Glucagon-Like Peptide-1 Receptor Regulates Macrophage Migration in Monosodium Urate-Induced Peritoneal Inflammation.
Glucagon-like peptide-1 (GLP-1) is an insulinotropic peptide that signals through the GLP-1 receptor (GLP-1R). GLP-1R, therefore, plays a critical role in diabetes and cardiovascular disease. Whether GLP-1R is involved in inflammatory disease such as gout remains unclear. Macrophages are critical effector cells in the pathogenesis of gout, a common form of inflammatory arthritis caused by the deposition of uric acid in joints. The expression of GLP-1R at the protein level is controversial due to the lack of specificity of existing antibodies against GLP-1R. Using a transgenic mouse model expressing enhanced green fluorescent protein (EGFP) under the control of GLP-1R promoter, here we confirmed the expression of GLP-1R by macrophages. M2 type macrophages and Ly6C+ macrophages expressed higher levels of GLP-1R, compared to their counterparts. GLP-1R deficient macrophages displayed a reduced the migratory ability and an enhanced expression of interleukin (IL)-6, while the expression of IL-1β was not affected. In monosodium urate (MSU) crystal-induced peritonitis, an experimental model of gout, the recruitment of macrophages, especially M2 macrophages, was significantly suppressed in GLP-1R knockout mice compared to wild-type mice. In conclusion, our data suggests that GLP-1R plays a critical role in macrophage migration in MSU-induced inflammation.


US forest response to projected climate-related stress: a tolerance perspective.
Although it is widely recognized that climate change will require a major spatial reorganization of forests, our ability to predict exactly how and where forest characteristics and distributions will change has been rather limited. Current efforts to predict future distribution of forested ecosystems as a function of climate include species distribution models (for fine-scale predictions) and potential vegetation climate envelope models (for coarse-grained, large-scale predictions). Here, we develop and apply an intermediate approach wherein we use stand-level tolerances of environmental stressors to understand forest distributions and vulnerabilities to anticipated climate change. In contrast to other existing models, this approach can be applied at a continental scale while maintaining a direct link to ecologically relevant, climate-related stressors. We first demonstrate that shade, drought, and waterlogging tolerances of forest stands are strongly correlated with climate and edaphic conditions in the conterminous United States. This discovery allows the development of a tolerance distribution model (TDM), a novel quantitative tool to assess landscape level impacts of climate change. We then focus on evaluating the implications of the drought TDM. Using an ensemble of 17 climate change models to drive this TDM, we estimate that 18% of US ecosystems are vulnerable to drought-related stress over the coming century. Vulnerable areas include mostly the Midwest United States and Northeast United States, as well as high-elevation areas of the Rocky Mountains. We also infer stress incurred by shifting climate should create an opening for the establishment of forest types not currently seen in the conterminous United States.


A practical base mediated synthesis of 1,2,4-triazoles enabled by a deamination annulation strategy.
A rapid and efficient base mediated synthesis of 1,3,5-trisubstituted 1,2,4-triazoles has been developed using the annulation of nitriles with hydrazines, which can be expanded to a wide range of triazoles in good to excellent yields. Ammonia gas is liberated during the reaction, and halo and hetero functional groups as well as free hydroxyl and amino groups are tolerated in this transformation. A variety of alkyl and aryl-substituted nitriles can be functionalized with aromatic and aliphatic hydrazines employing this procedure. This finding provides a practical and useful strategy for the synthesis of various 15N-labeled 1,2,4-triazole derivatives, and two types of mGlu5 receptor pharmaceuticals can be easily assembled in a one-pot manner.


Neurofibromatosis type II presenting as vertical diplopia.
Neurofibromatosis type II (NF II) is rare and most commonly presents with hearing loss, tinnitus and/or vestibular disturbance in the third decade of life. The authors describe a rare case presenting with NF II with vertical diplopia due to IV(th) nerve palsy. The patient was otherwise asymptomatic despite multiple extensive lesions on MRI.


Total ankle replacement versus arthrodesis (TARVA): protocol for a multicentre randomised controlled trial.
Total ankle replacement (TAR) or ankle arthrodesis (fusion) is the main surgical treatments for end-stage ankle osteoarthritis (OA). The popularity of ankle replacement is increasing while ankle fusion rates remain static. Both treatments have efficacy but to date all studies comparing the 2 have been observational without randomisation, and there are no published guidelines as to the most appropriate management. The TAR versus arthrodesis (TARVA) trial aims to compare the clinical and cost-effectiveness of TAR against ankle arthrodesis in the treatment of end-stage ankle OA in patients aged 50-85 years. TARVA is a multicentre randomised controlled trial that will randomise 328 patients aged 50-85 years with end-stage ankle arthritis. The 2 arms of the study will be TAR or ankle arthrodesis with 164 patients in each group. Up to 16 UK centres will participate. Patients will have clinical assessments and complete questionnaires before their operation and at 6, 12, 26 and 52 weeks after surgery. The primary clinical outcome of the study is a validated patient-reported outcome measure, the Manchester Oxford foot questionnaire, captured preoperatively and 12 months after surgery. Secondary outcomes include quality-of-life scores, complications, revision, reoperation and a health economic analysis. The protocol has been approved by the National Research Ethics Service Committee (London, Bloomsbury 14/LO/0807). This manuscript is based on V.5.0 of the protocol. The trial findings will be disseminated through peer-reviewed publications and conference presentations. NCT02128555.


Physicochemical properties, in vitro starch digestibility, and estimated glycemic index of resistant starch from cowpea (Vigna unguiculata) starch by autoclaving-cooling cycles.
Recently, legumes starch were studied extensively due to high amylose and resistant starch contents, and low glycemic index (GI). We evaluated the impact of autoclaving-cooling cycles (single, triple, five) on the physicochemical properties, in vitro starch digestibility, and estimated glycemic index (eGI) of cowpea starch. Autoclaving-cooling increased the amylose content, water/oil holding capacities, onset, peak, and conclusion gelatinization temperatures. Pasting temperature, gelatinization enthalpy, final and setback viscosities significantly decreased (P < 0.05) in modified cowpea starches. RS content increased from 32.14 ± 1.33% to 41.26 ± 0.81%. Autoclaving-cooling altered the crystalline structure of cowpea starch from C-type to a mixture of the B and V-types. FT-IR spectra indicated an increase in the ratio of 1049 cm-1/1018 cm-1 and 995 cm-1/1018 cm-1 which suggested an increase of the amount of crystallite and double helix in modified starch. The eGI decreased from 47.94 ± 0.45 to 41.46 ± 0.06 and was categorized as a low GI food. These results suggested that single autoclaving-cooling cycle could be a possible method to produce resistant starch from cowpea starch with better thermal stability and lower GI. Both native and modified cowpea starch were categorized as high RS and could be used as an alternative source of resistant starch from legume starch for developing functional foods.


[Morphological characteristics of chronic hepatopathy in combination of HCV and chronic alcoholic intoxication].
Biopsies from 35 patients and autopsy material from 20 patients who died of chronic hepatopathy were studied. Hydropic dystrophy and inflammation were predominant in HCV infection. Chronic alcoholic intoxication (CAI) was characterized by diffuse large-droplet fat dystrophy and liver fibrosis. In combination of HCV-infection with CAI sclerotic processes were pronounced and therefore liver cirrhosis is more frequent than in other groups.


Development of surgical palliative care as a field and community building in palliative care: past, present, and future directions.
The professionalization of hospice and palliative medicine has been well documented, as has its associated rise to specialty status. The movement to formalize hospice and palliative medicine in the United States included ten sponsoring boards for initial certification through a practice pathway. Thus, it began with the potential for subspecialty interests, advocacy, and training. This review will examine the emergence of surgical palliative care as a field within hospice and palliative medicine as well as its unique place within the specialty of surgery, where it is sometimes hailed as an inherent, historically present body of knowledge and skill, and just as often, remarked upon as an ahistorical oxymoron. The phases of formation, early adoption, popularization, and normalization will be described and illustrated by the benchmarks of formal education requirements, board eligibility and certification, and professional relationships fostered by medical societies and online communities. Community building in palliative care must acknowledge the diversity of its constituents and the differences in subspecialty identity formation and sources of professional credibility and legitimacy. Metaphors for practitioners of surgical palliative care range from the rarity of the unicorn to the swarm intelligence principles of the beehive. Future directions include facing the questions about the role of specialty training and practice in surgical palliative care compared to renewed emphasis on palliative principles in general surgical training and practice.


Preparation of nanoscale Ni-B amorphous alloys and their application in the selective hydrogenation of cinnamic acid.
A series of metal modified nanoscale Ni-B amorphous alloys was prepared by chemical reduction and tested in the selective hydrogenation of cinnamic acid. A Co modified Ni-B amorphous alloy (Ni-Co-B) exhibited excellent catalytic performance in this reaction with both 100.0% conversion of cinnamic acid and 100.0% selectivity for hydrocinnamic acid under the optimized reaction conditions. X-ray diffraction (XRD) results indicated that the addition of Co had not changed the amorphous structure of Ni-B; whereas, its addition was believed not only to favor decreased agglomeration of the active Ni species, as proven by transmission electron microscopy (TEM), but also to contribute to adsorption of hydrogen itself. Thus, Ni-Co-B showed a larger BET surface area, smaller particle size, and greater number of active species resulting in optimum H2-chemisorption compared to Ni-B and accounting for its excellent catalytic performance in cinnamic acid hydrogenation.


Prospective cohort 20 years after endovascular treatment for abdominal aortic aneurysm.
To describe the factors associated with survival 20 years after endovascular treatment of an abdominal aortic aneurysm (AAA) in a single center. Prospective cohort of asymptomatic patients with an infrarenal aortic aneurysm treated with a bifurcated endovascular graft (Talent) between June 1997 and August 2008. Cox proportional hazard multivariable regression was used for analysis of independent risk factors for survival. Kaplan-Meier curves were done with the long-rank test. P < .05 was considered significant. We followed 229 patients, 184 without an endoleak and 45 with an endoleak. Ages ranged between 52 and 89 years, and the mean diameter of the aneurysm was 59.51 ± 14.6 mm. Implantation of the endovascular graft was possible in 99% of the patients. The 30-day mortality rate was 3.4%. In the Cox regression, age <73 years (hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.27-0.64), aneurysm size ≤55 mm (HR, 0.62; 95% CI, 0.40-0.95), male sex (HR, 0.17; 95% CI, 0.05-0.52), American Society of Anesthesiologists surgical risk category I and II vs III and IV (HR, 0.51; 95% CI, 0.34-0.75), and aneurysm size reduction ≤3 mm after treatment (HR, 2.23; 95% CI, 1.11-4.51) were significantly correlated with the survival of the patients followed in this long-term case series. This 20-year prospective cohort included patients with an AAA treated with a bifurcated endovascular graft (Talent) at a university hospital in Brazil. This study supports that sex, age, aneurysm size, aneurysm size reduction, and American Society of Anesthesiologists surgical risk category are significantly correlated with patient survival after endovascular treatment of the AAA.


The role of media literacy in shaping adolescents' understanding of and responses to sexual portrayals in mass media.
This study was a theory-based, pretest-posttest quasi-experiment conducted in the field (N = 922) to determine whether and how a media literacy curriculum addressing sexual portrayals in the media would influence adolescents' decision-making processes regarding sex. Results of the evaluation, based on the Message Interpretation Process Model, indicated that participants who received media literacy training better understood that media influence teens' decision making about sex and were more likely to report that sexual depictions in the media are inaccurate and glamorized. In addition, participants who received media literacy lessons were more likely than were control group participants to believe that other teens practice abstinence and reported a greater ability to resist peer pressure. An interaction effect existed between gender and condition on attitudes toward abstinence, suggesting that the lessons helped girls and boys in somewhat different ways. Overall, the results indicated that media literacy strengthened key aspects of participants' logic-oriented decision-making process.


Characterization of a novel voltage-dependent outwardly rectifying anion current in Caenorhabditis elegans oocytes.
An inwardly rectifying swelling- and meiotic cell cycle-regulated anion current carried by the ClC channel splice variant CLH-3b dominates the whole cell conductance of the Caenorhabditis elegans oocyte. Oocytes also express a novel outwardly rectifying anion current termed I(Cl,OR). We recently identified a worm strain carrying a null allele of the clh-3 gene and utilized oocytes from these animals to characterize I(Cl,OR) biophysical properties. The I(Cl,OR) channel is strongly voltage dependent. Outward rectification is due to voltage-dependent current activation at depolarized voltages and rapid inactivation at voltages more hyperpolarized than approximately +20 mV. Apparent channel open probability is zero at voltages less than +20 mV. The channel has a 4:1 selectivity for Cl(-) over Na(+) and an anion selectivity sequence of SCN(-) > I(-) > Br(-) > Cl(-) > F(-). I(Cl,OR) is relatively insensitive to most conventional anion channel inhibitors including DIDS, 4,4'-dinitrostilbene-2,2'-disulfonic acid, 9-anthracenecarboxylic acid, and 5-nitro-2-(3-phenylpropylamino)benzoic acid. However, the current is rapidly inhibited by niflumic acid, metal cations including Gd(3+), Cd(2+), and Zn(2+), and bath acidification. The combined biophysical properties of I(Cl,OR) are distinct from those of other anion currents that have been described. During oocyte meiotic maturation, I(Cl,OR) activity is rapidly downregulated, suggesting that the channel may play a role in oocyte Cl(-) homeostasis, development, cell cycle control, and/or ovulation.


Successful smoking cessation and duration of abstinence--an analysis of socioeconomic determinants.
Smoking does not affect every socioeconomic subgroup of the population equally, resulting in major inequalities in terms of smoking-related morbidity and mortality. While previous studies mainly focused on inequalities in smoking prevalence, we have analysed the socioeconomic dimensions that might be associated with two other smoking-related outcomes: the odds of successfully quitting and the duration of abstinence. Using nationally representative Swiss data, we found evidence of a socioeconomic gradient in successful cessation and abstinence duration with respect to education level and income for both men and women.


Proximal Femoral Geometry as Fracture Risk Factor in Female Patients with Osteoporotic Hip Fracture.
Proximal femoral geometry may be a risk factor of osteoporotic hip fractures. However, there existed great differences among studies depending on race, sex and age of subjects. The purpose of the present study is to analyze proximal femoral geometry and bone mineral density (BMD) in the osteoporotic hip fracture patients. Furthermore, we investigated proximal femoral geometric parameters affecting fractures, and whether the geometric parameters could be an independent risk factor of fractures regardless of BMD. This study was conducted on 197 women aged 65 years or more who were hospitalized with osteoporotic hip fracture (femur neck fractures ; 84, intertrochanteric fractures; 113). Control group included 551 women who visited to check osteoporosis. Femur BMD and proximal femoral geometry for all subjects were measured using dual energy X-ray absorptiometry (DXA), and compared between the control and fracture groups. Besides, proximal femoral geometric parameters associated with fractures were statistically analyzed. There were statistically significant differences in the age and weight, cross-sectional area (CSA)/length/width of the femoral neck and BMD of the proximal femur between fracture group and control group. BMD of the proximal femur in the control group was higher than in the fracture group. For the femoral neck fractures group, the odds ratio (OR) for fractures decrease in the CSA and neck length (NL) of the femur increased by 1.97 times and 1.73 times respectively, regardless of BMD. The OR for fractures increase in the femoral neck width increased by 1.53 times. In the intertrochanteric fracture group, the OR for fractures increase in the femoral neck width increased by 1.45 times regardless of BMD. We found that an increase of the femoral neck width could be a proximal femoral geometric parameter which plays important roles as a risk factor for fracture independently of BMD.


Factors associated with excessive daytime sleepiness in informal drivers of buses on a high-altitude road.
To determine the factors associated with excessive daytime sleepiness (EDS) in informal interprovincial transport drivers of the Lima-Huancayo central highway (Peru) from January to March 2018. Cross-sectional study. The drivers were weighed and measured, then individual, sociodemographic, and occupational data were obtained which were recorded in a data collection form, then the Epworth Sleepiness Scale (ESS) was applied to the drivers. The prevalence and EDS-associated factors in drivers were obtained from this data. The multivariate analysis of the possible associated factors for EDS was performed with binary logistic regression, obtaining the adjusted odds ratio (AOR). 162 drivers participated in the study. The average age was 42.0 ± 10.2 years (Range of 21-62 years), all the participants were male. 55. 6% had a technical degree, 42.0% were married and 55.6% had two to three children. The mean time of experience as a driver was 17.0 ± 6.8 years, 54.9% were overweight, and 32.1% were obese. 27.8% of drivers had EDS, the multivariate analysis found that the EDS-associated factors of the drivers were obesity (AOR=3.8, 95% CI: 1.422- 10.233), having 10 or more years of experience as a driver (AOR=3.1, 95% CI: 1.342-7.189) and overweight (AOR=2.9 CI 95%: 1.216-7.096). There is a high prevalence of EDS in informal drivers of interprovincial transport of the central high-altitude highway studied. Obesity was the main factor associated with EDS, along with being overweight and having 10 or more years of experience as a driver.


Automated quantification of macular fluid in retinal diseases and their response to anti-VEGF therapy.
To objectively assess disease activity and treatment response in patients with retinal vein occlusion (RVO), neovascular age-related macular degeneration (nAMD) and centre-involved diabetic macular oedema (DME), using artificial intelligence-based fluid quantification. Posthoc analysis of 2311 patients (11 151 spectral-domain optical coherence tomography volumes) from five clinical, multicentre trials, who received a flexible antivascular endothelial growth factor (anti-VEGF) therapy over a 12-month period. Fluid volumes were measured with a deep learning algorithm at baseline/months 1, 2, 3 and 12, for three concentric circles with diameters of 1, 3 and 6 mm (fovea, paracentral ring and pericentral ring), as well as four sectors surrounding the fovea (superior, nasal, inferior and temporal). In each disease, at every timepoint, most intraretinal fluid (IRF) per square millimetre was present at the fovea, followed by the paracentral ring and pericentral ring (p<0.0001). While this was also the case for subretinal fluid (SRF) in RVO/DME (p<0.0001), patients with nAMD showed more SRF in the paracentral ring than at the fovea up to month 3 (p<0.0001). Between sectors, patients with RVO/DME showed the highest IRF volumes temporally (p<0.001/p<0.0001). In each disease, more SRF was consistently found inferiorly than superiorly (p<0.02). At month 1/12, we measured the following median reductions of initial fluid volumes. For IRF: RVO, 95.9%/97.7%; nAMD, 91.3%/92.8%; DME, 37.3%/69.9%. For SRF: RVO, 94.7%/97.5%; nAMD, 98.4%/99.8%; DME, 86.3%/97.5%. Fully automated localisation and quantification of IRF/SRF over time shed light on the fluid dynamics in each disease. There is a specific anatomical response of IRF/SRF to anti-VEGF therapy in all diseases studied.


Autoimmunity to beta IV spectrin in paraneoplastic lower motor neuron syndrome.
Paraneoplastic neurological disorders may result from autoimmunity directed against antigens shared by the affected neurons and the associated cancer cells. We have recently reported the case of a woman with breast cancer and paraneoplastic lower motor neuron syndrome whose serum contained autoantibodies directed against axon initial segments and nodes of Ranvier of myelinated axons, including the axons of motoneurons. Here, we show that major targets of the autoantibodies of this patient are betaIVSigma1 spectrin and betaIV spectrin 140, two isoforms of the novel betaIV spectrin gene, as well as a neuronal surface epitope yet to be identified. Partial improvement of the neurological symptoms following cancer removal was associated with a drastic reduction in the titer of the autoantibodies against betaIV spectrin and nodal antigens in general, consistent with the autoimmune pathogenesis of the paraneoplastic lower motor neuron syndrome. The identification of betaIV spectrin isoforms and surface nodal antigens as novel autoimmune targets in lower motor neuron syndrome provide new insights into the pathogenesis of this severe neurological disease.


Dynamic contact of the human fingerpad against a flat surface.
This paper investigates the dynamic, distributed pressure response of the human fingerpad in vivo when it first makes contact with an object. A flat probe was indented against the fingerpad at a 20 to 40 degree angle. Ramp-and-hold and sinusoidal displacement trajectories were applied to the fingerpad within a force range of 0-2 N. The dynamic spatial distribution of the pressure response was measured using a tactile array sensor. Both the local pressure variation and the total force exhibited nonlinear stiffness (exponential with displacement) and significant temporal relaxation. The shape of the contact pressure distribution could plausibly be described by an inverted paraboloid. A model based on the contact of a rigid plane (the object) and a linear viscoelastic sphere (the fingerpad), modified to include a nonlinear modulus of elasticity, can account for the principal features of the distributed pressure response.


Multi-mJ, 200-fs, cw-pumped, cryogenically cooled, Yb,Na:CaF2 amplifier.
Using a novel (to our knowledge) broadband Yb-doped Yb3+,Na+:CaF2 crystal cooled in a closed loop to 130 K we demonstrate a chirped pulse regenerative laser amplifier delivering the energy of up to 3 mJ at a repetition rate of 1 kHz and an average output power of 6 W at 20 kHz. The gain narrowing in the laser crystal is compensated by shaping the amplitude of the seed pulse spectrum. As the result, at the highest amplified pulse energy we obtain a 12 nm FWHM bandwidth supporting a 130 fs pulse duration, assuming ideal compression. Amplified pulses were recompressed from 250 ps to 195 fs with a 1700 lines/mm transmission grating compressor.


Racial variation in prostate specific antigen in a large cohort of men without prostate cancer.
Several studies have reported racial variation in serum prostate specific antigen (PSA) levels. Many of these studies, however, have included a significant number of men without a documented digital rectal examination (DRE) result or without prostate biopsies if abnormalities in PSA or DRE were detected. Thus, it is not clear that men with prostate cancer have been excluded in these analyses. In this report, data from 9,162 men (3,786 African-American men and 5,376 white men) are reviewed. All men had both serum PSA and DRE testing. Every man in this study had either a documented normal DRE and PSA (< 4 ng/mL) (3,422 African-American men and 4,795 white men) or a negative prostate biopsy (364 African-American men and 581 white men). Data were analyzed in age-matched decades. African-American men and white men had no difference in serum PSA levels between 30 and 39 years of age. At 40-49, 50-59, 60-69 and 70-79 years of age, African-American men had a statistically higher serum PSA level than white men. From these data, we conclude that racial variation in serum PSA is present in all decades above 40 years of age. Our data are unique in that this cohort included a substantial number of men between 30 and 39 years of age. In this group of young men, no racial differences in serum PSA were detected. These studies indicate, for the first time, that the onset of racial variation in PSA occurs after the fourth decade of life.


Bison alter the northern Yellowstone ecosystem by breaking aspen saplings.
The American bison (Bison bison) is a species that strongly interacts with its environment, yet the effects of this large herbivore on quaking aspen (Populus tremuloides) have received little study. We documented bison breaking the stems of aspen saplings (young aspen >2 m tall and ≤5 cm in diameter at breast height) and examined the extent of this effect in northern Yellowstone National Park (YNP). Low densities of Rocky Mountain elk (Cervus canadensis) after about 2004 created conditions conducive for new aspen recruitment in YNP's northern ungulate winter range (northern range). We sampled aspen saplings at local and landscape scales, using random sampling plots in 87 randomly selected aspen stands. Across the YNP northern range, we found that 18% of sapling stems had been broken. The causal attribution to bison was supported by multiple lines of evidence: (1) most broken saplings were in areas of high bison and low elk density; (2) saplings were broken in summer when elk were not foraging on them; (3) we directly observed bison breaking aspen saplings; and (4) mixed-effects modeling showed a positive association between scat density of bison and the proportion of saplings broken. In a stand heavily used by bison, most aspen saplings had been broken, and portions of the stand were cleared of saplings that were present in previous sampling in 2012. Bison numbers increased more than fourfold between 2004 and 2015, and their ecosystem effects have similarly increased, limiting and in some places reversing the nascent aspen recovery. This situation is further complicated by political constraints that prevent bison from dispersing to areas outside the park. Thus, one important conservation goal, the preservation of bison, is affecting another long-term conservation goal, the recovery of aspen and other deciduous woody species in northern Yellowstone.


In Vivo Microscopy of the Mouse Brain Using Multiphoton Laser Scanning Techniques.
The use of multiphoton microscopy for imaging mouse brain in vivo offers several advantages and poses several challenges. This tutorial begins by briefly comparing multiphoton microscopy with other imaging modalities used to visualize the brain and its activity. Next, an overview of the techniques for introducing fluorescence into whole animals to generate contrast for in vivo microscopy using two-photon excitation is presented. Two different schemes of surgically preparing mice for brain imaging with multiphoton microscopy are reviewed. Then, several issues and problems with in vivo microscopy - including motion artifact, respiratory and cardiac rhythms, maintenance of animal health, anesthesia, and the use of fiducial markers - are discussed. Finally, examples of how these techniques have been applied to visualize the cerebral vasculature and its response to hypercapnic stimulation are provided.


Control Theory and Cancer Chemotherapy: How They Interact.
Control theory arises in most modern real-life applications, not least in biological and medical applications. In particular, in biological and medical contexts, the role of control theory began to take shape in the early 1980s when the first works appeared on the application of control theory in models of pharmacokinetics and pharmacodynamics for antitumor therapies. Forty years after those first works, the theory of control continues to be considered a mathematical analysis tool of extreme importance and usefulness, but the challenges it must overcome in order to manage the complexity of biological processes are in fact not yet overcome. In this article, we introduce the reader to the basic ideas of control theory, its aims and its mathematical formalization, and we review its use in cell phase-specific models for cancer chemotherapy. We discuss strengths and limitations of the control theory approach to the analysis pharmacokinetics and pharmacodynamics models, and we will see that most of them are strongly related to data availability and mathematical form of the model. We propose some future research directions that could prove useful in overcoming the these limitations and we indicate the crucial steps preliminary to a useful and informative application of control theory to cancer chemotherapy modeling.


The combined effects of exercise and food intake on adipose tissue and splanchnic metabolism.
Seven young, healthy male subjects were each studied in two separate experiments. (1) Subjects exercised for 60 min at 55% of peak oxygen consumption in the fasted state ending 30 min before a meal (60% of energy as carbohydrate, and 20% of energy as lipid and protein each) comprising 25% of the total daily energy intake, and were then studied for another 150 min postprandially during rest (E-->M). (2) One hour after a similar meal, subjects exercised for 60 min and were then studied for another 180 min postexercise during rest (M-->E). Regional adipose tissue and splanchnic tissue metabolism were measured by Fick's Principle. Food intake before exercise reduced whole-body lipid combustion during exercise to about 50% of the combustion rate found during exercise in the fasted state. The increase in subcutaneous, abdominal adipose tissue lipolysis during exercise was not influenced by preexercise food intake, while the fatty acid mobilization was increased by only 1.5-fold during postprandial exercise compared to a fourfold increase during exercise in the fasted state. During exercise, catecholamine concentrations increased similarly in the fasted and the postprandial state, while the insulin concentration was twofold higher postprandially. These results indicate that the increase in catecholamine concentrations during exercise is a more important determinant of the adipose tissue lipolytic rate than the decrease in insulin concentration. Furthermore, food intake either 30 min after or 1 h before exercise prevents the postexercise increase in adipose tissue glycerol and fatty acid release which normally takes place in fasting subjects at least up to 2.5 h postprandially. Postprandial exercise led to a faster increase in postprandial lipaemia. This could not be accounted for by changes in the regional splanchnic tissue or adipose tissue triacylglycerol metabolism. Exercise was able to increase hepatic glucose production irrespective of food intake before exercise. It is concluded that exercise performed in the fasted state shortly before a meal leads to a more favourable lipid metabolism during and after exercise than exercise performed shortly after a meal.


Morphometric vertebral fractures in postmenopausal women with primary hyperparathyroidism.
An increased risk of fracture in patients with primary hyperparathyroidism (PHPT) compared to the general population has been reported, but available data are controversial. The aim of the study was to evaluate the rate of vertebral fractures (VFs) by dual-energy x-ray absorptiometry in postmenopausal women with sporadic PHPT and compare the results with a control group. A case-control study was performed at a referral center. A total of 150 consecutive patients and 300 healthy women matched for age and menopausal age participated in the study. VFs were detected in 37 of 150 (24.6%) patients and 12 of 300 (4.0%) controls (P < 0.0001). The majority of VFs were mild. Stepwise multiple logistic regression analysis showed that in PHPT patients lumbar spine bone mineral density was the only variable independently associated with the prevalence of VFs (P = 0.003). The rate of fracture was higher in symptomatic (34.1%) than asymptomatic (21.1%) patients, but this difference was not statistically significant (P = 0.15). Among asymptomatic patients, fracture rate was significantly higher in those who met the criteria for parathyroidectomy (28.1%) than in those who did not (11.1%) (P = 0.03). Compared to controls, the fracture rate was significantly higher in patients with symptomatic and asymptomatic PHPT who met the criteria for surgery (P < 0.0001), but not in those who did not meet the criteria (P = 0.06). VF rate is increased in postmenopausal women with PHPT compared to controls, independently of whether they are classified as symptomatic or asymptomatic. The question of whether the finding of mild morphometric VFs in the latter represents an indication for parathyroid surgery remains to be established.


A case of ileoileal intussusception caused by metastatic pedunculated tumor of cutaneous angiosarcoma.
Cutaneous angiosarcoma is a rare aggressive vascular tumor that occurs in elderly patients and is usually located on the head and face. Metastases often develop in the cervical lymph nodes, lungs, bone, liver and spleen. There have been no reports of ileoileal intussusception due to metastatic tumor from cutaneous angiosarcoma. We reported a case of cutaneous angiosarcoma in a 67-year-old Japanese male accompanied with ileoileal intussusception due to metastatic angiosarcoma. We assume that the metastatic tumor in the small intestine was metastasized hematogeneously from cutaneous angiosarcoma, resulting in the formation of nodules and the rapid growth of a pedunculated tumor as a forerunner of the ileoileal intessusception.


Combined Adenosquamous and Large Cell Neuroendocrine Carcinoma of the Gallbladder.
Large cell neuroendocrine carcinoma (LCNEC) of the gallbladder is extremely rare and usually combined with other type of malignancy, mostly adenocarcinoma. We report an unusual case of combined adenosquamous carcinoma and LCNEC of the gallbladder in a 54-year-old woman. A radical cholecystectomy specimen revealed a 4.3×4.0 cm polypoid mass in the fundus with infiltration of adjacent liver parenchyma. Microscopically, the tumor consisted of two distinct components. Adenosquamous carcinoma was predominant and abrupt transition from adenocarcinoma to squamous cell carcinoma was observed. LCNEC showed round cells with large, vesicular nuclei, abundant mitotic figures, and occasional pseudorosette formation. The patient received adjuvant chemotherapy. However, multiple liver metastases were identified at 3-month follow-up. Metastatic nodules were composed of LCNEC and squamous cell carcinoma components. Detecting LCNEC component is important in gallbladder cancer, because the tumor may require a different chemotherapy regimen and show early metastasis and poor prognosis.


An evaluation of family therapy in anorexia nervosa and bulimia nervosa.
A controlled trial comparing family therapy with individual supportive therapy in anorexia nervosa and bulimia nervosa was undertaken. Eighty patients (57 with anorexia nervosa; 23 with bulimia nervosa) were first admitted to a specialized unit to restore their weight to normal. Before discharge, they were randomly allocated to family therapy or the control treatment (individual supportive therapy). After one year of psychological treatment, they were reassessed, using body weight, menstrual function, and ratings on the Morgan and Russell scales. Family therapy was found to be more effective than individual therapy in patients whose illness was not chronic and had begun before the age of 19 years. A more tentative finding was the greater value of individual supportive therapy in older patients. To our knowledge, this is the first controlled trial of family therapy in anorexia nervosa and clarifies the specific indications for this treatment.


Vaccine tolerance in steroid substituted patients with congenital adrenal hyperplasia.
The tolerance and side effects of vaccinations were determined in patients with congenital adrenal hyperplasia (CAH) who receive physiological corticosteroid substitution. In a retrospective approach, questionnaires about the frequencies of vaccinations and observed side effects were sent to CAH patients, and medical records were reviewed. We received 82 questionnaires from 63 patients with CAH and salt-losing and 19 patients without salt-losing. Patients age ranged from 2-40 years. No statistical differences were found for vaccination frequencies between patients with or without salt-losing. CAH patients had received complete vaccinations against diphtheria, tetanus and poliomyelitis in 79%, 85% and 78%, respectively, whereas pertussis vaccination was complete in only 23%. Live vaccination against measles, mumps and rubella was performed in 63%, 50% and 38%. Side effects of vaccination were indicated in 5 out of 82 questionnaires who all belonged to CAH patients with salt-losing. Transient side effects were an anaphylactic reaction, probably to tetanus immunoglobulin, in 1 case, and fever and convulsions after diphtheria, pertussis and tetanus (DPT) vaccine in 2 cases. In 2 further patients putative complications were noted. Encephalitis with permanent disabilities was observed after the third DPT vaccination, but a causative relation could not be established. In another boy, encephalopathy noticed after measles vaccination was induced by previous toxicosis. Although encephalopathy was described in 2 patients after vaccinations, no vaccination damage could be proven in our retrospective study. As expected, an increased vaccination risk in CAH patients was not demonstrated.


A patient with partial duplication 2q and partial deficiency 11q.
A patient with partial duplication 2q and partial deficiency 11q is reported. The propositus was delivered at 30 weeks gestation, with a birth weight of 1,390 g. He had severe hyaline membrane disease, intraventricular hemorrhage, bronchopulmonary dysplasia, hypotonia, psychomotor retardation, hearing loss, and other anomalies including a short bitemporal diameter, prominent occiput, low-set ears, exophthalmos, short nose with depressed nasal root, downturned mouth corners, narrow high-arched palate, micrognathia, a deep longitudinal groove over the sacrococcygeal region, clinodactyly, and abnormal dermatoglyphics. Chromosome analysis showed the following karyotype: 46,XY,der11,t(2:11)(q32.2;q25)pat.


A novel family of Cys-Cys, His-Cys zinc finger transcription factors expressed in developing nervous system and pituitary gland.
A screen designed to identify proteins that specifically bind to retinoic acid response elements resulted in the identification of a rat cDNA encoding a novel protein containing six Cys-Cys, His-Cys zinc fingers. This gene is expressed in a restricted fashion exhibiting distinct temporal and spatial patterns in the developing nervous system, primarily brain, spinal cord, sensory ganglia, retina, and nasal epithelia, as well as in the pituitary, and is referred to as neural zinc finger factor 1 (NZF-1). NZF-1 binds specifically to a cis-regulatory element of the beta-retinoic acid receptor (RAR beta) gene, as well as to other related DNA elements, including two in the upstream enhancer region of the mouse Pit-1 gene. In heterologous cells, NZF-1 activates transcription from promoters containing specific binding sequences and can synergize with other factors, such as Pit-1, to regulate gene expression. These results suggest that NZF-1 may exert regulatory roles in the developing and mature nervous system and in the pituitary gland. Identification of a second mouse gene highly homologous to NZF-1, encoded by a distinct genomic locus, reveals a dispersed gene family encoding proteins containing Cys-Cys, His-Cys motifs.


Comparison of the clinical efficacy and tolerance of gentamicin PMMA beads on surgical wire versus combined and systemic therapy for osteomyelitis.
These data do not prove a statistical superiority of conventional antibiotics or Septopal in the treatment of chronic osteomyelitis. This result, however, is complicated by the biased data set represented by the combined treatment. The data do suggest that cost of treatment is considerably less in patients who are treated with local antibiotics (i.e., Septopal) alone. The rate of adverse experiences was directly related to the use of parenteral antibiotics, with higher rates of adverse experiences in the conventional and combined treatment groups. Furthermore, the Cierny-Mader Physiologic Class had the best correlation with outcome, suggesting that host factors are probably of critical importance in inducing remission of chronic osteomyelitis. This protocol was not designed to test the role of debridement in the treatment of osteomyelitis: it was assumed that debridement would be the same in both groups. It is the investigators' strong opinion, however, that adequacy of debridement was an important determinant in quiescence or recurrence in the study patients. Similarly, there was no strict control for adequacy of soft-tissue coverage provided by local or distant tissue transfer. Again, the investigators believe that adequacy, including viability and durability, of soft-tissue covering was an important determinant for the end result in these patients. Other covariants such as smoking, history, nutritional status, and other measures of general health will be added to this model when data are available. This analysis will allow definition of the appropriate clinical situations in which use of Septopal alone or combined with parenteral antibiotic is indicated.


Protein Kinase A is a Functional Component of Focal Adhesions.
Focal adhesions (FAs) form the junction between extracellular matrix (ECM)-bound integrins and the actin cytoskeleton and also transmit signals that regulate cell adhesion, cytoskeletal dynamics, and cell migration. While many of these signals are rooted in reversible tyrosine phosphorylation, phosphorylation of FA proteins on Ser/Thr residues is far more abundant yet its mechanisms and consequences are far less understood. The cAMP-dependent protein kinase (protein kinase A; PKA) has important roles in cell adhesion and cell migration and is both an effector and regulator of integrin-mediated adhesion to the ECM. Importantly, subcellular localization plays a critically important role in specifying PKA function. Here, we show that PKA is present in isolated FA-cytoskeleton complexes and, using a targeted biosensor, active within FAs in live cells. Furthermore, using kinase-catalyzed biotinylation of isolated FA-cytoskeleton complexes, we identify fifty-three high-stringency candidate PKA substrates within FAs. From this list, we validate tensin-3 (Tns3) - a well-established molecular scaffold, regulator of cell migration, and component of focal and fibrillar adhesions - as a novel direct substrate for PKA. These observations identify a new pathway for phospho-regulation of Tns3 and, importantly, establish a new and important niche for localized PKA signaling and thus provide a foundation for further investigation of the role of PKA in the regulation of FA dynamics and signaling.


Influence of endodontic sealers artifacts in the detection of vertical root fractures.
The aim of this study was to compare the influence of endodontic sealers artifacts on the detection of vertical root fracture in cone beam computed tomography (CBCT). Premolars and central incisors were assigned into five different groups: Control, Pulp Canal Sealer, AH Plus, Sealer 26, and BC Sealer (n= 10, per group). VRFs were mechanically induced and the teeth were inserted into an image phantom. Subsequently, CBCT (Cranex 3Dx, Soredex, Tuusula, Finland) images were obtained and two observers were asked separately to identify root fracture, by visual analysis. For both premolar and central incisors, kappa coefficients of intraobserver agreement varied from good to excellent (K: 80% - 87%), and the values for interobserver agreement varied from fair to moderate (K: 30% - 35%). As follows, the area under the curve (AUC) of receiver operating characteristic (ROC) values for VRFs highlighted that the use of BC sealer reduced the observers' ability to discriminate VRFs relative to other sealers. Moreover, sensitivity values for premolars teeth ranged from 20% to 60%, and specificity ranged from 60% to 100%; while sensitivity values for central incisors ranged from 30% to 70%, and specificity ranged from 70% to 100%. In conclusion, the low sensitivity values, mainly for premolars, demonstrated the difficulty in VRF diagnosis. Furthermore, BC Sealer induced significantly more imaging artifacts than other sealers. These results highlighting that endodontic sealers may interfere with the diagnosis of VRFs.


Combined soil washing and CDEO for the removal of atrazine from soils.
In this work, it is studied the removal of atrazine from spiked soils by soil washing using surfactant fluids, followed by the treatment of the resulting washing waste by electrolysis with boron doped diamond (BDD) anode. Results confirm that combination of both technologies is efficient for the removal and total mineralization of atrazine. Ratio surfactant/soil is a key parameter for the removal of atrazine from soil and influences significantly in the characteristic of the wastewater produced, affecting not only to the total organic load but also to the mean size of micelles. The higher the ratio surfactant soil, the lower is the size of the particles. Electrolyses of this type of waste attain the complete mineralization. TOC and COD are removed from the start of the treatment but the key of the treatment is the reduction in size of the micelles, which lead to a higher negative charge in the surface and to the faster depletion of the surfactant as compared with the pesticide.


Diversity of nitrifying bacteria in full-scale chloraminated distribution systems.
Chloramination for secondary disinfection of drinking water often promotes the growth of nitrifying bacteria in the distribution system due to the ammonia introduced by chloramine formation and decay. This study involved the application of molecular biology techniques to explore the types of ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) present in several full-scale chloraminated systems. The results of AOB community characterization indicated the ubiquitous detection of representatives from the Nitrosomonas genus, with Nitrosospira constituting a negligible or small fraction of the AOB community in all but one sample. Cloning and sequencing demonstrated the presence of AOB representatives within the Nitrosomonas oligotropha cluster, a phylogenetic subgroup of AOB from which isolates demonstrate a high affinity for ammonia. For the NOB communities, Nitrospira were detected in most of the samples, while Nitrobacter were only detected in a few samples. These results provide insight into the types of AOB responsible for nitrification episodes in full-scale chloraminated systems, which should help direct future studies aimed at characterizing relevant AOB growth and inactivation properties. Furthermore, the detection of NOB in most of the samples suggests a need to evaluate the contribution of biological nitrite oxidation relative to chemical oxidation in these systems.


Gnawing at Metchnikoff's paradigm.
In this issue of Blood, Rossi et al provide convincing evidence that extends and generalizes the importance of trogocytosis, a process in which effector cells use Fcg receptors to remove Immunoglobulin G (IgG)-chelated antigens from donor cells. Their work suggests that the process may be beneficial in the context of epratuzumab treatment of autoimmune diseases.


MicroRNA changes of bone marrow-derived mesenchymal stem cells differentiated into neuronal-like cells by Schwann cell-conditioned medium.
Bone marrow-derived mesenchymal stem cells differentiate into neurons under the induction of Schwann cells. However, key microRNAs and related pathways for differentiation remain unclear. This study screened and identified differentially expressed microRNAs in bone marrow-derived mesenchymal stem cells induced by Schwann cell-conditioned medium, and explored targets and related pathways involved in their differentiation into neuronal-like cells. Primary bone marrow-derived mesenchymal stem cells were isolated from femoral and tibial bones, while primary Schwann cells were isolated from bilateral saphenous nerves. Bone marrow-derived mesenchymal stem cells were cultured in unconditioned (control group) and Schwann cell-conditioned medium (bone marrow-derived mesenchymal stem cell + Schwann cell group). Neuronal differentiation of bone marrow-derived mesenchymal stem cells induced by Schwann cell-conditioned medium was observed by time-lapse imaging. Upon induction, the morphology of bone marrow-derived mesenchymal stem cells changed into a neural shape with neurites. Results of quantitative reverse transcription-polymerase chain reaction revealed that nestin mRNA expression was upregulated from 1 to 3 days and downregulated from 3 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. Compared with the control group, microtubule-associated protein 2 mRNA expression gradually increased from 1 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. After 7 days of induction, microRNA analysis identified 83 significantly differentially expressed microRNAs between the two groups. Gene Ontology analysis indicated enrichment of microRNA target genes for neuronal projection development, regulation of axonogenesis, and positive regulation of cell proliferation. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that Hippo, Wnt, transforming growth factor-beta, and Hedgehog signaling pathways were potentially associated with neural differentiation of bone marrow-derived mesenchymal stem cells. This study, which carried out successful microRNA analysis of neuronal-like cells differentiated from bone marrow-derived mesenchymal stem cells by Schwann cell induction, revealed key microRNAs and pathways involved in neural differentiation of bone marrow-derived mesenchymal stem cells. All protocols were approved by the Animal Ethics Committee of Institute of Radiation Medicine, Chinese Academy of Medical Sciences on March 12, 2017 (approval number: DWLI-20170311).


Trypanosoma cruzi: effect of parasite subpopulation on murine pregnancy outcome.
C3H/HeN female mice infected with distinct Trypanosoma cruzi subpopulations (RA strain [pantropic/reticulotropic] and K98 clone of the CA-I strain [myotropic]) show differences both in inflammatory compromise of the genital tract and in the outcome of pregnancy. The group of mice infected with the K98 clone show lymphomononuclear infiltrates in pelvian fat and in uterus interstitium, coexisting with the presence of T. cruzi DNA, and show moderate oophoritis, perioophoritis, and vasculitis. However, neither parasite DNA nor inflammatory foci were detected in the uterus, and only mild oophoritis was observed among RA-infected mice at mating time. Independently from the parasite subpopulation, females developed estrous 30 days postinoculation (PI), and at the same time, parasite counts were similar for K98 and for RA-infected mice. However, fertility was significantly diminished in K98-infected females. On day 14 of gestation, fetal resorptions increased in this group and cannot be attributed to hormonal disbalance because similar serum progesterone levels were found in all groups. At this time (44 days PI), parasitemia was higher in K98- than in RA-infected mice. However, resorptions were not triggered by massive infection because polymerase chain reaction failed to prove parasite DNA in resorbing fetuses. In contrast with K98 females, RA-infected mice delivered T. cruzi-infected newborns.


Superachromatic air-spaced triplet.
A theoretical analysis of properties of superachromatic air-spaced triplets composed of thin lenses is described in this paper. An interesting result is shown in that the superachromatic air-spaced triplet cannot simultaneously correct field curvature and transverse and longitudinal chromatic aberration. The formulas for the calculation of parameters of an air-spaced triplet are derived and the procedure for the calculation of the shape of individual lenses of the triplet is described using the third-order aberration theory. The application of the described analysis is presented in an example of the design of a superachromatic triplet.


Catalytic asymmetric total syntheses of quinine and quinidine.
The catalytic, asymmetric syntheses of quinine and quinidine were achieved in 16 steps. The recently developed salen(Al)-catalyzed enantioselective Michael addition of methyl cyanoacetate served to set the crucial C4 stereocenter in 92% ee, and a late-stage asymmetric dihydroxylation was used to differentiate the common intermediate and access the two desired diastereomeric products with high selectivity.


Technique development of high-throughput and high-sensitivity sample preparation and separation for proteomics.
Sample preparation and separation methods determine the sensitivity and the quantification accuracy of the proteomics analysis. This article covers a comprehensive review of the recent technique development of high-throughput and high-sensitivity sample preparation and separation methods in proteomics research.


Chronic pain and disability after pelvic and acetabular fractures--assessment with the Mainz Pain Staging System.
Chronic posttraumatic pelvic pain (PPP) after pelvic ring fractures impacts negatively on quality of life issues. This study aimed to more clearly identify and quantify the problem. For this cross-sectional study, patients were examined 52 (median) months after pelvic fractures. The following parameters were measured: pain chronicity (Mainz Pain Staging System [MPSS]), pain intensity (Numeric Rating Scale, 0-10), pelvic fracture outcome scores (Majeed, Pohlemann, and Bürk), pain severity (Chronic Pain Grading Questionnaire), pain-related interference with activities of daily living (Chronic Pain Grading Questionnaire), low back pain-related disability (Oswestry score), neuropathic pain (painDETECT), physical functioning (Short Form-12), and medical comorbidities (Weighted Illness Check List-20). Psychological distress was evaluated for anxiety and depression (Hospital Anxiety and Depression Scale) and mental quality of life (Short Form-12). Sixty-nine patients had a total of 49 pelvic and 41 acetabular fractures; 70% underwent osteosynthesis. The prevalence of PPP was 64%. Prevalence weighted with the dysfunctional pain chronicity stages MPSS II and III was 48%. Patients with pelvic fracture types (AO classification) A, B, and C had PPP prevalences of 38%, 67%, and 90%, respectively. Pain chronicity stages (MPSS) were moderately to strongly correlated with pelvic pain intensity (r = 0.57), the three pelvic fracture outcome scores (r = -0.78 to -0.90), pain-related interference (r = 0.72), Oswestry score (r = 0.68), nerve injury and neuropathic pain (r = 0.52), reduced physical (r = -0.72) and mental functioning (r = -0.58), trauma-related comorbidity (r = 0.53), anxiety (r = 0.51), and depression (r = 0.67). This study demonstrated that the intensity and prevalence of PPP are high even some 4 years after injury. The validated instruments MPSS (measuring pain chronicity) and Oswestry disability score proved to be appropriate for classifying outcome after pelvic ring fractures.


Shotgun phage display cloning.
Shotgun phage display cloning is a useful tool for studying interactions between bacterial and host proteins. Libraries are constructed by cloning randomly fragmented prokaryotic DNA into phage mid-vectors. Theoretically, these libraries will consist of phages that together display all proteins encoded by the bacterial genome. Selecting a gene III-based library, made from Staphylococcus aureus DNA, against IgG and fibronectin resulted in 20-40% positive clones after two pannings. Increasing the number of fusion proteins per phage particle by using gene VIII-based display, increased the frequency of correct clones to 75-100%.


Immune electron microscopic demonstration of hepatitis B core antigen (HBcAg) in liver cell plasma membranes.
Immune light and electron microscopic examinations were carried out to investigate the localization of HBcAg in biopsies from patients with persistent HBs antigenemia. In biopsies with severe intralobular inflammation HBcAg was mainly observed in the cytoplasm of hepatocytes in contrast to nuclear localization in specimens with less severe histological changes. Immune electron microscopic examination demonstrated two different appearances of HBcAg, according to whether it was or was not associated with core particles. In biopsies with more severe parenchymal damage, an increased amount of non-particulate HBcAg was observed in the cytoplasmic matrix; four such biopsies with intracytoplasmic HBcAg also revealed HBcAg on the plasma membrane of the hepatocytes. These findings support the concept that HBcAg may function as a viral target antigen for the immune response in type B hepatitis.


A2A adenosine receptor deficiency leads to impaired tracheal relaxation via NADPH oxidase pathway in allergic mice.
A(2A) adenosine receptor (A(2A)AR) has been shown to suppress superoxide generation in leukocytes via the cAMP-protein kinase A (PKA) pathway. However, no study has yet explored the role of A(2A)AR in relation to NADPH oxidase in murine tracheas in vitro, which may lead to altered smooth muscle relaxation in asthma. Therefore, the present study evaluated the effects of A(2A)AR deficiency on the NADPH oxidase pathway in tracheas of A(2A) wild-type (WT) and A(2A) knockout (KO) mice. A(2A)WT mice were sensitized with ovalbumin (30 microg i.p.) on days 1 and 6, followed by 5% ovalbumin aerosol challenge on days 11, 12, and 13. A(2A)AR (gene and protein expression), cAMP, and phosphorylated PKA (p-PKA) levels were decreased in A(2A)WT sensitized mice compared with controls. A(2A)KO mice also showed decreased cAMP and p-PKA levels. A(2A)WT sensitized and A(2A)KO control mice had increased gene and protein expression of NADPH oxidase subunits (p47phox and gp91phox) compared with the controls. Tracheal relaxation to specific A(2A)AR agonist, 4-[2-[[6-amino-9-(N-ethyl-beta-d-ribofuranuronamidosyl)-9H-purin-2-yl]amino]ethyl]benzenepropanoic acid hydrochloride (CGS 21680), decreased in A(2A)WT sensitized mice compared with the controls, although it was absent in A(2A)KO mice. Pretreatment with NADPH oxidase inhibitors apocyanin/diphenyliodonium reversed the attenuated relaxation to CGS 21680 in A(2A)WT sensitized tracheas, whereas specific PKA inhibitor (9S,10S,12R)-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i] [1,6]benzodiazocine-10-carboxylic acid hexyl ester (KT 5720) blocked CGS 21680-induced relaxation. Tracheal reactive oxygen species (ROS) generation was also increased in A(2A)WT sensitized and A(2A)KO control mice compared with the controls. In conclusion, this study shows that A(2A)AR deficiency causes increased NADPH oxidase activation leading to decreased tracheal relaxation via altered cAMP-PKA signaling and ROS generation.


Recipients' and providers' perspectives of obesity and potential barriers to weight management programmes in patients with Rheumatoid Arthritis (RA): a qualitative study.
The UK rheumatology community serves an ageing and ethnically diverse population, with a growing public health concern about obesity. Overweight and obesity contribute to 2.8 million preventable deaths annually. A raised Body Mass Index (BMI) in those with Rheumatoid Arthritis (RA) can have a significant negative impact on clinical outcomes. The aim of the study was to examine patients' and providers' perceptions of obesity and potential barriers to participation in a future weight management programme to contribute to an appropriate intervention design. Qualitative semi-structured interviews were carried out with 11 patients with RA and one focus group was held with 8 members of a multi-disciplinary team working in one Rheumatology outpatient clinic. Framework analysis (FA) contributed to the inductive thematic analysis, and was employed to assist with the identification of the emergent codes and final themes. Three core themes were ascertained from the semi-structured interviews: i) The psychosocial impact of living with RA and obesity, ii) Challenges of living with RA and obesity and iii) Considerations for future weight management programmes. The Focus group analysis also identified three core themes: i) Micro-dynamics between patient and provider, ii) The relationship between the provider and the host institution in relation to the development of a future weight management programme and iii) The social and political context of obesity as a public health concern. Perceptions of obesity and weight gain and associated barriers to participating in weight management programmes, differ significantly between patients and providers. Patients, require a holistic approach to weight management by clinicians and the acknowledgement of the significant psychosocial impact of a dual diagnosis of RA and being overweight or obese. In contrast, providers seem reluctant to address weight increase with patients and require education and support at an individual and institutional level to integrate weight management into routine care.


Comparison of myeloperoxidase detection by flow cytometry using two different clones of monoclonal antibodies.
Myeloperoxidase (MPO) is present in azurophilic granules which appear in the promyelocyte stage of differentiation and is expressed in granulomonocytic cells. MPO is usually detected by cytochemistry. The demonstration of peroxidase in at least 3% of bone marrow blasts defines an acute leukaemia as acute myeloblastic leukaemia (AML). MPO is important in distinguishing acute myeloblastic leukaemia (AML) from acute lymphoblastic leukaemia (ALL). It is difficult to diagnose AML with minimal evidence of myeloid differentiation (AML- M0) by conventional light microscopy. However, these AML-M0 blasts can be detected by monoclonal antibodies. Anti-MPO recognizes the enzymatically inactive precursor forms of MPO. There are a few commercially available monoclonal antibodies against MPO. In this study, we evaluated two monoclonal antibodies against MPO from different commercial sources. Anti-MPO were purchased from Dako (Denmark) and Becton Dickinson, BD (California, USA). MPO detection was done using the permeabilisation-staining technique, followed by analysis with flow cytometer (FASCalibur, California, USA). 63 cases of acute leukaemias (38 ALL and 25 AML) were studied. Anti-MPO by Dako showed that 12/38 (31.6%) of ALL cases were positive, but all these cases were clear-cut negative for anti-MPO from BD. 24/38 (63.2%) of these ALL cases were associated with aberrant expression of myeloid antigens. However, only 8/24 (33.3%) cases with aberrant myeloid antigen expression showed positive reaction to anti-MPO (Dako). 23/25 (92%) of AML showed concordance results for both anti-MPO by Dako and BD. Anti-MPO is a useful and reliable marker for the diagnosis of AML. However, this study had demonstrated that results vary with the monoclonal antibody used in ALL cases. Anti-MPO (Dako) had shown false positive result in 31.6% of ALL cases whereas anti-MPO (BD) had shown consistent negative result in ALL cases.


Human leptospirosis: management and prognosis.
As leptospirosis is a treatable disease, early diagnosis and prompt treatment are important for better prognosis. Early diagnosis depends on the knowledge of epidemiological factors, presenting features and use of appropriate laboratory tests. Early institution of appropriate antimicrobial therapy in combination with supportive therapy reduces the mortality from this disease. Leptospires are sensitive to a variety of antimicrobial agents, including penicillin, cephems, aminoglycosides, tetracyclines and macrolides. Of these antimicrobial agents, short-term treatment with streptomycin exterminates, leptospires. When penicillin, cephems, tetracylines and macrolides are used, long-term therapy with large doses may be required from the early stage of the disease until the appearance of antibodies.


Investigation of Antioxidant and Cytotoxicity Effects of Silver Nanoparticles Produced by Biosynthesis Using Lactobacillus gasseri.
The biosynthesis of silver nanoparticles (AgNPs) is a new approach in nanotechnology which was optimistically implemented in medicine, food control, and pharmacology. The present study aimed to investigate the antioxidant and cytotoxicity effects of AgNPs produced by Lactobacillus gasseri filtrate. Also, changing color from yellow to brown confirmed the production of AgNPs. AgNPs were characterized using ultraviolet-visible spectroscopy, FE-SEM, and Fourier Transform Infrared Spectroscopy (FTIR). The antioxidant activity of AgNPs was tested using the DPPH assay. The scavenging test for DPPH showed 19.3%, 32.6%, 47.6%, 72%, 85.3% at concentrations (6.25, 12.5, 25, 52, 100) µg/ml, respectively, which proved that the scavenging percentage increased with increasing concentration. The effect of AgNPs on the chromosomal pattern was also studied. The results of the experiment of AgNPs against SK-GT-4 cancer cells showed the toxic activity of the used particles against the strains of these human esophageal cancer cells and failed to affect normal cells.


Vasectomy techniques for male sterilization: systematic Cochrane review of randomized controlled trials and controlled clinical trials.
The review aimed to compare the effectiveness, safety and acceptability of vasectomy techniques for male sterilization. We searched five computerized databases and reference lists of relevant articles and book chapters for randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing vasectomy techniques. Two reviewers independently extracted data from eligible articles. Two poor-quality trials compared vas occlusion with clips versus a conventional technique, and four poor-quality trials examined vas irrigation with water versus no irrigation or irrigation with euflavine. No significant differences regarding the primary outcome of time to azoospermia were found. However, one trial reported fewer median number of ejaculations to azoospermia with euflavine rather than water irrigation. An interim report of a high-quality trial comparing vasectomy with and without fascial interposition found more azoospermia with fascial interposition but also more surgical difficulties. No conclusions can be reached regarding the effectiveness, safety and acceptability of vas occlusion techniques or vas irrigation since only low-quality, underpowered studies were available. Fascial interposition had improved vasectomy success but also increased surgical difficulty. High-quality, adequately reported RCTs are required. More work is also needed in the standardization of follow-up protocols, evaluation of vasectomy success and failure, recanalization and analytical methods.


Transcranial sonography in the evaluation of pineal lesions: two-year follow up study.
We have recently reported that transcranial sonography (TCS) is a method competitive to magnetic resonance neuroimaging (MRI) in the evaluation of pineal gland lesions. The aim of the present is study was to assess the usefulness of TCS in a larger patient sample during a two-year follow up. Twenty patients with incidental pineal gland cyst (PGC) detected by MRI scan of the brain and 40 healthy controls without any previous documented data on a disease related to pineal gland were evaluated by TCS and compared with MRI scans. There were no statistically significant differences in PGC size measured by TCS by two observers (p = 0.475), PGC size measured by TCS and MRI (first observer, p = 0.453; and second observer, p = 0.425), size of the pineal gland measured by TCS and MRI in control group (first observer, p = 0.497; and second observer, p = 0.370), and pineal gland size measured by TCS by two observers in control group (p = 0.473). Study results suggested TCS to be a suitable method in the evaluation of pineal gland lesions. Although its resolution cannot match the MRI resolution, its repeatability and accuracy might add to its practical value. We suggest that the repeat MRI scan of such lesions might be replaced by clinical and TCS follow up.


Change in Speech Perception and Auditory Evoked Potentials over Time after Unilateral Cochlear Implantation in Postlingually Deaf Adults.
Speech perception varies widely across cochlear implant (CI) users and typically improves over time after implantation. There is also some evidence for improved auditory evoked potentials (shorter latencies, larger amplitudes) after implantation but few longitudinal studies have examined the relationship between behavioral and evoked potential measures after implantation in postlingually deaf adults. The relationship between speech perception and auditory evoked potentials was investigated in newly implanted cochlear implant users from the day of implant activation to 9 months postimplantation, on five occasions, in 10 adults age 27 to 57 years who had been bilaterally profoundly deaf for 1 to 30 years prior to receiving a unilateral CI24 cochlear implant. Changes over time in middle latency response (MLR), mismatch negativity, and obligatory cortical auditory evoked potentials and word and sentence speech perception scores were examined. Speech perception improved significantly over the 9-month period. MLRs varied and showed no consistent change over time. Three participants aged in their 50s had absent MLRs. The pattern of change in N1 amplitudes over the five visits varied across participants. P2 area increased significantly for 1,000- and 4,000-Hz tones but not for 250 Hz. The greatest change in P2 area occurred after 6 months of implant experience. Although there was a trend for mismatch negativity peak latency to reduce and width to increase after 3 months of implant experience, there was considerable variability and these changes were not significant. Only 60% of participants had a detectable mismatch initially; this increased to 100% at 9 months. The continued change in P2 area over the period evaluated, with a trend for greater change for right hemisphere recordings, is consistent with the pattern of incremental change in speech perception scores over time. MLR, N1, and mismatch negativity changes were inconsistent and hence P2 may be a more robust measure of auditory plasticity in adult implant recipients. P2 was still improving at 9 months postimplantation. Future studies should explore longitudinal changes over a longer period.


Gene silencing: cosuppression at a distance.
When a plant carries a transgenic copy of an endogenous gene, both genes may be silenced. This 'cosuppression' can occur not only within individual cells, but also in distant cells through an agent that apparently moves through the plant's phloem.


X-ray crystal structure of human dopamine sulfotransferase, SULT1A3. Molecular modeling and quantitative structure-activity relationship analysis demonstrate a molecular basis for sulfotransferase substrate specificity.
Humans are one of the few species that produce large amounts of catecholamine sulfates, and they have evolved a specific sulfotransferase, SULT1A3 (M-PST), to catalyze the formation of these conjugates. An orthologous protein has yet to be found in other species. To further our understanding of the molecular basis for the unique substrate selectivity of this enzyme, we have solved the crystal structure of human SULT1A3, complexed with 3'-phosphoadenosine 5'-phosphate (PAP), at 2.5 A resolution and carried out quantitative structure-activity relationship (QSAR) analysis with a series of phenols and catechols. SULT1A3 adopts a similar fold to mouse estrogen sulfotransferase, with a central five-stranded beta-sheet surrounded by alpha-helices. SULT1A3 is a dimer in solution but crystallized with a monomer in the asymmetric unit of the cell, although dimer interfaces were formed by interaction across crystallographic 2-fold axes. QSAR analysis revealed that the enzyme is highly selective for catechols, and catecholamines in particular, and that hydrogen bonding groups and lipophilicity (cLogD) strongly influenced K(m). We also investigated further the role of Glu(146) in SULT1A3 using site-directed mutagenesis and showed that it plays a key role not only in defining selectivity for dopamine but also in preventing many phenolic xenobiotics from binding to the enzyme.


Ulysses S. Grant: Chronic Malaria and the myth of his alcoholism.
Ulysses S. Grant, Civil War general and twice-elected President of the United States, was highly respected in late-19th century America. Gradually however, it became the conventional wisdom that he was an alcoholic who had only succeeded as a general by using overwhelming force. This change began with his political enemies and those who resented his suppression of the Ku Klux Klan, his regard for the welfare of Native Americans and his support of Reconstruction. Jealous subordinates and those with an axe to grind added their voices to this and then the views of certain influential academic historians and romantic adherents of 'The Lost Cause' were unchallenged until the mid-1950s. Grant was undoubtedly an occasional binge drinker but this is not the same as being an alcoholic. Charles A. Dana is the most authoritative source for the claim that Grant was a frank alcoholic. In 1887 he wrote that Grant was drunk on a trip to Satartia, Mississippi in 1863 during the siege of Vicksburg. In this paper, the author shows that Grant was actually ill on that trip from the disease of malaria, alcohol was not involved at all, and that Grant suffered episodically from this disease both before and during the Civil War.


Leukocyte traffic in the central nervous system: the participants and their roles.
While the central nervous system has long been considered immunologically privileged, over the past decade it has become evident that a wide variety of leukocyte types traffic through the nervous system. It is also apparent that the rules governing the trafficking of these disparate cell types are different for each. Some arrive, and probably depart, continuously as part of normal physiology. Others only appear to seek a specific antigen or in response to tissue damage. In this review the nature and function of individual cell types are discussed and our current knowledge regarding the parameters governing their entry into the CNS is examined.


Predictors of success of methotrexate treatment in women with tubal ectopic pregnancies.
The use of methotrexate for the treatment of women with tubal ectopic pregnancies is now common practice. However, the clinical and hormonal determinants of the success of this treatment are not known. We studied 350 women with tubal ectopic pregnancies who were treated with methotrexate intramuscularly according to a single-dose protocol. Pretreatment serum concentrations of human chorionic gonadotropin and progesterone, the size and volume of the gestational mass, fetal cardiac activity, and the presence of fluid (presumably blood) in the peritoneal cavity were correlated with the efficacy of therapy, as defined by resolution of the ectopic pregnancy without the need for surgical intervention. There was no relation between the women's age or parity, the size or volume of the conceptus, or the presence of fluid in the peritoneal cavity and the efficacy of treatment. Among the 320 women in whom treatment was successful (91 percent), the mean (+/-SD) serum chorionic gonadotropin and progesterone concentrations were 4019+/-6362 mIU per milliliter and 6.9+/-6.7 ng per milliliter (21.9+/-21.3 nmol per liter), respectively, as compared with 13,420+/-16,590 mIU per milliliter and 10.2+/-5.5 ng per milliliter (32.4+/-17.5 nmol per liter) (P<0.001 and P=0.02) in the 30 women in whom treatment was not successful. Fetal cardiac activity was present in 12 percent of the successfully treated cases and 30 percent of those in which treatment was not successful (P=0.01). Regression analysis revealed the pretreatment serum chorionic gonadotropin concentration to be the only factor that contributed to the failure rate. Among women with tubal ectopic pregnancies, a high serum chorionic gonadotropin concentration is the most important factor associated with failure of treatment with a single-dose methotrexate protocol.


Use of complementary medicine in Switzerland.
Within the framework of the Swiss governmental Program of Evaluation of Complementary Medicine (PEK) we assessed the prevalence, use, perceived effectiveness and appreciation of complementary medicine (CAM) in Switzerland, according to published surveys. Search was performed through electronic databases, by hand-searching and by contacting experts at universities, hospitals, health insurances, patient organizations and pharmaceutical companies. Surveys were carried out among the general population (40%), physicians (20%), hospitalized patients (30%) and obstetric institutions (5%). The number of publications increased strongly between 1981 and 2004. The mean +/- SD prevalence (use) of CAM is 49 +/- 22% and varies depending on the survey's topic and the population group interviewed. The acceptance, appreciation or demand for CAM among individuals specifically interviewed on CAM is 91 +/- 6%. When asked about favored general improvements in healthcare, 6.5% of the individuals spontaneously mentioned CAM. CAM therapies are considered to be effective by the majority of CAM users and by about 40% of cancer patients using CAM. Approximately 50% of the population stated a preference for hospitals that also provide CAM. 85% of the population wishes the costs for CAM to be covered by the basic health insurance. Approximately half of the Swiss population has used CAM. CAM treatment is considered to be effective by the majority of CAM users. About 50% of the population would prefer hospitals that also provide CAM therapies and the majority of the population wishes the cost for CAM therapies to be covered by basic health insurance.


Complications Associated With Arthroscopic Labral Repair Implants: A Case Series.
Arthroscopic labral repair in the shoulder has become commonplace in recent years. A variety of implants have evolved in parallel with arthroscopic techniques. Any orthopedic implant that is placed in close proximity to the joint has the potential to cause subsequent damage to the articular surface if it is left prominent or dislodges secondary to improper surgical technique. This article focuses on a series of implant-related complications of labral surgery and their subsequent management. Additionally, correct patient selection and surgical technique are discussed.


Not All Nonverbal Tasks Are Equally Nonverbal: Comparing Two Tasks in Bilingual Kindergartners With and Without Developmental Language Disorder.
Purpose This study investigates the interaction of language ability status, cultural experience, and nonverbal cognitive skill performance in Spanish-English bilinguals with typical development (TD) and developmental language disorder (DLD). Method One hundred sixty-nine Spanish-English bilingual kindergartener's scores on the Symbolic Memory and Cube Design subtests from the Universal Nonverbal Intelligence Test (Bracken & McCallum, 1998) were analyzed by language ability (TD vs. DLD). Results t tests and analysis of variance showed bilingual children with TD and DLD performed comparably to the Universal Nonverbal Intelligence Test norming sample on the cube design task, while children with DLD had significantly lower performance on the symbolic memory task. Conclusion These results suggest that cultural experience minimally impacted performance for bilingual children with typically developing language. Bilingual children with DLD were differentially impacted on symbolic memory, a task that is verbally mediated despite nonverbal administration and performance. Findings are discussed within the Cattell-Horn-Carroll theory of cognitive abilities.


Prevalence and Impact of Work-Related Musculoskeletal Disorders on Job Performance of Call Center Operators in Nigeria.
Work-related musculoskeletal disorders (WMSDs) have been documented among various occupational groups in Nigeria. However, there is limited data on the prevalence of WMSDs among call center operators (CCOs). To determine the prevalence of WMSDs among CCOs in Nigeria and to explore the extent to which these discomforts impact the daily work activities of the respondents. 374 respondents who were randomly selected from 4 telecommunication companies in Lagos State, Nigeria, participated in this study. They were asked to complete a pre-tested questionnaire designed to capture the prevalence, impact and associated risk factors of WMSDs among CCOs. 42% and 65.2% of respondents experienced at least one WMSDs in the past 7 days, and 12 months, respectively. Women and CCOs who received calls with hand-held phones rather than headsets reported more discomforts during both 7 days and 12 months periods. Neck, shoulder, upper back, and lower back were the most affected areas during past 7 days and 12 months. Discomforts in the neck, low back, and knees prevented most of the respondents from performing their daily work. WMSDs have a serious impact on the daily job activities of the CCOs in Nigeria.


The effects of incentives on families' long-term outcome in a parenting program.
To examine the impact of paying for participation in a preventive parenting program on treatment outcomes, 197 families with preschool-aged children were randomized to paid or unpaid conditions. Although both groups improved on nearly all measures, paid families showed less improvement on 3 of 10 variables, including father-reported child prosocial behavior and parenting skills and maternal distress. The interaction between payment and treatment format (individual vs. group) was examined. Compared to unpaid group participants, paid group intervention participants had significantly worse mother and father parenting skills posttreatment, whereas paid individual intervention mothers had significantly better skills. These findings suggest payment may lead to smaller treatment effects, although the bulk of the data point to no impact on outcomes. Given that payment attracts families who would not otherwise receive treatment, this appears to be a viable strategy to recruit families without appreciably impacting outcomes.


Haematopoietic stem cell ageing.
The question of whether haematopoietic stem cells age has raised considerable controversy, and has been re-opened recently, as a result of the growing interest in stem cells for transplantation and gene therapy. Studies have focused on the generation of different blood cell elements and the capacity for self-renewal; properties that characterize stem cells. Taken together, it appears that basal haematopoiesis is maintained throughout life, yet, the capacity to cope with haematological stress is decreased in advanced age. In principle, stem cells derived from aged donors can be used for autologous transplantation, when needed to recover basic haematopoiesis. However, patterns of T cell development are altered in ageing, and intervention to augment T cell response still needs to be considered. Current methods for expansion and maintenance of stem cells in vitro enable examination of stem cell potential for long-term expansion and function. A critical evaluation of the possible risks of replicative senescence and developmental changes in stem cells has become feasible. Ageing effects may relate to cell replication, cell migration and lymphoid differentiation. Understanding of the mechanisms underlying these processes will enable the fidelity of stem cell expansion and maintenance of their potential for long-term function.


Self-assembled peptide architecture with a tooth shape: folding into shape.
Molecular self-assembly is the spontaneous association of molecules into structured aggregates by which nature builds complex functional systems. While numerous examples have focused on 2D self-assembly to understand the underlying mechanism and mimic this process to create artificial nano- and microstructures, limited progress has been made toward 3D self-assembly on the molecular level. Here we show that a helical β-peptide foldamer, an artificial protein fragment, with well-defined secondary structure self-assembles to form an unprecedented 3D molecular architecture with a molar tooth shape in a controlled manner in aqueous solution. Powder X-ray diffraction analysis, combined with global optimization and Rietveld refinement, allowed us to propose its molecular arrangement. We found that four individual left-handed helical monomers constitute a right-handed superhelix in a unit cell of the assembly, similar to that found in the supercoiled structure of collagen.


When Dark Humor and Moral Judgment Meet in Sacrificial Dilemmas: Preliminary Evidence With Females.
The influence of dark humor on moral judgment has never been explored, even though this form of humor is well-known to push the boundaries of social norms. In the present study, we examined whether the presence of dark humor leads female participants to approve a utilitarian response (i.e., to kill one to save many) in sacrificial dilemmas. The effects of two types of humorous contexts were compared (i.e., dark vs. nondark) on dilemmas, which differed according to whom benefits from the crime (i.e., oneself and others vs. others only). In addition to collecting moral responses, individuals' emotional states were assessed at three critical steps: Before and after reading the jokes and also after performing the moral judgment task. Our results revealed that dark and nondark humor similarly elicited a positive emotional state. However, dark humor increased the permissiveness of the moral violation when this violation created benefits for oneself. In self and other beneficial dilemmas, female participants in the dark humorous condition judged the utilitarian response more appropriate than those in the nondark condition. This study represents a first attempt in deepening our understanding of the context-dependent nature of moral judgment usually assessed in sacrificial dilemmas.


Rapid community health and needs assessments after Hurricanes Isabel and Charley--North Carolina, 2003-2004.
On September 18, 2003, Hurricane Isabel, a Category 2 hurricane, made landfall on the Outer Banks of North Carolina (NC). The storm, moving to the northeast with winds exceeding 100 mph, caused extensive power outages and structural damage in northeastern NC and southern Virginia. In NC, approximately 762,000 residents lost power during the storm, and the shelter population peaked at an estimated 16,600 persons. Six storm-related fatalities were reported, and 26 eastern NC counties were included in a federal disaster area declaration. The North Carolina Division of Public Health (NCDPH) activated the Office of Public Health Preparedness and Response (PHPR) and seven Public Health Regional Surveillance Teams (PHRSTs) to conduct a rapid community health and needs assessment for the affected population. CDC deployed staff to provide technical support to NCDPH. The assessment determined that the majority of public health emergencies resulted from electric power outages, which affected access to food, water, and medical care. Data and recommendations were provided immediately to local and state emergency responders, who used the information to direct Hurricane Isabel recovery efforts and also to improve the assessment, which was next deployed in August 2004 with Hurricane Charley.


Disparities in Life Course Outcomes for Transition-Aged Youth with Disabilities.
Close to 750,000 youth with special health care needs transition to adult health care in the United States every year; however, less than one-half receive transition-planning services. Using the "F-words" organizing framework, this article explores life course outcomes and disparities in transition-aged youth with disabilities, with a special focus on youth with autism, Down syndrome, and cerebral palsy. Despite the importance of transition, a review of the available literature revealed that (1) youth with disabilities continue to have poor outcomes in all six "F-words" domains (ie, function, family, fitness, fun, friends, and future) and (2) transition outcomes vary by race/ethnicity and disability. Professionals need to adopt a holistic framework to examine transition outcomes within a broader social-ecological context, as well as implement evidence-based transition practices to help improve postsecondary outcomes of youth with disabilities. [Pediatr Ann. 2017;46(10):e371-e376.].


[A structural and ultrastructural study of the inferior olivary complex in ground squirrels (Citellus citellus L.)].
Morphological characteristics of neurons in the inferior olivary complex of ground squirrels at various ages were studied by a light and electron microscope. This nuclear complex consists of three nuclei: medial accessory olivary nucleus, dorsal accessory olivary nucleus and main olivary nucleus. Its cytoarchitectonics cytoarchitecture was studied by serial sections at the coronary level, stained by kresyl-violet. Two types of olivary neurons were established by silver impregnation in accordance with dendrite ramifications. Nematosomes, special forms of granulated endoplasmic reticulum, which could be probably connected with advancement of age and the process of aging were observed by an electron microscope together with organelles and intranuclear inclusions typical for the relay neurons.


Pharmacologic management of diabetic retinopathy.
Diabetic retinopathy (DR) is a leading cause of vision loss in working-age populations, primarily attributable to retinal vascular hyperpermeability, hypoperfusion, and neoangiogenesis. In the past decade, laser photocoagulation and surgical interventions to treat DR have been replaced by topical administrations of anti-vascular endothelial growth factor drugs and corticosteroids. Although these drugs have revolutionized clinical management of DR, their limited efficacy and adverse effects have raised an increasing demand for new drug development. Meanwhile, mouse retinas have been prevalently employed as an experimental model system for angiogenic research, which has greatly contributed to the understanding of general principles in vascular biology. Therefore, clinical ophthalmology and basic research have complimentarily accumulated invaluable information for DR drug discovery. This review highlights the current pharmacologic management of DR, the utility of experimental mouse retinal models, and the perspectives on new drugs targeting the angioepoitin-Tie2 signals.


(1-Amino-2-propenyl) phosphonic acid, an inhibitor of alanine racemase and D-alanine:D-alanine ligase.
DL-(1-Amino-2-propenyl)phosphonic acid was synthesized through the sequential oxidation, sulfoxide elimination, and deprotection of diphenyl [1-[(benzyloxycarbonyl)amino]-3-(phenylthio)propyl] phosphonate. This analogue of vinylglycine is a strong inhibitor of the alanine racemases from Pseudomonas aeruginosa and Streptococcus faecalis and of the D-Ala:D-Ala ligase from this latter species. This molecule is ineffective against the whole bacterial cells. Unlike vinylglycine, this unsaturated phosphonate does not inhibit the following mammalian enzymes: aspartate aminotransferase, alanine aminotransferase, D-amino acid oxidase, which indicates its specificity. Thus, its incorporation in a peptide structure could induce interesting antimicrobial properties.


Pretreatment quality of life as a predictor of distant metastasis and survival for patients with nasopharyngeal carcinoma.
The purpose of this study was to examine the prognostic value of pretreatment quality of life (QoL) data on locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) in patients with nasopharyngeal carcinoma (NPC). A total of 347 new patients with NPC, who were curatively treated by conformal radiotherapy from March 2003 to December 2007, were recruited. The Taiwan Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 was completed before treatment. Multivariate Cox's proportional hazards models were used to analyze the impact of clinical and QoL variables on the treatment results. The 5-year LRC, DMFS, and OS rates were 72.9%, 79.1%, and 68.4%, respectively. After adjusting the clinical variables, 10 QoL variables were observed to be significantly (P < .05) related to OS, and four QoL variables were related to DMFS. No QoL variable was predictive of LRC. Among the QoL variables that significantly predicted OS and DMFS, physical functioning was the most powerful predictor. A 10-point increase in the physical functioning score was associated with a 23% (95% CI, 12% to 34%) reduction in the likelihood of death and a 22% (95% CI, 9% to 36%) reduction in the likelihood of distant metastasis. Our findings indicate that pretreatment QoL variables, especially physical functioning, provide easily available prognostic value for distant metastasis and survival in patients with NPC.


Short communication: The first report of Cyberlindnera rhodanensis associated with clinical bovine mastitis.
An acute case of clinical mastitis in a Holstein cow from second lactation is reported here. A milk sample from the affected quarter was cultured on 5% bovine blood agar and incubated at 37°C for 72 h. After 24 h of incubation, numerous colonies of yeast were observed: the Candida characteristic was not detected by CHROMagar Candida (Difco, Franklin Lakes, NJ). The DNA extraction of the isolate was performed, and DNA was subjected to amplification and sequencing of the D1/D2 region of the large subunit rRNA gene. The sequences were aligned using Mega 7.0 and used for searching GenBank by BLASTn (Basic Local Alignment Search Tool for nucleotides), revealing 98% of identity with Cyberlindnera rhodanensis. To date, this is the first report of this yeast associated with clinical bovine mastitis.


Proinsulin 2 knockout NOD mice: a model for genetic variation of insulin gene expression in type 1 diabetes.
Insulin is a major disease determinant in type 1 diabetes, type 2 diabetes, and related disorders. The role of variations in the expression of the insulin gene has been proposed in genetic susceptibility to the three pathological conditions in humans. In contrast to humans, rodents express two proinsulin isoforms. One isoform, proinsulin 1, is expressed exclusively in islets. The second, proinsulin 2, is expressed in islets and in other tissues, especially the thymus. We took advantage of the expression of these two isoforms to introduce a null proinsulin 2 allele in NOD mice and to evaluate the consequence of a variation of proinsulin 2 gene expression on the development of type 1 diabetes on the NOD genetic background. Heterozygote NOD mutant mice carrying a null proinsulin 2 mutation showed an increased incidence of type 1 diabetes at successive backcross generations. Plasma glucose and insulin levels were identical in prediabetic mutant and in wild-type mice at 4 weeks of age. Variation in insulin gene expression is hypothesized to interfere with diabetes development at both the islet and the thymus level.


Comparison of photoacoustic and fluorescence tomography for the in vivo imaging of ICG-labelled liposomes in the medullary cavity in mice.
Few reports quantitatively compare the performance of photoacoustic tomography (PAT) versus fluorescence molecular tomography (FMT) in vivo. We compared both modalities for the detection of signals from injected ICG liposomes in the tibial medullary space of 10 BALB/c mice in vivo and ex vivo. Signals significantly correlated between modalities (R² = 0.69) and within each modality in vivo versus ex vivo (PAT: R² = 0.70, FMT: R² = 0.76). Phantom studies showed that signals at 4 mm depth are detected down to 3.3 ng ICG by PAT and 33 ng by FMT, with a nominal spatial resolution below 0.5 mm in PAT and limited to 1 mm in FMT. Our study demonstrates comparable in vivo sensitivity, but superior ex vivo sensitivity and in vivo resolution for our ICG liposomes of the VevoLAZR versus the FMT2500. PAT provides a useful new tool for the high-resolution imaging of bone marrow signals, for example for monitoring drug delivery.