR (p < 0.05) than control cattle in 2017. Cattle with increased nutritional demands alter grazing behavior in a compensatory fashion when grazing late-season rangelands.


Transcriptomic Signatures and Upstream Regulation in Human Skeletal Muscle Adapted to Disuse and Aerobic Exercise.
Inactivity is associated with the development of numerous disorders. Regular aerobic exercise is broadly used as a key intervention to prevent and treat these pathological conditions. In our meta-analysis we aimed to identify and compare (i) the transcriptomic signatures related to disuse, regular and acute aerobic exercise in human skeletal muscle and (ii) the biological effects and transcription factors associated with these transcriptomic changes. A standardized workflow with robust cut-off criteria was used to analyze 27 transcriptomic datasets for the vastus lateralis muscle of healthy humans subjected to disuse, regular and acute aerobic exercise. We evaluated the role of transcriptional regulation in the phenotypic changes described in the literature. The responses to chronic interventions (disuse and regular training) partially correspond to the phenotypic effects. Acute exercise induces changes that are mainly related to the regulation of gene expression, including a strong enrichment of several transcription factors (most of which are related to the ATF/CREB/AP-1 superfamily) and a massive increase in the expression levels of genes encoding transcription factors and co-activators. Overall, the adaptation strategies of skeletal muscle to decreased and increased levels of physical activity differ in direction and demonstrate qualitative differences that are closely associated with the activation of different sets of transcription factors.


Quantifying the harmful effect of psoriasis on health-related quality of life.
Psoriasis affects 7 million people in the United States, causing substantial cost, social stigma, and disability. The purpose of this study was to evaluate the health effects of skin disease by comparing psoriasis to other primary medical disorders using 3 different scales of health-related quality of life. A self-administered questionnaire consisting of 3 health-related quality of life measures was given sequentially to 35 eligible patients with psoriasis presenting to the Dermatology Branch of the National Cancer Institute (NCI) for an investigational therapeutic protocol. All patients (100%) agreed to participate. The median Psoriasis Area and Severity Index (PASI) score was 13.0. Overall, 82.9% at least often felt the need to hide their psoriasis, and 74.3% claimed their self-confidence was at least often affected by their psoriasis. The median EQ-5D health state utility score was 13.0% less than healthy individuals (P <.001). On the SF-36, the mean general health score was 13.2% less (P =.005) and the median social functioning score 18.7% less (P =.005) than that of patients with no chronic conditions. Individuals with psoriasis are significantly affected in their health state utility, perception of general health, and social functioning when compared with individuals without chronic disease and those with certain primary medical conditions.


Role of Cingulin in Agonist-induced Vascular Endothelial Permeability.
Agonist-induced activation of Rho GTPase signaling leads to endothelial cell (EC) permeability and may culminate in pulmonary edema, a devastating complication of acute lung injury. Cingulin is an adaptor protein first discovered in epithelium and is involved in the organization of the tight junctions. This study investigated the role of cingulin in control of agonist-induced lung EC permeability via interaction with RhoA-specific activator GEF-H1. The siRNA-induced cingulin knockdown augmented thrombin-induced EC permeability monitored by measurements of transendothelial electrical resistance and endothelial cell permeability for macromolecules. Increased thrombin-induced permeability in ECs with depleted cingulin was associated with increased activation of GEF-H1 and RhoA detected in pulldown activation assays. Increased GEF-H1 association with cingulin was essential for down-regulation of thrombin-induced RhoA barrier disruptive signaling. Using cingulin-truncated mutants, we determined that GEF-H1 interaction with the rod + tail domain of cingulin was required for inactivation of GEF-H1 and endothelial cell barrier preservation. The results demonstrate the role for association of GEF-H1 with cingulin as the mechanism of RhoA pathway inactivation and rescue of EC barrier after agonist challenge.


Reporting guidelines: another perspective.
The following data are required when reporting results of a procedure for occlusive disease of the lower limb: (1) PREOPERATIVE PATIENT ASSESSMENT: This should include age, sex, diabetes, smoking habit, whether the ischemic symptoms are at rest or after exercise, and the resting ankle or toe pressure. (2) INTENTION TO TREAT: This should be stated as a percentage of the number of procedures that actually were properly performed against the number of procedures scheduled. Only those procedures that were performed should be subsequently analyzed. (3) ACUTE RESULTS: This is assessed by an imaging technique, such as angiography or duplex ultrasound, and defined in terms of patency and degree of maximal stenosis in the area treated and 5 cm on either side. Change in symptoms, complications, and ankle pressures should be reported but are not criteria for procedural success or failure. The assessment should be done from 10 to 30 days following the procedure. (4) LONG-TERM RESULTS: As assessed by appropriate imaging techniques, outcome should be reported in terms of primary, assisted primary, and secondary patency. The degree of maximal stenosis in the treated segments and 5 cm on either side should be stated. The surveillance intervals would depend on the answers being sought in the follow-up period, but the minimum would be an annual review. Three-year results are required to give an adequate assessment of the durability of a procedure. (5) REPORTING: Life-table analysis should be used to present the data on patencies and the degree of stenosis.


Tuning the Mechanical Properties of Polymer Nanocomposites Filled with Grafted Nanoparticles by Varying the Grafted Chain Length and Flexibility.
By employing coarse-grained molecular dynamics simulation, we simulate the spatial organization of the polymer-grafted nanoparticles (NPs) in homopolymer matrix and the resulting mechanical performance, by particularly regulating the grafted chain length and flexibility. The morphologies ranging from the agglomerate, cylinder, sheet, and string to full dispersion are observed, by gradually increasing the grafted chain length. The radial distribution function and the total interaction energy between NPs are calculated. Meanwhile, the stress⁻strain behavior of each morphology and the morphological evolution during the uniaxial tension are simulated. In particular, the sheet structure exhibits the best mechanical reinforcement compared to other morphologies. In addition, the change of the grafted chain flexibility to semi-flexibility leads to the variation of the morphology. We also find that at long grafted chain length, the stress⁻strain behavior of the system with the semi-flexible grafted chain begins to exceed that of the system with the flexible grafted chain, attributed to the physical inter-locking interaction between the matrix and grafted polymer chains. A similar transition trend is as well found in the presence of the interfacial chemical couplings between grafted and matrix polymer chains. In general, this work is expected to help to design and fabricate high performance polymer nanocomposites filled with grafted NPs with excellent and controllable mechanical properties.


Resource-Efficient Topological Fault-Tolerant Quantum Computation with Hybrid Entanglement of Light.
We propose an all-linear-optical scheme to ballistically generate a cluster state for measurement-based topological fault-tolerant quantum computation using hybrid photonic qubits entangled in a continuous-discrete domain. Availability of near-deterministic Bell-state measurements on hybrid qubits is exploited for this purpose. In the presence of photon losses, we show that our scheme leads to a significant enhancement in both tolerable photon-loss rate and resource overheads. More specifically, we report a photon-loss threshold of ∼3.3×10^{-3}, which is higher than those of known optical schemes under a reasonable error model. Furthermore, resource overheads to achieve logical error rate of 10^{-6}(10^{-15}) is estimated to be ∼8.5×10^{5}(1.7×10^{7}), which is significantly less by multiple orders of magnitude compared to other reported values in the literature.


Structural Optimization and Enhanced Prodrug-Mediated Delivery Overcomes Camptothecin Resistance in High-Risk Solid Tumors.
Camptothecins are potent topoisomerase I inhibitors used to treat high-risk pediatric solid tumors, but they often show poor efficacy due to intrinsic or acquired chemoresistance. Here, we developed a multivalent, polymer-based prodrug of a structurally optimized camptothecin (SN22) designed to overcome key chemoresistance mechanisms. The ability of SN22 vs. SN38 (the active form of irinotecan/CPT-11) to overcome efflux pump-driven drug resistance was tested. Tumor uptake and biodistribution of SN22 as a polymer-based prodrug (PEG-[SN22]4) compared with SN38 was determined. The therapeutic efficacy of PEG-[SN22]4 to CPT-11 was compared in: (i) spontaneous neuroblastomas (NB) in transgenic TH-MYCN mice; (ii) orthotopic xenografts of a drug-resistant NB line SK-N-BE(2)C (mutated TP53); (iii) flank xenografts of a drug-resistant NB-PDX; and (iv) xenografts of Ewing sarcoma and rhabdomyosarcoma. Unlike SN38, SN22 inhibited NB cell growth regardless of ABCG2 expression levels. SN22 prodrug delivery resulted in sustained intratumoral drug concentrations, dramatically higher than those of SN38 at all time points. CPT-11/SN38 treatment had only marginal effects on tumors in transgenic mice, but PEG-[SN22]4 treatment caused complete tumor regression lasting over 6 months (tumor free at necropsy). PEG-[SN22]4 also markedly extended survival of mice with drug-resistant, orthotopic NB and it caused long-term (6+ months) remissions in 80% to 100% of NB and sarcoma xenografts. SN22 administered as a multivalent polymeric prodrug resulted in increased and protracted tumor drug exposure compared with CPT-11, leading to long-term "cures" in NB models of intrinsic or acquired drug resistance, and models of high-risk sarcomas, warranting its further development for clinical trials. SIGNIFICANCE: SN22 is an effective and curative multivalent macromolecular agent in multiple solid tumor mouse models, overcoming common mechanisms of drug resistance with the potential to elicit fewer toxicities than most cancer therapeutics.


Salivary cortisol and nitrite concentrations in school teachers: A longitudinal pilot study.
Occupational/mental stressors, which may be evaluated with measurements of salivary cortisol concentrations, affect the endothelial function and has implications on cardiovascular health. Nitric oxide (NO) is known to have an important role in cardiac function and may also be assessed in the saliva, but its participation in physiological responses to hypothalamic-pituitary-adrenal (HPA) axis stimulation is still not completely understood. The aim of the present study was to test the hypothesis that salivary NO (as nitrite) and cortisol concentrations in school teachers vary throughout the academic year. Saliva samples were collected from 13 teachers distributed across five secondary schools. The samples were collected at 6:30 a.m., 11:30 a.m., and 5:30 p.m. in the months of March, July, and December. Salivary cortisol levels were measured by enzyme immunoassay (EIA), and salivary NO concentration was determined by the quantification of nitrite. The area under the curve in relation to ground (AUC) was calculated to assess the cortisol and nitrite concentrations throughout the day. No significant changes were observed in cortisol or nitrite concentrations across the three periods of the school year, while cortisol and nitrite levels showed a low positive and significant correlation (r=0.3455, p=0.0336). The results suggest that changes in salivary cortisol levels are accompanied by changes in salivary nitrite levels. This is the first time that such association has been demonstrated. These results encourage further studies aimed to confirm the importance of salivary NO measurement in relation to occupational stress and cardiovascular health.


Slow transit constipation: a review of a colonic functional disorder.
Constipation is a common gastrointestinal complaint that can cause significant physical and psychosocial problems. It has been categorized as slow transit constipation, normal transit constipation, and obstructed defecation. Both the definition and pathophysiology of constipation are unclear, but attempts to describe each of the three types have been made. Slow transit constipation, a functional colonic disorder represents approximately 15 to 30% of constipated patients. The theorized etiologies are disorders of the autonomic and enteric nervous system and/or a dysfunctional neuroendocrine system. Slow transit constipation can be diagnosed with a complete history, physical exam, and a battery of specific diagnostic studies. Once the diagnosis is affirmed and medical management has failed, there are several treatment options. Biofeedback, sacral nerve stimulation, segmental colectomy, and subtotal colectomy with various anastomoses have all been used. Of those treatment options, a subtotal colectomy with ileorectal anastomosis is the most efficacious with the data to support its use.


To probe the origin of activation effect of carboxylic acid and (+)-NLE in tridentated titanium catalyst systems.
The activation effect of carboxylic acid and positive nonlinear effect ((+)-NLE) in tridentated titanium catalyst systems for hetero Diels-Alder reaction and aldol-type reactions has been first elucidated on the basis of X-ray crystal structural analysis of homochiral (pseudo-octahedral coordination geometry with C2 symmetry) and heterochiral (pseudo-octahedral coordination geometry with C1 symmetry) titanium complexes and the observation of their different reactivities with carboxylic acid additive.


Temperature Effects on Oviposition by Rhagoletis indifferens (Diptera: Tephritidae) Vary in Different Developmental Stages of Sweet Cherry.
Fruit developmental stage affects oviposition responses by tephritid fruit flies, but the role temperature plays in these responses to different fruit stages remains largely unknown. Here, temperature effects on oviposition rates of western cherry fruit fly, Rhagoletis indifferens Curran, in different stages of Bing sweet cherry (Prunus avium L.) were determined in no-choice experiments. Stage 1 (green), stage 2 (green-yellow to orange red), stage 3 (yellow-orange to red), and stage 4 cherries (red to burgundy) were exposed to flies at 15.6, 21.1, 26.7, and 32.2°C for 3 h and oviposition recorded. Oviposition was lower at 15.6°C than at all other test temperatures within all four cherry stages. Regression analysis using the three higher temperatures indicated there were significant cherry stage and temperature effects and a significant cherry stage × temperature interaction. The oviposition-temperature relationship was best explained by linear or curvilinear equations, depending on cherry stage. Oviposition in stage 1 cherries was lowest of the four stages and was not or linearly related to temperature. Oviposition in stage 2 cherries was greater and was related to temperature in a linear or curvilinear response. Oviposition was greatest in stage 3 and 4 cherries, with curvilinear and linear equations, respectively, best explaining oviposition-temperature relationships. Results suggest that temperatures and cherry stage together rather than cherry stage alone may have selected for behaviors leading to oviposition responses in R. indifferens.


Single tooth replacement of missing molars: a retrospective study of 78 implants.
As experience with osseointegrated implants has grown, greater use has been made of placement in the posterior jaw. The aim of this study is to present the survival rate of 78 osseointegrated single implants, inserted in the molar area and to evaluate the prosthetic rehabilitation on these teeth. This retrospective study presents findings of 55 consecutive patients with 78 restored single osseointegrated implants in the molar area. The patients went through a clinical and radiological evaluation. The same maxillofacial surgeon inserted all implants. Three of the implants were inserted into the maxilla and 75 into the mandible; 4 of the 78 implants were immediate implants. The cumulative survival rate after one year was 93.6%. Follow-up was up to 80 months, with an average of 27 months. Out of all the implants, 6 failed (7. 7%): 5 failed in the surgical stage, and 1 after prosthetic loading. The main implant failures were among the titanium screw implants. Prosthetic complications occurred in 11 cases (14%), which included loosening of the abutment and/or the crown (9 cases), fracture of the abutment (1 case), and porcelain fracture (1 case). No incident of implant fracture occurred. Within the limits of this study, replacement of a single molar by a single implant is a valid and successful surgical treatment modality, with a high survival rate.


Nasogastric Tube Placement in Newborns Before Discharge.
The aim of this study was to assess the knowledge of medical staff (physicians) at different levels about insertion or placement of nasogastric tube (NGT) in a normal newborn before discharge. It was a survey-based, observational study conducted at King Khalid University Hospital. Atotal of 103 doctors were sent text message; among those 81 (78.6%) responded. Among the respondents, 27, 16, 11 and 27 were neonatologists, general physicians, obstetricians/ ENT/pediatric surgeons, and senior registrars neonatology (SRN), respectively. Majority of physicians, 57 (70.3%) rejected the idea of insertion of NGTin a normal newborn but in 24 (29.6%), answer was to insert NGTin all the newborns before discharge to check the patency of nasal cavities. Regarding the position, region of doctors and their response, majority from Center said 'No'(not in favour of insertion) but from South, 17/18 (94.4%) said 'Yes'(in favour of insertion). Regarding other specialties, majority of them showed rejection of this idea. In conclusion, most of the healthcare professionals, directly involved with neonatal care, rejected the idea of routine insertion of NGTin normal newborn examination before discharge; rather, some non-invasive technique could be opted.


The use of panoramic radiography for evaluating temporomandibular disorders.
Dentists typically are first exposed to panoramic imaging during radiology class while in dental school but understanding the advantages and disadvantages of this imaging technique requires experience. This article reviews the basic concept of panoramic imaging, its history and development, and the advantages and disadvantages of this imaging technique, particularly as they relate to temporomandibular disorders.


Simultaneous transfer and doping of CVD-grown graphene by fluoropolymer for transparent conductive films on plastic.
Chemical doping can decrease sheet resistance of graphene while maintaining its high transparency. We report a new method to simultaneously transfer and dope chemical vapor deposition grown graphene onto a target substrate using a fluoropolymer as both the supporting and doping layer. Solvent was used to remove a significant fraction of the supporting fluoropolymer, but residual polymer remained that doped the graphene significantly. This contrasts with a more widely used supporting layer, polymethylmethacrylate, which does not induce significant doping during transfer. The fluoropolymer doping mechanism can be explained by the rearrangement of fluorine atoms on the graphene basal plane caused by either thermal annealing or soaking in solvent, which induces ordered dipole moments near the graphene surface. This simultaneous transfer and doping of the graphene with a fluoropolymer increases the carrier density significantly, and the resulting monolayer graphene film exhibits a sheet resistance of ∼320 Ω/sq. Finally, the method presented here was used to fabricate flexible and a transparent graphene electrode on a plastic substrate.


[Heart transplantation--status and perspectives].
Transplantation of the heart (HTx) has become a realistic procedure in the treatment of terminal cardiac failure. However, several problems remain and are to be discussed on the basis of our experience in 160 cases of HTx. A dramatic widening of indications for HTx presently is not to be expected while the lack of donor organs is magnified by the growing transplantation frequency. This bottle neck only can be lessened by mobilization of all organ sources. Longterm survival rate in HTx patients seems to stabilize at well over 70%. Persisting mortality and morbidity of HTx are the result of imperfect recognition and treatment of rejection as well as infection. The use of circulatory aids in patients expecting HTx and in those with a failing transplant is of growing importance at the same time posing the problem of high urgency in patients thus instrumented. It is likely that the intermediate-term use of the totally implantable artificial heart will lessen this dilemma. Costs and efforts of cardiac transplantation are considerable. A plea therefore is made for concentration of organ transplantations of all types in special centers.


Rational Design of Right-Handed Heterogeneous Peptidomimetics as Inhibitors of Protein-Protein Interactions.
Peptidomimetics have gained great attention for their function as protein-protein interaction (PPI) inhibitors. Herein, we report the design and investigation of a series of right-handed helical heterogeneous 1:1 α/Sulfono-γ-AA peptides as unprecedented inhibitors for p53-MDM2 and p53-MDMX. The most potent helical heterogeneous 1:1 α/Sulfono-γ-AA peptides were shown to bind tightly to MDM2 and MDMX, with Kd of 19.3 and 66.8 nM, respectively. Circular dichroism spectra, 2D-NMR spectroscopy, and the computational simulations suggested that these helical sulfono-γ-AA peptides could mimic the critical side chains of p53 and disrupt p53/MDM2 PPI effectively. It was noted that these 1:1 α/Sulfono-γ-AA peptides were completely resistant to proteolytic degradation, boosting their potential for biomedical applications. Furthermore, effective cellular activity is achieved by the stapled 1:1 α/Sulfono-γ-AA peptides, evidenced by significantly enhanced p53 transcriptional activity and much more induced level of MDM2 and p21. The 1:1 α/Sulfono-γ-AA peptides could be an alternative strategy to antagonize a myriad of PPIs.


Huntington's disease: alterations of visual and somatosensory cortical evoked potentials in patients and offspring.
In 13 patients suffering form Huntington's chorea (H.Ch.), VEPs and SEPs were investigated in comparison to 9 clinically inconspicuous offspring and normal adults. 1. The mean amplitude of VEP was reduced in choreatic patients and in four out of nine offspring. 2. Latencies of P100 in VEP were normal in all subjects. 3. The late components were reduced in amplitude and rather irregular in shape. 4. The latencies of SEPs were slightly prolonged, less marked in the early peaks and more pronounced in the later ones. 5. The late components after 70 to 100 msec were often attenuated or even absent. 6. The mean amplitude of the first two peaks was reduced. 7. Interhemispheric asymmetries were pronounced in three out of nine offspring.


Genome-Wide Identification and Expression Analysis of the SWEET Gene Family in Annual Alfalfa (Medicago polymorpha).
SWEET (Sugars will eventually be exported transporter) proteins are a group of sugar transporters that are involved in sugar efflux, phloem loading, reproductive development, plant senescence, and stress responses. In this study, 23 SWEET transporter members were identified in the Medicago polymorpha genome, heterogeneously distributed on seven chromosomes. These MpSWEET genes were divided into four subfamilies, which showed similar gene structure and motif composition within the same subfamily. Seventeen MpSWEET genes encode seven transmembrane helices (TMHs), and all MpSWEET proteins possess conserved membrane domains and putative serine phosphorylation sites. Four and three pairs of MpSWEET genes were predicted to be segmentally and tandemly duplicated, respectively, which may have contributed to their evolution of M. polymorpha. The results of microarray and RNA-Seq data showed that some MpSWEET genes were specifically expressed in disparate developmental stages (including seedling stage, early flowering stage, and late flowering stage) or tissues such as flower and large pod. Based on protein network interaction and expression patterns of MpSWEET genes, six MpSWEET genes were selected for further quantitative real-time PCR validation in different stress treatments. qRT-PCR results showed that MpSWEET05, MpSWEET07, MpSWEET12, MpSWEET15, and MpSWEET21 were significantly upregulated for at least two of the three abiotic stress treatments. These findings provide new insights into the complex transcriptional regulation of MpSWEET genes, which facilitates future research to elucidate the function of MpSWEET genes in M. polymorpha and other legume crops.


Molecular imaging of adrenal gland by desorption electrospray ionization mass spectrometry.
Subtle differences in the spatial distributions of closely related compounds including norepinephrine and epinephrine as well multiple lipids are easily distinguished in adult porcine (17 x 8 mm) and rabbit (7 x 4 mm) adrenal glands in a DESI-MS imaging experiment at atmospheric pressure with a spatial resolution of approximately 200 microm. Sensitive and specific detection in the course of DESI imaging discloses details of catecholamine distribution in porcine adrenal medulla and cortex; the average mass of epinephrine interrogated in each pixel is estimated to be about 150 pg. The distribution of ascorbic acid was revealed in the negative ion mode. In addition, the distribution of cholesterol, which cannot be observed using conventional DESI, was obtained using in situ reaction with betaine aldehyde added to the DESI spray while imaging the porcine adrenal gland tissue. Four characteristic types of distributions were observed, with major amounts of the components in the medulla, the cortex, the reticular zone or in the fourth case, being homogeneously distributed. The results agree with and extend information available from histological studies.


Acute lymphoblastic leukemia presenting as cyclic neutropenia.
Clinical and laboratory parameters usually allow an easy diagnosis of acute lymphoblastic leukemia in most cases. Difficult arises, however, when presentation is atypical. A young child with membranous tonsillo-pharyngitis secondary to an isolated neutropenia is reported. The neutrophilic count later showed fluctuations reminiscent of cylic neutropenia. Bone marrow examination revealed the true nature of underlying disorder.


Heterogeneity in conducted arteriolar vasomotor response is agonist dependent.
Microiontophoresis of acetylcholine onto cheek pouch arterioles of the pentobarbital-anesthetized hamster results in both a local response at the pipette tip and a conducted dilator response. The conducted response is not dependent on blood flow, and its magnitude decays with distance from the site of stimulation. In an attempt to define the mechanism responsible for activation of arteriolar conduction, vasoactive agonists directed toward different vascular wall cell types, receptor types, and second messengers were applied to arterioles by pressure-pulse microejection. As expected, microapplication caused a consistent arteriolar response at the site of application with each of the agonists tested (local response). However, a high degree of variability was observed among agonists in their ability to produce conducted responses. Acetylcholine, muscarine, and phenylephrine, invariably induced both local and conducted responses. In contrast, bradykinin, substance P, papaverine, isoproterenol, and adenosine, though consistently inducing local responses, displayed a highly variable ability to induce the conducted responses. When conduction was observed, the arteriolar response was similar regardless of the agonist used to induce the response. Microejection of sodium nitroprusside or arginine vasopressin produced local arteriolar responses with no evidence of a conducted response regardless of the dose. These studies reveal previously undetected heterogeneity among microvessel responses and may reflect variations in the coupling mechanisms linking the local vasomotor response to the conducted response.


An Intelligent AIEgen with Nonmonotonic Multiresponses to Multistimuli.
Intelligent stimulus-response (S/R) systems are the basis of natural process and machine control, which are intensively explored in biomimetic design and analytical/biological applications. However, nonmonotonic multi-S/R systems are still rarely studied so far. In this work, a rational design strategy is proposed to achieve such a unique S/R system by integrating opposite luminescence behaviors in one molecule. When solvent polarity increases, many heterocyclic or carbonyl-containing compounds often become more emissive due to the suppression of the proximity effect, whereas molecules with donor-acceptor (D-A) structures tend to be less emissive because of the twisted intramolecular charge transfer. Meanwhile, protonation on D/A moieties will weaken/strengthen the D-A interaction to result in blue/redshifted emissions. By combining a protonatable heterocyclic acceptor and a protonatable donor together in one molecule, nonmonotonic brightness responses to polarity stimuli and nonmonotonic color responses to pH stimuli can be achieved. The design strategy is successfully verified by a simple molecule named 4-(dimethylamino)styryl)quinoxalin-2(1H)-one (ASQ). ASQ exhibits nonmonotonic responses to polarity and pH stimuli, and aggregation-induced emission (AIE) with a nonmonotonic AIE curve. Meanwhile, ASQ can be adjusted to emit white light in an acidic environment, and it shows multivalent functionalities including albumin protein sensing, ratiometric pH sensing, and amine gas sensing.


Identification of the G-protein alpha-subunit encoded by alpha o2 cDNA as a 39 kDa pertussis toxin substrate.
A novel form of the Go alpha-subunit (alpha o2) has been identified by molecular cloning (Hsu et al., J. Biol. Chem. 265, 11220-11226, 1990). An antibody was generated against a synthetic peptide corresponding to a region of the protein encoded by alpha o2 cDNA. The antibody reacted with an apparently single 39 kDa protein in membrane preparations of rodent brain and with a 39 kDa pertussis toxin substrate in membranes of rodent neuroendocrine and pituitary cells. A previously produced antibody raised against a region common to proteins encoded by alpha o2 cDNA and the previous cloned alpha o1 cDNA (Itoh et al., Proc. Natl. Acad. Sci. USA 83, 3776-3780, 1986) recognized proteins of 39 and 40 kDa in preparations of bovine, porcine and rodent brain and pertussis toxin substrates of 39 and 40 kDa in membranes of rodent neuroendocrine and pituitary cells. We conclude that the 39 kDa Go alpha subunit is encoded by alpha o2 cDNA.


Reversal by Light of Ethylene-induced Inhibition of Spore Germination in the Sensitive Fern Onoclea sensibilis: An Action Spectrum.
Spores of the fern Onoclea sensibilis L. normally germinate to produce two cells of unequal size. The larger cell divides to produce the familiar heart-shaped prothallus. The smaller cell elongates and differentiates into the rhizoid but normally does not divide again. Onoclea spores germinate in complete darkness. Dark germination can be completely inhibited by ethylene gas (10 microliters per liter is saturating). This inhibition can be reversed by light. Broad band colored light studies were designed to determine which area of the spectrum was most effective in overcoming ethylene inhibition. White light treatment resulted in 17% germination. Blue light treatment resulted in 1% germination. Red light treatment resulted in 15% germination. Red light, therefore, was most effective and accounted for most of the effects of white light. A detailed action spectrum was constructed using narrow band interference filters in the wavelength range from 350 to 764 nanometers. The action spectrum has only one major peak at 711 nanometers.


Limited life-table factors for estimating radiation-induced cancers over finite time periods.
A method is presented that allows the estimation of radiation-induced cancer incidence or mortality at varying times post-exposure in irradiated populations of males or females of ages ranging from 10 to 70 yr. Limited life-table factors are given in graphic form for 2 sets of conditions: when the latent period is 2 yr and the plateau 30 yr and when the latent period is 10 yr and the plateau extends to the end of life. Normal incidences for selected forms of cancer are also presented. Examples are given that show how to calculate the radiation excess cancers and to compare this excess with the normal. The implications of these numbers are also discussed.


Experience at a stricture clinic in a developing country.
To evaluate the experience of 37 years regarding etiology, complications and evolving practice of the management of stricture urethra patients at the Sindh Institute of Urology and Transplantation, Karachi. The retrospective descriptive study included 1600 cases of stricture urethra admitted to the Urology Section of the institute from 1972 to 2009. Files of all patients were reviewed; age, gender, site of stricture, etiology, diagnostic methods, clinical symptoms and management, as well trends and patterns were noted. There were 1600 patients of whom 1595 (99.4%) were males and 5 (0.4%) were females with age ranging from 14-80 years. Pelvic fracture urethral disfraction defects (n = 655; 49.5%) and fall astride (n = 123; 9.2%) were the commonest causes. Of the total, 92 percent presented with retention of urine. In the first decade, rail-road and dilatation was the mainstay of treatment. In the second decade, rail-road, dilatation and direct visual internal urethrectomy were the mainstay, but in the last 5 years, urethroplasty replaced the old methods. Trauma is the main cause of stricture. Over the years, urethroplasty and direct visual internal urethrotomy are the mainstay of management. Stricture clinic plays an important role in the early diagnosis of complications of stricture urethra and in the rehabilitation of these patients.


[Mitogenic activity of vasculotropin for peripheral human lymphocytes].
Vasculotropin is a growth factor with a unique specificity for vascular derived endothelial cells. We report that normal human peripheral lymphocytes represent another target for vasculotropin. The mitogenic activity of the medium conditioned by these cells cultured in the presence of Concanavalin A is potentiated by vasculotropin. This effect is exerted more likely through interactions with the soluble mediators rather than through the VAS receptors since VAS binds equally to Concanavalin A stimulated and to unstimulated lymphocytes.


The disaggregation theory of signal transduction revisited: further evidence that G proteins are multimeric and disaggregate to monomers when activated.
We have compared the sedimentation rates on sucrose gradients of the heterotrimeric GTP-binding regulatory (G) proteins Gs, G(o), Gi, and Gq extracted from rat brain synaptoneurosomes with Lubrol and digitonin. The individual alpha and beta subunits were monitored with specific antisera. In all cases, both subunits cosedimented, indicating that the subunits are likely complexed as heterotrimers. When extracted with Lubrol all of the G proteins sedimented with rates of about 4.5 S (consistent with heterotrimers) whereas digitonin extracted 60% of the G proteins with peaks at 11 S; 40% pelleted as larger structures. Digitonin-extracted Gi was cross-linked by p-phenylenedimaleimide, yielding structures too large to enter polyacrylamide gels. No cross-linking of Lubrol-extracted Gi occurred. Treatment of the membranes with guanosine 5'-[gamma-thio]triphosphate and Mg2+ yielded digitonin-extracted structures with peak sedimentation values of 8.5 S--i.e., comparable to that of purified G(o) in digitonin and considerably larger than the Lubrol-extracted 2S structures representing the separated alpha and beta gamma subunits formed by the actions of guanosine 5'-[gamma-thio]triphosphate. It is concluded that the multimeric structures of G proteins in brain membranes are at least partially preserved in digitonin and that activation of these structures in membranes yields monomers of G proteins rather than the disaggregated products (alpha and beta gamma complexes) observed in Lubrol. It is proposed that hormones and GTP affect the dynamic interplay between multimeric G proteins and receptors in a fashion analogous to the actions of ATP on the dynamic interactions between myosin and actin filaments. Signal transduction is mediated by activated monomers released from the multimers during the activation process.


Effect of age on the ability of rat liver tissues to transform chemical promutagens to mutagens.
Age-related changes in drug metabolism of the liver from male Lou rats were determined by measuring changes in the production of mutagens. Activation of aflatoxin B1 (AFB1), 2-aminoanthracene (2AA) and benzo[a]pyrene (B[a]P) to mutagenic derivatives was assayed using the Ames salmonella test system. The promutagens were incubated with tissue fractions isolated from rats ranging in age from 3 weeks to 18 months. Hepatic activation of AFB1 and 2AA changes with age and is maximal from 4 to 10 months. In contrast, no significant modification with age was observed for the activation of B[a]P. It is concluded that the composition of different cytochrome P-450 fractions is modified with age thereby altering the specific ability to convert different promutagens to mutagens.


Airway plaque presenting after alteration of immunosuppression in a pediatric patient remote from heart transplantation.
Success after solid organ transplantation is dependent on the proper balance of immunosuppression to prevent rejection of the allograft while limiting the risk of developing infections and malignancy. We present a 9-year-old girl, remote from transplant, who presented with airway plaque after a change in immunosuppression to include the mTOR inhibitor sirolimus. Differential diagnosis included direct medication side effect, infection, and neoplasia.


Familial pituitary adenoma--report of four cases from two unrelated families.
The authors report four cases of familial pituitary adenomas from two unrelated families. No clinical or biochemical evidence of multiple endocrine neoplasia, type I (MEN-I) was demonstrated. Detailed study of the family trees disclosed no other family members affected by MEN-I. Familial occurrence of pituitary adenomas unassociated with MEN-I is rare.


A genome scan for quantitative trait loci affecting three ear traits in a White Duroc x Chinese Erhualian resource population.
Chinese Erhualian pigs have larger and floppier ears compared with White Duroc pigs (small, half- or fully-pricked ears). To identify quantitative trait loci (QTL) for ear weight and area as well as erectness, a genome-wide scan with 194 microsatellites was performed in a White Duroc x Chinese Erhualian resource population (>1000 F(2) animals). Twenty-three genome-wide significant QTL and 12 suggestive QTL were identified. All QTL for ear erectness and size detected in two previous studies, bar two on SSC6 and 9, were confirmed here. The 1% genome-wide significant QTL at 70 cM on SSC5 and at 58 cM on SSC7 have profound and pleiotropic effects on the three ear traits, with Erhualian alleles increasing weight and area but decreasing erectness. Notably, the 95% confidence interval of the QTL for weight and area on SSC7 spanned only 3 cM. New QTL reaching 1% genome-wide significance were found on SSC8 (at 37 cM) for all three ear traits, on SSC4 and 16 for weight and area, and on SSCX for area. Unexpectedly, Erhualian alleles at these loci were associated with lighter and smaller or erect ear. Some new suggestive QTL were also found on other chromosome regions. Almost all the QTL for weight and area had essentially additive effects, while the QTL for erectness on SSC2, 5 and 7 showed not only additive effects but also partial dominance effects of Erhualian alleles. The two most significant QTL on SSC7 and SSC5 could be promising targets for fine mapping and identification of the causative mutations.


Neuropathological substrates of Alzheimer's disease and Parkinson's disease.
The pathology of Alzheimer's disease (AD) and Parkinson's disease (PD) is characterized by degeneration of certain vulnerable neuronal populations that display several types of cytoskeletal abnormalities (Alzheimer-type lesions and Lewy bodies, respectively). These may serve as diagnostic markers, although they can be found in both types of disorders and, less frequently, in brains of normal aged individuals. AD pathology shows a preponderance for hippocampal, neocortical, and forebrain cholinergic systems; the hallmark of PD is damage to the nigrostriatal dopaminergic system. Both disorders show frequent involvement of subcortical projection systems that can be similar in quality and distribution, with similar multiple neuromediator dysfunction. The results of morphometric studies of some subcortical nuclei in AD and PD are reported and related with neurochemical data. In addition to classical forms of AD and PD, both types of lesions can coexist suggesting an increased risk of PD in patients with AD and vice versa. The basis for an association between the two disorders is unknown. Many AD cases with signs of PD have additional PD pathology, while cortical Alzheimer lesions may be seen in demented PD patients. However, dementia in PD does not imply coexistent cortical AD pathology; prominent subcortical lesions alone, or in combination with cortical AD pathology, may occur. AD and PD may show some differences in the primary locus of degenerative changes in specific cortical and subcortical neuronal systems, but the causative factors, mutual relations, and relative contributions to the clinical syndromes remain to be elucidated.


Effect of gender on perinatal outcome in pregnancies complicated by diabetes.
The aim of this study was to determine whether there is a gender-related difference in the morbidity and mortality of infants of diabetic mothers. We also wanted to identify risk factors associated with adverse pregnancy outcome, and create a perinatal morbidity index. We performed a retrospective review of 107 women whose pregnancies were singleton and complicated by diabetes. The subjects were divided according to the gender of the infant. The morbidity, mortality and confounding variables between the two groups were compared. Logistic regression analysis was used to identify the independent factors associated with an adverse pregnancy outcome. The male group (n = 62) had higher morbidity than the female group (n = 45). This was due to a higher incidence of hypoglycemia (relative risk = 3.9, 95% CI 1.2-12.5, p = 0.011) and need to stay in the neonatal intensive care unit 2 or more days (relative risk = 1.8, 95% CI 1.1-2.9, p = 0.015). There was one female stillbirth due to an episode of ketoacidosis in the mother. Male gender (relative risk = 1.8, 95% CI 1.2-2.7, p = 0.002) was one of three independent predictors of poor outcome. There is a male disadvantage in infants of diabetic mothers with regards to perinatal morbidity. Advanced White's classification, male gender, and third trimester mean glucose > or = 110 mg% identify the pregnancies at risk for diabetes-related morbidity.


Increased CD69 Expression on Peripheral Eosinophils from Patients with Food Protein-Induced Enterocolitis Syndrome.
Food protein-induced enterocolitis syndrome (FPIES) is an uncommon, non-IgE-mediated food allergy. We recently described a significant increase in fecal eosinophil-derived neurotoxin (EDN) after ingestion of the causative food. However, little is known about the activation status of circulating eosinophils in patients with an acute FPIES reaction. Surface CD69 expression was assessed by flow cytometry on peripheral eosinophils from 5 patients with FPIES before and after ingestion of the causative food. Fecal EDN was measured by enzyme-linked immunosorbent assay. No eosinophil activation was observed before ingestion; however, a significant increase in CD69 expression on eosinophils after an acute FIPES reaction was demonstrated in all of the patients. There was no significant change in absolute eosinophil counts in the peripheral blood. The levels of fecal EDN increased on the day after ingestion of the causative food in all patients. These results suggest that circulating eosinophils as well as eosinophils in the intestinal mucosal tissue are activated in acute FPIES reactions and might be associated with systemic immune events in FPIES.


Inorganic binding peptide-mediated immobilization based on baculovirus surface display system.
The biomolecule-mediated assembly of novel composites has been the subject of numerous investigations during the last years, providing new insights into material science and engineering. Via molecular biology technology, we were able to introduce the genetically engineered polypeptide for inorganics (GEPI) as a molecular binder into biomolecules such as phage viruses, to assemble hybrid functional nanoarchitectures. In the present work, we introduced a novel nanocomposite comprising the Autographa californica nuclear polyhedrosis virus (AcNPV) and nanoparticles bound to it. Our results show that a GEPI-encoding gene was successfully introduced by recombination into a eukaryotic expression bacmid and finally displayed outside of the AcNPV after transfection into Sf9 insect cells using the Bac-to-Bac baculovirus expression system. The recombinant baculovirus maintained both the viral infectivity and the specific binding activity of the GEPI. The construction of the gene in the recombinant plasmid was examined by polymerase chain reaction analysis and enzymatic digestion identification, and verified by gene sequencing. Surface display of the fused peptide was revealed by Western blot analysis in dissolution studies and determined by immuno- gold electron microscopy. Adherence of nanoparticles to the recombinant baculovirus was visualized by transmission electron microscopy analysis. Here, we demonstrated the possibilities of combining peptide-mediated immobilization with baculovirus surface display technology.


The Glycemic Index of Sport Nutrition Bars Affects Performance and Metabolism During Cycling and Next-Day Recovery.
Low-glycemic index carbohydrates are potentially better for endurance performance as they result in greater fat oxidation and lower carbohydrate oxidation due to lower insulin release. We compared the effects of pre-exercise feeding with a low-glycemic index lentil-based sports nutrition bar, a commercially-available sports nutrition bar with moderate-glycemic index, and a non-caloric placebo on metabolism and performance during endurance cycling (Trial 1). Using a randomized, counterbalanced, crossover design, endurance-trained individuals (n = 11; eight males; 26 ± 6y; VO2peak 51.4 ± 1.6 mL/kg/min) consumed 1.5 g/kg available carbohydrate from a lentil bar and a moderate-glycemic index bar, as well as a placebo, 1h before endurance cycling (75 min at 65% VO2peak, followed by a 7 km time trial). We also compared post-exercise consumption of the low-glycemic index bar with another moderate-glycemic index bar on next-day exercise performance as an assessment of recovery (Trial 2). In Trial 1, fat or carbohydrate oxidation rates were not different between the bar conditions (p > 0.05). Blood lactate was lower during the low- versus the moderate-glycemic index condition after 75 minutes of cycling (2.6 versus 4.0 mmol/L, p < 0.05) and at the end of the time trial (7.4 versus 9.1 mmol/L, p < 0.05). Time trial performance improved (p < 0.05) after consumption of the low- (574 ± 55 s) and moderate-glycemic index (583 ± 59 s) bars compared to the placebo (619 ± 81 s). In Trial 2 (next-day recovery), performance improved (p < 0.05) with the low-glycemic index bar (547 ± 42 s) compared to the moderate-glycemic index bar (569 ± 42 s) and the placebo (566 ± 34 s). Low- and moderate-glycemic index sports nutrition bars improved cycling exercise performance; however, only the low-glycemic index bar improved next day performance.


Tec kinases regulate actin assembly and cytokine expression in LPS-stimulated human neutrophils via JNK activation.
The acute inflammatory response involves neutrophils wherein recognition of bacterial products, such as lipopolysaccharide (LPS), activates intracellular signaling pathways. We have shown that the mitogen-activated protein kinase (MAPK) c-Jun NH(2) terminal kinase (JNK) is activated by LPS in neutrophils and plays a critical role in monocyte chemoattractant protein (MCP)-1 expression and actin assembly. As the Tec family kinases are expressed in neutrophils and regulate activation of the MAPKs in other cell systems, we hypothesized that the Tec kinases are an upstream component of the signaling pathway leading to LPS-induced MAPKs activation in neutrophils. Herein, we show that the Tec kinases are activated in LPS-stimulated human neutrophils and that inhibition of the Tec kinases, with leflunomide metabolite analog (LFM-A13), decreased LPS-induced JNK, but not p38, activity. Furthermore, LPS-induced actin polymerization as well as MCP-1, tumor necrosis factor-alpha, interleukin-6, and interleukin-1beta expression are dependent on Tec kinase activity.


Surgical stage I endometrial cancer: predictors of distant failure and death.
The objective was to analyze the effect of various histopathologic characteristics on prognosis in surgical stage I (node-negative) endometrial carcinoma. During a 10-year period, 229 patients with stage I epithelial (all subtypes) endometrial cancer had hysterectomy and node dissection. Mean number of nodes harvested was 16.2 pelvic and 5.7 paraaortic. Median follow-up was 83 months. Sixty-seven patients (29%) received adjuvant radiotherapy. Five-year disease-related survival (DRS) was 95%, and 5-year relapse-free survival (RFS) 91%. We observed 7 (3%) isolated vaginal recurrences, 14 (6%) distant failures, and 1 (0.4%) simultaneous recurrence at both regional (pelvic sidewall) and distant sites. Only 1 of 7 patients (14%) with vaginal failure died of the disease (median follow-up of censored patients after failure was 110 months), compared with 10 of the 15 patients (67%) with distant failure. By univariate analysis, myometrial invasion (MI) >or= 66%, nonendometrioid histology, lymphovascular invasion, absence of associated hyperplasia, and tumor diameter >2 cm were significant predictors of poor prognosis with distant failure (P <or= 0.05). Cox regression analysis identified MI >or= 66% as the only independent predictor of DRS (P < 0.001, relative risk [RR] = 12.44), RFS (P < 0.001, RR = 8.67), and distant failure (P < 0.001, RR = 24.89). Only 2% of patients with MI < 66% had distant failure and died of the disease at 5 years, compared with a 29% 5-year distant failure rate and a 22% 5-year death rate among patients with MI >or= 66%. Stage I (negative nodes) endometrial cancer patients with MI >or= 66% are at significant risk for distant failure and death and should be considered candidates for new randomized trials of adjuvant systemic therapy.


Detection of Bitter Taste Molecules Based on Odorant-Binding Protein-Modified Screen-Printed Electrodes.
Bitter taste substances commonly represent a signal of toxicity. Fast and reliable detection of bitter molecules improves the safety of foods and beverages. Here, we report a biosensor using an easily accessible and cost-effective odorant-binding protein (OBP) of Drosophila melanogaster as a biosensitive material for the detection of bitter molecules. Based on the theoretical evaluation of the protein-ligand interaction, binding energies between the OBP and bitter molecules were calculated via molecular docking for the prediction and verification of binding affinities. Through one-step reduction, gold nanoparticles (AuNPs) and reduced graphene oxide (rGO) were deposited on the screen-printed electrodes for improving the electrochemical properties of electrodes. After the electrodes were immobilized with OBPs via layer-by-layer self-assembly, typical bitter molecules, such as denatonium, quinine, and berberine, were investigated through electrochemical impedance spectroscopy. The bitter molecules showed significant binding properties to the OBP with linear response concentrations ranging from 10-9 to 10-6 mg/mL. Therefore, the OBP-based biosensor offered powerful analytic techniques for the detection of bitter molecules and showed promising applications in the field of bitter taste evaluation.


Cryptococcal Immune Reconstitution Inflammatory Syndrome: From Blood and Cerebrospinal Fluid Biomarkers to Treatment Approaches.
Immune reconstitution inflammatory syndrome (IRIS) presents as an exaggerated immune reaction that occurs during dysregulated immune restoration in immunocompromised patients in late-stage human immunodeficiency virus (HIV) infection who have commenced antiretroviral treatments (ART). Virtually any opportunistic pathogen can provoke this type of immune restoration disorder. In this review, we focus on recent developments in the identification of risk factors for Cryptococcal IRIS and on advancements in our understanding of C-IRIS immunopathogenesis. We overview new findings in blood and cerebrospinal fluid which can potentially be useful in the prediction and diagnosis of cryptococcal meningitis IRIS (CM-IRIS). We assess current therapeutic regimens and novel treatment approaches to combat CM-IRIS. We discuss the utility of biomarkers for clinical monitoring and adjusting treatment modalities in acquired immunodeficiency syndrome (AIDS) patients co-infected with Cryptococcus who have initiated ART.


Evidence for rare capsular switching in Streptococcus agalactiae.
The polysaccharide capsule is a major antigenic factor in Streptococcus agalactiae (Lancefield group B streptococcus [GBS]). Previous observations suggest that exchange of capsular loci is likely to occur rather frequently in GBS, even though GBS is not known to be naturally transformable. We sought to identify and characterize putative capsular switching events, by means of a combination of phenotypic and genotypic methods, including pulsed-field gel electrophoretic profiling, multilocus sequence typing, and surface protein and pilus gene profiling. We show that capsular switching by horizontal gene transfer is not as frequent as previously suggested. Serotyping errors may be the main reason behind the overestimation of capsule switching, since phenotypic techniques are prone to errors of interpretation. The identified putative capsular transformants involved the acquisition of the entire capsular locus and were not restricted to the serotype-specific central genes, the previously suggested main mechanism underlying capsular switching. Our data, while questioning the frequency of capsular switching, provide clear evidence for in vivo capsular transformation in S. agalactiae, which may be of critical importance in planning future vaccination strategies against this pathogen.


The nonclinical fertility study design for pharmaceuticals.
Assessment of potential developmental and reproductive toxicity of human pharmaceuticals is currently guided by the ICH S5(R2) document, "Detection of Toxicity to Reproduction for Medicinal Products and Toxicity to Male Fertility." Studies that assess a candidate drug's effect on fertility are generally conducted in rats. The evolution of, and ultimate harmonization of, fertility study designs are reviewed, and specific elements of an acceptable design, as well as the recommendations for presentation of data, are described in detail. Additionally, the timing of nonclinical fertility studies in relation to clinical studies that enroll men and women of reproductive potential is reviewed. Possible strategies for combining fertility assessment with other study designs are also presented. This article provides testing laboratories, sponsors, and regulatory agencies with a comparison of current methods and designs, with the aim of providing a common understanding of the critical design features.


How I treat autoimmune lymphoproliferative syndrome.
Autoimmune lymphoproliferative syndrome (ALPS) represents a failure of apoptotic mechanisms to maintain lymphocyte homeostasis, permitting accumulation of lymphoid mass and persistence of autoreactive cells that often manifest in childhood with chronic nonmalignant lymphadenopathy, hepatosplenomegaly, and recurring multilineage cytopenias. Cytopenias in these patients can be the result of splenic sequestration as well as autoimmune complications manifesting as autoimmune hemolytic anemia, immune-mediated thrombocytopenia, and autoimmune neutropenia. More than 300 families with hereditary ALPS have now been described; nearly 500 patients from these families have been studied and followed worldwide over the last 20 years by our colleagues and ourselves. Some of these patients with FAS mutations affecting the intracellular portion of the FAS protein also have an increased risk of B-cell lymphoma. The best approaches to diagnosis, follow-up, and management of ALPS, its associated cytopenias, and other complications resulting from infiltrative lymphoproliferation and autoimmunity are presented.


The Development of the Gut Microbiota and Short-Chain Fatty Acids of Layer Chickens in Different Growth Periods.
A long-term observation of changes of the gut microbiota and its metabolites would be beneficial to improving the production performance of chickens. Given this, 1-day-old chickens were chosen in this study, with the aim of observing the development of the gut microbiota and gut microbial function using 16S rRNA gene sequencing and metabolites short-chain fatty acids (SCFAs) from 8 to 50 weeks. The results showed that the relative abundances of Firmicutes and genus Alistipes were higher and fiber-degradation bacteria were less at 8 weeks compared with 20 and 50 weeks (P < 0.05). Consistently, gut microbial function was enriched in ATP-binding cassette transporters, the energy metabolism pathway, and amino acid metabolism pathway at 8 weeks. In contrast, the abundance of Bacteroidetes and some SCFA-producing bacteria and fiber-degradation bacteria significantly increased at 20 and 50 weeks compared with 8 weeks (P < 0.05), and the two-component system, glycoside hydrolase and carbohydrate metabolism pathway, was significantly increased with age. The concentration of SCFAs in the cecum at 20 weeks was higher than at 8 weeks (P < 0.01), because the level of fiber and the number of dominant fiber-degradation bacteria and SCFA-producing bacteria were more those at 20 weeks. Notably, although operational taxonomic units (OTUs) and the gut microbial α-diversity including Chao1 and abundance-based coverage estimator (ACE) were higher at 50 than 20 weeks (P < 0.01), the concentration of SCFAs at 50 weeks was lower than at 20 weeks (P < 0.01), suggesting that an overly high level of microbial diversity may not be beneficial to the production of SCFAs.


Kidney function and the risk of cardiovascular events in HIV-1-infected patients.
Cardiovascular events (CVEs) are a significant cause of mortality in HIV/AIDS patients. The objective is to determine the correlation between kidney function and the risk of CVEs in the HIV-infected population. Nested, matched, case-control study design was employed. : We performed a single-center study of 315 HIV-infected patients (63 patients who had CVEs and 252 controls). Estimated glomerular filtration rate (eGFR), calculated by the Chronic Kidney Disease Epidemiology Collaboration formula and the Modification of Diet in Renal Disease equation, and proteinuria were the primary exposures of interest. Mean eGFR was significantly lower in the patients compared with controls (68.4 vs. 103.2 ml/min per 1.73 m, P < 0.001 by Chronic Kidney Disease Epidemiology Collaboration formula and 69.0 vs. 103.1 ml/min per 1.73 m, P < 0.001 by Modification of Diet in Renal Disease equation). In univariate analysis, an eGFR of less than 60 ml/min per 1.73 m was associated with a 15.9-fold increased odds of a CVE compared with an eGFR of at least 60 ml/min per 1.73 m (P < 0.001). In multivariate analysis, a 10 ml/min per 1.73 m decrease in eGFR was associated with a 20% increased odds of a CVE (odds ratio 1.2, 95% confidence interval 1.1-1.4). The prevalence of proteinuria in the patients was approximately twice that of controls (51 vs. 25%, P < 0.001). Proteinuria was associated with CVEs both in univariate and multivariate analyses (odds ratio 3.6, 95% confidence interval 1.9-7.0 and odds ratio 2.2, 95% confidence interval 1.1-4.8, respectively). Traditional cardiovascular risk factors, such as history of previous CVEs, diabetes mellitus, and dyslipidemia, along with low CD4 cell counts were also found as significant predictors of risk of CVEs. Our study shows a significant independent association between decreased kidney function and increased risk of CVE in HIV-1-infected patients.


Medical education: changes and perspectives.
As medical education undergoes significant internationalization, it is important for the medical education community to understand how different countries structure and provide medical education. This article highlights the current landscape of medical education in China, particularly the changes that have taken place in recent years. It also examines policies and offers suggestions about future strategies for medical education in China. Although many of these changes reflect international trends, Chinese medical education has seen unique transformations that reflect its particular culture and history.


The dynamics of morphological changes in the pyloric endocrine cells of rats with uremia.
Disturbances in renal homeostatic function lead to changes in endocrine cell secretory activity. The aim of this study was the histomorphological estimation of dependence of gastric APUD system cell morphology and function on the time after subtotal nephrectomy in Wistar rats. Fragments of gastric pylorus were collected 1. 2, 4, and 6 weeks after nephrectomy. Paraffin sections were stained with H+E and by silver impregnation. Immunohistochemical reactions with the use of specific antibodies against calcitonin gene-related peptide (CGRP), synaptophysin (SPh). somatostatin (ST), and neuron-specific enolase (NSE) were also performed. Immunoreactivity of the examined substances in the pyloric mucosa in the first week after nephrectomy was lower than in the control group. However, in the following time intervals, endocrine cells showed stronger immunostaining in comparison with the control rats. The results suggest that chronic renal failure can modulate secretory activity of APUD system cells.


Synthesis and in-vitro antimycobacterial activity of fluoroquinolone derivatives containing a coumarin moiety.
A series of gatifloxacin, ciprofloxacin, and 8-OCH(3) ciprofloxacin coumarin derivatives with remarkable improvement in lipophilicity as compared to the parent fluoroquinolones was designed, synthesized, and characterized by (1) H-NMR, MS, and HRMS. These derivatives were evaluated for their in-vitro activity against Mycobacterium smegmatis CMCC 93202 and MTB H37Rv ATCC 27294. All of the synthesized compounds were less active than the parent compounds against M. smegmatis CMCC 93202, but the activity of compound 6 was found to be 2-8-fold more potent than ciprofloxacin, 8-OCH(3) ciprofloxacin, moxifloxacin, and rifampin, and comparable to gatifloxacin against MTB H37Rv ATCC 27294. These results indicated that the lipophilicity of the tested compounds is not the sole parameter affecting antimycobacterial activity.


On the Ratio of Photosynthetic Reaction Centers RC2/RC1 in Chlorella.
Chlorella pyrenoidosa (Emerson strain) was grown under high and under low irradiance. Measurements of the O(2) flash yield and the P700 absorption change gave estimates for the ratio of photoreaction centers RC2/RC1 at 1.2 to 1.5. A background light 1 did not increase flash yield.


White-Eyed Blowout Fracture.
White-eyed blowout fracture is often found in pure orbital floor blowout fracture among pediatric patients. Unlike common orbital blowout fractures with apparent clinical signs, the diagnosis of white-eyed orbital blowout fractures is difficult because of minimal soft-tissue signs. This report describes an early missed-out diagnosis of a white-eyed blowout fracture in a 7-year-old child, due to negligible soft-tissue manifestation.


Effects of calcium channel blockers on hyaluronidase-induced capillary vascular permeability.
Inflammation and increased capillary permeability is a significant aspect of the pathogenesis of many diseases including atherosclerosis. L-type calcium channel blockers (CCB) are commonly used as cardiovascular drugs. Amlodipine, lacidipine, and nicardipine were evaluated for anti-inflammatory activity on the paw oedema produced by carrageenan. The effect of these drugs was compared with the activity of indomethacin. Their effects on vascular permeability were also tested by hyaluronidase-induced capillary permeability. In our animal experiments, amlodipine decreased the carrageenan-induced paw oedema at doses of 1, 3, and 6 mg kg(-1) by 27.3%, 43.7%, and 67.3% four hour after carrageenan administration; the same doses of lacidipine and nicardipine decreased paw oedema by 37.1%, 55.6%, 76.4%, 11.2%, 31.0%, 91%; and indomethacin decreased oedema by 38.2% at a dose of 6 mg kg(-1). Lacidipine significantly inhibited the hyaluronidase-induced increase in capillary permeability at doses of 1, 3, and 6 mg kg(-1) compared with the control group. However, amlodipine and nicardipine significantly inhibited the hyaluronidase-induced increase in capillary permeability at 3 and 6 mg kg(-1) doses. A 6 mg kg(-1) dose of indomethacin significantly decreased the capillary permeability which was increased by hyaluronidase. These results suggest that CCBs can be efficient anti-inflammatories, and can also significantly decrease capillary permeability.


Robotic vs. open surgery in obese women with low-grade endometrial cancer: comparison of costs and quality of life measures.
This retrospective study compared perioperative measures, costs, quality of life and survival after open vs. robotic surgery, among obese women diagnosed with low-grade endometrial cancer. Obese women (body mass index (BMI) ≥ 30) who underwent open or robotic surgery for endometrial cancer, in one of two tertiary medical centers in the center of Israel, 2013-2016, postoperative grade 1-2, were included. Costs per patient, including 30-days post-surgery were calculated. Quality of life was evaluated by Physical and Mental Components of the SF-36 and a recovery from surgery questionnaire. Overall survival outcomes were obtained from patients' files. Surgical outcomes, including operating and anesthesia times, length of hospital stay, and intraoperative and postoperative complications according to the Clavien-Dindo classification scale were reviewed. In all, 138 women with BMI ≥30 underwent open (n = 61) or robotic surgery (n = 77) during the study period. The groups had similar BMI, comorbidities, demographics and tumor characteristics. Robotic surgery was associated with shorter hospital stays (mean 1.7 vs. 4.8 days; P < .0001) and fewer postoperative complications (Clavien-Dindo > 2, 5.2% vs. 19.7%; P = .0008), but longer operating theater time (3.8 vs. 2.8 h; P < .001). Costs are equivalent when at least 350 robotic surgeries are performed annually, not including the initial system costs. Quality of life measures were better after robotic surgery. SF-36 showed better measures for robotic surgery (Physical 56 vs. 39 and Mental 73 vs. 56; P < .01). After robotic surgery, patients tended to recover quicker when compared to open surgery, as they returned to normal activities earlier, with less need for family and governmental assistance (mean recovery time, 23 vs. 70 days; P < 0.006 and mean change in preoperative total functioning score, - 1.5 vs. -3.9: P < 0.05, respectively). Overall, 5-year survival was 89.8% for the open surgery group vs. 94% for the robotic surgery group (log rank, P = 0.330). Obese women with low-grade endometrial cancer had better quality of life after robotic vs. open surgery. They also had shorter hospital stays and fewer postoperative complications. Centers with high volumes of robotic surgery can achieve similar costs when comparing both methods. These results were achieved without jeopardizing survival. Our results further emphasize the need for the Israeli healthcare system to include specific reimbursement for robotic procedures in the population we studied.


Prediction of stability changes upon mutation in an icosahedral capsid.
Identifying the contributions to thermodynamic stability of capsids is of fundamental and practical importance. Here we use simulation to assess how mutations affect the stability of lumazine synthase from the hyperthermophile Aquifex aeolicus, a T = 1 icosahedral capsid; in the simulations the icosahedral symmetry of the capsid is preserved by simulating a single pentamer and imposing crystal symmetry, in effect simulating an infinite cubic lattice of icosahedral capsids. The stability is assessed by estimating the free energy of association using an empirical method previously proposed to identify biological units in crystal structures. We investigate the effect on capsid formation of seven mutations, for which it has been experimentally assessed whether they disrupt capsid formation or not. With one exception, our approach predicts the effect of the mutations on the capsid stability. The method allows the identification of interaction networks, which drive capsid assembly, and highlights the plasticity of the interfaces between subunits in the capsid.


Temperature-dependent growth shapes of Ni nanoclusters on NiAl(110).
Scanning tunneling microscopy studies reveal that two-dimensional nanoscale Ni islands formed by deposition of Ni on NiAl(110) between 200-400 K exhibit far-from-equilibrium growth shapes which change systematically with temperature. Island structure reflects the two types of adsorption sites available for Ni adatoms, and island shapes are controlled by the details of adatom diffusion along island edges accounting for numerous local configurations. The temperature dependence of the island shapes is captured and elucidated by kinetic Monte Carlo simulation of a realistic atomistic-level multisite lattice-gas model incorporating precise diffusion barriers. These barriers are obtained by utilizing density functional theory to probe energetics not just at adsorption sites but also at transition states for diffusion. This success demonstrates a capability for predictive atomistic-level modeling of nanocluster formation and shape selection in systems that have a high level of energetic and kinetic complexity.