Outcomes of high-risk obstetric transfers in New South Wales and the Australian Capital Territory: The High-Risk Obstetric Transfer Study.
In New South Wales and the Australian Capital Territory, in utero transfers to manage maternal or neonatal risks are highly challenging owing to geography and centralisation of tertiary perinatal care. The study aims to document the outcomes of high-risk obstetric transfers. A prospective observational study was conducted from 2010 to 2011 documenting urgent requests for obstetric transfers to tertiary centres across NSW/ACT for pregnancies 20 weeks' gestation or greater. Outcomes of transfers were allocated apriori to 'delivered at the receiving hospital', 'failed/delayed transfer' or 'discharged/transferred undelivered'. Our hypothesis is that each outcome has a specific group of associated clinical factors. Of the 249 transfer requests included in the study, 40% delivered at the receiving hospital, 7% were failed/delayed transfers, and 45% were discharged/transferred undelivered. Cases delivering at the receiving hospital were significantly associated with older mothers, twin pregnancies, pregnancy induced hypertension (PIH) or premature rupture of membranes (PROM) with/without threatened preterm labour (TPL) as the indications for transfer and having three indications for transfer. Cases that were discharged/transferred undelivered were significantly associated with singleton pregnancies, TPL and/or antepartum haemorrhage (APH) as the indication for transfer and having one indication for transfer. There were no significantly associated factors for failed/delayed transfers. The study confirms the hypothesis that particular transfer outcomes are associated with different factors. The findings also show that less than half of urgent obstetric transfers result in delivery at the receiving hospital, suggesting that there exists significant opportunities for further research into predicting preterm delivery, thereby improving the care of women with high-risk pregnancies.


A SPECT imaging study of MRI white matter hyperintensity in patients with degenerative dementia.
We investigated the correlation between cortical perfusion and white matter hyperintensities on magnetic resonance images (MRI) of patients with dementia. The study included 40 subjects, each of whom had undergone both MRI and single-photon emission computed tomography (SPECT) studies as part of their diagnostic evaluation for degenerative dementia. Two neuroradiologists rated the MRI films for severity of periventricular white matter changes on a 0-5 point scale and severity of subcortical white matter changes on a 0-4 point scale. Twelve regions of interest from association cortex were sampled for the semiquantitative analysis of SPECT images. No relationship was found between these global MRI ratings and semiquantitative or qualitative SPECT findings. Dementia severity as measured by the Mini-Mental State Examination and the Clinical Dementia Rating was significantly correlated with SPECT, whereas age was significantly correlated with MRI ratings, particularly in the periventricular regions. These data support the view that cortical SPECT abnormalities are not associated with global MRI abnormalities in the subcortical and periventricular regions of patients with a clinical picture of degenerative dementia.


Prolonged activation of innate antiviral gene signature after childbirth is determined by IFNL3 genotype.
Maternal innate and adaptive immune responses are modulated during pregnancy to concurrently defend against infection and tolerate the semiallogeneic fetus. The restoration of these systems after childbirth is poorly understood. We reasoned that enhanced innate immune activation may extend beyond gestation while adaptive immunity recovers. To test this hypothesis, the transcriptional profiles of total peripheral blood mononuclear cells following delivery in healthy women were compared with those of nonpregnant control subjects. Interestingly, interferon-stimulated genes (ISGs) encoding proteins such as IFIT1, IFIT2, and IFIT3, as well as signaling proteins such as STAT1, STAT2, and MAVS, were enriched postpartum. Antiviral genes were primarily expressed in CD14(+) cells and could be stratified according to genetic variation at the interferon-λ3 gene (IFNL3, also named IL28B) SNP rs12979860. Antiviral gene expression was sustained beyond 6 mo following delivery in mothers with a CT or TT genotype, but resembled baseline nonpregnant control levels following delivery in mothers with a CC genotype. CT and TT IFNL3 genotypes have been associated with persistent elevated ISG expression in individuals chronically infected with hepatitis C virus. Together, these data suggest that postpartum, the normalization of the physiological rheostat controlling IFN signaling depends on IFNL3 genotype.


Oxidative Stress Indices as Markers of Lead and Cadmium Exposure Toxicity in Auto Technicians in Ibadan, Nigeria.
Auto technicians (auto mechanics, panel beaters, battery chargers, and auto painters) are among the most valuable work force in the society. Reports on oxidative stress in persons occupationally exposed to mixed chemicals abound; however, few have narrowed down specifically on auto technicians, while even fewer have stratified the exposure in the different subgroups of auto technicians. This study evaluated the antioxidant status in auto technicians routinely exposed to lead and cadmium and stratified the results of exposure by different subgroups of auto technicians in Ibadan, Nigeria. Sixty-five apparently healthy males (aged 18 to 65years) were selected based on specific inclusion criteria using a structured questionnaire. Thirty-four were cases consisting of participants routinely working as auto technicians or apprentices(≥2years) while controls were thirty-one nonoccupationally exposed male members of staff/students of the University College Hospital, Ibadan, Nigeria. Blood was collected from all participants and analyzed for the presence of lead, total antioxidant capacity (TAC), and total plasma peroxides (TPP); oxidative stress index (OSI) was calculated. Urine samples collected from all participants were analyzed for the presence of urinary lead and cadmium using standard laboratory methods. Although values of TAC in cases (22538 ± 8726.54) were not statistically different from what was obtained in controls (26741.87 ± 8696.68), TPP and OSI were statistically higher in cases than in controls (183.88 ± 53.39 and 120.16 ± 70.54, respectively, and 0.93 ± 0.45 and 0.49 ± 0.33, respectively). The blood lead level in cases (10.11 ± 4.47) was significantly higher than in controls (7.72 ± 1.22) while elevated urinary lead and cadmium levels were observed in cases (0.65 ± 0.21 and 0.34 ± 0.11, respectively) compared to controls (0.52 ± 0.19 and 0.27 ± 0.10, respectively). Raised TPP and OSI levels-hallmark of active lipid peroxidation-found to be highest among panel beaters compared to others may be prognostic of membrane-damaging diseases in this subgroup of auto technicians.


Marital status and risk for late life depression: a meta-analysis of the published literature.
This study assessed the relationship between marital status and the risk for depression in people ≥ 55 years old. Using the Medline™, EMBASE™ and Cochrane Library databases, clinical studies that published data on the association between marital status and risk of depression among individuals aged ≥ 55 years were identified. A quantitative meta-analysis of 24 cross-sectional and eight longitudinal studies was performed. Compared with married elderly people, unmarried elderly people had a higher risk for depression (odds ratio [OR], 1.55; relative risk [RR], 1.36). Compared with married elderly people, the widowed elderly people (OR 1.49; RR 1.71), divorced people (RR 2.14) and never-married people (OR 1.32) had a higher risk for depression. Among elderly unmarried people, widowed people had a higher risk for depression than those who never married (OR 1.51). In conclusion, being unmarried was an important risk factor for depression in elderly people.


Anti-human thyroid peroxidase and anti-human thyroglobulin antibodies present no cross-reactivity on recombinant peptides.
Thyroglobulin (Tg) and thyroid peroxidase (TPO) are two antigens largely recognized by the sera from patients with autoimmune thyroid disease (AITD). Recently, the complete mapping of both antigens was established with rabbit polyclonal antibodies by the use of recombinant proteins expressed in prokaryotic vector. Several investigators have argued for the existence of a cross-reactivity of some hetero- and autologous antibodies versus these two proteins. In the present study, using rabbit polyclonal antibody, mouse polyclonal antibody and autoimmune antibody (aAb), we observed no common epitope on human Tg (hTg) and human TPO (hTPO).


Development of flowering plant gametophytes.
Plant reproduction occurs through the production of gametes by a haploid generation, the gametophyte. Flowering plants have highly reduced male and female gametophytes, called pollen grains and embryo sacs, respectively, consisting of only a few cells. Gametophytes are critical for sexual reproduction, but detailed understanding of their development remains poor as compared to the diploid sporophyte. This article reviews recent progress in understanding the mechanisms underlying gametophytic development and function in flowering plants. The focus is on genes and molecules involved in the processes of initiation, growth, cell specification, and fertilization of the male and female gametophytes derived primarily from studies in model systems.


Is this a man's world? The effect of gender diversity and gender equality on firm innovativeness.
Gender diversity is known to have a positive effect on innovation in developed countries. However, it is unclear whether the benefits of gender diversity for innovation also apply to the particular context of developing countries, which is characterized by diverse and lower levels of gender equality. We propose that gender diversity positively impacts innovation in the developing countries participating in our study. In addition, we expect that this effect is moderated by country-specific levels of gender equality. In a cross-country study covering 18,547 firms in 15 developing countries, we find that gender diversity among a firm's owners and workforce as well as having a female top manager benefit innovation in developing countries. Yet, contradictory to our expectations, gender equality does not significantly moderate this relationship. As such, our results underline the importance of enabling and fostering gender diversity and have critical implications for firms and policy makers alike.


The role of T cell costimulation by CD80 in the initiation and maintenance of the immune response to human leukemia.
Most human myeloid leukemias express both class I and class II HLA and it has been postulated that leukemia-associated peptides are presented by those molecules. It is possible, however, that leukemia cells escape the immune surveillance by lacking expression of "costimulatory" molecules required for activating the immune response. Human erythroleukemia line (HEL) has been the subject of previous detailed studies demonstrating surface expression of bona fide HLA molecules but inability to stimulate allogeneic response of proliferative or cytolytic T cells. We found that an HLA-DR+ subclone (HEL-DR+) expresses LFA-1, LFA-3, ICAM-1, ICAM-3, but neither CD80 nor CD86 on the surface. Transfection of CD80 cDNA into HEL-DR+ cells induced the allogeneic response of purified T cells from both cord blood and peripheral blood of adult donors, demonstrating that CD80 expression could lead to accessory cell-independent activation of naive T cells. Priming allogeneic peripheral blood T cells by HEL-DR+/CD80+ also lead to generation of cytotoxic T lymphocytes that lysed both HEL-DR+/CD80+ and wild type HEL-DR+ equally well, confirming CD80 expression is required only in the CTL induction phase but not in the CTL effector phase. We established and maintained alloproliferative T cell clones from adult blood by stimulation with the HEL-DR+/CD80+ line. The clones could respond not only to HEL-DR+/CD80+ line but also to the HEL-DR+ line; however, the proliferative response to HEL-DR+/CD80+ was amplified and sustained compared to the short-lived response to wild type HEL-DR+ cells. Therefore, expression of CD80 by HEL-DR+ cells was determinant both to initiate and sustain the T cell response. These experiments support the hypothesis that lack of expression of "costimulatory" molecules for T cells contributes to leukemia escape from immune surveillance, and provide preliminary data for the use of CD80 transfection in the immunotherapy of human leukemia.


Injection therapies for patellar tendinopathy.
Patellar tendinopathy, or jumper's knee is a common musculoskeletal condition characterized by progressive activity-related pain on the anterior aspect of the knee and tenderness on the patellar tendon. A conservative method is often the first choice of treatment, which can include anti-inflammatory medication, injection therapies, physiotherapy, eccentric exercises, extra corporeal shock wave therapy, orthosis, etc. Although there are several treatment options available, the management of patellar tendinopathy is still controversial. The literature reveals many different injection methods are being used by clinicians for the treatment of patellar tendinopathy. Platelet rich plasma, corticosteroids, autologous blood, and aprotinin are the most commonly used injection treatments. Injection therapies give promising results in the management of Patellar tendinopathy. However, due to low quality research and variation in the protocol and population it is difficult to provide a firm conclusion on its effectiveness. More high-quality clinical studies are recommended to determine the effectiveness of injections and at which stage of Patellar tendinopathy they are the most effective. This review can provide insight to clinicians involved in the management of this condition.


Alteration of thiol pools in roots and shoots of maize seedlings exposed to cadmium : adaptation and developmental cost.
Roots of intact 5-day-old maize (Zea mays L.) seedlings were exposed to 3 micromolar Cd during a 7-day period. Cysteine, gamma-glutamylcysteine, glutathione (GSH), and Cd-induced acid-soluble thiols (ASTs), including phytochelatins, were quantified in roots and shoots. Adaptation to Cd and its cost to seedling development were evaluated by measuring Cd content, tissue fresh weight, and rate of root elongation. Roots contained 60 to 67% of the Cd in the seedlings between 4 and 7 days of exposure. Exposure to Cd decreased the fresh weight gain in roots from day 4 onward without affecting the shoots. Between days 1.5 and 3.5 of Cd treatment, roots elongated more slowly than controls; however, their growth rate recovered thereafter and exceeded that of controls. Exposure to Cd did not appreciably affect the concentration of cysteine in the seedlings. However, the initial low concentration of gamma-glutamylcysteine increased (after a lag of 6 hours in roots and 2 days in shoots), reaching a plateau by day 6 at 28.5 nanomoles per gram of fresh weight in roots and by day 5 at 19.1 nanomoles per gram of fresh weight in shoots. During the first 9 hours of Cd exposure, the concentration of GSH in roots decreased dramatically (at 31.6 nanomoles per gram of fresh weight per hour) and thereafter decreased more slowly than in controls. The depletion of GSH in the roots (366 nanomoles per gram of fresh weight) matched the synthesis of ASTs (349 nanomoles per gram of fresh weight) during the first 48 hours. The concentration of ASTs in roots increased steadily thereafter to reach 662.2 nanomoles per gram of fresh weight by 6 days of Cd exposure. In shoots, Cd had little influence on the concentration of GSH, but ASTs still accumulated to 173.3 nanomoles per gram fresh weight after 5 days. The molar ratio of thiols in ASTs to Cd increased to a maximum of 10.24 in roots after 4 hours and of 4.25 in shoots after 2 days of Cd exposure. After 4 days, the ratio reached a plateau of approximately 2 in roots and between 2 and 3 in shoots, as if a steady state of Cd chelation had been achieved in both organs. The plateau coincided with recovered root elongation or an adaptation to Cd. The reduced fresh weight gain of the roots during this time, however, indicated that the synthesis of Cd-induced thiols was at a cost to root development.


Distinct underlying mechanisms of limb and respiratory muscle fiber weaknesses in nemaline myopathy.
Nemaline myopathy is the most common congenital myopathy and is caused by mutations in various genes such as ACTA1 (encoding skeletal α-actin). It is associated with limb and respiratory muscle weakness. Despite increasing clinical and scientific interest, the molecular and cellular events leading to such weakness remain unknown, which prevents the development of specific therapeutic interventions. To unravel the potential mechanisms involved, we dissected lower limb and diaphragm muscles from a knock-in mouse model of severe nemaline myopathy expressing the ACTA1 His40Tyr actin mutation found in human patients. We then studied a broad range of structural and functional characteristics assessing single-myofiber contraction, protein expression, and electron microscopy. One of the major findings in the diaphragm was the presence of numerous noncontractile areas (including disrupted sarcomeric structures and nemaline bodies). This greatly reduced the number of functional sarcomeres, decreased the force generation capacity at the muscle fiber level, and likely would contribute to respiratory weakness. In limb muscle, by contrast, there were fewer noncontractile areas and they did not seem to have a major role in the pathogenesis of weakness. These divergent muscle-specific results provide new important insights into the pathophysiology of severe nemaline myopathy and crucial information for future development of therapeutic strategies.


A randomized controlled trial of outreach placement's effect on dental students' clinical confidence.
This randomized controlled trial compared the effects of outreach placement with traditional, exclusively dental school-based clinical experience on students' confidence in providing treatment for patients presenting with common dental problems. Senior dental students (n=49) were allocated at random to existing dental school-based clinics or placement in primary care clinics to work supervised by local dentists. At baseline, students self-rated their global confidence on a five-point scale. These measures were repeated at follow-up, augmented by a transition judgment and a then-test of confidence (asking students to look back and re-rate their pre-placement confidence). Groups were comparable at baseline. Follow-up scores for global confidence were similar between groups. The outreach group scored higher in the transition judgment (mean 3.7, SD 0.9) than the control group (mean 3.1, SD 1.1, P=0.05). In the then-test, on reflection, the outreach group considered their baseline ratings of confidence were overoptimistic (mean then-test scores 3.2, SD 0.9 and baseline 3.7, SD 0.5) while the control group thought theirs were accurate (mean then-test scores 3.8, SD 0.7 and baseline 3.6, SD 0.8, P=0.01). The findings suggest dental outreach training in primary care settings is more effective than dental school training alone in improving students' confidence in tackling clinical situations. The measurement of change in confidence is complicated by shifts in students' internal scales arising from insights gained on outreach.


Effects of magnesium sulphate on the cardiovascular system, coronary circulation and myocardial metabolism in anaesthetized dogs.
We have studied the effects of i.v. bolus doses of magnesium sulphate (MgSO4) 60, 90 and 120 mg kg-1 on haemodynamic state, the coronary circulation and myocardial metabolism in nine dogs anaesthetized with pentobarbitone and fentanyl. MgSO4 produced dose-dependent decreases in arterial pressure, heart rate, left ventricular dP/dtmax and left ventricular minute work index (LVMWI) and an increase in the time constant of left ventricular isovolumic relaxation. Stroke volume increased, systemic vascular resistance decreased and cardiac output did not change significantly. MgSO4 produced decreases in coronary perfusion pressure, coronary vascular resistance and myocardial oxygen consumption (MVO2). Coronary sinus blood flow, lactate extraction ratio and the ratio of LVMWI to myocardial MVO2, that is an index of cardiac efficiency, did not change significantly. This study indicated that the depressant effect of MgSO4 on cardiac function was offset by lowering of peripheral vascular resistance, so that cardiac pump function remained effective, and the almost constant coronary sinus blood flow resulted from the decrease in coronary vascular resistance even at higher doses.


Detection of thyroid hormone receptor disruptors by a novel stable in vitro reporter gene assay.
A stable luciferase reporter gene assay was developed based on the thyroid hormone responsive rat pituitary tumor GH3 cell line that constitutively expresses both thyroid hormone receptor isoforms. Stable transfection of the pGL4CP-SV40-2xtaDR4 construct into the GH3 cells resulted in a highly sensitive cell line (GH3.TRE-Luc), which was further optimized into an assay that allowed the detection of Triiodothyronine (T(3)) and Thyroxine (T(4)) concentrations in the picomolar range after only 24 h of exposure. The greater than 20-fold induction of T(3) relative to the solvent control is illustrative of the high responsiveness of the system. The assay was validated by the quantification of the agonistic effect of the natural hormones (T(3) and T(4)), the acetic acid derivatives of T(3) (triiodothyroaceticacid, or Triac) and T(4) (tetraiodothyroacetic acid, or Tetrac), hydroxy polybrominated diphenylethers (OH-PBDEs), hydroxy polychlorinated biphenyls (OH-PCBs) and the antagonistic action of sodium arsenite (NaAsO(2)). The putative antagonist Amiodarone, Bisphenol A (BPA) and its halogenated derivatives (TCBPA and TBBPA) for which effects reported in the literature are not consistent, showed comparable dose-response curves with a slight agonistic effect (5% of T(3)-max) followed by a slight antagonistic effect. The magnitude and reproducibility of the responses to various compounds confirms this assay as a promising tool for the identification and quantification of specific thyroid hormone receptor disrupting potency of compounds.


Early PSA response to antiandrogen therapy in metastatic castration-resistant prostate carcinoma patients: A predictive marker for progression-free survival?
Enzalutamide and abiraterone acetate (AA) are the main therapeutic approaches for the treatment of metastatic castration-resistant prostate cancer (mCRPC) after the failure of androgen deprivation therapy during or following docetaxel-based chemotherapy. The aim of the present study was to investigate the role of early prostate-specific antigen (PSA) decline (four weeks after anti-androgen therapy) in predicting long-term progression-free survival (PFS). In this retrospective study, we evaluated 65 patients who had histologically confirmed metastatic prostate cancer and were treated with AA or enzalutamide in the post-docetaxel period. Serum PSA levels were evaluated at 4th and then 12th week. The main goal of this study was to demonstrate that an early PSA decline predicts PFS. Between May 2015 and June 2019, the medical records of 65 patients were collected. Of these patients, 38 (58.5%) received AA and 27 (41.5%) enzalutamide. Early PSA response rate (RR; ≥ 30% and ≥ 50% from baseline at the 4th week) was identified in 38.5% (n=25) and 15.3% (n=10) of the patients, respectively. In multivariate analysis, we found that PSA RR≥ 30% in patients had a statistically significant advantage in terms of PFS ( HR: 0.38, 95% CI (0.13-0.71;p=0.03). In conclusion, 30% PSA RR was significantly associated with a better PFS.


Verification of absorbed dose determined with plane-parallel chambers in clinical electron beams following AAPM Task Group 39 protocol using ferrous sulphate dosimetry.
The absorbed dose values determined with the Exradin and PTW-Markus plane-parallel chambers were compared to the values obtained with the ferrous sulphate dosimetry for a number of the Philips SL25 and the Therac 20 electron beams. For the plane-parallel chambers, the cavity-gas calibration factor Ngaspp, was derived by a direct comparison with a calibrated cylindrical chamber using the three different calibration methods as proposed by the newly published AAPM TG 39 protocol. For the ferrous sulphate dosimetry, an epsilon mG value of 352 x 10(-6) m-2 kg-1 Gy-1 was adopted from ICRU Report No. 35. The average ratio of the dose values determined with the plane-parallel chambers and the dose values determined with the Fricke dosimetry system was 1.001 +/- 1.4%. These measurements are consistent with the AAPM TG 39 protocol.


Isolation and characterization of a phenolic antioxidant from the Pacific oyster (Crassostrea gigas).
Using an oxygen radical absorbance capacity (ORAC) assay, antioxidant activity was detected in the ethanol extract of the Pacific oyster, which was purified by sequential extraction with organic solvents. The ethyl acetate fraction showed the strongest antioxidant activity and was further purified, yielding a single compound [as assessed by thin-layer chromatography (TLC) and reverse-phase high-performance liquid chromatography (HPLC)]. This compound was identified as 3,5-dihydroxy-4-methoxybenzyl alcohol on the basis of (1)H and (13)C nuclear magnetic resonance (NMR), heteronuclear multiple-bond correlation (HMBC), and electrospray ionization-mass spectrometry (ESI-MS) spectral analyses, a conclusion that was confirmed by chemical synthesis. The concentration of the compound was 6.7 mg/100 g of whole oyster meat wet weight. This amphiphilic antioxidant retarded the copper-mediated oxidation of low-density lipoproteins (LDLs) and the generation of thiobarbituric acid reactive substances. Furthermore, the compound showed substantial antioxidant activity using the ORAC and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays compared to natural antioxidants. Although the same compound was previously found in brown algae, its presence in other organisms and antioxidant activity are reported here for the first time.


A simple assay for proteolysis of IGFBP-3.
An assay for assessing the proteolysis of IGFBP-3 by a biological fluid or protein has been developed using 125IhIGFBP-3 recombinantly derived from Escherichia coli as a substrate indicator. The labelled substrate is incubated at 37 degrees in the presence of the agent being tested and proteolysis is visualized by SDS-PAGE and autoradiography. The assay showed that the pregnancy associated protease is Ca++ dependent. The substrate is also proteolyzed by rat and mouse pregnancy sera, making the assay applicable to studies in those animal systems.


Flow cytometric analysis of lipid droplet formation in cells of the human monocytic cell line, U937.
Active uptake of a free fatty acid, oleate, and its incorporation into triacylglycerol and phospholipid in the human monocytic cell line, U937, was identified using 14C-labelled oleate. Excess triacylglycerol accumulates in the form of lipid droplets in the cytoplasm. The extent of lipid droplet formation in each cell can be assessed in the absence of any staining by 90 degrees light scatter intensity, one of the basic parameters of flow cytometry.


Sulfite Residues in Restaurant Salads.
Sulfiting agents, which have been used as salad fresheners to prevent the enzymatic browning of restaurant salads, may pose a hazard to sulfite-sensitive asthmatics. Chopped lettuce treated with a commercial salad freshener at the recommended level of 1 tablespoon per gallon (ca. 5.3 g/L) of dip solution can contain as much as 963 mg/kg (ppm) total SO2 equivalents. Most of the sulfite in chopped lettuce is free SO2. If commercial salad fresheners are abused by using levels in excess of 1 tablespoon per gallon, progressively higher levels of residual sulfite are retained on the lettuce. Cole slaw prepared according to a typical commercial formulation contained 350 mg/kg total SO2. A survey of lettuce salads, cole slaw and potato salads from 25 local and national chain restaurants and delicatessens in Madison, Wisconsin, showed sulfite residue levels to be well below those of a treated salad, indicating a lack of sulfite use.


[The synergistic effects of paclitaxel and gemcitabine on prostate cancer cell line PC-3].
To observe the synergistic effects of paclitaxel and gemcitabine on prostate cancer cell line PC-3 in vitro. Cell morphology, MTU, flow cytometer and immunocytochemical method were used to observe the effects of 10(-6), 10(-7), 10(-8) mol/L paclitaxel and 10(-7), 10(-8), 10(-9) mol/L gemcitabine on prostate cancer cell line PC-3 by single or synergistic administration for 48 hours in vitro. Gemcitabine above 10(-8) mol/L enhanced the growth suppression [suppression ratio > or = (50.8 +/- 4.2)%, P < 0.05] and apoptosis [apoptosis ratio > or = (22.9 +/- 2.3)%, P < 0.05] and down-regulation of the expression of cyclin D1 [expression ratio < or = (9.6 +/- 1.6)%, P < 0.01] induced by paclitaxel above 10(-7) mol/L in PC-3 cells. Gemcitabine changed the ratio of G2/M cell arrest induced by paclitaxel from (70.3 +/- 9.7)% to (38.2 +/- 4.2)%, and reversed the G2/M arrest partially (P < 0.01). Paclitaxel and gemcitabine can enhance the growth suppression and apoptosis induced by paclitaxel in a synergistic way. They show great potential in the treatment of androgen-independent carcinoma of the prostate.


Effect of limited feed intake on growth of subcutaneous adipose tissue layers and on carcass composition in swine.
Little is known about the function of individual backfat layers in swine. Our objective in this study was to evaluate differential growth of each backfat layer in pigs fed different amounts of the same diet. Relationships of growth of backfat layers to deposition of carcass protein and ether extract were also studied. Feed intake levels were ad libitum, 92.5% of ad libitum, and 85% of ad libitum for 36 barrows averaging 95 d of age and 37.8 kg of weight at the start of the study. Chemical composition of the carcass soft tissue was determined at the end of the 84-d study. Daily gain tended to decrease (P less than .10) and conversion of feed to gain improved (P less than .15) as feed intake decreased. The daily depositions (g/d) of protein and ether extract were 62.9 and 205 for the ad libitum group, 61.1 and 176 for the 92.5% intake group, and 59.3 and 153 for the 85% intake group, respectively. The compositional effect of limiting feed intake for 84 d was to produce less carcass soft tissue of greater lean content. Overall backfat depths were 31.5, 29.6, and 27.8 mm for the ad libitum, 92.5, and 85% intake groups, respectively. The outer backfat layer differed among groups; the 92.5 and 85% groups were thinner than the ad libitum group. Relative to the ad libitum group, the change in depth of the middle backfat layer was 86 and 75% for the 92.5 and 85% intake groups (P less than .01). The inner backfat layer was not affected significantly by level of feed intake.(ABSTRACT TRUNCATED AT 250 WORDS)


Photobiomodulation Therapy Reduces the Inflammatory Process without Inhibiting Bone Deposition in Rats in an Extraction Model.
Objective: We evaluated the influence of photobiomodulation therapy (PBMT) application during bone healing postexodontia in rats. Methods: We divided 84 male Wistar rats into a control group (CG), which received placebo treatment without PBMT, and a test group (TG), which was treated with PBMT. After exodontia, the animals were subjected to PBMT (TG) with an AsGaAI diode laser at 810 nm, 100 mW, 2 J, and 70 J/cm2 or placebo treatment (CG) every 72 h. After 1, 3, 7, 14, 21, and 28 days, the animals were weighed and euthanized to remove the left hemimandibles for radiographic (alveolar filling) and histomorphometric (inflammatory polymorphonuclear cell (PMN), mononuclear cell (MN), osteoclast (OC), and blood vessels counting) analysis. Statistic approach used two-way variance analysis followed by Bonferroni post hoc (p < 0.05, GraphPad Prism 5.0). Results: There was no significant difference in body mass variation (p = 0.828) and bone neoformation (p = 0.365) between the two groups, but the TG presented lower PMN (p < 0.001), MN (p < 0.001), and OC counts (p < 0.001) and higher blood vessels count (p < 0.001) throughout the repair process. Conclusions: PBMT attenuated the inflammatory process after exodontia without interfering with bone neoformation.


AKIP1, a cardiac hypertrophy induced protein that stimulates cardiomyocyte growth via the Akt pathway.
Cardiac adaptation to unremitting physiological stress typically involves hypertrophic growth of cardiomyocytes, a compensatory response that often fails and causes heart disease. Gene array analysis identified AKIP1 (A Kinase Interacting Protein 1) as a hypertrophic gene and we therefore hypothesized a potential role in the hypertrophic response. We show for the first time that both AKIP1 mRNA and protein levels increased in hypertrophic cardiomyocytes under conditions of sustained cardiac stress, including pressure overload and after myocardial infarction and in vitro in phenylephrine (PE) stimulated neonatal rat ventricular cardiomyocytes (NRVCs). AKIP1 overexpression in NRVCs markedly stimulated hypertrophic growth responses, including significantly increased cell size, augmented cytoskeletal organization and protein synthesis. Although, AKIP1 was not essential for PE induced hypertrophy in NRVCs, it did potentiate neurohormonal induced protein synthesis. AKIP1 did, however, not induce expression of pathological marker genes like ANP and β-MHC. ERK and Akt kinase signaling pathways have been linked to hypertrophy and AKIP1 specifically induced phosphorylation of Akt. This phosphorylation of Akt was essential for activation of ribosomal rpS6 and translation elongation factor eEF2 and this readily explains the increased protein synthesis. Akt inhibition fully blocked AKIP1 induced hypertrophy, showing that this pathway is critically involved. In conclusion, our results show that AKIP1 is induced in hypertrophic hearts and can stimulate adaptive cardiomyocyte growth, which involves Akt signaling.


Factors impacting hand hygiene compliance among new interns: findings from a mandatory patient safety course.
Residency is a critical transition during which individuals acquire lifelong behaviors important for professionalism and optimal patient care. One behavior is proper hand hygiene (HH), yet poor compliance with accepted HH practices remains a critical issue in many settings. This study explored the factors affecting hand hygiene compliance (HHC) in a diverse group of interns at the beginning of graduate training. During a required patient safety course, we observed HH behaviors using a standardized patient encounter. Interns were instructed to perform a focused exam in a simulated inpatient environment with HH products available and clearly visible. Participants were blinded to the HH component of the study. An auditory alert was triggered if participants failed to perform prepatient encounter HH. Compliance rates and the number of alerts were recorded. All encounters were videotaped. The HHC among the 169 participants was 37.9% pre-encounter and was higher among female interns than males, although this difference was not statistically significant (41.6% versus 31.5%, P = .176). International medical graduates had significantly lower HHC compared with US graduates (23.2% versus 45.1%, P = .006). Most initially noncompliant participants performed HH after 1 alert (87.6%). The initial low rate of HHC in our sample is comparable to other studies. Using direct video surveillance and auditory alarms, we improved our success rates for prepatient encounter HHC. Our study identified medical school origin as an important factor for HHC, and the significantly lower compliance for international medical graduates compared with US graduates has not been previously reported. These findings should be considered in designing interventions such as intern orientation and clinical education programs to improve HH behaviors.


A strategy for database interoperation.
To realize the full potential of biological databases (DBs) requires more than the interactive, hypertext flavor of database interoperation that is now so popular in the bioinformatics community. Interoperation based on declarative queries to multiple network-accessible databases will support analyses and investigations that are orders of magnitude faster and more powerful than what can be accomplished through interactive navigation. I present a vision of the capabilities that a query-based interoperation infrastructure should provide, and identify assumptions underlying, and requirements of, this vision. I then propose an architecture for query-based interoperation that includes a number of novel components of an information infrastructure for molecular biology. These components include a knowledge base that describes relationships among the conceptualizations used in different biological databases, a module that can determine the DBs that are relevant to a particular query, a module that can translate a query and its results from one conceptualization to another, a collection of DB drivers that provide uniform physical access to different database management systems, a suite of translators that can interconvert among different database schema languages, and a database that describes the network location and access methods for biological databases. A number of the components are translators that bridge the heterogeneities that exist between biological DBs at several different levels, including the conceptual level, the data model, the query language, and data formats.


Effects of dietary conjugated linoleic acid on DNA adduct formation of PhIP and IQ after bolus administration to female F344 rats.
Meats cooked at high temperatures contain mutagenic heterocyclic amines such as 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). In female Fischer 344 rats, IQ is a multiorgan carcinogen, whereas PhIP induces mammary adenocarcinomas. For IQ and PhIP, N-hydroxylation, catalyzed by microsomal cytochrome P-450 1A1 and/or 1A2, and then esterification, especially O-acetylation, are the principal steps leading to DNA adduct formation. Conjugated linoleic acid (CLA) is a mixture of conjugated linoleic acid isomers found in various meat and dairy products. We have examined the effect of dietary CLA on DNA adduct formation by PhIP and IQ in female Fischer 344 rats. Four-week-old animals were maintained on AIN-76A diet without or with CLA (4% wt/wt) and treated with IQ or PhIP (50 mg/kg by gavage) after two weeks. Animals were killed (4/group) one, four, and eight days later. DNA isolated from mammary epithelial cells, liver, colon, and white blood cells was analyzed for carcinogen-DNA adducts by 32P-postlabeling assays. On Day 1, dietary CLA significantly inhibited adduct formation (82.0%) in mammary epithelial cells in IQ--but not in PhIP-treated rats. In the colon, dietary CLA significantly inhibited PhIP-DNA adduct formation (18.7%) on Day 8 but increased IQ-DNA adduct formation (30.5%) on Day 8. Dietary CLA had no effect on adduct levels in liver or white blood cells. Calf thymus DNA was incubated with N-hydroxy-PhIP or -IQ in the presence of acetyl-CoA. Enzymatic activation was catalyzed by liver or mammary cytosol. A two-week pretreatment with 2% (wt/wt) dietary CLA had no effect on O-acetyltransferase-catalyzed IQ- or PhIP-DNA adduct formation. It is concluded, under certain conditions, that dietary CLA can lower IQ- and PhIP-DNA adduct formation. Overall, however, the major mode of action of CLA is probably by a mechanism other than the inhibition of the N-hydroxylation and subsequent O-acetylation of PhIP or IQ.


Treatment of hyperinsulinemic hypoglycemia due to diffuse nesidioblastosis in adults: a case report.
An 82-year-old man was admitted to our hospital with a complaint of hypoglycemic syncope in the early morning. Insulinoma was suspected, but an abdominal CT showed no mass. Abdominal angiography showed a slight stain fed from the splenic artery. Arterial stimulation and venous sampling (ASVS) showed an abnormal insulin response only from the splenic artery. Under a provisional diagnosis of insulinoma, surgical treatment was undertaken. Although no pancreatic masses were palpable, we performed a distal pancreatectomy. Subsequently, a pathological examination revealed diffuse nesidioblastosis. Reported cases of diffuse nesidioblastosis have had common clinical features: postprandial hyperinsulinemic hypoglycemia, no abnormal findings in radiological examinations, and the presence of the ductulo-insular complex on histological examination. Surgical resection is recommended, but the extent of surgery is controversial. Our case had some clinical features of insulinoma but was diagnosed as diffuse nesidioblastosis according to histopathologic criteria. Because ASVS showed that the pancreatic body and tail had a lesion producing insulin abnormally, we performed a distal pancreatectomy to cure the hypoglycemia. Clinically, it is very difficult to distinguish diffuse nesidioblastosis from insulinoma. When we treat hyperinsulinemic hypoglycemia, ASVS can be an essential examination to decide the extent of pancreatectomy.


Screening toward the Development of Fingerprints of Atomic Environments Using Bond-Orientational Order Parameters.
A combination of atomic numbers and bond-orientational order parameters is considered a candidate for a simple representation that involves information on both the atomic species and their positional relation. The 504 candidates are applied as the fingerprint of the molecules stored in QM9, a data set of computed geometric, energetic, electronic, and thermodynamic properties for 133 885 stable small organic molecules made up of carbon, hydrogen, oxygen, nitrogen, and fluorine atoms. To screen the fingerprints, a regression analysis of the atomic charges given by Open Babel was performed by supervised machine learning. The regression results indicate that the 60 fingerprints successfully estimate Open Babel charges. The results of the dipole moments, an example of a property expressed by charge and position, also had a high accuracy in comparison with the values computed from Open Babel charges. Therefore, the screened 60 fingerprints have the potential to precisely describe the chemical and structural information on the atomic environment of molecules.


Development of MAST: A Microscopy-Based Antimicrobial Susceptibility Testing Platform.
Antibiotic resistance is compromising our ability to treat bacterial infections. Clinical microbiology laboratories guide appropriate treatment through antimicrobial susceptibility testing (AST) of patient bacterial isolates. However, increasingly, pathogens are developing resistance to a broad range of antimicrobials, requiring AST of alternative agents for which no commercially available testing methods are available. Therefore, there exists a significant AST testing gap in which current methodologies cannot adequately address the need for rapid results in the face of unpredictable susceptibility profiles. To address this gap, we developed a multicomponent, microscopy-based AST (MAST) platform capable of AST determinations after only a 2 h incubation. MAST consists of a solid-phase microwell growth surface in a 384-well plate format, inkjet printing-based application of both antimicrobials and bacteria at any desired concentrations, automated microscopic imaging of bacterial replication, and a deep learning approach for automated image classification and determination of antimicrobial minimal inhibitory concentrations (MICs). In evaluating a susceptible strain set, 95.8% were within ±1 and 99.4% were within ±2, twofold dilutions, respectively, of reference broth microdilution MIC values. Most (98.3%) of the results were in categorical agreement. We conclude that MAST offers promise for rapid, accurate, and flexible AST to help address the antimicrobial testing gap.


Healing of sites within the dog periodontal ligament after application of cold to the periodontal attachment apparatus.
The potential of periodontal ligament-derived tissues to regenerate periodontal attachment after cryosurgical trauma to the PDL in dogs was evaluated. The buccal alveolar plate of each canine tooth was exposed by a semi-lunar excision. A 3 mm thick cryoprobe, cooled to -81 degrees C, was placed on the bone 5 mm apical to the crest for 10 s. This induced cellular devitalization in the bone directly in contact with the probe and the PDL under it. The freezing-thawing cycle was repeated 3 times. Control sites were sham-operated at room temperature. Histologic sections from the center of the lesions were obtained from 1 h, 48 h and 30 d specimens. 1-h control and experimental histologic sections were similar. At 48 h post-surgery, the cellular component of the frozen PDL could not be identified and inflammatory response was minimal. The collagenous framework, however, appeared to form a continuum between the alveolar bone and cementum. Lacunae in the bone at the frozen segment were empty. The injured PDL was surrounded by normal PDL. Control specimens appeared normal. At 30 d, the PDL space in the frozen segments was populated by PDL-like tissue which did not differ significantly from the PDL coronal or apical to it. Collagen fibers appeared to be attached to the cementum on one side and to the alveolar bone on the other. Bone resorption or ankylosis was not observed in the experimental sites. It is suggested that the extracellular matrix in the devitalized area was preserved, supporting regeneration of the cryolesion.


Time-series model to predict impact of H1N1 influenza on a children's hospital.
The spring of 2009 witnessed the emergence of a novel influenza A(H1N1) virus resulting in the first influenza pandemic since 1968. In autumn of 2010, the 2009 novel H1N1 influenza strain re-emerged. We performed a retrospective time-series analysis of all patients with laboratory-confirmed H1N1 influenza who presented to our institution during 2009. Cases of influenza were assembled into 3-day aggregates and forecasting models of H1N1 influenza incidence were created. Forecasting estimates of H1N1 incidence for the 2010-2011 season were compared to actual values for our institution to assess model performance. Ninety-five percent confidence intervals calculated around our model's forecasts were accurate to ±3·6 cases per 3-day period for our institution. Our results suggest that time-series models may be useful tools in forecasting the incidence of H1N1 influenza, helping institutions to optimize distribution of resources based on the changing burden of illness.


Comparative study of CeO2 and doped CeO2 with tailored oxygen vacancies for CO oxidation.
We report on the preparation and characterization of CeO(2) nanofibers (CeO(2)-NFs) and nanocubes (CeO(2)-NCs), as well as Sm- and Gd-doped CeO(2) nanocubes (Sm-CeO(2)-NCs and Gd-CeO(2)-NCs), synthesized by a simple hydrothermal process for CO catalytic oxidation. The samples were characterized by X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), Raman spectroscopy, and photoluminescence spectroscopy. Their oxygen-storing capacity (OSC) was examined by means of hydrogen temperature-programmed reduction (H(2)-TPR) and oxygen pulse techniques. Their catalytic properties for CO catalytic oxidation were comparatively investigated. The results showed that the CeO(2)-NFs possessed a higher catalytic activity compared to the CeO(2)-NCs because of their smaller size and the greater number of oxygen vacancies. The activity of the Sm-CeO(2)-NCs was higher than that of the CeO(2)-NCs due to an increase in the number of oxygen vacancies, which results from the substitution of Ce(4+) species with Sm(3+) ions. In contrast, Gd doping had a negative effect on the CO catalytic oxidation due to the special electron configuration of Gd(3+) (4f(7)). Our work demonstrates that the oxygen vacancies in pure CeO(2) and the electron configuration of the dopants in doped CeO(2) play an important role in CO oxidation.


Inflammatory mechanisms of adverse reactions to drug-eluting stents.
In-stent restenosis and stent thrombosis represent the main adverse reactions to coronary stents and individual susceptibility appears to play an important role in their onset. In particular, inflammatory status, classically assessed by C-reactive protein levels, predicts the risk of in-stent restenosis after bare-metal stent implantation but not after drug-eluting stent (DES) implantation. On the other hand, C-reactive protein seems to predict the risk of stent thrombosis after treatment with DES but not with bare-metal stent. If DES have considerably reduced, as compared to bare-metal stent, the rate of adverse reaction in the first year after implantation, concern is emerging about late events that seem to be related to delayed healing and allergic reactions to polymers, a process in which eosinophils play an important role by enhancing restenosis and thrombosis.


Estimates of the direct and indirect costs of acquired immunodeficiency syndrome in the United States, 1985, 1986, and 1991.
This study presents three estimates ranging from low to high of the direct and indirect costs of the acquired immunodeficiency syndrome (AIDS) epidemic in the United States in 1985, 1986, and 1991, based on prevalence estimates provided by the Centers for Disease Control (CDC). According to the author's best estimates, personal medical care costs of AIDS in current dollars will rise from $630 million in 1985 and $1.1 billion in 1986 and $8.5 billion in 1991. Nonpersonal costs (for research, screening, education, and general support services) are estimated to rise from $319 million in 1985 to $542 million in 1986 to $2.3 billion in 1991. Indirect costs attributable to loss of productivity resulting from morbidity and premature mortality are estimated to rise from $3.9 billion in 1985 to $7.0 billion in 1986 to $55.6 billion in 1991. While estimated personal medical care costs of AIDS in 1985 and 1986 represent only 0.2% and 0.3%, respectively, of such estimated expenditures for the U.S. population in these 2 years, they represent 1.4% of these estimated costs in 1991. Similarly, while estimated indirect costs of AIDS represent 1.2% in 1985 and 2.1% in 1986 of the estimated indirect costs of all illness, they are projected to rise to almost 12% in 1991. For estimating the indirect costs, the human capital method was used, and it was assumed that average wages and labor force participation rates of persons with AIDS were the same as those for the general population by age and sex.


Competences for self-care and self-control in diabetes mellitus type 2 in primary health care.
The purpose of the guidelines of self-care and self-control of type 2 diabetes mellitus proposed by the Brazilian Ministry of Health is to strengthen and qualify users and health care professionals through the integrality and longitudinality of care with this disease. This article aims to present the self-care and self-control of people with type 2 diabetes mellitus in objective terms, taking into account the current recommen-dations based on scientific evidence and also from the subjective point of view, that is, emphasizing the aspects related to experience and subjectivity of these people. Next, we present the essential skills for self-care and self-control of users and professionals working in primary health care.


Cytogenetic analysis of retinoblastoma: evidence for multifocal origin and in vivo gene amplification.
Retinoblastoma (Rb) is an uncommon childhood tumor of the neural retina with a significant genetic component in its etiology. A small proportion of patients have a deletion in chromosome 13 encompassing band 13q14, an observation which permitted the assignment of the RB1 locus to this region. About 20% of Rb tumors exhibit microscopic deletions of band 13q14 or monosomy 13. Trisomy 1q and i(6p) have also been reported in a high percentage of tumors. We analyzed the chromosome complements from direct preparations of 10 Rb tumors derived from seven patients. Modal chromosome numbers ranged from 45 to 48, and occasional duplications of the genomes were noted. In general, the tumors were chromosomally stable, although karyotypic evolution and random chromosome loss were encountered. Consistent abnormalities included trisomy 1q, i(6p), 6q-, and del(13)(q12----14). One patient with bilateral Rb had three tumor clones (two in one eye and one in the other) with chromosome abnormalities unrelated in origin. A second patient with unilateral Rb had two tumor clones with chromosome abnormalities again unrelated in origin. These two patients provide some of the first cytogenetic evidence for the multifocal origin of primary Rb. In the untreated tumor of a third patient, a homogeneously staining region (HSR) was detected in 1p32, indicating gene amplication in vivo; previously, an HSR at this site has been reported in the established Rb cell line Y79.


Endogenous angiotensin and pressure modulate brain angiotensinogen and AT1A mRNA expression.
In the coarctation hypertension model, we showed both dissociation of plasma renin activity from cardiovascular-induced effects and the reversal of hypertension-induced responses by losartan. In this study, we investigated the effects of hypertension on the expression of brain renin-angiotensin system components and the simultaneous functional responses and effects of long-term angiotensin II (AT) receptor blockade on these responses. Rats were given vehicle or losartan for 9 days and subjected to subdiaphragmatic aortic constriction or sham surgery after 4 days of treatment. On the fifth postsurgical day, pressure and heart rate were measured in the conscious state; the brain was perfused and removed afterward. Sequential slices of brainstem were hybridized with 35S-oligodeoxynucleotide probes for angiotensinogen, AT1A, and AT1B receptors and processed for autoradiography and densitometry. In vehicle-treated rats, hypertension was accompanied by tachycardia and marked increments in angiotensinogen and AT1A mRNA expression in the cardiovascular system-controlling brainstem areas. In the nucleus tractus solitarii, AT1A density was correlated with both pressure and heart rate values (P<0.01), whereas angiotensinogen levels were correlated with pressure only (P<0.05). Losartan did not change the pressure of hypertensive rats (142+/-4 versus 146+/-2 mm Hg, losartan versus vehicle) and the hypertension-induced angiotensinogen mRNA expression but did block both tachycardic response and hypertension-induced AT1A mRNA expression. Hypertension and losartan did not change AT1B mRNA expression. The hypertension-induced positive feedback on angiotensinogen and AT1A mRNA expression supports the concept of a permissive role for brain angiotensin II in orchestrating circulatory responses during the development of hypertension. These data also explain the efficacy of long-term AT1 receptor blockade to reverse hypertension-induced effects.


Serum antibody responses to polymorphic Cryptosporidium mucin antigen in Bangladeshi children with cryptosporidiosis.
Cryptosporidium is a significant cause of diarrheal disease in children in developing countries. The sporozoite antigen Muc4 is important for infection of host cells, and could be a candidate vaccine antigen. However, this antigen is polymorphic between Cryptosporidium hominis and C. parvum. We investigated antibody responses to C. hominis Muc4 and C. parvum Muc4 antigen in children in Bangladesh infected with C. hominis. Antibody responses were compared between children with cryptosporidial diarrhea (cases) and uninfected children with diarrhea (controls). There was a significant IgM response to Muc4 from both species in cases compared with controls, which increased over time, and was higher in children with persistent diarrhea. Despite sequence polymorphisms, antibody responses to C. hominis Muc4 and C. parvum Muc4 were significantly correlated. These results suggest that the human antibody response to Muc4 is cross-reactive between species, but in young children does not mature to an IgG response within the period observed in this study.


Detection of influenza a type-specific antibodies in chicken and turkey sera by enzyme linked immunosorbent assay.
An ELISA test for detection of influenza A virus type-specific antibodies in chicken and turkey sera is described. Antigen was prepared from infected allantoic fluids using an H7N1 virus. Virus particles were disrupted using sodium deoxycholate to release internal antigens and tests were standardised by testing batches of sera from influenza-free birds. A negative antigen was included in the test and was shown to be effective in eliminating the non-specific increase in absorbance values observed with influenza-negative sera from older birds. Sensitivity and group-specificity were demonstrated by infection of chickens and turkeys with influenza subtypes unrelated to the H7N1 virus from which the antigen was prepared, so that only type A specific responses were being detected. The sensitivity was equivalent to the haemagglutination-inhibition test. Antisera to all 13 haemagglutinin subtypes, prepared in chickens, were strongly positive, again highlighting the group reactivity of the test and demonstrating its suitability as a screening test.


Mesenchymal Stem Cells Home to Sites of Injury and Inflammation.
Mesenchymal stem cells (MSCs) have shown significant therapeutic potential in preclinical animal models of wound healing. However, the translation of MSC-based therapeutics to clinical practice has been delayed by questions including the mechanisms of MSC homing, engraftment, and ultimate function. Experimental models of MSC-based wound therapies often involve intravenous injection of cells followed by sacrifice of animals at various time points and detection of MSCs in wounds by histological methods. However, this methodology is limited by its sampling of only specific tissue at a single time point and provides no information about how exogenously transplanted MSCs home to the wound environment. Most systemically injected MSCs initially become entrapped within the lungs before migrating out to the liver and spleen in the normal state. When an injury is present, after the initial lung entrapment, MSCs migrate in response to inflammatory mediators and home to sites of wounding. As MSC-based wound therapies continue to advance toward clinical trials, the availability of noninvasive methods to track cells after injection into patients affords the opportunity to monitor stem cell behavior post-transplantation. MSCs have demonstrated great promise as an emerging therapeutic for wound management. However, further preclinical studies will be needed to elucidate the reparative mechanisms of these cells and to determine how to optimize their regenerative potential.


Electronic and steric effects of platinum(ii) di-yne and poly-yne substituents on the photo-switching behaviour of stilbene: experimental and theoretical insights.
A series of mono-, di-, and poly(platina-ynes) incorporating stilbene spacer units with the formulae trans-[R-C[triple bond, length as m-dash]C-Pt(PBu3)2-C[triple bond, length as m-dash]C-R] (R = (E)-1,2-diphenylethene), trans-[(Ph)-(Et3P)2PtC[triple bond, length as m-dash]C-R-C[triple bond, length as m-dash]CPt(PEt3)2(Ph)] (R = (E)-1,2-diphenylethene), and trans-[-(PnBu3)2PtC[triple bond, length as m-dash]C-R-C[triple bond, length as m-dash]C-]n (R = (E)-1,2-diphenylethene), respectively, have been synthesized and characterized to explore the effects of ligand topology on the photoisomerization and photophysical properties of these materials. The structural and photophysical properties of the complexes have been investigated and compared with those of the previously reported mono-, di- and poly(platina-ynes) incorporating azobenzene spacers. We found that the organometallic species 1M, 2M and 1P undergo topology-dependent reversible trans-to-cis photoisomerization in CH2Cl2 solution. Computational modelling supported the experimental findings.


Computational Radiology in Breast Cancer Screening and Diagnosis Using Artificial Intelligence.
Breast cancer screening has been shown to significantly reduce mortality in women. The increased utilization of screening examinations has led to growing demands for rapid and accurate diagnostic reporting. In modern breast imaging centers, full-field digital mammography (FFDM) has replaced traditional analog mammography, and this has opened new opportunities for developing computational frameworks to automate detection and diagnosis. Artificial intelligence (AI), and its subdomain of deep learning, is showing promising results and improvements on diagnostic accuracy, compared to previous computer-based methods, known as computer-aided detection and diagnosis.In this commentary, we review the current status of computational radiology, with a focus on deep neural networks used in breast cancer screening and diagnosis. Recent studies are developing a new generation of computer-aided detection and diagnosis systems, as well as leveraging AI-driven tools to efficiently interpret digital mammograms, and breast tomosynthesis imaging. The use of AI in computational radiology necessitates transparency and rigorous testing. However, the overall impact of AI to radiology workflows will potentially yield more efficient and standardized processes as well as improve the level of care to patients with high diagnostic accuracy.


[Field matching in breast irradiation]
INTRODUCTION: In this paper the authors have combined different irradiation techniques for breast and adjacent supraclavicular lymph nodes. The aim was to reduce inhomogeneity in the match-line. METHODS: The CadPlan 6.1.5 three-dimensional treatment planning system was applied in this study for CT based plan using a standard medial and lateral wedged tangential breast portals with the adjacent supraclavicular field. Isocenter is placed at depth on the match-line, where asymmetric jaws are used to produce non-divergent field edges. The tangential fields are shaped using multi-leaf collimator (MLC), by following the curvature of the thorax. In this way the cranial vertical match plane is maintaned without using the breast board. The prescribed dose was 50 Gy at the isocentre. RESULTS: The calculated dose distributions were evaluated in three dimension in the match region of supraclavicular field and the two opposing tangential fields. This method produces a more uniform dose distribution in the target volume and in the match-line. Set-up is fast, this is done without the need for table rotation, or vertical cephalad blocks. The average dose to the ipsilateral lung is reduced using the IMRT (intensity modulated radiotherapy) technique by approximately 10% compared with the conventional technique. Furthermore, this new technique has the possibility to improve the field match between the tangential fields and the parasternal field, while maintaning the field match between the tangential fields and the axillary and supraclavicular fields.


Evaluation of parameters in the isolation of viable protoplasts from cultured tobacco cells.
A systematic evaluation disclosed the following conditions to be optimum for the isolation of viable protoplasts from cultured cells of Nicotiana tabacum L. ;Bright Yellow' grown in liquid suspensions: (a) the cell culture in the early phase of cell number increase, (b) an enzyme mixture of 1% cellulase "Onozuka" and 0.2% Macerozyme, (c) an enzyme solution pH of 4.7 or 5.7, (d) a 2- to 3-hr incubation period, (e) 5 ml of enzyme solution per 500 mg cells and contained in a 50-ml Delong flask, (f) agitation on a gyrotory shaker at 50 rpm, and (g) 0.3 to 0.8 m mannitol as osmoticum in the cell enzyme mixture. The incubation temperature may be varied from 22 to 37 C. The procedure enabled 30% of the tobacco cells to form protoplasts, 80% of which regenerated cell walls in 4 days and 40% resumed cell division activity when returned to cell culture medium.


The RecU Holliday junction resolvase acts at early stages of homologous recombination.
Homologous recombination is essential for DNA repair and generation of genetic diversity in all organisms. It occurs through a series of presynaptic steps where the substrate is presented to the recombinase (RecA in bacteria). Then, the recombinase nucleoprotein filament mediates synapsis by first promoting the formation of a D-loop and later of a Holliday junction (HJ) that is subsequently cleaved by the HJ resolvase. The coordination of the synaptic step with the late resolution step is poorly understood. Bacillus subtilis RecU catalyzes resolution of HJs, and biochemical evidence suggests that it might modulate RecA. We report here the isolation and characterization of two mutants of RecU (recU56 and recU71), which promote resolution of HJs, but do not promote RecA modulation. In vitro, the RecU mutant proteins (RecUK56A or RecUR71A) bind and cleave HJs and interact with RuvB. RecU interacts with RecA and inhibits its single-stranded DNA-dependent dATP hydrolysis, but RecUK56A and RecUR71A do not exert a negative effect on the RecA dATPase and fail to interact with it. Both activities are important in vivo since RecU mutants impaired only in RecA interaction are as sensitive to DNA damaging agents as a deletion mutant.


Increases in serum estrogen levels during major illness are caused by increased peripheral aromatization.
Although serum testosterone levels decrease acutely in critically ill patients, estrogen levels rise. We hypothesized that increased rates of aromatization of androgens to estrogens underlie the increase in serum estrogen levels. Eleven men and three women (age 42-69 yr) were prospectively studied before and again after elective coronary artery bypass graft surgery (CABG). Each patient received priming doses of [(14)C]androgen and [(3)H]estrogen that were immediately followed by peripheral infusions for 210 min. Eight men and three women received androstenedione (A(4))/estrone (E(1)) and three men received testosterone (T)/estradiol (E(2)). Adipose tissue biopsies were obtained in another six men before and after CABG to evaluate levels of P450 aromatase mRNA. Serum T levels decreased postoperatively in all 17 men (P < 0.001), whereas E(1) levels rose (P = 0.004), with a trend toward a rise in E(2) (P = 0.23). Peripheral aromatization rates of androgens to estrogens rose markedly in all 14 patients (P < 0.0001). Estrogen clearance rates rose (P < 0.002). Mean serum A(4) levels increased slightly postoperatively (P = 0.04), although no increase in A(4) production rates (PRs) was observed. T PRs decreased in two of three men, whereas clearance rates increased in all three. Adipose tissue P450 aromatase mRNA content increased postoperatively (P < 0.001). We conclude that the primary cause of increased estrogen levels in acute illness is increased aromatase P450 gene expression, resulting in enhanced aromatization of androgens to estrogens, a previously undescribed endocrine response to acute illness. Both increased T clearance and decreased T production contribute to decreased serum T levels. Animal studies suggest that these opposing changes in circulating estrogen and androgen levels may be important to reduce morbidity and mortality in critical illness.


Factors Determining Quality of Care in Family Planning Services in Africa: A Systematic Review of Mixed Evidence.
Improving use of family planning services is key to improving maternal health in Africa, and provision of quality of care in family planning services is critical to support higher levels of contraceptive uptake. The objective of this systematic review was to synthesize the available evidence on factors determining the quality of care in family planning services in Africa. Quantitative and qualitative studies undertaken in Africa, published in English, in grey and commercial literature, between 1990 and 2015 were considered. Methodological quality of included studies was assessed using standardized tools. Findings from the quantitative studies were summarized using narrative and tables. Client satisfaction was used to assess the quality of care in family planning services in the quantitative component of the review. Meta-aggregation was used to synthesize the qualitative study findings. From 4334 records, 11 studies (eight quantitative, three qualitative) met the review eligibility criteria. The review found that quality of care was influenced by client, provider and facility factors, and structural and process aspects of the facilities. Client's waiting time, provider competency, provision/prescription of injectable methods, maintaining privacy and confidentiality were the most commonly identified process factors. The quality of stock inventory was the most commonly identified structural factor. The quality of care was also positively associated with privately-owned facilities. The qualitative synthesis revealed additional factors including access related factors such as 'pre-requisites to be fulfilled by the clients and cost of services, provider workload, and providers' behaviour. There is limited evidence on factors determining quality of care in family planning services in Africa that shows quality of care is influenced by multiple factors. The evidence suggests that lowering access barriers and avoiding unnecessary pre-requisites for taking contraceptive methods are important to improve the quality of care in family planning services. Strategies to improve provider behavior and competency are important. Moreover, strategies that minimize client waiting time and ensure client confidentiality should be implemented to ensure quality of care in family planning services. However, no strong evidence based conclusions and recommendations may be drawn from the evidence. Future studies are needed to identify the most important factors associated with quality of care in family planning services in a wider range of African countries.


Regulation of CTnDOT conjugative transfer is a complex and highly coordinated series of events.
CTnDOT is a 65-kb conjugative transposon that is found in Bacteroides spp., which are one of the more abundant members within the lower human gastrointestinal tract. CTnDOT encodes resistance to the antibiotics erythromycin and tetracycline (Tc). An interesting feature of CTnDOT is that exposure to low levels of Tc induces a cascade of events that ultimately results in CTnDOT conjugative transfer. However, Tc is apparently not a switch that activates transfer but rather a signal that appears to override a series of negative regulators that inhibit premature excision and transfer of CTnDOT. In this minireview, we summarize over 20 years of research that focused on elucidating the highly coordinated regulation of excision, mobilization, and transfer of CTnDOT. Bacteroides spp. are abundant commensals in the human colon, but they are also considered opportunistic pathogens, as they can cause life-threatening infections if they should escape the colon. Bacteroides spp. are the most common cause of anaerobic infections and are rather difficult to treat due to the prevalence of antibiotic resistance within this genus. Today over 80% of Bacteroides are resistant to tetracycline (Tc), and a study looking at both clinical and community isolates demonstrated that this resistance was specifically due to the conjugative transposon CTnDOT.


Functionalized congener approach to the design of ligands for G protein-coupled receptors (GPCRs).
Functionalized congeners, in which a chemically functionalized chain is incorporated at an insensitive site on a pharmacophore, have been designed from the agonist and antagonist ligands of various G protein-coupled receptors (GPCRs). These chain extensions enable a conjugation strategy for detecting and characterizing GPCR structure and function and pharmacological modulation. The focus in many studies of functionalized congeners has been on two families of GPCRs: those responding to extracellular purines and pyrimidines-i.e., adenosine receptors (ARs) and P2Y nucleotide receptors. Functionalized congeners of small molecule as ligands for other GPCRs and non-G protein coupled receptors have also been designed. For example, among biogenic amine neurotransmitter receptors, muscarinic acetylcholine receptor antagonists and adrenergic receptor ligands have been studied with a functionalized congener approach. Adenosine A(1), A(2A), and A(3) receptor functionalized congeners have yielded macromolecular conjugates, irreversibly binding AR ligands for receptor inactivation and cross-linking, radioactive probes that use prosthetic groups, immobilized ligands for affinity chromatography, and dual-acting ligands that function as binary drugs. Poly(amidoamine) dendrimers have served as nanocarriers for covalently conjugated AR functionalized congeners. Rational methods of ligand design derived from molecular modeling and templates have been included in these studies. Thus, the design of novel ligands, both small molecules and macromolecular conjugates, for studying the chemical and biological properties of GPCRs have been developed with this approach, has provided researchers with a strategy that is more versatile than the classical medicinal chemical approaches.


Structural Modifications of Deoxycholic Acid to Obtain Three Known Brassinosteroid Analogues and Full NMR Spectroscopic Characterization.
An improved synthesis route for obtaining known brassinosteroid analogues, i.e., methyl 2α,3α-dihydroxy-6-oxo-5α-cholan-24-oate (11), methyl 3α-hydroxy-6-oxo-7-oxa-5α-cholan-24-oate (15) and methyl 3α-hydroxy-6-oxa-7-oxo-5α-cholan-24-oate (16), from hyodeoxycholic acid (4) maintaining the native side chain is described. In the alternative procedure, the di-oxidized product 6, obtained in the oxidation of methyl hyodeoxycholate 5, was converted almost quantitatively into the target monoketone 7 by stereoselective reduction with NaBH₄, increasing the overall yield of this synthetic route to 96.8%. The complete ¹H- and (13)C-NMR assignments for all compounds synthesized in this work have been made by 1D and 2D heteronuclear correlation gs-HSQC and gs-HMBC techniques. Thus, it was possible to update the spectroscopic information of ¹H-NMR and to accomplish a complete assignment of all (13)C-NMR signals for analogues 5-16, which were previously reported only in partial form.


[Role of the canonical Wnt signaling pathway in heart valve development].
Formation of the heart valves is one of critical steps in vertebrate cardiac development. Valvular heart anomaly can induce severe cardiac impairment, which is one of most common symptoms for congenital heart defects (CHD). The canonical Wnt/β-catenin signaling pathway, which is essential for numerous developmental processes, has also been suggested to be involved in the regulation of proliferation, differentiation, and migration of myocardium, endocardium and valve primordia at different stages. The canonical Wnt signaling also regulates the endocardial-mesenchymal transformation (EMT) process during the endocardial cushion formation. This paper reviews current knowledge about the canonical Wnt signaling pathway in heart valve development, including the functional diversities of Wnt activity in heart valve development at different stages and its interaction with other valve-relevant signaling pathways and the potential role of canonical Wnt activity in heart valve mesenchymal stem cells at the late developmental stage.


Mouse model of hyperkinesis implicates SNAP-25 in behavioral regulation.
Although hyperkinesis is expressed in several neurological disorders, the biological basis of this phenotype is unknown. The mouse mutant coloboma (Cml+) exhibits profound spontaneous locomotor hyperactivity resulting from a deletion mutation. This deletion encompasses several genes including Snap, which encodes SNAP-25, a nerve terminal protein involved in neurotransmitter release. Administration of amphetamine, a drug that acts presynaptically, markedly reduced the locomotor activity in coloboma mice but increased the activity of control mice implicating presynaptic function in the behavioral abnormality. In contrast, the psychostimulant methylphenidate increased locomotor activity in both coloboma and control mice. When a transgene encoding SNAP-25 was bred into the coloboma strain to complement the Snap deletion, the hyperactivity expressed by these mice was rescued, returning these corrected mice to normal levels of locomotor activity. These results demonstrate that the hyperactivity exhibited by these mice is the result of abnormalities in presynaptic function specifically attributable to deficits in SNAP-25 expression.


[Psychosomatics and psychotraumatology of refugees and migrants : A Challenge for the Internist].
Many refugees experience severely stressful events in their home countries, during migration and occasionally even after arrival in the country of destination. The individual reactions not only influence the mental health but also somatic well being. Traumatic events may have an essential impact on psychosocial functioning; moreover, the social circumstances during the integration process influence mental stability. Physicians play an important role in identifying possible traumatization and subsequently guiding towards adequate treatment; hence, the healthcare of refugees should regularly include psychosomatic and psychotraumatological aspects. Knowledge of screening instruments, trauma-informed care and interpreter-assisted communication are necessary to meet required standards.


Body composition characteristics and body fat distribution in lean women with polycystic ovary syndrome.
Body composition, fat distribution and bone mineral density were examined in lean women suffering from polycystic ovary syndrome (PCOS) and compared with body composition and fat distribution characteristics of weight-matched lean controls. Ten women with PCOS and a body mass index (BMI) below 25.00 (kg/m(2)) and 10 healthy women with a BMI below 25.00 (kg/m(2)) matched for age and weight and BMI as controls were enrolled in this study. Body composition and bone density were measured by dual-energy- x-ray-absorptiometry and fat distribution patterns were calculated. Although matched for age, weight and BMI, lean PCOS patients showed a significantly higher amount of body fat and lower amount of lean body mass than the controls. The majority of PCOS patients showed an intermediate or android kind of fat distribution. Only 30% of the lean PCOS patients corresponded to the definition of gynoid fat distribution while this was true of all lean controls.


The cost-effectiveness of clinical pharmacist intervention on tobramycin prescribing.
The cost-effectiveness of clinical pharmacist intervention in reducing the use of tobramycin and in the pharmacokinetic monitoring of aminoglycoside therapy to prevent serious nephrotoxicity were evaluated. Prescribing practices for tobramycin were compared between two similar medical teams, one with clinical pharmacist services, the other without. A statistically significant difference was observed between the number of patients who received tobramycin in the two teams, and a cost saving of $5,072.85 was achieved in 3 months. The potential for hospitalwide cost savings is substantial if gentamicin can be substituted for tobramycin in selected circumstances and followed with appropriate monitoring.


[Clinical evaluation of the zirconia all ceramic crowns in 40 consecutive patients].
To investigate clinical application, aesthetics, stability and bio-compatibility of zirconia all-ceramic crowns in prosthodontic patients. Computer aided design and manufacturing techniques were used to make zirconia all ceramic crowns in 40 patients. They were divided into 2 groups according to the thickness of the gingival thickness. After 12 months of clinical observation, the aesthetics, stability, and bio-compatibility were evaluated by the crown color, crown edge fitness, losing ratio and gingival health. The data were analyzed using SPSS 13.0 software package. Slight marginal discrepancy was observed in 2 zirconia all ceramic crowns, no evidence of decay was observed at 1 year. Zirconia all ceramic crowns have a low fracture rate, good biological properties and excellent esthetic properties. It is ideal esthetic prosthesis.


Characteristics associated with falls among the elderly within aged care wards in a tertiary hospital: a retrospective.
Falls are the most frequently reported adverse events in inpatient settings. We conducted a retrospective case-control study of inpatient falls within aged care wards in a tertiary hospital to investigate the associated characteristics of elderly patients suffering from falls and fall-related characteristics. Consecutive retrospective cross-sectional design spanned July 2006 to December 2008. Information on all aged care inpatients who suffered from 1 or more falls was extracted from Incident Information Management System (IIMS). Further details about the particular admission(s) were obtained from patients' medical records, e.g., patients' characteristics and circumstances surrounding the falls. Randomly selected aged care patients who did not suffer from a fall and who were discharged from the hospital in the same period served control group. Characteristics among patients with single fall and recurrent falls, as well as non-fallers were compared. Of the 438 falls evaluated, 71.9% occurred in patients' room and 18.9% in patients' bathroom/toilet. The common activities were moving/transferring and taking shower/toileting, respectively, 70.3%, 12.1% while occurring falls; and time of falls had a high peak during 9:00-11:00 a.m. Many were unassisted while falling. The common contributing factors for fall were intrinsic factors. Patients with recurrent falls were more likely to have lower Mini-Mental State Examination (MMSE) score. Logistic regression analysis showed length of stay longer than five weeks, dementia and stroke were independent risk factors for recurrent falls; and living in hostel/nursing home preadmission, needing assistance with mobility, cognitive impairment, stroke, incontinence and arthritis/osteoporosis were independent risk factors for fall. In an aged care ward, falls are independently associated with recurrent factors. Cognitive impairment/dementia was a strong risk factor for falls, and main causes leading to fall were intrinsic factors. For patients with cognitive impairment/dementia and behavioral disorder providing special and effective interventions is of paramount importance for reducing the incidence of fall in an aged care ward in hospital settings.


Enlargement of taurocholate micelles by added cholesterol and monoolein: self-diffusion measurements.
The effect of solubilized cholesterol and 1-monoolein on the size of micellar aggregates of sodium taurocholate (3alpha,7alpha,12alpha-trihydroxy-5-cholanoyl taurine) has been determined in vitro. Measurements of the self-diffusion coefficient of sodium taurocholate (0.15 m in Na(+)) at 37 degrees C and pH 7.4 led to the conclusion that at concentrations above the critical micelle concentration (6.7 mm) the solutions contain, besides monomeric ions, a single micellar species containing five taurocholate ions. In the presence of cholesterol, much larger micelles are formed, apparently containing one molecule of cholesterol and 25 of taurocholate. These mixed micelles coexist with small micelles of pure taurocholate as well as the taurocholate monomers. The addition of 1-monoolein increases the solubility of cholesterol in the taurocholate solution, but not by reducing the size of the micelle into which the cholesterol will fit: three-component micelles (monoolein-taurocholate-cholesterol) are, if their diffusion coefficients are any guide, still larger than taurocholate-cholesterol micelles. The molar ratio of cholesterol to taurocholate is higher in these solutions than in the absence of monoolein. Comparison with work by other authors on taurodeoxy-cholate-cholesterol micelles suggests that more than 25 molecules of either dihydroxy or trihydroxy bile salts are needed to transport each molecule of cholesterol through an aqueous solution in the absence of other amphipathic molecules.


Has there been a change in the rates of UK sickness certification for back pain over time? An examination of historical data from 2000 to 2010.
This paper aims to investigate historical patterns of sickness certification for back pain from 2000 to 2010. Electronic medical records from 14 practices that are part of the National Institute for Health Research (NIHR) Clinical Research Network: West Midlands were reviewed. All records for back pain consultations from 2000 to 2010 were downloaded and matched, by date, to corresponding sickness certification records. Primary Care. A total of 93,896 back pain consultations were recorded over the 11-year period, resulting in 30,913 sickness certificates. There was a statistically significant decrease in the rate of certification over the period, falling from 376.8 (95% CI 362.1 to 392) per 1000 back pain consultations in 2000 to 246.5 (95% CI 236.5 to 332.9) per 1000 back pain consultations in 2010. There was also a statistically significant difference in certification between males and females, with males issued more certificates than females. There was a statistically significant difference in certification by age, with those aged 60 years and over being less likely to be issued a certificate compared to all other age groups. Rates of sickness certification for back pain demonstrated a downward trend between 2000 and 2010. While the reasons for this are not transparent, it may be related to changing beliefs around working with back pain.


Legionella - A threat to groundwater: Pathogen transport in recharge basin.
This study elucidates the potential risk posed by Legionella during aquifer recharge practices. Experiments were conducted using pilot-scale column simulating infiltration of bacterial surrogate and pathogen, E. coli and Legionella pneumophila, under central Arizona recharge basin conditions. A column was packed with a loamy sand media collected from a recharge basin and was fitted with six sampling ports at soil depths of 15, 30, 60, 92, 122cm and acclimated for a month with tertiary treated wastewater. Transport of Legionella appeared to be delayed compared to E. coli. The breakthrough of E. coli and Legionella at 122cm depth occurred at 3 and 24h, respectively. Slow transport of Legionella is consistent with its pleomorphic nature and variation in size and shape under low nutrient conditions. Legionella persisted for a longer time in the column, but at lower concentrations. Given the novel results of this study, the transport of Legionella into groundwater aquifers can occur through engineering recharge basin conditions creating a potential public health risk.


Massive genome inversion drives coexistence of divergent morphs in common quails.
The presence of population-specific phenotypes often reflects local adaptation or barriers to gene flow. The co-occurrence of phenotypic polymorphisms that are restricted within the range of a highly mobile species is more difficult to explain. An example of such polymorphisms is in the common quail Coturnix coturnix, a small migratory bird that moves widely during the breeding season in search of new mating opportunities, following ephemeral habitats,1,2 and whose females may lay successive clutches at different locations while migrating.3 In spite of this vagility, previous studies reported a higher frequency of heavier males with darker throat coloration in the southwest of the distribution (I. Jiménez-Blasco et al., 2015, Int. Union Game Biol., conference). We used population genomics and cytogenetics to explore the basis of this polymorphism and discovered a large inversion in the genome of the common quail. This inversion extends 115 Mbp in length and encompasses more than 7,000 genes (about 12% of the genome), producing two very different forms. Birds with the inversion are larger, have darker throat coloration and rounder wings, are inferred to have poorer flight efficiency, and are geographically restricted despite the high mobility of the species. Stable isotope analyses confirmed that birds carrying the inversion have shorter migratory distances or do not migrate. However, we found no evidence of pre- or post-zygotic isolation, indicating the two forms commonly interbreed and that the polymorphism remains locally restricted because of the effect on behavior. This illustrates a genomic mechanism underlying maintenance of geographically structured polymorphisms despite interbreeding with a lineage with high mobility.


Vaginal birth after Cesarean rates are declining rapidly in the rural state of Maine.
The American College of Obstetricians and Gynecologists (ACOG) revised its practice bulletin on vaginal birth after Cesarean (VBAC) in October 1998 and July 1999 to require the presence of a surgeon, anesthesiologist and operating personnel throughout the trial of labor for patients with prior Cesarean. This study measures the change in VBAC rates from 1998 to 2001 and examines possible reasons for this change. We examined birth certificate and hospital data in the State of Maine from 1998 to 2001. Hospital-specific rates for primary Cesareans, total Cesareans, repeat Cesareans and vaginal deliveries after previous Cesarean were obtained. Additionally, we surveyed current obstetric-care providers in Maine regarding reasons for change in VBAC rates at their institutions. VBAC rates declined by over 50% from 30.1 to 13.1%. The total Cesarean rate climbed from 19.4 to 24.0%. The most commonly reported reason for decrease in VBAC varied depending on whether a practitioner's hospital met ACOG guidelines. A marked decline in VBAC occurred after the change in ACOG vaginal birth after Cesarean policy. Multiple factors have contributed to this decline, including patients refusing VBAC after counseling and inability of institutions to meet ACOG guidelines.


Trinuclear heterometallic Cu(II)-Mn(II) complexes of a salen type Schiff base ligand: anion dependent variation of phenoxido bridging angles and magnetic coupling.
Five new trinuclear heterometallic Cu(II)-Mn(II) complexes [(CuL)2Mn(O2CPh)2] (1), [(CuL)2Mn(N3)2] (2), [(CuL)2Mn(NCO)2] (3), [(CuL)2Mn(NO3)2] (4) and [(CuL)2Mn(Sal)2]·CH2Cl2 (5) have been synthesized with the di-Schiff base ligand H2L (where H2L = N,N'-bis(salicylidene)-1,3-propanediamine and Sal = salicylate). These complexes with different anionic co-ligands have been synthesized to attain a large variation in phenoxido bridging angles and to investigate its consequence on magnetic properties. Single crystal X-ray diffraction analyses reveal that complexes 1, 2, 4 and 5 are linear, whereas 3 has an angular geometry. Variable temperature magnetic susceptibility measurements suggest that all five complexes possess an overall antiferromagnetic interaction between Cu(II) and Mn(II) ions, which results in a final ferrimagnetic ground state with spin 3/2 in the Cu(II)-Mn(II)-Cu(II) trinuclear structure. The weakest antiferromagnetic interaction (J(Cu-Mn) = -7.0 cm(-1)) is observed for 2 having the lowest value of the Cu-O-Mn angle (92.0°), while the strongest antiferromagnetic interaction (J(Cu-Mn) = -26.5 cm(-1)) is observed for 3 having the largest Cu-O-Mn angle (101.4°). Complexes 1, 4 and 5 show average Cu-O-Mn angles of 98.2°, 97.6° and 97.7°, respectively, that lead to intermediate antiferromagnetic interactions (J(Cu-Mn) = -9.6, -9.7, -9.3 cm(-1) respectively).


[Urine samples from children collected in their homes].
Children at high risk of urinary tract infection (UTI) enter a programme for domestic urine sampling at the Paediatric Department in Aarhus. Parents collect urine, describe symptoms and post the samples. We wanted to determine the value of domestic urine sampling and to evaluate the programme. All samples received in 2004 were studied. A total of 706 urine samples from children in the programme were cultivated. In all 76 children fulfilled the criteria for UTI when culture and symptoms were compared. Dip-slide analysis had a sensitivity of 72% and a negative predictive value of 96%. A total of 329 urine samples with negative dip-slide analyses were collected from children with no urinary tract symptoms. Only 27 of these samples were culture-positive and none of these children developed signs of UTI. The results from this study suggest that home urine sampling from children at high risk of UTI with no symptoms does not contribute towards avoiding the development of pyelonephritis. A home urine sample analysis programme for children with symptoms is, however, a valuable instrument for early and efficient treatment of UTI in children with high risk of UTI. Urine samples should only be cultivated if the child has symptoms or the dip-slide test is positive.


N-Heterocyclic Carbene-Copper-Catalyzed Group-, Site-, and Enantioselective Allylic Substitution with a Readily Accessible Propargyl(pinacolato)boron Reagent: Utility in Stereoselective Synthesis and Mechanistic Attributes.
The first instances of catalytic allylic substitution reactions involving a propargylic nucleophilic component are presented; reactions are facilitated by 5.0 mol % of a catalyst derived from a chiral N-heterocyclic carbene (NHC) and a copper chloride salt. A silyl-containing propargylic organoboron compound, easily prepared in multigram quantities, serves as the reagent. Aryl- and heteroaryl-substituted disubstituted alkenes within allylic phosphates and those with an alkyl or a silyl group can be used. Functional groups typically sensitive to hard nucleophilic reagents are tolerated, particularly in the additions to disubstituted alkenes. Reactions may be performed on the corresponding trisubstituted alkenes, affording quaternary carbon stereogenic centers. Incorporation of the propargylic group is generally favored (vs allenyl addition; 89:11 to >98:2 selectivity); 1,5-enynes can be isolated in 75-90% yield, 87:13 to >98:2 SN2'/SN2 (branched/linear) selectivity and 83:17-99:1 enantiomeric ratio. Utility is showcased by conversion of the alkynyl group to other useful functional units (e.g., homoallenyl and Z-homoalkenyl iodide), direct access to which by other enantioselective protocols would otherwise entail longer routes. Application to stereoselective synthesis of the acyclic portion of antifungal agent plakinic acid A, containing two remotely positioned stereogenic centers, by sequential use of two different NHC-Cu-catalyzed enantioselective allylic substitution (EAS) reactions further highlights utility. Mechanistic investigations (density functional theory calculations and deuterium labeling) point to a bridging function for an alkali metal cation connecting the sulfonate anion and a substrate's phosphate group to form the branched propargyl addition products as the dominant isomers via Cu(III) π-allyl intermediate complexes.


Changes in reaction time and search time with background luminance in the mesopic range.
Vision relies on both rod and cone signals over a large range of ambient illumination that encompasses a number of common situations. It is important, therefore, to understand how performance changes with light level in functional visual tasks. We measured reaction times and search times using achromatic targets to examine the relationship between latency and luminance contrast as a function of background luminance. Visual search was more robust to changes in luminance than reaction time; search performance could be made invariant by scaling the effects of contrast, but the range of reaction time changed significantly over the mesopic range. We also investigated the extent to which two mesopic visual performance models described the dependence of reaction time and search time on stimulus spectra, using coloured stimuli. The 'effective contrast' model that we examined described the spectral dependence of both reaction time and search time well. A model for mesopic luminous efficiency based on reaction times described the spectral dependence of each response only in conditions where there was little influence of chromatic signals.


Case-mix, severity systems provide DRG alternatives.
Since their adoption, diagnosis related groups (DRGs) have been criticized for relying too much on the principal discharge diagnosis, for not taking the secondary diagnoses into account, and for ignoring the severity of a patient's illness or illnesses. Four case-mix and severity systems, Disease Staging, Patient Management Categories, MedisGroups, and Computerized Severity of Illness, offer alternatives to DRGs by either classifying patients into diagnostic categories or producing overall case severity scores. While most hospitals are likely to continue using DRGs or whatever successor is prescribed by regulation, some may find it useful to look seriously at these alternatives as a means of measuring the consumption of healthcare resources.


OPA1 requires mitofusin 1 to promote mitochondrial fusion.
The regulated equilibrium between mitochondrial fusion and fission is essential to maintain integrity of the organelle. Mechanisms of mitochondrial fusion are largely uncharacterized in mammalian cells. It is unclear whether OPA1, a dynamin-related protein of the inner membrane mutated in autosomal dominant optic atrophy, participates in fusion or fission. OPA1 promoted the formation of a branched network of elongated mitochondria, requiring the integrity of both its GTPase and C-terminal coiled-coil domain. Stable reduction of OPA1 levels by RNA interference resulted in small, fragmented, and scattered mitochondria. Levels of OPA1 did not affect mitochondrial docking, but they correlated with the extent of fusion as measured by polyethylene glycol mitochondrial fusion assays. A genetic analysis proved that OPA1 was unable to tubulate and fuse mitochondria lacking the outer membrane mitofusin 1 but not mitofusin 2. Our data show that OPA1 functionally requires mitofusin 1 to regulate mitochondrial fusion and reveal a specific functional difference between mitofusin 1 and 2.