Reduced intracortical inhibition and facilitation of corticospinal neurons in musicians.
Interhemispheric inhibition between motor cortices is reduced in musicians. In the present study we have assessed intracortical inhibition (ICI) and facilitation (ICF) within ipsilateral motor cortex in 15 musicians and 15 non-musician controls. Transcranial magnetic stimulation (TMS) was used to elicit muscle evoked potentials (MEPs) from left first dorsal interosseous (FDI) muscle at rest, and during voluntary index finger abduction (0.5 N). Paired TMS with subthreshold conditioning was used to test early ICI with interstimulus intervals (ISIs) 1-5 ms, and ICF with ISIs 8-15 ms. Suprathreshold conditioning was used to test late ICI with ISIs 100-200 ms. TMS thresholds were similar in musicians and controls both at rest and with weak voluntary activation of FDI, indicating that postsynaptic excitability of corticospinal neurons was similar in both groups. ICI was less effective in musicians with FDI at rest and active, but only with an ISI of 3 ms. ICF was less effective in musicians under both rest and active conditions, and this was independent of ISI. There were no differences in late ICI between musicians and controls. We conclude that ICI and ICF circuits which are activated by weak TMS have less influence on corticospinal neuron excitability in musicians. Because of the dependence on ISI, the most likely explanation for the reduced ICI in musicians is an alteration of the interaction between the ICI circuit and neural elements responsible for the later I-waves evoked in corticospinal neurons by TMS. Excitability of the neural elements producing early and late ICI is not altered in musicians. Reduced ICF in musicians could be due to reduced excitability of neurons responsible for ICF, or an altered balance of excitatory inputs to corticospinal neurons which favours neurons that are not acted upon by the ICF circuit. The reduced influence of ICI and ICF circuits on corticospinal neuron excitability in musicians is likely to reflect a training-induced adaptation. It is not clear at present whether these differences represent an adaptive change related to their extraordinary control of finger movements, or alternatively a maladaptive change induced by "overuse" of the hands from extensive training.


Minimum domain of the Shiga toxin A subunit required for enzymatic activity.
The minimum sequence of the enzymatic (A) subunit of Shiga toxin (STX) required for activity was investigated by introducing N-terminal and C-terminal deletions in the molecule. Enzymatic activity was assessed by using an in vitro translation system. A 253-amino-acid STX A polypeptide, which is recognized as the enzymatically active portion of the 293-amino-acid A subunit, expressed less than wild-type levels of activity. In addition, alteration of the proposed nicking site between Ala-253 and Ser-254 by site-directed mutagenesis apparently prevented proteolytic processing but had no effect on the enzymatic activity of the molecule. Therefore, deletion analysis was used to identify amino acid residue 271 as the C terminus of the enzymatically active portion of the STX A subunit. STX A polypeptides with N-terminal and C-terminal deletions were released into the periplasmic space of Escherichia coli by fusion to the signal peptide and the first 22 amino acids of Shiga-like toxin type II, a member of the STX family. Although these fusion proteins expressed less than wild-type levels of enzymatic activity, they confirmed the previous finding that Tyr-77 is an active-site residue. Therefore, the minimum domain of the A polypeptide which was required for the expression of enzymatic activity was defined as StxA residues 75 to 268.


Medicinal and local food plants in the south of Alava (Basque Country, Spain).
Medicinal and food plants in the Basque Country are an integral part of a fast changing culture. With a distinct tradition and language, this region of Europe provides an important example demonstrating the changing role of local and traditional knowledge in industrial countries. As other Mediterranean regions it preserves a rich heritage of using plants as medicine and food, offering a unique opportunity for studying the medicine food interface in an ethnopharmacological context. Therefore, the key goal of this study has been to contribute to an understanding of local and traditional plant usage, to evaluate their uses as food and medicine as well as to critically assess the role of these plants in the south of the Basque Country contributing to an understanding of how foods and medicines are used. A mixed methods approach, including participant observation; open and semi structured interviews was used. Ethnobotanical field work included 183 people, ages ranged from 24 to 98 years old with a majority being between 70 and 80 years old (mean age 71) from 31 towns of three different regions. The basic interview was a one-to-one meeting, which often included field walking and collection of samples as directed by the informants. 700 voucher specimens (most of them with duplicates) were collected for the data obtained. Using SPSS version 20 the gathered information was processed and the replies of the different informants were subsequently organised in variables like medicine and food plants, part of the plants used, forms of preparations, zones preferred for collecting these plants. The data were analysed based on the frequency of records. This type of approach allows us to understand the way the informant's categorize the species, and how these categories are distributed along the sample. In order to analyse the data three main categories of use were distinguished: Medicine (M), Food (F) and an intermediate Health-Food (H-F). The three categories were divided in 27 subcategories (common uses). The informants recognise and use a total of 184 species from 49 families. During interviews, 5658 individual use-reports were collected relating to three use-categories - as medicines, food and health-food. The two main groups with almost the same number of species each are health-food (75 species) and (locally gathered) food only (73), with medicinal uses only (36) being the smallest group. This highlights the important overlap between food and medicines. Overall, three core families were identified (based on the number of use reports and in the number of species): Asteraceae (25 species), Lamiaceae and Rosaceae (24 each). The most frequently reported species are Jasonia glutinosa, Chamaemelum nobile, Prunus spinosa and Quercus ilex subsp. ballota. The most important general use-subcategories are as raw vegetables (27.43% of the use-reports and including 81 species), infusions (14.74%/42) and gastrointestinal (12.53%/42). Conceptually foods and medicines are clearly distinguished but the intermediate group of health foods is more ambiguous. Food and medicinal uses of plants are culturally closely linked. A wide range of plants are known and many still used. The analysis shows that the Basques use a wide range of species which are typical for Western European cultures. In comparison to other studies in the Mediterranean countries there are many similarities in the uses of different families, species of plants and their use and preparations. Some of these plants are key Mediterranean species, often used for a multitude of uses as food and medicine.


A comparison of the growth patterns of Chinese infants in Chengdu and Hong Kong: 0-2 years.
Factors affecting geographical differences in the growth of Chinese infants were examined by comparing data obtained from longitudinal growth studies on growth and feeding practices performed in two Chinese populations: Chengdu and Hong Kong infants from birth to 2 years. Their mean growth curves were fitted by the Reed model for the first year and the Count model for the second year. Chengdu mothers were significantly taller than Hong Kong mothers. Chengdu infants grew more rapidly than the Hong Kong infants during the first 6 months; it is likely that this is related to genetic differences in growth potential and earlier introduction of solids in Chengdu infants.


Insecticide Toxicity to Adelphocoris lineolatus (Hemiptera: Miridae) and its Nymphal Parasitoid Peristenus spretus (Hymenoptera: Braconidae).
In China, Adelphocoris lineolatus (Goeze) (Hemiptera: Miridae) is an important pest of alfalfa, cotton, and other crops, while Peristenus spretus (Chen & van Achterberg) (Hymenoptera: Braconidae) is the dominant nymphal parasitoid of this mirid bug. In the present study, the toxicity of 17 common insecticides to A. lineolatus was evaluated, and the susceptibility of P. spretus to the insecticides with high toxicity to A. lineolatus was tested under laboratory conditions. Of the 17 insecticides tested, 12 (beta cypermethrin, deltamethrin, carbosulfan, acetamiprid, emamectin benzoate, imidacloprid, phoxim, chlorpyrifos, acephate, profenophos, hexaflumuron, and abamectin) had a highly toxic effect on second-instar nymphs of A. lineolatus, with LC(50) values ranging from 0.58 to 14.85 mg a.i. (active ingredient) liter(-1). Adults of P. spretus were most sensitive to chlorpyrifos, with LC(50) values of 0.03 mg a.i. liter(-1), followed by phoxim, acetamiprid, profenophos, carbosulfan, acephate, deltamethrin, emamectin benzoate, imidacloprid, beta-cypermethrin, and abamectin, with LC(50) values ranging from 0.06 to 3.09, whereas hexaflumuron exhibited the least toxicity to the parasitoid, with LC(50) values >500 mg a.i. liter(-1). A risk quotient analysis indicated that beta-cypermethrin, emamectin benzoate, abamectin, and hexaflumuron when applied against A. lineolatus were the least toxic to P. spretus.


Transparent Figures: Researching and Preserving Objects of Cellulose Acetate.
In 1935, the Deutsches Hygiene-Museum Dresden began to produce the so-called Transparent Figures, which became icons of the 20th century. This study aims to explore the effects of external agents such as humidity and temperature on the aging mechanism of the materials of the Transparent Figures and to slow it down through preventive measures. The focus is on cellulose acetate (CA), which was used for the outer skin of the Transparent Figures. The original objects were investigated using FTIR, Raman, and GC-MS. On some Transparent Figures, liquid leakage of additives occurs when the relative humidity rises above 50-60% RH and is accompanied by a release of acetic acid. Based on these findings, original CA used for the production of the Transparent Figures was artificially re-aged at 70 °C while varying the relative humidity. The specimens were analyzed with colorimetry and GC-MS. Additive content, degree of substitution and degree of polymerization were determined. The results showed that the degradation is slowed down at 30% RH compared to aging at 50% RH or 70% RH. Thus, lowering the relative humidity seems effective in slowing down the degradation of the CA of the Transparent Figures. A relative humidity of 30% RH and a temperature of 15 °C are recommended.


Adolescent Alcohol Exposure-Induced Changes in Alpha-Melanocyte Stimulating Hormone and Neuropeptide Y Pathways via Histone Acetylation in the Brain During Adulthood.
Adolescent intermittent ethanol exposure causes long-lasting alterations in brain epigenetic mechanisms. Melanocortin and neuropeptide Y signaling interact and are affected by ethanol exposure in the brain. Here, the persistent effects of adolescent intermittent ethanol on alpha-melanocyte stimulating hormone, melanocortin 4 receptor, and neuropeptide Y expression and their regulation by histone acetylation mechanisms were investigated in adulthood. Male rats were exposed to adolescent intermittent ethanol (2 g/kg, i.p.) or volume-matched adolescent intermittent saline from postnatal days 28 to 41 and allowed to grow to postnatal day 92. Anxiety-like behaviors were measured by the elevated plus-maze test. Brain regions from adult rats were used to examine changes in alpha-melanocyte stimulating hormone, melanocortin 4 receptor, and neuropeptide Y expression and the histone acetylation status of their promoters. Adolescent intermittent ethanol-exposed adult rats displayed anxiety-like behaviors and showed increased pro-opiomelanocortin mRNA levels in the hypothalamus and increased melanocortin 4 receptor mRNA levels in both the amygdala and hypothalamus compared with adolescent intermittent saline-exposed adult rats. The alpha-Melanocyte stimulating hormone and melanocortin 4 receptor protein levels were increased in the central and medial nucleus of the amygdala, paraventricular nucleus, and arcuate nucleus of the hypothalamus in adolescent intermittent ethanol-exposed compared with adolescent intermittent saline-exposed adult rats. Neuropeptide Y protein levels were decreased in the central and medial nucleus of the amygdala of adolescent intermittent ethanol-exposed compared with adolescent intermittent saline-exposed adult rats. Histone H3K9/14 acetylation was decreased in the neuropeptide Y promoter in the amygdala but increased in the melanocortin 4 receptor gene promoter in the amygdala and the melanocortin 4 receptor and pro-opiomelanocortin promoters in the hypothalamus of adolescent intermittent ethanol-exposed adult rats compared with controls. Increased melanocortin and decreased neuropeptide Y activity due to changes in histone acetylation in emotional brain circuitry may play a role in adolescent intermittent ethanol-induced anxiety phenotypes in adulthood.


Development and validation of the Family Meaning of Nursing-Home Visits Scale.
The purpose of this study was to develop and test a Family Meaning of Nursing-Home Visits Scale that can be used to assess and document family members' rationale for visiting nursing home residents. Understanding the meaning ascribed by families for visiting nursing home residents is necessary to develop intervention programmes that facilitate the quality of families' nursing home visits. No valid and reliable instrument is available in Taiwan or elsewhere to accurately document the meaning of family visits to nursing home residents. A cross-sectional design was used to collect survey data from family members of nursing home residents as the quantitative component of a mixed-methods study. Items were developed based on qualitative data from our previous research and that of others. This initial pool of items was used to develop and validate the scale. The validity of the scale was confirmed by exploratory factor analysis and criterion-related validity testing. Internal consistency reliability was assessed by Cronbach's alphas. Factor analysis yielded a six-factor final solution (32 items), accounting for 66·76% of the variance. For criterion-related validity, 'responsibility for care quality' was negatively correlated with satisfaction with nursing home caregiving (r = -0·23, p < 0·01) and nursing home rehabilitation activities (r = -0·17, p < 0·05). Cronbach's α for each subscale ranged from 0·68-0·98, and Cronbach's α for the total scale was 0·83. The Family Meaning of Nursing-Home Visits Scale has acceptable internal consistency reliability, good content validity and acceptable construct validity. The Family Meaning of Nursing-Home Visits Scale provides nurses and healthcare providers an objective and consistent method to explore the priority of meanings family members assign to nursing home visits. Based on this priority for visiting, interventions could be designed to increase the quality of visits, thus promoting families' continued incentive to visit in person.


Evidence from 2100 index cases supports genome sequencing as a first-tier genetic test.
Genome sequencing (GS) is one of the most comprehensive assays that interrogate single-nucleotide variants, copy number variants, mitochondrial variants, repeat expansions, and structural variants in a single assay. Despite the clear technical superiority, the full clinical utility of GS has yet to be determined. We systematically evaluated 2100 clinical GS index cases performed in our laboratory to explore the diagnostic yield of GS as first-tier and as follow-up testing. The overall diagnostic yield was 28% (585/2100). The diagnostic yield for GS as the first-tier test was 26% (294/1146). Among cases with prior non-diagnostic genetic tests, GS provided a diagnosis for 27% (247/910) of cases, including 56 cases with prior exome sequencing (ES). Although re-analysis of previous ES might have resolved the diagnosis in 29 cases, diagnoses for 27 cases would have been missed because of the technical inferiority of ES. Moreover, GS further disclosed additional genetic etiology in 3 out of 44 cases with existing partial diagnosis. We present the largest-to-date GS data set of a clinically heterogeneous cohort from a single clinical laboratory. Our data demonstrate that GS should be considered as the first-tier genetic test that has the potential to shorten the diagnostic odyssey.


Dynamics of maternal antibodies to hemorrhagic disease viruses (Reoviridae: Orbivirus) in white-tailed deer.
Enzootic stability, potentially associated with acquired resistance and subsequent transfer of maternal antibodies, innate resistance, or both, has been hypothesized to explain the lack of reports of hemorrhagic disease (HD) in white-tailed deer (Odocoileus virginianus) from Texas. The objectives of this research were to determine the following: how long maternal antibodies to epizootic hemorrhagic disease (EHD) and bluetongue (BT) viruses persist; whether fawns from an enzootic site are naturally exposed to EHD and BT viruses while maternal antibodies are present; and whether field-challenged fawns develop clinical disease. Twelve of 52 fawns from Texas were moved to an indoor facility. All 12 (100%) were positive for maternal antibodies to EHD or BT viruses by agar gel immunodiffusion (AGID) and serum neutralization (SN) tests. Weekly monitoring demonstrated that precipitating antibodies disappeared by 23 wk of age and serum neutralizing antibodies disappeared by 17-18 wk of age. Fawns that remained outdoors in Texas were not observed with signs of HD. At 14-21 wk of age (October), 39 of 40 (98%) fawns that had remained outdoors were positive for EHD and/or BT virus antibodies by AGID and 32 (80%) had SN antibody titers to one or more of five viruses (EHDV-1, EHDV-2, BTV-10, BTV-11, BTV-17). Antibody titers to EHDV-1, EHDV-2, and BTV-11 all exceeded titers of same-age indoor fawns, suggesting recent exposure. Epizootic hemorrhagic disease viruses were isolated from seven (18%) of the outdoor fawns and all 40 remained clinically normal. Natural exposure of deer to EHD and BT viruses occurred at this site in the presence of maternal antibodies without causing disease. This may be due to acquired immunity and the subsequent transfer of maternal antibodies, but it does not exclude innate resistance as a possible factor in the enzootic stability of EHD and BT viruses at this location.


Alcohol and sedative drug use in neurotic outpatients.
One hundred and six adult neurotic patients attending a behavioural psychotherapy unit were asked about their use of alcohol and other drugs and the perceived anxiolytic effect of these substances. Their drinking behaviour was not significantly different from that of the general population. Alcohol and other drugs were not perceived as reliable anxiolytics and not regularly used as such. Where alcohol or drug abuse coexist with anxiety-related problems, it is helpful to ask the patient to withdraw from these substances prior to starting behavioural therapy of the latter. We ask patients having behavioural therapy to refrain from alcohol or drug use prior to therapy or homework tasks.


Enantioselective Access to Bicyclo[3.2.1]octadienone Skeleton: Total Syntheses of (+)-Engelharquinone and Its Epoxide.
The first enantioselective total syntheses of engelharquinone (2) and its epoxide 3 have been achieved. The key steps include (1) catalytic asymmetric 1,4-addition of a naphthylboronic acid derivative to a masked naphthoquinone derivative by using a chiral Rh-complex and (2) thiolate-promoted stereospecific construction of the bicyclo[3.2.1]octadienone scaffold.


Effectiveness of a long-lasting insecticide treatment kit (ICON® Maxx) for polyester nets over three years of household use: a WHO phase III trial in Tanzania.
ICON® Maxx (Syngenta) is an insecticide treatment kit of pyrethroid and binding agent for long-lasting treatment of mosquito nets. Interim recommendation for use on nets was granted by the World Health Organization (WHO) after successful evaluation in experimental huts following multiple washes. A full WHO recommendation is contingent upon demonstration of continued bio-efficacy after 3 years of use. A household-randomized prospective study design was used to assess ICON Maxx-treated nets over 3 years in north-eastern Tanzania. Conventional treated nets (with lambda-cyhalothrin, but without binder) served as a positive control. At 6-monthly intervals, cross-sectional household surveys monitored net use and physical integrity, while cone and tunnel tests assessed insecticidal efficacy. Pyrethroid content was determined after 12 and 36 months. A parallel cohort of nets was monitored annually for evidence of net deterioration and attrition. After 12 months' use, 97% of ICON Maxx-treated nets but only 67% of CTN passed the WHO efficacy threshold for insecticidal durability (> 80% mortality in cone or tunnel or 90% feeding inhibition in tunnel). After 24- and 36-months use, 67% and 26% of ICON Maxx treated nets met the cone criteria, respectively, and over 90% met the combined cone and tunnel criteria. Lambda-cyhalothrin content after 36 months was 17% (15.8 ± 4.3 mg/m2) of initial content. ICON Maxx nets were used year-round and washed approximately 4 times per year. In cross-sectional survey after 36 months the average number of holes was 20 and hole index was 740 cm2 per net. Cohort nets had fewer holes and smaller hole index than cross-sectional nets. However, only 15% (40/264) of cohort nets were not lost to follow-up or not worn out after 36 months. Because more than 80% of nets met the WHO efficacy criteria after 36 months use, ICON Maxx was granted WHO full recommendation. Cross-sectional and cohort surveys were complementary and gave a fuller understanding of net durability. To improve net usage and retention, stronger incentives and health messaging should be introduced in WHO LLIN longitudinal trials. Untreated polyester nets may be made long-lastingly insecticidal in Africa through simple household treatment using ICON Maxx pyrethroid-binder kits.


Cancer in Hiroshima: 35 years after the bomb.
After the 1945 atomic bomb explosions, attention was initially drawn to the leukemogenic effect of atomic radiation. Mortality studies over the years have shown that the leukemogenic effect has been gradually declining, and the incidence of solid tumors has been increasing. There was shorter latent period for the appearance of excess leukemia mortality than for solid tumors. It appears that the risk for developing solid tumors becomes greatest when the population enters the age group at which that particular form of cancer most commonly occurs. The leukemogenic and carcinogenic risks are also greater in those exposed to radiation in the younger age groups. There are implications in these studies for cancer control with regard to radiation safety in diagnostic radiology and the peaceful uses of atomic energy; in addition, they emphasize the moral obligation involved in limiting the proliferation of atomic weapons. These observations may also be parallel to the experience of oncologists with second primary cancers after the administration of chemotherapy.


NMRFAM-SPARKY: enhanced software for biomolecular NMR spectroscopy.
SPARKY (Goddard and Kneller, SPARKY 3) remains the most popular software program for NMR data analysis, despite the fact that development of the package by its originators ceased in 2001. We have taken over the development of this package and describe NMRFAM-SPARKY, which implements new functions reflecting advances in the biomolecular NMR field. NMRFAM-SPARKY has been repackaged with current versions of Python and Tcl/Tk, which support new tools for NMR peak simulation and graphical assignment determination. These tools, along with chemical shift predictions from the PACSY database, greatly accelerate protein side chain assignments. NMRFAM-SPARKY supports automated data format interconversion for interfacing with a variety of web servers including, PECAN , PINE, TALOS-N, CS-Rosetta, SHIFTX2 and PONDEROSA-C/S. The software package, along with binary and source codes, if desired, can be downloaded freely from http://pine.nmrfam.wisc.edu/download_packages.html. Instruction manuals and video tutorials can be found at http://www.nmrfam.wisc.edu/nmrfam-sparky-distribution.htm. email@example.com or email@example.com Supplementary data are available at Bioinformatics online.


Control of aldol reaction pathways of enolizable aldehydes in an aqueous environment with a hyperbranched polymeric catalyst.
A fundamental chemoselectivity challenge that remains intrinsically unsolved in aldol-type reactions is the suppression of self-aldol reactions with enolizable aldehydes in reactions such as cross-aldol processes. Contrasting with the usual practice of using large excesses of one component to compete with the undesired self-aldehyde condensation reactions, we have developed an enzyme-like polymer catalyst consisting of a hyperbranched polyethyleneimine derivative and proline that can eliminate the self-aldol reactions by suppressing an irreversible aldol condensation pathway. Control experiments and preliminary mechanistic studies suggest that the polymer catalyst provides an optimum environment for the aldol reaction to proceed selectively in water, and the catalytic conditions provided by the polymer are difficult to duplicate with typical small molecule analogues. This polymer catalyst system or its modified version has potential applications in developing a new or more efficient synthesis, as demonstrated in a dynamic catalytic process for the preparation of alpha,beta-unsaturated ketones using cross ketone/aldehyde reactions without the need for excess substrates.


Integrated optimization of fish oil microencapsulation process by spray drying.
An integrated approach through coupling response surface method (RSM) and genetic algorithm (GA) was applied to optimize the spray dryer operational condition for production of fish oil microcapsules. The inlet drying air temperature, aspirator rate, and peristaltic pump rate were independent and encapsulation efficiency (EE) and exergy efficiency were dependent variables. RSM was applied to establish the relationship between the independent and dependent variables followed by integrating the developed models using three mathematical approaches and measure the fitness value of GA. Consequently, the optimal drying condition for microencapsulation of fish oil was: inlet drying air temperature = 177.23°C, aspirator rate = 63.93%, and peristaltic pump rate = 14.04% yielding exergy efficiency of 8.10% and EE of 79.14%. The results of confirmation experiments for selected drying condition proved the capability of utilized approach for determination of sustainable and qualified process in fish oil microencapsulation by spray drying.


Retrievability of implant-retained crowns following cementation.
The purpose of this study was to assess the retrievability of cemented implant crowns using two different removal devices. The influence of five cement types and two cement application techniques was evaluated. Forty copings were cast from a CoCr alloy for 40 tapered titanium abutments (5 degrees taper, 4.3 mm diameter, 6 mm height, Camlog, Germany). Twenty copings were modeled as single crowns, whereas 20 copings were modeled with an extension to simulate fixed partial dentures (FPDs). Before cementation, the inner surfaces of the copings were air-abraded (50 mum Al(2)O(3) particles at 2.5 bars), while the abutments were used as delivered with machined surfaces. Copings were cemented with eugenol-free zinc oxide (Freegenol), zinc phosphate (Harvard), glass ionomer (Ketac Cem), polycarboxylate (Durelon) and so-called self-adhesive resin (RelyX Unicem) cement. Cement was applied in a thin film band of 1 or 3 mm to the cervical margin of the inner surface of the copings, respectively. After cementation, specimens were stored in saline solution for 24 h. The Coronaflex and a standardized custom-made removal device were used to remove the copings from the abutments. Using the same cement, no statistically significant influence with regard to the type of restoration (crown/FDP), cement application mode and device was detected (P>0.05). Therefore, data of specimens cemented with the same cement were pooled. Median attempts to remove the copings were: zinc oxide: 3, self-adhesive resin: 3, zinc phosphate: 5, glass ionomer: 16 and polycarboxylate: 58. Four levels of significance (P<0.0001) were found: (1) zinc oxide/self-adhesive resin; (2) zinc phosphate; (3) glass ionomer; and (4) polycarboxylate. Zinc phosphate and glass ionomer cement might be suitable for a so-called 'semipermanent' (=retrievable) cementation, while polycarboxylate seems to provide the most durable cementation.


Microtubule bundle formation and cell death induced by the human CLASP/Orbit N-terminal fragment.
Previously we have identified the Drosophila orbit gene whose hypomorphic mutations cause abnormal chromosome segregation (Inoue et al., 2000). The orbit encodes Orbit/Mast, a 165-kDa microtubule-associated protein (MAP) with GTP-binding motifs. Two human homologues of the Orbit/Mast, CLASP1 (hOrbit1) and CLASP2 (hOrbit2) have been identified. Using an antibody to CLASP1/hOrbit1 polypeptide, we confirmed that the polypeptide of about 150 kDa associates with microtubule purified from the porcine brain. Thus, we conjectured that CLASP1 may be a human orthologue of the Drosophila Orbit/Mast, and therefore we named it h (human) Orbit1. We constructed the plasmid for expression of a fusion protein of the putative microtubule-binding domain (1-662 out of 1289 residues) of hOrbit1 and the green fluorescent protein (GFP), and then, transfected the plasmid into Tet off cells derived from HeLa cell. Confocal laser scanning microscopic observation revealed that the GFP-fluorescence associated with short and thin filaments in the perinuclear region during the short period after plasmid transfection, and colocalized with only part of the microtubules. GFP fluorescence was later detected on the abnormally longer and thick bundles of microtubule filaments. Finally the bundles formed networks in the perinuclear region. The results suggest that the GFP-hOrbit1 N-terminal fragment (GFP-hOrbit1 NF) binds to the newly formed microtubules rather than the pre-formed ones, and that displacement of the endogenous hOrbit by the fragment might cause abnormal bundling of microtubules. Interestingly, the expression of the GFP-hOrbit1 NF results in cell death associated with nuclear fragmentation.


Comparative analysis of the tissue distribution of three fibroblast growth factor receptor mRNAs during amphibian morphogenesis.
We have used in situ hybridization to survey the expression pattern of three fibroblast growth factor receptor (FGFR) mRNAs (PFR-1, PFR-3 and PFR-4, which we previously identified as the amphibian Pleurodeles waltl homologs of human FGFR-1, FGFR-3 and FGFR-4, respectively) during morphogenesis. Previous work suggests that these FGFR mRNAs exhibit a distinct pattern of expression at early developmental stages. In the present study we have tested the functional activity of these receptors and shown that both FGF-1 (acidic FGF) and FGF-2 (basic FGF), but not FGF-7 (keratinocyte growth factor), can lead to their activation, suggesting that the three cDNAs encode functional receptors. Results from in situ hybridization indicate that various FGFRs are involved in various developmental events. Their involvement in these processes is both overlapping and distinct. During the differentiation of the central nervous system (CNS), PFR-1 and PFR-4 mRNAs show high levels of redundant expression, while the sites of expression of PFR-3 mRNA correlate with regions, such as the diencephalon and the rhombencephalon, undergoing important anatomic changes. The three FGFR mRNAs are distinctly expressed in the cranial ganglia, the pigmented epithelia of retina and the otic vesicles. Most significantly, we found that they are strongly expressed at cranial and branchial mesenchymal condensation sites. PFR-3 mRNA is expressed earlier in this process than PFR-1 and PFR-4 mRNAs. Furthermore PFR-3 mRNA is detected in the mesenchyme of the limb bud, while PFR-1 and PFR-4 mRNAs are found in the primordia of the skeletal elements. In addition, PFR-1 mRNA is expressed in axial mesenchyme and PFR-4 mRNA is detected in the melanophores, xanthophores and in the pronephros. These results suggest that various FGFRs may be involved in distinct developmental events including cell proliferation and differentiation. We also discuss the functional redundancy of the FGFR system during amphibian morphogenesis.


Targeted DNA methylation in pericentromeres with genome editing-based artificial DNA methyltransferase.
To study the impact of epigenetic changes on biological functions, the ability to manipulate the epigenetic status of certain genomic regions artificially could be an indispensable technology. "Epigenome editing" techniques have gradually emerged that apply TALE or CRISPR/Cas9 technologies with various effector domains isolated from epigenetic code writers or erasers such as DNA methyltransferase, 5-methylcytosine oxidase, and histone modification enzymes. Here we demonstrate that a TALE recognizing a major satellite, consisting of a repeated sequence in pericentromeres, could be fused with the bacterial CpG methyltransferase, SssI. ChIP-qPCR assays demonstrated that the fusion protein TALMaj-SssI preferentially bound to major chromosomal satellites in cultured cell lines. Then, TALMaj-SssI was expressed in fertilized mouse oocytes with hypomethylated major satellites (10-20% CpG islands). Bisulfite sequencing revealed that the DNA methylation status was increased specifically in major satellites (50-60%), but not in minor satellites or other repeat elements, such as Intracisternal A-particle (IAP) or long interspersed nuclear elements-1 (Line1) when the expression level of TALMaj-SssI is optimized in the cell. At a microscopic level, distal ends of chromosomes at the first mitotic stage were dramatically highlighted by the mCherry-tagged methyl CpG binding domain of human MBD1 (mCherry-MBD-NLS). Moreover, targeted DNA methylation to major satellites did not interfere with kinetochore function during early embryonic cleavages. Co-injection of dCas9 fused with SssI and guide RNA (gRNA) recognizing major satellite sequences enabled increment of the DNA methylation in the satellites, but a few off-target effects were also observed in minor satellites and retrotransposons. Although CRISPR can be applied instead of the TALE system, technical improvements to reduce off-target effects are required. We have demonstrated a new method of introducing DNA methylation without the need of other binding partners using the CpG methyltransferase, SssI.


Synthesis and characteristics of graphene oxide-derived carbon nanosheet-Pd nanosized particle composites.
Carbon nanosheet (CNS)-Pd nanosized particle (NP) composites were synthesized by using graphite oxide (GO) and bis(ethylenediamine)palladium(II) (Pd(en)(2)(2+)) as the precursors, and their structure and adsorption properties were examined. It was found that the Pd(en)(2)(2+) complex ions can be intercalated into GO layers highly efficiently to form a layered structure containing a large amount of Pd (approximately 12 wt %). By the subsequent chemical reduction, Pd NPs (2-6 nm in size) are well dispersed between CNS to form a CNS-Pd NP composite and serve as spacers to increase the porosity of the composite. Hydrogen adsorption results demonstrate that both Pd NPs and CNS play important roles in hydrogen adsorption, particularly at a lower temperature and for CNS with deficient sites, which bring about a H(2) adsorption greater than those on other Pd-loaded nanocarbon materials reported so far. The unique composite nanostructure having large contents of Pd NPs (20-25 wt %) stabilized by CNSs is hopeful to be applied to the fields of H(2)-related catalysis, sensing, and so forth.


A qualitative study of the experience of obstetric fistula survivors in Addis Ababa, Ethiopia.
Research on obstetric fistula has paid limited attention to the lived experiences of survivors. This qualitative study explored the evolution of survivors' perceptions of their social relationships and health since developing this obstetric complication. In-depth interviews were conducted with eight survivors who were selected based on purposive and snowball sampling techniques. Thematic categorization and content analysis was used to analyze the data. The resultant themes included participants' understanding of factors predisposing to fistula, challenges they encounter, their coping responses, and the meaning of their experiences. First, the participants had a common understanding of the factors that predisposed them to obstetric fistula. They mentioned poor knowledge about pregnancy, early marriage, cultural practices, and a delay in or lack of access to emergency obstetric care. Second, the participants suffered from powerlessness experienced during their childhood and married lives. They also faced prolonged obstructed labor, physical injury, emotional breakdown, depression, erosion of social capital, and loss of healthy years. Third, to control their negative emotions, participants reported isolating themselves, having suicidal thoughts, positive interpretation about the future, and avoidance. To obtain relief from their disease, the women used their family support, sold their properties, and oriented to reality. Fourth, the participants were struggling to keep going, to accept their changed reality, and to change their perspectives on life. In conclusion, obstetric fistula has significant physical, psychosocial, and emotional consequences. The study participants were not passive victims but rather active survivors of these challenges. Adequate support was not provided by their formal or informal support systems. To prevent and manage obstetric fistula successfully, there should be family-based interventions that improve access to and provision of emergency obstetric care. These initiatives should also ensure men's participation, women's empowerment, and the utilization of community-based institutions.


Traditional male circumcision: balancing cultural rights and the prevention of serious, avoidable harm.
The right to participate in cultural practices should be protected. However, it is a limited right, and does not entail a right to activities that cause serious and avoidable harms. I argue that the harms currently resulting from traditional circumcision are very serious, and that we have an obligation to ensure that the practice is effectively regulated so as to minimise them.


[Association between polymorphisms of insulin-like growth factor receptor gene and susceptibility to non-small-cell lung cancer in Fujian Chinese].
To assess the association between polymorphisms of insulin-like growth factor receptor (IGF-1R and IGF-2R) and genetic susceptibility and non-small-cell lung cancer (NSCLC). A case-control study of 260 patients with NSCLC and 258 cancer-free subjects from Fujian was carried out. Genotypes of polymorphisms of IGF-1R +1013 and IGF-2R +1619 were determined by DNA sequencing and polymerase chain reaction-restrictive fragment length polymorphism. (1) Significant differences in allele frequency and genotypes distribution of IGF-1R +1013 (G/A) were found between the two groups (P<0.05). On multivariate analysis after controlling age and gender, compared with GG genotype of the IGF-1R +1013 (G/A), the risk of lung cancer for individuals with GA genotype was increased by 0.80 times (95%CI: 1.24-2.59, P = 0.002), those with AA genotype was increased by 2.56 times (95%CI: 1.78-7.26, P = 0.000), and those with the polymorphic A variant (GA or AA) was increased by 0.98 times (95%CI: 1.39-2.83, P = 0.000). No significant differences in genotypic or allelic frequencies of IGF-2R +1619 (G/A) were found between the two groups (P> 0.05). (2) After stratification of the clinical status, the IGF-1R +1013 A allele increased the risk of lung squamous cell carcinoma (OR = 3.20, 95%CI: 1.75-5.84, P = 0.000), lung adenocarcinoma (OR = 1.55, 95%CI: 1.00-2.41, P = 0.049) and other types of lung cancer (OR = 1.96, 95% CI: 1.10-3.49, P = 0.023), but no association was found between the two SNPs and other clinical features. (3) IGF-1R +1013 (G/A) and IGF-2R +1619(G/A) polymorphisms showed a synergic effect (P = 0.003). The common IGF-1R gene polymorphism G1013A may influence the risk of lung cancer. The polymorphisms of IGF-1R +1013 (G/A) and IGF-2R +1619 (G/A) have synergistic influence on the risk of lung cancer.


Association of clot ultrastructure with clot perviousness in stroke patients.
Clot perviousness on computerized tomography (CT) is predictive of response to reperfusion therapy. This study aimed to determine the association of clot perviousness with ultrastructural features of clot in stroke patients undergoing endovascular thrombectomy. We quantitatively analyzed the ultrastructural components identified using scanning electron microscopy. The clot components were determined in the inner portions of the clots. Clot perviousness was assessed as thrombus attenuation increase (TAI) using noncontrast CT and CT angiography. We compared the association between the identified ultrastructural components and clot perviousness. The proportion of pores consisted of 3.5% on scanning electron microscopy images. The proportion of porosity in the inner portion was 2.5%. Among the ultrastructural components, polyhedrocytes were most commonly observed. The mean TAI was 9.3 ± 10.0 (median 5.6, interquartile range 1.1-14.3) Hounsfield units. TAI correlated positively with inner porosity (r = 0.422, p = 0.020). Among the ultrastructural clot components, TAI was independently associated with polyhedrocytes (B = - 0.134, SE = 0.051, p = 0.008). Clot perviousness is associated with porosity and the proportion of polyhdrocytes of clots.


[Evaluation of bone for using of bone metabolic markers in the diagnosis and treatment of osteoporosis].
Quantification of BMD is being used as the main method to diagnose osteoporosis and measurement accuracy has dramatically improved. However, essential clinical parameters of osteoporosis include more dynamic markers such as bone metabolic markers. Bone metabolism undergoes daily dynamic changes, and even with the same BMD, the metabolic state differs and the pathologic significance also differs. Therefore, to use BMD measurement as a dynamic marker, one must wait for an observation period of 6 months to 1 year before remeasurement, whereas bone metabolic markers accurately reflect the state of bone metabolism at the point in time of the measurement. Bone metabolic markers can also be used as a guide to selecting pharmacotherapy. When there is doubt about choosing a drug, the use of bone metabolic markers can enable more appropriate selection. Furthermore, to evaluate the effects of drug therapy on disease improvement, assessing the state of bone metabolism at the time of diagnosis is recommended whenever possible. However, if a decision is made to select treatment with little influence on bone metabolism, then measuring bone metabolic markers to monitor drug treatment effects has little clinical significance. Recently the clinical application of bone metabolic markers have been achieved significant progress and the measurements of these indices give us better understanding of pathological of osteoporosis. Therefore, it is very important to guide the proper application and assessment of bone metabolic markers in clinical practice.


An Attitudinal Survey of Undergraduate Neuroscience Students Regarding Their Views on the Relevance of Lectures to their Education.
Advances in technology have seen a significant growth in the integration of e-learning into university education. Coupled with this trend are the learning approaches used by "Generation Connected" or GenC students, whose prolific use of digital technology is a defining characteristic. This has resulted in questions being asked as to whether in-class university lecture time is still relevant to university education. Here we conducted a case study with a group of undergraduate neuroscience students to assess their views on the relevance of attending lectures, why they attend or the reasons for non-attendance, and on what makes a good lecture. This is with a view to informing the design of new teaching approaches that may be more beneficial in maximising student engagement, and facilitating learning. The survey instrument was a ten-item questionnaire that collected both qualitative and quantitative data. Over 90% of students were of the view that lectures were beneficial to their learning, while only 4% thought they were an outdated mode of education. Three main themes emerged when students were asked what makes a good lecture: 1. Engagement, 2. Time, and 3. Varied format. We discuss the implications of these findings and suggest how these student views could be woven into the design of teaching approaches to increase the relevance of in-class lecture time in undergraduate neuroscience education.


Spaceflight osteoporosis: current state and future perspective.
Osteoporosis is one of the established major consequences of long-duration spaceflights in astronauts seriously undermining their health after their returning on Earth. Indeed, astronauts typically lose more bone mass during one month than postmenopausal women on Earth lose in one year. To date, countermeasures mainly consist in exercise and supplementation while pharmacological treatment as those used in postmenopausal women are not routine. However, it is evident that exercise and supplementation alone are not enough to maintain bone homeostasis. In this paper we describe the current countermeasures for bone loss during long-term spaceflight, review the modern treatment which are successfully employed to prevent osteoporosis on Earth and that could be quickly used also for astronauts and finally focus on the recent cellular and molecular understanding of bone homeostasis which might provide the basis for the development of future targeted therapies.


Healthy aging among inner-city men.
Until now, prospective studies of aging have begun with 50- to 60-year olds, not adolescents. Premature deaths, childhood variables, and alcohol abuse have been often ignored. So has positive aging. As people live longer, gerontology needs to understand the determinants of health as well as illness in the later years. The present study follows a cohort of adolescent boys (332 inner-city youths) for 60 years or until death. Complete physical exams were obtained every 5 years and psychosocial data every 2 years. Predictor variables assessed prior to age 50 include six variables reflecting uncontrollable factors--parental social class, environmental strengths, number of family problems, major depression, ancestral longevity, and premorbid physical health at age 50--and six variables reflecting (at least some) personal control: alcohol abuse, smoking, marital stability, body mass index, coping mechanisms, and education. The four outcome variables chosen to assess healthy aging at 70 reflected both "mind" and "body." They included objectively assessed variables (death and/or disability prior to 70, and objective mental health) and two subjectively assessed variables (perceived instrumental activities of daily living and life enjoyment). Multivariate analysis suggested that positive aging at 70 could be predicted by variables assessed prior to age 50. More hopeful still, if the six variables under some personal control were controlled, depression was the only uncontrollable variable that affected the quality of subjective and objective aging. First, we may have greater personal control over our biopsychosocial health after retirement than previously recognized. Second, in this cohort, psychiatric rather than sociological predictors appeared more important.


Adamantinomatous craniopharyngioma: pathology, molecular genetics and mouse models.
Adamantinomatous craniopharyngiomas (ACPs) are histologically benign but clinically aggressive epithelial tumours of the sellar region that are associated with high morbidity and occasional mortality. Research from the last 3 years has provided important insights into the molecular and cellular pathogenesis of these tumours. It has become established that mutations in CTNNB1 (encoding β-catenin), leading to the over-activation of the WNT pathway, underlie the molecular aetiology of human ACP. Interestingly, the effect of these mutations is restricted to a small number of tumour cells, mostly forming clusters, which recent research has shown to be critical for tumorigenesis in mice and humans. Several pathways have been found to be activated in these clusters including the epidermal growth factor receptor and the sonic hedgehog pathways, offering potential therapeutic targets. A novel and unexpected role for pituitary stem cells has been proposed, which is fundamentally distinct from the cancer stem cell paradigm. The study of these benign tumours could reveal important insights into general mechanisms underlying the initial steps of tumorigenesis and facilitate novel tools to improve managements of the patients.


Characterization of protein immobilization on nanoporous gold using atomic force microscopy and scanning electron microscopy.
Nanoporous gold (NPG), made by dealloying low carat gold alloys, is a relatively new nanomaterial finding application in catalysis, sensing, and as a support for biomolecules. NPG has attracted considerable interest due to its open bicontinuous structure, high surface-to-volume ratio, tunable porosity, chemical stability and biocompatibility. NPG also has the attractive feature of being able to be modified by self-assembled monolayers. Here we use scanning electron microscopy (SEM) and atomic force microscopy (AFM) to characterize a highly efficient approach for protein immobilization on NPG using N-hydroxysuccinimide (NHS) ester functionalized self-assembled monolayers on NPG with pore sizes in the range of tens of nanometres. Comparison of coupling under static versus flow conditions suggests that BSA (Bovine Serum Albumin) and IgG (Immunoglobulin G) can only be immobilized onto the interior surfaces of free standing NPG monoliths with good coverage under flow conditions. AFM is used to examine protein coverage on both the exterior and interior of protein modified NPG. Access to the interior surface of NPG for AFM imaging is achieved using a special procedure for cleaving NPG. AFM is also used to examine BSA immobilized on rough gold surfaces as a comparative study. In principle, the general approach described should be applicable to many enzymes, proteins and protein complexes since both pore sizes and functional groups present on the NPG surfaces are controllable.


Attentional biases for betel nut cues in heavy and light chewers.
The betel nut (Areca catecu) is regarded by the World Health Organization as the fourth most prevalent human carcinogen. Our study aims to investigate whether habitual chewers show bias in their attention toward betel nut usage. In the current study, heavy and light betel nut chewers were instructed to respond to a probe presented immediately after either one of a pair of areca-related picture and non-areca-matched picture. The presentation durations of these pictures were manipulated to investigate attentional biases under awareness threshold (17 ms), in initial orienting (200 ms), and maintenance of attention (2,000 ms). Faster response to the probe replacing the areca-related picture, in comparison with a matched picture, indicated attentional bias. The results showed that neither group showed subliminal attentional biases. Further, heavy chewers, but not light chewers, exhibited supraliminal biases toward betel nut cues in initial orienting of attention and maintained attention. Moreover, attentional bias scores at 2,000 ms were also shown to be positively associated with betel nut craving and dependence. Implications of the current findings are thoroughly discussed in the article.


Novel Synthesis of Titanium Oxide Nanoparticles: Biological Activity and Acute Toxicity Study.
Titanium oxide nanoparticles (TiO2 NPs) have been attracting numerous research studies due to their activity; however, there is a growing concern about the corresponding toxicity. Here in the present study, titanium oxide nanoparticles were newly synthesized using propolis extract followed by antimicrobial activity, cytotoxicity assay using human cancer cell lines, and acute toxicity study. The physicochemical characterization of the newly synthesized TiO2 NPs had average size = 57.5 nm, PdI = 0.308, and zeta potential = -32.4 mV. Antimicrobial activity assessment proved the superior activity against Gram-positive compared to Gram-negative bacteria and yeast (lowest MIC values 8, 32, and 32, respectively). The newly synthesized TiO2 NPs showed a potent activity against the following human cancer cell lines: liver (HepG-2) (IC50 8.5 µg/mL), colon (Caco-2), and breast (MDA-MB 231) (IC50 11.0 and 18.7 µg/mL). In vivo acute toxicity study was conducted using low (10 mg/kg) and high (1000 mg/kg) doses of the synthesized TiO2 NPs in albino male rats. Biochemistry and histopathology of the liver, kidney, and brain proved the safety of the synthesized TiO2 NPs at low dose while at high dose, there was TiO2 NPs deposit in different vital organs except the cerebral tissue.


[Therapy of the "acute gallbladder"].
Acute stone-related cholecystitis is treated by early cholecystectomy. Percutaneous cholecystostomy seems more and more the preferred treatment of stress-related acalculous cholecystitis. Diagnosis is confirmed by ultrasound. Simultaneous combined operations, i.e. cholecystectomy and common bile duct revision, are performed in patients under 65 years of age without serious concomitant diseases and if the operation is not hazardous. The inhospital mortality amounts to about 3%.


Mutant huntingtin reduction in astrocytes slows disease progression in the BACHD conditional Huntington's disease mouse model.
Neuronal and non-neuronal cells express the huntingtin (HTT) protein, yet neurodegeneration in Huntington's disease (HD) is largely selective, affecting most prominently striatal medium spiny neurons and cortical pyramidal neurons. Selective toxicity of full-length human mutant HTT (fl-mHTT) may be due in part to its expression in non-neuronal cells. While studies suggest neuronal-glial interactions are important in HD and fl-mHTT is expressed in astrocytes, it has not been determined whether the expression of fl-mHTT in astrocytes is necessary for HD pathogenesis. To directly assess the necessity of fl-mHTT in astrocytes for HD pathogenesis, we used a mouse genetic approach and bred the conditional mHTT-expressing BACHD mouse model with GFAP-CreERT2 mice. We show that GFAP-CreERT2 expression in these mice is highly selective for astrocytes, and we are able to significantly reduce the expression of fl-mHTT protein in the striatum and cortex of BACHD/GFAP-CreERT2-tam mice. We performed behavioral, electrophysiological and neuropathological analyses of BACHD and BACHD/GFAP-CreERT2-tam mice. Behavioral analyses of BACHD/GFAP-CreERT2-tam mice demonstrate significant improvements in motor and psychiatric-like phenotypes. We observe improvements in neuropathological and electrophysiological phenotypes in BACHD/GFAP-CreERT2-tam mice compared to BACHD mice. We observed a restoration of the normal level αB-crystallin in the striatum of the BACHD/GFAP-CreERT2 mice, indicating a cell autonomous effect of mHTT on its expression. Taken together, this work indicates that astrocytes are important contributors to the progression of the behavioral and neuropathological phenotypes observed in HD.


Marrow donor immunity to herpes simplex virus: association with acute graft-versus-host disease.
The interactions between humoral and cellular immunity to herpes simplex virus (HSV) in bone marrow donors, the occurrence of active HSV infections, and the development of grades II-IV acute graft-versus-host disease (GVHD) in their HLA-A,B,C,DR-identical sibling recipients were studied. The absence of IgG-class HSV antibodies in the marrow donors was associated with a low incidence of GVHD: 38 of 53 recipients (72%) of marrow from HSV-seropositive donors developed GVHD versus only two of 15 recipients (13%) with HSV-seronegative donors (p = 0.0004). The cellular immunity to HSV was studied in vitro by evaluating the degree of lymphocyte proliferative responses to that virus and was also significantly associated with GVHD: 30 of 43 recipients (70%) of marrow from donors with a positive test developed GVHD versus 10 of 25 recipients (40%) of marrow from donors with a negative test (p = 0.03). The previously reported risk for GVHD attributed to donor CMV antibodies increased the risk of GVHD due to donor HSV antibodies. Of 31 recipients of marrow from donors who were both HSV- and CMV-seropositive, 27 (85%) developed GVHD versus 11 of 22 recipients (50%) of marrow from HSV-seropositive but CMV-seronegative donors (p = 0.008).


[An effective treatment by chemotherapy with CDDP+CPT-11 for recurrent gastric cancer which S-1 cannot be used owing to adverse effects].
We report a case of a 64-year-old man with multiple lung metastases after gastric cancer surgery. This patient was initially treated with S-1. However, he experienced adverse effects, and subsequently, he was effectively treated with cisplatin (CDDP) and irinotecan (CPT-11). In July 2010, the patient experienced a decrease in appetite and underwent a detailed examination. He also underwent distal gastrectomy in the same month. The postoperative diagnosis was T4a( SE), N2, M0, Stage IIIB. In November 2010, adjuvant chemotherapy with S-1 was initiated. In February 2011, the patient developed a skin disorder( grade 3) and generalized edema along with walking difficulty, which were identified as adverse effects of S-1. Evidently, S-1 was contraindicated for this patient, and adjuvant therapy was discontinued. In September 2011, contrast -enhanced thoracoabdominal computed tomography( CT) was performed and para-aortic lymph node metastasis and multiple lung metastases were detected. CDDP+CPT-11 therapy was initiated. By June 2012, 8 courses had been administered, and the patient had a good partial response. With regard to chemotherapy for advanced or recurrent gastric cancer, there is no consensus on a treatment policy for cases in which S-1 cannot be used owing to adverse effects. CDDP+CPT-11 therapy is considered a safe and effective choice.


A joint model for survival and longitudinal data measured with error.
The relationship between a longitudinal covariate and a failure time process can be assessed using the Cox proportional hazards regression model. We consider the problem of estimating the parameters in the Cox model when the longitudinal covariate is measured infrequently and with measurement error. We assume a repeated measures random effects model for the covariate process. Estimates of the parameters are obtained by maximizing the joint likelihood for the covariate process and the failure time process. This approach uses the available information optimally because we use both the covariate and survival data simultaneously. Parameters are estimated using the expectation-maximization algorithm. We argue that such a method is superior to naive methods where one maximizes the partial likelihood of the Cox model using the observed covariate values. It also improves on two-stage methods where, in the first stage, empirical Bayes estimates of the covariate process are computed and then used as time-dependent covariates in a second stage to find the parameters in the Cox model that maximize the partial likelihood.


Aminoglycoside adaptive resistance.
Aminoglycoside adaptive resistance is defined as reduced antimicrobial killing in originally susceptible bacterial populations after initial incubation with aminoglycoside. It is observed in vitro and in vivo, most commonly with Pseudomonas aeruginosa. It appears to correlate with a marked reduction in intracellular aminoglycoside accumulation, although its specific mechanism and the cellular structures responsible remain unknown in P. aeruginosa. Recent work suggests that adaptive resistance develops coincident with cytoplasmic membranes protein changes and regulated expression of genes in the anaerobic respiratory pathway of the organism. It is clinically most relevant in immunocompromised patients and in those with serious infections, especially infections due to gram-negative rods. Treatment of these patients by targeting high peak concentration:minimum inhibitory concentration ratios with once-daily dosing may result in the best outcome. A major unresolved issue concerns the effect of combination therapy on the development of aminoglycoside adaptive resistance.


Characterization of microRNAs expression profiles in human dental-derived pluripotent stem cells.
Induced pluripotent stem cells (iPSCs) technology provides a powerful means to generate and regenerate unlimited pluripotent stem cells directly from body tissue cells. Stem cells from apical papilla (SCAP) and Dental pulp stem cells (DPSCs) are present in 'cell-rich zones' within the dental pulp region, which are capable of regenerating pulp and dentin tissues in vivo. In this study, we investigated the difference of miRNAs expression in SCAPs and DPSCs before and after the reprogramming. Using miRNA microarray, 134 and 265 differentially expressed miRNAs in DPSCs- and SCAP-iPSCs were up-regulated compared to these before reprogramming. 117 specific miRNAs with enhanced more than 2-fold were identified in both DPSCs- and SCAP-iPSCs. Among the co-regulated miRNAs, miR-19a-3p, miR-92b-3p and miR-130b-3p showed the maximum difference, which had involvement in the cell cycle, TGF beta signaling pathway and epithelial mesenchymal transition. Using qRT-PCR analysis, the expression of miR-19a-3p, miR-92b-3p and miR-130b-3p indicated substantial increases in DPSCs-iPSCs and SCAP-iPSCs. The findings suggest that miRNAs play a part in the difference between DPSCs-iPSCs and DPSCs, as well as between SCAP-iPSCs and SCAP. The variation of miRNA expression in reprogrammed dental-derived pluripotent stem cells revealed different characteristics induced by iPSC generation.


Fertility therapies, infertility and autism spectrum disorders in the Nurses' Health Study II.
An increasing number of women are utilizing fertility treatments, but little is known about their relation to autism spectrum disorders (ASD). To determine the association between maternal fertility therapy use and risk of having a child with ASD, we conducted a nested case-control study within the Nurses' Health Study II (n = 116,430). Maternally reported diagnoses of ASD were confirmed through a supplementary questionnaire and, in a subgroup, the Autism Diagnostic Interview-Revised. Controls were randomly selected by frequency matching to case children's year of birth. Associations were examined by self-reported infertility and type of therapy using conditional logistic regression. In all, 9% of the 507 cases and 7% of 2,529 controls indicated fertility therapy use for the index pregnancy. No significant associations with self-reported fertility therapies or history of infertility were seen in primary analyses. In subgroup analyses of women with maternal age ≥ 35 years (n = 1,020), artificial insemination was significantly associated with ASD; ovulation inducing drug (OID) use was significantly associated in crude but not adjusted analyses (odds ratio 1.81, 95% CI 0.96-3.42). Results were similar by diagnostic subgroup, though within the advanced maternal age group, OID and artificial insemination were significantly associated with Asperger syndrome and pervasive developmental disorder not-otherwise specified, but not autistic disorder. [corrected] Assisted reproductive therapy and history of infertility did not increase risk of having a child with ASD in this study. However, the associations observed with OID and artificial insemination among older mothers, for whom these exposures are more common, warrant further investigation.


Histopathological aspects of some rare forms of facial basal cell carcinoma.
The main objective of the study was to highlight the histopathological aspects of some rare forms of facial basal cell carcinomas. The 65 selected patients were diagnosed with head basal cell carcinoma (BCC), during 2011-2013, and they underwent surgery. The excised tumor tissue fragments were processed for paraffin embedding and stained with Hematoxylin-Eosin (HE), Masson's trichrome with Aniline Blue, and Alcian Blue-Periodic Acid Schiff (AB-PAS). The youngest patient was 23 years old, while the oldest was 91 years. The facial BCC there was slightly higher prevalence in males of 34 out of 65 cases. Histopathologically, great varieties of morphological types have been identified in the 65 cases investigated. According to our data, by far the most common are nodular BCCs type, which represented 44.6% from the investigated cases, followed at some distance by morpheiform and superficial subtypes with 13.8% and 10.7%, respectively. The most rare cases of facial BCCs were: cystic, adenoid, fibroepithelial and basal with adnexal differentiation with in one single case each. Relatively rare were the following varieties: pigmented (four cases), combinations of several forms (four cases), metatypical (three cases), keratotic (three cases), and micronodular (two cases). Within the limits of this study, the data reported here shown that such a lesional pleomorphism very often requires to make a careful differential diagnosis with a number of other tumor or non-tumor entities.


Increased SCF in Follicular Fluid and Granulosa Cells Positively Correlates With Oocyte Maturation, Fertilization, and Embryo Quality in Humans.
Stem cell factor (SCF), which is derived from granulosa cells (GCs), plays a key role in the process of follicular development and oocyte maturation. The present study aimed to explore whether the levels of SCF in follicular fluid (FF) and GCs can be used as a potential marker for predicting oocyte developmental potential. Follicular fluid and GC samples from 150 female patients undergoing intracytoplasmic sperm injection were collected in this study. The SCF concentrations in FFs and SCF messenger RNA (mRNA) in GCs were evaluated by using enzyme-linked immunosorbent assay and real-time polymerase chain reaction, respectively. The results showed that the levels of SCF protein and mRNA were significantly associated with oocyte maturation, normal fertilization, cleavage, and embryo quality. Moreover, the levels of SCF protein and mRNA in pregnancy group were also higher than those in the nonpregnancy group. The cutoff value of SCF in FF for predicting high-quality embryo was 1.346, with a sensitivity of 57.8% and a specificity of 72.4%, and the cutoff value of SCF in GCs for predicting high-quality embryo was 6.650, with a sensitivity of 64.4% and a specificity of 78.1%. In conclusion, our results showed a positive and statistically significant relationship between SCF level and oocyte maturation, normal fertilization, cleavage, embryo quality, and clinical pregnancy. Therefore, the levels of SCF in FF and GCs might be considered as a new marker for predicting oocyte developmental potential.


Venous thromboembolism in adults screened for sickle cell trait: a population-based cohort study with nested case-control analysis.
To determine whether sickle cell carriers ('sickle cell trait') have an increased risk of venous thromboembolism (VTE). Cohort study with nested case-control analysis. General population with data from 609 UK general practices in the Clinical Practice Research Datalink (CPRD). All individuals registered with a CPRD general practice between 1998 and 2013, with a medical record of screening for sickle cell between 18 and 75 years of age. Incidence of VTE per 10 000 person-years (PY) among sickle cell carriers and non-carriers; and adjusted OR for VTE among sickle cell carriers compared with non-carriers. We included 30 424 individuals screened for sickle cell, with a follow-up time of 179 503 PY, identifying 55 VTEs in 6758 sickle cell carriers and 125 VTEs in 23 666 non-carriers. VTE incidence among sickle cell carriers (14.9/10 000 PY; 95% CI 11.4 to 19.4) was significantly higher than non-carriers (8.8/10 000 PY; 95% CI 7.4 to 10.4). Restricting analysis to confirmed non-carriers was non-significant, but performed on a small sample. In the case-control analysis (180 cases matched to 1775 controls by age and gender), sickle cell carriers remained at increased risk of VTE after adjusting for body mass index, pregnancy, smoking status and ethnicity (OR 1.78, 95% CI 1.18 to 2.69, p=0.006), with the greatest risk for pulmonary embolism (PE) (OR 2.27, 95% CI 1.17 to 4.39, p=0.011). Although absolute numbers are small, in a general population screened for sickle cell, carriers have a higher incidence and risk of VTE, particularly PE, than non-carriers. Clinicians should be aware of this elevated risk in the clinical care of sickle cell carriers, or when discussing carrier screening, and explicitly attend to modifiable risk factors for VTE in these individuals. More complete primary care coding of carrier status could improve analysis.


Navigating Monogamy: Nonapeptide Sensitivity in a Memory Neural Circuit May Shape Social Behavior and Mating Decisions.
The role of memory in mating systems is often neglected despite the fact that most mating systems are defined in part by how animals use space. Monogamy, for example, is usually characterized by affiliative (e.g., pairbonding) and defensive (e.g., mate guarding) behaviors, but a high degree of spatial overlap in home range use is the easiest defining feature of monogamous animals in the wild. The nonapeptides vasopressin and oxytocin have been the focus of much attention for their importance in modulating social behavior, however this work has largely overshadowed their roles in learning and memory. To date, the understanding of memory systems and mechanisms governing social behavior have progressed relatively independently. Bridging these two areas will provide a deeper appreciation for understanding behavior, and in particular the mechanisms that mediate reproductive decision-making. Here, I argue that the ability to mate effectively as monogamous individuals is linked to the ability to track conspecifics in space. I discuss the connectivity across some well-known social and spatial memory nuclei, and propose that the nonapeptide receptors within these structures form a putative "socio-spatial memory neural circuit." This purported circuit may function to integrate social and spatial information to shape mating decisions in a context-dependent fashion. The lateral septum and/or the nucleus accumbens, and neuromodulation therein, may act as an intermediary to relate socio-spatial information with social behavior. Identifying mechanisms responsible for relating information about the social world with mechanisms mediating mating tactics is crucial to fully appreciate the suite of factors driving reproductive decisions and social decision-making.


Hyoid bone insertion tendinitis: clinicopathologic correlation.
Hyoid bone insertion tendinitis is often not taken into consideration in clinical practice and neglected in the differential diagnosis while evaluating patients with chronic neck pain. One of the main important reasons why physicians do not bear this entity in mind is that it has not been well described histopathologically. Two patients, who had been diagnosed and treated surgically for hyoid bone insertion tendinitis, were presented in this study. Microscopically, degenerative changes in the striated muscle tissue, which are characterized by myocyte necrosis, atrophy along with fibrosis and calcification in some foci, were observed. These findings provide evidence for the clinical picture of hyoid bone insertion tendinitis.


Sequence and phylogenetic analysis of SH, G, and F genes and proteins of Human respiratory syncytial virus isolates from Singapore.
To study the genetic variability and molecular epidemiology of Human respiratory syncytial virus (HRSV) occurring in Singapore, nucleotide sequencing of three membrane-associated genes (SH, G and F) of four local isolates was performed. Comparison of their nucleotide and amino acid sequences with those of the prototype strains A2 (subgroup A) and CH-18537 (subgroup B) indicated that the Singapore isolates belong to the subgroup A. Comparison of the Singapore isolates with the reference strain A2 showed that whereas the G protein was the most divergent with up to 15% difference, the F and SH proteins showed less diversity of only up to 4%. Each gene exhibited its distinct variable and conserved regions. The N- and O-glycosylation sites within the G protein of the isolates were analyzed to ascertain their potential implications on the antigenicity of the viral glycoprotein. Based on the second variable region of the G protein, phylogenetic analysis of the Singapore isolates with 91 previously identified genotypes of subgroup A revealed that more than one genotype (GA2 and GA5) may circulate in the local population at a given time. This epidemiological study reflects the pattern of genetic relationships between the HRSV isolates from Singapore to those from other parts of the world.


Function and phenotype of immature CD4+ lymphocytes in healthy infants and early lymphocyte activation in uninfected infants of human immunodeficiency virus-infected mothers.
The function and phenotypes of CD4+ lymphocytes in infants are different than in adults and are modulated by maturational changes and exposure to environmental antigens. Infants of non-human immunodeficiency virus (HIV)-infected mothers and uninfected infants of HIV-infected mothers, 0 to 6 months of age, were examined for CD4+ lymphocyte function by in vitro interleukin-2 (IL-2) production and for CD4+ phenotypes by three-color flow cytometry. A minority of these uninfected infants (28%) had functional responses similar to those of healthy adult women (IL-2 production in response to anti-CD3, alloantigen, and mitogen), while the remainder were capable of responding to alloantigen and mitogen but not to anti-CD3. We did demonstrate reduced phytohemagglutinin-stimulated IL-2 production in uninfected infants born to HIV-seropositive mothers compared to that in infants from seronegative mothers. The proportions of CD3+ CD4+, CD4+ HLA-DR- CD38+, and CD4+ CD45RA+ RO- (naive) lymphocytes were much higher in infants than in adults, and the proportions of CD4+ CD45RA- RO+ (memory) and CD4+ CD25+ (IL-2 receptor-bearing) lymphocytes were lower in infants than in adults. The proportions of activated (CD4+ HLA-DR+ CD38+) and memory (CD4+ CD45RA- RO+) lymphocytes were increased in uninfected infants of HIV-infected mothers compared to infants of uninfected mothers. Therefore, T-helper-cell function is immature in many infants, but the CD4+ lymphocytes of some HIV-exposed, uninfected infants have been stimulated by antigen at an early age.


Prevalence of and factors associated with albuminuria in the Korean adult population: the 2011 Korea National Health and Nutrition Examination Survey.
Microalbuminuria is associated with increased risk of renal disease and cardiovascular diseases even in non-diabetic subjects. High incidence rates of microalbuminuria have been found in a number of population-based studies. However, the prevalence and risk factors associated with microalbuminuria in the general population in Korea are unclear. The present study was performed to estimate the prevalence of microalbuminuria and investigate the associated risk factors in the general adult population using the Fifth Korea National Health and Nutrition Examination Survey (KNHANES V-2) data from 2011. A total of 5,202 participants (mean age, 45.6 years; men, 2,337; women, 2,865) were included in the analysis. Microalbuminuria was evaluated in participants of KNHANES V-2 based on the urine albumin-creatinine ratio. Estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease study equation. The weighted prevalence of microalbuminuria was 5.2% (95% CI, 4.4-6.1) in the general population. The prevalence of albuminuria is increased with age. After adjustment for age and sex, the presence of albuminuria was associated with increased waist circumference, systolic and diastolic blood pressure, aspartate aminotransferase, triglyceride, fasting plasma glucose, and the presence of hypertension and diabetes. In logistic regression analyses, older age, female sex, diabetes, hypertension, and serum aspartate aminotransferase were independently associated with the presence of albuminuria. The prevalence of microalbuminuria was found to be 5.2%, and conventional risk factors for cardiovascular diseases are closely related to the presence of microalbuminuria in Korea. Microalbuminuria may be a useful marker to identify individuals with increased risk of cardiovascular disease.


Rapid fabrication of nickel molds for prototyping embossed plastic microfluidic devices.
The production of hot embossed plastic microfluidic devices is demonstrated in 1-2 h by exploiting vinyl adhesive stickers as masks for electroplating nickel molds. The sticker masks are cut directly from a CAD design using a cutting plotter and transferred to steel wafers for nickel electroplating. The resulting nickel molds are used to hot emboss a variety of plastic substrates, including cyclo-olefin copolymer and THV fluorinated thermoplastic elastomer. Completed devices are formed by bonding a blank sheet to the embossed layer using a solvent-assisted lamination method. For example, a microfluidic valve array or automaton and a droplet generator were fabricated with less than 100 μm x-y plane feature resolution, to within 9% of the target height, and with 90 ± 11% height uniformity over 5 cm. This approach for mold fabrication, embossing, and bonding reduces fabrication time and cost for research applications by avoiding photoresists, lithography masks, and the cleanroom.


Immune checkpoints and cancer immunotherapies: insights into newly potential receptors and ligands.
Checkpoint markers and immune checkpoint inhibitors have been increasingly identified and developed as potential immunotherapeutic targets in various human cancers. Despite valuable efforts to discover novel immune checkpoints and their ligands, the precise roles of their therapeutic functions, as well as the broad identification of their counterpart receptors, remain to be addressed. In this context, it has been suggested that various putative checkpoint receptors can be induced upon activation. In the tumor microenvironment, T cells, as crucial immune response against malignant diseases as well as other immune central effector cells, such as natural killer cells, are regulated via co-stimulatory or co-inhibitory signals from immune or tumor cells. Studies have shown that exposure of T cells to tumor antigens upregulates the expression of inhibitory checkpoint receptors, leading to T-cell dysfunction or exhaustion. Although targeting immune checkpoint regulators has shown relative clinical efficacy in some tumor types, most trials in the field of cancer immunotherapies have revealed unsatisfactory results due to de novo or adaptive resistance in cancer patients. To overcome these obstacles, combinational therapies with newly discovered inhibitory molecules or combined blockage of several checkpoints provide a rationale for further research. Moreover, precise identification of their receptors counterparts at crucial checkpoints is likely to promise effective therapies. In this review, we examine the prospects for the application of newly emerging checkpoints, such as T-cell immunoglobulin and mucin domain 3, lymphocyte activation gene-3, T-cell immunoreceptor with Ig and ITIM domains (TIGIT), V-domain Ig suppressor of T-cell activation (VISTA), new B7 family proteins, and B- and T-cell lymphocyte attenuator, in association with immunotherapy of malignancies. In addition, their clinical and biological significance is discussed, including their expression in various human cancers, along with their roles in T-cell-mediated immune responses.


Association of Familial Hyperkalemia and Hypertension (FHHt) with proximal renal tubular acidosis and epileptic seizures.
Abstract: Introduction: Familial Hyperkalemic Hypertension (FHHt) is an inherited disease characterized by hyperkalemia, hypertension and hyperchloremic acidosis. The primary defect is a hyperactive sodium chloride co-transporter, expressed in the renal distal tubule (DCT). FHHt is caused by mutation in either, WNK1, WNK4, KLHL3 or Cul3. The mechanism of hyperchloremic acidosis is not completely understood. Clinical and genetic data were collected from the largest family with FHHt described in the literature. Urine ammonia was measured in 26 family members. Epilepsy was diagnosed clinically. Of the 85 family members, 44 are affected by the Q565E WNK4 mutation, and 28 are newly described. In genetically engineered mice urinary ammonium was decreased. In our study, urine ammonium did not change. In 11 unaffected subjects urine ammonia per creatinine was 8.013±3.620 mM/mM , and in 15 subjects affected by FHHt it was 8.990± 4.300 mM/mM (p=0.546, not significant). Due to the large family size and prolonged follow up, rare conditions can be identified. Indeed, two children have genetic generalized epilepsy, and one child has migraine. The prevalence of epilepsy is 4.545% (2/44) much higher than in the general population ( 0.681%). This difference is statistically significant (Chi square with Yates correction = 5.127, P =0.023). We provide further evidence that the origin of hyperchloremic acidosis in FHHt lies in the proximal renal tubule. The association of FHHt with epilepsy leads us to speculate that the raised serum K in susceptible subjects may cause a rise in CSF K, and extracellular cerebral K, leading to epilepsy.


TCA cycle tailoring facilitates optimal growth of proton-pumping NADH dehydrogenase-dependent Escherichia coli.
The bacterial lifestyle is plastic, requiring transcriptional, translational, and metabolic tailoring for survival. These dynamic cellular processes are energy intensive; therefore, flexible energetics is requisite for adaptive plasticity. An intricate network of complementary and supplementary pathways exists in bacterial energy metabolism. There are two main entry points for electrons in the aerobic electron transport system, NADH dehydrogenase (NDH) and succinate dehydrogenase (SDH), receiving electrons from NADH and succinate, respectively. Aerobic bacterial phyla have a non-proton-pumping NADH dehydrogenase, which is often the primary dehydrogenase under aerobiosis. Here, we report adaptive changes supporting growth restoration in an Escherichia coli strain lacking the primary dehydrogenase. Growth optimization is achieved by reducing the activity of succinate dehydrogenase, and thus we demonstrate a physiological discord between proton-pumping NADH dehydrogenase and succinate dehydrogenase in supporting growth. Beyond the fundamental understanding of the bioenergetic network, identifying this compensatory feature provides impetus to rational antimicrobial combinations for targeting the non-proton-pumping dehydrogenase. IMPORTANCE Energy generation pathways are a potential avenue for the development of novel antibiotics. However, bacteria possess remarkable resilience due to the compensatory pathways, which presents a challenge in this direction. NADH, the primary reducing equivalent, can transfer electrons to two distinct types of NADH dehydrogenases. Type I NADH dehydrogenase is an enzyme complex comprising multiple subunits and can generate proton motive force (PMF). Type II NADH dehydrogenase does not pump protons but plays a crucial role in maintaining the turnover of NAD+. To study the adaptive rewiring of energy metabolism, we evolved an Escherichia coli mutant lacking type II NADH dehydrogenase. We discovered that by modifying the flux through the tricarboxylic acid (TCA) cycle, E. coli could mitigate the growth impairment observed in the absence of type II NADH dehydrogenase. This research provides valuable insights into the intricate mechanisms employed by bacteria to compensate for disruptions in energy metabolism.


[Angiosarcoma of the temporal bone].
A case of 55-yrs old female was reported, in whom angiosarcoma of temporal bone had been diagnosed. A mode of treatment was surgery including partial petrosectomy and labyrinthectomy. Radiotherapy was not given because of a possibility of further cerebrospinal liquid leakage after dura mater rupture, which was seen during first operation. Local recurrence had developed about 2 months after surgery and a patient died 10 months after the time of diagnosis. It was stressed that angiosarcoma is a very rare neoplasm and in our case it was presented as few--symptomatic lesion despite of it's high extent in temporal bone. A review of literature concerning angiosarcoma was also reported.


Pulmonary nodules: detection with low-dose vs conventional-dose spiral CT.
The purpose of the study was the evaluation of low-dose spiral CT in the detection and assessment of contours of pulmonary nodules. In a prospective investigation 71 consecutive chest CT examinations were acquired both at 30 and 200 mA. Films were interpreted independently by two radiologists. According to the size, nodules were divided into four categories: </= 3, 4-5, 6-10, and > 10 mm; nodule shape was registered. With both protocols, 240 nodules were detected. The correlation coefficient for both methods was 0.89. Discrepancies were found most frequently in nodules near to pulmonary vessels. Nodule size estimation did not differ more than one size category. Eight spiculated nodules were identified by both techniques. Low-dose spiral CT of the chest has a high sensitivity in the detection of pulmonary nodules. If clinical circumstances require dose minimization, low-dose spiral CT may be advocated as an alternative screening method to conventional dose spiral CT.


[The clinical incidence of frontal dementia].
Although the neuropathology of Pick s disease and the frontal lobe dementias has been well defined, the complexity of the clinical diagnosis makes epidemiological studies difficult. The objective of this study was to determine the annual clinical incidence of fronto temporal dementia. A retrospective observational study was made of the diagnoses of all persons attended in UVAMID during the period 1999 2000. Clinical evaluation was standardized following a protocol of the UVAMID. This included a clinical history obtained by interviewing the patient and a reliable informant, general medical and neurological examination, neuropsychological examination and a battery of complementary tests. In clinical practice the incidence of the different types of dementia varies between 93/100,000 in Alzheimer type dementia and 14/100,000 in DFT f. When age groups are considered, there is a progressive increase in the incidence of DFT f with 12/100,000 in the age group 46 69 years and 57/100,000 in the group of 75 79 years. The results of this study show that cases of DFT f form 2.7% of the new cases occurring annually. The main limitation of this study is that since these patients were referred for consultation from primary care centres, they form a non representative clinically biased sample which limits extrapolation of the results.


The efficacy and safety of additional bypass graft during isolated coronary artery bypass grafting.
In 19 patients with an undesirable hemodynamic condition (n=15) or with regional asynergy and coexistent ST-T change (n=4) during isolated coronary artery bypass grafting (CABG) surgery, one (n=17) or two (n=3) additional saphenous vein grafts were placed onto left anterior descending (LAD) (n=16), right (n=4), and left circumflex (LCx) (n=2) coronary arteries. Diagnosis of the cause of the suboptimal condition was insufficient graft flow in 16 patients, and spasm of the ungrafted coronary artery in 3. Additional myocardial ischemic time was 17 9 minutes, and the graft flow was 59 25 ml/min. Additional bypass was effective in 94.5%. Eighteen patients could be weaned from cardiopulmonary bypass, and 17 (89.5%) survived and were discharged from hospital. Median duration of mechanical ventilatory support and intensive care unit stay was 15 hours and 4 days, respectively. During 63 44 months follow-up, the additional graft was occluded and the treadmill test was positive for ischemia in 2 patients, and one child patient is now considered for redo CABG. Placement of additional bypass grafts thus appeared to be an effective and relatively safe strategy, although the decision has to be made cautiously.


Infrared emission spectra and equilibrium bond lengths of gaseous ZnH2 and ZnD2.
A detailed analysis of the high resolution infrared emission spectra of gaseous ZnH2 and ZnD2 in the 800-2200 cm(-1) spectral range is presented. The nu3 antisymmetric stretching fundamental bands of 64ZnH2, 66ZnH2, 67ZnH2, 68ZnH2, 64ZnD2, 66ZnD2 and 68ZnD2, as well as several hot bands involving nu1, nu2 and nu3 were rotationally analyzed, and spectroscopic constants were obtained. Rotational l-type doubling and l-type resonance, local perturbations, and Fermi resonances were observed in the vibration-rotation bands of both ZnH2 and ZnD2, and equilibrium vibrational frequencies (omega1, omega2 and omega3) were estimated. Using the rotational constants of the 000, 100, 01(1)0 and 001 vibrational levels, the equilibrium rotational constants (B(e)) of 64ZnH2 and 64ZnD2 were determined to be 3.600 269(31) cm(-1) and 1.801 985(25) cm(-1), respectively, and the associated equilibrium bond lengths (r(e)) are 1.524 13(1) angstroms and 1.523 94(1) angstroms, respectively. The difference between the r(e) values of 64ZnH2 and 64ZnD2 is about 0.01%, and is mainly due to the breakdown of the Born-Oppenheimer approximation.


Anesthesiologist preference for postoperative analgesia in major surgery patients with obstructive sleep apnea.
Obstructive sleep apnea (OSA) is prevalent and presents perioperative challenges. There are guidelines regarding perioperative care of OSA, but analgesia management of OSA patients is inconsistent or inadequate. This is a study of the United Kingdom anesthesiologists' postoperative analgesia preferences for OSA patients. Overall, the 1st choice of main analgesia was continuous epidural local anesthetic (LA) without opioid, at 30% rate; P = 0.001. The 2nd choice was continuous epidural LA plus fentanyl, at 21% rate; P = 0.001. The 3rd choice was intrathecal diamorphine, at 19% rate; P = 0.001. The 4th choice was nerve block catheter LA infusion, at 13% rate; P = 0.001. The 5th choice was wound infiltration with LA ± epinephrine, at 8% rate; P = 0.001. The 6th choice was systemic opioid, at 7% rate; P = 0.007. The 7th choice was systemic nonsteroidal anti-inflammatory drugs, at 2% rate; P = 0.001. The hospital setting or anesthesiologists' experience did not significantly impact analgesia choice: P =0.411. This study shows that current practice by anesthesiologists has a preference for regional or opioid-sparing analgesia for OSA patients. This safe approach conforms to guidelines and should be encouraged.


Dermatofibrosarcoma Protuberans: Pathological and Imaging Review.
Dermatofibrosarcoma protuberans (DFSP) is a rare, low-to-intermediate grade sarcoma that typically arises in the dermis and infiltrates subcutaneous tissue. Due to superficial appearance of DFSP, imaging techniques are not always utilized. However, they may be useful in large or atypical cases. The standard treatment for DFSP is excision of the lesion. In this article, we review the role of different imaging modalities in the assessment and management of DFSP.


Chikungunya Virus Infections Among Patients with Dengue-Like Illness at a Tertiary Care Hospital in the Philippines, 2012-2013.
Chikungunya virus (CHIKV) often co-circulates with dengue virus (DENV). A cross-sectional surveillance study was conducted at a tertiary hospital in Manila, Philippines, to describe the prevalence and characteristics of DENV and CHIKV infections among patients seeking care for dengue-like illness. Acute blood samples from patients ≥ 6 months of age clinically diagnosed with dengue from November 2012 to December 2013 underwent reverse transcription polymerase chain reaction (RT-PCR) to detect DENV and CHIKV RNA. A total of 118 patients with clinically diagnosed dengue (age range = 1-89 years, mean = 22 years; male-to-female ratio = 1.51) were tested by DENV RT-PCR; 40 (34%) were DENV PCR-positive (age range = 1-45 years, mean = 17 years). All DENV serotypes were detected: 11 (28%) DENV-1, 6 (15%) DENV-2, 6 (15%) DENV-3, and 17 (42%) DENV-4. Of 112 patients clinically diagnosed with dengue and tested by CHIKV RT-PCR, 11 (10%) were CHIKV PCR-positive (age range = 2-47 years, mean = 20.3 years). No coinfections were detected. Presenting signs/symptoms did not differ between DENV- and CHIKV-positive cases. Sequencing of envelope 1 gene from two CHIKV PCR-positive samples showed Asian genotype. This study highlights the potential for misdiagnosis of medically attended CHIKV infections as DENV infection and the difficulty in clinically differentiating dengue and chikungunya based on presenting signs/symptoms alone. This underscores the necessity for diagnostic laboratory tests to distinguish CHIKV infections in the background of actively co-circulating DENV.


Quantitative bone scintigraphy using SPECT.
A quantitative single photon emission computed tomography (SPECT) technique for measuring radiopharmaceutical uptake in humans has been applied to bone scintigraphy. The method was validated by comparing SPECT measured percent of injected [99mTc]MDP in 16 normal skulls with well counter measurements of samples of the same bones obtained at surgery. A very good correlation (r = 0.96) was found. A very good interobserver correlation (r = 0.99) and agreement were also obtained when using quantitative bone scintigraphy (QBS). Control SPECT studies of uptake in the right and left iliac bones and the right and left sacroiliac regions in each patient showed no significant differences between the contralateral sides. Studies done in seven subjects at 2 and 4 hr after the same injection and in nine subjects 4 to 8 mo later in the same subjects showed a very good agreement and no significant differences between the two measurements were found. QBS is suggested as an accurate and reproducible index for assessment of the mass of remodeling bone. Preliminary results showed differences in QBS of normal subjects at different ages. A group of 68 young patients aged 18-26 yr showed a significant higher QBS (p less than 0.001) when compared to an older group of 62 patients aged 50-85 yr. There was, however, a wide range of uptake values for the same bone in the same group, suggesting that the method should best be used for following individual patients over time.


Unfolding the Role of Calreticulin in Myeloproliferative Neoplasm Pathogenesis.
In 2013, two seminal studies identified gain-of-function mutations in the Calreticulin (CALR) gene in a subset of JAK2/MPL-negative myeloproliferative neoplasm (MPN) patients. CALR is an endoplasmic reticulum (ER) chaperone protein that normally binds misfolded proteins in the ER and prevents their export to the Golgi and had never previously been reported mutated in cancer or to be associated with hematologic disorders. Further investigation determined that mutated CALR is able to achieve oncogenic transformation primarily through constitutive activation of the MPL-JAK-STAT signaling axis. Here we review our current understanding of the role of CALR mutations in MPN pathogenesis and how these insights can lead to innovative therapeutics approaches.


CT and MRI assessment of symptomatic organized pancreatic fluid collections and pancreatic duct disruption: an interreader variability study using the revised Atlanta classification 2012.
Compare CT and MRI for fluid/debris component estimate and pancreatic duct (PD) communication with organized pancreatic fluid collections in acute pancreatitis. Evaluate fat density globules on CT as marker for debris. 29 Patients with 46 collections with CECT and MRI performed ≥4 weeks of symptom onset assessed for necrotizing pancreatitis, estimated percentage of fluid volume and PD involvement by two radiologists on separate occasions. T2WI used as standard for estimated percentage of fluid volume. Presence of fat globules and fluid attenuation on CT was recorded. Spearman rank correlation and kappa statistics were used to assess the correlation between imaging techniques and interreader agreement, respectively. Necrotizing pancreatitis seen on CT in 27 (93%, κ 0.119) vs. 20 (69%, κ 0.748) patients on MRI. CT identified 42 WON and 4 pseudocysts vs. 34 WON, and 12 pseudocysts on MRI. Higher interreader agreement for percentage fluid volume on MRI (κ = 0.55) vs. CT (κ = 0.196). Accuracy of CT in evaluation of percentage fluid volume was 65% using T2WI MRI used as standard. Fat globules identified on CT in 13(65%) out of 20 collections containing <75% fluid vs. 4(15%) out of 26 collections containing >75% fluid (p = 0.0001). PD involvement confidently excluded on CT in 68% collections vs. 93% on MRI. MRI demonstrates higher reproducibility for fluid to debris component estimation. Fat globules on CT were frequently seen in organized pancreatic fluid collections with large amount of debris. PD disruption more confidently excluded on MRI. This information may be helpful for pre-procedure planning.