Early liver transplantation for patients with acute alcoholic hepatitis: public views and the effects on organ donation.
Patients with severe acute alcoholic hepatitis may not survive to fulfill the standard 6 months of abstinence and counseling prior to transplantation. A prospective study demonstrated that early liver transplantation in such patients improved 2 year survival from 23% to 71% and only 3 of 26 patients returned to drinking after 1140 days; graft function was unaffected. Nonetheless, this treatment protocol may raise public concerns and affect organ donation rates. A total of 503 participants took a survey made available at an online crowdsourcing marketplace. The survey measured attitudes on liver transplantation generally and early transplantation for this patient population, in addition to measuring responses to nine vignettes describing fictional candidates. The majority of respondents (81.5%, n = 410) was at least neutral toward early transplantation for these patients; only a minority (26.3%) indicated that transplantation in any vignette would make them hesitant to donate their organs. Middle-aged patients with good social support and financial stability were viewed most favorably (p < 0.001). Age was considered the most important selection factor and financial stability the least important factor (each p < 0.001). Results indicate early transplantation for carefully selected patients with acute alcoholic hepatitis may not be as controversial to the public as previously thought.


Specific patterns of oncogene activation in transplacentally induced tumors.
Transplacental exposure of rats to a single dose of the direct acting carcinogen methylnitrosourea (MNU) results in the induction of a variety of neoplasias of neuroectodermal, epithelial, and mesenchymal origin. Molecular analysis of the oncogenes present in these tumors revealed a striking degree of tissue specificity. neu oncogenes were found to be reproducibly activated in tumors derived from the peripheral nervous system (PNS), but not in those arising from the central nervous system (CNS). No ras oncogenes were found in either PNS- or CNS-derived tumors. However, Ha-ras oncogenes were detected in each of three mammary carcinomas and Ki-ras oncogenes were present in each of five kidney mesenchymal tumors. These results illustrate that phenotypic expression of activated oncogenes in vivo is not a random process and suggest that normal developmental programs may play an important role in modulating the activation of specific oncogenes by chemical carcinogens. PCR analysis revealed that each of the ras oncogenes detected in these transplacentally induced tumors became activated by the same G----A transition in the second base of codon 12. Since G----A transitions are the preferred mutations induced by MNU, it is likely that these ras oncogenes may have been directly targeted by MNU during embryonic development.


A Matter of Taste: Lineage-Specific Loss of Function of Taste Receptor Genes in Vertebrates.
Vertebrates can perceive at least five different taste qualities, each of which is thought to have a specific role in the evolution of different species. The avoidance of potentially poisonous foods, which are generally bitter or sour tasting, and the search for more nutritious ones, those with high-fat and high-sugar content, are two of the most well-known examples. The study of taste genes encoding receptors that recognize ligands triggering taste sensations has helped to reconstruct several evolutionary adaptations to dietary changes. In addition, an increasing number of studies have focused on pseudogenes, genomic DNA sequences that have traditionally been considered defunct relatives of functional genes mostly because of the presence of deleterious mutations interrupting their open reading frames. The study of taste receptor pseudogenes has helped to shed light on how the evolutionary history of taste in vertebrates has been the result of a succession of gene gain and loss processes. This dynamic role in evolution has been explained by the "less-is-more" hypothesis, suggesting gene loss as a mechanism of evolutionary change in response to a dietary shift. This mini-review aims at depicting the major lineage-specific loss of function of taste receptor genes in vertebrates, stressing their evolutionary importance and recapitulating signatures of natural selection and their correlations with food habits.


Pro-Inflammatory Biomarkers in Stable Versus Acutely Decompensated Heart Failure With Preserved Ejection Fraction.
Underlying inflammation has been increasingly recognized in heart failure with a preserved ejection fraction (HFpEF). In this study we tested the hypothesis that pro-inflammatory biomarkers are elevated in patients with acutely decompensated HFpEF (AD-HFpEF) compared with patients with stable HFpEF (S-HFpEF). Using a post hoc analysis the serum biomarkers tumor necrosis factor-alpha, high-sensitivity C-reactive protein interleukin 6 and pentraxin 3 (PTX3) and clinical, demographic, echocardiographic-Doppler and clinical outcomes data were analyzed in HFpEF patients enrolled in NHLBI Heart Failure Research Network clinical trials which enrolled patients with either AD-HFpEF or S-HFpEF. Compared to S-HFpEF, AD-HFpEF patients had higher levels of PTX3 (3.08 ng/mL versus 1.27 ng/mL, P<0.0001), interleukin-6 (4.14 pg/mL versus 1.71 pg/mL, P<0.0001), tumor necrosis factor-alpha (11.54 pg/mL versus 8.62 pg/mL, P=0.0015), and high-sensitivity C-reactive protein (11.90 mg/dL versus 3.42 mg/dL, P<0.0001). Moreover, high-sensitivity C-reactive protein, interleukin-6 and PTX3 levels were significantly higher in AD-HFpEF compared with S-HFpEF patients admitted for decompensated HF within the previous year. PTX3 was positively correlated with left atrial volume index (r=0.41, P=0.0017) and left ventricular mass (r=0.26, P=0.0415), while tumor necrosis factor-alpha was inversely correlated with E/A ratio (r=-0.31, P=0.0395). Levels of pro-inflammatory biomarkers are strikingly higher in AD-HFpEF compared with S-HFpEF patients. PTX3 and tumor necrosis factor-alpha are correlated with echocardiographic-Doppler evidence of diastolic dysfunction. Taken together these data support the concept that a heightened pro-inflammatory state has a pathophysiologic role in the development of AD-HFpEF.


Modulation of urea transport across sheep rumen epithelium in vitro by SCFA and CO2.
Urea transport across the gastrointestinal tract involves transporters of the urea transporter-B group, the regulation of which is poorly understood. The classical stimulatory effect of CO(2) and the effect of short-chain fatty acids (SCFA) on the ruminal recycling of urea were investigated by using Ussing chamber and microelectrode techniques with isolated ruminal epithelium of sheep. The flux of urea was found to be phloretin sensitive and passive. At a luminal pH of 6.4, but not at 7.4, the addition of SCFA (40 mmol/l) or CO(2)/HCO3- (10% and 25 mmol/l) led to a fourfold increase in urea flux. The stepwise reduction of luminal pH in the presence of SCFA from 7.4 to 5.4 led to a bell-shaped modification of urea transport, with a maximum at pH 6.2. Lowering the pH in the absence of SCFA or CO(2) had no effect. Inhibition of Na(+)/H(+) exchange increased urea flux at pH 7.4, with a decrease being seen at pH 6.4. In experiments with double-barreled, pH-sensitive microelectrodes, we confirmed the presence of an apical pH microclimate and demonstrated the acidifying effects of SCFA on the underlying epithelium. We confirm that the permeability of the ruminal epithelium to urea involves a phloretin-sensitive pathway. We present clear evidence for the regulation of urea transport by strategies that alter intracellular pH, with permeability being highest after a moderate decrease. The well-known postprandial stimulation of urea transport to the rumen in vivo may involve acute pH-dependent effects of intraruminal SCFA and CO(2) on the function of existing urea transporters.


Receptors, inositol polyphosphates and intracellular Ca2+.
1. A large number of cell-surface receptors catalyse the activation of phospholipase C via a guanine nucleotide exchange protein and generate at least two important intracellular second messengers. One of these, inositol(1,4,5) trisphosphate, binds to specific intracellular receptors and releases Ca2+ from intracellular stores. 2. Subsequent metabolism of this messenger is complex, proceeding either by dephosphorylation or phosphorylation routes with the latter generating inositol(1,3,4,5) tetrakisphosphate which may have additional functional significance in Ca2+ homeostasis. 3. Calculations of the relative rates of metabolism through these routes as well as the development of new analogues of inositol polyphosphates have helped our understanding of these important cell signalling systems.


[Anesthesia for ten patients with Prader-Willi syndrome].
Previous reports indicate that Prader-Willi syndrome may present various problems during anesthesia and the perioperative period. We retrospectively investigated anesthesia records of 10 patients (2 adults and 8 children) who were diagnosed to have Prader-Willi syndrome, and who had an operation under anesthesia. Three patients had small mouths, small jaws or both. Decreased musle mass was observed in 2 patients. Two patients were morbidly obese (BMI 33, and 51). General anesthesia was used in 9 patients. Spinal anesthesia under fluoroscopy was performed in the remaining one patient who was morbidly obese (BMI 51). Among 9 patients who received general anesthesia, mask ventilation was difficult in one patient, but insertion of an oral airway relieved the problem. Difficult tracheal intubation occurred in one patient. No other major problems occurred. We conclude that the incidence of problems during anesthesia and postoperative period in patients with Prader-Willi syndrome would be less than previously considered.


Nondestructive near-infrared analysis of intact tablets for determination of degradation products.
Near-infrared spectrometry was used in this study to examine intact aspirin tablets in order to demonstrate the usefulness of the technique as a nondestructive method of quality control. Unique sampling optics were used to simultaneously illuminate the entire surface of the tablets, including the top, bottom, and side. Changes in individual tablet spectra were correlated to (a) the time that the tablets spent in a hydrator, (b) the mass of water absorbed by the tablets, and (c) the mass of salicylic acid formed by base-catalyzed hydrolysis of acetylsalicylic acid. A prediction equation for each of these three parameters was constructed using near-infrared spectral reflectance values obtained from intact tablets. Prediction errors were low for (a) the time that tablets spent in the hydrator (+/- 19 h over a period of 168 h), (b) the mass of water absorbed (+/- 0.04% of tablet mass), and (c) the mass of salicylic acid formed (+/- 0.04% of tablet mass).


Metabolomic profiling with NMR discriminates between biphosphonate and doxorubicin effects on B16 melanoma cells.
The metabolomic profiles of B16 melanoma cells were investigated in vitro with high resolution-magic angle spinning proton magnetic resonance spectroscopy and OPLS multivariate statistical analyse. We compared the profiles for untreated melanoma B16-F10 cells and Ca(2+) chelating EGTA, doxorubicin or BP7033 bisphosphonate treated cells. The two last molecules are known to induce anti-proliferative effects by different mechanisms of action in cells. Untreated and EGTA treated cells had similar profiles and were considered together as control cells. Several spectral regions could discriminate control from doxorubicin as well as BP7033 treated cells. Doxorubicin and BP7033 displayed distinct metabolic profiles. Important changes in neutral lipids and inositol were related to doxorubicin activity whereas BP7033 affected essentially phospholipids and alanine/lactate metabolism. These results provide new putative targets for both drugs. Metabolomics by NMR is shown here to be a good tool for the investigation of the mechanisms of action of drugs in pre-clinical studies.


Oncogenic events associated with endometrial and ovarian cancers are rare in endometriosis.
Endometriosis displays some features that resemble malignant processes, including invasive growth, resistance to apoptosis and distant implantation. The objective of this study was to investigate whether gene alterations that are frequent in endometrial and/or ovarian cancers contribute to the pathogenesis of endometriosis. Biopsies were obtained from ectopic endometriosis lesions from 23 patients with revised American Fertility Score stage 1 (n= 1), 2 (n= 10), 3 (n= 11) or 4 (n= 1) endometriosis. Six genes (APC, CDKN2A, PYCARD, RARB, RASSF1 and ESR1) were analyzed for promoter hypermethylation using methylation-specific melting curve analysis, and 9 genes (BRAF, HRAS, NRAS, CTNNB1, CDK4, FGFR3, PIK3CA, TP53 and PTEN) were analyzed for mutations using denaturing gradient gel electrophoresis and direct sequencing. An oncogenic mutation in KRAS (c.34G > T; p.G12C) was detected in a single lesion. No gene alterations were found in the remaining samples. Our data suggest that genetic and epigenetic events contributing to endometrial and ovarian cancers are rare in endometriosis. However, other proto-oncogenes and tumor suppressor genes should be tested for alterations in order to identify the molecular basis of the susceptibility of endometriosis to malignant transformation.


Prebiotic synthesis from CO atmospheres: implications for the origins of life.
Most models of the primitive atmosphere around the time life originated suggest that the atmosphere was dominated by carbon dioxide, largely based on the notion that the atmosphere was derived via volcanic outgassing, and that those gases were similar to those found in modern volcanic effluent. These models tend to downplay the possibility of a strongly reducing atmosphere, which had been thought to be important for prebiotic synthesis and thus the origin of life. However, there is no definitive geologic evidence for the oxidation state of the early atmosphere and bioorganic compounds are not efficiently synthesized from CO(2) atmospheres. In the present study, it was shown that a CO-CO(2)-N(2)-H(2)O atmosphere can give a variety of bioorganic compounds with yields comparable to those obtained from a strongly reducing atmosphere. Atmospheres containing carbon monoxide might therefore have been conducive to prebiotic synthesis and perhaps the origin of life. CO-dominant atmospheres could have existed if the production rate of CO from impacts of extraterrestrial materials were high or if the upper mantle had been more reduced than today.


Efficacy of a prophylactic epidural blood patch in preventing post dural puncture headache in parturients after inadvertent dural puncture.
Postdural puncture headache (PDPH) occurs in up to 80% of parturients who experience inadvertent dural puncture during epidural catheter placement. The authors performed a randomized double blind study to assess the effect of prophylactic epidural blood patch on the incidence of PDPH and the need for therapeutic epidural blood patch. Sixty-four parturients who incurred inadvertent dural puncture were randomized to receive a prophylactic epidural blood patch with 20 ml autologous blood (prophylactic epidural blood patch group) or a sham patch (sham group). Subjects were evaluated daily for development of PDPH for a minimum of 5 days after dural puncture. Those who developed a PDPH were followed daily for a minimum of 3 days after resolution of the headache. Subjects with moderate headaches who reported difficulties performing childcare activities and all those with severe headaches were advised to receive a therapeutic epidural blood patch. Eighteen of 32 subjects in each group (56%) developed PDPH. Therapeutic blood patch was recommended in similar numbers of patients in each group. The groups had similar onset time of PDPH, median peak pain scores, and number of days spent unable to perform childcare activities as a result of postural headache. The median duration of PDPH, however, was shorter in the prophylactic epidural blood patch group. A decrease in the incidence of PDPH or the need for criteria-directed therapeutic epidural patch was not detected when a prophylactic epidural blood patch was administered to parturients after inadvertent dural puncture. However, prophylactic epidural blood patch did shorten the duration of PDPH symptoms.


High-power actively mode-locked sub-nanosecond Tm³⁺-doped silica fiber laser.
A diode-pumped actively mode-locked Tm³⁺-doped double-clad silica fiber laser providing up to 11.8 W of average output power and pulse widths in mode-locked operation of 38 ps at a repetition rate of 37.88 MHz is reported. Pulse energies of up to 314 nJ were obtained.


Porous Aromatic Framework with Tailored Binding Sites and Pore Sizes as a High-Performance Hemoperfusion Adsorbent for Bilirubin Removal.
Highly efficient removal of bilirubin from blood by hemoperfusion for liver failure therapy remains a challenge in the clinical field due to the low adsorption capacity and slow adsorption kinetics of currently used bilirubin adsorbents (e.g., activated carbon and ion-exchange resin). Recently, porous aromatic frameworks (PAFs) with high surface areas, tunable structures, and remarkable stability provide numerous possibilities to obtain satisfying adsorbents. Here, a cationic PAF with more mesopores, named iPAF-6, is successfully constructed via a de novo synthetic strategy for bilirubin removal. The prepared iPAF-6 exhibits a record-high adsorption capacity of 1249 mg g-1 and can adsorb bilirubin from 150 mg L-1 to normal concentration in just 5 min. Moreover, iPAF-6 shows a removal efficiency of 96% toward bilirubin in the presence of 50 g L-1 bovine serum albumin. It is demonstrated that positively charged aromatic frameworks and large pore size make a significant contribution to its excellent adsorption ability. More notably, iPAF-6/polyethersulfone composite fibers or beads are fabricated for practical hemoperfusion adsorption, which also show better removal performance than commercial adsorbents. This work can offer a new possibility for designing PAF-based bilirubin adsorbents with an appealing application prospect.


New insights into mechanisms driving carbon allocation in tropical forests.
The proportion of carbon allocated to wood production is an important determinant of the carbon sink strength of global forest ecosystems. Understanding the mechanisms controlling wood production and its responses to environmental drivers is essential for parameterization of global vegetation models and to accurately predict future responses of tropical forests in terms of carbon sequestration. Here, we synthesize data from 105 pantropical old-growth rainforests to investigate environmental controls on the partitioning of net primary production to wood production (%WP) using structural equation modeling. Our results reveal that %WP is governed by two independent pathways of direct and indirect environmental controls. While temperature and soil phosphorus availability indirectly affected %WP via increasing productivity, precipitation and dry season length both directly increased %WP via tradeoffs along the plant economics spectrum. We provide new insights into the mechanisms driving %WP, allowing us to conclude that projected climate change could enhance %WP in less productive tropical forests, thus increasing carbon sequestration in montane forests, but adversely affecting lowland forests.


Comprehensive immunohistochemical analysis based on the origin of leiomyosarcoma.
Diagnostic criteria, biological behavior, and treatment approaches of leiomyosarcomas (LMS) may differ according to the origin of the tumor. This is important in terms of patient's management, especially in tumors located in the peritoneum and retroperitoneal sites. In our study, we aimed to demonstrate the immunophenotypic characteristics of uterine and extra-uterine LMS using a large antibody panel, and to determine whether they potentially play a role in the differences among these tumor groups. Between 2006 and 2018, 29 uterine and 42 extra-uterine primary LMS were included in this study. Using tissue samples taken from the areas that best represented the tumor, an immunohistochemical study was performed on the blocks prepared by tissue micro-array method with estrogen and progesterone receptor (PR), WT-1, SMA, desmin, caldesmon, calponin, p16, p53, MDM2, CDK4, bcl-2, cyclin D1, fascin, EMMPRIN, FOXM1, c-erb-B2, c-Myc, PAX8, and CD117. Staining results of uterine and extra-uterine LMS were evaluated with these 20 antibodies. In uterine LMS compared with extra-uterine LMS, estrogen receptor (48% vs. 12%), PR (62% vs. 21%), desmin (79% vs. 50%), and EMMPRIN (69% vs. 45%) staining rate was detected higher. In extra-uterine LMS, caldesmon (88% vs. 69%), c-Myc (33% vs. 10%), and cyclin D1 (52% vs. 28%) were stained higher than uterine LMS (p < 0.05). No significant staining difference was detected with other antibodies. We concluded that estrogen receptor, PR, desmin, EMMPRIN, caldesmon, c-Myc, and cyclin D1 antibodies may help to determine primary origin of the tumor in LMS cases.


Plasma protein and venous thromboembolism: prospective cohort and mendelian randomisation analyses.
We conducted cohort and Mendelian randomisation (MR) analyses to examine the associations of circulating proteins with risk of venous thromboembolism (VTE) to provide evidence basis for disease prevention and drug development. Cohort analysis was performed in 11 803 participants without baseline VTE. Cox regression was used to estimate the associations between 257 proteins and VTE risk. A machine-learning model was constructed to compare the importance of identified proteins and traditional risk factors. Genetic association data on VTE were obtained from a genome-wide meta-analysis (26 066 cases and 624 053 controls) and FinnGen (14 454 cases and 294 700 controls). The cohort analysis, including 353 incident VTE cases diagnosed during a 6.6-year follow-up, identified 21 proteins associated with VTE risk after false discovery rate correction. The machine-learning model indicated that body mass index and von Willebrand factor (vWF) made the same as well as most of the contributions to the overall model prediction. MR analysis found that genetically predicted levels of vWF, SERPINE1 (plasminogen activator inhibitor 1, known as PAI-1), EPHB4 (ephrin type-B receptor 4), TYRO3 (tyrosine-protein kinase receptor TYRO3), TNFRSF11A (tumour necrosis factor receptor superfamily member 11A), and BOC (brother of CDO) were causally associated with VTE risk.


Eastern Cooperative Oncology Group phase II studies in advanced measurable colorectal cancer. I. Razoxane, Yoshi-864, piperazinedione, and lomustine.
During a 6-month interval, Eastern Cooperative Oncology Group randomized 127 patients who had received prior chemotherapy, and who had advanced measurable, surgically incurable colorectal cancer, to receive piperazinedione (PZD), Yoshi-864, or razoxane (ICRF-159). The observed response (and median survival) rates were: PZD, one of 35 patients (17 weeks); Yoshi-864, one of 34 (19 weeks), and ICRF-159, none of 38 (23 weeks). Among 107 evaluable patients, there were five episodes of life-threatening toxicity with PZD (one death) and four with ICRF-159 (two deaths). In the same protocol, 42 evaluable patients who had not received prior chemotherapy were randomized to be treated with lomustine (CCNU) or one of the three drugs in the "previously treated" trial. One CR (41 weeks) was seen with ICRF-159 and two PRs were seen with CCNU. Life-threatening toxicity occurred in three patients, two who received CCNU (one death) and one who received PZD. No survival advantage was seen. We do not encourage further phase II trials in colorectal cancer with the agents studied.


Bacterial Community Composition in Oligosaline Lake Bosten: Low Overlap of Betaproteobacteria and Bacteroidetes with Freshwater Ecosystems.
Oligosaline lakes in arid regions provide indispensable water resources for humans; however, information on the bacterial community composition (BCC) of this ecosystem is limited. In the present study, we explored seasonal and vertical variations in BCC in Lake Bosten, a unique oligosaline lake (1.2‰ salinity) in arid, northwestern China, using denaturing gradient gel electrophoresis and 16S rRNA gene sequencing. We obtained 544 clones and 98 operational taxonomic units (OTUs) from six clone libraries. The top 10 OTUs represented 59.4% of the entire bacterial community. Betaproteobacteria (22.1%), Gammaproteobacteria (19.9%), Bacteroidetes (18.8%), and Firmicutes (11.4%) dominated in Lake Bosten. Although seasonal variations were recorded in BCC, the vertical changes observed were not significant. Water temperature and salinity were the most important factors shaping the dynamics of BCC. A low degree of overlap was observed in BCC between Lake Bosten and freshwater ecosystems, especially for Betaproteobacteria and Bacteroidetes. An RDP seqmatch analysis showed that 169 sequences (31%) were novel bacterial sequences (<97% similarity to the closest sequences in GenBank), which suggested that specific indigenous bacteria inhabit this oligosaline environment. Our results support bacterial endemicity being more common than previously considered, particularly in oligosaline lakes. An analysis of these communities may reveal how bacteria respond to increases in salinity and nutrients in the early stage of salinization and eutrophication.


A comparative study of Chinese cosmology cum-humorology with eight elements.
As agriculturist, man recognized Earth, Heat and Water as essential to plant life and projected them as cosmic elements. Pastoral man observed animals multiply due to reproduction. He realized that reproduction resulted from the union of opposites as male and female. Projecting reproduction, he conceived creation, which then resulted as the union of the cosmic pair of opposites. Heaven and Earth. The Chinese conceived of creation as starting with creative energy in its latent form, as Thai-Chi, meaning the absolute existence. Later, it assumed its dynamic form called Chhi. It was dual-natured with the opposites called Yang (light) and Yin (darkness). The reproductive power was projected as creative energy called Chhi and male and female opposites were projected as the universal pair of opposites as Yang and Yin. Creative energy produced the cosmic elements which in turn produced all creation. The cosmic elements of Chinese cosmology were Wood, Fire, Water, Earth and Metal. They also included the factors of humorology when the following elements had, as contents, items belonging to humorology, Wood-contained Air, Earth.....Moisture; Metal.......Dryness. By assigning dual-sense to three cosmic elements, Chinese humorology came into existence but has incorporated it in its cosmology. It is easy to equate Air = Vayu of Tridosha doctrine of India, Moisture = Kapha, Dryness = Pitta. Then with five elements of cosmology including three with dual-sense, as belonging to humorology, we have eight elements in all as cosmology-cum-humorology. It is obvious that Air, so important in the cosmologies of India and Greece, is no where explicit in Chinese cosmology.(ABSTRACT TRUNCATED AT 250 WORDS)


Epidemiology of erythema ab igne at a moderately cold weather station.
Erythema ab igne is a localized red brown reticular pigmentation, resulting from chronic, repetitive exposure to sub maximal heat, insufficient to cause burn. A study was carried out at the dermatology outpatient department of Combined Military Hospital, Abbottabad during January-April 2005 with the purpose to see frequency of erythema ab igne. Fourteen patients were identified, interviewed and examined in detail. Nine were females, eight of them housewives, and five were males. Age of the patients ranged from 9 to 60 years with a mean of 36.5 +/- 14.8 years. Body Mass Index (BMI) of the patients ranged from 13.5 to 33.5, six of them were in the BMI range of between 25.1 and 30. Nine patients belonged to rural areas. Erythema ab igne was not associated with thyroid disease or any other systemic or psychiatric illness.


Leukoencephalomalacia in a white-tailed deer from North Carolina.
Leukoencephalomalacia similar to equine leukoencephalomalacia occurred in a white-tailed deer (Odocoileus virginianus) from North Carolina. The deer was recumbent and stuporous when presented for examination. It was believed that the disease resulted from ingestion of moldy field corn, infected with Fusarium moniliforme.


What's new in MR safety: the latest on the safe use of equipment in the magnetic resonance environment.
Magnetic resonance (MR) scanners present a unique set of safety risks for the healthcare facility. In the space surrounding an MR scanner, ferromagnetic objects can become deadly projectiles, device cables can become hot enough to cause burns, and medical equipment can cease to function properly. ECRI detailed these risks--and provided recommendations to help healthcare facilities minimize them--in a December 2001 Guidance Article. In this supplement to that article, we detail some recent MR safety developments and offer additional guidance. In particular, we describe changes in the terminology used to characterize the safety of devices in the MR environment, we outline new guidance on MR safe practices published by the American College of Radiology, and we review the safety issues that facilities need to be aware of when implementing 3-tesla (3 T) MR systems. We also present an updated Starter List of medical device models that have been designed for use in the MR environment. In addition, supplementary articles address the use of ferromagnetic detection systems and the selection of a fire extinguisher for use in the MR environment.


[Which studies are needed for the prediction of postoperative serum creatinine in unilateral nephrectomy? A retrospective analysis of 136 nephrectomies].
Among 136 patients with unilateral nephrectomy between 1985 and 1988 at the Marienhospital Gelsenkirchen the renal function was evaluated in the postoperative course. The serum creatinine value did increase from 88.4 +/- 5.3 mumol/l preoperatively to 168.8 +/- 13.3 mumol/l on the 10th postoperative day. The elevation was significantly higher in patients with more than one associated disease (e.g. diabetes, hypertension). The extent of creatinine elevation could predicated safe by both preoperative creatinine value and isotope renal split function analysis. Therefore, functional isotope examination may not be indicated in patients without impairment of renal function.


Wolbachia wAlbB remains stable in Aedes aegypti over 15 years but exhibits genetic background-dependent variation in virus blocking.
The ability of the maternally transmitted endosymbiotic bacterium Wolbachia to induce cytoplasmic incompatibility (CI) and virus blocking makes it a promising weapon for combatting mosquito-borne diseases through either suppression or replacement of wild-type populations. Recent field trials show that both approaches significantly reduce the incidence of dengue fever in humans. However, new questions emerge about how Wolbachia-mosquito associations will co-evolve over time and whether Wolbachia-mediated virus blocking will be affected by the genetic diversity of mosquitoes and arboviruses in the real world. Here, we have compared the Wolbachia density and CI expression of two wAlbB-infected Aedes aegypti lines transinfected 15 years apart. We have also assessed wAlbB-mediated virus blocking against dengue (DENV), Zika (ZIKV), and Chikungunya (CHIKV) viruses and examined whether host genetic backgrounds modulate viral blocking effects by comparing ZIKV infection in mosquitoes with a Mexican genetic background to those with a Singaporean background. Our results show that over 15 years, wAlbB maintained the capacity to form a stable association with Ae. aegypti in terms of both density and CI expression. There were variations in wAlbB-induced virus blocking against CHIKV, DENV, and ZIKV, and higher inhibitory effects on ZIKV in mosquitoes on the Singaporean genetic background than on the Mexican background. These results provide important information concerning the robustness and long-term stability of Wolbachia as a biocontrol agent for arbovirus disease control.


[Effects of 50 Hz sinusoidal electromagnetic field with different intensities on rat peak bone mass].
Studying effects of 50 Hz sinusoidal electromagnetic fields (SEMFs) with different intensities on peak bone mass (PBM) of rats may provide a theoretical basis for application of electromagnetic clinical field. 30 female SD rats, 6 weeks of age, were randomly divided into three groups: the control group, 0.1 mT electromagnetic field group (EMFs) and 0.6 mT EMFs. The EMFs groups were treated for 3 h/day. After 8 weeks, we examined their bone mineral densities (BMD) , measured their bone biomechanical properties, and made serum levels of osteocalcin (OC), tartrate-resistant acid phosphatase 5b (TRACP 5b), and histomorphometry. It was found that the BMD (P < 0.01), maximum mechanical load (P < 0.01) in the 0.1 mT group were significantly higher than those in the control group, and Yield strength (P < 0.05), the analyses of serum bone turnover markers and histomorphometric parameters were better than those in the control group (P < 0.05). However, the 0.6 mT group did not have significantly difference comparing with that in the control group. This study proved that 50 Hz 0.1 mT SEMFs can increased BMD, bone strength, and bone tissue microstructure. Therefore, 50 Hz 0.1 mT SEMFs can improve peak bone mass of rats.


Multilocus test for introgression between the cactophilic species Drosophila mojavensis and Drosophila arizonae.
Information obtained from laboratory studies regarding the efficacy of barriers to gene flow (reproductive isolation) between species is often incomplete or misleading, so detailed genetic analyses are needed to determine whether hybridization and introgression occur in nature. Previous laboratory studies of the cactophilic species Drosophila mojavensis and Drosophila arizonae suggest that reproductive isolation is incomplete and that gene flow may occur in sympatry. We sampled 18 nuclear and one mitochondrial loci from multiple populations of D. arizonae and D. mojavensis to test for the signature of recent or historic gene flow between these two species. We located chromosomal regions that were inverted between these species and analyzed those regions independently of others. Statistical tests for introgression using all loci or only collinear loci failed to reject expectations of an isolation model. Further tests using average nucleotide differences between species and phylogenetic analyses also failed to find support for introgression between D. mojavensis and D. arizonae. Additional ecological and behavioral studies of these species in their natural habitats are required to explain why the signature of gene flow was not detected at the DNA sequence level in populations when laboratory studies suggest such gene flow should be possible.


Stratum corneum integrity as a predictor for peristomal skin problems in ostomates.
Peristomal skin problems are common, most often the result is disruption of the skin barrier and this may account for more than one in three visits to ostomy nurses. Therefore a specific assessment of individual risk factors relating to the skin barrier function would be of great interest. Skin barrier integrity in ostomy patients with peristomal skin problems (PSP) was compared with that of ostomy patients with normal skin (controls) using transepidermal water loss (TEWL). Mechanical barrier disruption was determined by a tape stripping test and chemical barrier disruption [sodium lauryl sulphate (SLS) 0.25%]. Patients and controls had a highly significant increase in TEWL value in the peristomal area compared with nonperistomal contralateral abdominal skin (P < 0.0001 for both groups). The skin barrier of normal-looking contralateral skin of ostomates was found to be borderline impaired in patients with PSP compared with those without. A linear association was seen between the number of tape strips removed and TEWL for both cases and controls. Tape stripping suggested that patients with PSP had less resilient skin (P = 0.002). A significant difference in TEWL value between cases and controls was also seen for the SLS patch test on the dorsal skin (P = 0.02). Successive tape stripping, a situation analogous to the normal use of a pouching system, caused a higher degree of barrier damage more rapidly in patients with PSP, indicating an impaired mechanical quality of the barrier. The SLS exposure test suggested a generally increased susceptibility to irritant dermatitis as assessed by TEWL. Our findings suggest tape stripping and SLS testing may have a role as predictive tests to identify patients at risk of PSP.


[Impact of unilateral acute testicular ischemia on the contralateral testis of rabbits in anesthetic and conscious states].
To compare the impact of unilateral acute testicular ischemia on the hemodynamics and histology of the contralateral testis of the rabbits under consistent anesthesia with that of the rabbits in the conscious state. Forty-two healthy male white rabbits were randomly divided into an anesthetic group (Group A) to receive injection of sodium pentobarbital (PS) and a non-anesthetic group (Group B), each including a control group of 5 animals (A0 and B0), an incomplete testicular ischemia group of 8 (A1 and B1), and a complete testicular ischemia group of 8 (A2 and B2). Testicular ischemia models were constructed by color Doppler ultrasonography. Contrast-enhanced ultrasound (CEUS) was used to observe the perfusion of the contralateral testes before and after ligating and loosening the unilateral spermatic cord in each experimental group. The control animals also underwent CEUS and measurement of the heart rate (HR) and blood pressure (BP) at the corresponding time. Histological structure changes in the contralateral testes of the rabbits were observed in both anesthetic and conscious states. PS anesthesia markedly suppressed the HR and BP of the rabbits. The parameters in Groups of A0, A1 and A2 showed no statistically significant changes after unilateral ligation of the spermatic cord, while Groups B1 and B2 displayed significantly decreased peak-base difference (PBD) and prolonged arrival time (AT) and half time of descending peak intensity (HT). Groups A1, B1 and B2 showed significantly increased PBD and prolonged HT shortly after loosening the spermatic cord. Focal pathological and ultrastructural changes were observed in the contralateral testes of the ischemic rabbits, but no significant difference was found in Johnson's score in comparison with the controls. The apoptotic cells were remarkably increased in Groups A1, B1 and B2. Acute testicular ischemia may induce injury to the contralateral testis to some degree, and a reflexive sympathetic response may cause hemodynamic changes in the non-anesthetic state. And the neural and vascular inhibitory effects of anesthesia could make insignificant changes of blood perfusion in the contralateral testis.


Epidemiological survey of hepatitis B virus infections in various groups of population.
An epidemiological survey of hepatitis B virus (HBV) infection has been carried out from 1974 up to 1978 in four laboratories, with the aim of identifying high-risk groups in the population. Radioimmunoassay procedures were used in order to detect the hepatitis B surface antigen (HBsAg) and the corresponding antibody (anti-HBs) in serum samples from over 100,000 individuals of various geographical origin (mainly from Ligury or from other areas in Northern Italy). The groups of population under monitoring included: individuals without hepatic illness just after admittance into hospitals (these groups were found to be adequately representative of the corresponding open population), groups of children and boys from the open school population, individuals living in various communities (foundling hospital, children college, recruits, institutionalized old people, subnormal individuals and their assistance staff), non-assistance working categories (workers from metallurgical and chemical industries, shipped seamen), hospital assistance personnel, dialyzed and transplanted renal patients, blood donors. The results obtained showed a considerable variability of HBV infections among the examined groups of population. In particular, the frequency of HBsAg and/or anti-HBs detection appeared to be significantly affected by each of the following epidemiological parameters: geographical area, sex, age, pregnancy, life in communities and contacts with hepatitis patients, mental deficiency, non-assistance working activities, assistance activity in the hospital environment, hemodialysis and transplants, selection of population groups by HBsAg screening.


[The provocation test in extrinsic allergic alveolitis].
The Authors review the use of provocation test, added to other diagnostic procedures, in the study of extrinsic allergic alveolitis (E.A.A.). In the light of the still present uncertainty on the pathogenesis of the disease and on the ethics of these tests, the Authors assert that the provocation tests in E.A.A. are inadvisable because on the one hand they are uncertain as regards execution and evaluation and on the other hand they are dangerous for the patient.


Long-term results of partial pancreaticoduodenectomy for ductal adenocarcinoma of the pancreatic head: 25-year experience.
The prognosis of patients who undergo resection for pancreatic ductal adenocarcinoma with curative intention is generally poor unless they have early-stage disease. Based on our 25-year experience, the results of 194 patients after a standardized Kausch-Whipple resection for adenocarcinoma of the pancreatic head were analyzed and the prognostic factors were evaluated. Between 1972 and 1998 a total of 221 patients were diagnosed for ductal adenocarcinoma of the pancreatic head, and 194 of them subsequently underwent a standardized Kausch-Whipple resection. Long-term results and prognostic factors were examined by multivariate and univariate analyses. The overall postoperative mortality was 3.09%, and the morbidity was 29.9%. By multivariate analysis only curative resection (R0) was significantly related to a favorable prognosis ( p < 0.0001). Furthermore, in case of a curative resection, the presence of lymph node metastases showed prognostic significance in the multivariate analysis ( p = 0.005). Cumulative survival analysis revealed a 5-year survival rate of 25.4%, a 7-year survival rate of 12.3%, and a 10-year survival rate of 8.2% for patients who underwent curative resection (R0) for adenocarcinoma of the pancreatic head. We demonstrated that the R0 status is the only independent prognostic factor after surgery for adenocarcinoma of the pancreatic head. In the case of a curative resection, the presence of lymph node metastases is of prognostic relevance. In view of considerable surgical morbidity and mortality, resection for cancer of the pancreatic head is the only option if the lesion is resectable. We concluded that surgical treatment is "as good as it gets," as extended techniques have not proved to produce better results.


Multicomponent Reaction of Isocyanide, Ditelluride, and Mn(III) Carboxylate: Synthesis of N-Acyl Tellurocarbamate.
A multicomponent reaction of isocyanides, ditellurides and manganese(III) carboxylates under mild reaction conditions leads to the synthesis of various N-acyl tellurocarbamates. This method demonstrates good functional tolerance and broad substrate scope and, as a result, is especially suitable for the postfunctionalization of complicated molecules such as drugs. The given method can be further extended to the synthesis of selenocarbamates.


Adult-onset MELAS syndrome in a 51-year-old woman without typical clinical manifestations: a case report.
Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a multi-organ disorder resulting from mitochondrial DNA (mtDNA) mutations. We report a case of suspected MELAS syndrome that progressed to left ventricular dysfunction 24 years after an initial diagnosis of atrioventricular block (AVB). A 51-year-old woman was referred to heart failure clinic because of dyspnoea on exertion and progressive cardiomegaly. She had a dual-chamber pacemaker implanted for 24 years because of a high-degree AVB. She was treated for diabetes mellitus for 23 years and used hearing aids for 12 years because of sensorineural hearing loss. Transthoracic echocardiography revealed reduced left ventricular ejection fraction (26%), with increased thickness and unusual texture of the myocardium. The absence of abnormal findings on serum and urine protein electrophoresis suggested that light-chain amyloidosis was unlikely. In addition, 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy revealed no definite uptake in the myocardium. Endomyocardial biopsy revealed a hypertrophy of myocytes in haematoxylin-eosin staining, and electron microscopy revealed a disarrangement of mitochondrial cristae, which were suggestive of mitochondrial cardiomyopathy. A mtDNA test detected the m.3243A > G mutation in the MT-TL1 gene. According to these findings, MELAS syndrome was the most probable diagnosis despite the absence of common symptoms such as stroke-like episodes or lactic acidosis. The patient had progressed to heart failure with reduced ejection fraction 24 years after the first cardiac manifestation. An identification of the mutation in the MT-TL1 gene, indicative of MELAS syndrome, enabled the diagnosis of MELAS syndrome without typical manifestations.


The Current Status of Microvascular Decompression for the Treatment of Hemifacial Spasm in Japan: An Analysis of 2907 Patients Using the Japanese Diagnosis Procedure Combination Database.
Microvascular decompression (MVD) is widely used as a safe and effective treatment for hemifacial spasm (HFS). However, the extent of application of this therapeutic method and its outcomes in Japan are currently unclear. To address these questions, we analyzed the utilization of MVD for the treatment of HFS during the 33- month period from July 2010 to March 2013. We conducted an analysis on data contained in the Diagnosis Procedure Combination database in Japan. This analysis showed that MVD was used for the treatment of HFS in 2907 cases (men, 916; women, 1991) with 2.2 times more women treated than men. MVD for HFS was most frequently performed in women aged 50 to 69 years; however, most men were aged between 40 and 59 years at the time of the procedure. The numbers of procedures performed per 100,000 population/year were 0.83 overall in Japan, with the numbers larger in prefectures with larger populations. Regarding discharge outcomes, the mortality rate was 0.1%. The mean length of hospital stay in patients undergoing MVD for HFS was 14.7 days. This analysis provides preliminary information regarding the trends in the performance of MVD for the treatment of HFS in Japan. Further studies on other registries that contain data obtained by standardized assessment methods and that include long-term outcomes and postoperative complications are required.


Ultramicroporous Metal-Organic Framework with Inert Pore Surfaces for Inversed Separation of Ethylene from C2 Hydrocarbons Mixtures.
The achievement of direct C2H4 separation from C2 hydrocarbons is very challenging in the petrochemical industry due to their similar molecular sizes, boiling points, and physicochemical properties. In this work, a nonpolar/inert ultramicroporous metal-organic framework (MOF), [Co3(μ3-OH)(tipa)(bpy)1.5]·3DMF·6H2O (1), with stand-alone one-dimensional square tubular channels was successfully constructed, its pore enriched with plenty of aromatic rings causing nonpolar/inert pore surfaces. The MOF shows preferential adsorption of C2H6 compared to C2H4 and C2H2 in the low-pressure region, which is further verified by adsorption heats and selectivities. The C2H4 separation potential in one step for binary C2H6/C2H4 (50/50 and 10/90) and ternary C2H4/C2H6/C2H2 (89/10/1) is also examined by transient breakthrough simulations. Moreover, grand canonical Monte Carlo simulations demonstrate that the unique reversed adsorption mechanism is due to the shortest and most number of C-H···π interactions between C2H6 and the framework.


The quantitative relationship between "the metabolic syndrome" and abdominal obesity in women.
Abdominal obesity is closely associated with the presence of metabolic risk factors and elevated blood pressure in selected materials. This has, however, never been analyzed quantitatively in a non-selected cohort. Therefore, in a population-based study of 1462 Swedish women, four selected risk factors for non-insulin dependent diabetes mellitus (NIDDM) and cardiovascular disease (CVD), serum triglycerides, blood glucose and systolic blood pressure and also serum insulin in a subsample, were examined in relation to regional and overall obesity. This was performed by subdividing the age adjusted sample into quintiles of waist to hip circumference ratio (WHR) or body mass index (BMI) as indicators of abdominal distribution of body fat and overall obesity, respectively. The risk factors serum triglycerides, blood glucose, blood pressure and serum insulin were defined as being elevated when the value of the risk factor was higher than the mean plus one or two standard deviations of the total age-adjusted cohort. The percentage of women with elevated risk factors according to this definition was then calculated in each of these quintiles. Having a risk factor which was elevated according to the definition was significantly correlated to WHR and BMI (p<0.0001) independent of age. The presence of one or several of these elevated risk factors was clearly higher than expected in the fifth quintile of WHR, and to a lesser extent in the fifth quintile of BMI while this was not the case in the lower quintiles of WHR and BMI. When studying the combination of the WHR and BMI, the presence of risk factors higher than the mean plus two standard deviations increased gradually with WHR in all five quintiles of BMI. A significant association was observed between WHR and presence of risk factors independent of BMI (p<0.0001) but BMI did not remain significantly correlated to presence of risk factors when controlling for WHR (p=0.09). These results indicate that abdominal distribution of body fat in women independently of general obesity is closely associated with metabolic risk factors including elevated blood pressure, a metabolic syndrome with increased risk for cardiovascular disease and non-insulin dependent diabetes mellitus.


Determination of Total and Unbound Meropenem, Imipenem/Cilastatin, and Cefoperazone/Sulbactam in Human Plasma: Application for Therapeutic Drug Monitoring in Critically Ill Patients.
Critically ill patients show several pathophysiological alterations that can complicate antibiotic dosing. Hence, there is a strong rationale to individualize anti-infective dosing in these patients by using therapeutic drug monitoring (TDM). The current study aimed to develop and validate a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of total and unbound plasma concentrations of 3 commonly used antibiotics (meropenem, imipenem/cilastatin, and cefoperazone/sulbactam) in the treatment of infections in critically ill patients in China, which could be suitable for routine TDM in hospital laboratories. The unbound drug was separated from the bound drug by ultrafiltration. Simple protein precipitation was used for sample preparation. Meropenem, imipenem/cilastatin, cefoperazone/sulbactam, and their corresponding internal standards were then resolved using the Waters CORTECS C18 column. All the compounds were detected using electrospray ionization in the positive/negative ion-switching mode. The calibration curves were linear for all compounds, with correlation coefficients (R) above 0.99 for total concentrations in human plasma and unbound concentrations in the plasma ultrafiltrate. For both total and unbound drugs, the relative errors and intra-assay/interassay relative standard deviations were below 15%. The limit of quantification was 0.05 mcg/mL for both total plasma concentrations and plasma ultrafiltrate concentrations of all compounds. The method was simple, rapid, and reliable and is currently being used to provide a TDM service to enhance the efficacious use of the 3 antibiotics.


Current control and future risk in asthma management.
Despite international and national guidelines, poor asthma control remains an issue. Asthma exacerbations are costly to both the individual, and the healthcare provider. Improvements in our understanding of the therapeutic benefit of asthma therapies suggest that, in general, while long-acting bronchodilator therapy improves asthma symptoms, the anti-inflammatory activity of inhaled corticosteroids reduces acute asthma exacerbations. Studies have explored factors which could be predictive of exacerbations. A history of previous exacerbations, poor asthma control, poor inhaler technique, a history of lower respiratory tract infections, poor adherence to medication, the presence of allergic rhinitis, gastro-oesophageal reflux disease, psychological dysfunction, smoking and obesity have all been implicated as having a predictive role in the future risk of asthma exacerbation. Here we review the current literature and discuss this in the context of primary care management of asthma.


The effect of device-based cardiac contractility modulation therapy on myocardial efficiency and oxidative metabolism in patients with heart failure.
Cardiac contractility modulation (CCM) is a device-based therapy that involves delivery of nonexcitatory electrical signals resulting in improved ventricular function and a reversal of maladaptive cardiac fetal gene programmes. Our aim was to evaluate whether acute application of CCM leads to an increase in myocardial oxygen consumption (MVO(2)) in patients with chronic heart failure using (11)C-acetate positron emission tomography (PET). We prospectively enrolled 21 patients with severe heart failure. (11)C-acetate PET was performed before and after activation of the CCM device. In 12 patients an additional stress study with dobutamine was performed. Under resting conditions, the values of myocardial blood flow (MBF), MVO(2) and work metabolic index (WMI, reflecting myocardial efficiency) with the CCM device activated did not differ significantly from the values with the device deactivated. MBF was 0.81 ± 0.18 ml min(-1) g(-1) with the device off and 0.80 ± 0.15 ml min(-1) g(-1) with the device on (p = 0.818), MVO(2) was 6.81 ± 1.69 ml/min/100 g with the device off and 7.15 ± 1.62 ml/min/100 g with the device on (p = 0.241) and WMI was 4.94 ± 1.14 mmHg ml/m(2) with the device off and 5.21 ± 1.36 mmHg ml/m(2) with the device on (p = 0.344). Under dobutamine stress, the values of MBF, MVO(2) and WMI with the CCM device activated did not differ from the values with the device deactivated, but were significantly increased compared with the values obtained under resting conditions. These results indicate that CCM does not induce increased MVO(2), even under stress conditions.


Translating Analytical Techniques in Geochemistry to Environmental Health.
From human health exposure related to environmental contamination to ancient deep-Earth processes related to differentiation of the Earth's geochemical reservoirs, the adaptability of inductively coupled plasma mass spectrometry (ICP-MS) has proven to be an indispensable standard technique that transcends disciplines. Continued advancements in ICP-MS, including improved auxiliary applications such as laser ablation (LA), ion/liquid chromatography (IC), automated pre-concentration systems (e.g., seaFAST), and improved desolvating nebulizer systems (e.g., Aridus and Apex) have revolutionized our ability to analyze almost any sample matrix with remarkable precision at exceedingly low elemental abundances. The versatility in ICP-MS applications allows for effective interdisciplinary crossover, opening a world of analytical possibilities. In this communication, we discuss the adaptability of geochemical techniques, including sample preparation and analysis, to environmental and biological systems, using Pb isotopes for source apportionment as a primary example.


N-methylnicotinamide inhibits arterial thrombosis in hypertensive rats.
There are few findings indicating that nicotinamide may potentially influence intravascular thrombosis. Interestingly, N-methylnicotinamide, one of the metabolites of nicotinamide - could be more potent than its parent compound. In the present study we have investigated the influence of N-methylnicotinamide on arterial thrombosis in normotensive and renovascular hypertensive rats. The contribution of platelets, coagulation and fibrinolytic systems in the mode of N-methylnicotinamide action was also determined. Furthermore, we examined the role of nitric oxide/prostacyclin in the mechanisms of N-methylnicotinamide action. N-methylnicotinamide, but not nicotinamide, administered intravenously into renovascular hypertensive rats developing electrically induced arterial thrombosis caused dose-dependent decrease of thrombus weight, collagen-induced platelet aggregation and plasma antigen/activity of plasminogen activator inhibitor - 1, without changing of occlusion time, routine coagulation parameters and plasma activity of tissue plasminogen activator. Indomethacin - an inhibitor of prostacyclin synthesis, completely abolished the antithrombotic and antiplatelet effect of N-methylnicotinamide, and the plasma level of 6-keto-PGF(1alpha) , prostacyclin metabolite, increased simultaneously with the inhibition of thrombus formation. Our study shows that N-methylnicotinamide via production/release of prostacyclin inhibits arterial thrombosis development. The antithrombotic effect of N-methylnicotinamide is accompanied by platelet inhibition and enhanced fibrinolysis, due to the decrease production of plasminogen activator inhibitor - 1.


Preparation of the 2'-deoxynucleosides of 2,6-diaminopurine and isoguanine by direct glycosylation.
The purine nucleoside 2,6-diaminopurine-2'-deoxyriboside is prepared by the direct glycosylation of the 2,6-bis(tetramethylsuccinimide) derivative of the parent purine heterocycle 4 with 2-deoxy-3,5-di-O-(p-toluoyl)-alpha-D-erythro-pentofuranosyl chloride 5 using the sodium salt method. 2'-Deoxyisoguanosine is prepared from 2,6-diaminopurine by a five-step procedure. The purine heterocycle isoguanine is prepared by selective diazotization of 2,6-diaminopurine and then converted to the N9-trityl derivative to increase solubility. After silylation of the O(2)-carbonyl with TMSCl, the N(6)-amino group is protected as the tetramethylsuccinimide (M(4)SI). The O(2)-carbonyl is protected as the DPC derivative, and the trityl group is removed. The resulting product is glycosylated in good yield to generate fully protected 2'-deoxyisoguanosine.


Expression and clinical relevance of SPOPL in medulloblastoma.
Medulloblastoma (MB) is a type of malignant brain tumor in children. Although knowledge of MB is increasing and the survival rate of patients with MB has improved in previous years, the long-term treatment-associated complications remain unfavorable. Early diagnosis and treatment is critical for patients with MB, but effective molecular markers for MB remain elusive. The Speckle-type POZ protein (SPOP) is a member of the MATH-BTB protein family and is a type of joint molecule for Cullin-3. SPOP inhibits tumor growth. However, the SPOP-like (SPOPL) gene, which is a SPOP paralog gene and shares an overall 85% sequence identity with SPOP, has not been explored in cancer studies at present. The results of the present study demonstrate that the SPOPL expression is decreased in MB cells and tissues compared with normal cells and tissues at the protein and mRNA levels. Immunohistochemical analysis revealed decreased expression of SPOPL in 42/56 (75%) paraffin-embedded archival MB biopsies, and SPOPL expression may be associated with the MB differentiation level (P=0.011). Patients with increased SPOPL expression exhibit improved survival rates compared with those with decreased SPOPL expression, and the SPOPL gene may be a potentially valuable molecular marker of MB.


Incidence of Laryngotracheal Stenosis after Thermal Inhalation Airway Injury.
Inhalation injury is independently associated with burn mortality, yet little information is available on the incidence, risk factors, or functional outcomes of thermal injury to the airway. In patients with thermal inhalation injury, we sought to define the incidence of laryngotracheal stenosis (LTS), delineate risk factors associated with LTS development, and assess long-term tracheostomy dependence as a proxy for laryngeal function. Retrospective cohort study of adult patients treated for thermal inhalation injury at a single institution burn critical care unit from 2012 to 2017. Eligible patients' records were assessed for LTS (laryngeal, subglottic, or tracheal stenosis). Patient characteristics, burn injury characteristics, and treatment-specific covariates were assessed. Descriptive statistics, Mann-Whitney U-tests, odds ratio, and chi-square tests compared LTS versus non-LTS groups. Of 129 patients with thermal inhalation injury during the study period, 8 (6.2%) developed LTS. When compared with the non-LTS group, patients with LTS had greater mean TBSA (mean 30.3, Interquartile Range 7-57.5 vs 10.5, Interquartile Range 0-15.12, P = .01), higher grade of inhalation injury (mean 2.63 vs 1.80, P = .05), longer duration of intubation (12.63 vs 5.44; P < .001), and greater inflammatory response (mean white blood cell count on presentation 25.8 vs 14.9, P = .02, mean hyperglycemia on presentation 176.4 vs 136.9, P = .01). LTS patients had a significantly higher rate of tracheostomy dependence at last follow-up (50 vs 1.7%, P < .001). Six percent of patients with thermal inhalation injury develop LTS. LTS was associated with more severe thermal airway injury, longer duration of intubation, and more severe initial host inflammation. Patients with inhalation injury and LTS are at high risk for tracheostomy dependence. In burn patients with thermal inhalation injury, laryngeal evaluation and directed therapy should be incorporated early into multispecialty pathways of care.


Genetic control of resistance to mercury-induced immune/autoimmune activation.
Previous studies have shown that genetic factors control the susceptibility to mercury-induced immunoglobulin (Ig)G1 antibody formation, IgE synthesis, renal IgG deposits and antinucleolar autoantibodies (ANolA) production in the susceptible mice. In this study, we examined the genetic control of resistance to these characteristics after HgCl2 injection in F1 hybrid crosses between the highly mercury resistant DBA/2 and mercury susceptible NZB (H-2d), SJL (H-2 s), A.CA (H-2f) and DBA/1 (H-2q) mice and also in backcross hybrids between (DBA/2 x SJL)F1 and SJL mice. We observed that mercury-induced immune/autoimmune manifestations were profoundly downregulated in most (if not all) of the F1 hybrids, indicating that the resistance to mercury was a dominant trait. Analysis of mercury-induced immune/autoimmune responses in the (DBA/2 x SJL) x SJL backcross hybrids suggested that only one gene or a cluster of genes determined the resistance to the ANolA production, whereas the resistance to other characteristics was controlled by two and/or three gene loci. By H-2 genotyping the backcross mice, it was found that H-2d haplotype per se could confer resistance to ANolA production. However, we did not find any significant association between the H-2d haplotype and the resistance to increase of IgG1 and IgE synthesis and the development of renal IgG1 deposits. Thus, while in DBA/2 mice, gene(s) in the H-2 loci strictly contribute to the inheritance of resistance to ANolA production; non-H-2 genes mainly govern the inheritance of unresponsiveness regarding other characteristics.


Effects of discontinuation of phenytoin, carbamazepine, and valproate on concomitant antiepileptic medication.
We report a prospective, controlled study of the effects of the reduction and discontinuation of phenytoin (PHT) (22 patients), carbamazepine (CBZ) (23 patients), and valproate (VPA) (25 patients) with concomitant antiepileptic drugs (AEDs). The principal changes in the serum concentrations of concomitant AEDs were (a) phenobarbital (PB) concentrations decreased by a mean of 30% on discontinuation of PHT; (b) total CBZ concentrations increased by a mean of 48% and free CBZ concentrations increased by a mean of 30% on discontinuation of PHT, with no change in CBZ-10, 11-epoxide (CBZ-E) concentrations; (c) VPA concentrations increased by a mean of 19% on discontinuation of PHT; (d) VPA concentrations increased by a mean of 42% on discontinuation of CBZ; (e) ethosuximide (ESM) concentrations increased by a mean of 48% on discontinuation of CBZ; (f) PHT concentrations decreased by a mean of 26% on discontinuation of CBZ; (g) PHT free fraction decreased from a mean of 0.11 to 0.07 on discontinuation of VPA; and (h) the mean concentrations of total and free CBZ increased by a mean of 10 and 16%, respectively, on VPA discontinuation, with a concomitant mean 24% decrease in total CBZ-E and a 22% decrease in free CBZ-E. Apart from the decrease in PB concentrations on PHT discontinuation, all significant changes had occurred by 1 week after the end of AED discontinuation. The implication for clinical practice is that a serum AED concentration at this time reflects the new steady state. Free concentrations did not add any clinically useful information to that gained from analysis of total serum concentrations.


Robust Learning Control for Shipborne Manipulator With Fuzzy Neural Network.
The shipborne manipulator plays an important role in autonomous collaboration between marine vehicles. In real applications, a conventional proportional-derivative (PD) controller is not suitable for the shipborne manipulator to conduct safe and accurate operations under ocean conditions, due to its bad tracing performance. This paper presents a real-time and adaptive control approach for the shipborne manipulator to achieve position control. This novel control approach consists of a conventional PD controller and fuzzy neural network (FNN), which work in parallel to realize PD+FNN control. Qualitative and quantitative tests of simulations and real experiments show that the proposed PD+FNN controller achieves better performance in comparison with the conventional PD controller, in the presence of uncertainty and disturbance. The presented PD+FNN eliminates the requirements for precise tuning of the conventional PD controller under different ocean conditions, as well as an accurate dynamics model of the shipborne manipulator. In addition, it effectively implements a sliding mode control (SMC) theory-based learning algorithm, for fast and robust control, which does not require matrix inversions or partial derivatives. Furthermore, simulation and experimental results show that the angle compensation deviation of the shipborne manipulator can be improved in the range of ±1°.


[Research Progress in Technology of Using Soil Micro-organisms to Generate Electricity and Its Potential Applications].
Microbial fuel cells ( microbial fuel cells, MFCs) are devices in which micro-organisms convert chemical energy into electrical power. Soil has electrogenic bacteria and organic substrates, thus can generate electrical current in MFCs. Soil MFCs can be operated and applied to real-time and continuously monitor soil pollution, remove soil pollutants and to reduce methane emitted from flooded rice paddy, without energy consumption and the application of chemical reagents to the soil. Instead, the operation of soil MFCs generates small amount of electrical power. Therefore, soil MFCs are useful in the development of environment-friendly technology for monitoring and remediating soil pollution, which have potential value for applications in the domain of environmental science and engineering. However, much of advanced technology hasn't been applied into soil MFCs since the studies on soil MFCs was not started until recently. This paper summarized the research progress in related to soil MFCs combining with the frontier of MFCs technology, and brought forward the possible direction in studies on soil MFCs.


Clinical study of the sensitivity and dynamic range of three digital systems, E-speed film and digitized film.
The objective of the present study was to clinically evaluate the sensitivity and dynamic range of three digital systems (Sens-A-Ray, CDR, Digora), digitized film and E-speed film. Five objects were submitted to three different kilovoltages and seven exposure times. In order to evaluate the relationship between exposure time and dosage, measurements were made in a dental x-ray unit with an ion chamber, X-ray timer and kVp meter. For each system, 105 radiographs were taken, totalling 525 images, that were evaluated by six trained observers by means of scoring from 0 to 4. The scores attributed to the images for each of the systems were submitted to analysis of variance and Turkey's test. The results showed statistically significant differences (p < 0.01) with the storage phosphor system producing the wider dynamic range, followed by the digitized film. The CDR system showed the greater sensitivity, followed by the Digora system.


Removal of Painful Os Paracuneiforme: A Case Report.
Os paracuneiforme (OPC) is an extremely rare accessory bone located either medial to the medial cuneiform or to the naviculocuneiform joint. Although OPC often appears on the list of accessory ossicles, there are few reported cases regarding this bone. OPC can cause symptoms that require surgical intervention, but only 2 surgically treated cases have been published in the literature in English. Here, we report the case of a patient with painful OPC who was surgically treated. The patient showed no restriction in his daily living and recreational activities 6 months postoperatively. This is the first report showing not only preoperative and postoperative radiographs, but also preoperative CT images, photographs of intraoperative findings, and the resected ossicle. Level of Evidence: Level V.


Actinomyces in infected osteoradionecrosis--underestimated?
Infected osteoradionecrosis (IORN) is a severe complication of radiation therapy for head and neck cancer. Infected osteoradionecrosis can lead to fracture and often requires subsequent jaw resection. It is known that irradiated bone is highly susceptible to infections, mainly with Candida species and cariogenic bacteria. Only very few data exist on Actinomyces in IORN. The study population consisted of 31 patients (7 female, 24 male; median age, 58.3 years). All patients exhibited clinical and radiological signs of IORN (infection, mucosa or skin fistula, and sequestrated bone). To detect Actinomyces colonies, histological examination was performed using several staining procedures (hematoxylin-eosin, Gram, Grocott, periodic acid-Schiff). In addition, a semi-nested polymerase chain reaction (PCR) approach was designed targeting the 16S ribosomal RNA gene. We found prominent Actinomyces colonies in 20 (64.5%) of 31 patients. Most of these lesions were localized in the mandible (16/20). Most interestingly, Actinomyces were almost exclusively found attached to the necrotic bone. PCR testing confirmed the presence of Actinomyces-specific DNA sequences (Actinomyces israelii). We show that Actinomyces is considerably more frequent in IORN than previously demonstrated. We suggest that these organisms are involved in the chronic, nonhealing inflammatory processes and the purulent discharge, which are known as characteristics of IORN. It remains to be investigated whether Actinomyces could be involved in the osteolytic mechanisms. From the histopathologic perspective, detection of Actinomyces is important because these bacteria have been shown to be associated with prolonged treatment duration.


[Nitroglycerin ointment v.s. sublingual nitroglycerin on peripheral venomotricity in man (author's transl)].
Topical administration of nitroglycerin ointment (NGO) was suggested as a useful therapeutic approach for angina pectoris in man. In six healthy volunteers the effects of NGO (15 mg) on venous motricity (VM) were compared to those of a placebo ointment and of the sublingual form (NGS) (0.75 mg). VM was assessed at regular intervals by an original atraumatic technique involving simultaneous measurement of dorsal hand vein diameter (HVD) and whole hand volume changes (VH) during short inflation periods of a sphygmomanometer cuff around the upper arm. A venous distensibility ratio (VDR = HVD/VH) was used as VM index. With NGS, the maximum increase in VDR (from 0.60 to 2.30)(230.6 +/- 13.9%) occurs after 10 min but the effect completely disappears after 1.5 hours. With NGO, the increase in VDR is slightly less marked (from 0.81 to 1.80) (120.1 +/- 4.2%) but occurs as early as with NGS; subsequently VDR stabilizes at a plateau value of 1.6 for at least 6 hours, thus demonstrating the early and long-lasting efficacy of NGO.


Singular and combined effects of electrical stimulation, post-mortem ageing and blade tenderisation on the palatability attributes of beef from young bulls.
Thirty Santa Gertrudis bulls (approximately 15-18 months old) were slaughtered, dressed and split into siides. The right side of each carcass was electrically stimulated (ES) with seventeen impulses (1·8s impulse duration; 1·8s interval between impulses) of 550 V (AC) and 5 A while the left side served as a non-stimulated control (not-ES). At 24h post morten, USDA quality and yield grade data were obtained from each side. On the second day post mortem, all sides were fabricated and strip loins, top sirloin butts and ribeyes were obtained from each side for post-mortem ageing and blade tenderisation studies. Steaks were removed after a post-mortem ageing period of 4 or 18 days and before (not-BT) or after blade tenderisation (BT) for sensory panel evaluations or shear force determinations. ES sides had more youthful lean maturity (P < 0·0001), higher marbling (P < 0.·002), higher USDA quality grades (P < 0·0.0001) and finer-textured lean (P < 0·002) than did not-stimulated (not-ES) sides. ES significantly improved (P < 0·05) palatability traits in two of twenty-four comparisons; BT significantly improved palatability traits in twelve of twenty-four comparisons and 18-day post-mortem ageing significantly improved palatability traits in seven of twelve comparisons. No significant reductions (P < 0·05) in shear force values were observed for steaks from ES versus not-ES sides while significant reductions (P < 0·05) were observed for steaks from BT versus non-BT cuts (four of six comparisons) and for steaks from cuts aged for 18 versus 4 days (ten of twelve comparisons). BT and 18-day post-mortem ageing were more effective for increasing palatability or for decreasing shear force requirements than was ES; however, ES greatly improved lean colour of meat from bulls.


FTY720 story. Its discovery and the following accelerated development of sphingosine 1-phosphate receptor agonists as immunomodulators based on reverse pharmacology.
Fingolimod (FTY720) is the first of a novel class: sphingosine 1-phosphate (S1P) receptor modulator and is currently in phase 3 clinical trials for multiple sclerosis (MS). FTY720 was first synthesized in 1992 by chemical modification of an immunosuppressive natural product, ISP-I (myriocin). ISP-I was isolated from the culture broth of Isaria sinclairii, a type of vegetative wasp that was an 'eternal youth' nostrum in traditional Chinese medicine. ISP-I is an amino acid having three successive asymmetric centers and some functionalities. We simplified the structure drastically to find a nonchiral symmetric 2-substitued-2-aminopropane-1,3-diol framework for an in vivo immunosuppressive activity (inhibition of rat skin allograft rejection test or prolonging effect on rat skin allograft survival) and finally discovered FTY720. During the course of the lead optimization process, we encountered an unexpected dramatic change of the mechanism of action with an in vivo output unchanged. Since it proved that FTY720 did not inhibit serine palmitoyltransferase that is the target enzyme of ISP-I, reverse pharmacological approaches have been preformed to elucidate that FTY720 is mainly phosphorylated by sphingosine kinease 2 in vivo and the phosphorylated drug acts as a potent agonist of four of the five G protein coupled receptors for S1P: S1P(1), S1P(3), S1P(4) and S1P(5). Evidence has accumulated that immunomodulation by FTY720-P is based on agonism at the S1P(1) receptor. Medicinal chemistry targeting S1P(1) receptor agonists is currently in progress. The FTY720 story provides a methodology where in vivo screens rather than in vitro screens play important roles in the lead optimization. Unlike recent drug discovery methodologies, such a strategy as adopted by the FTY720 program would more likely meet serendipity.


5-Demethylnobiletin mediates cell cycle arrest and apoptosis via the ERK1/2/AKT/STAT3 signaling pathways in glioblastoma cells.
5-Demethylnobiletin is the active ingredient in citrus polymethoxyflavones that could inhibit the proliferation of several tumor cells. However, the anti-tumor effect of 5-Demethylnobiletin on glioblastoma and the underlying molecular mechanisms are remains unknown. In our study, 5-Demethylnobiletin markedly inhibited the viability, migration and invasion of glioblastoma U87-MG, A172 and U251 cells. Further research revealed that 5-Demethylnobiletin induces cell cycle arrest at the G0/G1 phase in glioblastoma cells by downregulating Cyclin D1 and CDK6 expression levels. Furthermore, 5-Demethylnobiletin significantly induced glioblastoma cells apoptosis by upregulating the protein levels of Bax and downregulating the protein level of Bcl-2, subsequently increasing the expression of cleaved caspase-3 and cleaved caspase-9. Mechanically, 5-Demethylnobiletin trigged G0/G1 phase arrest and apoptosis by inhibiting the ERK1/2, AKT and STAT3 signaling pathway. Furthermore, 5-Demethylnobiletin inhibition of U87-MG cell growth was reproducible in vivo model. Therefore, 5-Demethylnobiletin is a promising bioactive agent that might be used as glioblastoma treatment drug.


Laser irradiation on growth of trichophyton rubrum: an in vitro study.
Trichophyton rubrum is one of the most common species of dermatophytes which affects superficial keratinous tissue. It is not especially virulent but it can be responsible for considerable morbidity. Although there are different therapeutic modalities to treat fungal infections, clinicians are searching for alternative treatment because of the various side effects of the present therapeutic methods. As a new procedure, Laser therapy has brought on many advantages in clinical management of dermatophytes. Possible inhibitory potential of laser irradiation on fungal colonies was investigated invitro in this study. A total of 240 fungal plates of standard size of trichophyton rubrum colonies that had been cultured from the lesions of different patients at the mycology laboratory, were selected. Each fungal plate was assigned as control or experimental group. Experimental plates were irradiated by a laser system (low power laser or different wavelength of high power laser). The effects of different laser wavelengths and energies on isolated colonies were assessed. After laser irradiation, final size of colonies was measured on the first, the 7th and the 14th day after laser irradiation. Although low power laser irradiation did not have any inhibitory effect on fungal growth, the Q-Switched Neodymium-Doped Yttrium Aluminium Garnet (Nd:YAG) laser 532nm at 8j/cm(2), Q-Switched Nd:YAG laser 1064nm at 4j/cm(2) to 8j/cm(2) and Pulsed dye laser 595nm at 8j/cm(2) to 14j/cm(2) significantly inhibited growth of trichophyton rubrum in vitro. Q-Switched Nd:YAG 532nm at 8j/cm(2), Q-Switched Nd:YAG laser 1064nm at 4j/cm(2) to 8j/cm(2) and pulsed dye laser (PDL) 595nm at 8j/cm(2) to 14j/cm(2) can be effective to suppress trichophyton rubrum growth.


[New aspects of the vibration disease. Results of a study in a large factory].
The vibration syndrome includes the frequently observed polysystemic symptom complex, and also encompasses dermatological symptoms as well. Under conditions where vibration and noise exceed the acceptable norms, a very high illness index must be reckoned with. Aside from the characteristic symptoms in the periphery and the vascular and bone systems, numerous symptoms in the central nervous system (still not recognised as occupational disease) have been diagnosed. The present study was carried out by the Cracaw Medical Academy, Poland, who performed medical examinations on the employees of large companies. The results of these examinations are linked to pathogenic vibration. Because of these findings, new recommendations were made concerning changes needed in prophylactic examinations.


Detecting of a Patient's Condition From Clinical Narratives Using Natural Language Representation.
The rapid progress in clinical data management systems and artificial intelligence approaches enable the era of personalized medicine. Intensive care units (ICUs) are ideal clinical research environments for such development because they collect many clinical data and are highly computerized. Goal: We designed a retrospective clinical study on a prospective ICU database using clinical natural language to help in the early diagnosis of heart failure in critically ill children. Methods: The methodology consisted of empirical experiments of a learning algorithm to learn the hidden interpretation and presentation of the French clinical note data. This study included 1386 patients' clinical notes with 5444 single lines of notes. There were 1941 positive cases (36% of total) and 3503 negative cases classified by two independent physicians using a standardized approach. Results: The multilayer perceptron neural network outperforms other discriminative and generative classifiers. Consequently, the proposed framework yields an overall classification performance with 89% accuracy, 88% recall, and 89% precision. Conclusions: This study successfully applied learning representation and machine learning algorithms to detect heart failure in a single French institution from clinical natural language. Further work is needed to use the same methodology in other languages and institutions.


[The effect of simvastatin on osteoblastic bionomics of rats].
To study the effect of simvastatin on osteoblast proliferation, differentiation and mineralization and to explore the mechanism of stimulation of bone formation by simvastatin. Six 8-hour healthy SD rats were used for the experiment. In order to harvest vital osteoblast, this research modified the traditional tissue piece method to culture primary osteoblast of rat calvarias.The effect of simvastatin in different concentration(1.0micromol/L,0.5micromol/L,0.25micromol/L,0.125micromol/L) on osteoblast was measured using MTT to assay osteoblasts proliferation, alkaline phosphatase activity of osteoblasts was measured, the level of osteocalcin (OC) was detected, the capacity of mineralization was investigated by counting the mean mineralization area with Image-Pro Plus 6.0.The data was analyzed with SPSS 13.0 software package for one-way ANOVA. Compared with the control group, the osteoblasts proliferation was inhibited in the experimental groups in a dose-dependent manner. It showed that the alkaline phosphatase activity of osteoblast was increased in all experimental groups. The level of OC of osteoblasts showed a significant increase in all treatment groups. With regard to osteoblast capability of mineralization, the mineralization area was also increased, compared with the control group (P<0.05). Simvastatin inhabits the proliferation of osteoblasts in vitro, but promotes differentiation and mineralization of osteoblast.


Cutaneous melanoma: role of ultrasound in the assessment of locoregional spread.
This article illustrates the various aspects of locoregional spread of cutaneous melanoma, as imaged with grayscale ultrasound (US) and Doppler techniques. High-resolution US allows recognition of small, clinically occult melanomatous foci within the skin and lymph nodes. Consequently, it plays a major role in locoregional staging and follow-up of patients with cutaneous melanoma. We discuss the possibilities and limitations of US in the initial staging (primary melanoma, satellite metastasis, in-transit metastasis, and lymphadenopathy), selection for sentinel lymph node biopsy procedure, patient follow-up, detection of recurrence, and US-guided intervention.


Transcriptional and post-transcriptional events affect the production of secreted hen egg white lysozyme by Aspergillus niger.
The relationship between heterologous gene copy number, mRNA and secreted protein yields has been studied in Aspergillus niger transformants containing either the hen egg-white lysozyme (HEWL) cDNA gene or a glucoamylase-HEWL gene fusion (incorporating the A. niger glaA gene). The results support a direct relationship between HEWL gene copy number, mRNA and secreted HEWL protein levels at low (< 25) copy numbers. High protein yields are associated with multiple copies of the recombinant gene at a single site. Fusion of the HEWL gene to the glucoamylase gene resulted in higher steady-state levels of heterologous mRNA. Transformants with the HEWL cDNA alone exhibited a ten-fold higher mRNA:protein ratio than transformants with the gene fusion indicating that post-transcriptional events significantly affect final secreted protein yields.


Clinical Approach to Diagnosis and Management of Endometrial Hyperplasia and Carcinoma.
This article focuses on the most important neoplastic epithelial lesions of the uterus, endometrial hyperplasia and carcinoma. The primary management of hyperplastic lesions and carcinoma is often surgical but nonsurgical options are possible for both, depending on specific patients and tumor characteristics. Many controversies still exist regarding the optimal medical and surgical treatments of hyperplasias and carcinomas of the endometrium. There is a need to more accurately select patients for lymph node sampling or dissection. The role of adjuvant therapies for endometrial carcinomas is still under investigation. This review covers current understanding in the diagnosis and clinical management of endometrial hyperplasias and carcinomas.


The role of structural characteristics in video-game play motivation: a Q-methodology study.
Until recently, there has been very little naturalistic study of what gaming experiences are like, and how gaming fits into people's lives. Using a recently developed structural characteristic taxonomy of video games, this study examined the psycho-structural elements of computer games that motivate gamers to play them. Using Q-Sort methodology, 40 gamers participated in an online Q-sort task. Results identified six distinct types of gamers based on the factors generated: (a) story-driven solo gamers; (b) social gamers; (c) solo limited gamers; (d) hardcore online gamers; (e) solo control/identity gamers; and (f ) casual gamers. These gaming types are discussed, and a brief evaluation of similar and unique elements of the different types of gamer is also offered. The current study shows Q-methodology to be a relevant and applicable method in the psychological research of gaming.


Bending and looping of long DNA by Polycomb repressive complex 2 revealed by AFM imaging in liquid.
Polycomb repressive complex 2 (PRC2) is a histone methyltransferase that methylates histone H3 at Lysine 27. PRC2 is critical for epigenetic gene silencing, cellular differentiation and the formation of facultative heterochromatin. It can also promote or inhibit oncogenesis. Despite this importance, the molecular mechanisms by which PRC2 compacts chromatin are relatively understudied. Here, we visualized the binding of PRC2 to naked DNA in liquid at the single-molecule level using atomic force microscopy. Analysis of the resulting images showed PRC2, consisting of five subunits (EZH2, EED, SUZ12, AEBP2 and RBBP4), bound to a 2.5-kb DNA with an apparent dissociation constant ($K_{\rm{D}}^{{\rm{app}}}$) of 150 ± 12 nM. PRC2 did not show sequence-specific binding to a region of high GC content (76%) derived from a CpG island embedded in such a long DNA substrate. At higher concentrations, PRC2 compacted DNA by forming DNA loops typically anchored by two or more PRC2 molecules. Additionally, PRC2 binding led to a 3-fold increase in the local bending of DNA's helical backbone without evidence of DNA wrapping around the protein. We suggest that the bending and looping of DNA by PRC2, independent of PRC2's methylation activity, may contribute to heterochromatin formation and therefore epigenetic gene silencing.


Design and evaluation of antibiotic releasing self- assembled scaffolds at room temperature using biodegradable polymer particles.
Biodegradable polymer-based drug-eluting implants offer many advantages such as predictable drug release kinetics, safety, and acceptable drug loading under ambient conditions. Herein, we describe fabrication and evaluation of antibiotic loaded scaffolds for localized delivery and tissue engineering applications. PDLLA particles entrapping gentamycin were formulated using solvent evaporation method and used for scaffold fabrication. Optimization of formulation parameters such as pH of the internal aqueous phase and combination of excipients like glycerol, polyvinyl alcohol (PVA) resulted in high entrapment efficiencies up to 96% of gentamicin in particles with drug load of 16-18μg/mg of polymer particles. These microparticles were fused in presence of methanol at ambient temperatures to form scaffolds of different geometry having reasonable mechanical strength. Porosity of these scaffolds was found to be more than 80%. Antibiotic released from the scaffolds was found to be bioactive as tested against Staphylococcus aureus and the release pattern was biphasic over a period of one week. The scaffolds were found to be non-toxic to murine fibroblasts cultures in vitro as well as to mice upon subcutaneous implantation. This method provides a novel and easy way of fabricating antibiotic loaded polymer scaffolds for varieties of applications.


Corticotropin-releasing factor stimulation of adrenocorticotropin and beta-endorphin release: effects of acute and chronic stress.
The effects of acute and chronic stress on the release of ACTH and beta-endorphin in response to stimulation by ovine corticotropin-releasing factor (CRF) and arginine vasopressin were examined. Pituitaries were removed from rats who had received either acute stress, chronic stress daily for 14 days with the last stress occurring 24 h before decapitation, or chronic stress followed by an acute stress immediately before decapitation (chronic stress-acute stress). Pituitaries from naive unstressed animals were used as the control group. After processing into single cell suspensions, the pituitaries were incubated with various doses of CRF (10(-11) M to 10(-9) M) and AVP (10(-10) M to 10(-8) M). Release of ACTH and beta-endorphin into the medium was measured by RIA. A clear dose-dependent response to both releasers was seen in control pituitaries. In acute stress, a decreased responsiveness to arginine vasopressin and CRF was seen. This same blunted response was not seen in chronic stress even if the animals are stressed immediately before decapitation. At higher doses of CRF (10(-9) M) a substantially increased release of ACTH and beta-endorphin was seen in the chronically stressed rats. When the content of the anterior pituitary lobe was assayed in these animals, both chronic stress groups show increased content of ACTH and beta-endorphin, which may indicate an increase amount of ACTH and beta-endorphin in the releasable pools in chronic stress. In addition, the failure of further stress to alter the response to CRF in the chronic stress-acute stress group may indicate a down-regulation of the steroid feedback on the pituitary. However, it is clear that no down-regulation of the CRF receptor occurs in this chronic stress paradigm.


The Epigenetic Role of Vitamin C in Neurodevelopment.
The maternal diet during pregnancy is a key determinant of offspring health. Early studies have linked poor maternal nutrition during gestation with a propensity for the development of chronic conditions in offspring. These conditions include cardiovascular disease, type 2 diabetes and even compromised mental health. While multiple factors may contribute to these outcomes, disturbed epigenetic programming during early development is one potential biological mechanism. The epigenome is programmed primarily in utero, and during this time, the developing fetus is highly susceptible to environmental factors such as nutritional insults. During neurodevelopment, epigenetic programming coordinates the formation of primitive central nervous system structures, neurogenesis, and neuroplasticity. Dysregulated epigenetic programming has been implicated in the aetiology of several neurodevelopmental disorders such as Tatton-Brown-Rahman syndrome. Accordingly, there is great interest in determining how maternal nutrient availability in pregnancy might affect the epigenetic status of offspring, and how such influences may present phenotypically. In recent years, a number of epigenetic enzymes that are active during embryonic development have been found to require vitamin C as a cofactor. These enzymes include the ten-eleven translocation methylcytosine dioxygenases (TETs) and the Jumonji C domain-containing histone lysine demethylases that catalyse the oxidative removal of methyl groups on cytosines and histone lysine residues, respectively. These enzymes are integral to epigenetic regulation and have fundamental roles in cellular differentiation, the maintenance of pluripotency and development. The dependence of these enzymes on vitamin C for optimal catalytic activity illustrates a potentially critical contribution of the nutrient during mammalian development. These insights also highlight a potential risk associated with vitamin C insufficiency during pregnancy. The link between vitamin C insufficiency and development is particularly apparent in the context of neurodevelopment and high vitamin C concentrations in the brain are indicative of important functional requirements in this organ. Accordingly, this review considers the evidence for the potential impact of maternal vitamin C status on neurodevelopmental epigenetics.


Endothelin receptor in osteoblastic cells is coupled to multiple messenger signals.
We analyzed the functional characteristics of endothelin (ET) peptides in the osteoblastic UMR-106 cells by studying receptor binding as well as dose-response curves for ET-1 and ET-3 on two biological responses: 1) induction of Ca2+ transients and 2) activation of the Na(+)-H+ exchanger. ET specifically binds to a single class of receptor with a rank order of affinity ET-1 >> ET-3. ET-1 and ET-3 dose dependently stimulated a rise in intracellular Ca2+ ([Ca2+]i), with ET-1 being two orders of magnitude more potent than ET-3 [50% effective concentration (EC50) = 8 x 10(-10) and 9 x 10(-8) M for ET-1 and ET-3, respectively; P < 0.01]. The effect of ET-1 on [Ca2+]i was 90% inhibitable by the ETA antagonist BQ-123. The activity of Na(+)-H+ exchange was studied by using the pH-sensitive dye 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein as well as by 22Na+ fluxes. ET-1 and ET-3 activated the exchange in a concentration-dependent manner and with similar potencies (EC50 approximately 10(-10) M). The action of ETs on Na(+)-H+ exchange was mimicked neither by phorbol esters nor by Ca2+ ionophores. It was, however, blocked by BQ-123 as well as by the protein tyrosine kinase inhibitor genistein. We conclude that in UMR-106 cells, a single ET receptor subtype is coupled to multiple effectors, a Ca2+ message system and a tyrosine-kinase system which, in turn, activates the Na(+)-H+ exchanger.


Segmental spinal myoclonus and syringomyelia: A case report.
We report the case of a 75-year-old woman who developed involuntary jerks of the abdominal musculature. They occurred spontaneously or triggered by a forced inspiration or attempts to rise from the supine position. Electromyography (EMG) recorded abnormal bursts of muscle activity in the abdominal, thoracic paraspinal, and intercostal muscles up to the 3rd intercostal space. The bursts were bilateral, arrythmic and synchronous in all muscles. Magnetic resonance imaging (MRI) of the spine revealed a syringomyelic cavity between the T3 and T10 levels. The topological correlation between the EMG muscle activities and the MRI findings was consistent with spinal myoclonus arising from the thoracic spinal cord. The synchronous bursts in muscles depending from few adjacent spinal segments suggested the diagnosis of segmental spinal myoclonus (SSM). There are few reports of SSM related to syringomyelia in the literature.