A clinical and histologic comparison between free temporoparietal and scapular fascial flaps.
It is universally accepted that the fascial flap is one of the best reconstructive strategies for contour and tendon-gliding function. In this study we compare the free temporoparietal fascial flap (n = 20) and the free scapular fascial flap (n = 6) mainly for these reconstructions and discuss their characteristics, including different clinical applications and histologic examination. Our histologic analysis reveals that the free temporoparietal fascial flap has a potential like a muscle flap; moreover, it is very thin. The free scapular fascial flap is very rich in adipose tissues to prevent adhesion between the flap and underlying tissues. Both flaps in our experience can bring satisfaction to the recipient site, but the donor site of the free temporoparietal fascial flap sometimes suffers from conspicuous widened scars in short-haired patients, and the scapular fascia has a tendency to be thicker in obese patients. Therefore, we recommend using the free temporoparietal fascial flap for women, who tend to have more fat and longer hair, and the free scapular fascial flap for men, who tend to be lean and shorten their side hair.


Evaluation of the relative biological effectiveness of a clinical epithermal neutron beam using dog brain.
This investigation was designed to determine the relative biological effectiveness (RBE) of an epithermal neutron beam (FiR 1 beam) using the brains of dogs. The FiR 1 beam was developed for the treatment of patients with glioma using boron neutron capture therapy. Comparisons were made between the effects of whole-brain irradiation with epithermal neutrons and 6 MV photons. For irradiations with epithermal neutrons, three dose groups were used, 9.4 +/- 0.1, 10.2 +/- 0.1 and 11.5 +/- 0.2 Gy. These physical doses were given as a single exposure and are quoted at the 90% isodose. Four groups of five dogs were irradiated with single doses of 10, 12, 14 or 16 Gy of 6 MV photons to the 100% isodose. Different reference isodoses were used to obtain the most comparable dose distribution in the brain for the two different irradiation modalities. Sequential magnetic resonance images (MRI) were taken for 77-115 weeks after irradiation to detect changes in the brain. Dose-effect relationships were established for changes in the brain as detected either by MRI or by subsequent gross morphology and histology. The doses that caused a specified response in 50% of the animals (ED(50)) were calculated from these dose-effect curves for each end point, and these values were used to calculate the RBE values for the different end points. The RBE values for the FiR 1 beam, based on changes observed on MRI, were in the range 1.2-1.3. For microscopic and gross pathological lesions, the values were in the range 1.2-1.4. The corresponding RBE values for the MRI and pathological end points for the high-LET components (protons from nitrogen capture and recoil protons from fast neutrons) were in the ranges 3.5-4.0 and 3.4-4.4, respectively. This assumed a dose-rate reduction factor of 0.6 for the low-dose-rate gamma-ray component of this beam. Finally, a comparison was made between experimentally derived photon doses, for a specified end point, with calculated photon equivalent doses, which were obtained using the weighting factors for clinical studies on the epithermal neutron beam on the Brookhaven Medical Research Reactor (BNL) in New York. This indicated that the radiation-induced lesions seen in the present study were, on average, detected at a 12% lower photon dose than predicted by the use of the BNL clinical weighting factors. This indicates the need for caution in the extrapolation of results from one reactor-based epithermal neutron beam to another.


Effects of moisture absorption by clothing on thermal responses during intermittent exercise at 24 degrees C.
The effects of two kinds of clothing with different properties with respect to moisture absorption on thermophysiological responses and pulse rate were studied during intermittent exercise at an ambient temperature (Ta) of 24 degrees C. The two kinds of clothing ensemble tested were cotton T-shirt with short sleeves and cotton long-sleeved working dress with full-length trousers (C), and polyester T-shirt with short sleeves and polyester long-sleeved working dress with full-length trousers (P), the thermal resistances of which were nearly equal. Five women aged 21-32 years, served as subjects. The environmental conditions were 24 degrees C Ta, 50% relative humidity and 0.14 m.s-1 air velocity. The subjects, wearing either C or P, exercised for 10-min on a cycle ergometer at an intensity of 30% maximal oxygen uptake and then 10-min rest. This sequence was repeated four times. Rectal and skin temperatures at several sites, local sweating rate, pulse rate and clothing microclimates were continuously compared between C and P throughout the experiment. The major findings were firstly, rectal temperature rose significantly higher in P; secondly, pulse rate was higher in P both during exercise and rest; thirdly, clothing surface temperature on the back rose highly significantly during the fourth exercise period and then fell significantly during the fourth rest period in C; and fourthly, four out of five subjects felt wetter in P during the latter half of the experiment. These results are discussed from the viewpoint that the reduced thermal insulation due to the absorption of moisture in C accelerated dry heat loss, resulting in an inhibition of the increases in core temperature and pulse rate.


[Fixed angle carbon fiber reinforced polymer composite plate for treatment of distal radius fractures : Pilot study on clinical applications].
The clinical implementation of a new carbon-fiber-reinforced polyetheretherketon (PEEK) plate for distal radius fractures might offer advantageous properties over the conventional metallic devices. This includes similar elastic modulus to cortical bone, radiolucency, low artifacts on MRI scans and the lack of metal allergies. The aim of this study was to evaluate the clinical results at 6-week and 12-month follow-up using either a new fixed angle (monoaxial) PEEK plate system or a fixed angle (polyaxial) titanium plate. We included 26 patients (mean age 59.3) with displaced fractures of the distal radius (all AO types). Radiological and functional outcomes were measured prospectively at a 6-week and 12 month follow-up. We documented no cases of hardware breakage or significant loss of the surgically achieved fracture reduction with the usage oft the new PEEK device. Operating time was 101.0 min using PEEK versus 109.3 min in titanium plates, recorded times were including preparation, draping, and postoperative processing (ns, p 0.156). At the 6-week follow up the PEEK plate showed a trend for better range of motion and functional results (DASH-score, Mayo-wrist score, VAS) with no statistical significance. Results of 12 month follow up with PEEK showed comparable results with corresponding studies examining titanium plate after this period. First experience with PEEK plate osteosynthesis demonstrate quick clinical implementation with good clinical outcome and the advantage of excellent postoperative radiological assessment. At early follow-up PEEK even showed a trend for improved functional results.


Cone opsin genes of african cichlid fishes: tuning spectral sensitivity by differential gene expression.
Spectral tuning of visual pigments is typically accomplished through changes in opsin amino acid sequence. Within a given opsin class, changes at a few key sites control wavelength specificity. To investigate known differences in the visual pigment spectral sensitivity of the Lake Malawi cichlids, Metriaclima zebra (368, 488, and 533 nm) and Dimidiochromis compressiceps (447, 536, and 569 nm), we sequenced cone opsin genes from these species as well as Labeotropheus fuelleborni and Oreochromis niloticus. These cichlids have five distinct classes of cone opsin genes, including two unique SWS-2 genes. Comparisons of the inferred amino acid sequences from the five cone opsin genes of M. zebra, D. compressiceps, and L. fuelleborni show the sequences to be nearly identical. Therefore, evolution of key opsin sites cannot explain the differences in visual pigment sensitivities. Real-time PCR demonstrates that different cichlid species express different subsets of the available cone opsin genes. Metriaclima zebra and L. fuelleborni express a complement of genes which give them UV-shifted visual pigments, while D. compressiceps expresses a different set to produce a red-shifted visual system. Thus, variations in cichlid spectral sensitivity have arisen through evolution of gene regulation, rather than through changes in opsin amino acid sequence.


Cancer vaccines: Uses of HLA transgenic mice compared to genetically modified mice.
Many tumor antigens have been identified that can be targeted by the immune system. Animal models that have been genetically modified to express human HLA molecules instead of their own MHC antigens have shown to be valuable in the discovery of peptides derived from tumor antigens many of which have since been used in clinical trials with varying degrees of success. Although these models are not perfect, they nonetheless allow transplantable tumor models to be developed to evaluate novel vaccination strategies that can then be applied in humans. In addition animals that have been genetically modified to "spontaneously" generate tumors that will grow within their correct environment are of greater value for studying angiogenesis, metastasis and the relationship between the immune system and tumor in a physiological setting. In this review, mice genetically modified to express HLA genes or to spontaneously develop tumors are discussed, highlighting their advantages and limitations as preclinical models for cancer immunotherapy.


Indirect calculation of monoclonal antibodies in nanoparticles using the radiolabeling process with technetium 99 metastable as primary factor: Alternative methodology for the entrapment efficiency.
The use of monoclonal antibodies (Mab) in the current medicine is increasing. Antibody-drug conjugates (ADCs) represents an increasingly and important modality for treating several types of cancer. In this area, the use of Mab associated with nanoparticles is a valuable strategy. However, the methodology used to calculate the Mab entrapment, efficiency and content is extremely expensive. In this study we developed and tested a novel very simple one-step methodology to calculate monoclonal antibody entrapment in mesoporous silica (with magnetic core) nanoparticles using the radiolabeling process as primary methodology. The magnetic core mesoporous silica were successfully developed and characterised. The PXRD analysis at high angles confirmed the presence of magnetic cores in the structures and transmission electron microscopy allowed to determine structures size (58.9 ± 8.1 nm). From the isotherm curve, a specific surface area of 872 m2/g was estimated along with a pore volume of 0.85 cm3/g and an average pore diameter of 3.15 nm. The radiolabeling process to proceed the indirect determination were well-done. Trastuzumab were successfully labeled (>97%) with Tc-99m generating a clear suspension. Besides, almost all the Tc-99m used (labeling the trastuzumab) remained trapped in the surface of the mesoporous silica for a period as long as 8 h. The indirect methodology demonstrated a high entrapment in magnetic core mesoporous silica surface of Tc-99m-traztuzumab. The results confirmed the potential use from the indirect entrapment efficiency methodology using the radiolabeling process, as a one-step, easy and cheap methodology.


Molecular effects of cyclosporine and oncogenesis: a new model.
Cyclosporine A is the most commonly used immunosuppressive agent during organ transplantation. One of the most feared adverse effects of cyclosporine A is the appearance of de novo cancers. The mechanisms that lead to the genesis of such cancers are thought to be only related to a side effect of cyclosporine A: a depressed immune system. Here, we review different molecular effects induced by cyclosporine A (inhibition of DNA repair, synthesis of TGF Beta, induction of apoptosis of activated T cells, inhibition of apoptosis through the inhibition of the opening of the mitochondrial Permeability Transition Pore) and propose that cyclosporine A can promote the genesis and the spread of cancer not only because of immunosuppression but also because of its ability to facilitate DNA mutations accumulation, to diminish the clearance of altered cells and to transform cancer cells into aggressive cancer cells. This new insights into the mechanisms of genesis of cyclosporine A-related cancers should be taken into account to develop preventive strategies or new immunosuppressive strategies.


Brain vascular malformations in the fetus: diagnosis and prognosis.
DIAGNOSIS OF BRAIN VASCULAR MALFORMATIONS IN THE FETUS: Vein of Galen aneurysms can be diagnosed in utero. Other malformations are not seen. Ultrasound makes the diagnosis by showing a "cystic" structure in the posterior fossa. Colour Doppler shows the high flow. The prognosis can be established by MRI. Bad prognosis factors are brain atrophy, cardiac insufficiency and complexity of the malformation. If these factors are absent, postnatal treatment by embolisation can be scheduled.


Effect of Ozonation on the biodegradability of atrazine in GAC columns.
The biodegradation of atrazine as influenced by preozonation was studied in biological GAC columns. Metabolism of isopropyl-14C atrazine produced more 14CO2 than ring-UL-14C atrazine, indicating dealkylation was more rapid than ring cleavage. Preozonation increased mineralization of ring-UL-14C atrazine and, consequently, enhanced the performance of GAC columns. Sixty-two percent of the influent atrazine was converted to 14CO2 in columns that received ozonated atrazine and ozonated surface water, while 50% of the influent atrazine was converted to 14CO2 in columns that received untreated atrazine and ozonated surface water, and only 38% of the influent atrazine was converted to 14CO2 in columns with untreated influent.


Effect of decentration and tilt on the image quality of aspheric intraocular lens designs in a model eye.
To determine the impact of decentration and tilt on the imaging quality of aspheric intraocular lens (IOL) designs in a schematic model eye. Institute of Medical Physics, University of Erlangen-Nuremberg, Erlangen, Germany. A model eye was used to calculate the impact of misalignment on the imaging quality of 6 IOL designs. The crystalline lens in the model eye was replaced with IOL designs with 22.0 diopters nominal refractive power, and the anterior chamber depth (ACD) was set to the estimated ACD value provided by the manufacturer. The retinal position was optimized for the best image quality. The IOLs were decentered up to +/-1.0 mm and tilted up to +/-5 degrees relative to the line of sight. At each position, the modulation transfer function was recorded with 3.0 mm and 4.5 mm pupil diameters. The results between the IOL designs and those of the phakic model eye were then compared. Aberration-correcting IOLs were very sensitive to decentration and tilt. However, the impact of misalignment depended on IOL design. Aberration-free IOLs showed less sensitivity within a wide range of displacement but provided better results than the spherical IOL. Overall, modern aspheric IOLs provided better imaging quality than conventional spherical IOL designs. Aberration-free IOLs were less sensitive to decentration and tilt than aberration-correcting IOLs but provided better image quality than spherical IOLs. Aberration-correcting IOLs have the potential to provide diffraction-limited imaging quality when perfectly aligned.


A new synthesis of allyl sulfoxides via nucleophilic addition of sulfinyl carbanions to group 6 Fischer carbene complexes.
[reaction: see text] A novel synthesis of allyl sulfoxides has been developed. Primary alpha-lithiosulfinyl carbanions react with group 6 Fischer carbene complexes to give allyl sulfoxides as products. The Fischer carbene complex experiments involve a 1,2-addition of two molecules of sulfinyl carbanion to give an intermediate that, after a beta-elimination, furnishes the mentioned product.


Interpretation of scattering by oceanic particles around 120 degrees and its implication in ocean color studies.
Field observations and theoretical studies have found that the volume scattering functions (VSFs) of oceanic particles exhibit minimum variability at angles near 120°. However, its physical interpretation is still unknown. We find this minimum variability angle represents the intersection of two backscattering-normalized VSFs, one representing particles of sizes smaller than the wavelength of light and the other larger than the wavelength of light. This also suggests that the VSFs of oceanic particles at angles between 90° and 180°, which play a critical role in ocean color study, can be modeled by linear mixing of these two end members. We further validate this mixing model using measured VSFs in coastal and oceanic waters around the US and develop a two-component model predicting the backward shapes of the VSFs.


Identification and validation of the mitochondrial F1F0-ATPase as the molecular target of the immunomodulatory benzodiazepine Bz-423.
Bz-423 is a 1,4-benzodiazepine that suppresses disease in lupus-prone mice by selectively killing pathogenic lymphocytes, and it is less toxic compared to current lupus drugs. Cells exposed to Bz-423 rapidly generate O(2)(-) within mitochondria, and this reactive oxygen species is the signal initiating apoptosis. Phage display screening revealed that Bz-423 binds to the oligomycin sensitivity conferring protein (OSCP) component of the mitochondrial F(1)F(0)-ATPase. Bz-423 inhibited the F(1)F(0)-ATPase in vitro, and reconstitution experiments demonstrated that inhibition was mediated by the OSCP. This target was further validated by generating cells with reduced OSCP expression using RNA interference and studying the sensitivity of these cells to Bz-423. Our findings help explain the efficacy and selectivity of Bz-423 for autoimmune lymphocytes and highlight the OSCP as a target to guide the development of novel lupus therapeutics.


Hepatic cytochrome P450 and related drug biotransformation during an outbreak of mouse hepatitis virus in a colony of Swiss BALB/c mice.
Mouse hepatitis is a common highly infectious virus of the Coronaviridae family that commonly infects laboratory colonies of BALB/c mice. In a natural outbreak of this disease in our institution we demonstrated that mouse hepatitis virus appears to have little or no effect on the levels of cytochrome P450 or on the activities of ethoxyresorufin O-dealkylase and benzyloxy resorufin O-dealkylase in hepatic microsomes. Antibody titers for the virus were elevated in all mice tested and were negative in a control uninfected group. In a number of studies carried out over a period of months during the active outbreak we did not observe lower levels of cytochrome P450 in comparison with infectious free periods. Although the activation of host defence mechanisms and infections are well known to diminish the cytochrome P450 enzyme system in the liver, these results indicate that during a period of confirmed active infection with mouse hepatitis virus there was no evidence of an impairment in drug biotransformation enzymes.


Functional promoter variant in zinc finger protein 202 predicts severe atherosclerosis and ischemic heart disease.
This study was designed to test the hypotheses that single nucleotide polymorphisms (SNPs), in zinc finger protein 202 (ZNF202), predict severe atherosclerosis and ischemic heart disease (IHD). ZNF202 is a transcriptional repressor controlling promoter elements in genes involved in vascular maintenance and lipid metabolism. We first determined genotype association for 9 ZNF202 SNPs with severe atherosclerosis (ankle brachial index >0.7 vs. <or=0.7) in a cross-sectional study of 5,355 individuals from the Danish general population. We then determined genotype association with IHD in 10,431 individuals from the Danish general population, the CCHS (Copenhagen City Heart Study), including 1,511 incident IHD events during 28 years of follow-up. Results were verified in 2 independent case-control studies including, respectively, 942 and 1,549 cases with IHD and 8,998 controls. Finally, we determined whether g.-660A>G altered transcriptional activity of the ZNF202 promoter in vitro. Cross-sectionally, ZNF202 g.-660 GG versus AA homozygosity predicted an odds ratio for severe atherosclerosis of 2.01 (95% confidence interval [CI]: 1.34 to 3.01). Prospectively, GG versus AA homozygosity predicted a hazard ratio for IHD of 1.21 (95% CI: 1.02 to 1.43). In the 2 case-control studies, the equivalent odds ratios for IHD were 1.29 (95% CI: 1.02 to 1.62) and 1.60 (95% CI: 1.34 to 1.92), confirming the results from the prospective study. Only 2 other SNPs, which were highly correlated with g.-660A>G, also predicted risk of severe atherosclerosis and IHD. Finally, ZNF202 g.-660G versus g.-660A was associated with a 60% reduction in transcriptional activity in vitro, whereas none of the 2 correlated SNPs were predicted to be functional. Homozygosity for a common functional promoter variant in ZNF202 predicts severe atherosclerosis and an increased risk of IHD.


Tachykinin receptor expression and function in human esophageal smooth muscle.
Tachykinins are present in enteric nerves of the gastrointestinal tract and cause contraction of esophageal smooth muscle; however, the mechanisms involved are not understood. Our aim was to characterize tachykinin signaling in human esophageal smooth muscle. We investigated functional effects of tachykinins on human esophageal smooth muscle using tension recordings and isolated cells, receptor expression with reverse transcription (RT)-polymerase chain reaction (PCR) and immunoblotting, intracellular Ca2+ responses using fluorescent indicator dyes, and membrane currents with patch-clamp electrophysiology. The mammalian tachykinins [substance P and neurokinin (NK) A and NKB] elicited concentration-dependent contractions of human esophageal smooth muscle. These responses were not affected by muscarinic receptor or neuronal blockade indicating a direct effect on smooth muscle cells (SMCs). Immunofluorescence and RT-PCR identified tachykinin receptors (NK1, NK2, and NK3) on SMCs. Contraction was mediated through a combination of Ca2+ release from intracellular stores and influx through L-type Ca2+ channels. NK2 receptor blockade inhibited the largest proportion of tachykinin-evoked responses. NKA evoked a nonselective cation current (I(NSC)) with properties similar to that elicited by muscarinic stimulation. The following paradigm is suggested: tachykinin receptor binding to SMCs releases Ca2+ from stores along with activation of I(NSC), which in turn results in membrane depolarization, L-type Ca2+ channel opening, rise of Ca2+ concentration, and contraction. These studies reveal new aspects of tachykinin signaling in human esophageal SMCs. Excitatory tachykinin pathways may represent targets for pharmacological intervention in disorders of esophageal dysmotility.


[Surveillance of gastroenteritic infections in lower Saxony: results and experiences from a regional public-health project over six years].
In Lower Saxony, a regional public health project on a pathogen-specific surveillance of Enteritis infectiosa was carried out from 1994 to 2000. In a separate reporting procedure thirteen health departments transmitted data on the specific pathogen collected from laboratory reports for a joint analysis. The results were distributed among the participants, providing them with information on the situation and trends in their districts and in addition giving them the possibility to compare their data with those of other districts. The incidence of Enteritis infectiosa was 199 reported cases per 100,000 person years. Salmonella was reported most frequently (51 %; S. enteritidis: 33 %, S. TYPHIMURIUM: 14 %, 111 other serotypes: 4 %), followed by Campylobacter (18 %), Rotavirus (17 %), Yersinia enterocolitica (6 %) and Adenovirus (5 %). The incidences of Salmonella and Yersinia enterocolitica were found to be nearly constant over the project period while the incidences of Campylobacter, Rotavirus and Adenovirus increased. This, however, may be due to intensified diagnostics and better reporting behaviour rather than to a real increase. The incidence rates and their trends differed from other German states. This observation emphasizes the need for a regional analysis of infectious disease surveillance data.


Hedgehog signaling pathway: development of antagonists for cancer therapy.
The hedgehog pathway, initially discovered in Drosophila by two Nobel laureates, Dr. Eric Wieschaus and Dr. Christiane Nüsslein-Volhard, is a major regulator for cell differentiation, tissue polarity, and cell proliferation. Studies from many laboratories--including ours--reveal activation of this pathway in most basal cell carcinomas and nearly one third of extracutaneous human cancers, including medulloblastomas and gastrointestinal and prostate cancers. Even more exciting is the discovery and synthesis of specific signaling antagonists for the hedgehog pathway, which have significant clinical implications in novel cancer therapeutics. This review discusses the current understanding of the hedgehog signaling pathway and its activation in human cancers. It also discusses putative and confirmed signaling antagonists and their perspectives in therapeutic applications.


Premature chromatin condensation induced by loss of RCC1 is inhibited by GTP- and GTPgammaS-Ran, but not GDP-Ran.
RCC1 is a guanine nucleotide exchanging factor acting on nuclear G protein Ran. Premature chromatin condensation occurs in the temperature-sensitive rcc1- mutant of the BHK21 cell line, tsBN2, at the restrictive temperature. This observation can be explained if the premature activation of MPF is normally inhibited by GTP-Ran. In the absence of RCC1, GDP-Ran predominates, resulting in MPF activation. However, experiments with Ran mutants to determine whether GTP- or GDP-Ran prevents activation of MPF have yielded conflicting results. In order to clarify this point, we have microinjected nucleotide-bound Ran, instead of mutated Ran, into the nuclei of tsBN2 cells treated to reduce RCC1-mediated guanine nucleotide exchange. GTP-Ran, GTPgammaS-Ran, and GDP-Ran all inhibited chromatin condensation. However, the inhibition of chromatin condensation by GDP-Ran could be completely abolished by co-injection with GDP, but not GTP. Thus, we conclude that GTP-Ran blocks the activation of MPF and that hydrolysis of GTP is not required to prevent MPF activation.


[Diabetes mellitus type II: when convert to insulin?].
About 5% of patients with type II diabetes per year have to switch over to an insulin regimen because of critical metabolic disturbances. This becomes particularly urgent in catabolic states. Further situations necessitating an insulin regimen are secondary failure of oral antidiabetic therapy, painful peripheral neuropathy and late manifestations of type I diabetes (late autoimmune diabetes mellitus in adults, LADA). Today's state of knowledge suggests for the change to an insulin regimen to start with bedtime injections of depot insulin, eventually combined with oral medication over the day. This regimen allows to keep the weight increase lower than with two or more insulin injections. Exogen insulin substitution ameliorates typical abnormalities in type II diabetes, such as increased hepatic glucose production, reduced peripheral glucose utilization, reduced function of beta-cells and dyslipidemia. It carries, however, the risk for hypoglycemia and weight-increase.


Paclitaxel-coated balloon reduces target lesion revascularization compared with standard balloon angioplasty.
Peripheral arterial disease (PAD) is a highly prevalent condition that contributes significantly to the morbidity and mortality of affected patients. PAD creates a significant economic burden on health care systems around the world. We reviewed all available literature to provide a meta-analysis assessing the outcome of patients treated with drug-eluting balloons (DEBs) compared with percutaneous transluminal balloon angioplasty (PTA) through measuring the rate of target lesion revascularization (TLR). An electronic search of the MEDLINE, Scopus, Embase, Web of Science, and Cochrane Library databases was performed. Articles reporting randomized controlled trials that compared treatment with DEBs vs PTA were selected for inclusion. A meta-analysis was performed by pooling data on rates of TLR, binary restenosis (BR), and late lumen loss (LLL). The 10 included articles comprised a sample size of 1292 patients. Meta-analysis demonstrated the rate of TLR in DEB-treated patients was significantly lower compared with patients treated with PTA at 6 months (odds ratio [OR], 0.24; 95% confidence interval [CI], 0.11-0.53; P = .0004), 12 months (OR, 0.28; 95% CI, 0.13-0.62; P = .002), and 24 months (OR, 0.25; 95% CI, 0.10-0.61; P = .002). Decreased LLL and BR was demonstrated at 6 months in patients treated with DEBs compared with patients treated with PTA (mean difference, -0.74; 95% CI, -0.97 to -0.51; P = .00001; OR, 0.34; 95% CI, 0.23-0.49; P = .00001). This meta-analysis demonstrates that treatment with DEBs compared with PTA results in reduced rates of reintervention in patients with PAD. Comparison of DEBs to other emerging treatments to determine which method results in the lowest reintervention rates and in the greatest improvement in quality of life should be the focus of future trials.


Aging in community: mobilizing a new paradigm of older adults as a core social resource.
Dignity and independence are widely considered as core concepts to aging well, yet little research has explored how older adults perceive these issues in the context of community life. Moreover, little is known regarding the ways in which the broader public views and enhances aging with dignity and independence with their older residents. Using participatory action research, multiple methods of qualitative inquiry, and tenets of appreciative inquiry, this article reports on a community-based initiative aimed to better understand the positive aspects of aging with dignity and independence. Synthesized findings yielded 6 "actionable themes": (1) meaningful involvement, (2) aging in place, (3) respect and inclusion, (4) communication and information, (5) transportation and mobility, and (6) health and well-being. The findings invoke a new paradigm for community aging that highlights the unique contributions of older adults as a core social resource. Implications for mobilizing community action to promote aging with dignity and independence are discussed.


Localization of apoptotic cells in the cystic ovarian follicles of cows: a DNA-end labeling histochemical study.
We examined the frequency of apoptosis in cystic follicular cells to investigate the cause of the delay in regression of cystic follicles. Paraffin sections of healthy antral follicles, early and late atretic ones, and early and late cystic ones were stained using the terminal deoxynucleotidyl transferase (Tdt)-mediated biotinylated deoxyuridine triphosphates (dUTP) nick end-labeling (TUNEL) method to detect apoptotic cells. In the granulosa layer of early cystic and atretic follicles, TUNEL-positive cells were evident. In the theca interna of both early and late atresia, high frequencies of TUNEL-positive cells were observed. In the theca interna, a high frequency of TUNEL-positive cells was noted in the early cystic follicles, whereas their frequency decreased in late cystic follicles. These results suggest that apoptosis occurs in the granulosa and theca interna cells of cystic as well as atretic follicles, but the frequency of apoptosis in theca interna cells decreases in late cystic follicles, which may be responsible for the delay of follicular regression.


HLA-Ig-based artificial antigen-presenting cells: setting the terms of engagement.
Recent advances in molecular medicine have shown that soluble MHC-multimers can be valuable tools for both the stimulation of as well as the analysis of antigen-specific T cells in vitro. In this review, we describe the use of dimeric major histocompatibility complexes, HLA-Ig, to visualize antigen-specific T cells as well as their potential to stimulate immune responses as part of an artificial antigen-presenting cell (aAPC). The use of HLA-Ig-based aAPC represents an exciting new approach to generate antigen-specific CTL for adoptive immunotherapy that helps to overcome many of the obstacles associated with limitations in current approaches to adoptive immunotherapy.


Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement for Severe Aortic Stenosis in Patients With Chronic Kidney Disease Stages 3b to 5.
There are scarce data on outcomes after transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) in patients with renal failure. We evaluated the impact of renal failure on outcomes after TAVI and SAVR and compared the results of these procedures in patients with chronic kidney disease stages 3b to 5 from the Observational Study of Effectiveness of AVR-TAVI Procedures for Severe Aortic Stenosis Treatment (OBSERVANT) study. Chronic kidney disease (CKD) stages 3b to 5 was associated with an increased risk of mortality after either TAVI or SAVR compared with CKD stages 1 to 3a. Among 170 propensity score-matched pairs with CKD stages 3b to 5, patients who underwent TAVI had a significantly higher rate of permanent pacemaker implantation, vascular damage, and mild to moderate paravalvular regurgitation, and tended to have a higher 30-day mortality (7.1% versus 2.9%; p = 0.09). Thirty-day mortality after transapical TAVI was 7.1%. SAVR had a significantly higher rate of blood transfusions, stroke, and acute kidney injury. At 2 years, patients undergoing TAVI had somewhat higher all-cause mortality (31.2% versus 23.4%; p = 0.118), major cardiac and cerebrovascular events (37.2% versus 31.0%; p = 0.270), and a lower risk of dialysis (12.4% versus 21.2%; p = 0.052) compared with SAVR. CKD stages 3b to 5 increases the risk of mortality after TAVI and SAVR. In this subset of patients, SAVR was associated with somewhat better early and late survival. The risk of acute kidney injury was higher after SAVR. These findings suggest that CKD stages 3b to 5 does not contraindicate SAVR. Strategies to prevent severe acute kidney injury should be implemented with either SAVR or TAVI.


Contemporary management of frontal sinus mucoceles: a meta-analysis.
To analyze trends in the surgical management of frontal and fronto-ethmoid mucoceles through meta-analysis. Meta-analysis and case series. A systematic literature review on surgical management of frontal and fronto-ethmoid mucoceles was conducted. Studies were divided into historical (1975-2001) and contemporary (2002-2012) groups. A meta-analysis of these studies was performed. The historical and contemporary cohorts were compared (surgical approach, recurrence, and complications). To study evolution in surgical management, a senior surgeon's experience over 28 years was analyzed separately. Thirty-one studies were included for meta-analysis. The historical cohort included 425 mucoceles from 11 studies. The contemporary cohort included 542 mucoceles from 20 studies. More endoscopic techniques were used in the contemporary versus historical cohort (53.9% vs. 24.7%; P = <0.001). In the authors' series, a higher percentage was treated endoscopically (82.8% of 122 mucoceles). Recurrence (P = 0.20) and major complication (P = 0.23) rates were similar between cohorts. Minor complication rates were superior for endoscopic techniques in both cohorts (P = 0.02 historical; P = <0.001 contemporary). In the historical cohort, higher recurrence was noted in the external group (P = 0.03). Results from endoscopic and open approaches are comparable. Although endoscopic techniques are being increasingly adopted, comparison with our series shows that more cases could potentially be treated endoscopically. Frequent use of open approaches may reflect efficacy, or perhaps lack of expertise and equipment required for endoscopic management. Most contemporary authors favor endoscopic management, limiting open approaches for specific indications (unfavorable anatomy, lateral disease, and scarring). N/A.


Pulmonary nodules and metastases in colorectal cancer.
Patients with newly diagnosed colorectal cancer (CRC) are subjected to a preoperative thoraco-abdominal CT scan to determine the cancer stage. This staging is of relevance with regard to treatment and prognosis. About 20% of the patients have distant metastatic spread at the time of diagnosis, i.e. synchronous metastases. Most common are hepatic metastases followed by pulmonary involvement. The optimal staging modality for detecting synchronous pulmonary metastases is debated. It has been argued, that synchronous pulmonary metastases (SPCM) are rare in CRC and that the consequence of detecting SPCM is minimal. Furthermore, the current staging practice is complicated by a high number of incidental findings on the thoracic CT, so-called indeterminate pulmonary nodules (IPN). IPN can potentially represent SPCM. The purpose of this thesis was to estimate the prevalence, characteristics and clinical significance of IPN and SPCM detected at the primary staging in CRC. Study I was a systematic review of published studies on IPN in CRC focusing on the prevalence and radiological characteristics of IPN proving to be malignant. This knowledge would be of value in management strategies for IPN. On average 9% of all patients staged with a thoracic CT had IPN, however, the prevalence varied significantly between patients series. This was mainly attributed to varying/lacking definitions on IPN and variable radiological expertise in the assessment of the scans. Data were too inconsistently reported in the case series for a robust statement to be made on potential radiological characteristics suggestive of malignancy in IPN. Lymph node metastasis was the most common clinicopathological finding associated with malignancy of IPN. In conclusion, one patient of every 100 scanned patients had an IPN proving to a SPCM at follow-up, but we found no evidence that IPN should result in intensified diagnostic work-up besides routine follow-up for CRC. Study II was an analysis of the prevalence of and risk factors for SPCM in a Danish nationwide cohort of patients with newly diagnosed CRC from 2001 to 2011. SPCM were detected in 7.5% of the patients and in 37% of these cases the metastatic spread was confined to the lungs. The prevalence of SPCM increased with the implementation of thoracic CT in CRC staging. SPCM impaired survival significantly and was associated with increasing age and rectal cancer. Resection of the primary tumour, resection of the SPCM and treatment with chemotherapy were associated with improved survival. Unfortunately, however, only very few patients were subjected to all three treatment measures, and the improved prognosis could simply be the result of a selection bias. The inter-observer variation in classification of findings at thoracic CT scans was investigated in study III and was based on staging CT scans from a local cohort of patients with newly diagnosed CRC. Based on an experienced thoracic radiologist's assessment of the scans, we searched for radiological characteristics of IPN that could predict malignancy of the nodule. There was a significant difference in the number of IPNs detected between the primary and the thoracic radiologist's assessment. The thoracic radiologist classified fewer nodules as IPN and even reported with higher specificity and sensitivity for SPCM. More than 20% of IPNs (as classified by the thoracic radiologist) proved to be SPCM. Unfortunately, no radiological characteristics could be associated with a malignant outcome. In continuation of these findings we suggested a secondary review of scans with IPN be a group of dedicated thoracic radiologists. This approach might reduce the need for additional work-up for IPN and calls for clarification in future prospective studies. Identification of patients in particular risk of SPCM could be of value in the assessment of pulmonary nodules. Several biomarkers have been proposed for differential metastatic patterns in CRC. In study IV we investigated the significance of mismatch repair status (MMR) for the location of metastatic spread in a nationwide Danish cohort of patients with newly diagnosed CRC between 2010 and 2012. Deficient MMR was associated with a reduced risk of synchronous metastatic disease, however, the risk reduction only applied to hepatic metastases. MMR had no impact on SPCM and is therefore currently of no use in the assessment of IPN.


Two types of mitochondrial crystals in diseased human skeletal muscle fibers.
Mitochondrial crystalline inclusions, frequently found in mitochondrial myopathies, were analyzed by crystallographic techniques and computer-aided image processing. It could be shown that these structures were real crystals. There are two distinct types of crystal, which can be distinguished by shape, size, and pattern. So-called type I crystals are usually present in the intracristal space, whereas the type II crystals are preferentially located in the intermembrane space between outer and inner mitochondrial membranes. The unit cell dimensions were found to be 38 x 34 x 8 nm for the type I crystals and 20 x 17 x 8 nm for the type II crystals. These results strongly suggest that the crystals are composed of macromolecules, presumably proteins. Arguments are presented that indicate that type I crystals occur only in type 1 muscle fibers and type II crystals in type 2 muscle fibers.


Eimeria spp. (Apicomplexa: Eimeriidae) from great horned owls, Bubo virginianus (Gmelin) (Aves: Strigiformes) from Arkansas and Oklahoma, USA, with novel molecular information on Eimeria bubonis Cawthorn & Stockdale, 1981.
Although nine nominal species of Eimeria Schneider, 1875 have been reported from owls (Strigiformes Wagler), molecular data are available for only one, Eimeria megabubonis Upton, Campbell, Weigel & McKown, 1990. This species has been reported from the great horned owl, Bubo virginianus (Gmelin) at the type-locality of Kansas, USA, and the additional localities of Oklahoma and Mississippi, USA. Eimeria bubonis Cawthorn & Stockdale, 1981, also from B. virginianus, is represented in the literature only by its original description from Saskatchewan, Canada. The present work reports a novel host locality of E. bubonis from B. virginianus in Arkansas, USA. Additionally, novel molecular data from the 18S ribosomal RNA gene and the cytochrome c oxidase subunit 1 mitochondrial gene is provided for E. bubonis. Phylogenetic analysis using the newly generated and previously published sequence data for Eimeria spp. is also presented.


Prandtl number scaling of unsteady natural convection boundary layers for Pr>1 fluids under isothermal heating.
In this paper, the scalings incorporating the Prandtl number (Pr) dependence have been obtained by a scaling analysis for the unsteady natural convection boundary layer of an initially quiescent isothermal Newtonian fluid of Pr>1 produced by the sudden imposition of a higher temperature on a vertical plate. It is shown that the transient flow behavior of the resulting boundary layer can be described by a three-region structure and at the start-up stage the boundary layer development is one dimensional and independent of height due to the dominance of pure conduction; however, at steady state it becomes two dimensional and height dependent as the flow becomes dominated by convection. Numerical results demonstrate that the scalings representing the thermal boundary layer development accurately represent their Pr dependence over the whole stage of flow development. The scalings representing the viscous boundary layer development are generally in good agreement with the numerical results with the Pr variation over the whole stage of flow development, although there are small deviations from the numerical results with the Pr variation that are within acceptable limits for scaling.


Bacterial communities associated with the midgut microbiota of wild Anopheles gambiae complex in Burkina Faso.
Plasmodium falciparum is transmitted by mosquitoes from the Anopheles gambiae sensu lato (s.l) species complex and is responsible for severe forms of malaria. The composition of the mosquitoes' microbiota plays a role in P. falciparum transmission, so we studied midgut bacterial communities of An. gambiae s.l from Burkina Faso. DNA was extracted from 17 pools of midgut of mosquitoes from the Anopheles gambiae complex from six localities in three climatic areas, including cotton-growing and cotton-free localities to include potential differences in insecticide selection pressure. The v3-v4 region of the 16S rRNA gene was targeted and sequenced using Illumina Miseq (2 × 250 nt). Diversity analysis was performed using QIIME and R software programs. The major bacterial phylum was Proteobacteria (97.2%) in all samples. The most abundant genera were Enterobacter (32.8%) and Aeromonas (29.8%), followed by Pseudomonas (11.8%), Acinetobacter (5.9%) and Thorsellia (2.2%). No statistical difference in operational taxonomic units (OTUs) was found (Kruskal-Wallis FDR-p > 0.05) among the different areas, fields or localities. Richness and diversity indexes (observed OTUs, Chao1, Simpson and Shannon indexes) showed significant differences in the cotton-growing fields and in the agroclimatic zones, mainly in the Sudano-Sahelian area. OTUs from seven bacterial species that mediate refractoriness to Plasmodium infection in An. gambiae s.l were detected. The beta diversity analysis did not show any significant difference. Therefore, a same control strategy of using bacterial species refractoriness to Plasmodium to target mosquito midgut bacterial community and affect their fitness in malaria transmission may be valuable tool for future malaria control efforts in Burkina Faso.


Role of STAT3 decoy oligodeoxynucleotides on cell invasion and chemosensitivity in human epithelial ovarian cancer cells.
Recent studies have reported that STAT3 activation is associated with poor prognosis in human epithelial ovarian cancer. STAT3 has been proposed to play an important role in ovarian cancer metastasis and chemoresistance. This mechanism, however, is still not thoroughly understood. In this study, to investigate the role of STAT3 on ovarian cancer cells, we used decoy oligodeoxynucleotide (ODN) technology to regulate STAT3 in SKOV3 and OVCAR3 cells in vitro. Cell invasive power and chemo-sensitivity were assessed in the cells transfected with STAT3 decoy ODN and control ODN. Western blot analysis was used to examine the expression of EMMPRIN, P-gp, and Akt. Results showed that STAT3 decoy ODN inhibited cancer cell invasive power and enhanced sensitivity to paclitaxel for SKOV3 and OVCAR3 cells. The mechanism involved the inhibition of EMMPRIN, P-gp, and pAkt by STAT3 decoy ODN. These three proteins were probably the target proteins of STAT3. These findings suggest that STAT3 is a key factor for ovarian cancer metastasis and chemoresistance. STAT3 decoy ODN may prove to be a beneficial therapeutic agent, especially for invasive or chemoresistant ovarian cancer.


[Diagnosis and treatment of tethered spinal cord syndrome--based on experience of 77 cases].
Since 1976, the author has experienced 77 cases that have been diagnosed as the tethered spinal cord syndrome. These cases could be divided into two groups by the relative level of conus medullaris to that of L3 body, i.e. 34 cases in which the conus medullaris is tethered below the superior border of L3 body were classified into low placed conus medullaris (LPCM) and 43 in which the conus medullaris is located above the same level into the tight filum terminale (TFT). As to symptoms and signs, incontinence, gait disturbance, foot and toe deformities, lumbosacral tumor and sacral dimple were seen more often in the LPCM group. On the other hand, nocturia, pain in the back and in the lower limbs, positive Lasègue sign and tight back were seen more often in the TFT group. Neurological signs were seen more often in the LPCM group. In 3 cases of LPCM, and 10 of TFT, spina bifida was not visualized on the plain X-ray film of the spinal column. LPCM could be definitively diagnosed by myelography taken with the patient lying in the supine position, on the other hand myelography did not always give definitive diagnosis of TFT. Surgery for releasing the tethering conus was carried out in 58 of 77 cases. Of which 49 have been followed up more than 2 months after operation. Some degree of improvement of various symptomes and signs, was noted in 35 (68%) of these patients.


Effect of nebivolol vs. hydrochlorothiazide on the walking capacity in hypertensive patients with intermittent claudication.
Whereas product labels of beta blockers list peripheral arterial disease (PAD) as a contraindication, current PAD guidelines state otherwise. We aimed to evaluate the clinical efficacy and safety of the ß(1) selective blocker nebivolol in hypertensive patients with PAD. This multicentre, prospective, double-blind, active controlled, parallel-group study compared once-daily treatment with nebivolol (Neb) 5 mg vs. hydrochlorothiazide (HCTZ) 25 mg, in hypertensive patients with Fontaine stage II (intermittent claudication). The primary endpoint was the initial claudication distance (ICD) during treadmill exercise after 24-week treatment in the per protocol population, using a noninferiority statistical approach. A total of 177 patients (mean age was 66.3 ± 9.2 years, 76.7% men) were randomized to study treatment and 127 completed the study; the intent-to-treat (ITT) analysis was performed on 163 patients, the per protocol analysis on 127 patients. Both drugs lowered blood pressure significantly. After 24-week treatment, ICD increased in the Neb group in the ITT population by 28.3% (95% CI 15.6-41.0) vs. in the HCTZ group by 26.5% (14.4-38.5), and in the per protocol population in the Neb group by 26.4% (13.4-39.4) vs. in the HCTZ group by 32.1% (18.4-45.7). Thus, noninferiority of Neb could neither be confirmed nor rejected. An increase of absolute claudication distance (ACD, mean percentage increase after 24 weeks on Neb 15.8 ± 33.2 vs. on HCTZ 20.2 ± 46.6) was observed without statistical differences between groups. Ankle-brachial index (ABI) increased slightly in both groups. Generally, both treatments were well tolerated. The increases in ICD, ACD and ABI with nebivolol suggest that this medication does not have negative effects on hypertensive patients with symptomatic PAD, and can be used for treatment of hypertension in these patients at high cardiovascular risk without reducing the walking ability.


Apolipoprotein E in Cardiovascular Diseases: Novel Aspects of an Old-fashioned Enigma.
The presence of different APOE isoforms represents a well-known risk factor for cardiovascular diseases. Besides the pleiotropic effects of APOE polymorphism on heart and neurological diseases, this review summarizes the less-known functions of APOE and the possible implications for cardiovascular disorders. Beyond the role as lipid transporting protein, its involvement in lipid membrane homeostasis and signaling, as well as its nuclear transcriptional effects suggests a more complex role of APOE, receiving great interest from researchers and physicians from all medical fields. Due to the presence of different APOE isoforms in human population, understanding APOE's role in pathological processes represents not only a challenge, but a demand for further development of therapeutic strategies for cardiovascular diseases.


Detection of 1q polysomy in interphase nuclei of human solid tumors with a biotinylated probe.
A biotinylated probe (L23-21) specific for the 1q12 band of human karyotype was used to detect the 1q segment in interphase nuclei of breast and colon carcinomas. This probe was selected because trisomy or polysomy 1q is the most frequent chromosomal change observed in solid tumors. This method enables cancerous cells, including near-diploid ones carrying an unbalanced rearrangement of 1q, to be easily identified.


Identification and Characterization of the First Selective Y4 Receptor Positive Allosteric Modulator.
The human Y4 receptor (Y4R) and its cognate ligand, pancreatic polypeptide (PP), are involved in the regulation of energy expenditure, satiety, and food intake. This system represents a potential target for the treatment of metabolic diseases and has been extensively investigated and validated in vivo. Here, we present the compound tBPC (tert-butylphenoxycyclohexanol), a novel and selective Y4R positive allosteric modulator that potentiates Y4R activation in G-protein signaling and arrestin3 recruitment experiments. The compound has no effect on the binding of the orthosteric ligands, implying its allosteric mode of action at the Y4R and evidence for a purely efficacy-driven positive allosteric modulation. Finally, the ability of tBPC to selectively potentiate Y4R agonism initiated by PP was confirmed in mouse descending colon mucosa preparations expressing native Y4R, demonstrating Y4R positive allosteric modulation in vitro.


Prostate Cancer Screening.
To review the current state of prostate cancer screening and future directions. Nursing, medical and scientific literature related to prostate cancer screening, and national and international professional recommendations. Prostate cancer screening has been a topic of robust discussion for a number of years. Research continues to examine novel options for prostate cancer screening to either replace or compliment the prostate specific antigen test, but require additional validation before they will be widely accepted into clinical practice. As new data emerges and professional organizations update their recommendations, it is important for oncology nurses to keep abreast of the latest developments to educate patients.


Screening for Cervical Cancer Among Low-Risk Populations: Orthodox Jewish Women as a Model.
To explore the prevalence of abnormal Papanicolaou (PAP) smears among asymptomatic Orthodox Jewish women, characterized by conservative sexual habits, in comparison to secular Jewish women. A retrospective analytical cohort study of 600 consecutive PAP smears, performed as a screening test on asymptomatic Orthodox Jewish women (mean age 43.4 ± 12.6 years), compared to 600 consecutive smears performed on secular Jewish women (mean age 38.2 ± 11.5 years). Primary outcome measures comprised incidence and clinical significance of abnormal cytological findings among the two subgroups. Secondary outcome measures included possible risk factors for abnormal cytological findings within the study population. In the Orthodox group, only seven (1.2%) PAP smears were interpreted as abnormal, compared with 33 (5.5%) abnormal smears among the secular group (p < 0.001). All seven abnormal PAP smears from the Orthodox Jewish group were classified as atypical squamous cells of undetermined significance (ASCUS), compared with 16 ASCUS smears and 17 low-grade squamous intraepithelial lesion smears in the secular group (2.67% and 2.83% of the secular women, respectively). The vast majority of ASCUS cases in the Orthodox Jewish group were followed up with repeated normal PAP smears. The incidence rate of abnormal PAP smears taken as a routine screening test among Orthodox Jewish women is very low (1.2%). Furthermore, the vast majority of abnormal smears in these women were later found to be false positive, with no clinical significance. These findings raise doubt as to the need for systematic screening and/or comprehensive vaccination against the papilloma virus among low-risk populations.


Wlds protection distinguishes axon degeneration following injury from naturally occurring developmental pruning.
Axon pruning by degeneration remodels exuberant axonal connections and is widely required for the development of proper circuitry in the nervous system from insects to mammals. Developmental axon degeneration morphologically resembles injury-induced Wallerian degeneration, suggesting similar underlying mechanisms. As previously reported for mice, we show that Wlds protein substantially delays Wallerian degeneration in flies. Surprisingly, Wlds has no effect on naturally occurring developmental axon degeneration in flies or mice, although it protects against injury-induced degeneration of the same axons at the same developmental age. By contrast, the ubiquitin-proteasome system is intrinsically required for both developmental and injury-induced axon degeneration. We also show that the glial cell surface receptor Draper is required for efficient clearance of axon fragments during developmental axon degeneration, similar to its function in injury-induced degeneration. Thus, mechanistically, naturally occurring developmental axon pruning by degeneration and injury-induced axon degeneration differ significantly in early steps, but may converge onto a common execution pathway.


Cystic mesenchymal hamartoma of the liver report of a case and review of the literature.
Mesenchymal Hamartoma (MH) of the liver constitutes the third or the fourth most common tumour of the liver in childhood and occurs most commonly in the first two years of life. It is often misdiagnosed clinically as a malignant tumour because of its rapid increase in size within a short period of time, or as a hepatic collections or abscess because of its cystic appearance. Although a benign lesion, MH may cause heart failure due to arteriovenous shunts, or death as a result of respiratory complications. A typical case of MH was recently encountered in a 6-years-old-boy. The patient presented with progres sive abdominal distension; surgery revealed a large mass arising from the right lobe of the liver. The mass was predominantly formed by fluid collections. Loose mesenchymal tissue and branched, tortuous bile ducts were the key diagnostic features. When predominantly cystic, MH may mimic lymphangioma both grossly and microscopically. Prudent examination of the cystic structures can establish a correct diagnosis.


Determinants of pain perception in labour among parturients at the University College Hospital, Ibadan.
This cross-sectional study of one thousand parturients aims to evaluate the factors, which are associated with pain perception in labour and to identify women who will benefit most from analgesia in labour. The instrument applied was a structured questionnaire incorporating the Box numerical scale (BNS) for pain assessment. Patients who delivered by elective or emergency caesarean section and women who did not give informed consent were excluded from the study. Spearman's and Pearson's correlational analyses were applied. Pain scores showed significant correlation with age (r=- 0.087, p<0.01), parity (r=- 0.226, p<0.01), gestational age at delivery (r=- 0.074, p<0.05), onset of labour (rho=0.195, p<0.01), mode of delivery (rho=0.160, p<0.01), booking status (rho=- 0.070, p<0.05) and educational status (rho=0.182, p<0.01). Certain groups of patients would benefit from obstetric analgesia. These patients include, nulliparous patients, young patients, patients who have had labour induced, those with preterm deliveries and those with an assisted vaginal delivery especially if they are well educated.


Comparison of nuclear 5 alpha-reductase activities in the stromal and epithelial fractions of human prostatic tissue.
The nuclear conversion of testosterone (T) to dihydrotestosterone (DHT) was compared in the separated stromal and epithelial fractions of hyperplastic (n = 20), malignant (n = 5) and normal (n = 1) prostatic tissues. Standard assay conditions were: 1 microM testosterone, plus 4-6 X 10(5) DPM [3H]T, 1.0 mM NADPH, 2.0 mM EDTA and 0.5-1.0 mg nuclear protein in a total volume of 1.1 ml HEPES buffer, pH 7.4 (stroma) or MES buffer, pH 6.5 (epithelium). The apparent Km values for the stromal enzyme were 0.2, 0.2 and 0.3 microM, respectively, for the enzymes in hyperplastic, malignant and normal tissues. The Vmax values were 26 +/- 4.2, 2.8 +/- 0.6 and 4.1 pmol/mg protein/30 min incubation, respectively, for these same tissues. The apparent Km values for the epithelial enzymes, from the same tissues, were 0.03, 0.07 and 0.08 microM. The Vmax values for the epithelial enzymes were 4.8 +/- 1.2, 0.69 +/- 0.08 and 1.1 pmol/mg protein/30 min incubation. The pH optimum for the stromal enzyme lay between pH 6.5 and 7.5, whereas the pH optimum for the epithelial enzyme lay between 5.5 and 6.5. Enzymatic activity in both fractions revealed a biphasic response to zinc. In the absence of EDTA, microM quantities of zinc enhanced enzymatic activity while mM quantities inhibited this activity. These results would suggest that differences in the conversion of T to DHT help to explain, at least in part, the higher DHT levels seen in hyperplastic tissue and the higher T levels seen in the malignant prostate.


Efficacy of continuous versus intermittent administration of penicillin G in Streptococcus pneumoniae pneumonia in normal and immunodeficient rats.
An experimental Streptococcus pneumoniae pneumonia was used to study the influence of continuous versus intermittent administration of penicillin G on therapeutic efficacy in normal rats and in rats whose phagocytic capacities were impaired by decomplementation with cobra venom factor. Response to antibiotic treatment was evaluated with respect to numbers of bacteria in left lung, blood and pleural fluid. Penicillin treatment was started 36 h after bacterial inoculation, and continued for four days. With intermittent intramuscular administration of penicillin normal rats were cured after daily doses of 4 mg/kg at 12 h intervals, whereas decomplemented rats recovered only after daily doses of 100 or 102 mg/kg at 12 h or 8 h intervals, respectively. When penicillin was administered by way of continuous infusion, daily doses of 3.5 mg/kg were required for a cure of infections in both normal rats and in decomplemented rats. This treatment resulted in a constant level of 0.05 micrograms of penicillin per ml, which was slightly above the minimum bactericidal concentration for the infecting strain. These findings show that maintenance of bactericidal levels of penicillin were particularly important in curing severe infection in rats with impaired defense.


Guest editorial. Body sensor networks: from theory to emerging applications.
The use of sensor networks for healthcare, well-being, and working in extreme environments has long roots in the engineering sector in medicine and biology community. With the maturity of wireless sensor networks, body area networks (BANs), and wireless BANs (WBANs), recent efforts in promoting the concept of body sensor networks (BSNs) aim to move beyond sensor connectivity to adopt a system-level approach to address issues related to biosensor design, interfacing, and embodiment, as well as ultralow-power processing/communication, power scavenging, autonomic sensing, data mining, inferencing, and integrated wireless sensor microsystems. As a result, the system architecture based on WBAN and BSN is becoming a widely accepted method of organization for ambulatory and ubiquitous monitoring systems. This editorial paper presents a snapshot of the current research and emerging applications and addresses some of the challenges and implementation issues.


Area 18 cell responses in cat during reversible inactivation of area 17.
1. A region of area 17 in the cat was temporarily inactivated by cooling, and cells in a topographically corresponding part of area 18 were studied during the blockage of area 17 input. 2. The responses of most area 18 cells were markedly reduced by cooling area 17 and recovered on rewarming primary visual cortex. 3. The selectivity of area 18 cells for oriented stimuli was not affected by inactivating area 17. These cells also, in general, retained their selectivities for the direction of stimulus movement and for the sign of contrast (light or dark) of a moving edge in the absence of input from area 17. 4. There was a greater decrease, on the average, of area 18 cell responses to slowly moving stimuli than to rapidly moving stimuli when area 17 was cooled; however, the exact pattern of change varied considerably from cell to cell. 5. These results suggest that cells in area 18 are to some degree dependent on input from area 17 for their responses, but to a large extent are independent in their selectivity for those stimulus parameters (orientation, direction of movement, sign of contrast) studied.


fMRI-based Neuronal Response to New Odorants in the Newborn Brain.
The sense of smell is one of the oldest and the most primitive senses mammals possess, it helps to evaluate the surrounding environment. From birth, smell is an important sensory modality, highly relevant for neonatal behavioral adaptation. Even though human newborns seem to be able to perceive and react to olfactory stimuli, there is still a lack of knowledge about the ontogeny of smell and the underlying central processing involved in odor perception in newborns. Brain networks involved in chemosensory perception of odorants are well described in adults, however in newborns there is no evidence that central olfaction is functional given the largely unmyelinated neonatal central nervous system. To examine this question, we used functional magnetic resonance imaging (fMRI) in the newborn to characterize cortical response to olfactory and trigeminal odorants. Here we show that brain response to odors can be measured and localized using functional MRI in newborns. Furthermore, we found that the developing brain, only few days after birth, processes new artificial odorants in similar cortical areas than adults, including piriform cortex, orbitofrontal cortex and insula. Our work provides evidence that human olfaction at birth relies on brain functions that involve all levels of the cortical olfactory system.


Microcapsule preparation of allyl isothiocyanate and its application on mature green tomato preservation.
Studies have shown that AITC can effectively control pathogenic fungi, which cause fruits and vegetables decay and rotting during storage. However, because of its strong irritant, AITC has not been conveniently used in fruits and vegetables preservation. Microencapsulation techniques may solve this problem. Up to 2% (w/v) gelatin and 2% (w/v) gum arabic (as wall material and materials), as well as AITC (as core material) were prepared used to form microcapsules with a ratio of 1:2 (the core material: to wall material). On the basis of the microcapsule option conditions, the AITC microcapsule encapsulation efficiency is above 90%, which can effectively control AITC release decrease irritant. Compared with control group, the storage time of the tomato of AITC microcapsule preservation was prolonged significantly, and the sensory quality of the tomato was better. Thus, the AITC microcapsule preservation has broad application prospects and development value prospects.


Egg quality and productive performance of laying hens fed different levels of skimmed milk powder added to a diet containing Lactobacillus acidophilus.
The current trial was carried out on a commercial poultry farm to study the effect of skim milk powder (SMP) added to a diet containing Lactobacillus acidophilus on performance and egg quality of laying hens from 20 to 49 wk of age. A total of 2,400 Hy-Line W-36 laying hens were housed in 600 unenriched cages (4 hens each) located over 4 tier levels. Animals were assigned to 1 of 3 experimental treatments (0, 3, and 4). The laying hens assigned to treatments 3 and 4 received a diet enriched respectively with 3 and 4% SMP, whereas the animals in treatment 0 were fed a diet without SMP. All diets, moreover, were supplemented with L. acidophilus D2/CSL. Hen performance was determined throughout the experimental period and egg quality was measured on 30 eggs per treatment every week. Results showed that productive performance in terms of egg production, egg weight, and feed conversion ratio was not influenced by SMP at 3 or 4% of the diet. Egg quality was significantly affected by SMP included at 3 or 4% of the diet. Eggs from treatments 3 and 4, in fact, displayed higher shell thickness than those from treatment 0 (P < 0.0001). Likewise, specific gravity, Haugh unit, and shell percentage were significantly affected by the addition of SMP. In conclusion, in our study, SMP added to a diet containing L. acidophilus had no significant effects on the productive parameters of hens during the laying period, whereas significant improvements were found in certain egg quality characteristics.


[Concepts of healthy diet as expressed by primary health care workers in the national capital of Brazil].
Dietary changes in Western society highlight the need for individual and collective health providers to use their strategic positions to actively promote healthy eating habits. Using the research-action methodology in various clinics in the Federal District of Brazil, the present study aimed to identify what these professionals consider a healthy diet. The results indicate an apparent conceptual dichotomy: on the one hand, an idealized version of eating for good health based on the scientific literature; on the other, a concept derived from the ideal, but based on people's day-to-day reality. In their pursuit of the latter concept, people in social situations make connections between various pieces of information, and what emerges are the eating habits most closely associated with a particular lifestyle. However, both concepts tend to transcend the implicit biological character of the conceptual constructs and to find support in the sociocultural conditions that shape them and which in turn are shaped at the concrete level of reality.


Female pattern hair loss and its relationship to permanent/cicatricial alopecia: a new perspective.
Female pattern hair loss (FPHL) is a common hair disorder of the central scalp. The clinical change in hair density, related to a change in the hair cycle and miniaturization of the hair follicle, is generally considered to be potentially reversible. However, there is now evidence of a permanent hair loss that develops in a subset of women with FPHL. The presence of a perifollicular lymphohistiocytic infiltrate and fibrosis is seen without follicular drop-out in biopsies of women with FPHL and with a notable follicular drop-out in a cicatricial form of this condition (heretofore called cicatricial pattern hair loss) as well as in fibrosing alopecia in a pattern distribution, currently classified as a subset of lichen planopilaris. The potential relationship of these conditions as well as frontal fibrosing alopecia and central centrifugal cicatricial alopecia, two other conditions of permanent hair loss seen primary in women, is discussed.


Competitive polymerase chain reaction to quantify tumor cells in peripheral blood of patients with T(14;18)-bearing follicular non-Hodgkin's lymphoma: an exploratory study in 8 patients.
Detection of residual disease in follicular lymphoma is hampered by the observation of t(14;18)-bearing cells in the blood of healthy adult humans. To overcome this problem, we decided to validate a quantification method of t(14;18)-bearing cells and test it in t(14;18)-bearing follicular lymphomas (FL). We designed a competitive PCR method to quantify t(14;18)-bearing cells in peripheral blood. First, we controlled overall reliability (specificity, sensitivity, reproducibility, precision and accuracy); then we used our method to study 16 peripheral blood samples collected in 8 patients with t(14;18)-bearing FL. There were considerable variations in the number of circulating tumor cell (CTC) in FL patients, ranging from zero to 17,813 cells/ml. In 2 patients who were sampled before and after treatment and who attained complete remission (CR), a significant decrease in the number of CTC was observed. In 3 patients with detectable CTC during CR, relapse occurred 4 to 11 months later. Of 3 patients with no detectable CTC, 2 remain in CR 35 and 95 months later, but one relapsed 11 months after sample collection. These preliminary results suggest that quantification of CTC may be worthwhile in follicular lymphoma. It may improve our ability to predict relapse occurrence, but also may help in understanding this peculiar disease. Int. J. Cancer (Pred. Oncol.) 84:558-561, 1999.


Formulation and evaluation of ethiodized oil emulsion for intravenous hepatography.
A study was conducted to prepare and evaluate an ethiodized oil emulsion for intravenous administration that would selectively opacify the liver. Several formulations with differing globule size were prepared and compared for their in vivo activity (degree of liver opacification obtained) and stability. Results of studies conducted in rabbits and monkeys revealed that the oil globules that concentrate most in liver were 2.0--3.0 micrometer in diameter. The formulation of choice was stable for 6 months at refrigeration temperature (2--6 degree). In monkeys, this formulation produced an improved diagnostic image of the liver using computerized tomography at a dose of 0.2 ml/kg. The potential use of such emulsions in diagnostic radiology is briefly discussed.


A technique to recover tracer as carboxyl-carbon and alpha-nitrogen from amino acids in soil hydrolysates.
Isotope analysis of biochemical compounds provides an unequivocal means for detecting assimilation of tracer C and N into microbial biomass. A diffusion method recently developed to determine amino acid-N by ninhydrin oxidation of soil hydrolysates was modified to permit simultaneous collection of the CO2 liberated during this oxidation. In the technique described herein, this is accomplished after removal of (NH4+ + amino sugar)-N, by performing ninhydrin oxidation at 90 degrees C for 7 h in a 1.9 L Mason jar sealed with a lid equipped to support a petri dish containing 5 mL 0.2N NaOH. Recoveries of carboxyl-C and alpha-N ranged from 98 to 101% in evaluations with standard solutions of amino acids, whereas these recoveries exceeded 90% for 14C and 94% for 15N when soil hydrolysates amended with labeled amino acids were analyzed.


[Condensed and dispersed chromatin in the nuclei of thyroid follicular cells under normal conditions and following thyrotropic stimulation].
The author examined the changes in the nuclear size, in its form and optical density as well as the changes in the condensed and dispersed chromatin of the follicular cells of the thyroid gland after thyroid stimulation by means of the method of scanning cytophotometry. He found that after a 20-day treatment of the animals with methythyouracyl-an agent, which blocks thyroid hormonal synthesis and in this way raised the level of the thyreothropic hormone in circulation, the size of the cell nuclei was increased and at the same time its concentration of DNA was reduced. The amount of the particles of the condensed chromatin after thyreotropic stimulation diminished, but the integral space remained unchanged and the area of the dispersed chromatine was mainly increased. The obtained data are discussed in view of the possibilities of the scanning cytophotometry for evaluation of the functional activity of the cell.


The Ras effectors NORE1A and RASSF1A are frequently inactivated in pheochromocytoma and abdominal paraganglioma.
NORE1A (RASSF5) and RASSF1A are newly described Ras effectors with tumour suppressor functions. Both molecules are frequently inactivated in various cancers. In this study, we aimed to explore the potential involvement of NORE1A and RASSF1A in pheochromocytoma and abdominal paraganglioma tumorigenesis. A panel of 54 primary tumours was analysed for NORE1A and RASSF1A mRNA expression by TaqMan quantitative RT-PCR. Furthermore, NORE1A and RASSF1A promoter methylation was assessed by combined bisulphite restriction endonuclease assay and methylation-sensitive Pyrosequencing respectively. The anti-tumorigenic role of NORE1A was functionally investigated in Nore1A-transfected PC12 rat pheochromocytoma cells by fluorescent inhibition of caspase activity and soft agar assays. Significantly suppressed NORE1A and RASSF1A mRNA levels were detected in primary tumours compared with normal adrenal medulla (P<0.001). Methylation of the NORE1A promoter was not observed in primary tumours. On the other hand, 9% (5/54) of the primary tumours examined showed RASSF1A promoter methylation greater than 20% as detected by Pyrosequencing. Methylation of the RASSF1A promoter was significantly associated with malignant behaviour (P<0.05). Transient expression of Nore1a resulted in enhanced apoptosis and impaired colony formation in soft agar. Our study provides evidence that NORE1A and RASSF1A are frequently suppressed in pheochromocytoma and abdominal paraganglioma. Silencing of NORE1A contributes to the transformed phenotype in these tumours.


The role of nutrients in the biodegradation of 2,4,6-trinitrotoluene in liquid and soil.
The widely used explosive 2,4,6-trinitrotoluene (TNT) has residues that are potentially explosive, toxic, and mutagenic. TNT and other explosives can be degraded by microorganisms; however, biostimulation is needed for process efficiency. To investigate the effectiveness of using biostimulation to degrade TNT, we added varying concentrations of a nutrient amendment consisting of inorganic salts, plant extracts, and molasses to soil and liquid media. For the inoculum we used a consortium of bacteria AM 06 that had exhibited the ability to degrade TNT and which had been previously isolated from explosives-contaminated soils. Phylogenetically, the clones clustered into seven different genera: Klebsiella, Raoultella, Serratia, Stenotrophomonas, Pseudoxanthomonas, Achromobacter and Pseudomonas. The addition of AM 06 consortium to a liquid environment along with 100% nutrient amendment decreased the amount of TNT (and its degradation products) by up to 90% after 14 days incubation. At the total amount of TNT was less than 100 mg/l, the concentration of TNT did not influence the amount of sugar consumed by the bacteria consortium. In soil media, the TNT degradation process was dependent on the concentration of nutrient amendment added. At higher initial concentrations of TNT (500 mg/kg), bioaugmentation (i.e., addition of bacteria inoculum) had a demonstrated effect, especially when nutrient concentrations of 50% and 100% were added to the soil. Findings of this study could further the understanding of the TNT biodegradation processes in water and soil and provide for optimization of the technological conditions for bioremediation.


Decreasing 203Hg retention by intraperitoneal treatment with monoalkyl esters of meso-2,3-dimercaptosuccinic acid in rats.
The effect of nine monoalkyl esters of meso-2,3-dimercaptosuccinic acid (DMSA) on 203Hg retention after a single i.p. dose was evaluated in 6-7 week-old female albino rats. The monoesters were the monomethyl (MMDMS), monoethyl (MEDMS), mono-n-propyl (Mn-PDMS), monoisopropyl (Mi-PDMS), mono-n-butyl (Mn-BDMS), monoisobutyl (Mi-BDMS), mono-n-amyl (Mn-ADMS), monoisoamyl (Mi-ADMS) and mono-n-hexyl (Mn-HDMS). Dimercaptosuccinic acid or one of the monoesters were administered at a dose of 0.25 mmol kg-1 body wt. twice, i.e. 30 min and 24 h after 203Hg administration. The whole body (WB) radioactivity was determined on the 2nd, 4th and 6th days. The radioactivity in the carcass (C) (whole body without the gastrointestinal tract), liver (L), both kidneys (K) and brain (B) was determined 6 days after 203Hg administration. All treated animals had a significantly lower body burden of mercury than the controls. The reduction of 203Hg retention in WB and other body compartments was higher in animals treated with monoesters than in rats treated with DMSA. The relative effectiveness of the monoesters was dependent on the nature of the alkyl groups, the efficiency being higher in higher analogues. Maximum activity was attained with the C5 (Mn-ADMS, Mi-ADMS) and C6 (Mn-HDMS) esters. These chelators reduced WB, C, L, K and B mercury retention by 90, 89, 76, 93 and 80%, respectively. Iso derivatives were more efficient than the normal isomers (Mi-PDMS > Mn-PDMS; Mi-BDMS > Mn-BDMS; Mi-ADMS > Mn-ADMS).(ABSTRACT TRUNCATED AT 250 WORDS)


[Determination of bacterial endotoxin admixtures in inactivated influenza vaccines].
The materials substantiating the possibility of using the method for the determination of the lethal effect of endotoxin on dactinomycin-treated mice are presented. This determination is made with a view to detecting the admixtures of endotoxins in whole-virion and subvirion inactivated influenza vaccines at different stages of their manufacture, as well as in the final product. The proposed test is highly sensitive, rather simple in its practical realization and can be used for evaluating the degree of the purification of influenza vaccines from endotoxins.


C-reactive protein and myocardial infarction.
C-reactive protein (CRP) has been shown to predict cardiovascular disease. Whether predictions differ across risk factor strata and for short and long-term follow-up has not been clearly examined. The purpose of this report is to assess the relation between CRP and the development of myocardial infarction (MI) over a 20-year period in men in the Honolulu Heart Program. Subjects were aged 48 to 70 years and free of prevalent disease at the time when CRP levels were measured and follow-up began. Using a case-control design, 369 cases of MI were compared with 1,348 control subjects. After risk factor adjustment, the odds of an MI rose with increasing levels of CRP as early as 5 years into follow-up (P = 0.009). Associations appeared to persist beyond this time, but after 15 years, effects became modest. Adverse effects of an elevated CRP level were observed in middle-aged men (< or =55 years), in men without hypertension or diabetes, and in those who were nonsmokers (P < 0.05). Although positive effects were also observed in those who were hypertensive and smoking at the time of CRP measurement, findings suggest that in clinically healthy men, atherosclerosis could have origins more closely linked with inflammation than with other processes.


Comparison of different clinical development plans for confirmatory subpopulation selection.
Given ever increasing costs to develop a new drug and intense competition, adaptive enrichment designs are an attractive option for a development program that allows selecting a potential subgroup defined by a binary biomarker. Such designs explicitly factor in the possibility that the new drug might differentially benefit distinct biomarker subgroups. We have compared three clinical development plans for a time-to-event endpoint, such as overall survival, that all lead to a decision in a pivotal trial either in all comers only, in allcomers and biomarker positive, in the biomarker positive only, or to declare the drug futile. The decision about which hypothesis to test at the final analysis is made based on a fast time-to-event endpoint, such as progression-free survival, at an interim analysis. We quantify the time gain when using an adaptive enrichment Phase II/III design versus alternative development approaches and we outline what type of biomarker needs to be available prior to Phase II in each scenario. We conclude with a discussion of further features of each of the considered development plans.


Targeting cellular drivers and counter-regulators of hyperglycaemia- and transforming growth factor-β1-associated profibrotic responses in diabetic kidney disease.
Diabetic kidney disease occurs in >30% of patients with type 2 diabetes mellitus and is characterized at source by a maladaptive response in the renal parenchyma to exposure to a glucotoxic-lipotoxic diabetic milieu that courses coincident with hypertension. The consequence of these maladaptive responses is progressive renal injury, which is exacerbated by the development of a chronic inflammatory infiltrate associated with the development of tubulointerstitial fibrosis. The evolution of tubulointerstitial fibrosis is correlated with the loss of functional renal mass and descent towards renal failure. Transforming growth factor-β1 (TGF-β1) is a recognized mediator of the profibrotic response of mesangial cells and renal tubular epithelial cells to hyperglycaemia. While euglycaemia remains the goal in the treatment of type 2 diabetes mellitus, the prevention, arrest and reversal of microvascular complications, such as diabetic kidney disease, may be assisted by pharmacological modulation of the effectors of glucotoxicity, such as TGF-β1. This review focuses on describing how, through reductionist in vitro experimentation focusing on TGF-β1-related responses to hyperglycaemia, we have identified induced in high glucose-1 (IHG-1), induced in high glucose-2 (IHG-2/Grem1) and the lipoxin-inducible microRNA let-7c as potential targets for harnessing new therapeutic approaches to limit the bioactivity of TGF-β1 in diabetic kidney disease.


Bicyclic hydantoins with a bridgehead nitrogen. Comparison of anticonvulsant activities with binding to the neuronal voltage-dependent sodium channel.
The anticonvulsant activity of diphenylhydantoin (DPH or phenytoin) is consistent with its actions on the neuronal voltage-dependent sodium channel. To further elucidate the binding requirements for this site, we synthesized several hydantoin analogs and evaluated these in in vitro sodium channel-binding and/or in vivo whole animal anticonvulsant assays. 5-Pentyl-5-phenylhydantoin (8), the most potent binder to the sodium channel in this study, had the same affinity as DPH (IC50 = 40 microM), revealing that one phenyl ring is sufficient for good interactions. Since our previous studies with monophenyl-substituted bicyclic 2,4-oxazolidinediones suggested that N3-alkylation and the conformational constraint of a 5-alkyl substituent over one face of the oxazolidinedione ring improved activity, we synthesized two examples of analogous bicyclic hydantoins. However, the bicyclic hydantoins were much less potent binders to the neuronal voltage-dependent sodium channel than their monocyclic counterparts. The binding activity for the more potent bicyclic hydantoin, 1,8-diaza-9,10-dioxo-7-phenylbicyclo[5.2.1]decane (4) (IC50 = 427 microM), was comparable to that of the ring-opened, N3-methylated monocyclic hydantoin model, 5-butyl-3-methyl-5-phenylhydantoin (9) (IC50 = 285 microM), and these were 8-11 times less potent than the monocyclic model 8, which contains a free imide NH. Furthermore, 5-butyl-5-phenylhydantoin (7; IC50 = 103 microM) was less potent than 8, suggesting that increased log P may enhance binding. Thus, unlike 2,4-oxazolidinediones, N3-alkylation of hydantoins dramatically decreases sodium channel-binding activity. Bicyclic hydantoin 4 was nevertheless a good anti-MES anticonvulsant in mice (ED50 = 86 mg/kg), although this activity likely results from mechanisms other than interactions at the neuronal voltage-dependent sodium channel. Compound 4 was also relatively neurotoxic (TD50 = 124 mg/kg). These results suggest that the binding of hydantoins to the sodium channel may be enhanced by (a) a free imide NH group and (b) an increased log P. Furthermore, 2,4-oxazolidinediones and hydantoins must either orient differently in the same binding site or interact with different sites on the neuronal voltage-dependent sodium channel.


The gender composition of the medical profession in Mexico: implications for employment patterns and physician labor supply.
The gender composition of the medical profession is changing rapidly in many parts of the world, including Mexico. We analyze cross-sectional and longitudinal data on sex differences in physician employment from household employment surveys. The results suggest that Mexico is a particularly interesting example of the feminization of physician employment. Female enrollment in medical school increased from 11% in 1970 to about 50% in 1998. The increased participation of women in medicine seems to be accompanied by differences in employment patterns that could generate significant reductions in the total supply of physician hours of service. Women physicians are unemployed at a much higher rate than men and hence account for half of underused physician human capital. The results suggest that improved educational opportunities do not translate automatically into equal employment opportunities.


[The air belongs to us: the importance of maintaining air quality].
Interest in identifying the long-term harmful effects of atmospheric pollution on respiratory health, and concern about this issue, has prompted several studies, whose results have been published throughout this year. On the occasion of the Spanish Society of Pneumology and Thoracic Surgery's Year of the Environment, from the Section of Occupational and Environmental Respiratory Diseases, we review the advances made in the effects of atmospheric pollution on respiratory health and the actions undertaken by the Society. The main objective of the Society's Year of the Environment is to inform citizens in general and respiratory patients in particular of the benefits of breathing clean air. The first step in achieving this aim is education. The goal is to educate young people in lasting habits that promote a respectful attitude to the environment, inculcating them with the need for sustainable development through responsible energy consumption and reduction of the emission of pollutants. Informed citizens will demand public health policies aimed at maintaining the quality of the air we breathe from politicians. The website www.elaireesnuestro.com provides information and educational material on the subject.


Albendazole and its derivative JVG9 induce encystation on Giardia intestinalis trophozoites.
In the present study, we evaluated the effect of an albendazole (ABZ) derivative JVG9 on cultured Giardia intestinalis. To assess the JVG9 effects, we evaluated the tubulin cytoskeleton by confocal microscopy, and we found that the characteristic staining was modified. The scanning electron microscopy images revealed extremely damaged trophozoites and cyst-like cells. The confocal images revealed that this drug triggered the expression of cyst wall protein 1 and encystation. We also found that at low doses, AL triggered the encystation process too.


Strontium Ameliorates Glucocorticoid Inhibition of Osteogenesis Via the ERK Signaling Pathway.
Glucocorticoid (GC) has been widely used in clinical work due to its anti-inflammatory and immune-inhibitory properties. However, long-term or high-dose administration is associated with side effects, such as GC-induced osteoporosis (GIOP), which causes great pain for and poses a heavy financial burden on patients. We sought to investigate the potential effects of strontium on GIOP and further explore its underlying mechanisms, including its reversal of the inhibitory effect of GC on osteogenesis of bone marrow-derived mesenchymal stem cells (BMSCs). We incubated BMSCs with Dexamethasone (DEX) in combination with or without strontium and then measured osteogenic and adipogenic gene expression levels by RT-qPCR and Western blot. We added a specific ERK signaling pathway inhibitor, U0126, to evaluate the involvement of that pathway. Strontium promoted osteogenic differentiation and matrix mineralization in DEX-treated BMSCs, accompanied by upregulation of RUNX2, Osx, ALP, BSP, COL1A1, and OCN. DEX blocked the expression of several osteogenesis-related marker genes by activating the ERK signaling pathway. U0126 attenuated the suppression of osteogenesis in DEX-treated BMSCs. These results suggested that strontium could enhance osteogenic differentiation and matrix mineralization by counteracting DEX's inhibitory effect on osteogenesis via the ERK signaling pathway. Therefore, strontium might be a promising therapeutic agent for GIOP.


Expression of chemokine receptor CCR7 is associated with lymph node metastasis of gastric carcinoma.
The interactions of chemokine receptor CCR7 and its ligands are essential for migration of lymphocytes and dendritic cells to lymph nodes. In this study, we found that 4 of 6 (67%) gastric carcinoma cell lines tested expressed functional CCR7 for the chemokine CCL21/6Ckine, as demonstrated by calcium mobilization and actin polymerization assays. Moreover, we also showed that signaling through CCR7 induced chemotactic and invasive responses in CCR7-positive gastric carcinoma cells. In clinical samples, immunohistochemical assay showed that CCR7-positive carcinoma cells were detected in 42 of 64 (66%) cases and a significant difference in both lymph node metastasis (P < 0.001) and lymphatic invasion (P < 0.001) between CCR7-positive and -negative cases. Patients with CCR7-positive tumors had a significantly poorer prognosis than those with CCR7-negative tumors (P < 0.05). Stepwise regression analysis revealed that the most important factor related to lymph node metastasis was the expression of CCR7. These results indicated that CCR7 and its ligands interaction is associated with preferential lymph node metastasis of gastric carcinoma.


Reporting on pediatric unintentional firearm injury--who's responsible.
Gun injury is a leading cause of death among US children and adolescents. Unintentional firearm death disproportionately affects youth. Reports have shown that at least a third of US homes with children have firearms. When children are fatally injured by guns, the location is most often a home, the shooter is family, the gun owner is a relative, and the gun most often originates from the home, where it was left unlocked. We conducted an Internet search of pediatric (0-18 years old) fatal and nonfatal firearm injuries from January 1 to August 31, 2014, in the United States, querying the terms shot, gun, accident, and year-old for media reports. Cases were screened for intent and coded for demographics, location, gun specifics, circumstances, relationship between the victim, shooter, gun owner, and any resultant charges. A total of 277 unintentional pediatric gun injury events were reviewed, two-thirds were nonfatal. Half of the victims were younger than 13 years; 25.3% were younger than 7 years, 80% of the victims and 85.6% of the shooters were male. Of shooters, 84.3% were the child victim themselves, a family member, or a friend/acquaintance. Seventy-seven percent of the events took place in a residence. When gun ownership was reported, 68% were owned by a family member. When charges were reported, a third were against minors. This study reinforced previous studies that unintentional child firearm injuries predominantly involve the home, family guns, young children, and males, and most could be prevented through adult responsibility for minimizing child access and securing storage of firearms. We further learned that media accounts frequently did not report on gun ownership or charges, details which might increase community awareness or inform policies useful to prevention. Shooters, not owners, were more often charged in unintentional child injuries, and minors were charged even when Child Access Prevention laws could be applied. Epidemiologic study, level 4.


Factors involved in the early pathogenesis of bovine Staphylococcus aureus mastitis with emphasis on bacterial adhesion and invasion. A review.
Staphylococcus aureus is the most important and prevalent contagious mammary pathogen; it causes clinical and subclinical intramammary infection with serious economic loss and herd management problems in dairy cows. In vitro studies have shown that Staphylococcus aureus adheres to mammary epithelial cells and extracellular matrix components and invades into mammary epithelial as well as other mammary cells. Staphylococcus aureus strains from intramammary infection produce several cell surface-associated and extracellular secretory products. The exact pathogenic roles of most of the products and their effects on adhesion and invasion are not well evaluated. It is also known that mammary epithelial cell-associated molecules and extracellular matrix components interact with S. aureus during the pathogenesis of mastitis, but their roles on adhesion and invasion have not been characterized. The adhesion of S. aureus to epithelial cells may involve non-specific physicochemical interactions and/or specific interactions between bacterial cell-associated ligands and host cell surface receptors. In vitro adhesion depends on the S. aureus strain, the growth phase of the bacteria, the growth medium and the origin of the epithelial cells. Adhesion is hypothesized to be a prerequisite and crucial early step for mammary gland infection. Staphylococcus aureus invades mammary epithelial cells. It also invades other cells such as endothelial cells and fibroblasts. Bacteria are found enclosed in membrane bound vacuoles in the cytoplasm of mammary epithelial cells. Recent observations indicate that S. aureus escapes from the phagosome into the cytoplasm and induces apoptosis. The invasion into mammary epithelial cells may occur through an endocytic process that requires involvement of elements of the cytoskeleton or by direct binding of bacteria to epithelial cells through a process mediated by specific receptors that needs de novo protein synthesis by both cells. Thus, the recurrent subclinical infection may result from this intracellular existence of bacteria that are protected from host defenses and effects of antibiotics. This review emphasizes on recent findings on S. aureus adhesion to mammary epithelial cells and extracellular matrix components and invasion into mammary epithelial cells.