Participation of Histones in DNA Damage and Repair within Nucleosome Core Particles: Mechanism and Applications.
DNA is damaged by various endogenous and exogenous sources, leading to a diverse group of reactive intermediates that yield a complex mixture of products. The initially formed products are often metastable and can react to yield lesions that are more biologically deleterious. Mechanistic studies are frequently carried out on free DNA as the substrate. The observations do not necessarily reflect the reaction environment inside human cells where genomic DNA is condensed as chromatin in the nucleus. Chromatin is made up of monomeric structural units called nucleosomes, which are comprised of DNA wrapped around an octameric core of histone proteins (two copies each of histones H2A, H2B, H3, and H4).This account presents a summary of our work in the past decade on the mechanistic studies of DNA damage and repair in reconstituted nucleosome core particles (NCPs). A series of metastable lesions and reactive intermediates, such as abasic sites (AP), N7-methyl-2'-deoxyguanosine (MdG), and 2'-deoxyadenosin-N6-yl radical (dA•), have been independently generated in a site-specific manner in bottom-up-synthesized NCPs. Detailed mechanistic studies on these NCPs revealed that histones actively participate in DNA damage and repair processes in diverse ways. For instance, nucleophilic residues in the flexible histone N-terminal tails, such as Lys and N-terminal α-amine, react with electrophilic DNA damage and reactive intermediates. In some cases, transient intermediates are produced, leading to the promotion or suppression of damage and repair processes. In other examples, reactions with histones yield reversible or stable DNA-protein cross-links (DPCs). Histones also utilize acidic and basic residues, such as histidine and aspartic acid, to catalyze DNA strand cleavage through general acid/base catalysis. Alternatively, a Tyr in histone plays a vital role in nucleosomal DNA damage and repair via radical transfer. Finally, the reactivity discovered during the mechanistic studies has facilitated the development of new reagents and methods with applications in biotechnology.This research has enriched our knowledge of the roles of histone proteins in DNA damage and repair and their contributions to epigenetics and may have significant biological implications. The residues in histone N-terminal tails that react with DNA lesions also play pivotal roles in regulating the structure and function of chromatin, indicating that there may be cross-talk between DNA damage and repair in eukaryotic cells and epigenetic regulation. Also, in view of the biased amino acid composition of histones, these results provide hints about how the proteins have evolved to minimize their deleterious effects but maximize beneficial ones for maintaining genome integrity. Finally, previously unreported DPCs and histone post-translational modifications have been discovered through this research. The effects of these newly identified lesions on the structure and function of chromatin and their fates inside cells remain to be elucidated.


Evidence of glycosylated sites on the endothelin-1 receptor in Swiss 3T3 cells.
The effects of incubation of intact cells with six different lectins on the specific binding of [125I]endothelin-1 (ET-1) were determined in Swiss 3T3 fibroblasts. ET-1 binding was unaffected by pretreatment of cells for 1 h at 37 degrees C with concanavalin A, soybean agglutinin, Ulex europaeus agglutinin I, peanut agglutinin, or Galanthus nivalis agglutinin. However, preincubation of cells with 300 micrograms/ml of wheat germ agglutinin resulted in a 70% decrease in specific binding of ET-1 to cell-surface receptors. The inhibitory effects of wheat germ agglutinin were diminished by brief incubation of lectin-treated cells with 100 mM N-acetylglucosamine, a monosaccharide specifically recognized by wheat germ agglutinin. Neither glucose nor mannose had any effect on wheat germ agglutinin-mediated inhibition of the specific binding of ET-1. These results suggest that the ET-1 receptor on 3T3 cells is a glycoprotein that contains one or more N-acetylglucosamine residues at or near the ligand binding site.


Nuclear Wiskott-Aldrich syndrome protein co-regulates T cell factor 1-mediated transcription in T cells.
The Wiskott-Aldrich syndrome protein (WASp) family of actin-nucleating factors are present in the cytoplasm and in the nucleus. The role of nuclear WASp for T cell development remains incompletely defined. We performed WASp chromatin immunoprecipitation and deep sequencing (ChIP-seq) in thymocytes and spleen CD4+ T cells. WASp was enriched at genic and intergenic regions and associated with the transcription start sites of protein-coding genes. Thymocytes and spleen CD4+ T cells showed 15 common WASp-interacting genes, including the gene encoding T cell factor (TCF)12. WASp KO thymocytes had reduced nuclear TCF12 whereas thymocytes expressing constitutively active WASpL272P and WASpI296T had increased nuclear TCF12, suggesting that regulated WASp activity controlled nuclear TCF12. We identify a putative DNA element enriched in WASp ChIP-seq samples identical to a TCF1-binding site and we show that WASp directly interacted with TCF1 in the nucleus. These data place nuclear WASp in proximity with TCF1 and TCF12, essential factors for T cell development.


[Identification of susceptibility genes for age-related macular degeneration--a success story of molecular genetics].
The number of persons over 70 years of age with advanced age-related macular degeneration in Finland can be estimated to be approximately 50,000. Milder forms are additionally present in a considerably larger group. Smoking and age are undisputed non-genetic risk factors of age-related macular degeneration. Of the genetic factors, polymorphisms of the complement factor H (CFH) and LOC387715 genes have a strong impact on the risk of developing the disease, whereas alleles of the C3, CFB, and the C1 inhibitor SERPING1 genes of the complement system exhibit only minor effects.


Infantile sexuality, primary object-love and the anthropological significance of the Oedipus complex: re-reading Freud's 'Female sexuality'.
The author attempts to show why and in what respect Freud's famous article 'Female sexuality' can still be a source of inspiration for a contemporary metapsychology. In this text, Freud acknowledges the importance of the child's tie to its mother for the first time. Both Balint and Bowlby consider this text to be a distant forerunner of their own theories on primary object-love and attachment respectively. At the same time, Freud's text contains some elements of a 'theory of generalized seduction' as it was developed in the last decades by Jean Laplanche. 'Female sexuality' therefore presents itself as the perfect point of departure for a discussion of the relation between primary object-love (and attachment) and sexuality. Based on his reading of Freud's text, the author argues that human subjectivity is characterized by the lack of attunement between the world of the adult and the world of the child. This insight allows for a reformulation of the anthropological significance of the Oedipus and castration complexes. They are no longer interpreted as universal problems that every child has to face, but as historical and contingent solutions to the lack of attunement between the child and the adult that is essential to human subjectivity.


Dentate granule cell function after neonatal treatment with parachloroamphetamine or 5,7-dihydroxytryptamine.
In vitro, extracellular electrophysiological recording was used to test granule cell responses in P60 rats after neonatal PCA and 5, 7-DHT. Granule cell population EPSP and spike responses were in the normal range for both PCA and 5,7-DHT groups. However, the degree of paired pulse facilitation was reduced in both of these groups relative to control, reflecting a diminished synaptic drive. Synaptic potentiation in the 5,7-DHT group was not different from control, but was significantly reduced in slices from PCA-treated rats.


Risk Group and Death From Prostate Cancer: Implications for Active Surveillance in Men With Favorable Intermediate-Risk Prostate Cancer.
Active surveillance (AS), per the National Comprehensive Cancer Network (NCCN) guidelines, is considered for patients with low-risk prostate cancer (PC) and a life expectancy of at least 10 years. However, given the grade migration following the 2005 International Society of Urologic Pathology consensus conference, AS may be appropriate for men presenting with favorable intermediate-risk PC. To estimate and compare the risk of PC-specific mortality (PCSM) and all-cause mortality (ACM) following brachytherapy among men with low and favorable intermediate-risk PC. Prospective cohort study of 5580 consecutively treated men (median age, 68 years) with localized adenocarcinoma of the prostate treated with brachytherapy at the Prostate Cancer Foundation of Chicago between October 16, 1997, and May 28, 2013. Standard of practice per the NCCN guidelines. Fine and Gray competing risks regression and Cox regression analyses were used to assess whether the risks of PCSM and ACM, respectively, were increased in men with favorable intermediate-risk vs low-risk PC. Analyses were adjusted for age at brachytherapy, year of treatment, and known PC prognostic factors. After median follow-up of 7.69 years, 605 men had died (10.84% of total cohort), 34 of PC (5.62% of total deaths). Men with favorable intermediate-risk PC did not have significantly increased risk of PCSM and ACM compared with men with low-risk PC (adjusted hazard ratio [HR], 1.64; 95% CI, 0.76-3.53; P = .21 for PCSM; adjusted HR, 1.11; 95% CI, 0.88-1.39; P = .38 for ACM). Eight-year adjusted point estimates for PCSM were low: 0.48% (95% CI, 0.23%-0.93%) and 0.33% (95% CI, 0.19%-0.56%) for men with favorable intermediate-risk PC and low-risk PC, respectively. The respective estimates for ACM were 10.45% (95% CI, 8.91%-12.12%) and 8.68% (95% CI, 7.80%-9.61%). Men with low-risk PC and favorable intermediate-risk PC have similarly low estimates of PCSM and ACM during the first decade following brachytherapy. While awaiting the results of ProtecT, the randomized trial of AS vs treatment, our results provide evidence to support AS as an initial approach for men with favorable intermediate-risk PC.


Alcohol-Soluble Cross-Linked Poly( nBA) n- b-Poly(NVTri) m Block Copolymer and Its Applications in Organic Photovoltaic Cells for Improved Stability.
In this study, a series of alcohol-soluble cross-linked block copolymers (BCPs) consisting of poly( n-butyl acrylate) (poly( nBA)) and poly( N-vinyl-1,2,4-triazole) (poly(NVTri)) blocks with different individual functions and lengths are designed and developed. These presynthesized cross-linked BCPs (PBA n-Tri m) were, for the first time, revealed to exhibit many advantages in serving as the electron-extraction layer (EEL) for organic photovoltaics (OPVs). The cross-linked BCPs possessed intense ionic functionality, showing well capability to form effective interfacial dipoles at the indium tin oxide interface to facilitate the charge extraction at the corresponding interface. Furthermore, it also consisted a core-shell structure, wherein the polar poly(NVTri) core was well protected by the poly( nBA) shell to endow improved robustness against solvent erosion and thermal/photo inputs. Consequently, the PBA70-Tri30 device yielded a decent power conversion efficiency of 8.03% with a Voc of 0.83 V, much exceeding the performance of the control device without using any EEL. Moreover, this device showed superior thermal stability/photostability. More than 80% of its initial performance was retained after being heated at 60 °C for 1000 h or exposed under continuous illumination (1 sun) for 1000 h, greatly surpassing the lifetime of the control device and the reference device using a common poly[(9,9-bis(3'-( N, N-dimethylamino)propyl)-2,7-fluorene)-alt-2,7-(9,9-dioctylfluorene)] (PFN) EEL. The results revealed the merit of using cross-linked BCPs in improving the long-term stability of OPVs.


The knock-down of overexpressed EZH2 and BMI-1 does not prevent osteosarcoma growth.
Polycomb group proteins control the transcriptional memory of cells by maintaining the stable silencing of specific sets of genes through chromatin modifications. Polycomb group protein complexes control gene repression through recruitment of histone deacetylase. This recruitment leads to trimethylation of Lys27 of histone H3 (H3K27). Histone H3K27 trimethylation is a property of stably silenced heterochromatin. EZH2 and BMI-1 are pivotal components of polycomb group protein complexes. Increased EZH2 levels have been found in several malignancies and reported as a molecular biomarker of poor prognosis. Similarly, BMI-1 has also been found to be associated with malignant transformation. In addition, inhibition of EZH2 or BMI-1 inhibits the growth of various types of malignancies. The expression of BMI-1 and EZH2 in human osteosarcoma has not been clearly determined. We examined the potential involvement of aberrant polycomb group protein expression in the pathogenesis of osteosarcoma. Real-time PCR revealed that expression of EZH2 in 143B, HOS, NOS-1 and Saos2 was increased compared to normal osteoblasts. BMI-1 was also up-regulated in 143B, HOS and NOS-1. Expression of EZH2 and BMI-1 were up-regulated in osteosarcoma patient biopsy specimens compared to normal bone. Immunohistochemical examinations showed that EZH2 and BMI-1 were up-regulated in osteosarcoma cells and that trimethylation of histone H3K27 was increased. We examined the effects of knock down of EZH2 and BMI-1 by shRNA. Unexpectedly, the knock-down of EZH2 and BMI-1 did not prevent osteosarcoma growth either in vitro or in vivo. Our findings suggest that EZH2 and BMI-1 may be tumor-associated antigens of osteosarcoma, but are not useful molecular targets of osteosarcoma treatment.


Sudden death due to undiagnosed Wilms' tumor in an adult.
Sudden unexpected deaths due to natural causes constitute a large number of cases encountered by the forensic pathologist. In a majority of such cases, heart disease is responsible for sudden death. Rare disease entities resulting in sudden death are occasionally encountered and may not fit the classic epidemiological profile. We present a case of sudden death due to a previously undiagnosed Wilms' tumor (WT) in an adult. The pathology of WT is discussed, as is the topic of sudden death due to previously unrecognized malignancy.


Single-energy metal artifact reduction in postimplant computed tomography for I-125 prostate brachytherapy: Impact on seed identification.
To evaluate the effectiveness of the single-energy metal artifact reduction (SEMAR) technique for improving the accuracy of I-125 seed identification in postimplant computed tomography (CT) after prostate brachytherapy. Postimplant CT images of 40 patients treated with I-125 prostate brachytherapy were acquired. For all patients, 2 data sets were reconstructed, 1 with SEMAR algorithms (SEMAR image), and the other without SEMAR algorithms (non-SEMAR image). Seed locations are automatically detected by the automatic seed finder tool, and their locations were compared between the SEMAR and non-SEMAR images. Dosimetric parameters using seed locations as detected were compared. The true-positive fraction of properly detected seeds on the SEMAR image as determined from a reference seed distribution defined by one investigator was significantly higher than the true-positive fraction on the non-SEMAR image (p = 0.011). The variabilities in D90 (p = 0.001), V100 (p = 0.007), and V150 (p = 0.007) were significantly reduced for seed location on the SEMAR image as compared with non-SEMAR image. Prostate postimplant CT with SEMAR improved the accuracy of seed localization and postimplant dosimetric parameters.


Origin of Invariant Gel Melting Temperatures in the c-T Phase Diagram of an Organogel.
Binary c-T phase diagrams of organogelators in solvent are frequently simplified to two domains, gel and sol, even when the melting temperatures display two distinct regimes, an increase with T and a plateau. Herein, the c-T phase diagram of an organogelator in solvent is elucidated by rheology, DSC, optical microscopy, and transmitted light intensity measurements. We evidence a miscibility gap between the organogelator and the solvent above a threshold concentration, cL. In this domain the melting or the formation of the gel becomes a monotectic transformation, which explains why the corresponding temperatures are nonvariant above cL. As shown by further studies by variable temperature FTIR and NMR, different types of H-bonds drive both the liquid-liquid phase separation and the gelation.


Two-Dimensional Dion-Jacobson Perovskite (NH3C4H8NH3)CsPb2Br7 with High X-ray Sensitivity and Peak Discrimination of α-Particles.
Two-dimensional (2D) halide perovskites have attracted extensive interest because of their excellent optoelectronic properties, structural diversity, and promising stability. Herein, we grow a novel 2D Dion-Jacobson halide perovskite, (BDA)CsPb2Br7 (BDA = 1,4-butanediamine, NH3C4H8NH32+), which exhibits a large bandgap (∼2.76 eV), high resistivity (∼4.35 × 1010 Ω·cm), and considerable switching ratio (>700), indicating great potential for radiation detection. Both experimental and calculated results demonstrate that (BDA)CsPb2Br7 has a significantly improved mobility compared to those of Ruddlesden-Popper perovskites (BA)2CsPb2Br7 and (i-BA)2CsPb2Br7, which is attributed to the shorter interlayer distance leading to the enhanced orbital interactions. The resulting (BDA)CsPb2Br7 detector along the out-of-plane direction achieves a high X-ray sensitivity of 725.5 μC·Gy-1·cm-2. Another fascinating attribute is that the detector exhibits good peak discrimination with an energy resolution of ∼37% when illuminated by the email@example.com MeV α-particles under a negative bias of 260 V. These results provide a broad prospect for 2D Dion-Jacobson perovskites for future radiation detection applications.


Development of a new ultrasound scoring system to evaluate glandular inflammation in Sjögren's syndrome: an OMERACT reliability exercise.
The aim of this exercise from the OMERACT Ultrasound subgroup on Sjögren's syndrome was to develop and assess the reliability of a consensus-based semiquantitative colour Doppler US scoring system for pathologic salivary gland vascularization in patients with primary Sjögren's syndrome (pSS). Using the Delphi method, a colour Doppler semiquantitative scoring system for vascularization of bilateral parotid and submandibular glands was developed and tested in static images and on patients (9 pSS patients and 9 sonographers). Intra-reader and inter-reader reliability of grading the salivary glands were computed by weighted Cohen and Light's kappa analysis, respectively. The consensus-based semiquantitative score was: grade 0, no visible vascular signals; grade 1, focal, dispersed vascular signals; grade 2, diffuse vascular signals detected in <50% of the gland; grade 3, diffuse vascular signals in >50% of the gland. In static images, the intra- and inter-reader reliability showed excellent kappa values (95% CI) of 0.90 (0.87, 0.93) and 0.80 (0.74, 0.84), respectively, for all four salivary glands together. In patients, the intra- and inter-reader reliability for all four salivary glands together was kappa = 0.84 (0.73, 0.92) and 0.70 (0.64, 0.76), respectively. The consensus-based colour Doppler US scoring for the evaluation of salivary gland vascularization in pSS showed a good inter-reader reliability and excellent intra-reader reliability in static images and in patients. The clinical application of the developed scoring system should be tested in clinical settings.


[Effect of decreasing hydrodynamic resistance of a polymer on localization of sclerotic plaques. A model study].
Flow structure and wall shear stress and the changes in these parameters induced by the administration of a drag-reducing polymer polyethylene oxide WSR-301 at a concentration of 10(-5) g/ml were studied in a glass tube with a T-junction by the laser Doppler anemometry technique. The pattern of wall shear stresses is in a good agreement with the data, obtained for rabbits in [1]. For tubes with rigid walls, the location of plaques corresponds to regions of a high wall shear stress.


Solvent-Driven Formation of Worm-Like Micelles Assembled from a CO₂-Responsive Triblock Copolymer.
Polymer worm-like micelles (WLMs) are difficult to target due to the narrow composition window. In this work, we report polymer WLMs self-assembled from a linear ABC triblock copolymer consisting of an intermediate fluorinated block of poly(2,2,3,4,4,4-hexafluorobutyl methacrylate) (F), a hydrophilic segment of poly(ethylene oxide) (O) and a CO2-responsive flank of poly(2-(diethylamino)ethyl methacrylate) (E). In the mixed solvent of water and ethanol, the polymer aggregates evolve from spheres to short rods, then long cylinders and finally WLMs when the volume ratio of water increases from 0 to 50%. Upon the stimulus of CO2, the E block is protonated, thus transforms from hydrophobic to hydrophilic. However, the WLMs just partially return back to spheres even the protonation degree of E block is up to 95%. The closely packed arrangement of fluorinated block caused by the increasing interfacial tension of the fluorinated blocks and solvent could account for the formation of WLMs and its shape alternation under CO2 stimulus.


Determination of the energy dependence of the BC-408 plastic scintillation detector in medium energy x-ray beams.
The energy dependence of the response of BC-408 plastic scintillator (PS), an approximately water-equivalent material, has been investigated by employing standardized x-ray beams. IEC RQA and ISO N series x-ray beam qualities, in the range of 40-100 kVp, were calibrated using a PTW-type ionization chamber. The energy response of a thick BC-408 PS detector was measured using the multichannel pulse height analysis method. The response of BC-408 PS increased gradually with increasing energy in the energy range of 40-80 kVp and then showed a flat behavior at about 80 to 120 kVp. This might be due to the self-attenuation of scintillation light by the scintillator itself and may also be partly due to the ionization quenching, leading to a reduction in the intensity of the light output from the scintillator. The results indicated that the sensitivity drop in BC-408 PS material at lower photon energies may be overcome by adding some high-Z elements to its polyvinyltoluene (PVT) base. The material modification may compensate for the drop in the response at lower photon energies. Thus plastic scintillation dosimetry is potentially suitable for applications in diagnostic radiology.


Carbon dioxide compensation values in citronella and lemongrass.
Carbon dioxide compensation values of mature leaves from 10 selections of citronella (Cymbopogon nardus [L.] Rendle) grown at 32/27 or 27/21 C day/night temperatures and three strains of lemongrass (Cymbopogon citratus [D.C.] Stapf. and Cymbopogon flexuosus [D.C.] Stapf.) grown at 8- or 15-hour photoperiods were measured in a controlled environment at 25 C. All leaves had low compensation values but citronella varied from 1.3 to 9.7 mul/liter and lemongrass from 0.7 to 3.5 mul/liter. Lower growing temperature generally resulted in lower compensation values for citronella but there was no consistent photoperiod effect on lemongrass.


Posterior nutcracker syndrome: a case report.
Posterior nutcracker syndrome is defined by the compression of the left renal vein between the abdominal aorta and a lumbar vertebral body. It can be clinically manifest with intermittent hematuria, gonadal or spermatic reflux resulting in varicocele. Ultrasound is the first-line imaging which require more accurate study with contrast-enhanced computed tomography. Management can be conservative in younger patients with mild hematuria due to the high spontaneous remission rate and invasive with open surgical and endovascular interventions. We describe a very rare case with compression of the left renal vein due to an osteophyte of the spine. A 62-year-old Caucasic male came to our radiology department for chronic hepatitis B virus (HBV)-related liver disease follow-up and mild scrotal pain. The ultrasound examination revealed a compression of the left retro-aortic renal vein in the aorto-vertebral space caused by an osteophyte. Duplex Doppler ultrasound revealed flow congestion in the left renal vein and renal failure; power Doppler ultrasound showed left varicocele. Doppler ultrasound is the first-line imaging and allows the detection of all the typical signs of posterior nutcracker: left renal vein stenosis, flow congestion and renal failure. Nutcracker syndrome should be suspected in older patients with left varicocele associated with hematuria. Failure to diagnose and treat these patients could have serious consequences for their health.


Large beta-delayed neutron emission probabilities in the 78Ni region.
The beta-delayed neutron branching ratios (P{betan}) for nuclei near doubly magic 78Ni have been directly measured using a new method combining high-resolution mass separation, reacceleration, and digital beta-gamma spectroscopy of 238U fission products. The P{betan} values for the very neutron-rich isotopes ;{76-78}Cu and 83Ga were found to be much higher than previously reported and predicted. Revised calculations of the betan process, accounting for new mass measurements and an inversion of the pi2p{3/2} and pi1f{5/2} orbitals, are in better agreement with these new experimental results.


Prevalence of hypertension among teenage students in Kano, Nigeria.
Hypertension has been reported among young people worldwide. It is known to track from youth to adulthood, which makes it a useful predictor of essential hypertension in adulthood. This study determined the prevalence of hypertension and associated cardiovascular risk factors among secondary school teenagers in Kano, Nigeria. A questionnaire was administered on a cross section of 1000 teenage students to inquire about cardiovascular risk factors. Participants' blood pressure, height and weight were measured. Relevant investigations were done for those with raised blood pressure. The participants' ages ranged from 13 to 19 years with a mean of 15.91.62 years. Seventy of the students had systolic blood pressure 140mmHg and/or diastolic blood pressure 90mmHg giving a prevalence rate of hypertension of 7.2% [95% CI = 5.6-8.9%]. Specifically, 32 (6.7%) of the 476 males were hypertensive compared to 38 (7.7%) of the 492 female participants. This difference was not statistically significant (2 =1.6 df = 1 p > 0.05). The prevalence rate of hypertension rose from 4.3% (among the younger participants) to 11.8% among the oldest students. Of the 70, a majority (88.5%) had grade 1 hypertension, 10.0% had Grade 2 hypertension and 1.5% had Grade 3 hypertension. The hypertensives were about twice more likely to have a family history of hypertension compared to their normotensive counterparts. This difference was statistically significant [OR = 2.1, 95% CI = 1.12-3.83] (2 = 6.4 df = 1 p = 0.01). Hypertension exists among teenage students in Kano, Nigeria. Early detection can reduce risk of cardiovascular changes and end organ damage.


Learning curve of percutaneous endoscopic transforaminal lumbar discectomy by a single surgeon.
To evaluate the learning curve of percutaneous endoscopic transforaminal lumbar discectomy (PETLD) from the novice stage to the proficient stage, we performed retrospective study for patients with lumbar disc herniation who underwent PETLD performed by a single surgeon and evaluated the surgeon's learning curve and the effect of surgical proficiency on outcomes.A total of 48 patients who underwent PETLD at the lower lumbar level (L3-S1) with a minimum 1-year follow-up were enrolled. The learning curve of the surgeon was assessed using cumulative study of operation time and linear regression analyses to reveal the correlation between operation time and case series number.Because the cutoff of familiarity was 25 cases according to the cumulative study of operation time, the patients were allocated into two groups: early group (n = 25) and late group (n = 23). The clinical, surgical, and radiological outcomes were retrospectively evaluated and compared between the two groups.According to linear regression analyses, the operation time was obtained using the following formula: operation time (minutes) = 69.925-(0.503 × [case number]) (P < .001).As expected, the operation time was significantly different between the two groups (mean 66.00 ± 11.37 min in the early group vs 50.43 ± 7.52 min in the late group, P < .001). No differences were found between the two groups in demographic data and baseline characteristics. Almost all clinical outcomes (including pain improvement and patient satisfaction), surgical outcomes (including failure, recurrence, and additional procedure rates), and radiological outcomes (including change of disc height and sagittal angles) did not differ between the two groups.However, the late group demonstrated a more favorable postoperative volume index of the remnant disc (362.91 mm3 [95% confidence interval, 272.81-453.02] in the early group vs 161.14 mm3 [95% confidence interval, 124.31-197.97] in the late group, P < .001), and a lower complication rate related to exiting nerve root (16.0% in the early group vs 0% in the late group, P = .045).The learning curve of PETLD is not as difficult as that of other minimally invasive spine surgery technique. Although the overall outcomes were not different between the groups, the risks of incomplete decompression and exiting root injury-related complication were higher in the novice stage.


Herbicide discovery in light of rapidly spreading resistance and ever-increasing regulatory hurdles.
According to the United Nations, the global population is expected to grow to almost 10 billion people in 2050. This means that the demand for food, feed and fiber will double while at the same time, agriculture is being challenged by a scarcity of water, global warming, less land available for farming, protection of natural habitats, a demand for biodiversity on farms and other factors. In addition, crop protection products are under pressure from rapidly spreading resistance and increasing regulatory requirements. Many regulatory bodies are also moving away from a risk assessment approach to a more hazard-based approach to grant registrations. Nevertheless, chemical crop protection compounds remain attractive and necessary to combat pests, particularly weeds. Industry has increased its efforts to find new molecules that are highly biologically effective on target species, including resistant populations, but safe for non-target organisms. To manage resistance in the future, a diverse toolbox is needed that includes herbicides with a variety of different chemistries and modes of action, combined with non-chemical measures in integrated systems. However, discovering a herbicide and getting it registered and to the market is an extremely complex endeavor full of risk, much of it incalculable. © 2017 Society of Chemical Industry.


Sensing metal ions with DNA building blocks: fluorescent pyridobenzimidazole nucleosides.
We describe novel fluorescent N-deoxyribosides (1 and 2) having 2-pyrido-2-benzimidazole and 2-quino-2-benzimidazole as aglycones. The compounds were prepared from the previously unknown heterocyclic precursors and Hoffer's chlorosugar, yielding alpha anomers as the chief products. X-ray crystal structures confirmed the geometry and showed that the pyridine and benzimidazole ring systems deviated from coplanarity in the solid state by 154 degrees and 140 degrees , respectively. In methanol compounds 1 and 2 had absorption maxima at 360 and 370 nm, respectively, and emission maxima at 494 and 539 nm. Experiments revealed varied fluorescence responses of the nucleosides to a panel of 17 monovalent, divalent, and trivalent metal ions in methanol. One or both of the nucleosides showed significant changes with 10 of the metal ions. The most pronounced spectral changes for ligand-nucleoside 1 included red shifts in fluorescence (Au(+), Au(3+)), strong quenching (Cu(2+), Ni(2+), Pt(2+)), and substantial enhancements in emission intensity coupled with red shifts (Ag(+), Cd(2+), Zn(2+)). The greatest spectral changes for ligand-nucleoside 2 included a red shift in fluorescence (Ag(+)), a blue shift (Cd(2+)), strong quenching (Pd(2+), Pt(2+)), and substantial enhancements in emission intensity coupled with a blue shift (Zn(2+)). The compounds could be readily incorporated into oligodeoxynucleotides, where an initial study revealed that they retained sensitivity to metal ions in aqueous solution and demonstrated possible cooperative sensing behavior with several ions. The two free nucleosides alone can act as differential sensors for multiple metal ions, and they are potentially useful monomers for contributing metal ion sensing capability to DNAs.


[Contraception by cyclic treatment with buserelin and progesterone].
Hormonal contraception with a combination of a GnRH-agonist (Buserelin) and progesterone was achieved in 47 high risk patients in 547 cycles. In these patients, oral contraceptives were contraindicated because of severe cardiovascular diseases, thromboembolic complications, benign liver tumours, advanced diabetes, terminal kidney insufficiency and severe migraine. Buserelin was administered intranasally in one daily dose of 300-400 micrograms from the 1st day to the 21st day, one dose of 100 mg of Progesterone was given intravaginally daily from the 12th day to the 21st day. Under these conditions, average E2 concentrations were found in the range of 50-60 pg/ml. The discontinuation of progesterone replacement resulted in withdrawal bleeding. Cycle control was acceptable. In 4 cases, this contraceptive regimen had to be discontinued because of side effects or paradox reactions. One patient conceived. In conclusion, GnRH-analogues in a moderate dose can be used to inhibit ovulation without inhibiting follicular maturation and adequate oestrogen production. This costly regimen of contraception requires strict indication and careful monitoring.


Oxidation of bilirubin by rat brain mitochondrial membranes-genetic variability.
Bilirubin is oxidized by brain mitochondrial membranes at a rate which may contribute significantly to clearance of bilirubin from brain. Different strains of congenitally jaundiced rats (Gunn rats) vary widely as far as the mortality rate of the homozygous (jaundiced) pups. Because the ability to oxidize bilirubin in brain may protect against toxicity, we hypothesized that the ability to oxidize bilirubin would be lower in Gunn rat strains (ACI/N-j) with a high mortality rate in the homozygous pups. Mitochondria were obtained from young rat brains by differential centrifugation in sucrose gradients. The mitochondria were ruptured by sonication. The change in optical density of a bilirubin solution at 440 nm was measured over time following addition of the membrane suspension. The rate of bilirubin oxidation was significantly lower in rats of the RHA/N-j strain both at 7-8 days of age and in adults, compared to rats of the ACI/N-j and the Sprague-Dawley strains at the same age points. Differences in mortality rates between the RHA/N-j and the ACI/N-j strains of Gunn rats could not be explained on the basis of differences in the ability of brain mitochondrial membranes to oxidize bilirubin, as these activities were lower in the RHA/N-j rats, which also have lower mortality rates, but higher in the ACI/N-j rats, which have remarkably high mortality rates. This study also confirmed previous findings relative to age maturation of the enzyme activity.


Surgical management of posterior epistaxis: a changing paradigm.
To demonstrate that surgery, as the initial treatment option for posterior epistaxis, can provide comparable success and complication rates to nonsurgical management with fewer associated costs. A retrospective chart review and cost analysis. Two hundred three consecutive charts were reviewed for patient outcome, complications, and hospitalization time. Average costs were calculated from hospital department and physician fee schedules. Average success rate of all surgical procedures performed for posterior epistaxis was 90%, anterior-posterior packing success was 62%, and embolization success was 75%. The packing-only group had a significantly greater mean hospitalization time (5.29 d) than patients who were treated either surgically (2.1 d) or with embolization (2.6 d). The average per-patient admission charges were, for successful posterior packing, $5136 per patient; for surgical treatment, $3851 per patient; and for embolization, $5697 per patient. Surgery offered a cost savings of $1846 per patient over traditional packing. There was no significant difference in complication rates between the groups. The review suggests that a better success rate, a comparable complication rate, and a cost savings can be achieved with surgical intervention as the first-line treatment for intractable epistaxis when compared with traditional anterior-posterior packing and embolization.


Beneath the rhetoric: the role of rights in the practice of non-anonymous gamete donation.
The use of rights based arguments to justify claims that donor offspring should have access to information identifying their gamete donor has become increasingly widespread. In this paper, I do not intend to revisit the debate about the validity of such rights. Rather, the purpose is to examine the way such alleged rights have been implemented by those legislatures that have allowed access to identifying information. I will argue that serious inconsistencies exist between the claim that donor offspring have a right to know the identity of their gamete donor and the way such a right is currently met in practice. I hope to show that in systems where non-anonymous donation is practised, an understanding of the proclaimed right of donor offspring to know their genetic identity is one composed of two different rights--the right to know the circumstances of their conception and the right to information identifying the gamete donor--can provide important insights into this important area of public policy.


Validation of the Scale of Preferences and Expectations in Close Interpersonal Relationships (EPERIC).
The most commonly used instruments for assessing adult attachment have shown differing combinations of items and divergences in the resulting sub-scales. This study presents the Scale of Preferences and Expectations in Close Interpersonal Relationships ( Escala de Preferencias y Expectativas en las Relaciones Interpersonales Cercanas, EPERIC), made up of 22 items, and based upon the Relationship Scales Questionnaire (RSQ) of Griffin and Bartholomew. Exploratory and confirmatory factorial analyses (EFA and CFA) were undertaken using data from a sample of 594 people. Factor analysis distinguishes three sub-scales: Fear of rejection or abandonment , Desire for closeness and Preference for independence , which explains 42.78% of the total variance. The alpha coefficients reveal a high internal consistency of the instrument and its sub-scales. Regarding validity, CFA showed an adequate fit for the trifactorial solution, and the expected correlations with other instruments for assessing attachment style in adults were found. EPERIC is also suitable for predicting affective states and psychological well-being. The EPERIC is a potentially useful and valid instrument for research and clinical purposes. The discussion focuses on the fact that our results support a model of three factors rather than two, as is usual in studies on adult attachment.


Metastatic testicular germ cell tumor presenting with abdominal pain: CT and MRI findings.
Testicular tumors are the most common solid tumors in young adult males. Patients with testicular tumor often present with painless scrotal mass. Rarely, symptoms are related to metastases. We describe the case of a patient presenting with abdominal pain due to retroperitoneal lymphadenopathy. We describe the magnetic resonance imaging findings of lumbar spine osseous metastasis.


Prior exposure to methylenedioxyamphetamine (MDA) induces serotonergic loss and changes in spontaneous exploratory and amphetamine-induced behaviors in rats.
The substituted amphetamine 3,4 methylenedioxyamphetamine (MDA) is a popular recreational drug of abuse. Administration of MDA to experimental animals has been shown to induce damage to serotonergic axons and nerve terminals. However, there is a lack of information on whether these treatments can produce any long-term changes in behavioural performance particularly under stressful conditions. In the present study, MDA (7.5 mg/kg; i.p.) was administered twice daily to adult male Sprague Dawley rats for four days. Four weeks following the last dose, spontaneous behaviors of these animals were tracked and scored in a novel "open field" environment using an automated video registration and computer interpretation system. Changes in behavior were observed in MDA treated animals including reductions in exploratory oriented behaviors (locomotion and rearing) and increases in grooming behavior when compared to vehicle treated controls. MDA-treated animals also displayed an enhanced locomotor and stereotyped response to d-amphetamine (12 mg/kg; i.p.). Significant reductions in 5-HT concentrations (20-30%) were observed in the frontal cortex, amygdala, striatum, and hypothalamus as a result of MDA treatment. In addition, [3H] paroxetine binding was reduced by (40%) in the cortex of MDA treated rats indicating that the decrease in 5-HT concentrations were accompanied by a reduction in intact presynaptic 5-HT nerve terminals. Changes in behavioural performance in a novel "open field" environment and following d-amphetamine challenge might be considered as a behavioural model of serotonergic deficit induced by MDA. The findings of this study also suggest that MDA use may increase both the abuse potential, and the propensity to develop psychosis as a result of abusing other psychostimulants such as d-amphetamine.


Endogenous interferon-gamma impairs bacterial clearance from lungs during Pseudomonas aeruginosa pneumonia.
Interferon (IFN-)gamma is thought to play a role in the resistance to various pathogens. To study the role of IFN-gamma in the pathogenesis of Pseudomonas pneumonia, IFN-gamma receptor (R) alpha-subunit-deficient [IFN-gammaR(-/-)] mice and wild type mice were intranasally inoculated with Pseudomonas aeruginosa (10(5) CFU). IFN-gammaR(-/-) mice demonstrated an enhanced clearance of P. aeruginosa from their lungs when compared to normal wild type mice (P < 0.05 at 24 hours after the infection), which was associated with a tendency towards an improved survival. These findings were not accompanied by a more effective activation of several components of the innate immune system known to contribute to host defense against pneumonia, i.e. the lung concentrations of cytokines and chemokines were similar in IFN-gammaR(-/-) and wild type mice, while the influx of neutrophils in bronchoalveolar lavage fluid (BALF) was even higher in wild type mice than in IFN-gammaR(-/-) mice. Remarkably, IFN-gammaR(-/-) mice had higher nitric oxide levels in the BALF at 24 hours after infection (P < 0.05). Endogenous IFN-gamma impairs rather than augments host defense during pneumonia caused by P. aeruginosa.


Impact of bone scintigraphy on the clinical management of a patient with sickle cell anemia and recent chest pain.
The authors present a cases of acute chest syndrome that was originally thought to be due to pneumonia, in which bone imaging obtained 4 weeks later for knee pain showed a secondary finding of multiple rib infarcts that clarified the etiology of the patient's chest manifestations and led to a change in the management of the patient. Bone scintigraphy should be considered in the work-up of patients with sickle cell anemia and concurrent chest symptoms.


Regions in the G protein gamma subunit important for interaction with receptors and effectors.
G betagamma dimers containing the gamma11 or gamma1 subunits are often less potent and effective in their ability to regulate effectors compared with dimers containing the gamma2 subunit. To explore the regions of the gamma subunit that affect the activity of the betagamma dimer, we constructed eight chimeric gamma subunits from the gamma1 and gamma2 subunits. Two chimeras were made in which the N-terminal regions of gamma1 and gamma2 were exchanged and two in which the C-terminal regions were transposed. Another set of chimeras was made in which the CAAX motifs of the chimeras were altered to direct modification with different prenyl groups. All eight gamma chimeras were expressed in Sf9 cells with the beta1 subunit, G betagamma dimers were purified, and then they were assayed in vitro for their ability to bind to the G alpha(i1) subunit, to couple G alpha(i1) to the A1 adenosine receptor, to stimulate phospholipase C-beta, and to regulate type I or type II adenyl cyclases. Dimers containing the C-terminal sequence of the gamma2 subunit modified with the geranylgeranyl lipid had the highest affinity for G(i1)alpha (range, 0.5-1.2 nM) and were most effective at coupling the G(i1)alpha subunit to receptor. These dimers were most effective at stimulating the phosphatidylinositol-specific phospholipase C-beta isoform and inhibiting type I adenyl cyclase. In contrast, betagamma dimers containing the N-terminal sequence of the gamma2 subunit and a geranylgeranyl group are most effective at activating type II adenyl cyclase. The results indicate that both the N- and C-terminal regions of the gamma subunit impart specificity to receptor and effector interactions.


Vitamin A degradation and light-oxidized flavor defects in milk.
To determine the effects of light exposure on vitamin A degradation and on light-oxidized flavor development, samples of whole, reduced fat, and nonfat milk were exposed to fluorescent light (either 1000 or 2000 lx) at time intervals of 2, 4, 8, or 16 h. Measurable vitamin A losses occurred at 2, 4, and 16 h at 2000 lx for nonfat, reduced fat and whole milk, respectively. Moderate light-oxidized flavors were detected after 4 h of light exposure (2000 lx) in the whole and reduced fat milk and after 8 h in nonfat milk. The different types of milk show a significant difference in relative flavor scores. By 16 h at 2000 lx, relative light-oxidized flavor development was lower in nonfat milk than in whole or reduced fat milk. The presence of milk fat appears to protect against vitamin A degradation in fluid products, but adversely affects the flavor quality of milk after exposure to light. In summary, these findings demonstrate that even a brief, moderate light exposure (2 h; 2000 lx) can reduce the nutritional value and flavor quality of fluid milk products.


Sex and the single cell: meiosis in yeast.
Recent studies of Saccharomyces cerevisiae have significantly advanced our understanding of the molecular mechanisms of meiotic chromosome behavior. Structural components of the synaptonemal complex have been identified and studies of mutants defective in synapsis have provided insight into the role of the synaptonemal complex in homolog pairing, genetic recombination, crossover interference, and meiotic chromosome segregation. There is compelling evidence that most or all meiotic recombination events initiate with double-strand breaks. Several intermediates in the double-strand break repair pathway have been characterized and mutants blocked at different steps in the pathway have been identified. With the application of genetic, molecular, cytological, and biochemical methods in a single organism, we can expect an increasingly comprehensive and unified view of the meiotic process.


Potential of Insect Meals as Protein Sources for Meat-Type Ducks Based on In Vitro Digestibility.
There has been a dramatic increase in duck meat consumption. As a result, ducks are an interesting alternative type of livestock. Animal-based proteins such as fishmeal and animal by-products are valuable nutrients with high digestibility, but they are associated with cost fluctuations, pathogen contamination, and environmental impacts. Therefore, plant-based proteins are used, but they have the disadvantages of inappropriate amino acid profiles, anti-nutritional factors, and mycotoxin contamination. Insect meal contains favorable nutrients and low production costs and is environmentally friendly; however, there is a large number of insect species. Therefore, the purpose of this investigation is to screen insects for their potential use as a protein source in the duck diet. Insect meal with a high proportion of low-digestible components was shown to have low digestibility. Yellow mealworm larvae, giant mealworm larvae, lesser wax moth larvae, house fly larvae, mulberry silkworm pupae, and American cockroach nymph have the potential to be alternative protein sources for ducks. Insect meal has been widely studied and is used in animal nutrition to replace common protein sources that have several disadvantages and to promote sustainability in animal production. Two-step in vitro digestibility using crude enzyme extracts from digestive tracts of meat-type ducks (Cherry Valley) was performed on general protein sources and insect meals to compare the in vitro digestibility of organic matter (OMd) and crude protein (CPd). Variation in chemical components between different types of insect meal was found. A positive correlation was found between OMd and the ether extract composition in insect meal, whereas a negative correlation was shown between crude fiber and acid detergent fiber. Contrasting relationships were found between CPd and crude fiber and acid detergent fiber in insect meal. In conclusion, the yellow mealworm larvae (Tenebrio molitor), giant mealworm larvae (Zophobas morio), lesser wax moth larvae (Achroia grisella), house fly larvae (Musca domestica), mulberry silkworm pupae (Bombyx mori), and American cockroach nymph (Periplaneta americana) are potential protein sources for ducks based on OMd and CPd digestibility after screening with an in vitro digestibility technique.


Deletion of the carboxyl-terminal exons of K-sam/FGFR2 by short homology-mediated recombination, generating preferential expression of specific messenger RNAs.
The K-sam gene was first identified as an amplified gene from human gastric cancer cell line KATOIII, and its product is identical to fibroblast growth factor receptor 2. The K-sam gene is located on human chromosome 10q26 and is preferentially amplified in the poorly differentiated types, especially in the scirrhous type, of gastric cancers. During the course of studies on the structural characterization of the amplification units, we found that the carboxyl-terminal exons of K-sam were deleted in three of four of the scirrhous type of gastric cancer cell lines. These deletions generate preferential expression of mRNAs encoding K-sam proteins lacking the carboxyl-terminal region containing the tyrosine residues at positions 780, 784, and 813. The carboxyl-terminal region has been reported to have a sequence required for the inhibition of NIH3T3 transformation, indicating that cells with amplification of the truncated K-sam gene have a growth advantage during the carcinogenic process for the scirrhous type of gastric cancers. This is the first report showing the deletion of the carboxyl-terminal exons of the receptor-type of the protein tyrosine kinase gene. Sequence analysis of the DNA sequences surrounding the deletion junctions shows the presence of unique sequences and indicates the involvement of short homology-mediated recombination in the generation of these deletions.


A survey on the experience with dental tourism in a sample of Italian patients.
Dentistry in Italy is mainly private and therefore perceived as forcedly expensive. Dental tourism is becoming popular in order to get cheap dental care. The aim of this study was to carry out a survey aimed at investigating the perception of dental tourism by Italian patients who have recently received such dental care abroad. A questionnaire was posted on the web site of an Italian consumers association (Altroconsumo) and members were invited to fill in the questionnaire in case they had experienced dental treatment abroad. Eighty-one complete forms were included in the study. The main motivation for turning to dental tourism was saving money. Another frequent reason for choosing dental tourism was that full rehabilitation was offered in a short time span, usually one week. Patients have often underlined that they appreciated different aspects of the foreign dentists, like speed, kindness, humanity, interest in the course of the treatment, the feeling of ease conveyed by the environment and the personnel. Past negative experiences with Italian dentists were in some cases advocated as reasons for searching dental care abroad. Such negative experiences resulted in a lack of trust in Italian dentists. Some patients reported that while the overall treatment abroad was carried out in a short time, single prosthetic sessions were very long, up to 6 hours. Most patients were satisfied with dental tourism.


Widely divergent biochemical properties of the complete set of mouse DC-SIGN-related proteins.
The mouse genome sequence has been examined to identify the complete set of proteins related to the human glycanbinding receptor, DC-SIGN. In addition to five SIGNR proteins previously described, a pseudogene, encoding a hypothetical SIGNR6, and a further two expressed proteins, SIGNR7 and SIGNR8, have been identified. The ligand-binding properties of these novel proteins and of the previously described mouse SIGNs have been systematically investigated in order to define the mouse proteins that most resemble human DC-SIGN and DC-SIGNR. Results from screening of a glycan array demonstrate that only mouse SIGNR3 shares with human DC-SIGN the ability to bind both high mannose and fucose-terminated glycans in this format and to mediate endocytosis. The finding that neither SIGNR1 nor SIGNR5 binds with high affinity to specific ligands in a large panel of mammalian glycans is consistent with the suggestion that these receptors bind surface polysaccharides on bacterial and fungal pathogens in a manner analogous to serum mannose-binding protein. The data also reveal that two of the mouse SIGNs have unusual binding specificities that have not been previously described for members of the C-type lectin family; the newly identified SIGNR7 binds preferentially to the 6-sulfo-sialyl Lewis(x) oligosaccharide, whereas SIGNR2 binds almost exclusively to glycans that bear terminal GlcNAc residues. The results presented demonstrate that the mouse homologs of DC-SIGN have a diverse set of ligand-binding and intracellular trafficking properties, some of which are distinct from the properties of any of the human receptors.


Sleepiness after glucose in narcolepsy.
The issue of whether a high carbohydrate intake affects sleepiness and sleep variables has been studied in normals but not in patients suffering from narcolepsy, despite anecdotal evidence that sugars may facilitate sleepiness in this population. This study investigated whether the intake of 50 g glucose exacerbated sleepiness in narcolepsy subjects. A double-blind cross-over study, involving 12 narcolepsy subjects and 12 matched controls, measured behaviour after a light lunch supplemented with a drink of either 50 g glucose or placebo (artificially sweetened drink). The main dependent variables were the performance and EEG measures from the Wilkinson Auditory Vigilance Task (WAVT) and sleep variables from a 45 minute nap. The results indicate that in the narcolepsy subjects glucose was associated with decreased wake duration, reduced sleep onset latency and more spontaneous and induced sleep stage changes during the WAVT, while the nap revealed an increased intensity of sleepiness after glucose as measured by the Polygraphic Score of Sleepiness. Eleven of the twelve narcolepsy subjects showed increased REM duration in the nap after glucose. The findings are discussed in relation to serotonin synthesis, basal sleepiness and possible irregularities in the action of insulin.


Cross-frontier information provision in the ALIAS European project.
The ALIAS project addresses medical services and information inadequacy to ensure healthcare provisions in Alpine space where telemedicine services are not widely exploited and linguistic barriers represent an obstacle. Alpine space touristic vocation makes its healthcare structures periodically inadequate to face a widened request of services supply. On the other hand, a major receptivity of those structures during the rest of the year is unnecessary due to the low density of local residents. ALIAS is aimed at linking together a number of hospitals enabling the creation of a network shaping the ALIAS Virtual Hospital Network for sharing medical information and adopting telemedicine services to improve the efficiency of hospitals in Alpine Space areas. This article focuses on the clinical information provision service provided in ALIAS and on the translation service that has been associated to it.


Retinitis pigmentosa, growth hormone deficiency, and acromelic skeletal dysplasia in two brothers: possible familial RHYNS syndrome.
Here we report two brothers with retinitis pigmentosa, growth hormone deficiency, and acromelic skeletal dysplasia. We propose that their clinical picture is consistent with RHYNS syndrome (retinitis pigmentosa, hypopituitarism, nephronophthisis, and skeletal dysplasia) and that they represent the first instance of a familial occurrence of this syndrome. The presence of RHYNS in two siblings supports an autosomal recessive mode of inheritance; however, since all four known cases were male, an X-linked mode of inheritance cannot be excluded. The combination of clinical features found in these affected males is unique and supports the existence of RHYNS syndrome as a separate and distinct entity.


Renal tumor with overlapping distal nephron morphology and karyotype.
Although most renal epithelial tumors are derived from the proximal nephron, approximately 10% are believed to originate in the distal nephron. This latter group encompasses oncocytoma, chromophobe renal cell carcinoma, and several rare types, including collecting duct carcinoma and renal medullary carcinoma. Despite progress in the classification of renal tumors, a small subset of renal carcinomas remains unclassified (ie, renal cell carcinoma, not otherwise specified). We describe a metastatic tumor consisting of cells with overlapping distal nephron morphologies, including foci of oncocytoma, chromophobe renal cell carcinoma, and collecting duct carcinoma, as well as sarcomatoid dedifferentiation. Special stains were inconclusive, and ultrastructural study demonstrated abundant mitochondria and no microvesicles. The karyotype was hypodiploid with 41 chromosomes and abnormalities reported in all 3 phenotypes present. Rearrangements of 1p and of 11q13 previously seen in divergent subsets of oncocytomas were concomitantly present in the current tumor. Thus, this malignancy has features consistent with distal nephron derivation and demonstrates the convergence of the varied tumor morphologies arising within this site. Furthermore, this case exemplifies the value of cytogenetic analysis in the characterization of renal cell carcinoma, not otherwise specified. In view of recent advances in treatment approach, especially for collecting duct carcinoma, further categorization of this nondescript and heterogeneous group of renal cell carcinomas, not otherwise specified, at least by its derivation in relationship to the renal nephron (distal vs proximal), may be of value in the choice of treatment modality.


Improvement of hyperglycemia and hyperlipemia in streptozotocin-diabetic rats by a methanolic extract of Prunus davidiana stems and its main component, prunin.
Blood glucose and total lipid levels in rats with streptozotocin-induced diabetes were determined after intraperitoneal administration of a methanolic extract of Prunus davidiana Fr. stems and its main component, prunin (= naringenin 7-O-beta-D-glucoside). From the data obtained it was concluded that intraperitoneal administration of the methanolic extract and prunin produced a significant hypoglycemic effect. Total blood lipids were also decreased by these substances. Thus, it is suggested that this methanolic extract contains one or more hypoglycemic principles including the main flavanone glycoside, prunin, which can significantly reduce the levels of blood glucose and total lipids in streptozotocin-diabetic rats.


Impaired kidney structure and function in spinal muscular atrophy.
To determine changes in serum profiles and kidney tissues from patients with spinal muscular atrophy (SMA) type 1 compared with age- and sex-matched controls. In this cohort study, we investigated renal structure and function in infants and children with SMA type 1 in comparison with age- and sex-matched controls. Patients with SMA had alterations in serum creatinine, cystatin C, sodium, glucose, and calcium concentrations, granular casts and crystals in urine, and nephrocalcinosis and fibrosis. Nephrotoxicity and polycystic kidney disease PCR arrays revealed multiple differentially expressed genes, and immunoblot analysis showed decreased calcium-sensing receptors and calbindin and increased insulin-like growth factor-binding proteins in kidneys from patients with SMA. These findings demonstrate that patients with SMA type 1, in the absence of disease-modifying therapies, frequently manifest impaired renal function as a primary or secondary consequence of their disease. This study provides new insights into systemic contributions to SMA disease pathogenesis and the need to identify coadjuvant therapies.


Epidermal growth factor in mammary glands and milk from rats: the influence of insulin.
Epidermal growth factor (EGF) is one of the major growth-promoting agents in milk. Using immunohistochemistry we localized EGF in the mammary glands of lactating rats to the luminal border of the secretory cells. Following proteolytic pretreatment of the histological sections, the EGF-immunoreactivity was revealed homogeneously in the cytoplasm of the secretory cells, which might suggest that EGF is present as a precursor molecule in the mammary glands. Altered glucose metabolism during lactation results in secondary hypoinsulinaemia in the lactating rat. As insulin is also known to affect lactation in several species, we treated normal lactating rats daily with insulin and studied the effect on the composition of milk. A significant increase in the content of total protein and milk fat was observed after a few days of insulin-treatment, as compared to a control group [total protein: 50 (36-97) g/l vs. 42 (35-72) g/l], [milk fat: 35 (22-40)% vs. 29 (23-36)%], [median (range)]. On day 16 the EGF concentration in milk was significantly increased in insulin-treated rats, as compared to controls [2.66 (1.40-5.08) nM vs. 1.98 (1.04-3.16) nM]. A similar significant increase was found for the secretion of the cobalamin-binding protein, haptocorrin (HC) [37.7 (15.8-110.4) nM vs. 23.5 (15.5-70.1) nM]. In conclusion, the highly insulin-sensitive lactating mammary glands were affected by exogenous insulin, since the milk concentrations of EGF, HC, total protein and the fat percentage were increased.


Lysine 2,3-aminomutase from Clostridium subterminale SB4: mass spectral characterization of cyanogen bromide-treated peptides and cloning, sequencing, and expression of the gene kamA in Escherichia coli.
Lysine 2,3-aminomutase (KAM, EC 188.8.131.52.) catalyzes the interconversion of L-lysine and L-beta-lysine, the first step in lysine degradation in Clostridium subterminale SB4. KAM requires S-adenosylmethionine (SAM), which mediates hydrogen transfer in a mechanism analogous to adenosylcobalamin-dependent reactions. KAM also contains an iron-sulfur cluster and requires pyridoxal 5'-phosphate (PLP) for activity. In the present work, we report the cloning and nucleotide sequencing of the gene kamA for C. subterminale SB4 KAM and conditions for its expression in Escherichia coli. The cyanogen bromide peptides were isolated and characterized by mass spectral analysis and, for selected peptides, amino acid and N-terminal amino acid sequence analysis. PCR was performed with degenerate oligonucleotide primers and C. subterminale SB4 chromosomal DNA to produce a portion of kamA containing 1,029 base pairs of the gene. The complete gene was obtained from a genomic library of C. subterminale SB4 chromosomal DNA by use of DNA probe analysis based on the 1,029-base pair fragment. The full-length gene consisted of 1,251 base pairs specifying a protein of 47,030 Da, in reasonable agreement with 47, 173 Da obtained by electrospray mass spectrometry of the purified enzyme. N- and C-terminal amino acid analysis of KAM and its cyanogen bromide peptides firmly correlated its amino acid sequence with the nucleotide sequence of kamA. A survey of bacterial genome databases identified seven homologs with 31 to 72% sequence identity to KAM, none of which were known enzymes. An E. coli expression system consisting of pET 23a(+) plus kamA yielded unsatisfactory expression and bacterial growth. Codon usage in kamA includes the use of AGA for all 29 arginine residues. AGA is rarely used in E. coli, and arginine clusters at positions 4 and 5, 25 and 27, and 134, 135, and 136 apparently compound the barrier to expression. Coexpression of E. coli argU dramatically enhanced both cell growth and expression of KAM. Purified recombinant KAM is equivalent to that purified from C. subterminale SB4.


Activation of colonic mucosal 5-HT(4) receptors accelerates propulsive motility and inhibits visceral hypersensitivity.
5-hydroxytryptamine receptor (5-HT(4)R) agonists promote gastrointestinal motility and attenuate visceral pain, but concerns about adverse reactions have restricted their availability. We tested the hypotheses that 5-HT(4) receptors are expressed in the colonic epithelium and that 5-HT(4)R agonists can act intraluminally to increase motility and reduce visceral hypersensitivity. Mucosal expression of the 5-HT(4)R was evaluated by reverse-transcriptase polymerase chain reaction and immunohistochemical analysis of tissues from 5-HT(4)R(BAC)-enhanced green fluorescent protein mice. Amperometry, histology, and short-circuit current measurements were used to study 5-HT, mucus, and Cl(-) secretion, respectively. Propulsive motility was measured in guinea pig distal colon, and visceromotor responses were recorded in a rat model of colonic hypersensitivity. 5-HT(4)R compounds included cisapride, tegaserod, naronapride, SB204070, and GR113808. Mucosal 5-HT(4) receptors were present in the small and large intestines. In the distal colon, 5-HT(4) receptors were expressed by most epithelial cells, including enterochromaffin and goblet cells. Stimulation of 5-HT(4)Rs evoked mucosal 5-HT release, goblet cell degranulation, and Cl(-) secretion. Luminal administration of 5-HT(4)R agonists accelerated propulsive motility; a 5-HT(4)R antagonist blocked this effect. Bath application of 5-HT(4)R agonists did not affect motility. Oral or intracolonic administration of 5-HT(4)R agonists attenuated visceral hypersensitivity. Intracolonic administration was more potent than oral administration, and was inhibited by a 5-HT(4)R antagonist. Mucosal 5-HT(4) receptor activation can mediate the prokinetic and antinociceptive actions of 5-HT(4)R agonists. Colon-targeted, intraluminal delivery of 5-HT(4)R agonists might be used to promote motility and alleviate visceral pain, while restricting systemic bioavailability and resulting adverse side effects.


Diagnostic accuracy of computed tomography urography and visual assessment during ureterorenoscopy in upper tract urothelial carcinoma.
To investigate diagnostic accuracy of multiphase computed tomography urography (MCTU) and visual assessment at ureterorenoscopy (URS) for detection of upper tract urothelial carcinoma (UTUC). Consecutive patients referred to our tertiary care centre were included in a prospective study covering the period 2005 to 2012. The patients underwent initial imaging and URS with focal samples taken. Cytopathological results served as reference standard. We investigated 174 renal units (RUs; renal pelvis and adjacent ureter) in 148 patients. UTUC was found in 104 RUs. MCTU had an accuracy of 0.74, sensitivity of 0.89, specificity of 0.51, positive predictive value of 0.73, and negative predictive value of 0.75; corresponding values for URS were 0.84, 0.84, 0.85, 0.89, and 0.78, respectively. MCTU had significantly higher sensitivity and accuracy compared with other imaging techniques (P<0.05). Compared with MCTU, URS had similar sensitivity but significantly greater specificity and accuracy. Both MCTU and URS are important tools in the diagnostic evaluation of UTUC although neither of those techniques achieves 100% accuracy. MCTU should be chosen as the radiographical method if there are no contraindications and URS should always be combined with focal cytology and biopsies of suspicious lesions. To enhance diagnostic precision both MCTU and URS with focal samples should be included in the diagnostic procedure. The present results add impact to current diagnostic guidelines.


Emerging Roles of Microfluidics in Brain Research: From Cerebral Fluids Manipulation to Brain-on-a-Chip and Neuroelectronic Devices Engineering.
Remarkable progress made in the past few decades in brain research enables the manipulation of neuronal activity in single neurons and neural circuits and thus allows the decipherment of relations between nervous systems and behavior. The discovery of glymphatic and lymphatic systems in the brain and the recently unveiled tight relations between the gastrointestinal (GI) tract and the central nervous system (CNS) further revolutionize our understanding of brain structures and functions. Fundamental questions about how neurons conduct two-way communications with the gut to establish the gut-brain axis (GBA) and interact with essential brain components such as glial cells and blood vessels to regulate cerebral blood flow (CBF) and cerebrospinal fluid (CSF) in health and disease, however, remain. Microfluidics with unparalleled advantages in the control of fluids at microscale has emerged recently as an effective approach to address these critical questions in brain research. The dynamics of cerebral fluids (i.e., blood and CSF) and novel in vitro brain-on-a-chip models and microfluidic-integrated multifunctional neuroelectronic devices, for example, have been investigated. This review starts with a critical discussion of the current understanding of several key topics in brain research such as neurovascular coupling (NVC), glymphatic pathway, and GBA and then interrogates a wide range of microfluidic-based approaches that have been developed or can be improved to advance our fundamental understanding of brain functions. Last, emerging technologies for structuring microfluidic devices and their implications and future directions in brain research are discussed.


[The importance of hyperdynamic circulation in the progression of liver cirrhosis and its therapeutic strategies].
Portal hypertension is one of the main performance of liver cirrhosis, in addition to anatomical factors, hyperdynamic circulatory status caused by abnormal splanchnic vascular tension is also very important in this procession. We summarised the mechanism and treatment strategies of hyperdynamic circulation in cirrhosis, so as to provide some recommendation for clinical practice.


Discounting in Pigeons When the Choice is between Two Delayed Rewards: Implications for Species Comparisons.
Studies of delay discounting typically have involved choices between smaller, immediate outcomes and larger, delayed outcomes. In a study of delay discounting in humans, Green et al. (2005) added a period of time prior to both outcomes, creating a delay common to both. They found that the subjective value of the more delayed reward was well described by a hyperboloid discounting function and that the degree to which that outcome was discounted decreased as the common delay increased. In two experiments, we examined the effect of adding a common delay on the discounting of food rewards in pigeons. In Experiment 1, an adjusting-amount procedure was used to establish discounting functions when the common delay was 0, 3, 5, and 10 s, and different stimuli signaled time to the smaller, sooner and larger, later rewards. In contrast to humans, the pigeons showed increases in the degree of discounting when a common delay was added. In Experiment 2, the delay common to both rewards and the delay unique to the larger, later reward were each specifically signaled. With this procedure, the degree of discounting decreased as the common delay increased, a result consistent with that obtained with humans (Green et al., 2005). These findings reveal fundamental similarities between pigeons' and humans' choice behavior, and provide strong interspecies support for the hypothesis that choice between delayed outcomes is based on comparison of their hyperbolically discounted present subjective values.


Anti-inflammatory activity of the oriental herb medicine, Arisaema cum Bile, in LPS-induced PMA-differentiated THP-1 cells.
Arisaema cum Bile is widely used as a folk medicine in Korea. However, the systematic biological properties of Arisaema cum Bile have seldom been addressed. In this study, we evaluated the anti-inflammatory activity of Arisaema cum Bile extract on lipopolysaccharide (LPS)-induced inflammation in phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophages. The Arisaema cum Bile extract markedly inhibited the production of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, and also suppressed the mRNA and protein expressions of these cytokines. Furthermore, the Arisaema cum Bile extract also inhibited LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein and gene expressions in PMA-differentiaed THP-1 macrophages. These results suggest that Arisaema cum Bile extract may have potential for development into an effective anti-inflammatory agent, and/or as an ingredient of functional foods.


Interactions of the Mcm1 MADS box protein with cofactors that regulate mating in yeast.
The yeast Mcm1 protein is a member of the MADS box family of transcriptional regulatory factors, a class of DNA-binding proteins that control numerous cellular and developmental processes in yeast, Drosophila melanogaster, plants, and mammals. Although these proteins bind DNA on their own, they often combine with different cofactors to bind with increased affinity and specificity to their target sites. To understand how this class of proteins functions, we have made a series of alanine substitutions in the MADS box domain of Mcm1 and examined the effects of these mutations in combination with its cofactors that regulate mating in yeast. Our results indicate which residues of Mcm1 are essential for viability and transcriptional regulation with its cofactors in vivo. Most of the mutations in Mcm1 that are lethal affect DNA-binding affinity. Interestingly, the lethality of many of these mutations can be suppressed if the MCM1 gene is expressed from a high-copy-number plasmid. Although many of the alanine substitutions affect the ability of Mcm1 to activate transcription alone or in combination with the alpha 1 and Ste12 cofactors, most mutations have little or no effect on Mcm1-mediated repression in combination with the alpha 2 cofactor. Even nonconservative amino acid substitutions of residues in Mcm1 that directly contact alpha 2 do not significantly affect repression. These results suggest that within the same region of the Mcm1 MADS box domain, there are different requirements for interaction with alpha 2 than for interaction with either alpha1 or Ste12. Our results suggest how a small domain, the MADS box, interacts with multiple cofactors to achieve specificity in transcriptional regulation and how subtle differences in the sequences of different MADS box proteins can influence the interactions with specific cofactors while not affecting the interactions with common cofactors.


CMV-infected subependymoma in the fourth ventricle of an HIV-1 infected patient.
A case of an AIDS patient with a CMV-infected subependymoma of the fourth ventricle is presented. The tumor was incidentally found at autopsy and was not suspected during the clinical course. This is the first report of a subependymoma in HIV-1 infection. Moreover, infection of a tumor with CMV is an extremely rare condition, which has until now been described only once in an anaplastic astrocytoma.


Unstable pelvic fractures associated with femoral shaft fractures: a retrospective analysis.
Both pelvic fractures and femoral shaft fractures are caused by high-energy injuries. When unstable pelvic fractures and femoral shaft fractures occur concomitantly, the optimal treatment method is controversial. The aim of this study was to establish a reasonable principle for treating such complicated injuries. Forty patients sustaining unstable pelvic fractures and concomitant femoral shaft fractures were treated in a 7-year period. The initial management of the fractures was started at the emergency service according to the Advanced Trauma Life Support protocol. Unstable pelvic fractures were wrapped by cloth sheets and femoral shaft fractures were immobilized with a splint. Angiography was performed on patients with unstable hemodynamic status. The definitive treatment for combined fractures was performed after stabilizing the hemodynamics. Closed nailing was used for femoral shaft fractures, and pelvic fractures were treated with various techniques. The mortality rate was 12.5% (5/40) during admission. Thirty-three patients were followed up for an average of 32 months (range, 12-76 months). There were 33 cases of unstable pelvic fractures and 36 instances of femoral shaft fractures. The union rate for pelvic fractures was 100% (33/33), while femoral shaft fractures had a 94.4% (34/36) union rate. The average healing time was 3.3 months (range, 1.6-8.1 months) and 4.1 months (range, 2.5-18.2 months) for pelvic and femoral shaft fractures, respectively. After fracture, 34 hips (94%) achieved a satisfactory result in the Harris hip score and 30 knees (83%) achieved a satisfactory result in the Mize knee score. Stabilization of the hemodynamics in patients with combined fractures should be the first aim. Angiography to stop arterial bleeding in the pelvis is often life-saving. The definitive treatment for combined fractures, such as pelvic fractures and femoral shaft fractures, should wait until hemodynamics is stabilized.


The double-layer of penetrable ions: an alternative route to charge reversal.
We investigate a double-layer of penetrable ions near a charged wall. We find a new mechanism for charge reversal that occurs in the weak-coupling regime and, accordingly, the system is suitable for the mean-field analysis. The penetrability is achieved by smearing-out the ionic charge inside a sphere, so there is no need to introduce non-electrostatic forces and the system in the low coupling limit can be described by a modified version of the Poisson-Boltzmann equation. The predictions of the theory are compared with the Monte Carlo simulations.


A Strategy for Prompt Phase Transfer of Upconverting Nanoparticles Through Surface Oleate-Mediated Supramolecular Assembly of Amino-β-Cyclodextrin.
Lanthanide-doped upconverting nanoparticles (UCNPs) are promising for applications as wide as biosensing, bioimaging, controlled drug release, and cancer therapy. These applications require surface engineering of as-prepared nanocrystals, commonly coated with hydrophobic ligand of oleic acid, to enable an aqueous dispersion. However, literature-reported approaches often require a long time and/or multiple step treatment, along with several fold upconversion luminescence (UCL) intensity decrease. Here, we describe a strategy allowing oleate-capped UCNPs to become water-soluble and open-modified, with almost undiminished UCL, through ultrasonication of minutes. The prompt phase transfer was enabled by oleate-mediated supramolecular self-assembly of amino modified β-cyclodextrin (amino-β-CD) onto UCNPs surface. We showed that this method is valid for a wide range of UCNPs with quite different sizes (6-400 nm), various dopant types (Er, Tm, and Ho), and hierarchical structures (core, core-shell). Importantly, the amino group of amino-β-CD on the surface of treated UCNPs provide possibilities to introduce entities for biotargeting or functionalization, as exemplified here, a carboxylic-containing near infrared dye (Cy 7.5) that sensitizes UCNPs to enhance their UCL by ~4,820 fold when excited at ~808 nm. The described method has implications for all types of oleate-capped inorganic nanocrystals, facilitating their myriad bioapplications.


I. SPATIAL SKILLS, THEIR DEVELOPMENT, AND THEIR LINKS TO MATHEMATICS.
Understanding the development of spatial skills is important for promoting school readiness and improving overall success in STEM (science, technology, engineering, and mathematics) fields (e.g., Wai, Lubinski, Benbow, & Steiger, 2010). Children use their spatial skills to understand the world, including visualizing how objects fit together, and can practice them via spatial assembly activities (e.g., puzzles or blocks). These skills are incorporated into measures of overall intelligence and have been linked to success in subjects like mathematics (Mix & Cheng, 2012) and science (Pallrand & Seeber, 1984; Pribyl & Bodner, 1987). This monograph sought to answer four questions about early spatial skill development: 1) Can we reliably measure spatial skills in 3- and 4-year-olds?; 2) Do spatial skills measured at 3 predict spatial skills at age 5?; 3) Do preschool spatial skills predict mathematics skills at age 5?; and 4) What factors contribute to individual differences in preschool spatial skills (e.g., SES, gender, fine-motor skills, vocabulary, and executive function)? Longitudinal data generated from a new spatial skill test for 3-year-old children, called the TOSA (Test of Spatial Assembly), show that it is a reliable and valid measure of early spatial skills that provides strong prediction to spatial skills measured with established tests at age 5. New data using this measure finds links between early spatial skill and mathematics, language, and executive function skills. Analyses suggest that preschool spatial experiences may play a central role in children's mathematical skills around the time of school entry. Executive function skills provide an additional unique contribution to predicting mathematical performance. In addition, individual differences, specifically socioeconomic status, are related to spatial and mathematical skill. We conclude by exploring ways of providing rich early spatial experiences to children.


Rescue therapy in adult and pediatric patients with pH1N1 influenza infection: a tertiary center intensive care unit experience from April to October 2009.
Severe respiratory failure is a well-recognized complication of pH1N1 influenza infection. Limited data regarding the efficacy of rescue therapies, including high-frequency oscillatory ventilation and extracorporeal membrane oxygenation, have been previously reported in the setting of pH1N1 influenza infection in the United States. Retrospective, single-center cohort study. Pediatric, cardiac, surgical, and medical intensive care units in a single tertiary care center in the United States. One hundred twenty-seven consecutive patients with confirmed influenza A infection requiring hospitalization between April 1, 2009, and October 31, 2009. Electronic medical records were reviewed for demographic and clinical data. The number of intensive care unit admissions appears inversely related to age with 39% of these admissions <20 yrs of age. Median duration of intensive care unit care was 10.0 days (4.0-24.0), and median duration of mechanical ventilation was 8.0 days (0.0-23.5). Rescue therapy (high-frequency oscillatory ventilation or extracorporeal membrane oxygenation) was used in 36% (12 of 33) of intensive care unit patients. The severity of respiratory impairment was determined by Pao²/Fio² ratio and oxygenation index. High-frequency oscillatory ventilation at 24 hrs resulted in improvements in median Pao²/Fio² ratio (71 [58-93] vs. 145 [126-185]; p < .001), oxygenation index (27 [20-30] vs. 18 [12-25]; p = .016), and Fio2 (100 [70-100] vs. 45 [40-55]; p < .001). Extracorporeal membrane oxygenation resulted in anticipated improvement in parameters of oxygenation at both 2 hrs and 24 hrs after initiation of therapy. Despite the severity of oxygenation impairment, overall survival for both rescue therapies was 75% (nine of 12), 80% (four of five) for high-frequency oscillatory ventilation alone, and 71% (five of seven) for high-frequency oscillatory ventilation + extracorporeal membrane oxygenation. In critically ill adult and pediatric patients with pH1N1 infection and severe lung injury, the use of high-frequency oscillatory ventilation and extracorporeal membrane oxygenation can result in significant improvements in Pao²/Fio² ratio, oxygenation index, and Fio². However, the impact on mortality is less certain.


Blueberry husks and multi-strain probiotics affect colonic fermentation in rats.
The aim was to investigate how blueberry husks and/or mixtures of probiotic strains (Lactobacillus crispatus DSM16743, L. gasseri DSM16737 and L. plantarum DSM15313 (LABmix), or Bifidobacterium infantis DSM15159 and DSM15161 (BIFmix)) affect colonic fermentation, caecal counts of lactobacilli, bifidobacteria and Enterobacteriaceae, body weight gain, and blood concentrations of carboxylic acids (CA) and ammonia in rats. Dietary fibres in blueberry husks were fermented to 61 % in colon, and the elevated faecal excretion of fibre and protein contributed to the high faecal bulking capacity (1.3). The caecal pool of CA was higher in rats fed blueberry husks than the fibre-free control (P < 0.05), and the propionic acid proportion was higher in the distal colon than in the control group (P < 0.05). Probiotics lowered the caecal amount of CA when added to blueberry husks (P < 0.001), while the propionic acid proportion was higher with LABmix (P < 0.01) than blueberry husks only. The propionic acid and butyric acid concentrations in blood were higher in rats fed blueberry husks and probiotics than those fed blueberry husks only (P < 0.01), implying that the absorption of these acids was facilitated by the bacteria. The caecal counts of lactobacilli, bifidobacteria and Enterobacteriaceae were lower in rats fed blueberry husks than the control diet (P < 0.05). The body weight gain was partly influenced by the caecal tissue and contents weights, and BIFmix decreased the ammonia concentration in blood (P < 0.05). We conclude that colonic fermentation is differentially affected by dietary fibre and probiotics, which may be of importance when developing foods with certain health effects.


Regional influenza A (H1N1) 2009 monovalent vaccination campaign - Skokie, Illinois, October 16-December 31, 2009.
On July 29, 2009, the Advisory Committee on Immunization Practices (ACIP) recommended a phased approach for administration of influenza A (H1N1) 2009 monovalent vaccine, with certain high-risk groups in the United States receiving the first doses. In Illinois, state authorities gave responsibility for initial vaccine administration to local health departments and hospitals. This report describes the vaccination campaign of the Skokie Health Department (SHD), during October 16-December 31, 2009. The SHD campaign initially was planned to cover the 67,000 persons residing in Skokie only, but that plan was expanded on November 4, when, in response to a nationwide vaccine shortage, the state health director urged local health departments to vaccinate any person in the ACIP priority groups regardless of jurisdictional boundaries. SHD, with the assistance of 1,075 volunteers, either administered or distributed to medical providers 40,850 H1N1 vaccine doses during a 9-week period, including 8,904 doses administered at 52 Skokie schools and day-care facilities, and 12,876 doses at mass vaccination clinics visited by residents of 193 of the 1,313 Illinois municipalities. At the time of the campaign, widespread illness from 2009 H1N1 in Illinois, with highly publicized deaths, contributed to a public sense of urgency about vaccination. Consistent with published studies, mass clinics in Skokie were an effective means to vaccinate large populations rapidly. The campaign highlighted the need for flexible plans, including the possibility of vaccinating persons who resided well beyond SHD's jurisdictional borders.


Drug-like Properties and ADME of Xanthone Derivatives: The Antechamber of Clinical Trials.
Xanthone derivatives have been described as compounds with a privileged scaffold exhibiting diverse biological/pharmacological activities, what directed the interest to pursue the development of these derivatives into drug candidates. Nevertheless, to achieve this purpose it is crucial to study their pharmacokinetics and toxicity (PK/tox) properties as decision endpoints to continue or interrupt the development investment. This review aims to expose the most relevant analytical methods used in the physicochemical and PK/tox studies in order to detect, quantify, and identify different bioactive xanthones. Analyzing the main results from in vitro and in vivo systems towards ADME properties such as solubility, lipophilicity, pKa, chemical and metabolic stability, permeability, transporters modulation, and plasma protein binding, it is possible to uncover some threats governing the PK properties and to understand the bioavailability and drugability of xanthone derivatives. The last section of this review focuses on a case-study of the development of the drug candidate DMXAA, which has reached clinical trials, to provide the paths and the importance of PK/tox parameters of this scaffold. The data assembled in this review intends to guide for tackling issues in the design of potential lead compounds and drug candidates with a xanthone scaffold.


UDP-glucose: Glucan Synthetase in Developing Cotton Fibers: I. Kinetic and Physiological Properties.
A uridine diphosphate(UDP)-glucose:glucan synthetase can be demonstrated in detached cotton fibers (Gossypium hirsutum L.) and in an isolated particulate fraction from such fibers. When assayed with detached fibers, the kinetics of the glucan synthetase activity with respect to variation in substrate concentration is complex and indicates activation of the enzyme by the substrate. Activity is stimulated by Ca(2+) or Mg(2+) and beta-linked glucosides; the effect of the beta-linked glucosides is to shift the range in which substrate activation occurs to lower concentrations of UDP-glucose. At concentrations of UDP-glucose below 50 mum, addition of uridine triphosphate, in addition to beta-linked glucoside, results in significant stimulation of activity. This effect can be explained by the conversion of uridine triphosphate to UDP-glucose by UDP-glucose pyrophosphorylase, thereby raising substrate concentration to the activating range. In detached fibers, glucan synthetase activity is high at all stages of fiber development. The properties of the glucan synthetase of the isolated particulate fraction closely resemble those of the enzyme assayed in detached fibers; however, in contrast to detached fibers, the ability to detect enzyme activity is more dependent on fiber age, showing maximal activity between 16 and 18 days postanthesis, coincident with the time of rapid onset of secondary wall cellulose deposition.


Dopamine Burden Induced the Inactivation of Sonic Hedgehog Signaling to Cognitive Decline in Minimal Hepatic Encephalopathy.
Minimal hepatic encephalopathy (MHE) is induced by elevated intracranial dopamine (DA). The relationship of the Shh pathway with memory loss in MHE, however, is elusive. In the current study, rats with MHE induced with DA displayed downregulation of the Shh pathway. Additionally, injection of Shh into MHE/DA-treated rats reversed downregulation of BDNF/NT3, whereas administration of cyclopamine (Cyc) enhanced the inhibition of expression of BDNF/NT3. Furthermore, naringin (Nrg) substantially prevented cognitive impairment in MHE/DA-treated rats and upregulated the Shh pathway, paralleling the elevated expression of BDNF/NT3. Overall, our results indicate that the Shh pathway can induce the expression of BDNF/NT3, and DA causes memory loss by inactivation of Shh pathway signaling to BDNF/NT3 in MHE rats, which is reversed by Nrg. Our study may provide new theory basis of pathogenesis and therapeutic target of MHE.


Greasing the wheels of managing overweight and obesity with omega-3 fatty acids.
The epidemic of overweight and obesity around the world and in the US is a major public health challenge, with 1.5 billion overweight and obese adults worldwide, and 68% of US adults and 31% of US children and adolescents overweight or obese. Obesity leads to serious health consequences, including an increased risk of type 2 diabetes mellitus and heart disease. Current preventive and medical treatments include lifestyle modification, medication, and bariatric surgery in extreme cases; however, they are either not very efficacious or are very expensive. Obesity is a complex condition involving the dysregulation of several organ systems and molecular pathways, including adipose tissue, the pancreas, the gastrointestinal tract, and the CNS. The role of the CNS in obesity is receiving more attention as obesity rates rise and treatments continue to fail. While the role of the hypothalamus in regulation of appetite and food intake has long been recognized, the roles of the CNS reward systems are beginning to be examined as the role of environmental influences on energy balance are explored. Omega-3 polyunsaturated fatty acids are essential nutrients that play a beneficial role in several disease processes due to their anti-inflammatory effects, modulation of lipids, and effects on the CNS. Omega-3 fatty acids, specifically EPA and DHA, have shown promising preliminary results in animal and human studies in the prevention and treatment of obesity. Given their effects on many of the pathways involved in obesity, and specifically in the endocannabinoid and mesocorticolimbic pathways, we hypothesize that EPA and DHA supplementation in populations can reduce the reward associated with food, thereby reduce appetite and food intake, and ultimately contribute to the prevention or reduction of obesity. If these fatty acids do harbor such potential, their supplementation in many parts of the world may hold great promise in reducing the global burden of obesity.


Chondroitin sulfate and neuronal disorders.
The brain extracellular matrix (ECM) is involved in several aspects of neuronal development, plasticity, and pathophysiology. Chondroitin sulfate proteoglycans (CSPGs), consisting of core proteins with covalently attached chondroitin sulfate (CS) chains, are essential components of the brain ECM. During late postnatal development, CSPGs condense around parvalbumin-expressing inhibitory neurons (PV-cells) and form lattice-like ECM structures called perineuronal nets (PNNs). Enzymatic or genetic manipulation of PNNs reactivates neuronal plasticity in the adult brain, probably by resetting the excitatory/inhibitory balance in neural networks. Recent studies have indicated that PNNs control PV-cell function by enhancing the accumulation of specific proteins at the cell surface and/or acting as neuroprotective shields against oxidative stress. Since dysfunction of PV-cells and remodeling of CSPGs are commonly observed in several disorders, including schizophrenia, Costello syndrome, Alzheimer's disease, and epilepsy, modulation of PV-cell function by CSPGs may provide a novel strategy for these neuronal disorders. Here we review the potential roles of CSPGs as therapeutic targets for neuronal disorders, with particular focus on structural changes of CS chains under pathological conditions.


Antimicrobial and α-glucosidase inhibitory activities of chemical constituents from Gardenia aqualla (Rubiaceae).
An aliphatic alkene namely pentapentacontene (4) was isolated for the first time from a natural source, Gardenia aqualla, along with fourteen other compounds including nonacosanol (1), tetratriacontanol (2), octatriacontanol (3), β-sitosterol (5) and stigmasterol (6), daucosanol (7), ursolic acid (8), uvaol (9), 3β,19α,23β,24α-tetrahydroxyurs-12-en-28-oic acid (10), lupenone (11), oleanolic acid (12), vanillin (13), vanillic acid (14) and D-mannitol (15). α-glucosidase inhibitory assay revealed that MeOH and EtOAc extracts of leaves had the best activity with IC50 of 9.65 and 20.03 µg/ml respectively. All the tested compounds showed dose dependent inhibition of α-glucosidase and some of them were found to be comparable to acarbose. Compound 10 was the most potent with IC50 = 1.72 μM. It also showed the most interesting antibacterial activity, against the isolate strain of S. typhi and P. aeruginosa and also exhibited the most significant antifungal activities against all the tested yeasts.