Developing a DNA variant database.
Disease- and locus-specific variant databases have been a valuable resource to clinical and research geneticists. With the recent rapid developments in technologies, the number of DNA variants detected in a typical molecular genetics laboratory easily exceeds 1,000. To keep track of the growing inventory of DNA variants, many laboratories employ information technology to store the data as well as distributing the data and its associated information to clinicians and researchers via the Web. While it is a valuable resource, the hosting of a web-accessible database requires collaboration between bioinformaticians and biologists and careful planning to ensure its usability and availability. In this chapter, a series of tutorials on building a local DNA variant database out of a sample dataset will be provided. However, this tutorial will not include programming details on building a web interface and on constructing the web application necessary for web hosting. Instead, an introduction to the two commonly used methods for hosting web-accessible variant databases will be described. Apart from the tutorials, this chapter will also consider the resources and planning required for making a variant database project successful.


Gastric epithelial cell death caused by Helicobacter suis and Helicobacter pylori γ-glutamyl transpeptidase is mainly glutathione degradation-dependent.
Helicobacter (H.) suis is the most prevalent non-H. pylori Helicobacter species colonizing the stomach of humans suffering from gastric disease. In the present study, we aimed to unravel the mechanism used by H. suis to induce gastric epithelial cell damage. H. suis lysate induced mainly apoptotic death of human gastric epithelial cells. Inhibition of γ-glutamyl transpeptidase (GGT) activity present in H. suis lysate and incubation of AGS cells with purified native and recombinant H. suis GGT showed that this enzyme was partly responsible for the observed apoptosis. Supplementation of H. suis or H. pylori GGT-treated cells with glutathione strongly enhanced the harmful effect of both enzymes and resulted in the induction of oncosis/necrosis, demonstrating that H. suis and H. pylori GGT-mediated degradation of glutathione and the resulting formation of glutathione degradation products play a direct and active role in the induction of gastric epithelial cell death. This was preceded by an increase of extracellular H(2)O(2) concentrations, generated in a cell-independent manner and causing lipid peroxidation. In conclusion, H. suis and H. pylori GGT-mediated generation of pro-oxidant glutathione degradation products brings on cell damage and causes apoptosis or necrosis, dependent on the amount of extracellular glutathione available as a GGT substrate.


Follicular fluid and supernatant from cultured cumulus-granulosa cells improve in vitro maturation in patients with polycystic ovarian syndrome.
To study the effectiveness of a new in vitro maturation (IVM) approach based on heterologous follicular fluid (HFF) and supernatant of cumulus-granulosa cells (CGCs) mimicking the intact follicular microenvironment to rescue immature denuded oocytes (IDOs) of patients with polycystic ovary syndrome (PCOS) whose IVM or IVF outcomes remain poor. Randomized controlled trial. University-affiliated private center. One hundred fifty-nine IDOs were obtained from 47 patients with PCOS. First, a simple IVM system (S-IVM; 40 IDOs; control group) was compared with different protocols based on the addition of autologous follicular fluid (AFF-IVM; 44 IDOs), HFF (HFF-IVM; 42 IDO), or HFF with CGC isolated from seven women without PCOS and presenting 100% in vivo oocyte maturation (HFF/CGC-IVM; 33 IDOs). None. IVM outcomes were compared among the four groups (S-IVM, AFF-IVM, HFF-IVM, HFF/CGC-IVM); then the vitro and in vivo maturation results (from controlled ovarian stimulation of PCOS patients) were compared for each group. The HFF/CGC-IVM method gave the best yield of developed blastocysts per IDO compared with S-IVM, AFF-IVM, and HFF-IVM (27% vs. 2%, 2%, and 12%, respectively). The IVM rate with the HFF/CGC-IVM method was even higher than that compared with the in vivo maturation rate (79% vs. 42%), with significant improvement in the cleavage rate (71% vs. 61%). This adapted IVM system could be used to reach an acceptable result in meiotic competence and competent metaphase II oocytes capable of developing into intact embryos after fertilization and before transfer.


Interaction Between Race and Income on Cardiac Outcomes After Percutaneous Coronary Intervention.
Background Compared with White Americans, Black Americans have a greater prevalence of cardiac events following percutaneous coronary intervention. We evaluated the association between race and neighborhood income on post-percutaneous coronary intervention cardiac events and assessed whether income modifies the effect of race on this relationship. Methods and Results Consecutive patients (n=23 822) treated with percutaneous coronary intervention from January 1, 2000, to December 31, 2016, were included. All-cause mortality and major adverse cardiac event were assessed at 3 years. Extended 10-year follow-up was performed for those residing locally (n=1285). Neighborhood income was derived using median adjusted annual gross household income reported within the patient's zip code. We compared differences in treatment and outcomes, adjusting for race, income, and their interaction. In total, 3173 (13.3%) patients self-identified as Black Americans, and 20 649 (86.7%) self-identified as White Americans. Black Americans had a worse baseline cardiac risk profile and lower neighborhood income compared with White Americans. Although risk profile improved with increasing income in White Americans, no difference was observed across incomes among Black Americans. Despite similar long-term outpatient cardiology follow-up and medication prescription, risk profiles among Black Americans remained worse. At 3 years, unadjusted all-cause mortality (18.0% versus 15.2%; P<0.001) and major adverse cardiac event (37.3% versus 34.6%; P<0.001) were greater among Black Americans and with lower income (both P<0.001); race, income, and their interaction were not significant predictors in multivariable models. At 10-year follow-up, increasing income was associated with improved outcomes only in White Americans but not Black Americans. In multivariable models for major adverse cardiac event, income (hazard ratio [HR], 0.97 [95% CI, 0.96-0.98]; P=0.005), Black race (HR, 1.77 [95% CI, 1.58-1.96]; P=0.006), and their interaction (HR, 0.98 [95% CI, 0.97-0.99]; P=0.003) were significant predictors. Similar findings were observed for cardiac death. Conclusions Early 3-year post-percutaneous coronary intervention outcomes were driven by worse risk factor profiles in both Black Americans and those with lower neighborhood income. However, late 10-year outcomes showed an independent effect of race and income, with improving outcomes with greater income limited to White Americans. These findings illustrate the importance of developing novel care strategies that address both risk factor modification and social determinants of health to mitigate disparities in cardiac outcomes.


Gutsy memory T cells stand their ground against pathogens.
Elegant fate-mapping models to label intestinal tissue-resident memory CD8+ T (TRM) cells demonstrate retention and lack of expansion of CD103+ TRM cells, whereas intestinal CD103- memory cells expand, forming both new tissue-localized CD103+ and CD103- TRM cells (see related Research Articles by Fung et al. and von Hoesslin et al.).


Effects of Chemotherapy on Neuroinflammation, Neuronal Damage, Neurogenesis, and Behavioral Performance in Bone Marrow Transplantation Recipient Mice.
As bone marrow transplant (BMT) is gradually applied to the study of central nervous system (CNS) disease, it is needed to investigate the proper dose of chemotherapy to eradicate bone marrow cells while bringing little damage to brain. In the present study, we established a BMT model with varied busulfan and cyclophosphamide (Bu-Cy) dosages. The recipient mice's chimera rate, neuronal death, neuroinflammation, and behavioral functions were all investigated. Chimerism of peripheral blood cells was shown to rise with Bu-Cy treatment doses, with 60.7% in the Bu(20 mg/kg)/Cy(100 mg/kg) group and 93.0% in the Bu(35 mg/kg)/Cy(100 mg/kg) group. Recipients with Bu(35 mg/kg)/Cy(100 mg/kg) therapy had brain injury, increased neuroinflammation, diminished neurogenesis and cognitive abnormalities, whereas animals given a lesser dosage had no such brain damages. Conclusively, considering the chimerism and the possibility to damage brain, we recommend Bu(20 mg/kg)/Cy(100 mg/kg) is the ideal dose in BMT for studying CNS diseases in the C57/BL6 mouse strain.


Quercetin's antibiofilm effectiveness against drug resistant Staphylococcus aureus and its validation by in silico modeling.
Staphylococcus aureus is typically treated with antibiotics, however, due to its widespread and unselective usage, resistant strains of S. aureus have increased to a great extent. Treatment failure and recurring staphylococcal infections are also brought on by biofilm development, which boosts an organism's ability to withstand antibiotics and is thought to be a virulence factor in patients. The present study investigates the antibiofilm activity of naturally available polyphenol Quercetin against drug-resistant S. aureus. Micro dilution plating and tube adhesion methods were performed to evaluate the antibiofilm activity of quercetin against S. aureus. Quercetin treatment resulted in remarkably reduction of biofilm in S. aureus cells. Further we performed a study to investigate binding efficacies of quercetin with genes icaB and icaC from ica locus involved in biofilm formation. 3D structure of icaB, icaC and quercetin were retrieved from Protein data bank and PubChem chemical compound database, respectively. All computational simulation were carried out using AutoDock Vina and AutoDockTools (ADT) v 1.5.4. In silico study demonstrated a strong complex formation, large binding constants (Kb) and low free binding energy (ΔG) between quercetin and icaB (Kb = 1.63 × 10-5, ΔG = -7.2 k cal/mol) and icaC (Kb = 1.98 × 10-6, ΔG = -8.7 kcal/mol). This in silico analysis indicates that quercetin is capable of targeting icaB and icaC proteins which are essential for biofilm formation in S. aureus. Our study highlighted the antibiofilm activity of quercetin against drug resistant pathogen S.aureus.


Rat tracheal organ culture supports replication of parainfluenza 1 (6/94) virus and promotes 6/94 virus rescue from latently infected human brain cells.
Rat tracheal organ culture (TOC) supported replication of parainfluenza 1 (6/94) virus. Cell-associated and cell-free viruses were found after primary infection of TOC. In contrast to other mammalian systems, rat TOC was capable of maintaining 6/94 virus infectivity after primary infection. Rat TOC may be considered a potential indicator system that could be used to detect virus latent in human tissue.


Comparison of the quantitative performances and measurement uncertainty estimates obtained during method validation versus routine applications of a novel hydrophilic interaction chromatography method for the determination of cidofovir in human plasma.
Method validation is essential to ensure that an analytical method is fit for its intended purpose. Additionally, it is advisable to estimate measurement uncertainty in order to allow a correct interpretation of the results generated by analytical methods. Measurement uncertainty can be efficiently estimated during method validation as a top-down approach. However, method validation predictions of the quantitative performances of the assay and estimations of measurement uncertainty may be far away from the real performances obtained during the routine application of this assay. In this work, the predictions of the quantitative performances and measurement uncertainty estimations obtained from a method validation are compared to those obtained during routine applications of a bioanalytical method. For that purpose, a new hydrophilic interaction chromatography (HILIC) method was used. This method was developed for the determination of cidofovir, an antiviral drug, in human plasma. Cidofovir (CDV) is a highly polar molecule presenting three ionizable functions. Therefore, it is an interesting candidate for determination by HILIC mode. CDV is an acyclic cytidine monophosphate analog that has a broad antiviral spectrum and is currently undergoing evaluation in clinical trials as a topical agent for treatment of papillomavirus infections. The analytical conditions were optimized by means of design of experiments approach in order to obtain robust analytical conditions. These ones were absolutely necessary to enable the comparisons mentioned above. After a sample clean-up by means of solid phase extraction, the chromatographic analysis was performed on bare silica stationary phase using a mixture of acetonitrile-ammonium hydrogen carbonate (pH 7.0; 20mM) (72:28, v/v) as mobile phase. This newly developed bioanalytical method was then fully validated according to FDA (Food and Drug Administration) requirements using a total error approach that guaranteed that each future result will fall within acceptance limits of ±30% with a probability of 95% over a concentration range of 92.7-1020ng/mL. A routine application of the cidofovir determination in two pre-clinical trials demonstrated that the prediction made during the pre-study validation was consistent by retrospective analysis of the quality control (QC) samples. Finally, comparison of the measurement uncertainty estimations calculated from the method validation with those obtained from the routine application of the method was performed, stressing that the estimations obtained during method validation underestimated those obtained from routine applications and that the magnitude of this underestimation was function of the cidofovir concentration. Finally, this new HILIC method is reliable, easily applicable to routine analysis and transposable at low cost in other laboratories.


Olanzapine reduces craving for alcohol: a DRD4 VNTR polymorphism by pharmacotherapy interaction.
Separate investigations have suggested that olanzapine, a D4 antagonist, decreases craving after a priming dose of alcohol and that the DRD4 variable number of tandem repeats (VNTR) polymorphism influences the expression of craving after a priming dose of alcohol. The present study tested the hypothesis that olanzapine may be differentially effective at reducing cue-elicited craving based on individual differences in DRD4 VNTR in a sample of heavy social drinkers. Participants were randomly assigned to receive olanzapine (5 mg) or a control medication (cyproheptadine, 4 mg) prior to consuming three alcoholic drinks. Participants completed subjective measures of craving and euphoria after each drink. Participants who were homozygous or heterozygous for the 7 (or longer) repeat allele of the DRD4 VNTR were classified as DRD4 L, while the other participants were classified as DRD4 S. The findings indicated that olanzapine reduces craving for alcohol at baseline for both DRD4 S and DRD4 L individuals, but only reduces craving after exposure to alcohol cues and after a priming dose of alcohol for DRD4 L individuals.


Mechanistic Insights on Spontaneous Moisture-Driven Healing of Urea-Based Polyurethanes.
Self-healing polymeric materials that can spontaneously repair in a perpetual manner are highly appealing to address safety and restoration issues in different key applications. Usually built from reversible moieties that require to be activated using, for example, temperature, light, or pH changes, most of these self-healing materials rely on energy-demanding processes and/or external interventions to promote self-healing. In this work, we propose to exploit rapid dynamic exchanges between urea-based moieties and moisture as an alternative to promote local and spontaneous healing responses to damage using atmospheric moisture as an external stimulus. Non-hygroscopic urea-based polyurethanes with repetitive moisture-induced healing abilities at different degrees of humidity were thus designed through coupling reactions with non-hygroscopic polypropylene glycol and urea moieties. As supported by density functional theory (DFT) calculations coupled to local FTIR experimental studies, we furthermore established that the healing mechanism is ultimately related to the formation of water-urea clusters. Obviously, this work represents a platform for designing more advanced spontaneous self-healing materials beyond the present study, which hold promise for use in a wide range of technological applications.


Uptake, distribution and release of 3H-arachidonic acid from human endometrium.
The lysophosphatide acyltransferase blocking agent ethylmercurisalicylate (merthiolate) was used to investigate the uptake and release of arachidonic acid from explants of human endometrium in short term tissue culture. Tissue explants were (a) incubated with 3H-arachidonic acid for 1-24 h in the presence or absence of 0.5-50 microM merthiolate, and (b) prelabelled with 3H-arachidonic acid for 18 h followed by incubation with or without 50 microM merthiolate for 1-24 h. Neutral lipids, phospholipids and arachidonic acid were separated by thin layer chromatography and uptake and release of 3H-arachidonic acid expressed as % total uptake. The triglyceride pool was the main target for arachidonic acid uptake. Incorporation increased from 9.1% at 1 h to 56.6% at 24 h. Uptake into phospholipids increased from 8.1% at 1 h to 19.6% at 24 h with phosphatidylcholine accounting for 3.8% and 8.8% respectively. Incubation with 50 microM merthiolate rapidly reduced uptake into triglycerides (to 1.8% at 1 h and 0.9% at 24 h), whereas the effect on uptake into phospholipids (5.9% at 1 h, 3.4% at 24 h) was much less marked. There was a dose related inhibition of arachidonic acid incorporation into both triglycerides and phospholipids, but a lower dose of merthiolate (1 microM) was required to reduce uptake into triglycerides than into phospholipids (5 microM). Uptake into mono- and diglycerides was low and unaffected by merthiolate. Incubation of prelabelled tissue with 50 microM merthiolate resulted in a 20% increase in the release of arachidonic acid from triglycerides and a corresponding accumulation of labelled monoglyceride.(ABSTRACT TRUNCATED AT 250 WORDS)


Fracture of the pancreas in two patients after a go-kart accident.
After blunt abdominal trauma, an isolated injury to the pancreatic duct is uncommon. Physical signs and laboratory parameters are often inaccurate, and missing this diagnosis can cause serious clinical problems. Two young women (aged 18 and 20 years) are reported who sustained isolated trauma to the pancreatic duct in go-kart accidents. Each patient sustained a fracture of the pancreas.This injury was diagnosed only after a period of clinical observation with repeated laboratory parameters, ultrasound and CT scan. Pancreatic tissue was conserved by performing a pancreaticojejunostomy. After any episode of blunt abdominal trauma, isolated injury to the pancreatic duct should be considered. Serum analysis, ultrasonography and CT scanning can be helpful in early diagnosis. Preservation of pancreatic tissue can be achieved with a good clinical outcome.


Effectiveness of TBE vaccination in southern Germany and Latvia.
Tick-borne encephalitis (TBE) is a vaccine-preventable disease which may cause long-term sequelae and even death. The data on the long-term effectiveness of TBE vaccines are limited. Additionally, the vaccination schedule is complex which in part contributes towards sub-optimal uptake in TBE-endemic areas. The current ecological study measures vaccine effectiveness (VE) in two European countries. TBE VE was measured from 2007 to 2018 in Latvia and Southern German states by age group, vaccination history, and schedule compliance. TBE cases and vaccination history were obtained from the public health agencies for Latvia and the southern German federal states of Bavaria and Baden-Wuerttemberg. Cases were "within schedule" if a TBE infection was diagnosed within the time interval preceding the next scheduled dose and "outside schedule" if the diagnosis occurred after the next scheduled dose. Vaccine uptake was estimated via representative nationwide surveys. VE after 2, 3, and ≥4 doses was high in both countries at 97.2%, 95.0%, and 95.4% for southern Germany, and 98.1%, 99.4%, and 98.8% for Latvia while within- schedule, and only showed marginal differences outside schedule at 90.6%, 89.9%, and 95.6% for southern Germany, and 97.4%, 98.4%, and 99.0% for Latvia regardless of age groups. In both countries, VE after two and three primary doses within-schedule was very high in all age groups. Once receiving booster doses, high VE continued to be observed even in persons with extended intervals since the last dose received, suggesting that longer and more flexible booster intervals may be considered for sustainable long-term protection.


Expression of connexin 43 in the human hair follicle: emphasis on the connexin 43 protein levels in the bulge and through the keratinization process.
Gap junctions form communication compartments between cells. These channels assemble from connexin subunits. To investigate the immunoexpression of connexin 43 (Cx43) in adult human hair follicles. Cases were retrospectively obtained from our archives. We identified immunoexpression of Cx43 in the matrix, the papilla, the outer root sheath, the bulge, the medulla, the cortex, the shaft and the secretory part of the sebaceous gland. There was very low expression (VLE) of Cx43 in the perifollicular sheath, the mantle and the arrector pili muscle. The internal root sheath showed high-density expression in the bulb. Such expression abruptly decreased at different points in each of its layers at the point of keratinization. The isthmus showed Cx43-positive staining in the middle layers and all along, whereas there was VLE in the two outermost layers. The infundibulum showed expression all along the middle layers, whereas it showed VLE in the 2 outermost layers and in the 2 or 3 innermost layers. The bulge contains Cx43. Our results suggest that keratinization in the hair follicle is closely related to the decrease in Cx43 expression.


Beyond U0126. Dianion chemistry leading to the rapid synthesis of a series of potent MEK inhibitors.
Employing phenylmalonitrile dianion chemistry, a large number of analogues of MEK inhibitor lead SH053 (IC(50)=140 nM) were rapidly synthesized leading to single digit nM inhibitors, displaying submicromolar AP-1 transcription inhibition in COS-7 cells. Compound 41, exhibiting a MEK IC(50)=12 nM showed ip activity in a TPA-induced ear edema model with an ED(50)=5 mg/kg.


Site specific point mutation changes specificity: a molecular modeling study by free energy simulations and enzyme kinetics of the thermodynamics in ribonuclease T1 substrate interactions.
We have theoretically and experimentally studied the binding of two different ligands to wild-type ribonuclease T1 (RNT1) and to a mutant of RNT1 with Glu-46 replaced by Gln. The binding of the natural substrate 3'-GMP has been compared with the binding of a fluorescent probe, 2-aminopurine 3'-monophosphate (2AP), and relative free energies of binding of these ligands to the mutant and the wild-type (wt) enzyme have been calculated by free energy perturbation methods. The free energy perturbations predict that the mutant RNT1-Gln-46 binds 2AP better than 3'GMP, in agreement with experiments on dinucleotides. Four free energy perturbations, forming a closed loop, have been performed to allow the detection of systematic errors in the simulation procedure. Because of the larger number of atoms involved, it was necessary to use a much longer simulation time for the change in the protein, i,e., the perturbation from Glu to Gln, than in the perturbation from 3'-GMP to 2AP. Finally the structure of the binding site is analyzed for understanding differences in catalytic speed and binding strength.


[The choice of surgical tactics in the treatment of extensive scalp wounds in children].
For evaluation of the viability of the skin flaps in treatment of the scalped wounds in 40 children, the oxygen tension, initial and after the 2-minute oxygen load, and as well the rate of oxygen consumption by the tissue of an autotransplant after its saturation under the conditions of hyperbaric oxygenation were defined. These indices permit to predict the survival of the skin flaps.


Quantitative and qualitative differences in the distribution of HLA class I antigenic determinants in the human thymic compartments.
The topographical distribution of HLA class I antigens has been investigated by the immunoperoxidase technique on normal frozen thymic tissue sections with a panel of mono- and polymorphic monoclonal anti-HLA antibodies. HLA class I framework determinants detected by the monoclonal antibody W6/32.HL were present on 80-90% of cortical thymocytes, as well as on all cortical epithelial and medullary cells. However the staining intensity of cortical thymocytes with this reagent was about threefold weaker than that of the medullary thymocytes. Labelling patterns of selected monoclonal antibodies against matching HLA-A/B allospecificities revealed striking variations in the quantitative expression of certain HLA-A vs. HLA-B locus alloantigenic determinants on cortical thymocytes compared to a consistent staining on almost all medullary cells.


First Occurrence of Saffold Virus in Sewage and River Water Samples in Karaj, Iran.
Saffold virus as a newly discovered virus, which seems to be related to acute gastroenteritis as with other enteric viruses and to human airway diseases in children belongs to Cardiovirus genus in picornaviridae family with 11 genotypes. Saffold virus initially was detected in America from infant stool sample. Saffold virus has also been detected in environmental water samples. Until now, two reports have demonstrated that sewage water sources are contaminated with Saffold viruses. Molecular detection of Saffold virus mostly depended on reverse transcription PCR methods and RT-qPCR, which had targeted 5'UTR region of the viral genome. The present study aims to evaluate the molecular detection and quantity of Saffold virus in sewage water and river water specimens by RT-qPCR assay in Karaj, Iran. Fifty samples collected from environmental waters containing treated and untreated sewage water and river water samples were included in this study. After viral RNA extraction, the Real-time PCR was developed to amplify the 5'UTR sequence of Saffold virus genome and viral load was assessed. Out of the 50 samples tested (consisting 28 river water samples and 22 sewage water samples), the Saffold virus genomic RNA was identified in 10/28 (35.7%) of river water samples and in 4/12 (33.3%) of treated and 4/10 (40%) of untreated sewage samples. The maximum viral load was 6.8 × 106 copies/l in untreated sewage water sample in December, and the lower viral load was 1.2 × 106 copies/l related to treated sewage water taken in October. Our results for the first time indicate that Saffold virus has apparently been circulating among Iranian peoples. Also, the viral prevalence of Saffold virus in each of the three sets of tested samples was within moderate to high in range.


Caring behaviours and stress perception among student nurses in different nursing programmes: A cross-sectional study.
Caring is central to providing high-quality nursing. Little research exists concerning the relationship between caring behaviours and stress perception among student nurses. This study aimed to explore this relationship among student nurses in different nursing programmes. A sample of 792 student nurses from three nursing education programmes in one academic institution completed Chinese versions of the Caring Behaviors Scale and the Nurse Stress Checklist to assess participants' caring behaviour and psychosocial responses to work-related stress, respectively. We found a statistically significant negative correlation between caring behaviour and stress perception among participants. The three most frequently reported caring behaviours were related to 'knowing the patient': (a) recognising that each patient holds unique values, (b) taking a patient's chief complaints seriously, and (c) stating that the family's best interests should be respected regarding health decisions. Completion of work, time limitations, and lack of personal interactions were sources of stress. Nursing education curricula involve the fundamentals of caring and the preparation of nursing students for clinical practice. The study recommends that nursing faculty and administrators should educate students in stress management in order to foster, support, and promote caring behaviours among nursing professionals.


High-performance liquid chromatographic assay of nesosteine in human plasma and urine.
A high-performance liquid chromatographic method for the quantitation of the mucoactive drug sodium 2-(3-thiazolidinylcarbonyl)benzoate in plasma and urine was developed, involving liquid-liquid extraction under acidic conditions and reversed-phase chromatography using ultraviolet detection at 210 or 235 nm. The extraction efficiency, linearity, limit of detection, precision and accuracy were determined. Products of the main biotransformation of the drug, involving hydrolysis of the amidic bond, do not interfere. The method is selective, precise, reproducible and applicable to studies of the pharmacokinetic behaviour of the drug in humans. Pharmacokinetic parameters derived from six healthy subjects following acute intravenous administration of the drug (150 mg) are presented.


Crystal structure of JlpA, a surface-exposed lipoprotein adhesin of Campylobacter jejuni.
The Campylobacter jejuni JlpA protein is a surface-exposed lipoprotein that was discovered as an adhesin promoting interaction with host epithelium cells, an early critical step in the pathogenesis of C. jejuni disease. Increasing evidence ascertained that JlpA is antigenic, indicating a role of JlpA in immune response during the infectious process. Here, we report the crystal structure of JlpA at 2.7Å resolution, revealing a catcher's mitt shaped unclosed half β-barrel. Although the apparent architecture of JlpA is somewhat reminiscent of other bacterial lipoproteins such as LolB, the topology of JlpA is unique among the bacterial surface proteins reported to date and therefore JlpA represents a novel bacterial cell surface lipoprotein. The concave face of the structure results in an unusually large hydrophobic basin with a localized acidic pocket, suggesting a possibility that JlpA may accommodate multiple ligands. Therefore, the structure provides framework for determining the molecular function of JlpA and new strategies for the rational design of small molecule inhibitors efficiently targeting JlpA.


Neurons in the parabrachial nuclei respond to hemorrhage.
To examine the organization of pathways in the dorsal rostral pons that process information from cardiovascular receptors, 62 neurons in the parabrachial nuclei were tested, in rats anesthetized with urethane, for their response to hemorrhage (10 ml/kg.min) and reinfusion. Of these neurons, 21 exhibited patterns of activity in response to hemorrhage that were significantly different from those seen prior to hemorrhage. The patterns of activity appeared to depend, at least in part, on the location of the neurons within the parabrachial nuclei. The activity of 8 neurons in the external lateral and central lateral parabrachial nuclei (LT) and adjacent Kolliker-Fuse nucleus (KF) increased during hemorrhage and remained elevated during reinfusion. Multivariate regression analysis indicated that the activity of these neurons was best predicted by mean arterial pressure. In contrast, the activity of 8 neurons in the dorsal cap of the central lateral parabrachial nucleus (DR) and in the caudal medial parabrachial nucleus (MD) increased during hemorrhage and decreased during reinfusion, and appeared to be best predicted by blood volume. The activity of 5 neurons in the region between the caudal medial parabrachial nucleus and the locus coeruleus (BT) responded inversely to those in the caudal medial parabrachial nucleus, and was predicted well both by blood volume and by mean arterial pressure. Together, these data reveal a complex processing of hemodynamic signals within the parabrachial nuclei which may play a critical role in the control of neuroendocrine and sympathetic responses in relation to regulation of arterial pressure, blood volume and fluid balance.


Data on eye behavior during idea generation and letter-by-letter reading.
This article includes the description of data information from an idea generation task (alternate uses task, (Guilford, 1967) [1]) and a letter-by-letter reading task under two background brightness conditions with healthy adults as well as a baseline measurement and questionnaire data (SIPI (Huba et al., 1981) [2]; DDFS (Singer and Antrobus, 1972) [3], 1963; RIBS (Runco et al., 2001) [4]). Data are hosted at the Open Science Framework (OSF): https://osf.io/fh66g/ (Walcher et al., 2017) [5]. There you will find eye tracking data, task performance data, questionnaires data, analyses scripts (in R, R Core Team, 2017 [6]), eye tracking paradigms (in the Experiment Builder (SR Research Ltd., [7]) and graphs on pupil and angle of eye vergence dynamics. Data are interpreted and discussed in the article 'Looking for ideas: Eye behavior during goal-directed internally focused cognition' (Walcher et al., 2017) [8].


Insights into atherosclerosis therapy in antiphospholipid syndrome.
The presence of early atheroma in antiphospholipid syndrome (APS) underscores the necessity of new therapies for this disorder. Inflammation plays an essential role in the pathogenesis of both APS secondary to systemic lupus erythematosus and atheroma. Several drugs currently used in APS have also anti-atherogenic properties via their anti-inflammatory effect. Furthermore, in addition to screening and treatment of traditional cardiovascular risk factors, it has been suggested that the introduction of some new medication such as statins in APS patients could be useful. This review assesses the current knowledge in this field and the justification for this new therapeutical approach. Furthermore, these data underscore the necessity for the use of other medication for atherosclerosis in APS patients, such as immunomodulatory drugs, which would be complementary to the anti-thrombotic and anti-platelet therapy.


Penetrating Spinal Cord Injury in civilians: analysis of a national database.
Spinal trauma is common in polytrauma; spinal cord injury (SCI) is present in a subset of these patients. Penetrating SCI has been studied in the military; however, civilian SCI is less studied. Civilian injury pathophysiology varies given the generally lower velocity of the projectiles. We sought to investigate civilian penetrating SCI in the United States. We queried the National Inpatient Sample for data regarding penetrating spinal cord injury from the past 10 years (2006-2015). The National Inpatient Sample includes data of 20% of discharged patients from U.S. hospitals. We analyzed trends of penetrating SCI regarding its diagnosis, demographics, surgical management, length of stay, and hospital costs. In the past 10 years the incidence of penetrating SCI in all SCI patients has remained stable with a mean of 5.5% (range 4.3%-6.6%). Of the patients with penetrating SCI, only 17% of them underwent a surgical procedure, compared with 55% for nonpenetrating SCI. Patients with penetrating SCI had a longer length of stay (average 23 days) compared with nonpenetrating SCI (15 days). Hospital charges were higher for penetrating SCI: $230,186 compared with $192,022 for closed SCI. Males patients were more affected by penetrating SCI, as well as black and Hispanic populations compared with whites. Penetrating SCI represents 5.5% of all SCI patients. Men, blacks, and Hispanics are disproportionally more affected by penetrating SCI. Patients with penetrating SCI have fewer surgical interventions, but their overall length of stay and hospital costs are greater compared with nonpenetrating SCI.


Unaltered hormonal response to stress in a mouse model of fragile X syndrome.
Reports in the clinical literature and studies of fmr1 knockout mice have led to the hypothesis that, in addition to mental retardation, fragile X syndrome is characterized by a dysregulation of hypothalamic-pituitary-adrenal axis function. We have systematically examined this hypothesis by studying the effects of stress on adrenocorticotrophic hormone and corticosterone levels in adult, male fmr1 knockout mice. Initially we determined the circadian rhythms of the plasma hormone levels in both wild-type and fmr1 knockout mice and established the optimal time to impose the stress. We found no genotypic differences in the circadian rhythms of either hormone. We studied two types of stressors, immobilization and spatial novelty; spatial novelty was 5min in an elevated plus-maze. We varied the duration of immobilization and followed the time course of recovery of hormones to their pre-stress levels. Despite the lower anxiety exhibited by fmr1 knockout mice in the elevated plus-maze, hormonal responses to and recovery from this spatial novelty were similar in both genotypes. Further, we found no genotypic differences in hormonal responses to immobilization stress. The results of our study indicate that, in FVB/NJ mice, the hormonal response to and recovery from acute stress is unaltered by the lack of fragile X mental retardation protein.


Genetic dosage and position effect of small supernumerary marker chromosome (sSMC) in human sperm nuclei in infertile male patient.
Chromosomes occupy specific distinct areas in the nucleus of the sperm cell that may be altered in males with disrupted spermatogenesis. Here, we present alterations in the positioning of the human chromosomes 15, 18, X and Y between spermatozoa with the small supernumerary marker chromosome (sSMC; sSMC(+)) and spermatozoa with normal chromosome complement (sSMC(-)), for the first time described in the same ejaculate of an infertile, phenotypically normal male patient. Using classical and confocal fluorescent microscopy, the nuclear colocalization of chromosomes 15 and sSMC was analyzed. The molecular cytogenetic characteristics of sSMC delineated the karyotype as 47,XY,+der(15)(pter->p11.2::q11.1->q11.2::p11.2->pter)mat. Analysis of meiotic segregation showed a 1:1 ratio of sSMC(+) to sSMC(-) spermatozoa, while evaluation of sperm aneuploidy status indicated an increased level of chromosome 13, 18, 21 and 22 disomy, up to 7 × (2.7 - 15.1). Sperm chromatin integrity assessment did not reveal any increase in deprotamination in the patient's sperm chromatin. Importantly, we found significant repositioning of chromosomes X and Y towards the nuclear periphery, where both chromosomes were localized in close proximity to the sSMC. This suggests the possible influence of sSMC/XY colocalization on meiotic chromosome division, resulting in abnormal chromosome segregation, and leading to male infertility in the patient.


Responses of enzymatically isolated mammalian vascular smooth muscle cells to pharmacological and electrical stimuli.
A modified method for enzymatically isolating mammalian vascular smooth muscle cells has been developed and tested for ferret portal vein smooth muscle. This method produces a high proportion of fully relaxed cells and these cells appear to have normal pharmacological responsiveness. The ED50 values for both alpha stimulation and potassium depolarization are not significantly different in the isolated cells from those obtained from intact strips of ferret portal vein, suggesting that the enzymatic treatment does not destroy receptors or alter the electrical responsiveness of the cells. It was also possible to demonstrate a vasodilatory action of papaverine, nitroprusside and adenosine directly on the isolated cells indicating that the pathways involved are intact in the isolated cells. This method should be of considerable usefulness, particularly in combination with the new fluorescent indicators and cell sorter techniques which require isolated cells.


Perioperative complication rates of primary and repeat hysteroscopic endometrial ablations.
To determine perioperative complication rates at primary and repeat endometrial ablations. Prospective cohort study (Canadian Task Force classification II-2). Tertiary care teaching hospital. Seventy-five women who underwent a repeat ablation and 800 who had a primary ablation by the same surgeon (GAV) between 1990 and 2000 for a diagnosis of menorrhagia and/or dysmenorrhea. Hysteroscopic ablation involving coagulation or resection of endometrium, and second ablation after failure of the first. Serious perioperative complications were uterine perforation, hemorrhage, excess fluid absorption, and genital tract burns. They occurred in 9.3% of repeat ablations compared with 2.05% of primary ablations (p = 0.006). Repeat endometrial ablation has a significantly higher rate of perioperative complications than primary ablation.


Optimization of ceragenins for prevention of bacterial colonization of hydrogel contact lenses.
We provided contact lens hydrogels with an antibacterial innate immune function using nonpeptide mimics of endogenous antimicrobial peptides. Antimicrobial peptide mimics, ceragenins, were prepared for either covalent attachment to hydrogels or for controlled elution from lenses. The lipophilicity of the ceragenins was varied incrementally to provide differing levels of association with hydrophobic domains in lenses. Ceragenin-containing lenses were challenged repeatedly with Staphylococcus aureus or Pseudomonas aeruginosa in nutrient media. Bacterial growth and biofilm formation on lenses were quantified. A ceragenin covalently fixed in lenses effectively inhibited S. aureus biofilm formation on lenses in 10% tryptic soy broth (approximately 3-log reduction), but did not reduce biofilm formation in 100% tryptic soy broth. Ceragenins designed to elute from lenses were incorporated at 1% relative to the dry weight of the lenses. The ceragenin with the optimal lipid content, CSA-138, prevented bacterial colonization of lenses for 15 days with P. aeruginosa and for 30 days with S. aureus (daily exchange of growth media and reinoculation with 10⁶ CFU). Measurement of CSA-138 elution showed that concentrations of the ceragenin never exceeded 5 μg/mL in a 24-hour period and that after 4 days of elution, concentrations dropped to <0.5 μg/mL, while maintaining antibacterial activity. Ceragenin CSA-138 appears well suited for providing an innate immune-like function to abiotic hydrogel contact lenses for extended periods of time. Elution of even low concentrations of CSA-138 (<0.5 μg) is sufficient to eliminate inocula of 10⁶ CFU of S. aureus and P. aeruginosa.


[Verification of the effectiveness of preventing altitude decompression disorders by nitrogen desaturation of the organism through surrounding the body with an oxygen envelope].
The purpose of the present investigation was to assess the effect of nitrogen penetrating the human skin from the ambient atmosphere on the level of denitrogenization achieved by oxygen breathing. Young healthy male test subjects were exposed to denitrogenization for 5, 6 or 8 hours by breathing pure oxygen. During that time they wore an oxygen filled suit. Then they ascended an altitude of 11,000 m and remained there for 6 hours doing exercises. Altogether 38 investigations were carried out on 13 subjects, with and without a pressure suit. The investigation did not demonstrate any specific differences in the occurrence of decompression disease at an altitude of 11,000 m with or without a pressure suit. Nitrogen penetrating through the skin from the ambient atmosphere during oxygen breathing did not influence the level of denitrogenization.


Type 1 astrocytes and oligodendrocyte-type 2 astrocyte glial progenitors migrate toward distinct molecules.
During central nervous system (CNS) development, glial precursors proliferate in subventricular zones and then migrate throughout the CNS to adopt their final destinations and differentiate into various types of mature glial cells. Although several growth factors promoting the proliferation and/or differentiation of glial precursors have been identified, very little is known about the nature of signals that guide glial cell migration in the CNS. Therefore, we have investigated whether polypeptide growth factors and/or extracellular matrix molecules may mediate the migration of two major glial cell types, type 1 astrocytes and oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells. We show that, in a microchemotaxis chamber assay, type 1 astrocytes move toward laminin and complement-derived C5a. Astrocyte migration toward laminin is inhibited by a laminin-specific pentapeptide, YIGSR-NH2. In contrast, O-2A progenitors migrate toward platelet-derived growth factor (PDGF), which also functions as a mitogen for these cells. Using a new method to simultaneously assay migration and DNA synthesis, we also demonstrate that O-2A progenitors can migrate toward PDGF even when DNA replication is inhibited with an antimitotic agent. Thus, migration of different types of glial cells can be induced in vitro by specific signaling molecules, which are present in the developing brain and may stimulate migration of glial cells prior to CNS myelination.


Can cancer chemotherapy enhance the malignant behaviour of tumours?
Cancer chemotherapy is currently undergoing an intensive reappraisal because of its unimpressive performance against the major common cancers. There are a number of possible reasons for this lack of success; one considered here is that under some circumstances anti-neoplastic drug treatment actually increases the malignant behaviour of tumours. Support for this idea comes mainly from experimental studies in which drug treatments increased metastatic spread. Investigation of this phenomenon shows that drug induced modifications of the host, including immunosuppression and vascular damage, can indeed facilitate metastasis. In addition, new data are presented demonstrating that the direct action of drugs on the tumour cells themselves can have similar enhancing effects. The possible mechanisms underlying such direct effects are discussed and the ability of anti-cancer drugs to cause genetic mutations, amplify genes, and alter gene expression are considered. While the nature and extent of this facilitation of tumour malignancy is not fully understood, it is suggested that this possibility should be considered in the design of treatment protocols.


Insulin resistance, but not insulin response, during oral glucose tolerance test (OGTT) is associated to worse histological outcome in obese NAFLD.
Obese subjects are at high risk of nonalcoholic fatty liver disease (NAFLD) and diabetes (T2D) due to insulin resistance (IR). Since high glucose levels are as toxic as lipids for hepatic metabolism, we hypothesize that altered response to oral glucose tolerance test (OGTT) is associated to more severe NAFLD with significant/advanced liver damage. We studied 90 subjects with morbid obesity (73F/17M, BMI = 43.2 ± 5,9 kg/m2) undergoing bariatric surgery and intraoperative liver biopsy, and measured HbA1c, HOMA-IR (fasting Glucose x Insulin/22.5), OGTT glucose and insulin profile, and calculated OGIS (muscle insulin sensitivity), hepatic-IR (glucose [AUC0-30] x insulin [AUC0-30]) during OGTT, insulin response as (insulin [dAUC0-120]/glucose [dAUC0-120] or Insulinogenic Index (IGI = (I30-I0)/(G30-G0)). Patients were divided in 3 groups according to liver biopsy: A (no-NAFLD, 23%), B (simple steatosis (SS), 53%) and C (NASH, 24%) with similar age, gender and BMI. Diabetes was 0% in no-NAFLD, 13% in SS, 35% in NASH. During OGTT, OGIS decreased from A to C (422 vs 360 vs 338, p < 0.01). Increased insulin concentrations, HbA1c, HOMA-IR and OGIS, not Hep-IR, were strongly associated to hepatic steatosis (p = 0.03, p = 0.0001 and p = 0.01 respectively). Hepatic fibrosis stage was mild as most of the patients had fibrosis grade-1 (69% vs. 8% no fibrosis) and associated to fasting insulin, HbA1c and HOMA-IR. dAUC-I/dAUC-G was similar in the 3 groups, while only AUC-I was strongly associated to steatosis (r = 0.35, p = 0.005), but not to fibrosis. In morbid obesity indexes of IR, and not of insulin response, are markers of histological severity of liver disease.


Iloprost administration in acrodermatitis of Hallopeau complicated by acquired toes syndactyly: a case report and review of the literature.
Acrodermatitis Continua of Hallopeau (ACH) is a variant of pustular psoriasis often very difficult to treat. Secondary syndactyly, also called "pseudosyndactyly", is rare and can be a complication of burns, dystrophic epidermolysis bullosa or trauma. If left untreated, joint complications and definitive functional impairments may occur. We report a case of a 74-year-old man with acrodermatitis continua of Hallopeau involving the toes and complicated by syndactyly. ACH regression following Iloprost administration was also observed. Published studies are mainly limited to case reports only, due to the rarity of the disease. Therefore, there are no clear-cut therapeutic management guidelines available for this chronic and sometimes debilitating disease. ACH is often recalcitrant to the available therapies. Topical and systemic treatments have been described in literature with no long-lasting results. To our knowledge, this is the first report of foot syndactyly associated to ACH. In our patient, ACH symptoms regressed with Iloprost administration: this finding has never been previously described in literature. If confirmed by other clinical experiences, Iloprost could be a further therapeutic option in ACH.


Individual identification with high frequency ECG : preprocessing and classification by neural network.
In this research, we proposed that high frequency component of HFECG was applicable biometric feature for new identification system. We developed identification method by using neural network (NN), and aimed at the improvement of the classification rate. Preprocessing prior to NN is performed by justification on time axis and normalization on amplitude. As a result, an average of 99% classification rate was obtained from 9 subjects. We also made an attempt to identify in shorter time by shifting of the HFECG by a few samples to NN.


Enhanced photocatalytic activity of 3D hierarchical RP/BP/BiOCOOH via oxygen vacancies and double heterojunctions.
A 3D hierarchical RP/BP/BiOCOOH double heterostructures with abundant oxygen vacancies (OVs) was obtained by hydrothermal process and its photocatalytic activity was investigated by degradation of TC-HCl with different light sources and various natural water. The physicochemical characteristics of RP/BP/BiOCOOH heterojunctions were systematically characterized via TEM, XPS, EPR, EIS et al. Compared with BiOCOOH, the photocatalytic activity of RP/BP/BiOCOOH was obviously enhanced. Under simulated solar light irradiation, 60.5% of TC-HCl was removed by 3%RP/BP/BiOCOOH. And the rate constant of 3%RP/BP/BiOCOOH was 2.95 times than that of BiOCOOH. Traces of small molecular organics were beneficial to improve photocatalytic efficiency. The process of photocatalytic degradation and the cytotoxicity of intermedia products of TC-HCl were discussed via HPLC-MS, 3D-EEM, and antibacterial properties test. Based on the results of trapping experiments and ESR tests, •OH and •O2- were the most significant reactive oxygen species. The enhanced photocatalytic activity was ascribed to two reasons: 1 double heterojunctions structure enhanced the separation efficiency of carriers, 2 the introduction of OVs and BP/RP expanded the response range of light. This work provides a feasible strategy that non-metallic element semiconductor is used to modify the wide band gap semiconductor to enhance the photocatalytic efficiency.


[Radiological diagnosis of primitive hepatic tumors in infants (author's transl)].
Six primitive hepatic tumours (two benign and four malignant) collected over a period of seven years, are studied. The symptoms were mild or absent in many of the cases, and all were discovered after investigation of hepatomegaly or abdominal mass. The importance of the co-ordinated use of radiological and gammagraphical findings is pointed out.


Evaluation of colorimetric dipstick test to detect alcohol in saliva: a pilot study.
The Alco Screen Saliva Dipstick is an inexpensive, easy-to-use, colorimetric test that gives a semiquantitative estimation of the blood alcohol value by measuring the relative concentration of salivary alcohol. To evaluate its accuracy, we compared the results from tests with the Alco dipstick with values from simultaneously measured blood alcohol tests in 53 patients who were suspected of having ingested alcohol. The correlation between Alco dipstick results and blood alcohol values was strong (r [Spearman's rho], + .91). When the blood alcohol concentration was 0.1 g/dL or more, the Alco dipstick test was 90.9% sensitive, 71.4% specific, and 92% efficient. At Alco dipstick values of 0.02 and 0.05 g/dL, however, semiquantitative concordance was unsatisfactory. Nevertheless, even at the 0.05-g/dL value of salivary alcohol, the test was still valuable as a screen of de facto alcohol ingestion. Definitive diagnosis of relative alcohol intoxication requires confirmatory breath or blood alcohol concentrations by standard methodologies.


Joining Forces to Overcome Cancer: The Kenya Cancer Research and Control Stakeholder Program.
Cancer is the third leading cause of mortality in Kenya, accounting for 7% of annual deaths. The Kenyan Ministry of Health (MOH) is committed to reducing cancer mortality, as evidenced by policies such as the National Cancer Control Strategy (2011-2016). There are many Kenyan and international organizations devoted to this task; however, coordination is lacking among stakeholders, resulting in inefficient and overlapping expenditure of resources. The MOH and the NCI Center for Global Health collaboratively executed a two day workshop to improve coordination among government, NGO, and private organizations. Over 80 stakeholders participated from leading cancer research and control institutions in Kenya and the international sphere. Actionable recommendations include: establishment of a nationally representative population-based cancer registry; enhanced training for community health workers, nurses, researchers, pathologists, and oncology specialists; a reconfigured referral process, including leveraging of existing resources to improve access to cancer care; and coordinated community outreach and education. The MOH is in the process of forming a Technical Working Group (TWG) and has elected a Board of Directors for the newly established Kenyan National Cancer Institute (KNCI), with both entities committed to advancing the cancer control work of the MOH. This stakeholder meeting enhanced in-country networks, identified priority needs and developed actionable proposals for coordinated improvement of cancer research and control. Active, persistent follow-up by the TWG, KNCI, and other partners will be needed to turn proposals into reality and ensure that partners' investments are integrated into larger cancer control efforts prioritized by MOH.


Analysis and Research on Audience Satisfaction of Performing Arts Projects in Tourist Scenic Spots Based on the ASCI Model and Big Data.
The development trend of tourism performance networking, although convenient for audience consumption, also makes the performance information present the development trend of big data. In the mass of information, how to accurately locate products and improve audience satisfaction is an urgent problem to be solved. In order to better explore the evaluation of tourism performance by the customer satisfaction evaluation model, analyze the development prospect of tourism in Jiangxi Province in the future, improve the customer satisfaction evaluation model with rough set, and propose a composite customer satisfaction evaluation model. By setting the adjustment value of the evaluation index, the model not only avoids the "false eigenvalue" of the satisfaction evaluation result but also simplifies the calculation process of the model and improves the accuracy, calculation efficiency, and single data processing capacity of the satisfaction evaluation. According to the MATLAB simulation results, the composite customer satisfaction evaluation model constructed in this study is better, the calculation accuracy is >97%, and the calculation time is 40 seconds, which are better than the original customer satisfaction evaluation model. Therefore, the composite customer satisfaction evaluation model can be applied to the evaluation of tourism performance products to provide data support for the evaluation price of audience satisfaction in Jiangxi Province.


Evidence suggesting an evolutionary relationship between transposable elements and immune system recombination sequences.
Sequence similarity between the termini of invertebrate Tcl-like transposable sequences and the signal sequences of the vertebrate immunoglobulin somatic recombination pathway is described. These similarities suggest that the Tcl transposition pathway may share common sequence-specific binding factors with the immunoglobulin somatic recombination pathway.


Karyotypic evolution of human meningioma. Progression through malignancy.
Cytogenetic analysis of an untreated sarcomatous meningioma from a patient submitted to two surgeries separated by 1 year are reported. The material from the first surgery was mostly hypodiploid, with a modal chromosome number of 42. Alterations of chromosome 22 were found in 80.6% of the cells. Four chromosome markers were found involving chromosomes 1, 2, 6, and 22, and numerical alterations involving chromosomes 8, 9, 10, 13, 14, 15, 18, 19, 20, 21, and Y. Although the modal chromosome number of the material from the second surgery was 45 (17.9% of the cells), 43.1% of its cells were hyperdiploid, 73% of these being in the triploid-tetraploid range. Dicentric and ring chromosomes were very frequent. Alterations involving chromosome 22 were still present. There was a recurrent trisomy of chromosome 3. To our knowledge, this is the first cytogenetic description, with banding techniques, of a malignant meningioma.


Impaired procedural memory in narcolepsy type 1.
Sleep enhances the consolidation of memories. Here, we investigated whether sleep-dependent memory consolidation differs between healthy subjects and narcolepsy type 1 (NT1) patients. We recruited 18 patients with NT1 and 24 healthy controls. The consolidation of spatial (declarative memory; 2-dimensional object location) and procedural (non-declarative memory; finger sequence tapping) memories was examined across one night of at-home sleep. Sleep was measured by an ambulatory sleep recording device. The overnight gain in the number of correctly recalled sequences in the finger-tapping test was smaller for NT1 patients than healthy subjects (+8.1% vs. +23.8% from pre-sleep learning to post-sleep recall, p = .035). No significant group differences were found for the overnight consolidation of spatial memory. Compared to healthy subjects, the sleep of NT1 patients was significantly more fragmented and shallow. However, no significant correlations were found between sleep parameters and overnight performance changes on the memory tests in the whole group. The sleep-dependent consolidation of procedural but not spatial memories may be impaired among patients with NT1. Therefore, future studies are warranted to examine whether sleep improvement, for example, using sodium oxybate, can aid the sleep-dependent formation of procedural memories among NT1 patients.


Increased racial differences on breast cancer care and survival in America: historical evidence consistent with a health insurance hypothesis, 1975-2001.
This study examined whether race/ethnicity had differential effects on breast cancer care and survival across age strata and cohorts within stages of disease. The Detroit Cancer Registry provided 25,997 breast cancer cases. African American and non-Hispanic white, older Medicare-eligible and younger non-eligible women were compared. Successive historical cohorts (1975-1980 and 1990-1995) were, respectively, followed until 1986 and 2001. African American disadvantages on survival and treatments increased significantly, particularly among younger women who were much more likely to be uninsured. Within node positive disease all treatment disadvantages among younger African American women disappeared with socioeconomic adjustment. Growth of this racial divide implicates social, rather than biological, forces. Its elimination will require high quality health care for all.


A positive pneumococcal urinary antigen test promotes narrow spectrum antibiotic use in patients with non-invasive pneumococcal pneumonia.
We compared changes in antibiotics in patients diagnosed with noninvasive pneumococcal pneumonia (NPP) by pneumoccocal urinary antigen tests or respiratory cultures. We compared patients diagnosed by pneumococcal urinary antigen tests or respiratory cultures that grew Streptococcus pneumoniae. We assessed the time from sample receipt to final result and antibiotic regimens, including an Antibiotic Spectrum Index (ASI). Seventy-two cases of NPP were diagnosed by pneumococcal urinary antigen and 87 by respiratory cultures, with a median time from sample receipt to final result of 0.21 days (interquartile range (IQR) 0.17-1.17) and 3.21 days (IQR 3.17-4.21 days), respectively. Among 123 cases without antibiotic allergies, between days 0 and 2, the ASI decreased in 36% (18/50) of cases diagnosed by urinary antigen compared to 10% (7/73) of cases diagnosed by respiratory culture (P < 0.01). Positive pneumococcal urinary antigen tests lead to early deescalation of antibiotics more frequently than respiratory cultures.


Analysis of arterial function in adults with a history of Kawasaki disease.
It remains controversial whether Kawasaki disease (KD) is a risk factor for the early onset of atherosclerosis. The purpose of the present study was to assess endothelial function and arterial stiffness as markers of the early onset of atherosclerosis in adult patients with a history of KD. We compared 14 adult patients with a history of KD with 41 healthy controls. To assess arterial endothelial function, we measured the reactive hyperemia-peripheral arterial tonometry (RH-PAT) index and augmentation index adjusted to 75 bpm (AIx@75) using the Endo-PAT 2000 (Itamar Medical, Caesarea, Israel). In addition, we analyzed medical history, blood pressure, lifestyle habits, and atherosclerosis-related serum biochemical markers [asymmetric dimethylarginine, adiponectin, lipoprotein (a), cholesterols, atherogenic index of plasma]. There was no difference between the KD and control groups with regard to the RH-PAT index values (2.10 ± 0.43 and 1.84 ± 0.49, respectively; p=0.19). However, in the KD group, the RH-PAT index values were negatively correlated with the febrile period in the acute phase of disease (r(2)=0.458, p=0.048). In addition, the AIx@75 values were higher in KD patients compared to healthy controls (-7.69 ± 11.86% and -15.87 ± 8.72%, respectively; p=0.01). No significant differences existed between the KD and control groups with regard to the serum biomarkers of atherosclerosis. We speculate that endothelial dysfunction in former KD patients is affected by the febrile period of the acute phase, and antiplatelet drugs may improve endothelial function. The increased arterial stiffness of patients caused by post-inflammatory fibrotic changes in the arterial wall indicates that adults with a history of KD have an increased risk of developing atherosclerosis.


Exploring the influential factors in incident clearance time: Disentangling causation from self-selection bias.
Understanding the relationships between influential factors and incident clearance time is crucial to make effective countermeasures for incident management agencies. Although there have been a certain number of achievements on incident clearance time modeling, limited effort is made to investigate the relative role of incident response time and its self-selection in influencing the clearance time. To fill this gap, this study uses the endogenous switching model to explore the influential factors in incident clearance time, and aims to disentangle causation from self-selection bias caused by response process. Under the joint two-stage model framework, the binary probit model and switching regression model are formulated for both incident response time and clearance time, respectively. Based on the freeway incident data collected in Washington State, full information maximum likelihood (FIML) method is utilized to estimate the endogenous switching model parameters. Significant factors affecting incident response time and clearance time can be identified, including incident, temporal, geographical, environmental, traffic and operational attributes. The estimate results reveal the influential effects of incident, temporal, geographical, environmental, traffic and operational factors on incident response time and clearance time. In addition, the causality of incident response time itself and its self-selection correction on incident clearance time are found to be indispensable. These findings suggest that the causal effect of response time on incident clearance time will be overestimated if the self-selection bias is not considered.


Novel dual-emission sulfur quantum dot sensing platform for quantitative monitoring of pesticide 2,4-dichlorophenoxyacetic acid.
In this work, a novel environment-friendly dual-emission Rhodamine B modified sulfur quantum dots (RhB-SQDs) sensing platform was established to economically monitor organochlorine pesticide 2,4-dichlorophenoxyacetic acid (2,4-D) through regulating the activity of alkaline phosphatase (ALP). This dual emission RhB-SQDs exhibited excellent fluorescence and high photostability with emission wavelengths of 455 nm and 580 nm. ALP catalyzed the hydrolysis of the substrate p-nitrophenyl phosphate to p-nitrophenol, which quenched RhB-SQDs fluorescence at 455 nm due to the internal filtration effect, but had no effect the fluorescence intensity of RhB-SQDs at 580 nm. When 2,4-D was present, the activity of ALP was specifically inhibited and enzymatic reaction was interrupted, leading to the reduction of p-nitrophenol production, so the fluorescence of RhB-SQDs at 455 nm was restored. It demonstrated a good linear relationship between the concentration of 2,4-D and F455/F580 in the range of 0.050-0.500 μg mL-1, with a detection limit of 17.3 ng mL-1. The dual-emission fluorescent probe was successfully realized in the identification of 2,4-D in natural water samples and vegetables with the advantages of exceptional accuracy, immunity to interference, and selectivity. The platform offers a fresh look at pesticide monitoring and has the potential to prevent pesticide-related health issues.


[Instrumental means of psychophysiological studies of higher mental functions in children and adolescents--from devices and complexes to medical engineering technologies of diagnosis, rehabilitation and monitoring].
The paper outlines new engineering decisions of provision of medical engineering technologies of the quantitative assessment of the status and rehabilitation of higher mental functions of children and adolescents in health and in diseases. The theoretical and experimental rationales for the development of new technologies, basic principles and examples of their realization are given.


Occipital midline EEG and subjective rating of task difficulty as indices of mental task strain.
Three measures of mental task strain, namely performance level, occipital midline beta-2 (Oz beta 2) amplitude and subjective rating of task difficulty, were taken in 34 healthy male students aged 19-24 years as they performed either a paced or a self-paced calculating task for 4 h. The performance levels were so constant throughout the work periods that they were of no use in evaluating mental task strain. The Oz beta 2 amplitudes increased significantly with the execution of both tasks, and a significant increase took place during the self-paced task work periods. From this, a critical value of Oz beta 2 amplitude for a heavy task strain was estimated to be about 3.5 microV (the difference between the values at work and at rest). The subjective ratings of task difficulty rose linearly with work time in both tasks. The subjective task strain attributable to work time was found to exceed the critical level long before the objective measure. In addition, other results suggest that the Oz beta 2 activity attributable to task execution is related to the capacity for achieving the task.


Cyclic AMP compartmentation due to increased cAMP-phosphodiesterase activity in transgenic mice with a cardiac-directed expression of the human adenylyl cyclase type 8 (AC8).
Hearts from AC8TG mice develop a higher contractility (LVSP) and larger Ca2+ transients than NTG mice, with (surprisingly) no modification in L-type Ca2+ channel current (ICa,L) (1). In this study, we examined the cardiac response of AC8TG mice to beta-adrenergic and muscarinic agonists and IBMX, a cyclic nucleotide phosphodiesterase (PDE) inhibitor. Stimulation of LVSP and ICa,L by isoprenaline (ISO, 100 nM) was twofold smaller in AC8TG vs. NTG mice. In contrast, IBMX (100 microM) produced a twofold higher stimulation of ICa,L in AC8TG vs. NTG mice. IBMX (10 microM) increased LVSP by 40% in both types of mice, but contraction and relaxation were hastened in AC8TG mice only. Carbachol (10 microM) had no effect on basal contractility in NTG hearts but decreased LVSP by 50% in AC8TG mice. PDE assays demonstrated an increase in cAMP-PDE activity in AC8TG hearts, mainly due to an increase in the hydrolytic activity of PDE4 and PDE1 toward cAMP and a decrease in the activity of PDE1 and PDE2 toward cGMP. We conclude that cardiac expression of AC8 is accompanied by a rearrangement of PDE isoforms, leading to a strong compartmentation of the cAMP signal that shields L-type Ca2+ channels and protects the cardiomyocytes from Ca2+ overload.


Integrating the patients' voice in designing and delivering a research study: The Yorkshire Cancer Research funded PREHABS study's experience.
Engaging with patients when designing a clinical or research project is beneficial; feedback from the intended audience provides invaluable insight form the patients' perspective. Working with patients can result in developing successful research grants and interventions. The benefit of including the voice of the patient in the Yorkshire Cancer Research funded PREHABS study is described in this article. Patients were included in the PREHABS study from inception to completion. The Theory of Change methodology was used to provide a framework to implement patient feedback to refine the study intervention. In total, 69 patients engaged with the PREHABS project. Two patients were recruited as co-applicants on the grant and were members on the Trial Management Group. Six patients attended the pre application workshop and provided feedback on their lived experiences of being a lung cancer patient. Commentary from the patients influenced the interventions selected and the design of the prehabs study. Following ethical approval (21/EE/0048) and informed written consent, 61 patients were recruited into the PREHABS study between October 2021 and November 2022. The breakdown of recruited patients was 19 males: mean age 69.1 years (SD 8.91) and 41 females; mean age 74.9 years (SD 8.9). It is practicable and beneficial to include patients at all stages of designing and delivering a research study. Patient feedback can help refine the study interventions to allow for maximum acceptance, recruitment and retention. Including patients in the design of radiotherapy research studies can provide invaluable insight that can support the selection and delivery of interventions that are acceptable to the patient cohort.


Hepatic Resection for Non-functional Neuroendocrine Liver Metastasis: Does the Presence of Unresected Primary Tumor or Extrahepatic Metastatic Disease Matter?
The objective of this study was to assess the impact of unresected primary tumor, as well as extrahepatic metastasis, on the long-term prognosis of patients undergoing hepatic resection for non-functional neuroendocrine liver metastasis (NF-NELM). Patients who underwent hepatic resection for NF-NELM were identified from a multi-institutional database. Data on clinical and pathological details, as well as the long-term overall survival (OS) were obtained and compared. Propensity score matching was performed to generate matched pairs of patients. Among the 332 patients with NF-NELM, 281 (84.6%) underwent primary tumor resection, while 51 (15.4%) did not. Patients who underwent primary resection were more likely to have a pancreatic primary and metachronous NELM. The long-term OS of patients who did and did not have the primary neuroendocrine tumor (NET) resected was comparable on both unmatched (10-year survival rate 66.8% vs. 54.0%, p = 0.192) and matched (10-year survival rate 75.7% vs. 60.4%, p = 0.271) analyses. In contrast, patients with NF-NELM and extrahepatic metastasis had a worse OS following resection compared with patients who had intrahepatic-only metastasis on unmatched (10-year survival rate 37.5% vs. 69.3%, p = 0.002) and matched (10-year survival rate 37.5% vs. 86.3%, p = 0.011) analyses. On multivariable analysis, while resection of the primary NET was not associated with OS (hazard ratio [HR] 0.7, 95% confidence interval [CI] 0.4-1.2, p = 0.195), the presence of extrahepatic metastasis was independently associated with long-term risk of death (HR 3.9, 95% CI 1.7-9.2, p = 0.002). While surgery should be considered for patients with NF-NELM who have an unresectable primary tumor, operative resection of NF-NELM may not be as beneficial in patients with extrahepatic disease.


Stereospecific entry to [4.5]spiroketal glycosides using alkylidenecarbene C-H insertion.
[reaction: see text] A novel method for the stereospecific preparation of [4.5]spiroketal glycosides utilizing the 1,5 C-H bond insertion of alkylidenecarbenes is described. Treatment of 2-oxopropyl beta-pyranosides A with lithium (trimethylsilyl)diazomethane in THF at -78 degrees C afforded 1,6-dioxaspiro[4,5]decenes B in good yield. Submission of the corresponding alpha-glycosides C to the same reagent gave the isomeric insertion products D in moderate to high yield.


The broad reach and inaccuracy of men's health information on social media: analysis of TikTok and Instagram.
Social media (SoMe) offers great potential to expand access to health information, but a significant proportion of users consume its content instead of consulting a physician. We sought to quantify the volume and characterize the accuracy of men's health-related content on TikTok and Instagram. We searched TikTok and Instagram for the terms: testosterone, erectile dysfunction, male infertility, semen retention, Peyronie's disease, and vasectomy. The top 10 hashtags for each term were used to estimate the total impressions for each term on each platform, and posts were then characterized by creator type, content type, and accuracy (1 to 5 scale). TikTok had 2,312,407,100 impressions and Instagram had 3,107,300 posts across all topics. Semen retention had the most impressions on TikTok (1,216,074,000) and posts on Instagram (1,077,000). Physicians created only a small portion of total TikTok and Instagram posts (10.3% and 12.9%, respectively). Across all topics, the accuracy of content was poor (2.6 ± 1.7), however, physician posts were more accurate than non-physician posts (mean 4.2 ± 1.2 vs 2.3 ± 1.6, p < 0.001, respectively). Men's health content is popular on TikTok and Instagram but is not accurate. We recommend that physicians actively engage in SoMe to address misinformation.


Changes in blood flow velocity in the middle and anterior cerebral arteries evoked by walking.
Transcranial Doppler sonography (TCD) is an established method for assessing changes in blood flow velocity (BFV) coupled to brain activity. Our objective was to investigate whether walking induces measurable changes in BFV in healthy subjects. Changes in BFV in both middle cerebral arteries (MCAs) of 40 healthy adult subjects during walking on a treadmill were measured using bilateral TCD. In 8 of the 40 subjects, 1 anterior cerebral artery (ACA) was monitored simultaneously with the contralateral MCA. The percentage increase in BFV (BFVI%) compared with the baseline velocity (V(0)), the percentage decrease in BFV (BFVD%) compared with the V(0), and the normalized ACA-MCA ratio were analyzed. The overall mean (+/- standard deviation [SD]) V(0) was 59.9 +/- 11.6 cm/second in the left MCA and 60.1 +/- 12.9 cm/second in the right MCA. Women had higher V(0) values than men had. Walking evoked an initial mean overall BFVI% in both left (8.4 +/- 5.1%) and right MCAs (9.1 +/- 5.1%), followed by a decrease to below baseline values in 38 of 40 subjects. A statistically significant increase of the normalized ACA-MCA ratio was measured, indicating that changes in BFV in the ACA territory were coupled to brain activation during walking. The use of functional TCD showed different changes in BFV in the ACAs and MCAs during walking. This method may be an interesting tool for monitoring progress in patients with motor deficits of the legs, such as paresis.


[Establishment of the necessity for a review of the vascular endothelium: an introduction].
The vascular endothelium despite of its relative small total mass is distributed all over the organism and is obligatory for nearly all vital processes. The following review will show, how many structural and functional properties of the endothelium are accessible to modern morphological research and will summarize results obtained by the authors of this review in context with the modern literature. The intentions of the authors are to contribute to a better understanding of morphological results and to find new access to scientific and clinical problems of endothelium.


Suppression and enhancement of humoral immune response to Toxoplasma gondii by passive antibody.
Anti-toxoplasma antibodies administered passively to mice may lead to suppression of enhancement (reported for the first time with Protozoan parasites) of subsequent antibody response when these animals are later infected with Toxoplasma gondii. The outcome is dependent on infecting strain of Toxoplasma and the antigen-antibody ratio.


Successfully completed total cavopulmonary connection with a right-sided maze procedure after a modified Starnes' operation in a neonate with Ebstein's anomaly.
The symptomatic newborn infant with Ebstein's anomaly is in critical condition and is difficult to treat successfully. Furthermore, supraventricular tachyarrhythmia in patients with Ebstein's anomaly may determine the early and late results. We report a successfully treated case of extracardiac total cavopulmonary connection with a right-sided maze procedure after a modified Starnes' operation during the neonatal period.


Insulin provision therapy and mortality in older adults with diabetes mellitus and stable ischemic heart disease: Insights from BARI-2D trial.
Optimal strategies for glucose control in very old adults with diabetes and stable ischemic heart disease (SIHD) are unclear. To compare the effects of insulin provision (IP) therapy versus insulin sensitizing (IS) therapy for glycemic control in older (≥75years) and younger (<75years) adults with type II diabetes (DM) and SIHD. Adults enrolled in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) were studied. The BARI 2D study population (all with type II DM and SIHD) was randomized twice: (1) between revascularization plus intensive medical therapy versus intensive medical therapy alone, and (2) between IP versus IS therapies. The primary endpoint was all-cause-mortality over five-year follow-up. In this substudy outcomes related to IP vs. IS are assessed in relation to age. Adults aged ≥75years who received IP versus IS are compared to those <75years who received IP versus IS. Multivariate Cox regression analysis was used to evaluate the effects of IP vs. IS on outcomes in the two age groups. 2368 subjects with SIHD and DM were enrolled in BARI 2D; 182 (8%) were ≥75years. Compared to younger subjects, the older cohort had lower BMI, higher diuretic use, worse kidney function, and increased history of heart failure. Within the older cohort, the IP and IS subgroups were similar in respect to baseline cardiovascular risk factors, medications, and coronary artery disease severity. During follow-up, the older subjects receiving IP therapy had higher cardiovascular mortality compared to those receiving IS therapy (16% vs. 11%, p=0.040). Using Cox proportional hazards analysis, the older IP subjects were at increased risk for all-cause-mortality (hazard ratio 1.89, CI 1.1-3.2, p=0.020). No mortality difference between IP and IS was observed in those <75years of age. Among adults with diabetes and SIHD aged ≥75years, IP therapy may be associated with increased mortality compared to IS therapy. Additional studies are needed to further refine optimal treatment strategies for diabetes and SIHD in old age.


Classification of mild Parkinson's disease: data augmentation of time-series gait data obtained via inertial measurement units.
Data-augmentation methods have emerged as a viable approach for improving the state-of-the-art performances for classifying mild Parkinson's disease using deep learning with time-series data from an inertial measurement unit, considering the limited amount of training datasets available in the medical field. This study investigated effective data-augmentation methods to classify mild Parkinson's disease and healthy participants with deep learning using a time-series gait dataset recorded via a shank-worn inertial measurement unit. Four magnitude-domain-transformation and three time-domain-transformation data-augmentation methods, and four methods involving mixtures of the aforementioned methods were applied to a representative convolutional neural network for the classification, and their performances were compared. In terms of data-augmentation, compared with baseline classification accuracy without data-augmentation, the magnitude-domain transformation performed better than the time-domain transformation and mixed-data augmentation. In the magnitude-domain transformation, the rotation method significantly contributed to the best performance improvement, yielding accuracy and F1-score improvements of 5.5 and 5.9%, respectively. The augmented data could be varied while maintaining the features of the time-series data obtained via the sensor for detecting mild Parkinson's in gait; this data attribute may have caused the aforementioned trend. Notably, the selection of appropriate data extensions will help improve the classification performance for mild Parkinson's disease.


The β-cell GHSR and downstream cAMP/TRPM2 signaling account for insulinostatic and glycemic effects of ghrelin.
Gastric hormone ghrelin regulates insulin secretion, as well as growth hormone release, feeding behavior and adiposity. Ghrelin is known to exert its biological actions by interacting with the growth hormone secretagogue-receptor (GHSR) coupled to G(q/11)-protein signaling. By contrast, ghrelin acts on pancreatic islet β-cells via Gi-protein-mediated signaling. These observations raise a question whether the ghrelin action on islet β-cells involves atypical GHSR and/or distinct signal transduction. Furthermore, the role of the β-cell GHSR in the systemic glycemic effect of ghrelin still remains to be defined. To address these issues, the present study employed the global GHSR-null mice and those re-expressing GHSR selectively in β-cells. We here report that ghrelin attenuates glucose-induced insulin release via direct interaction with ordinary GHSR that is uniquely coupled to novel cAMP/TRPM2 signaling in β-cells, and that this β-cell GHSR with unique insulinostatic signaling largely accounts for the systemic effects of ghrelin on circulating glucose and insulin levels. The novel β-cell specific GHSR-cAMP/TRPM2 signaling provides a potential therapeutic target for the treatment of type 2 diabetes.


Blood level of cimetidine in relation to age.
The blood level versus time curve for unchanged cimetidine after a 200 mg oral dose has been determined in 20 apparently healthy subjects, ranging from 22 to 84 years of age. A significant relationship between the area under the curve (AUC) and age was found (r = 0.81; P less than 0.001). The peak concentrations of cimetidine were significantly inversely related to body weight (r = -0.71; P less than 0.001). The age-related increase in bioavailability of oral cimetidine, as measured by AUC, was probably due to decreased total clearance of the drug, which resulted from the opposed changes (by themselves not significant) of distribution volume towards a decrease and of half-life towards an increase with age. Reduction in the standard oral dose of cimetidine by one third to one half should be feasible in the elderly without loss of efficacy, and it may be advisable in order to obviate extreme individual responses that may occur in this population.


Isolation of Chlamydia spp. from ostriches (Struthio camelus) (short report).
Post mortem examination of ostrich chicks (Struthio camelus) originating from a flock with a high mortality rate is described. The main pathological lesions found, indicated colibacillosis which was further corroborated by the isolation of pure culture E. coli. Furthermore Chlamydia spp. was isolated for the first time from ostriches. A detailed isolation procedure is presented. The association of colibacillosis with Chlamydia and the latency of Chlamydia is discussed.


Cecal infarct: report of a case.
The purpose of this article is to present a case of an uncommon opportunistic fungal infection that appears in immunologically or metabolically compromised patients and is usually fatal. A 54-year-old woman with an acute lymphoblastic leukemia had acute abdominal pain with peritoneal symptoms during her hospital stay. A laparotomy was performed and a cecal infarct firmly adherent to about 30 cm of infiltrated jejunal loop was discovered. Microscopic studies revealed an infiltration of the jejunal wall by abnormal lymphocytes. The cecal and ileal walls were infiltrated by leukocytes. Blood vessels were invaded by giant cells and large, unseptated, right-angle branching hyphea. These findings were considered typical of invasive mucormycosis of the cecum and the terminal ileum.


Epigenetic markers in basal cell carcinoma: universal themes in oncogenesis and tumor stratification? - a short report.
Advanced basal cell carcinomas (BCCs) suffer from a scarcity of effective treatment options. Previously, we found that the targetable histone methyltransferase EZH2 was upregulated in aggressive BCC subtypes, suggesting that epigenetics may play a role in BCC progression. The purpose of this study was to determine whether EZH2-associated proteins and marks may be employed for the stratification of BCC histologic subtypes. Sixty-two specimens (from 61 patients), representing more or less aggressive BCC histologic subtypes and matching non-malignant epidermal cells, were included in this study. Immunohistochemistry of H3K27me3, 5hmC, NSD2, MOF and JARID1B was performed to assess their putative associations with BCC histologic subtypes, as well as with EZH2 and Ki67 expression levels. We found that H3K27me3 and 5hmC upregulation was positively correlated with the occurrence of a less aggressive BCC histology. The modifications were also positively correlated with each other. Interestingly, we found that they were negatively correlated with the expression of EZH2, a marker for an aggressive BCC histology. The levels of NSD2, MOF, H3K27me3 and 5hmC were found to be universally upregulated in BCCs versus non-malignant epidermal cells. Our data reveal an EZH2-associated epigenetic marker profile that correlates with histologic signs of BCC aggressiveness. Our findings may have diagnostic and therapeutic implications, and indicate that epigenetic markers may be shared even with relatively less aggressive tumor types, thereby suggesting universal themes.


[Clinical study on treatment of non-alcoholic fatty liver of damp-heat syndrome type by danning tablet].
To evaluate the therapeutic effect of Danning Tablet (DNT) on patients with non-alcoholic fatty liver (NAFL) of damp-heat Syndrome type. Multi-center randomized double-blinded positive medicine parallel controlled method was adopted. One hundred and two patients were treated with DNT and 33 patients treated with Ursodeoxycholic acid (UDCA) as control. Indexes including body mass index (MBI), principal symptom, liver function, blood lipids, iconographic parameters and comprehensive efficacy were measured before and after treatment in the two groups respectively. DNT and UDCA had the effect in improving BMI, distress in hepatic region, fatigue, anorexia, liver function, blood lipids and iconographic parameters, etc. DNT showed effects in improving BMI and distress in hepatic region better than those of UDCA. Histological examination also showed that DNT had good therapeutic effect. DNT is an effective medicine for NAFL patients of damp-heat Syndrome type, and its efficacy is better than that of UDCA.


From bench to board-side: Academic teaching careers.
Teaching positions provide a rewarding career pathway for Ph.D.s wishing to stay in academia outside of the research-focused position. The balance of teaching and research expectations on faculty can vary greatly depending on the type of institution. Faculty at primarily undergraduate institutions may be required to be researchactive and mentor undergraduates in the laboratory, while teaching faculty at a research-centered university may not have a research lab. In addition, faculty are expected to actively contribute to the shared governance of the institution, in the name of service. The career in teaching has become highly competitive and offers unexpected rewards and benefits. Considered here are the differences found among teaching positions to serve as a guide when considering teaching as a career option. We include our personal career narratives to illustrate the driving forces that led each of us to this challenging yet fulfilling academic path.


Corticotropin-releasing factor is present in intestinal tissue of patients with gastrointestinal dysfunction following shock and abdominal surgery.
Corticotropin-releasing factor (CRF) is implicated in stress-related gastrointestinal dysfunction, possibly causing gut dysfunction following trauma and surgery. We investigated plasma and intestinal tissue CRF levels and gut function in patients with traumatic shock or those undergoing elective abdominal surgery. In a prospective, parallel, observational study in a university hospital surgical intensive care unit (ICU), 8 shocked patients (systolic blood pressure <90 mmHg and/or acidosis and/or urine output <1 mL/kg/hr and/or requiring >2 L of intravenous fluid resuscitation) undergoing small bowel resection during emergency laparotomy following abdominal injury and 17 stable patients undergoing elective hepatobiliary surgery were included if they required postoperative ICU management. Serial plasma and intestinal CRF was measured and postoperative gastric emptying and intestinal permeability were evaluated. Plasma CRF was significantly increased in the shocked patients compared with the elective surgery patients at all times. CRF peptide was quantified in intestinal tissue at similar levels in both groups. Intestinal permeability was increased and associated with shock and resuscitation fluid volume. Gastric emptying was retarded and correlated significantly with shock but not with plasma CRF. Delayed gastric emptying in shocked patients was associated with longer ICU stay. The novel finding is the presence of CRF in the small bowel of both elective and emergency gastrointestinal surgery patients with concomitant gastrointestinal dysfunction. Circulating CRF is associated with poor gastric emptying, which prolongs ICU stay, whereas shock significantly impairs gastric emptying and gut permeability.


Augmentation ureterocystoplasty in boys with valve bladder syndrome.
Children with valve bladder syndrome represent the worst end of the posterior urethral valve spectrum. When conservative measures fail to control recurrent infections, prevent deterioration of the upper tract (in the form of increasing hydronephrosis and or worsening of kidney function) and improve incontinence, augmentation cystoplasty is considered. In most of these boys, renal insufficiency precludes the use of intestine for augmenting the bladder. Our aim was to evaluate the efficacy and safety of ureterocystoplasty in managing children with valve bladder syndrome. Eight boys (mean age 5 years) with valve bladder syndrome were included in this study. All boys had successful valve ablation at the time of presentation. When conservative treatment failed, ureterocystoplasty was scheduled. The entire ureter was folded and used in four boys after nephrectomy for a non-functioning kidney. The lower dilated ureter was used to augment the bladder, and transureteroureterostomy in two and re-implantation of the remaining ureter in two were performed. Radiological and urodynamic investigation was performed preoperatively and postoperatively at 3, 6 and 12 months. Improvement of hydroureteronephrosis was judged by ultrasound. Bladder capacity (as measured during cystometry at 30 cmH(2)O) and compliance were significantly improved in all children following the procedure (P<0.001), and reached or exceeded the normal calculated capacity for age-matched boys. Hydroureteronephrosis improved in six boys (75%). The procedure avoids almost all the complications of enterocystoplasty. Clean intermittent self-catheterization was performed in all cases routinely after surgery, weaning off as judged by the voiding pattern of the child. Ureterocystoplasty is an ideal option for augmenting the hypocompliant bladder in boys with valve bladder syndrome. The entire ureter or the dilated lower part can be used. This is a solution for boys with impaired renal function when enterocystoplasty cannot be performed.


Community structure and quality after 10 years in two central Ohio mitigation bank wetlands.
We evaluate two 10-year-old mitigation bank wetlands in central Ohio, one created and one with restored and enhanced components, by analysis of vegetation characteristics and by comparison of the year-10 vegetation and macroinvertebrate communities with reference wetlands. To assess different measures of wetland development, we compare the prevalence of native hydrophytes with an index of floristic quality and we evaluate the predictability of these parameters in year 10, given 5 years of data. Results show that the mitigation wetlands in this study meet vegetation performance criteria of native hydrophyte establishment by year 5 and maintain these characteristics through year 10. Species richness and floristic quality, as well as vegetative similarity with reference wetlands, differ among mitigation wetlands in year 1 and also in their rate of change during the first 10 years. The prevalence of native hydrophytes is reasonably predictable by year 10, but 5 years of monitoring is not sufficient to predict future trends of floristic quality in either the created or restored wetland. By year 10, macroinvertebrate taxa richness does not statistically differ among these wetlands, but mitigation wetlands differ from reference sites by tolerance index and by trophic guild dominance. The created wetland herbivore biomass is significantly smaller than its reference, whereas detritivore biomass is significantly greater in the created wetland and smaller in the restored wetland as compared with respective reference wetlands. These analyses illustrate differences in measures of wetland performance and contrast the monitoring duration necessary for legal compliance with the duration required for development of more complex indicators of ecosystem integrity.


Density changes at the proximal tibia after medial meniscectomy.
Trabecular bone density changes at the proximal tibia were studied after total and partial meniscectomy using quantitative computerized tomography. Thirty-seven medially meniscectomized patients (5- and 10-year follow-up) and 10 control persons were included. In the partially and the totally meniscectomized knees, the area of maximal density in the medial tibial condyle was displaced approximately 4 mm in a posteromedial direction relative to the position in the intact knees. In both partially and totally meniscectomized knees, the density in the region of tibiofemoral contact in the medial tibial condyle was higher compared with the density in the same region in the contralateral intact knees. This difference was of the same order in the 5- and 10-year follow-up groups. The density difference between the meniscectomized and the intact knees in the region of tibiofemoral contact in the medial condyle was significantly higher in totally than in partially meniscectomized patients. It is concluded that not only total but also partial medial meniscectomy is followed by density changes, occurring within the first 5 years after meniscectomy. The results emphasize the importance of the utmost conservatism in surgery on the meniscus.


Ligand-assisted rate acceleration in transacylation by a yttrium-salen complex. Demonstration of a conceptually new strategy for metal-catalyzed kinetic resolution of alcohols.
[reaction: see text]. Yttrium-salen complexes effect transacylation between enolesters and chiral secondary alcohols, resulting in varying degrees of kinetic resolution. Even though the enantioselectivity remains modest (k(fast)/k(slow) up to 4.81), these results represent the first demonstration of a conceptually new metal-catalyzed acyl transfer process that results in kinetic resolution. On the basis of the solid-state structure of the catalyst, a novel associative mechanistic pathway is proposed for the reaction.