Breeding of the northern grasshopper mouse (Onychomys leucogaster) as a laboratory animal.
Laboratory matings were attempted to establish breeding colonies of Northern grasshopper mice, Onychomys leucogaster (which were captured in New Mexico, U.S.A.), as experimental animals. The results were as follows. The rate of pregnancy was 75% with cohabitation for more than 30 days, and 4% with cohabitation from 1 to 7 days. Both cases were of monogamous mating. The mean litter size was 3.5 +/- 1.2, with a range of 1 to 6. The rate of weaning was 78.8%. The mean gestation period was 27.4 +/- 2.0 days, with a range of 25 to 31. The gestation period was achieved by the method of confirming sperm from smears. Further, it was possible to breed all year round in a rearing room with fixed temperature and humidity.


Hot Corrosion and Mechanical Performance of Repaired Inconel 718 Components via Laser Additive Manufacturing.
Hot corrosion is one of the crucial failure modes of Ni-based superalloy components operating at high temperatures, which inevitably affects the subsequent mechanical properties of the alloys. In this research, damaged Inconel 718 alloy components with a pre-made trapezoid groove are repaired using laser additive manufacturing technique, and the change mechanisms of the microstructure and tensile properties of the repaired Inconel 718 alloy due to the hot corrosion in the salt mixture of 87.5 wt.% Na2SO4 + 5 wt.% NaCl + 7.5 wt.% NaNO3 at 650 °C for different durations are investigated. The results show that oxidation and Cr-depletion occur on the repaired components due to the hot corrosion, and the corrosion products are mainly composed of Cr2O3, Fe3O4, and Ni3S2. The tensile strength and elongation of the as-repaired specimens are 736.6 MPa and 12.5%, respectively. After being hot corroded for 50 h, the tensile strength increases to 1022.9 MPa and elongation decreases to 1.7%. However, after being hot corroded for 150 h, both tensile strength and elongation of the repaired specimens drop to 955.8 MPa and 1.2%, respectively. The mechanical performance alteration is highly related to thermal effects instead of the molten salt attack.


Ceftriaxone Etest non-susceptible methicillin susceptible Staphylococcus aureus time-kill responses.
We determined the correlation between Etest and BMD MICs with bactericidal activity in MSSA blood isolates. Ceftriaxone was bactericidal in 36% and 9% of isolates exposed to the Etest and BMD MIC, respectively. With the sub-optimal activity of ceftriaxone, the Etest MIC may be a conservative method in identifying clinical utility.


Embryonic stem cells from blastomeres maintaining embryo viability.
A wide variety of cell and tissue types that are sought in regenerative medicine can be generated from embryonic stem cells (ESCs), and currently two derivatives of human embryonic stem cells (hESCs) have entered human clinical trials. However, the ethical controversy surrounding this technology, which uses preimplantation human embryos to generate cell lines, is limiting research and the development of new therapies. Several new technologies such as induced pluripotent cells or parthenogenetically derived pluripotent cells hold great promise, but more research is needed before their derivatives can be proven to be safe and functional for use in human patients. The blastomere biopsy-based technique allows the derivation of human ESClines without sacrificing a human embryo and was shown to be robust and produce safe and functional derivatives of therapeutic value.


Genetically predicted plasma cortisol and common chronic diseases: A Mendelian randomization study.
Cushing's syndrome is characterized by hypercortisolaemia and is frequently accompanied by comorbidities such as type 2 diabetes, hypertension, osteoporosis, depression and schizophrenia. It is unclear whether moderate but lifelong hypercortisolaemia is causally associated with these diseases in the general population. We aimed to address this research gap using a Mendelian randomization approach. We used three cortisol-associated genetic variants in the SERPINA6/SERPINA1 region as genetic instruments in a two-sample, inverse-variance-weighted Mendelian randomization analysis. We obtained summary-level statistics for cortisol and disease outcomes from publicly available genetic consortia, and meta-analysed them as appropriate. We conducted a multivariable Mendelian randomization analysis to assess potential mediating effects. A 1 standard deviation higher genetically predicted plasma cortisol was associated with greater odds of hypertension (odds ratio: 1.12; 95% confidence interval [CI]: 1.05-1.18) as well as higher systolic blood pressure (mean difference [MD]: 0.03 SD change; 95% CI: 0.01-0.05) and diastolic blood pressure (MD: 0.03 SD change; 95% CI: 0.01-0.04). There was no evidence of association with type 2 diabetes, osteoporosis, depression and schizophrenia. The association with hypertension was attenuated upon adjustment for waist circumference, suggesting potential mediation through central obesity. There is strong evidence for a causal association between plasma cortisol and greater risk for hypertension, potentially mediated by obesity.


Salidroside Promotes Random Skin Flap Survival in Rats by Enhancing Angiogenesis and Inhibiting Apoptosis.
Background Flap necrosis is frequently observed in flap transfer operations. Salidroside has been reported to reduce cell apoptosis by alleviating inflammation and oxidative stress. We investigated the effects of salidroside on the survival of random skin flaps. Materials and Methods The McFarlane flap model was established in 80 rats that were divided into two groups and administered salidroside or saline solution intraperitoneally over 7 days. The area of necrosis and the extent of tissue edema were measured. Angiogenesis was assessed via lead oxide-gelatin angiography, immunohistochemistry for CD34, and VEGF expression. Cell apoptosis was evaluated by expression of cleaved caspase 3, caspase 3, Bax, and Bcl-2. The inflammatory response was evaluated using an ELISA kit for TNF-α and IL-6 in serum. Oxidative stress was assessed by measuring the activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA). Results Compared with controls, salidroside-treated flaps featured a greater area of surviving tissue and less edema. It also promoted the expression of VEGF and increased skin flap angiogenesis. Cell apoptosis, inflammation reaction, and oxidative stress were significantly attenuated in the salidroside group. Conclusion Salidroside has a positive effect on improving random skin flap survival.


HIV status disclosure among postpartum women in rural Tanzania: predictors, experiences and uptake of a nurse-facilitated disclosure intervention.
HIV status disclosure is a key support strategy to start and maintain HIV care and treatment and to reduce HIV transmission. We explored the patterns and correlates of disclosure and described the effectiveness of nurse-facilitated disclosure among HIV-infected mothers of infants in coastal Tanzania. We enrolled 400 HIV positive women in an observational longitudinal study in 2011, interviewed them about maternal sociodemographic and economic characteristics, maternal and child health and history of HIV disclosure experiences and offered nurse-facilitated HIV disclosure at enrolment or at follow-up 1 month later. Mothers frequently disclosed their status to husbands and/or female relatives and experienced predominantly positive reactions. Economically vulnerable women disclosed more often to elderly female relatives, indicating that Infant and Young Child Feeding counseling given to HIV positive women should garner the support of elderly female relatives for implementing appropriate feeding practices. Nurse-facilitated disclosure was feasible in this low resource setting and was used by patients to help them with both first-time disclosure and disclosure to new persons.


Calcium in secretory vesicles of neurohypophysial nerve endings: quantitative comparison by X-ray microanalysis of cryosectioned and freeze-substituted specimens.
The calcium content of individual secretory vesicles in rat neurohypophysial nerve endings was measured by quantitative electron probe X-ray microanalysis. Directly frozen control and potassium-depolarized isolated endings were analysed using two presumably equivalent preparative techniques: (1) freeze-substitution in presence of oxalic acid followed by sectioning of resin-embedded pellets; or (2) direct cryosectioning of the frozen pellets followed by freeze-drying in the column of the microscope. In the pellets of stimulated endings, both approaches revealed an increase in the calcium content of neurosecretory vesicles. This increase was statistically more significant in the specimens prepared by cryosectioning, probably because in this case the contribution of 'dead' nerve endings could be eliminated on the basis of excessive cytoplasmic sodium and chloride. The results demonstrate that an increase in cytosolic calcium can lead to an increase in intravesicular calcium, and that when this occurs, it occurs within a subpopulation of vesicles in a given nerve ending. In addition, measured intravesicular calcium was dispersed over a wide range of concentrations, as predicted by the hypothesis of intravesicular calcium priming. When the vesicular calcium content was averaged per nerve ending, a relatively wide distribution of concentrations was again observed, indicating that some nerve endings respond more strongly to the stimulation than others.


Astronium fraxinifolium Schott Exerts Leishmanicidal Activity by Providing a Classically Polarized Profile in Infected Macrophages.
Leishmania braziliensis is prevalent in Latin American countries, including Brazil. It causes cutaneous and mucocutaneous leishmaniasis, leading to high morbidity, and has a low cure rate. Treatment is based on pentavalent antimonials; nonetheless, there are problems related to high toxicity, high cost, and parasitic resistance. Discovery of new leishmanicidal drugs without these limitations and that stimulate the cellular immune response is necessary. The present work evaluates whether Astronium fraxinifolium Schott exerts leishmanicidal activity against L. braziliensis by providing a classically polarized profile in infected macrophages. For the evaluation of the A. fraxinifolium Schott leishmanicidal activity, amastigote cell death was demonstrated in infected RAW 267.4 macrophages treated with an ethanolic extract from the plant sapwood (EEAF). For the evaluation of the EEAF capacity in providing a classically polarized profile in infected macrophages, the following analyses were done: detection of LAMP-1 protein by the baculovirus technology, measurement of superoxide anion by the NBT testing, quantification of TNF-α, IL-12p40, IL-10, IL-4, and TGF-β by sandwich-type enzyme immune assays, and iNOS and COX-2 expression by RT-PCR technique. The EEAF significantly reduced amastigote counts inside the cells. Vacuoles were visualized in infected and treated cells before and after May-Grünwald-Giemsa staining. A strong LAMP-1 protein fluorescence revealed phagosome maturation in infected cells treated with the EEAF. No production of superoxide was visualized in infected cells treated with the plant material. Nonetheless, high levels of TNF-α, IL-12p40, and IL-10 were found in cell supernatants, but reduced levels of TGF-β and no IL-4 production. We identified augmented mRNA expression for COX-2, but no expression of iNOS mRNA. Our results demonstrated that A. fraxinifolium induced a classically polarized profile in infected macrophages but also provided a less harmful environment by stimulating the production of certain anti-inflammatory mediators, such as IL-10.


Celiac disease: from gluten to autoimmunity.
Celiac disease, also known as gluten-sensitive enteropathy and nontropical sprue, is a prevalent autoimmune disorder that is triggered by the ingestion of wheat gluten and related proteins of rye and barley in genetically susceptible individuals. The immune response in celiac disease involves the adaptive, as well as the innate, and is characterized by the presence of anti-gluten and anti-transglutaminase 2 antibodies, lymphocytic infiltration in the epithelial membrane and the lamina propria, and expression of multiple cytokines and other signaling proteins. The disease leads to inflammation, villous atrophy, and crypt hyperplasia in the small intestine. In addition to the intestinal symptoms, celiac disease is associated with various extra-intestinal complications, including bone and skin disease, anemia, endocrine disorders, and neurologic deficits. Gluten-free diet is currently the only effective mode of treatment for celiac disease, but better understanding of the mechanism of the disease is likely to add other choices for therapy in the future.


Paternal physical exercise improves spatial learning ability by enhancing hippocampal neuroplasticity in male pups born from obese maternal rats.
Maternal obesity exerts negative effects on cognitive function and behavior of the offspring. In the present study, we assessed the effects of paternal physical exercise on spatial learning ability in relation with hippocampal neuroplasticity in the rat pups born from the obese maternal rats. There were four experimental groups: paternal nonexercised male pups from normal maternal rats, paternal exercised male pups from normal maternal rats, paternal nonexercised male pups from obese maternal rats, and paternal exercised male pups from obese maternal rats. Normal diet was supplied for normal maternal rats and high-fat diet was supplied for obese maternal rats for a 12-week period until mating, and the same diet for each group continued throughout pregnancy and lactation period. Male rats in the exercising groups exercised for a 12-week period. Spatial learning ability was reduced in the male rat pups born from the obese maternal rats. Expressions of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B receptor (TrkB) in the hippocampus were suppressed and cell proliferation and differentiation in the hippocampus were reduced in the male rat pups born from the obese maternal rats. Paternal treadmill exercise improved spatial learning ability, increased BDNF and TrkB expressions, and enhanced cell proliferation and differentiation in the male rat pups born from the obese maternal rats. It can be suggested that paternal exercise enhances hippocampal neuroplasticity and consequently improved spatial learning ability in the rat pups born from the obese maternal rats.


Cs3Zn6B9O21: a chemically benign member of the KBBF family exhibiting the largest second harmonic generation response.
Nonlinear optical (NLO) crystals are essential materials for generation of coherent UV light in solid state lasers. KBBF is the only material that can achieve coherent light below 200 nm by direct second harmonic generation (SHG). However, its strong layer habits and the high toxicity of the beryllium oxide powders required for synthesis limit its application. By substituting Be with Zn and connecting adjacent [Zn2BO3O2]∞ layers by B3O6 groups, a new UV nonlinear optical material, Cs3Zn6B9O21, was synthesized. It overcomes the processing limitations of KBBF and exhibits the largest SHG response in the KBBF family.


Two proximal activating protein-1-binding sites are sufficient to stimulate transcription of the ovine follicle-stimulating hormone-beta gene.
FSH is an important regulator of mammalian gametogenesis and the female reproductive cycle. Although little is known about the transcriptional regulation of the beta-subunit (the rate-limiting subunit of FSH synthesis), sequence analysis of the ovine FSHbeta promoter has revealed a number of potential activating protein-1 (AP-1; Jun/Fos)-binding sites. To determine whether the gene encoding the beta-subunit of ovine FSH (oFSHbeta) is responsive to AP-1 transcriptional complexes, chimeric constructs containing deleted portions of the oFSHbeta promoter fused to a luciferase reporter were transiently transfected along with c-Jun and c-Fos expression constructs into JAR cells. Analysis of these deletion constructs revealed that the proximal promoter of oFSHbeta is highly stimulated by c-Jun and c-Fos proteins (typically 20-fold with a reporter construct containing oFSHbeta sequences from -215 to +759 bp). This stimulation was lost when a similar construct containing sequences from -84 to +759 bp was tested. Transcriptional start site analysis using reverse transcription-PCR verified that the transcriptional initiation of the -215-bp deletion construct, with or without cotransfected c-Jun/c-Fos, was the same as that observed in vivo. Computer analysis of oFSHbeta sequences from -215 to +1 bp identified four putative AP-1-like elements, located at -155, -120, -83, and -10 bp. Gel retardation experiments using oligonucleotides corresponding to the four putative AP-1-like sites revealed that only -120 and -83 sites in oFSHbeta bound AP-1 proteins in vitro. Site-directed mutagenesis of the -120 and -83 sites showed that each element was required for stimulation by c-Jun and c-Fos proteins as well as 12-O-tetradecanoyl phorbol-13-acetate in transient transfection assays. Finally, immunocytochemical dual labeling was used to show that more than 75% of all FSHbeta-containing cells in ovine pituitary sections from cycling ewes contained nuclear c-Jun, JunB, JunD, and Fos proteins. These data, taken together, show that oFSHbeta transcription can be stimulated by c-Jun and c-Fos proteins via two functionally linked AP-1-like sites in the oFSHbeta proximal promoter and that these sites are likely to be important regulators of FSH production in vivo.


Targeting Lyn regulates Snail family shuttling and inhibits metastasis.
The acquisition of an invasive phenotype by epithelial cells occurs through a loss of cellular adhesion and polarity, heralding a multistep process that leads to metastatic dissemination. Since its characterization in 1995, epithelial-mesenchymal transition (EMT) has been closely linked to the metastatic process. As a defining aspect of EMT, loss of cell adhesion through downregulation of E-cadherin is carried out by several transcriptional repressors; key among them the SNAI family of transcription factors. Here we identify for the first time that Lyn kinase functions as a key modulator of SNAI family protein localization and stability through control of the Vav-Rac1-PAK1 (Vav-Rac1-p21-activated kinase) pathway. Accordingly, targeting Lyn in vitro reduces EMT and in vivo reduces metastasis of primary tumors. We also demonstrate the clinical relevance of targeting Lyn as a key player controlling EMT; patient samples across many cancers revealed a strong negative correlation between Lyn and E-cadherin, and high Lyn expression in metastatic tumors as well as metastasis-prone primary tumors. This work reveals a novel pancancer mechanism of Lyn-dependent control of EMT and further underscores the role of this kinase in tumor progression.


HDAC inhibitor AR-42 decreases CD44 expression and sensitizes myeloma cells to lenalidomide.
Multiple myeloma (MM) is a hematological malignancy of plasma cells in the bone marrow. Despite multiple treatment options, MM is inevitably associated with drug resistance and poor outcomes. Histone deacetylase inhibitors (HDACi's) are promising novel chemotherapeutics undergoing evaluation in clinical trials for the potential treatment of patients with MM. Although in preclinical studies HDACi's have proven anti-myeloma activity, but in the clinic single-agent HDACi treatments have been limited due to low tolerability. Improved clinical outcomes were reported only when HDACi's were combined with other drugs. Here, we show that a novel pan-HDACi AR-42 downregulates CD44, a glycoprotein that has been associated with lenalidomide and dexamethasone resistance in myeloma both in vitro and in vivo. We also show that this CD44 downregulation is in part mediated by miR-9-5p, targeting insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), which directly binds to CD44 mRNA and increases its stability. Importantly, we also demonstrate that AR-42 enhances anti-myeloma activity of lenalidomide in primary MM cells isolated from lenalidomide resistant patients and in in vivo MM mouse model. Thus, our findings shed light on potential novel combinatorial therapeutic approaches modulating CD44 expression, which may help overcome lenalidomide resistance in myeloma patients.


Validation of the OptoGait System for Monitoring Treatment and Recovery of Post-Concussion Athletes.
This study sought to investigate correlations between OptoGait motion analysis technology and 2 commonly used concussion assessment instruments, the Balance Evaluation Scoring System (BESS) and the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) computerized neurocognitive assessment software, to see if OptoGait might be a valid concussion assessment tool. Twenty Division-1 college women varsity soccer players completed trials of 8 different conditions of the OptoGait test battery. Then participants completed the BESS and ImPACT tests. One hundred twenty-eight total spatiotemporal variables were recorded for each trial of OptoGait. Pearson's r correlations among these variables and BESS and ImPACT results were calculated, and pattern analysis was completed to evaluate for emergent patterns in the data. Correlations for the 8 OptoGait mean-score subtests were related to the balance double-leg foam test (BESS). Correlations for the 8 OptoGait mean-score subtests were related to the balance double-leg foam test (BESS), and correlations between OptoGait standard deviation measures and the balance tandem hard surface test (BESS) both indicated potentially significant patterns. No consistent patterns of correlation existed between the OptoGait variables and the ImPACT results. OptoGait conditions correlate at higher than predicted rates with subtests of the BESS instruments but not the ImPACT measures.


A placebo controlled crossover trial of subcutaneous salmon calcitonin in the treatment of patients with fibromyalgia.
The objective of this study was to evaluate the relative efficacy and tolerability of subcutaneously (s.c.) administered salmon calcitonin (sCT) in the treatment of patients with fibromyalgia. Eleven patients who fulfilled the American College of Rheumatology classification criteria for fibromyalgia were studied in a double-blind, crossover trial in which they alternatively received salmon calcitonin (100 IU s.c.) and isotonic saline (1 cc s.c.) for four weeks, with a four weeks wash-out period between the treatments. None of the 11 outcomes measures (seven analog scales, dolorimetry score, and three SIP scores) showed a significant improvement with sCT. The principal side effect observed with sCT was nausea in ten patients and erythema in four patients. These data suggest that sCT given at a dose of 100 IU daily for one month is not effective in the treatment of fibromyalgia.


Prediction of the therapeutic dose for benzodiazepine anxiolytics based on receptor occupancy theory.
Many benzodiazepines (BZPs) are now used as anxiolytics with nearly 200-fold variety of therapeutic doses. The variation of the doses of BZPs is due to differences both in their pharmacokinetics and in their receptor binding characteristics. The purpose of this study is to clarify the mechanism of the differences in therapeutic dose by retrospective analyses and to develop a system for the quantitative estimation of optimal doses of BZPs. The values of receptor dissociation constant (Kd), which indicates the binding affinity of each BZP at the receptor site, were obtained from a number of works based on in vitro binding experiments. The plasma unbound concentrations of the BZPs and their active metabolites were calculated using the reported values of their total plasma concentrations after average oral doses of the BZPs and the values of their plasma unbound fractions, which were also taken from the literature. There were log-linear relationships between the Kd values of BZPs and their average therapeutic doses or maximum plasma concentrations, but the correlation coefficients were relatively small (r < 0.77). In contrast, a good log-linearity (r = 0.96) was observed in the correlation between their Kd values and the effective plasma unbound concentrations considering the active metabolites. This finding indicates that the receptor occupancy after administration of therapeutic dose of BZPs is consistent (52.3 +/- 3.2%) among the BZPs. In this study, we also develop a possible system for estimating the appropriate doses of BZPs based on receptor occupancy theory.


[Treatment of endometrial hyperplasia with Goserelin depot, an LH-RH analog].
Nineteen patients with simple endometrial hyperplasia presenting metrorrhagia or menometrorrhagia were treated with 4 injections of Goserelin depot, one every 4 weeks. 12/19 patients were refractory after previous medical therapy. The treatment with Goserelin depot resulted in a complete remission of the symptoms, occurring within the first month of treatment and still present after a median follow-up of 12 months, and in the normalization of the histological profile. No patient experienced clinically relevant side effects.


Estradiol Priming Improves Gonadotrope Sensitivity and Pro-Inflammatory Cytokines in Obese Women.
Obesity is associated with a pro-inflammatory state and relative hypogonadotropic hypogonadism. Estrogen (E2) is a potential link between these phenomena because it exhibits negative feedback on gonadotropin secretion and also inhibits production of pro-inflammatory cytokines. We sought to examine the effect of estrogen priming on the hypothalamic-pituitary-ovarian axis in obesity. This was an interventional study at an academic center of 11 obese and 10 normal-weight (NW) women. A frequent blood-sampling study and one month of daily urinary collection were performed before and after administration of transdermal estradiol 0.1 mg/d for one entire menstrual cycle. Serum LH and FSH before and after GnRH stimulation, and urinary estrogen and progesterone metabolites were measured. E2 increased LH pulse amplitude and FSH response to GnRH (P = .048, and P < .03, respectively) in obese but not NW women. After E2 priming, ovulatory obese but not NW women had a 25% increase in luteal progesterone (P = .01). Obese women had significantly higher baseline IL-6, IL-10, TGF-β, and IL-12 compared with NW (all P < .05); these levels were reduced after E2 (-6% for IL-1β, -21% for IL-8, -5% for TGF-β, -5% for IL-12; all P < .05) in obese but not in NW women. E2 priming seems to improve hypothalamic-pituitary-ovarian axis function and systemic inflammation in ovulatory, obese women. Reducing chronic inflammation at the pituitary level may decrease the burden of obesity on fertility.


Prevention of unrecognized joint penetration during internal fixation of hip fractures: a geometric model based on Steinmetz Solid.
Unrecognized joint penetration (UJP) by screw penetration through the articular surface undetectable on routine anteroposterior (AP) and lateral radiographs can cause serious complications. We have developed a geometric model to analyze UJP, and methods for the prevention of the problem. A Steinmetz Solid (SS) is the overlapping portion between two identical, vertically intersecting cylinders. The AP and lateral radiographs of a femoral head (simplified as a sphere) are projections of two cylinder-shaped images. A screw that appears to be within the femoral head in fact only lies within the cylinder. A screw apparently within the femoral head on both AP and lateral images is only confined to the SS generated by two cylinders, but not necessarily confined to the femoral head itself. We have therefore analyzed UJP using a geometric model based on SS. The geometric basis of UJP lies in the fact that the SS is larger than the sphere (femoral head) with a volume ratio of 4: π. The theoretical risk of UJP for any screw therefore can be as high as 21.5% ((4-π)/4). In reality, screws are always carefully placed to ensure a distance between the screw's tip and the edge of femoral head (tip-to-edge distance, or TED). This TED effectively lowers the risk of UJP by reducing the size of the screw-confining SS. When the SS entirely fits into (internally tangential to) the femoral head, the risk of UJP approaches zero. A TED fulfilling this requirement can be regarded as safe (approximately 0.29 x femoral head radius). With a femoral head diameter of 5 cm, the safe TED is approximately 7 mm.


Nonoxynol-9 spermicide contraception use--United States, 1999.
Most women in the United States with human immunodeficiency virus (HIV) become infected through sexual transmission, and a woman's choice of contraception can affect her risk for HIV transmission during sexual contact with an infected partner. Most contraceptives do not protect against transmission of HIV and other sexually transmitted diseases (STDs), and the use of some contraceptives containing nonoxynol-9 (N-9) might increase the risk for HIV sexual transmission. Three randomized, controlled trials of the use of N-9 contraceptives by commercial sex workers (CSWs) in Africa failed to demonstrate any protection against HIV infection; one trial showed an increased risk. N-9 contraceptives also failed to protect against infection with Neisseria gonorrhoeae and Chlamydia trachomatis in two randomized trials, one among African CSWs and one among U.S. women recruited from an STD clinic. Because most women in the African studies had frequent sexual activity, had high-level exposure to N-9, and probably were exposed to a population of men with a high prevalence of HIV/STDs, the implications of these studies for U.S. women are uncertain. To determine the extent of N-9 contraceptive use among U.S. women, CDC assessed data provided by U.S. family planning clinics for 1999. This report summarizes the results of that assessment, which indicate that some U.S. women are using N-9 contraceptives. Sexually active women should consider their individual HIV/STD infection risk when choosing a method of contraception. Providers of family planning services should inform women at risk for HIV/STDs that N-9 contraceptives do not protect against these infections.


GENETIC VARIATION AND POLYMORPHISM IN THE INDUCIBLE SPINES OF A MARINE BRYOZOAN.
Of particular value in understanding the evolution of genotypes with broad phenotypic ranges (phenotypic plasticity) are the few examples of organisms with adaptive plasticity, such as those that develop a defensive morphology in response to cues from predators. We know little about the heritability of inducible defensive characters or the range of phenotypes available for selection to act on in the field. Membranipora membranacea is a colonial marine bryozoan that produces spines within two days of exposure to waterborne predator extracts. Surveys done in 1993 and 1995 showed that the population at Friday Harbor Labs, Washington, was polymorphic for inducible spine type and was composed of a constitutively spined type that produced spines in the absence of a predator stimulus, an unspined phenotype that did not produce spines irrespective of a stimulus, and an inducibly spined phenotype that would produce spines if exposed to the appropriate cue. In 1995, the frequencies of these types were determined through a laboratory common-garden experiment; 178 colonies were cultured from metamorphosis through approximately 30 days and then exposed to the cue. The inducible type was the dominant, comprising 80.3% of the population. The constitutive type made up 6.2% of the population, and the remaining 13.4 % was the unspined type. The frequency of the three types was similar to a preliminary trial of the experiment run in 1993. Experiments also showed that the lengths of the spines of the inducible type varied continuously among genotypes. To assess causes of variation in the inducible spine response and its clonal heritability, 16 clones were subdivided and grown in a common environment and exposed to a single dosage of spine inducing substance (SIS). Spine length showed high clonal heritability. The range of colony responses from a single environment varied from relatively unresponsive to highly responsive colonies with a very low threshold of response. Norms of reaction were quantified for spine lengths of inducible genotypes originating from two field environments by testing them in a concentration series of SIS. Both spine length and spine type varied with concentration of inducer. Within a clone, colonies were more likely to produce membranous spines than corner spines at higher concentrations. At low concentrations, only straight spines were produced. This study showed that populations of M. membranacea at Friday Harbor are a mix of inducible, nonspined and constitutively spined individuals. Even the inducible individuals showed high heritable variation in the length of spine activated, suggesting that there is considerable scope for the evolution of this character. A norm-of-reaction experiment further showed that the type of spine produced, membranous or corner, varied with the concentration of the cue. Factors maintaining the polymorphism and the broad range of genotypes could include high costs of defending the spined types coupled with a shifting biotic regime.


Commentary: Will Mandatory Reporting of Health Professional Misconduct, Incompetence or Incapacity Make Patients Safer?
Public expectations of safety are a given in all aspects of our daily lives and certainly in the delivery of health services. Can enhanced legislation and regulatory requirements strengthen the very systems established to support safe care and safe practice by those professionals delivering this care? The delivery of health services is a complex matrix of public and private systems and care providers. Individual regulated health professionals play a key role in ensuring safe care as do legislators, employers, regulators and unions.


Development and Validation of an HPLC-MS/MS Method for Rapid Simultaneous Determination of Cefprozil Diastereomers in Human Plasma.
Both cis- and trans-cefprozil have antimicrobial activity, but their potencies are quite different. It is therefore necessary to develop a sensitive method to simultaneously determine both isomers for pharmacokinetic and bioequivalence studies. An LC-MS/MS method, using stable isotope-labeled cefprozil as the internal standard, was developed and validated. The analytes were extracted from plasma by protein precipitation and separated on a reverse-phase C18 column using a gradient program consisting of 0.5% formic acid and acetonitrile within 4 min. The mass spectrometry acquisition was performed with multiple reaction monitoring in positive ion mode using the respective [M+H]+ ions, m/z 391.2→114.0 for cefprozil and 395.0→114.5 for cefprozil-D4. The calibration curves were linear over the ranges of 0.025-15 μg/mL for cis-cefprozil and 0.014-1.67 μg/mL for trans-cefprozil. The accuracies for the cis and trans isomers of cefprozil were 93.1% and 103.0%, respectively. The intra- and interassay precisions for the QC samples of the isomers were < 14.3%. The intra- and interassay precisions at the LLOQ were < 16.5%. The method was sensitive and reproducible and was applied in a pilot pharmacokinetic study of healthy volunteers.


Changing attitudes towards third-party reproductive techniques.
A growing number of children around the world are conceived through third-party reproductive techniques. The increased demand for these programs has resulted in an ongoing trend towards greater openness and less anonymity in gamete donation. This has led to changes in public policy regarding the identity of donors, to a greater concern for the well-being of donors, and to calls for disclosure to offspring about their donor gamete conception.


Self-entwinement of an active fixation pacemaker electrode.
We report a case in which an active fixation atrial lead tip became entwined on the proximal lead body during implantation. It was not possible to disengage the tip or to remove the resultant lead loop atraumatically through the insertion site. Removal of the lead was accomplished using a Dotter intravascular snare inserted via a femoral vein, with subsequent successful implantation of a new lead. This unusual technique-related complication emphasizes the need for meticulous fluoroscopic visualization during lead manipulation.


Kinetics of Lagging-strand DNA Synthesis In Vitro by the Bacteriophage T7 Replication Proteins.
Here we provide protocols for the kinetic examination of lagging-strand DNA synthesis in vitro by the replication proteins of bacteriophage T7. The T7 replisome is one of the simplest replication systems known, composed of only four proteins, which is an attractive feature for biochemical experiments. Special emphasis is placed on the synthesis of ribonucleotide primers by the T7 primase-helicase, which are used by DNA polymerase to initiate DNA synthesis. Because the mechanisms of DNA replication are conserved across evolution, these protocols should be applicable, or useful as a conceptual springboard, to investigators using other model systems. The protocols described here are highly sensitive and an experienced investigator can perform these experiments and obtain data for analysis in about a day. The only specialized piece of equipment required is a rapid-quench flow instrument, but this piece of equipment is relatively common and available from various commercial sources. The major drawbacks of these assays, however, include the use of radioactivity and the relative low throughput.


Gas chromatographic determination of pentachlorophenol in gelatin.
A method is described for the determination of pentachlorophenol (PCP) in gelatin. The method employs acid and heat to hydrolyze the gelatin matrix, a base partition and wash for separation and cleanup, and a reacidification and extraction with hexane for direct determination of PCP, without preparation of a derivative, using gas chromatography (GC) with a 1% SP- 124ODA liquid phase and a 63Ni electron capture detector. Recoveries averaged 106% for fortifications between 0.02 and 1.0 ppm. The limit of quantitation is 20 ppb. The limit of detection is 4-6 ppb. The method, which has undergone a successful intralaboratory trial, is simple and rapid, and requires only general laboratory reagents and equipment. GC of the acetate derivative of PCP is used for confirmation of identity.


[Compression vertebral fracture in osteoporosis--prevention and treatment].
Vertebral fractures are the earliest and most common osteoporotic fractures. Usually vertebral fractures are associated with following clinical symptoms: back pain, posture change, loss of height, functional impairment, disability and decreasing quality of life. After 3 years of treatment raloxifene reduced the risk of first vertebral fracture by 55%. The fracture risk within one year was reduced by as much as 68%. The continued observation proved its sustained efficacy in further reduction of the fracture risk by 50% in the fourth year.


The effect of temporary treatment of animal half embryos with lithium and the modification of this effect by simultaneous exposure to actinomycin D.
Sixteen-cell stages of the sea urchin Paracentrotus lividus were separated into animal and vegetal halves. The former were reared in four different media: pure sea water, sea water with 10 μg/ml actinomycin D, sea water with 0.043 mol lithium, sea water containing the same concentration of lithium together with 10 μg/ml actinomycin D. The main result of the study was that the development had a more animal character after combined exposure to actinomycin D and lithium than after exposure to lithium alone. The inference from this result is that transcription processes are involved in the vegetalization of lithium treated sea urchin embryos.The differentiation of the animal halves occurring in normal sea water is widely repressed in the presence of actinomycin D. Particularly obvious is the fact that the transformation of the acron with ensuing substitution of the long stereocilia by short motile cilia fails to occur in the presence of actinomycin D. The transformation of the acron and its stereocilia seem thus to be dependent on transcription processes.In animal halves reared in normal medium droplets, dark in phase contrast, may appear near the tip of the stereocilia. This is followed very soon by the shedding of the stereocilia. In animal halves treated with actinomycin D, the droplets appear in a somewhat later stage than in the halves reared in normal sea water. After their appearance, the stereo cilia acquire a certain motility. The droplet formation may correspond to the elimination of a component which stiffens the stereocilia. The elimination of this component does not seem to be directly dependent of transcription processes. On the other hand, the stability of the stereocilia decreases with the distance from the animal pole.The data obtained in this investigation may be integrated into the double gradient concept, also in its recent elaboration (Runnström, 1967).The present investigation was carried out at Stazione Zoologica, Naples. We are deeply indebted to Professor M. Pantaleo, head of this institution, for his interest and generous support. We express also our gratitude to Professors R. Martin and R. Rocca for their help and friendly interest. One of us expresses his gratitude to Professor M. Pantaleo for the award of a research grant from the Stazione. He recognizes also his indebtedness to Professor M. De Vincentiis, director of the Department of Histology and Embryology at the University of Naples. The second of us expresses his thanks for financial support from the "Swedish Natural Sciences Research Council", from the "Swedish Cancer Society" and from the "Research group of embryology for the study of cellular differentiation " of the Department of Zoology, University of Rome. He expresses his sincere thanks to the Director of this Department, Professor P. Pasquini, for his stimulating interest.


Improved technique of portal vein reconstruction in pediatric liver transplant recipients with portal vein hypoplasia.
Children with small or hypoplastic portal veins represent a challenge for liver transplantation. Graft loss of up to 70% has been reported in these patients in the past. A variety of techniques has been used in both cadaveric and living related transplants in an effort to overcome this problem. Variability arises as to whether to use a vascular graft and where on the portal system to attach the graft. We present our usage of a simple and straightforward interposition iliac vein allograft fashioned in a manner to achieve large anastomotic cross-sectional area on the confluence of the superior mesenteric/splenic veins. The procedure also overcomes problems of graft vein/portal vein size mismatch in the cases where liver and vein grafts are procured from much larger donors. A total of 14 children presented with hypoplastic portal vein (diameter<5 mm), of a total of 30 consecutive patients requiring cadaveric liver transplants, and benefited from this technique. Median recipient age was 10.5 months. Revascularization times ranged from 22 to 43 min with a mean of 33 min. All patients are alive and well at a mean follow-up of 329 days (10 months). All liver grafts are well and functioning. No portal vein problem was detected. Results from this technique are clearly encouraging. Because portal vein hypoplasia is a common problem in pediatric transplant candidates, we believe this alternative technique is of interest and should be added to the transplant surgeon's armamentarium.


Influence of device selection on angiographic outcomes for the treatment of in-stent restenosis. A sub analysis from the Washington Radiation for In-Stent restenosis Trial (WRIST).
Treatment of in-stent restenosis is still a challenge. Despite promising results obtained with intracoronary brachytherapy (ICB), the ideal strategy of device selection has not been identified. The aim of this study was to evaluate the influence of device selection on ICB for the treatment of instant restenosis. The outcomes of 130 patients from the Washington Radiation for In-Stent restenosis Trial (WRIST) were studied. Patients were analyzed on the basis of device selection, prior to randomization to gamma-radiation (n = 65) or placebo (n = 65): balloon angioplasty (PTCA) (n = 15, 12%), rotational atherectomy (RA) (n = 40, 31%), excimer laser coronary angioplasty (ELCA) (n = 28, 22%) or additional stent implantation (n = 47, 36%). PTCA was less frequently used in lesions with prior in-stent restenosis (14.8%, p < 0.05); ELCA was less frequently used in saphenous vein grafts (57.1%, p < 0.05). The procedural outcomes and restenosis rates were similar among groups. In the RA group, patients assigned or Ir192 had a larger minimal lumen diameter (1.6 +/- 0.5 vs 0.9 +/- 0.4 mm, p < 0.05) and lower diameter stenosis (39 +/- 7 vs 65 +/- 16%, p < 0.05) at follow-up angiography and a reduced late loss (0.2 +/- 0.5 v 0.9 +/- 0.5 mm, P < 0.05) and loss index (0 +/- 0.4 vs 0.8 +/- 0.4, p < 0.05) when compared to placebo. The incidence of delayed thrombosis was 7.7% in the ICB and 4.6% in the placebo group (p = 0.71); additional stenting, either alone (relative risk 12.36, 95% confidence interval 1.56 divided by 94.43) or followed by ICB (relative risk 3.80, 95% confidence interval 1.02 divided by 14.27), was correlated with an increased risk of late thrombosis. ICB reduces the recurrence of in-stent restenosis through a reduction in late loss. In view of the higher risk of delayed thrombosis, additional stenting, either alone or followed by ICB, should be used with caution.


Analysis of temperature behavior in biological tissue in photothermal therapy according to laser irradiation angle.
The type of death of biological tissue varies with temperature and is broadly classified as apoptosis and necrosis. A new treatment called photothermal therapy is being studied on this basis. Photothermal therapy is a treatment technique based on photothermal effects and has the advantage of not requiring incisions and, therefore, no bleeding. In this study, a numerical analysis of photothermal therapy for squamous cell carcinoma was performed. Photothermal agents used were gold nanoparticles, and the photothermal therapy effect was confirmed by changing the angle of the laser irradiating the tumor tissue. The effectiveness of photothermal therapy was quantitatively assessed on the basis of three apoptotic variables. Further, the volume fraction of gold nanoparticles in the tumor tissue and laser intensity with optimal therapeutic effect for different laser irradiation angles were studied. Thus, the findings of this study can aid the practical implementation of photothermal therapy in the future.


Determination of the parameters controlling swelling of chemically cross-linked pH-sensitive poly(N-vinylimidazole) hydrogels.
The number of variables controlling the behavior of ionic gels is large and very often some of them are unknown. The aim of this work is to interpret quantitatively the swelling behavior of pH sensitive gels, with the minimum number of simplifying assumptions. With this purpose, the equilibrium degree of swelling (S) and protonation (alpha) of chemically cross-linked poly(N-vinylimidazole) (PVI) immersed in aqueous salt solutions were measured as a function of the ionic strength (mu), in the whole range of pH. In acid solutions with pH in the range 0 to 4, imidazole moieties become protonated, and PVI behaves as a polyelectrolyte gel: S decreases upon increasing mu both for NaCl and for CaCl(2), with HCl as protonating acid. In aqueous solutions with larger pH, between 4 and 12, the hydrogel is practically neutral, and S increases as mu rises, showing a salting-in effect. From the quantitative analysis of these results, the following facts emerged. Protonation induces chain stiffness (as measured by the non-Gaussian factor) and worsening of the solvent quality of the aqueous media (as measured by the polymer-solvent interaction parameter). For alpha below 33%, swelling seems to be governed by the excess of mobile counterions inside the gel with respect to the bath, with a minor but still significantly negative contribution of the osmotic swelling pressure due to polymer-solvent mixing. Above 33% protonation, it is necessary to consider Manning counterion condensation to get parameters with physical meaning. The crossover between polyelectrolyte and salting-in effects corresponds to alpha and mu values with the same ionic and mixing contributions to the osmotic swelling pressure. The formation of ionic nonpermanent cross-links, with H(2)SO(4) as the protonating acid, was discarded.


[Effects of 4-(4'-chlorobenzyloxy) benzyl nicotinate (KCD-232) on lipid metabolism in rats and mice].
The hypolipidemic properties of KCD-232[4-(4'-chlorobenzyloxy) benzyl nicotinate], a new compound, were studied in rats fed a basal diet and mice fed a high-cholesterol diet with the following results: KCD-232 reduced serum cholesterol (CH), triglyceride (TG) and phospholipid (PL) levels in a dose-dependent manner (20 approximately 160 mg/kg/day) in rats fasted for 16 hr. KCD-232 significantly reduced (LDL + VLDL)-CH and decreased the (LDL + VLDL)-CH/HDL-CH ratio designated as the "atherogenic index" unlike clofibrate which was used as a reference. KCD-232 slightly increased relative liver weight, but not in the dose-dependent manner of clofibrate. KCD-232 also inhibited the elevation of serum CH level in mice fed a high-cholesterol diet in a dose-dependent manner, and this inhibitory effect was more pronounced than those of clofibrate and nicotinic acid (NA). Liver CH and fatty acid (FA) synthesis from [1-14C] acetate were inhibited both in vitro and in vivo in rats orally administered KCD-232. Clofibrate also decreased CH synthesis, whereas it increased FA synthesis. NA had no effect on either synthesis. After oral administration of [4-14C] cholesterol to rats that were cannulated into the thoracic-duct lymph, KCD-232 markedly depressed the appearance of 14C-cholesterol in lymph. KCD-232 induced no proliferation of hepatic peroxisomes in rats, unlike clofibrate. The detailed hypolipidemic mechanism of KCD-232 is not yet clear, but as shown, it decreased CH synthesis in the liver, exogenous CH absorption from the intestine and FA synthesis in the liver. These results suggest that the serum lipid-lowering profiles of KCD-232 differ from those of clofibrate and NA.


GJA1-20k attenuates Ang II-induced pathological cardiac hypertrophy by regulating gap junction formation and mitochondrial function.
Cardiac hypertrophy (CH) is characterized by an increase in cardiomyocyte size, and is the most common cause of cardiac-related sudden death. A decrease in gap junction (GJ) coupling and mitochondrial dysfunction are important features of CH, but the mechanisms of decreased coupling and energy impairment are poorly understood. It has been reported that GJA1-20k has a strong tropism for mitochondria and is required for the trafficking of connexin 43 (Cx43) to cell-cell borders. In this study, we investigated the effects of GJA1-20k on Cx43 GJ coupling and mitochondrial function in the pathogenesis of CH. We performed hematoxylin-eosin (HE) and Masson staining, and observed significant CH in 18-week-old male spontaneously hypertensive rats (SHRs) compared to age-matched normotensive Wistar-Kyoto (WKY) rats. In cardiomyocytes from SHRs, the levels of Cx43 at the intercalated disc (ID) and the expression of GJA1-20k were significantly reduced, whereas JAK-STAT signaling was activated. Furthermore, the SHR rats displayed suppressed mitochondrial GJA1-20k and mitochondrial biogenesis. Administration of valsartan (10 mg· [Formula: see text] d-1, i.g., for 8 weeks) prevented all of these changes. In neonatal rat cardiomyocytes (NRCMs), overexpression of GJA1-20k attenuated Ang II-induced cardiomyocyte hypertrophy and caused elevated levels of GJ coupling at the cell-cell borders. Pretreatment of NRCMs with the Jak2 inhibitor AG490 (10 µM) blocked Ang II-induced reduction in GJA1-20k expression and Cx43 gap junction formation; knockdown of Jak2 in NRCMs significantly lessened Ang II-induced cardiomyocyte hypertrophy and normalized GJA1-20k expression and Cx43 gap junction formation. Overexpression of GJA1-20k improved mitochondrial membrane potential and respiration and lowered ROS production in Ang II-induced cardiomyocyte hypertrophy. These results demonstrate the importance of GJA1-20k in regulating gap junction formation and mitochondrial function in Ang II-induced cardiomyocyte hypertrophy, thus providing a novel therapeutic strategy for patients with cardiomyocyte hypertrophy.


Oral methadone for chronic noncancer pain: a systematic literature review of reasons for administration, prescription patterns, effectiveness, and side effects.
To assess the indications, prescription patterns, effectiveness, and side effects of oral methadone for the treatment of chronic noncancer pain. We conducted searches of several electronic databases, textbooks and reference lists for controlled or uncontrolled studies in humans. Effectiveness was assessed using a dichotomous classification of "meaningful" versus "nonmeaningful" outcomes. Twenty-one papers (1 small randomized trial, 13 case reports, and 7 case series) involving 545 patients with multiple noncancer pain conditions were included. In half of the patients, no specific diagnosis was reported. Methadone was administered primarily when previous opioid treatment was ineffective or produced intolerable side effects. Starting dose ranged from 0.2 to 80 mg/day and maximum dose ranged from 20 to 930 mg/day. Pain outcomes were meaningful in 59% of the patients in the uncontrolled studies. The randomized trial demonstrated a statistically significant improvement in pain for methadone (20 mg/day) compared to placebo. Side effects were considered minor. Oral methadone is used for various noncancer pain syndromes, at different settings and with no prescription pattern that could be identifiable. Starting, maintenance, and maximum doses showed great variability. The figure of 59% effectiveness of methadone should be interpreted very cautiously, as it seems overrated due to the poor quality of the uncontrolled studies and their tendency to report positive results. The utilization of oral methadone for noncancer pain is based on primarily uncontrolled literature. Well-designed controlled trials may provide more accurate information on the drug's efficiency in pain syndromes and in particular neuropathic pain.


Impact of warming on phyto-bacterioplankton coupling and bacterial community composition in experimental mesocosms.
Global warming is assumed to alter the trophic interactions and carbon flow patterns of aquatic food webs. The impact of temperature on phyto-bacterioplankton coupling and bacterial community composition (BCC) was the focus of the present study, in which an indoor mesocosm experiment with natural plankton communities from the western Baltic Sea was conducted. A 6 °C increase in water temperature resulted, as predicted, in tighter coupling between the diatom-dominated phytoplankton and heterotrophic bacteria, accompanied by a strong increase in carbon flow into bacterioplankton during the phytoplankton bloom phase. Suppressed bacterial development at cold in situ temperatures probably reflected lowered bacterial production and grazing by protists, as the latter were less affected by low temperatures. BCC was strongly influenced by the phytoplankton bloom stage and to a lesser extent by temperature. Under both temperature regimes, Gammaproteobacteria clearly dominated during the phytoplankton peak, with Glaciecola sp. as the single most abundant taxon. However, warming induced the appearance of additional bacterial taxa belonging to Betaproteobacteria and Bacteroidetes. Our results show that warming during an early phytoplankton bloom causes a shift towards a more heterotrophic system, with the appearance of new bacterial taxa suggesting a potential for utilization of a broader substrate spectrum.


Association of Serum Apolipoprotein B with the Increased Risk of Diabetes in Korean Men.
This study aimed to investigate the association of Apolipoprotein B (ApoB) with the risk of diabetes in Koreans. Korean men (n = 790, 40-79 years) who had been never diagnosed for diabetes before participating were enrolled. Subjects were categorized into normal fasting glucose (NFG, n = 519), impaired fasting glucose (IFG, n = 188) and newly-onset diabetes (n = 83) according to fasting glucose levels. Age was not significantly different among the subgroups. Mean values of BMI, waist circumference, Blood pressure(BP), triglyceride, non-HDL cholesterol were significantly higher in IFG or newly-onset diabetic subjects compared to NFG subjects. The levels of glucose, insulin, free fatty acid, insulin resistance and ApoB were highest in diabetic patients and lowest in NFG subjects. According to ApoB level, subjects were divided into two groups (high-ApoB group: ≥ 87.0 mg/dL vs. low-ApoB group: < 87.0 mg/dL). The risk of diabetes was higher in the high-ApoB group than the low-ApoB group [OR0: 2.392, (95% CI: 1.470-3.893), P0 < 0.001]. This association was maintained after adjusted for age and BMI [OR1: 2.228, (95% CI: 1.362-3.646), P1 = 0.001] and further adjustment for blood pressure, triglyceride, HDL-cholesterol, LDL-cholesterol, non-HDL-cholesterol, ApoA1 and adiponectin [OR2: 1.984, (95% CI: 1.001-4.064), P2 = 0.049]. The association was much greater in subjects with metabolic syndrome (MetS) [OR1: 2.805 (95% CI: 1.137-5.737), P1 = 0.005] than in those without [OR1: 1.917 (95% CI: 0.989-3.718), P1 = 0.054]. After 3-month, further investigation was randomly performed in subjects with NFG or IFG who agreed to reinvestigation. Multiple stepwise regression analysis revealed that net change of ApoB levels was a main contributor to the net change of glucose levels (standardized b-coefficient: 0.315, p = 0.002). In conclusion, ApoB levels are closely associated with the increased risk of diabetes in Korean men.


Antibacterial, antioxidant, and anticholinesterase activities of plant seed extracts from Brazilian semiarid region.
The antimicrobial, antioxidant, and anticholinesterase activities of ethanolic seed extracts of twenty-one plant species from Brazilian semiarid region were investigated. The extracts were tested for antimicrobial activity against six bacteria strains and three yeasts. Six extracts presented activity against the Gram (-) organism Salmonella choleraesuis and the Gram (+) organisms Staphylococcus aureus and Bacillus subtilis. The MIC values ranged from 4.96 to 37.32 mg/mL. The Triplaris gardneriana extract presented activity against the three species, with MIC values 18.8, 13.76, and 11.15 mg/mL, respectively. Five extracts presented antioxidant activity, with EC50 values ranging from 69.73 μ g/mL (T. gardneriana) to 487.51 μ g/mL (Licania rigida). For the anticholinesterase activity, eleven extracts were capable of inhibiting the enzyme activity. From those, T. gardneriana, Parkia platycephala and Connarus detersus presented the best activities, with inhibition values of 76.7, 71.5, and 91.9%, respectively. The extracts that presented antimicrobial activity were tested for hemolytic assay against human A, B, and O blood types and rabbit blood. From those, only the Myracrodruon urundeuva extract presented activity (about 20% of hemolysis at the lowest tested concentration, 1.9 µg/mL). Infrared spectroscopy of six representative extracts attested the presence of tannins, polyphenols, and flavonoids, which was confirmed by a qualitative phytochemical assay.


Dynamical variability in the modelling of chemistry-climate interactions.
We have used a version of the Met Office's climate model, into which we have introduced schemes for atmospheric chemistry, to study chemistry-dynamics-climate interactions. We have considered the variability of the stratospheric polar vortex, whose behaviour influences stratospheric ozone loss and will affect ozone recovery. In particular, we analyse the dynamical control of high latitude ozone in a model version which includes an assimilation of the equatorial quasi-biennial oscillation (QBO), demonstrating the stability of the linear relation between vortex strength and high latitude ozone. We discuss the effect of interactive model ozone on polar stratospheric cloud (PSC) area/volume and winter-spring stratospheric ozone loss in the northern hemisphere. In general we find larger polar ozone losses calculated in those model integrations in which modelled ozone is used interactively in the radiation scheme, even though we underestimate the slope of the ozone loss per PSC volume relation derived from observations. We have also looked at the influence of changing stratosphere-to-troposphere exchange on the tropospheric oxidizing capacity and, in particular, have considered the variability of tropospheric composition under different climate regimes (El Niño/La Niña, etc.). Focusing on the UT/LS, we show the response of ozone to El Niño in two different model set-ups (tropospheric/ stratospheric). In the stratospheric model set-up we find a distinct signal in the lower tropical stratosphere, which shows an anti-correlation between the Niño 3 index and the ozone column amount. In contrast ozone generally increases in the upper troposphere of the tropospheric model set-up after an El Niño. Understanding future trends in stratospheric ozone and tropospheric oxidizing capacity requires an understanding of natural variability, which we explore here.


Standardized ileal digestible lysine requirements of male pigs immunized against gonadotrophin releasing factor.
An experiment was conducted to determine the standardized ileal digestible (SID) Lys requirement of entire male and male pigs immunized against gonadotrophin releasing factor (GnRF; immunocastrates). A total of 420 entire male and immunocastrated (IC) male pigs weighing 60.1 kg BW (SEM 0.49) were used in a 2 × 5 factorial experiment with the main effects being gender (entire males or IC males) and 5 concentrations of SID Lys:DE ratio (0.32, 0.43, 0.54, 0.64, or 0.75 g SID Lys/MJ DE). The diets were fed for 6 wk until slaughter at 107.5 kg BW (SEM 5.72). Over the entire period, IC males had a greater ADG ( < 0.001), greater ADFI ( < 0.001), and lower G:F ( < 0.001) compared with entire males. Immunocastrated males had increased plasma urea nitrogen (PUN) concentrations compared with entire males from d 10 to 42 ( < 0.001 for all days). Plasma urea nitrogen concentration also increased as Lys concentrations increased from d 3 to 42 ( < 0.001 for all days). Using the linear-plateau model, the optimal ADG for entire males was achieved at SID Lys concentrations of 0.68, 0.62, 0.54, and 0.58 g/MJ DE whereas optimal G:F was achieved at SID Lys concentrations of 0.72, 0.60, 0.54, and 0.51 g/MJ DE for the time periods d 0 to 14, d 15 to 28, d 29 to 42, and d 0 to 42, respectively. For IC males, optimal ADG was achieved at SID Lys concentrations of 0.64, 0.43, 0.38, and 0.40 g/MJ DE whereas optimal G:F was achieved at SID Lys concentrations of 0.64, 0.43, 0.36, and 0.42 g/MJ DE for the same respective time periods. Using the quadratic polynomial model, maximum ADG for entire males was achieved at SID Lys concentrations of 0.62 and 0.58 g/MJ DE whereas maximum G:F was achieved at SID Lys concentrations of 0.59 and 0.68 g/MJ DE for d 29 to 42 and d 0 to 42, respectively. For IC pigs, maximum ADG was achieved at SID Lys concentrations of 0.69, 0.54, and 0.64 g/MJ DE whereas maximum G:F was achieved at SID Lys concentrations of 0.81, 0.54, and 0.64 g/MJ DE for d 0 to 14, d 29 to 42, and d 0 to 42, respectively. A solution could not be found using the quadratic polynomial model for entire males for d 0 to 14 for both ADG and G:F and for both entire males and IC males for d 15 to 28 within the range of Lys values tested. When both the growth performance and PUN values are considered, the results suggest that IC males show a response to dietary SID Lys similar to that of entire males for 2 wk after the second immunization against GnRF. After this, IC males have a lower requirement for SID Lys than entire males.


[Allograft nephrectomy - a single-center experience].
Indication and timing of allograft nephrectomy is still uncertain in some cases. The aim of the authors was to summarize their experience with graftectomies. Data from patients who underwent kidney transplantation between January 1, 2004 and December 31, 2015 were retrospectively analyzed. Frequency, indications, timing, complications as well as early and late allograft nephrectomies were reviewed. From 480 renal transplants, 55 graftectomies were performed (11%). Frequent indications included chronic allograft nephropathy (47%), arterial blood supply complications (13%), ureter complications (9%). 22 cases (40%) of allograft nephrectomies were urgent while 33 cases (60%) were elective. 24% of graftectomies were performed within 30 days after transplantation and 76% thereafter. The main indications for early graftectomies were arterial complications (31%) and chronic allograft nephropathy (62%) in cases of late graftectomies. The majority of the graftectomies were elective. Leading indication was chronic allograft nephropathy. Early and late graftectomies have different characteristics.


Aroma profile of Garnacha Tintorera-based sweet wines by chromatographic and sensorial analyses.
The aroma profiles obtained of three Garnacha Tintorera-based wines were studied: a base wine, a naturally sweet wine, and a mixture of naturally sweet wine with other sweet wine obtained by fortification with spirits. The aroma fingerprint was traced by GC-MS analysis of volatile compounds and by sensorial analysis of odours and tastes. Within the volatiles compounds, sotolon (73 μg/L) and acetoin (122 μg/L) were the two main compounds found in naturally sweet wine. With regards to the odorant series, those most dominant for Garnacha Tintorera base wine were floral, fruity and spicy. Instead, the most marked odorant series affected by off-vine drying of the grapes were floral, caramelized and vegetal-wood. Finally, odorant series affected by the switch-off of alcoholic fermentation with ethanol 96% (v/v) fit for human consumption followed by oak barrel aging were caramelized and vegetal-wood. A partial least square test (PLS-2) was used to detect correlations between sets of sensory data (those obtained with mouth and nose) with the ultimate aim of improving our current understanding of the flavour of Garnacha Tintorera red wines, both base and sweet. Based on the sensory dataset analysis, the descriptors with the highest weight for separating base and sweet wines from Garnacha Tintorera were sweetness, dried fruit and caramel (for sweet wines) vs. bitterness, astringency and geranium (for base wines).


[MR of the shoulder joint with surface coils at 1.5 tesla. Its anatomy and possible clinical use].
High spatial resolution magnetic resonance images of the shoulder were obtained in axial, sagittal and coronal orientations using a 1.5 T imaging system and anatomically shaped, wrap-around surface coils. Variations in scapular position induced by patient positioning change the relationship of the planes to the shoulder anatomy and make reproducibility of sagittal and coronal planes difficult. We, therefore, use--after axial orientation--image-oblique planes perpendicular and parallel to the glenoid fossa. In this manner MRI can visualise the anatomic structures of the shoulder including rotator cuff, long biceps tendon, articular capsule, articular cartilage, muscles and bones due to the high soft tissue contrast of MRI.


Epidemiological characteristics of crashes and pattern of motorcycle injuries presenting to hospitals in Kisumu City, Kenya: a cross-sectional study.
motorcycle injuries comprise considerable morbidity, disability and mortality of road traffic casualties. The study aimed to assess the pattern and characteristics of motorcycle crash injuries that sought care at the Emergency Departments in Tier III hospitals in Kisumu City during a six-month period from May to November 2019. this was a cross-sectional study of all motorcycle injury patients presenting to three tier III public and private hospitals in Kisumu City. Using a structured questionnaire, data were collected on human and injury characteristics. Multiple logistic regression model was used to determine the predictors of fatality. Statistical significance was set at p<0.05. a total of 1073 of motorcycle crash injury patients sought and obtained care at the hospitals. The majority (73.6%) were males. Seventy-three cases resulted in death (case-fatality rate of 6.80%. The age range was 2-84 years, with a mean of 29.6 years (± SD 12.19). Majority, (43.3%) were aged 21-30 years. Most of the crashes occurred during the daytime (79.1%). Of all motorcycle riders and pillion passengers 30.6% wore helmets at the time of the crash. Head injuries (43.6%) were the most common. Injury seventy scores (ISS) ranged from 1 to 51. Glasgow comma scale <3, un-helmeted patients and major trauma (ISS > 16), significantly influenced mortality (P< 0.001). these findings confirmed and strengthened the documented substantial morbidity, mortality that motorcycle crashes place on individuals and society, contribute to the body of literature on motorcycle injuries and potentially assist in policy decisions on motorcycle transport safety.


Tissue nitrogen elimination in oxygen-breathing pigs is enhanced by fluorocarbon-derived intravascular micro-bubbles.
The present study tested the hypothesis that intravascular micro bubbles generated by i.v. infusion of a 2 % dodecafluoropentane (DDFP) emulsion will enhance tissue denitrogenation during oxygen breathing. Eleven spontaneously breathing pentobarbital anesthetized pigs were studied. Six pigs were treated with 0.08 ml/kg of DDFP-emulsion infused over 30 min and five (control) pigs received a matching dose of emulsion vehicle. Circulatory parameters were recorded. The pigs were connected via a tracheal tube to a closed circuit oxygen-primed breathing loop allowing volume measurements and nitrogen analysis by gas chromatography every 7 min. The nitrogen washout was recorded for up to four hrs in each group. The cumulative nitrogen yield during oxygen breathing was considerably larger in treated animals than in controls. Thus, the amount of nitrogen eliminated in the controls in 120 min was achieved already after 65 min in animals treated with the DDFP-emulsion. Blood pressure and cardiac output remained stable and were not different between the two groups during the four hrs of nitrogen washout. The central venous oxygen tension was significantly higher in the treated animals during oxygen breathing than in the controls. This difference was, in all probability due to enhanced oxygen transport by the micro-bubbles. Intravascular micro-bubbles generated by i.v. infusion of a small dose of 2 % DDFP-emulsion very effectively enhanced denitrogenation by oxygen breathing and deserve study as a means to improve prevention and treatment of decompression sickness.


[The use of CO2 laser in bone surgery].
Authors examined during the trial of a CO2 laser of type TUNGSRAM TLS-61 the possibility of its use in the orthopaedic surgery. The output necessary to cut the skin and bony tissue, the speed of cutting and the extension of tissue necrosis were determined in experiments in vitro and in vivo. According to their observation the fusion of the bone cut with CO2 laser takes the same time as after the traditional osteotomy, however in the first three weeks the callus formation falls behind. The possibility of a curved cutting and of the coagulation haemostasis may ensure a fine prospect to this method.


Germline variants of base excision repair genes and breast cancer: A polymorphism in DNA polymerase gamma modifies gene expression and breast cancer risk.
Base excision repair (BER) removes DNA damage induced by endogenous reactive oxygen species or ionizing radiation, important breast cancer risk factors. Genetic variation associated with impaired BER might thus increase breast cancer risk. Therefore, we assessed risk associations of 123 common single nucleotide polymorphisms (SNPs) in 19 BER genes in 1,639 postmenopausal breast cancer cases and 1,967 controls from the German population-based case-control study MARIE. SNPs were tagging SNPs representing genetic variation across the gene together with potentially functional SNPs. Risk associations were assessed using conditional logistic regression, adjusted for potential breast cancer risk factors. Significant associations between polymorphisms and breast cancer risk were found for one SNP in PARP2 and three SNPs in the mitochondrial DNA polymerase gamma, POLG. A SNP in the promoter region of POLG (rs2856268, A>G) showed a protective effect for homozygous GG carriers (odds ratio 0.81, 95% confidence intervals 0.65-1.00). Joint analysis of an enlarged sample set and haplotype analysis supported the results for POLG. Quantification of POLG mRNA expression in lymphocytes of 148 breast cancer patients revealed higher mRNA levels for rs2856268 GG carriers (p value = 0.038). A luciferase promoter assay showed significant differences between constructs harboring the respective alleles. Taken together, our results suggest that genetic variation in the POLG promoter region affects DNA polymerase gamma levels in mitochondria. This could contribute to the reported increase in mitochondrial mutation frequency resulting in dysfunction and altered breast cancer risk. Risk effects and the functional impact of the POLG promoter variant require further confirmation.


Trends in college binge drinking during a period of increased prevention efforts. Findings from 4 Harvard School of Public Health College Alcohol Study surveys: 1993-2001.
The 2001 Harvard School of Public Health College Alcohol Study surveyed students at 119 4-year colleges that participated in the 1993, 1997, and 1999 studies. Responses in the 4 survey years were compared to determine trends in heavy alcohol use, alcohol-related problems, and encounters with college and community prevention efforts. In 2001, approximately 2 in 5 (44.4%) college students reported binge drinking, a rate almost identical to rates in the previous 3 surveys. Very little change in overall binge drinking occurred at the individual college level. The percentages of abstainers and frequent binge drinkers increased, a polarization of drinking behavior first noted in 1997. A sharp rise in frequent binge drinking was noted among students attending all-women's colleges. Other significant changes included increases in immoderate drinking and harm among drinkers. More students lived in substance-free housing and encountered college educational efforts and sanctions resulting from their alcohol use.


miR-203 suppresses tumor growth and angiogenesis by targeting VEGFA in cervical cancer.
MicroRNA (miRNA) plays important roles in the development of different cancers. In this study, we investigated the roles and mechanisms of miR-203 in human cervical cancer. miR-203 expression was detected in cervical cancer tumors and cell lines by qRT-PCR. The methylation status in the promoter region of miR-203 was examined by methylation-specific PCR. The functional effect of miR-203 was determined by both in vitro and in vivo assays. miR-203 was frequently down-regulated in cervical cancer tumors and cell lines. This down-regulation of miR-203 was associated with methylation of the miR-203 promoter. Furthermore, miR-203 down-regulated vascular endothelial growth factor alpha (VEGFA) expression by directly targeting its 3'-untranslated region. Functional assays revealed that miR-203 suppressed cervical cancer cell proliferation, tumor growth, and angiogenesis in nude mice, whereas forced expression of VEGFA rescued this inhibitory effect. Our collective findings indicate that miR-203 functions as a tumor suppressor by targeting VEGFA, resulting in the inhibition of tumor growth and angiogenesis. Thus, miR-203 may be a potential therapeutic target and prognostic marker in cervical cancer.


In vivo lability of glucose-6-phosphate dehydrogenase in GdA- and GdMediterranean deficiency.
A decreased level of glucose-6-phosphate dehydrogenase might result from decreased rate of synthesis, synthesis of an enzyme of lower catalytic efficiency, increased lability, or a combined mechanism. To test the hypothesis of increased lability, the rate of decline of the enzyme in vivo was measured in three groups of individuals, controls, Gd(-),A-males, and Gd(-), Mediterranean males, by the slope of decline of activity in fractions containing erythrocytes of progressively increasing mean age. These fractions were obtained by ultracentrifugation on a discontinuous density gradient of erythrocyte suspensions free of contaminating platelets and leukocytes. The rate of in vivo decline of pyruvate kinase (another age-dependent enzyme) was also measured and found very similar in the three groups. The in vivo decline of glucose-6-phosphate dehydrogenase was found to follow an exponential rate, with a half-life of 62 days for controls and 13 days for Gd(-),A- erythrocytes. The activity in normal reticulocytes was estimated at 9.7 U and in Gd(-),A- reticulocytes at 8.8 U. These estimates were confirmed by direct measurements in reticulocytes isolated from patients with extreme reticulocytosis. In Gd(-),Mediterranean erythrocytes activity could be demonstrated only in reticulocytes, which were estimated to average 1.4 U. The rate of decline is so extreme that no activity could be detected in mature erythrocytes. These data suggest that the glucose-6-phosphate dehydrogenase deficiency of both the Gd(A-) and the GdMediterranean variant results from different degrees of in vivo instability of the abnormal enzyme.


A Small-Molecule Inhibitor of Prion Replication and Mutant Prion Protein Toxicity.
Into the fold: Prion diseases are neurodegenerative disorders characterized by the accumulation in the brain of a self-replicating, misfolded isoform (PrPSc ) of the cellular prion protein (PrPC ). No therapies are available for these pathologies. We capitalized on previously described cell-based assays to screen a library of small molecules, and identified 55, a compound capable of counteracting both prion replication and toxicity. Compound 55 may represent the starting point for the development of a completely new class of therapeutics for prion diseases.


Memory CD4 T cell subsets are kinetically heterogeneous and replenished from naive T cells at high levels.
Characterising the longevity of immunological memory requires establishing the rules underlying the renewal and death of peripheral T cells. However, we lack knowledge of the population structure and how self-renewal and de novo influx contribute to the maintenance of memory compartments. Here, we characterise the kinetics and structure of murine CD4 T cell memory subsets by measuring the rates of influx of new cells and using detailed timecourses of DNA labelling that also distinguish the behaviour of recently divided and quiescent cells. We find that both effector and central memory CD4 T cells comprise subpopulations with highly divergent rates of turnover, and show that inflows of new cells sourced from the naive pool strongly impact estimates of memory cell lifetimes and division rates. We also demonstrate that the maintenance of CD4 T cell memory subsets in healthy mice is unexpectedly and strikingly reliant on this replenishment.


Comparison of lycopene and fluvastatin effects on atherosclerosis induced by a high-fat diet in rabbits.
We evaluated the antiatherogenic effect of lycopene in rabbits fed a high-fat diet. Forty adult male rabbits were divided into five groups that were fed a standard diet, a high-fat diet, a high-fat diet plus 4 mg/kg of lycopene, a high-fat diet plus 12 mg/kg of lycopene, and a high-fat diet plus 10 mg/kg of fluvastatin, respectively. Lycopene and fluvastatin were administered intragastrically. The level of serum total cholesterol, total triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total antioxidant capacity, and malondialdehyde were measured before and after 4 and 8 wk of experimental treatment. In addition, plasma levels of lycopene, oxidized low-density lipoprotein, serum nitric oxide, and interleukin-1 were measured after the experiment. The area of atherosclerotic plaque and pathologic changes of the aorta were evaluated. Compared with the control, levels of total cholesterol, total triacylglycerol, low-density lipoprotein cholesterol, malonaldehyde, oxidized low-density lipoprotein, and interleukin-1 were increased and total antioxidant capacity and nitric oxide were decreased in the animals with a high-fat diet (P < 0.05). Intragastric administration of lycopene counteracted the change in these parameters (P < 0.05). In this case, the data showed that lycopene in the used dose was better than the fluvastatin intervention. Morphologic analysis revealed that lycopene and fluvastatin markedly reduced the formation of atherosclerotic plaques in the aorta compared with the situation in rabbits on a high-fat diet alone. Lycopene, like fluvastatin, significantly attenuated atherogenesis in rabbits fed a high-fat diet.


High Volumetric Energy Density Asymmetric Supercapacitors Based on Well-Balanced Graphene and Graphene-MnO2 Electrodes with Densely Stacked Architectures.
The well-matched electrochemical parameters of positive and negative electrodes, such as specific capacitance, rate performance, and cycling stability, are important for obtaining high-performance asymmetric supercapacitors. Herein, a facile and cost-effective strategy is demonstrated for the fabrication of 3D densely stacked graphene (DSG) and graphene-MnO2 (G-MnO2 ) architectures as the electrode materials for asymmetric supercapacitors (ASCs) by using MnO2 -intercalated graphite oxide (GO-MnO2 ) as the precursor. DSG has a stacked graphene structure with continuous ion transport network in-between the sheets, resulting in a high volumetric capacitance of 366 F cm-3 , almost 2.5 times than that of reduced graphene oxide, as well as long cycle life (93% capacitance retention after 10 000 cycles). More importantly, almost similar electrochemical properties, such as specific capacitance, rate performance, and cycling stability, are obtained for DSG as the negative electrode and G-MnO2 as the positive electrode. As a result, the assembled ASC delivers both ultrahigh gravimetric and volumetric energy densities of 62.4 Wh kg-1 and 54.4 Wh L-1 (based on total volume of two electrodes) in 1 m Na2 SO4 aqueous electrolyte, respectively, much higher than most of previously reported ASCs in aqueous electrolytes.


Partial hypoxanthine-guanine phosphoribosyltransferase deficiency presenting as acute renal failure.
Hyperuricemia and secondary urate nephropathy are uncommon in the paediatric setting outside of tumour lysis syndrome. We describe the case of a 12-year-old boy who presented at 3 years of age with acute renal failure. The cause of this remained unknown until the development of uric acid renal calculi 9 years later. This, and the availability of the previously unknown family history, provided the subsequent diagnosis of partial hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency. Detailed family history is important for early detection of this heterogeneous group of disorders. Early treatment may minimise long-term renal morbidity and mortality from renal insufficiency.


Isolation, characterization, and complete genome analysis of P1312, a thermostable bacteriophage that infects Thermobifida fusca.
Thermobifida fusca is a moderately thermophilic and cellulolytic actinobacterium. It is of particular interest due to its ability to not only produce a variety of biotechnologically relevant enzymes but also serve as an alternative host for metabolic engineering for the production of valuable chemicals from lignocellulosic agricultural wastes. No bacteriophage that infects T. fusca has been reported, despite its potential impacts on the utilization of T. fusca. In this study, an extremely thermostable bacteriophage P1312 that infects T. fusca was isolated from manure compost. Electron microscopy showed that P1312 has an icosahedral head and a long flexible non-contractile tail, a characteristic of the family Siphoviridae. P1312 has a double-stranded DNA genome of 60,284 bp with 93 potential ORFs. Thirty-one ORFs encode proteins having putative biological functions. The genes involved in phage particle formation cluster together in a region of approximately 16 kb, followed by a segment containing genes presumably for DNA degradation/modification and cell wall disruption. The genes required for DNA replication and transcriptional control are dispersed within the rest of the genome. Phylogenetic analysis of large terminase subunit suggests that P1312 is a headful packaging phage containing a chromosome with circularly permuted direct terminal repeats.


Peripheral Arterial Disease: A Narrative Review.
Peripheral arterial disease (PAD) describes the partial or complete occlusion of blood flow in the distal arteries of the body. A decreased arterial patency may occur due to a reduction in the elasticity or diameter of the vessel. The goal of interventions is to decrease incidence and reduce complications by identifying and minimizing the primary causes. This paper discusses PAD affecting the aortoiliac, common femoral, and femoropopliteal arteries. In a significant portion of the population, PAD may lack usual symptoms such as limb pain, claudication, and diminished pulses. Imaging techniques become crucial to ensuring timely diagnosis, monitoring treatment effectiveness, and preventing recurrence. Duplex ultrasound (DUS) is a cheap and non-invasive preliminary technique to detect atherosclerotic plaques and grade arterial stenosis. Magnetic resonance angiography (MRA) provides the added advantage of minimizing artifacts. Digital subtraction angiography (DSA) remains the gold standard for grading the degree of stenosis but is only employed second-line to DUS or MRA due to the high dose of nephrotoxic contrast. Computed tomography angiography (CTA) is able to overcome the anatomical limitations of DUS and MRA and proves to be a suitable alternative to DSA in patients with renal disease. Preventative measures involve monitoring blood pressure, cholesterol levels, and tobacco usage. First-line treatment options include endovascular procedures as well as surgical interventions in cases of significant arterial involvement. Endovascular treatments involve the use of balloon angioplasty, drug-coated balloons, and drug-coated stents, to name a few, that serve as minimally invasive techniques to manage PAD. Surgical procedures, although more complex, are considered gold-standard treatment options for long and intricate lesions. Endovascular methods are generally preferred over surgical options as the complication risk is severely reduced and the rates of reintervention are comparable to surgical options.


Endoscopic plasma argon coagulation in treatment of weight regain after bariatric surgery: what does the patient think about this?
Bariatric surgery, especially Roux-en-Y gastric bypass is an effective treatment for refractory morbid obesity, causing the loss of 75% of initial excess weight. After the surgery, however, weight regain can occur in 10-20% of cases. To help, endoscopic argon plasma coagulation (APC) is used to reduce the anastomotic diameter. Many patients who undergo this treatment, are not always familiar with this procedure and its respective precautions. The aim of this study was to determine how well the candidate for APC understands the procedure and absorbs the information provided by the multidisciplinary team. We prepared a questionnaire with 12 true/false questions to evaluate the knowledge of the patients about the procedure they were to undergo. The questionnaire was administered by the surgeon during consultation in the preoperative period. The patients were invited to fill out the questionnaire. We found out that the majority learned about the procedure through the internet. They knew it was an outpatient treatment, where the anesthesia was similar to that for endoscopy, and that they would have to follow a liquid diet. But none of them knew that the purpose of this diet was to improve local wound healing. Bariatric patients who have a second chance to resume weight loss, need continuous guidance. The internet should be used by the multidisciplinary team to promote awareness that APC will not be sufficient for weight loss and weight-loss maintenance in the long term. Furthermore, there is a need to clarify again the harm of drinking alcohol in the process of weight loss, making its curse widely known.


Identification of Novel A2/C2 Inter-Genotype Recombinants of Hepatitis B Virus from a Korean Chronic Patient Co-Infected with Both Genotype A2 and C2.
Nearly all cases of Hepatitis B virus (HBV) infections in South Korea have the C2 genotype. Here, we have identified a chronically infected patient who was co-infected with HBV of both the A2 and C2 genotypes by screening 135 Korean chronically infected patients using direct sequencing protocols targeting the 1032-bp polymerase reverse transcriptase (RT) region. Further polymerase chain reaction (PCR)-cloning analysis (22 clones) of the RT showed that this patient had genotype C2 (12 clones), genotype A2 (six clones) and A2/C2 inter-genotype HBV recombinants (four clones). BootScan analysis showed that three of the four recombinants have different types of recombination breakpoints in both the RT and overlapping hepatitis B surface antigen (HBsAg) region. Given the significance of HBsAg as a diagnostic or vaccination target against HBV infection, clinical implications of these identified recombinants should be studied in the future. To our knowledge, this is the first report on A2/C2 inter-genotype HBV recombinants.


[The scientific development in dermatology in Germany in relation to the emigration of Jewish dermatologists during national socialism].
The anti-semitic laws let to the persecution of the Jews in Germany during the time of National Socialism. About 600 Jewish dermatologists had to suffer from the prohibition of their profession. 63% of them left Germany. The emigrants mainly preferred to move out to the U.S. The policy of coordination and elimination of the National Socialists led to the reappointment of dermatological chairs in universities. The National Socialists also forced the change in the boards of dermatological societies and the change of the editorial boards of dermatological journals. All papers of the three leading dermatological journals were analysed for the evaluation of the development of science. The assessment included the number of articles, the origin of the authors and the contents of articles (research, clinics, diagnostic, therapy). From 1933 to 1945 the number of papers per year decreased consequently, especially during the Second World War. During the whole time the number of German authors increased and the number of abroad living authors decreased. There was a very good and interesting international exchange of information in the journal "Archiv für Dermatologie und Syphilis". The activity reduced clearly after the beginning of the Second World War in 1939. The analysis of contents resulted in a reduction of basis science research and an orientation to the clinical research. Papers about therapeutical possibilities were always published. The emigration of Jewish dermatologists led to a continuous reduction of scientific activities and to an extensive international isolation.


Identification of a high molecular weight endothelial cell surface glycoprotein, endoGlyx-1, in normal and tumor blood vessels.
The vascular endothelium participates in diverse physiologic and pathologic processes, ranging from blood clotting to leukocyte trafficking and tumor metastasis. Many of these functions are mediated by endothelial surface molecules, and monoclonal antibodies (mAb) have been used extensively to define endothelial cell surface structures in normal and lesional tissues. MAbs raised against human umbilical vein endothelial cells were tested on a panel of cultured cell types representing diverse cell lineages. In vivo antigen expression was examined through immunohistochemical tests with normal and lesional tissues. Immunochemical methods were employed to characterize mAb-defined antigens in endothelial cell extracts. The newly-derived mAbH572 reacts with a high molecular weight glycoprotein complex of cultured endothelial cells comprised of disulfide-bonded subunits of molecular weight 190,000, 140,000, 125,000, and 110,000. This antigen, designated endoGlyx-1, is expressed on the surface of cultured endothelium, with no changes in expression after cytokine-stimulation. Immunohistochemical assays detect endoGlyx-1 in endothelial cells of large, medium-sized, and small blood vessels, including capillaries, in all human organs tested; only hepatic and splenic sinusoids lack the molecule. EndoGlyx-1 is not found in any of the normal fetal and adult nonendothelial cell types tested. In a study of > 100 tumors, endoGlyx-1 immunostaining was consistently found in tumor capillaries, including "hot spots" of neoangiogenesis in certain tumors. EndoGlyx-1 is also expressed in hemangiomas and angiosarcomas. The highly restricted expression of endoGlyx-1 in normal and tumor blood vessels suggests a role for this molecule unique to endothelial cell physiology. In fact, endoGlyx-1 appears to be the only endothelial lineage-specific cell surface glycoprotein identified to date. The availability of endoGlyx-1 antibodies may aid in the characterization and quantification of the angiogenic phase of solid tumors and facilitate the search for endothelial precursors in bone marrow or peripheral blood.


Skin blood flow influences near-infrared spectroscopy-derived measurements of tissue oxygenation during heat stress.
Near-infrared (NIR) spectroscopy is a noninvasive optical technique that is increasingly used to assess muscle oxygenation during exercise with the assumption that the contribution of skin blood flow to the NIR signal is minor or nonexistent. We tested this assumption in humans by monitoring forearm tissue oxygenation during selective cutaneous vasodilation induced by locally applied heat (n = 6) or indirect whole body heating (i.e., heating subject but not area surrounding NIR probes; n = 8). Neither perturbation has been shown to cause a measurable change in muscle blood flow or metabolism. Local heating (approximately 41 degrees C) caused large increases in the NIR-derived tissue oxygenation signal [before heating = 0.82 +/- 0.89 optical density (OD), after heating = 18.21 +/- 2.44 OD; P < 0.001]. Similarly, whole body heating (increase internal temperature 0.9 degrees C) also caused large increases in the tissue oxygenation signal (before heating = -0.31 +/- 1.47 OD, after heating = 12.48 +/- 1.82 OD; P < 0.001). These increases in the tissue oxygenation signal were closely correlated with increases in skin blood flow during both local heating (mean r = 0.95 +/- 0.02) and whole body heating (mean r = 0.89 +/- 0.04). These data suggest that the contribution of skin blood flow to NIR measurements of tissue oxygenation can be significant, potentially confounding interpretation of the NIR-derived signal during conditions where both skin and muscle blood flows are elevated concomitantly (e.g., high-intensity and/or prolonged exercise).


Hypertrophic Cardiomyopathy Predicts Thromboembolism and Heart Failure in Patients With Nonvalvular Atrial Fibrillation - A Prospective Analysis From the Hokuriku-Plus AF Registry.
The prognostic effect of concomitant hypertrophic cardiomyopathy (HCM) on adverse events in patients with atrial fibrillation (AF) has not been evaluated in a multicenter prospective cohort study in Japan.Methods and Results: Using the Hokuriku-Plus AF Registry, 1,396 patients with nonvalvular AF (1,018 men, 72.3±9.7 years old) were assessed prospectively; 72 (5.2%) had concomitant HCM. During a median follow-up of 5.0 years (interquartile range 3.5-5.3 years), 79 cases of thromboembolism (1.3 per 100 person-years) and 192 of heart failure (HF) (3.2 per 100 person-years) occurred. Kaplan-Meier analysis revealed that the HCM group had a significantly greater incidence of thromboembolism (P=0.002 by log-rank test) and HF (P<0.0001 by a log-rank test) than the non-HCM group. The Cox proportional hazards model demonstrated that persistent AF (adjusted hazard ratio 2.98, 95% confidence interval 1.56-6.21), the CHA2DS2-VASc score (1.35, 1.18-1.54), and concomitant HCM (2.48, 1.16-4.79) were significantly associated with thromboembolism. Conversely, concomitant HCM (2.81, 1.72-4.43), older age (1.07, 1.05-1.10), lower body mass index (0.95, 0.91-0.99), a history of HF (2.49, 1.77-3.52), and lower left ventricular ejection fraction (0.98, 0.97-0.99) were significantly associated with the development of HF. Concomitant HCM predicts the incidence of thromboembolism and HF in AF patients.