Spatially heterogeneous selection in nature favors phenotypic plasticity in anuran larvae.
Theory holds that adaptive phenotypic plasticity evolves under spatial or temporal variation in natural selection. I tested this prediction in a classic system of predator-induced plasticity: frog tadpoles (Rana temporaria) reacting to predaceous aquatic insects. An outdoor mesocosm experiment manipulating exposure to Aeshna dragonfly larvae revealed plasticity in most characters: growth, development, behavior, and external morphology. I measured selection by placing 1927 tadpoles into enclosures within natural ponds; photographs permitted identification of the survivors six to nine days later. Fitness was defined as a linear combination of growth, development, and survival that correlates with survival to age 2 in another anuran species. In enclosures with many predators, selection-favored character values similar to those induced by exposure to Aeshna in mesocosms. The shift in selection along the predation gradient was strongest for characters that exhibited high predator-induced plasticity. A field survey of 50 ponds revealed that predator density changes over a spatial scale relevant for movement of individual adults and larvae: 17% of variation in predation risk was among ponds separated by tens to thousands of meters and 81% was among sites ≤10 m apart within ponds. These results on heterogeneity in the selection regime confirm a key tenant of the standard model for the evolution of plasticity.


Epidemiological study of self-reported sleep problems in Turkish high school adolescents.
The aim of the present study was to investigate the frequency and correlates of a variety of sleep problems in adolescents. A representative school-based sample of 3485 8th-12th graders was selected according to the cluster sampling technique. A sleep questionnaire and the Strengths and Difficulties Questionnaire were completed by the students along with their parents. Logistic regression analysis was used to identify the independent variables of insomnia, parasomnia and excessive daytime sleepiness (EDS). Initiation insomnia, maintenance insomnia, non-restorative sleep (NRS) and EDS were described by 12.4%, 10.7%, 9% and 9.7%, respectively. At least one parasomnia with a frequency above the median was reported by 23.4% (nightmare, 12.8%; sleep terror, 3.6%; sleepwalking, 2.5%; bruxism, 2.5%; and sleep talking, 10.9%). Insomnias and parasomnias were highly associated with each other. Female gender was related to maintenance insomnia, NRS and night terror. Emotional problems correlated with initiation insomnia, maintenance insomnia, NRS, EDS, nightmares and bruxism; hyperactivity/inattention with initiation insomnia, NRS and sleep talking. Conduct problems were associated with NRS, whereas poor school performance was associated with initiation insomnia. Self-reported sleep problems were prevalent and highly associated with each other and behavioral and emotional difficulties in Turkish adolescents.


Middle molecule clearance with high cut-off dialyzer versus high-flux dialyzer using continuous veno-venous hemodialysis with regional citrate anticoagulation: A prospective randomized controlled trial.
Regional anticoagulation with citrate during renal replacement therapy (RRT) reduces the risk of bleeding, extends dialyzer lifespan and is cost-effective. Therefore, current guidelines recommend its use if patients are not anticoagulated for another reason and if there are no contraindications against citrate. RRT with regional citrate anticoagulation has been established in critically ill patients as continuous veno-venous hemodialysis (CVVHD) to reduce citrate load. However, CVVHD is inferior regarding middle molecule clearance compared to continuous veno-venous hemofiltration (CVVH). The use of a high cut-off dialyzer in CVVHD may thus present an option for middle molecule clearance similar to CVVH. This may allow combining the advantages of both techniques. In this prospective, randomized, single-blinded single-center-trial, sixty patients with acute renal failure and established indication for renal replacement therapy were randomized 1:1 into two groups. The control group was put on CVVHD using regional citrate anticoagulation and a high-flux dialyzer, while the intervention group was on CVVHD using regional citrate anticoagulation and a high-cut-off dialyzer. The concentrations of urea, creatinine, β2-microglobulin, myoglobin, interleukin 6 and albumin were measured pre- and post-dialyzer 1, 6, 12, 24 and 48 hours after initiating CVVHD. Mean plasma clearance for β2-microglobulin was 19.6±5.8 ml/min in the intervention group vs. 12.2±3.6 ml/min in the control group (p<0.001). For myoglobin (8.0±4.5 ml/min vs. 0.2±3.6 ml/min, p<0.001) and IL-6 (1.5±4.3 vs. -2.5±3.5 ml/min, p = 0.002) a higher mean plasma clearance using high-cut-off dialyzer could be detected too, but no difference for urea, creatinine and albumin could be observed concerning this parameter between the two groups. CVVHD using a high cut-off dialyzer results in more effective middle molecule clearance than that with high-flux dialyzer. German Clinical Trials Register (DRKS00005254, registered 26th November 2013).


The Social Construction of Infertility Among Iranian Infertile Women: A Qualitative Study.
Infertility is considered an important phenomenon in couples' life. Infertility and its treatment process influence all aspects of the individual's life. This study aimed to explain the psycho-social process of social construction of infertility among Iranian infertile women. This was a qualitative study using a grounded theory approach. The study setting was the Vali-e-Asr Fertility Health Research Center and Avicenna Fertility clinic in Tehran. The sampling started purposefully and it was continued theoretically. The data collection was performed by using 36 semi-structured interviews, observation and field notes with 27 women who suffered from primary and secondary infertility having no living child. The method suggested by Strauss and Corbin was used for data analysis. Results indicate that "Concerns over life instability" and "being judged by others" were the participants' most important preoccupation. Attempts to stabilize life and get rid of being judged by others were key aspects of the social construction of infertility and the main strategies for resolving their preoccupation. This core concept explained the basic psychological-social process of infertility in relation to axial codes. The results of the study show that various interactive factors affect the social construction of infertility among infertile women who focus on the central concept of attempts to stabilize life and get rid of being judged by others. Therefore, in order to achieve this goal, infertile women should be empowered by effective coping strategies.


Second-harmonic generation in a bent-core nematic liquid crystal.
Second-harmonic generation (SHG) is studied in the magnetically aligned nematic phase of a bent-core liquid crystal (BCN) and compared to similar measurements made on a conventional rodlike (calamitic) nematic compound. The second-harmonic (SH) light detected from both materials is predominantly due to scattering and therefore incoherent. Results on the calamitic are consistent with a polarization induced by ordinary director fluctuations in the nematic phase. However, the SH scattering collected in the BCN exhibits a different temperature and angular dependence. We discuss how these differences could arise from the effects of short-range correlated, smectic-C-type molecular clusters, which have been detected in recent studies on various BCN materials.


LD Score regression distinguishes confounding from polygenicity in genome-wide association studies.
Both polygenicity (many small genetic effects) and confounding biases, such as cryptic relatedness and population stratification, can yield an inflated distribution of test statistics in genome-wide association studies (GWAS). However, current methods cannot distinguish between inflation from a true polygenic signal and bias. We have developed an approach, LD Score regression, that quantifies the contribution of each by examining the relationship between test statistics and linkage disequilibrium (LD). The LD Score regression intercept can be used to estimate a more powerful and accurate correction factor than genomic control. We find strong evidence that polygenicity accounts for the majority of the inflation in test statistics in many GWAS of large sample size.


Problem Gambling Messages on College Counseling Center Websites: An Over-Time and Cross-Country Comparison.
Gambling problems remain more prevalent among college students than any other adult population. Among the different informational services available to students struggling with this issue, the convenience, anonymity, and accessibility of the college counseling center website (CCW) make this a particularly appealing resource. This updated assessment explored the nature and frequency of problem gambling messages on U.S. CCWs. and assessed whether differences existed between U.S. and U.K. sites. Results showed that problem gambling remains disproportionately underrepresented on U.S. CCWs compared to other mental health concerns. Furthermore, in only one instance-links to pamphlets-did findings indicate any over-time increase in website communications. Overall, <11 % of U.S. CCWs mentioned anything regarding this topic. When assessing U.K. CCWs, results were relatively consistent with U.S. CCWs. Specifically, while significantly more U.K. sites mentioned anything regarding problem gambling than U.S. CCWs, this was mostly limited to links to self-help groups and issue-specific websites. Given the substantial health, social, and financial consequences linked to problem gambling behaviors, universities must focus on incorporating more information about this issue on CCWs and pursue initiatives to promote this service.


Upregulation of death pathway molecules in rat cerebellar granule neurons undergoing apoptosis.
Cerebellar granule neurons can be maintained in culture in a medium containing high serum and depolarising levels of KCl. When serum is removed and the KCl levels lowered from 25 to 5 mM, the cells undergo apoptosis. Apoptosis can be prevented by inhibitors of transcription or translation, suggesting a need for macromolecular synthesis in the apoptotic process. Using quantitative reverse transcription-polymerase chain reaction the levels of mRNA for a range of genes postulated to be important in apoptosis have been examined. Elevated levels of caspase 3, c-Jun, and Fas ligand were found, in addition to a corresponding increase in c-Jun protein and activation of caspase-3. These results suggest that cerebellar granule neurons upregulate components of both death receptor-mediated and the mitochondrial-mediated death pathways.


Shear Conditioning of Adipose Stem Cells for Reduced Platelet Binding to Engineered Vascular Grafts.
Conferring antithrombogenicity to tissue-engineered vascular grafts remains a major challenge, especially for urgent bypass grafting that excludes approaches based on expanding autologous endothelial cells (ECs) that requires weeks of cell culture. Adipose-derived stem cells (ASCs) are available from most patients in sufficient number for coronary bypass graft seeding and may be effective as allogeneic cells. We thus compared the adhesion and platelet binding of human ASCs that were shear conditioned with constant and pulsatile shear stress (SS) after seeding the cells on a biologically engineered matrix suitable for arterial grafts. A monolayer of cells was maintained up to 15 dyn/cm2 constant SS and up to 15 dyn/cm2 mean pulsatile SS for 6 days of shear flow. Platelet binding was reduced from 83% to 6% of surface area and nitric oxide production was increased 23-fold with 7.5-15 dyn/cm2 constant SS, but not pulsatile SS, relative to cells cultured statically on the matrix for 6 days. The reduction in platelet binding varied from no reduction to maximum reduction over a constant shear range of ∼2 to 4 dyn/cm2, respectively. Collectively, the study supports the potential use of ASCs to seed the luminal surface of a vascular graft made from this biologically engineered matrix to confer an antithrombogenic surface during the development of an endothelium from the seeded cells or the surrounding blood and tissue.


Thrombus aspiration plus intra-infarct-related artery administration of tirofiban improves myocardial perfusion during primary angioplasty for acute myocardial infarction.
We developed a new combined strategy of thrombus aspiration plus intra-infarct-related artery (IRA) bolus administration of tirofiban via the aspiration catheter in patients with ST-segment elevation myocardial infarction (STEMI). This strategy can reduce the distal embolism and achieve highly localized concentrations of tirofiban, which can improve myocardial reperfusion without increasing the risk of bleeding. The aim of this study was to investigate whether this combined strategy is superior to thrombus aspiration alone in improving myocardial perfusion in patients with STEMI undergoing primary angioplasty. This single center study included 108 matched control patients with STEMI, angioplasty after thrombus aspiration, and 108 study patients with STEMI plus intra-IRA administration of 500 microg of tirofiban. Both groups had subsequent 12-hour intravenous infusion of 0.1 microg x kg(-1) x min(-1) of tirofiban after angioplasty. The primary end points were Thrombolysis in Myocardial Infarction (TIMI) flow immediately after angioplasty, ST-segment elevation resolution (STR) (> 70%) at 90 minutes after angioplasty, and the peak of creatine kinase-MB (CK-MB) and troponin I (TnI). The secondary end points were the left ventricular ejection fraction (LVEF) in the hospital and at nine months follow-up, cardiac death, target vessel revascularization (TVR), re-infarction and the combination of these three as major adverse cardiac events (MACE) within nine months and any bleeding events. Baseline characteristics of the two groups were well-balanced. The TIMI 3 flow showed a better tendency in the intra-IRA group than in the aspiration alone group (97.22% vs. 87.04%, chi(2) = 7.863, P = 0.049). The peak of CK-MB (83.9 (68.9 - 310.5) U/L vs. 126.1 (74.7 - 356.7) U/L, P = 0.034) and TnI (42.7 (14.7 - 113.9) ng/ml vs. 72.5 (59.8 - 135.3) ng/ml, P = 0.029) were lower in the intra-IRA group than in the aspiration alone group. LVEF in the hospital favored the intra-IRA group, (45.7 +/- 8.3)% to (42.9 +/- 12.1)%, t = 1.98, P = 0.049. There was a tendency towards a lower MACE at 9-month follow-up in the intra-IRA group although it did not reach statistical difference (Log-rank chi(2) = 2.865, P = 0.09). There was no statistical difference in any bleeding events between the two groups. Thrombus aspiration plus intra-IRA bolus administration of tirofiban combined with angioplasty may be related with improved myocardium perfusion, saved more myocardium, and resulted in a better clinical prognosis.


[Fever and chills due to leptospirosis after travel to Thailand].
Two weeks after rafting on a river in Thailand a Dutch 54-year-old male experienced chills and high fever. While rafting he had wounded his hand. Because of the history (water contact, the wound, high fever with chills), of the findings at examination (fever, conjunctivitis) and of the laboratory findings (leukocytosis, albuminuria, disturbance of liver enzymes), a clinical diagnosis of 'leptospirosis' was made. This was confirmed by serological tests and culturing of Leptospirae from the blood. Leptospirosis is a zoonosis, in man associated with certain occupations, water sports and inundations. The clinical picture varies from a mild febrile disease (sometimes pyrexia of unknown origin) to a severe condition with kidney and liver failure, bleeding tendency, lung oedema (Weil's syndrome). In travellers with fever, water contact, leukocytosis and neutrophilia, leptospirosis must be considered and specific diagnostic tests applied.


Diagnosis and Treatment of Vestibular Neuritis/Neuronitis or Peripheral Vestibulopathy (PVP)? Open Questions and Possible Answers.
: The acute vestibular syndrome is a clinically defined entity consisting of vertigo or dizziness that develops acutely over minutes to hours and is accompanied by nausea/vomiting, gait instability, head motion intolerance, and nystagmus, while persisting over a day or more. When it is caused by a peripheral vestibular lesion and is not associated with clinically manifest auditory deficits, it is mostly labeled vestibular neuritis/neuronitis/neuropathy or sometimes peripheral vestibulopathy. Here, we propose hypotheses and discuss current research advances on viral or vascular factors in the pathogenesis, the recurrence, the site of lesion, old and new treatment options, contraindicated measures, the differential diagnosis, and the prognosis of vestibular neuritis/neuronitis/neuropathy or vestibulopathy. Possibly, other structures than the vestibular nerve are also involved in the pathogenetic process and the label peripheral vestibulopathy would be more apt.


[A psycholinguistic study in a patient with echolalia].
Language is often impaired in patients with a primary degenerative dementia syndrome. Severe dementia may even lead to mutism, a condition in which the person does not produce any spontaneous speech, despite preservation of consciousness. The question is if there are any language abilities left in patients who do not speak. In this single case-study the echolalic behaviour of a patient with severe dementia and mixed transcortical aphasia (or isolation of the speech area) was analysed by means of special linguistic tasks. In repeating sentences violating number agreement, the patient spontaneously corrected the pronoun, the noun or the verb. Furthermore, her verbal output during repetition tasks was highly constrained to lexically acceptable Dutch nouns. Despite extremely poor comprehension, this patient did not repeat verbal utterances in a parrot-like fashion. There are not many reports in the literature of patients who develop a mixed transcortical aphasia as a consequence of primary degenerative dementia. A comparable case was described by H. Whitaker. Single case-studies, such as these, are essential to our insight into the course of language breakdown in senile dementia. The preserved repetition ability of this patient demonstrates the robustness of the articulatory loop system, even if there is a severe comprehension deficit.


[Mutation frequency test for isepamicin (HAPA-B)].
Mutation frequency tests for isepamicin (HAPA-B), a new aminoglycoside antibiotic, were carried out using Salmonella typhimurium strains TA98, TA100, TA1535 and Escherichia coli WP2uvrA. After a 30-minute exposure of bacterial cells at 37 degrees C to HAPA-B in a buffer solution, the cells were washed twice with a buffer solution to minimize the cytotoxicity of the drug. Then washed cells were inoculated on minimum glucose agar plates to determine mutation frequency. The results should no significant increase in mutation frequency with increasing HAPA-B concentration; suggesting that the drug has no mutagenicity detectable by this test system.


Productivity of medical research in Switzerland.
Little evidence exists about what contributes to successful medical research, an increasingly important issue in an era of limited research budgets. This study examined predictors of productivity of Swiss medical research. Principal investigators of clinical research projects funded by the Swiss National Science Foundation between 1990 and 1994 were surveyed by mail. They provided information about the research question, whether changes were made to the protocol and why, their assessment of the importance of results for science and for public health, and additional funding of the project. The amount of the grant and the project priority score were obtained from the Foundation. Indicators of scientific productivity were the number of peer-reviewed articles and the summed impact factor per grant. The size of the grant predicted scientific output (number of articles and summed impact factor), but the marginal return decreased with the total sum awarded. The award of a continuation grant by the same agency and additional funding from other sources were also positively linked with productivity. In addition, the initial priority rating of the project by the funding agency's scientific committee and the assessment of scientific importance of the results by the principal investigator were also independently associated with productivity. Finally, modifications of the initial research plan in response to new scientific opportunities were linked with greater productivity, whereas modifications induced by technical or other difficulties were associated with lower productivity. Productivity in medical research, measured by peer-reviewed articles produced, requires adequate resources and ability to respond to new scientific challenges, and it can be anticipated by peer-review.


Excited-states of a rhenium carbonyl diimine complex: solvation models, spin-orbit coupling, and vibrational sampling effects.
We present a quantum-chemical investigation of the excited states of the complex [Re(CO)3(Im)(Phen)]+ (Im = imidazole; Phen = 1,10-phenanthroline) in solution including spin-orbit couplings and vibrational sampling. To this aim, we implemented electrostatic embedding quantum mechanics/molecular mechanics (QM/MM) in the Amsterdam Density Functional program suite, suitable for time-dependent density functional calculations including spin-orbit couplings. The new implementation is employed to simulate the absorption spectrum of the complex, which is compared to the results of implicit continuum solvation and frozen-density embedding. Molecular dynamics simulations are used to sample the ground state conformations in solution. The results demonstrate that any study of the excited states of [Re(CO)3(Im)(Phen)]+ in solution and their dynamics should include extensive sampling of vibrational motion and spin-orbit couplings.


Temperature limited fed-batch technique for control of proteolysis in Pichia pastoris bioreactor cultures.
BACKGROUND: A temperature limited fed-batch (TLFB) technique is described and used for Pichia pastoris Mut+ strain cultures and compared with the traditional methanol limited fed-batch (MLFB) technique. A recombinant fusion protein composed of a cellulose-binding module (CBM) from Neocallimastix patriciarum cellulase 6A and lipase B from Candida antarctica (CALB), was produced and secreted by this strain. RESULTS: A protein concentration of about 1 g L-1 was produced in the MLFB process. However, this product was considerably degraded by protease(s). By applying the TLFB process, the yield was increased to 2 g L-1 full-length product and no proteolytic degradation was observed. Flow cytometry analysis showed that the percentage of dead cells increased rapidly during the initial methanol feed phase in the MLFB process and reached a maximum of about 12% after about 40-70 hours of methanol feeding. In the TLFB process, cell death rate was low and constant and reached 4% dead cells at the end of cultivation (about 150 hours methanol feeding time). The lower cell death rate in the TLFB correlated with a lower protease activity in the culture supernatant. The specific alcohol oxidase (AOX) activity in the TLFB process was 3.5 times higher than in the MLFB process. CONCLUSION: Three mechanisms that may contribute to the much higher accumulation of product in the TLFB process are: 1) reduced proteolysis due to lower temperature, 2) reduced proteolysis due to lower cell death and protease release to the medium, 3) increased synthesis rate due to higher AOX activity.


CDC Online Course: Reproductive Health in Emergency Preparedness and Response.
In an emergency, the needs of women of reproductive age, particularly pregnant and postpartum women, introduce unique challenges for public health and clinical care. Incorporating reproductive health issues and considerations into emergency preparedness and response is a relatively new field. In recent years, several resources and tools specific to reproductive health have been developed. However, there is still a need for training about the effects of emergencies on women of reproductive age. In an effort to train medical and public health professionals about these topics, the CDC Division of Reproductive Health developed Reproductive Health in Emergency Preparedness and Response, an online course that is available across the United States.


A rapid method for isolation of purified, physiologically active chloroplasts, used to study the intracellular distribution of amino acids in pea leaves.
A procedure is described for the rapid (<5 min) isolation of purified, physiologically active chloroplasts from Pisum sativum L. Mitochondrial and microbody contamination is substantially reduced and broken chloroplasts are excluded by washing through a layer containing a treated silica sol. On average the preparations contain 93% intact chloroplasts and show high rates of (14)CO2 fixation and CO2-dependent O2 evolution (over 100 μmol/mg chlorophyll(chl)/h); they are also able to carry out light-driven incorporation of leucine into protein (4 nmol/mg chl/h). The amino-acid contents of chloroplasts prepared from leaves and from leaf protoplasts have been determined. Asparagine is the most abundant amino acid in the pea chloroplast (>240 nmol/mg chl), even thought it is proportionately lower in the chloroplast relative to the rest of the cell. The chloroplasts contain about 20% of many of the amino acids of the cell, but for individual amino acids the percentage in the chloroplast ranges from 8 to 40% of the cell total. Glutamic acid, glutamine and aspartic acid are enriched in the chloroplasts, while asparagine, homoserine and β-(isoxazolin-5-one-2-yl)-alanine are relatively lower. Leakage of amino acids from the chloroplast during preparation or repeated washing was ca. 20%. Some differences exist between the amino-acid composition of chloroplasts isolated from intact leaves and from protoplasts. In particular, γ-aminobutyric acid accumulates to high levels, while homoserine and glutamic acid decrease, during protoplast formation and breakage.


The olfactory system as a puzzle: playing with its pieces.
The mammalian olfactory bulb (OB) has all the features of a whole mammalian brain but in a more reduced space: neuronal lamination, sensory inputs, afferences, or efferences to other centers of the central nervous system, or a contribution of new neural elements. Therefore, it is widely considered as "a brain inside the brain." Although this rostral region has the same origin and general layering as the other cerebral cortices, some distinctive features make it very profitable in experimentation in neurobiology: the sensory inputs are driven directly on its surface, the main output can be accessed anatomically, and new elements appear in it throughout adult life. These three morphological characteristics have been manipulated to analyze further the response of the whole OB. The present review offers a general outlook into the consequences of such experimentation in the anatomy, connectivity and neurochemistry of the OB after (a) sensory deprivation, mainly by naris occlusion; (b) olfactory deinnervation by means of olfactory epithelium damage, olfactory nerve interruption, or even olfactory tract disruption; (c) the removal of the principal neurons of the OB; and (d) management of the arrival of newborn interneurons from the rostral migratory stream. These experiments were performed using surgical or chemical methods, but also by means of the analysis of genetic models, some of whose olfactory components are missing, colorless or mismatching within the wild-type scenario of odor processing.


Conflicts of interest in government-funded studies.
Conflict of interest in scientific publications has become a topic of critical importance. A primary focus has been the relationship between authors, journals and the pharmaceutical industry. That focus must be expanded to include government funding organizations. There are significant benefits to authors and investigators in participating in government-funded research, and to journals in publishing it. There are substantial risks to patients in not considering the potential for conflict of interest.


Synthesis of (R)-2-trimethylsilyl-2-hydroxyl-ethylcyanide catalyzed with (R)-oxynitrilase from loquat seed meal.
The synthesis of optically active (R)-2-trimethylsilyl-2-hydroxyl-ethylcyanide by asymmetric trans-cyanation of acetyltrimethylsilane with acetone cyanohydrin in a biphasic system was achieved using (R)-oxynitrilase from loquat seed meal. Diisopropyl ether was the most suitable organic phase among the organic solvents examined. The optimal concentration of acetyltrimethylsilane, concentration of crude enzyme, volume ratio of the aqueous to the organic phase, temperature and the buffer pH value were 14 mM: , 61.4 U ml-1, 13% (v/v), 30 degrees C and 4, respectively. The substrate conversion and the product enantiomeric excess were 95% and 98% under the optimized conditions. Acetyltrimethylsilane was a better substrate of the enzyme than its carbon counterpart.


Mitochondrial Bax translocation partially mediates synergistic cytotoxicity between histone deacetylase inhibitors and proteasome inhibitors in glioma cells.
The effects of combining histone deacetylase (HDAC) inhibitors and proteasome inhibitors were evaluated in both established glioblastoma multiforme (GBM) cell lines and short-term cultures derived from the Mayo Clinic xenograft GBM panel. Coexposure of LBH589 and bortezomib at minimally toxic doses of either drug alone resulted in a striking induction of apoptosis in established U251, U87, and D37 GBM cell lines, as well as in GBM8, GBM10, GBM12, GBM14, and GBM56 short-term cultured cell lines. Synergism of apoptosis induction was also observed in U251 cells when coexposing cells to other HDAC inhibitors, including LAQ824 and trichostatin A, with the proteasome inhibitor MG132, thus demonstrating a class effect. In U251 cells, bortezomib alone or in combination with LBH589 decreased Raf-1 levels and suppressed Akt and Erk activation. LBH589 or bortezomib alone increased expression of the cell cycle regulators p21 and p27. Additionally, the combination, but not the individual agents, markedly enhanced JNK activation. Synergistic induction of apoptosis after exposure to LBH589 and bortezomib was partially mediated by Bax translocation from the cytosol to the mitochondria resulting from Bax conformational changes. Bax translocation precedes cytochrome c release and apoptosis, and selective down-regulation of Bax using siRNA significantly mitigates the cytotoxicity of LBH589 and bortezomib. This combination regimen warrants further preclinical and possible clinical study for glioma patients.


Access to care for children of migratory agricultural workers: factors associated with unmet need for medical care.
To assess the correlates of unmet need for medical care among migrant children. A cross-sectional household survey used multistage sampling to identify migrant families in eastern North Carolina. Three hundred adult caretakers of 1 (per household) randomly selected child <13 years old. Fifty-three percent of the children had an unmet medical need. The most common reasons for unmet medical need were lack of transportation (80%) and lack of knowledge of where to go for care (20%). Unmet medical need was associated inversely with less than very good health (odds ratio [OR]: 0.31; 95% confidence interval [CI]: 0.16-0.61) and less than high school caretaker education (OR: 0.62; 95% CI: 0.39-0.98) and was associated directly with 1) having bed-days due to illness (OR: 2.46; 95% CI: 1.42-4.26), 2) lacking an annual well examination (OR:1.89; 95% CI: 1.12-3.20), 3) transportation dependence (OR:1.97; 95% CI: 1.24-3.13), 4) female gender (OR: 1.69; 95% CI: 1.07-2.67), 5) preschool age (OR: 2.24; 95% CI: 1.28-3.92), and 6) very high caretaker work pressure (OR: 5.01; 95% CI: 2.98-8.42). Adjustment using multiple logistic regression reveals unmet medical need to be independently associated with preschool age (OR: 2.08; 95% CI: 1.05-4.13) and very high caretaker pressure to work (OR: 5.93; 95% CI: 3.24-10.85). Of sampled children, 27% were preschool aged, and 40% had caretakers categorized with high work pressure. Medical-access barriers among migrant children are largely nonfinancial. Preschool-aged migrant children disproportionately experience unmet medical need. Decreasing forgone care among migrant children will likely require a combination of individual, health-system, and labor-policy modifications.


Depression and eating styles are independently associated with dietary intake.
Depression and eating styles are two important, interrelated factors associated with dietary intake. However, it remains unclear whether depression and eating styles are independently associated with dietary intake, and whether associations between depression and dietary intake are mediated by eating styles. Therefore, the aim of the current study was to investigate the associations of, and interplay between depression and eating styles in relation to different aspects of dietary intake. Cross-sectional data from 1442 participants (healthy controls (22.7%), remitted (61.0%) and current patients (16.3%)) from the Netherlands Study of Depression and Anxiety were used. Linear regression analyses were used to determine associations of depressive disorders (DSM-IV based psychiatric interview), self-reported depressive symptoms (Inventory of Depressive Symptomatology), emotional, external and restrained eating (Dutch Eating Behavior Questionnaire) with 4 measures of dietary intake (total energy intake (kcal/d), Mediterranean diet score (MDS), intake of sweets foods (g/d), and snack/fast-food (g/d)) measured with a 238-item food frequency questionnaire. Statistical mediation analyses were used to study whether associations between depression and dietary intake were mediated by eating styles. Current depression diagnosis and severity were associated with lower MDS and higher intake of sweet foods and snack/fast-food. Emotional and external eating were associated with higher intakes of snack/fast-food; external eating was also associated with higher total energy intake. Restrained eating was associated with lower total energy and intake of sweet foods, and higher MDS. Associations between current depression or severity and intake of snack/fast-food were mediated by external eating. In general, depression and eating styles contributed independently to poorer diet quality and higher intake of sweet and snack/fast-food. The association between depression and higher intake of snack/fast-food was mediated by external eating.


Specific class II histocompatibility gene polymorphism in BB rats.
The BB rat spontaneously develops insulin-dependent diabetes mellitus of autoimmune etiology. From breeding studies, one of the genes necessary for the development of diabetes in these animals is linked to RT1, the rat major histocompatibility complex. To better define the BB rat's RT1-linked diabetogenic gene (RT1-DM), we have used restriction endonucleases BamH1 and EcoR1 in conjunction with an I-A alpha (class II mouse major histocompatibility complex) gene probe to study RT1 class II gene polymorphisms among diabetes-prone BB rats and the related non-diabetes-prone BBN rats. Both BB and BBN rats are indistinguishable RT1u by serologic methods. Four polymorphic chromosome types (la, lb, lla, and llb) were recognized among the control BBN rats. In contrast, all BB rats were homozygous (lla/lla). From the multiple breeding programs involved, we hypothesize that the BB rat's RT1-linked diabetogenic gene is linked to an l-A alpha-defined gene of the type lla chromosome. The ability to split the RT1u of BB rats will provide a powerful tool to localize and characterize RT1-DM.


Adsorption, intrusion and freezing in porous silica: the view from the nanoscale.
This review presents the state of the art of molecular simulation and theory of adsorption, intrusion and freezing in porous silica. Both silica pores of a simple geometry and disordered porous silicas which exhibit morphological and topological disorders are considered. We provide a brief description of the numerical models of porous silicas available in the literature and present the most common molecular simulation and theoretical methods. Adsorption in regular and irregular pores is discussed in the light of classical theories of adsorption and capillary condensation in pores. We also present the different evaporation mechanisms for disordered systems: pore blocking and cavitation. The criticality of fluids confined in pores, which is still the matter of debate, is then discussed. We review theoretical results for intrusion/extrusion and freezing in silica pores and discuss the validity of classical approaches such as the Washburn-Laplace equation and Gibbs-Thomson equation to describe the thermodynamics of intrusion and in-pore freezing. The validity of the most widely used characterization techniques is then discussed. We report some concluding remarks and suggest directions for future work.


Accelerating T2 mapping of the brain by integrating deep learning priors with low-rank and sparse modeling.
To accelerate T2 mapping with highly sparse sampling by integrating deep learning image priors with low-rank and sparse modeling. The proposed method achieves high-speed T2 mapping by highly sparsely sampling (k, TE)-space. Image reconstruction from the undersampled data was done by exploiting the low-rank structure and sparsity in the T2 -weighted image sequence and image priors learned from training data. The image priors for a single TE were generated from the public Human Connectome Project data using a tissue-based deep learning method; the image priors were then transferred to other TEs using a generalized series-based method. With these image priors, the proposed reconstruction method used a low-rank model and a sparse model to capture subject-dependent novel features. The proposed method was evaluated using experimental data obtained from both healthy subjects and tumor patients using a turbo spin-echo sequence. High-quality T2 maps at the resolution of 0.9 × 0.9 × 3.0 mm3 were obtained successfully from highly undersampled data with an acceleration factor of 8. Compared with the existing compressed sensing-based methods, the proposed method produced significantly reduced reconstruction errors. Compared with the deep learning-based methods, the proposed method recovered novel features better. This paper demonstrates the feasibility of learning T2 -weighted image priors for multiple TEs using tissue-based deep learning and generalized series-based learning. A new method was proposed to effectively integrate these image priors with low-rank and sparse modeling to reconstruct high-quality images from highly undersampled data. The proposed method will supplement other acquisition-based methods to achieve high-speed T2 mapping.


Risk factors for nursing home placement in a population-based dementia cohort.
To examine risk factors for nursing home placement in a population-based dementia cohort. The Mayo Clinic Medical Records linkage system was used to identify all patients with onset of dementia between 1980 and 1984. The patient group included 314 cases who met DSM-III-R criteria for dementia, including 220 cases who were community dwelling at onset. All dementia patients were followed until death. A control group included 323 patients who did not, at any point, meet DSM-III-R criterion for dementia. The groups were initially matched on age, gender, and year of initial registration. Demographic, medical, social, and functional predictors were examined as static and time-dependent risk factors for nursing home placement in the initial community-dwelling subgroups, using stepwise Cox regression modeling. Of the 314 dementia patients, 282 took residence in licensed skilled nursing homes for at least 6 weeks, suggestive of custodial care, at some point during the course of their illness. In the control group, 162 of the 323 people required nursing home placement. Within controls, the predictor variables of time to nursing home placement included initial age, being divorced, living in a townhome, apartment or assisted living apartment, change in Charlson comorbidity score, and change in amount of daily assistance required. Within the dementia sample, seven predictors were eventually determined to be associated with time to nursing home placement. These included total number of years of education, age at onset of dementia, being single, living in a retirement or supervised apartment at onset, change in Charlson comorbidity score, and a change in the amount of daily assistance required. Cumulative incidence of placement was 90% in the dementia cohort and 50% in the controls. Certain variables seem to impact time to nursing home placement in all older persons, whether they have dementia or not. Among these are age, living in assisted living settings, increasing comorbidity scores, and increasing need for functional assistance. Certain additional factors may have a specific impact in dementia. Among these is education, which seems to provide a protective effect. These predictors may be important covariates in clinical dementia studies that include time to nursing home placement as an outcome variable.


Sustaining improvement of hospital-wide initiative for patient safety and quality: a systematic scoping review.
Long-term sustained improvement following implementation of hospital-wide quality and safety initiatives is not easily achieved. Comprehensive theoretical and practical understanding of how gained improvements can be sustained to benefit safe and high-quality care is needed. This review aimed to identify enabling and hindering factors and their contributions to improvement sustainability from hospital-wide change to enhance patient safety and quality. A systematic scoping review method was used. Searched were peer-reviewed published records on PubMed, Scopus, World of Science, CINAHL, Health Business Elite, Health Policy Reference Centre and Cochrane Library and grey literature. Review inclusion criteria included contemporary (2010 and onwards), empirical factors to improvement sustainability evaluated after the active implementation, hospital(s) based in the western Organisation for Economic Co-operation and Development countries. Numerical and thematic analyses were undertaken. 17 peer-reviewed papers were reviewed. Improvement and implementation approaches were predominantly adopted to guide change. Less than 6 in 10 (53%) of reviewed papers included a guiding framework/model, none with a demonstrated focus on improvement sustainability. With an evaluation time point of 4.3 years on average, 62 factors to improvement sustainability were identified and emerged into three overarching themes: People, Process and Organisational Environment. These entailed, as subthemes, actors and their roles; planning, execution and maintenance of change; and internal contexts that enabled sustainability. Well-coordinated change delivery, customised local integration and continued change effort were three most critical elements. Mechanisms between identified factors emerged in the forms of Influence and Action towards sustained improvement. The findings map contemporary empirical factors and their mechanisms towards change sustainability from a hospital-wide initiative to improve patient safety and quality. The identified factors and mechanisms extend current theoretical and empirical knowledgebases of sustaining improvement particularly with those beyond the active implementation. The provided conceptual framework offers an empirically evidenced and actionable guide to assist sustainable organisational change in hospital settings.


Anaerobic stimulated mixed culture system.
A compartmented, autoclavable culture vessel has been developed for the purpose of studying interactive associations of microorganisms which are essential to the anaerobic decomposition of sewage sludge. The unit employs sterile filter membranes to subdivide the interior culture space into individual compartments. Bacteria cultured in one compartment are denied access to adjacent compartments, even though rapid interchange of nutrients and metabolic waste products occurs throughout the unit. The obligate methane-forming anaerobe, Methanobacillus omelianskii has been successfully grown and concentrated in this system by use of a synthetic medium reduced with sodium sulfide. The feasibility of using this system to study microbial interactions was, in part, demonstrated by growing M. omelianskii in a thoroughly aerated medium which had been biologically reduced by Escherichia coli prior to inoculation with the anaerobe. Under this condition of simulated mixed culture growth, the cell yield of both microorganisms, as well as specific metabolic activities ascribed to each organism, was readily monitored.


Eating Behavior in Aging and Dementia: The Need for a Comprehensive Assessment.
Eating behavior can change during aging due to physiological, psychological, and social changes. Modifications can occur at different levels: (1) in food choice, (2) in eating habits, and (3) in dietary intake. A good dietary behavior, like the Mediterranean dietary pattern, can be a protective factor for some aging related pathologies, such as dementia, while a worse eating behavior can lead to pathological conditions such as malnutrition. Changes in eating behavior can also be linked to the onset of dementia: for some types of dementia, such as frontotemporal dementia, dietary changes are one of the key clinical diagnostic feature, for others, like Alzheimer's disease, weight loss is a clinical reported feature. For these reasons, it is important to be able to assess eating behavior in a proper way, considering that there are normal age-related changes. An adequate assessment of dietary behavior can help to plan preventive intervention strategies for heathy aging or can help to identify abnormal behaviors that underline aging related-diseases. In this review, we have analyzed normal age-related and dementia-related changes and the tools that can be used to assess eating behavior. Thus, we make recommendations to screening and monitoring eating behavior in aging and dementia, and to adopt these tools in clinical practice.


Suspected Primary Adrenal Lymphoma (PAL) Associated With Hemophagocytic Lymphohistiocytosis (HLH).
Adrenal incidentalomas, masses noted on imaging performed for other purposes, are common, with 10% to 15% presenting as bilateral adrenal masses. These cases can be challenging as the differential diagnosis is broad, including metastatic disease, primary adrenal lymphoma (PAL), or infection, and often requiring a biopsy if initial biochemical workup is unrevealing. We present here a relevant case description, laboratory and radiologic imaging studies, and discussion of literature. A 62-year-old Korean woman presented with altered mental status and fevers. She was found to have bilateral adrenal incidentalomas and retained acupuncture needles. Adrenal workup did not show biochemical evidence of hormonal excess. Infectious workup was unrevealing, as was a metal/toxin workup due to retained acupuncture needles. Fevers and episodes of hypotension persisted which prevented the patient from obtaining an adrenal biopsy. Bone marrow biopsy was obtained for pancytopenia and revealed B-cell lymphoma with large cell morphology and few histiocytes with hemophagocytosis, raising concern for lymphoma-induced hemophagocytic lymphohistiocytosis (HLH). PAL associated with HLH was highly suspected in our patient, given the large (7 cm) bilateral adrenal masses and bone marrow biopsy findings of lymphoma. The patient was treated for diffuse large B-cell lymphoma, with clinical improvement. PAL is a rare but aggressive lymphoma with few reported cases. It should be considered in the differential for both unilateral and bilateral adrenal masses. An early diagnosis is crucial as the main treatment is chemotherapy rather than surgery and it confers a significant survival benefit.


[Radionuclide visualization of non-skeletogenous tumors using 99mTc-phosphates].
The paper is concerned with the results of radionuclide investigation of 51 patients with different tumors located beyond the osseous tissue. In spite of the fact that 99mTc-phosphates were well known as agents for radionuclide diagnosis of bone tumors, they can be employed for obtaining certain diagnostic information concerning topical diagnosis and the determination of a degree of the distribution of processes of nonskeletogenous nature. Of 51 patients with soft tissue pathology clear visualization of lesion foci was obtained in 34 patients (66.7%). Positive results of radionuclide diagnosis with 99mTc-pyrophosphate were noted in scintigraphy of patients with breast, ovarian, soft tissue and maxillofacial tumors. Besides, clear visualization of lesion foci was achieved in 6 of 11 patients with benign diseases: postoperative scars, inflammatory infiltrates, synovioma. The results obtained indicated the absence of necessary specificity of 99mTc-phosphates to osseous tissue.


Gender Differences in Grant Submissions across Science and Engineering Fields at the NSF.
There has been great growth in women's participation in the US academic doctoral workforce, but underrepresentation remains in all science and engineering fields, especially at high academic ranks. We obtained estimates of the numbers of professorial women and men in fields likely to seek funding from the National Science Foundation and aligned those numbers with each of six research directorates to investigate temporal trends in submission patterns. We found that women are as likely to be funded as men, but the percentage of women submitting proposals was less than expected in every field but engineering. Women are as likely as men to be employed at the most research active institutions, but women are less likely than men to self-report research as their primary work activity in almost all fields but engineering. This work imbalance ultimately limits the diversity of basic science research ideas in science and engineering.


Metarhizium robertsii ammonium permeases (MepC and Mep2) contribute to rhizoplane colonization and modulates the transfer of insect derived nitrogen to plants.
The endophytic insect pathogenic fungi (EIPF) Metarhizium promotes plant growth through symbiotic association and the transfer of insect-derived nitrogen. However, little is known about the genes involved in this association and the transfer of nitrogen. In this study, we assessed the involvement of six Metarhizium robertsii genes in endophytic, rhizoplane and rhizospheric colonization with barley roots. Two ammonium permeases (MepC and Mep2) and a urease, were selected since homologous genes in arbuscular mycorrhizal fungi were reported to play a pivotal role in nitrogen mobilization during plant root colonization. Three other genes were selected on the basis on RNA-Seq data that showed high expression levels on bean roots, and these encoded a hydrophobin (Hyd3), a subtilisin-like serine protease (Pr1A) and a hypothetical protein. The root colonization assays revealed that the deletion of urease, hydrophobin, subtilisin-like serine protease and hypothetical protein genes had no impact on endophytic, rhizoplane and rhizospheric colonization at 10 or 20 days. However, the deletion of MepC resulted in significantly increased rhizoplane colonization at 10 days whereas ΔMep2 showed increased rhizoplane colonization at 20 days. In addition, the nitrogen transporter mutants also showed significantly higher 15N incorporation of insect derived nitrogen in barley leaves in the presence of nutrients. Insect pathogenesis assay revealed that disruption of MepC, Mep2, urease did not reduce virulence toward insects. The enhanced rhizoplane colonization of ΔMep2 and ΔMepC and insect derived nitrogen transfer to plant hosts suggests the role of MepC and Mep2 in Metarhizium-plant symbiosis.


Genetic diversity of Schizolobium parahyba var. amazonicum (Huber ex. Ducke) Barneby, in a forest area in Brazil.
Schizolobium parahyba var. amazonicum (Fabaceae) is an arboreal species, endemic to the Amazon Rainforest, popularly known as paricá. It is used on a commercial scale in the timber sector, pulp and paper production, reclamation projects in degraded and landscaped areas. However, there is no availability of genetically improved material selected for the environmental conditions of the State of Espírito Santo, Brazil. In this sense, the present study aimed to characterize the genetic diversity in a population of S. amazonicum, established in a forest area in the southern region of the State of Espírito Santo, using inter-simple sequence repeat (ISSR) molecular markers. DNA samples from 171 individuals were analyzed using 11 ISSR primers, which generated 79 polymorphic bands in a total of 136 fragments (58%). The polymorphic information content performed for the ISSR markers revealed a mean of 0.37, classifying them as moderately informative. The number of loci found (N = 79) was greater than that established as the optimal number (N = 69) for the analyses. High genetic diversity was found with the parameters, genetic diversity of Nei (HE = 0.375) and Shannon index (I = 0.554). The data demonstrated in the dendrogram, based on the UPGMA cluster analysis, corroborated by the Bayesian analysis performed by the STRUCTURE program, which indicated the formation of two distinct clusters (K = 2). One of the groups was formed with the majority of the individuals (153 genotypes) and the second with the minority (18 genotypes). The results revealed high genetic diversity in the population of S. amazonicum evaluated in the present study, determining the potential of the population to be used as an orchard for seed collection and production of seedlings with confirmed genetic variability.


Surgical site infections in older adults: epidemiology and management strategies.
Surgical site infections (SSIs) represent a major source of morbidity and mortality among older adults. In this review we discuss the epidemiology and risk factors for SSIs among older adults. We also offer an overview of current treatment and management strategies for several common SSIs. Our comments focus on the following areas in order to illustrate issues of clinical importance in the older patient: (i) cardiac surgery; (ii) vascular grafts; (iii) total joint arthroplasty; (iv) breast surgery; and (v) spinal surgeries. Besides being common and relatively specific to older adults, several of these surgical procedures require the use of prosthetic materials or devices, which present unique treatment challenges in the context of infection. When an older adult does develop an SSI, it is critical for clinicians to establish an overall treatment goal for each patient. In the majority of patients, this will be either complete cure or remission followed by suppressive therapy. However, clinicians caring for older adults must consider not only the possibility of microbiological cure, but also balance the need to preserve functional status and overall quality of life. Infections associated with devices and prosthetic material can present unique treatment challenges. Treatment of significant infections often requires prolonged courses of parenteral and/or oral antimicrobial therapy, which can raise issues related to the safety and tolerability of antimicrobial agents, including higher rates of nephrotoxicity. Issues concerning overall functional status, nutritional reserve and medical co-morbidities must be taken into consideration when approaching SSIs in an older adult.


Temporal pitch perception and the binaural system.
Two experiments examined the relationship between temporal pitch (and, more generally, rate) perception and auditory lateralization. Both used dichotic pulse trains that were filtered into the same high (3,900-5,400-Hz) frequency region in order to eliminate place-of-excitation cues. In experiment 1, a 1-s periodic pulse train of rate Fr was presented to one ear, and a pulse train of rate 2Fr was presented to the other. In the "synchronous" condition, every other pulse in the 2Fr train was simultaneous with a pulse in the opposite ear. In each trial, subjects concentrated on one of the two binaural images produced by this mixture: they matched its perceived location by adjusting the interaural level difference (ILD) of a bandpass noise, and its rate/pitch was then matched by adjusting the rate of a regular pulse train. The results showed that at low Fr (e.g., 2 Hz), subjects heard two pulse trains of rate Fr, one in the "higher rate" ear, and one in the middle of the head. At higher Fr (>25 Hz) subjects heard two pulse trains on opposite sides of the midline, with the image on the higher rate side having a higher pitch than that on the "lower rate" side. The results were compared to those in a control condition, in which the pulses in the two ears were asynchronous. This comparison revealed a duplex region at Fr > 25 Hz, where across-ear synchrony still affected the perceived locations of the pulse trains, but did not affect their pitches. Experiment 2 used a 1.4-s 200-Hz dichotic pulse train, whose first 0.7 s contained a constant interaural time difference (ITD), after which the sign of the ITD alternated between subsequent pulses. Subjects matched the location and then the pitch of the "new" sound that started halfway through the pulse train. The matched location became more lateralized with increasing ITD, but subjects always matched a pitch near 200 Hz, even though the rate of pulses sharing the new ITD was only 100 Hz. It is concluded from both experiments that temporal pitch perception is not driven by the output of binaural mechanisms.


Higher CO2-insufflation pressure inhibits the expression of adhesion molecules and the invasion potential of colon cancer cells.
To investigate the influence of CO(2)-insufflation pressure on adhesion, invasion and metastatic potential of colon cancer cells based on adhesion molecules expression. With an in vitro artificial pneumoperitoneum model, SW1116 human colon carcinoma cells were exposed to CO(2)-insufflation in 5 different pressure groups: 6 mmHg, 9 mmHg, 12 mmHg, 15 mmHg and control group, respectively for 1 h. Expression of E-cadherin, ICAM-1, CD44 and E-selectin was measured at 0, 12, 24, 48 and 72 h after CO(2)-insufflation using flow cytometry. The adhesion and invasion capacity of SW1116 cells before and after exposure to CO(2)-insufflation was detected by cell adhesion/invasion assay in vitro. Each group of cells was injected intraperitoneally into 16 BALB/C mice. The number of visible abdominal cavity tumor nodules, visceral metastases and survival of the mice were recorded in each group. The expression of E-cadherin, ICAM-1, CD44 and E-selectin in SW1116 cells were changed significantly following exposure to CO(2) insufflation at different pressures (P < 0.05). The expression of E-cadherin, CD44 and ICAM-1 decreased with increasing CO(2)-insufflation pressure. The adhesive/invasive cells also decreased gradually with increasing pressure as determined by the adhesion/invasion assay. In animal experiments, the number of abdominal cavity tumor nodules in the 15 mmHg group was also significantly lower than that in the 6 mmHg group (29.7 +/- 9.91 vs 41.7 +/- 14.90, P = 0.046). However, the survival in each group was not statistically different. CO(2)-insufflation induced a temporary change in the adhesion and invasion capacity of cancer cells in vitro. Higher CO(2)-insufflation pressure inhibited adhesion, invasion and metastatic potential in vitro and in vivo, which was associated with reduced expression of adhesion molecules.


Mutations of the SH3BP2 gene in 2 families of cherubism.
Cherubism is a rare autosomal dominant syndrome characterized by abnormal bone tissue in the lower part of the face. Mutations in the gene coding for SH3BP2 have been identified in about 80% of people with cherubism. The aim of this study was to determine whether a mutation in the SH3BP2 gene was the molecular basis of cherubism in two unrelated families. Two cases of the aggressive form of Cherubism were described in two Turkish families with extensive bilateral swelling in the mandible, typical pathological features and familial history. Genomic DNA was extracted from six affected and three unaffected individuals from two families, and mutations in the SH3BP2 were detected by PCR, and direct DNA sequencing was carried out. In the first family, a missense mutation Arg415Gln was found in exon 9 of the SH3BP2 in all affected individuals. The unaffected individuals did not have this mutation. In the second family, another missense mutation Pro418Thr was identified in exon 9 of the SH3BP2 in the patient and his mother with cherubism. We detected the point mutations in the SH3BP2 gene in the patients with multiple affected individuals. Genotype-phenotype association studies in individuals with cherubism are necessary to provide important knowledge about molecular mechanisms of the disease.


Physical activity does not attenuate the obesity risk of TV viewing in youth.
This study aimed to examine the association of television (TV) time, the frequency of meals while watching TV and the presence of TV set in the bedroom with total and abdominal obesity and to assess whether physical activity (PA) attenuates the obesity risk of TV viewing. Cross-sectional data were obtained from 2200 adolescents (46% boys) from 10 European cities, The Healthy Lifestyle in Europe by Nutrition in Adolescence study, between 2006 and 2007. TV viewing, PA (by accelerometry) and body composition were measured. Binary logistic regression analyses were performed. Even adjusting by vigorous PA, TV in the bedroom (odds ratio [OR]: 1.33, 95% confidence interval [CI], 1.01-1.74) and >4 h d(-1) TV during week days (OR: 1.30, 95% CI, 1.02-1.67) (in boys) and eating every day with TV (OR: 1.18, 95% CI, 1.07-1.30) and >2 h d(-1) TV during weekend days (OR: 1.68, 95% CI, 1.25-2.26) (in girls) were significantly associated with total obesity. Likewise, in both sexes, having a TV set at bedroom was significantly associated with abdominal obesity. Adolescents spending excessive TV time are prone to obesity independently of their PA levels. Families should put TV sets out of adolescents' bedroom and keep TV sets off during meal times.


Genetic, morphological and chemical investigations reveal the genetic origin of Pompia (C. medica tuberosa Risso & Poiteau) - An old endemic Sardinian citrus fruit.
Citrus fruits have been introduced to the Mediterranean area from Asia for centuries and spontaneous crosses have generated several hybrid forms, some of which have had agricultural or industrial success while others have remained niche food or ornamental products, or have disappeared. Pompia (C. medica tuberosa Risso & Poiteau) is an old endemic citrus fruit from Sardinia of unknown genetic origin. Initial phenotypic and molecular characterizations revealed a high degree of similarity with lemon (C. limon (L.) Burm.) and citron (C. medica L.). To identify the ancestors of Pompia, 70 citrus species of the Citrus genus were genotyped with 36 codominant molecular markers (SSR and InDel) of nuclear and cytoplasmic genomes. Diversity analysis and allelic comparisons between each citrus species at each locus indicated that Pompia resembles lemon and limonette of Marrakech, i.e. the result of a cross between sour orange (C. aurantium L.) and citron, where citron was the pollinator. Two Italian citron varieties were identified as potential male parents, i.e. Diamante and Common Poncire. However, we were unable to differentiate varieties of sour oranges because varietal diversification in this horticultural group resulted from DNA sequence variations that SSR or InDel markers could not reveal. Rhob el Arsa and Poncire de Collioure were found to be two synonyms of Pompia. Pompia appeared to be equally distinct from citron, lemon and sour orange based on the overall analysis of the fruit, leaf and seed phenotype, and juice chemical composition. At the leaf level, the Pompia essential oil (EO) composition is close to that of citron whereas the zest is much closer to that of sour orange.


Angiotensin-converting enzyme inhibition or mineralocorticoid receptor blockade do not affect prevalence of atrial fibrillation in patients undergoing cardiac surgery.
This study tested the hypothesis that interruption of the renin-angiotensin system with either an angiotensin-converting enzyme inhibitor or a mineralocorticoid receptor antagonist will decrease the prevalence of atrial fibrillation after cardiac surgery. Randomized double-blind placebo-controlled study. University-affiliated hospitals. Four hundred forty-five adult patients in normal sinus rhythm undergoing elective cardiac surgery. One week to 4 days prior to surgery, patients were randomized to treatment with placebo, ramipril (2.5 mg the first 3 days followed by 5 mg/day, with the dose reduced to 2.5 mg/day on the first postoperative day only), or spironolactone (25 mg/day). The primary endpoint was the occurrence of electrocardiographically confirmed postoperative atrial fibrillation. Secondary endpoints included acute renal failure, hyperkalemia, the prevalence of hypotension, length of hospital stay, stroke, and death. The prevalence of atrial fibrillation was 27.2% in the placebo group, 27.8% in the ramipril group, and 25.9% in the spironolactone group (p=.95). Patients in the ramipril (0.7%) or spironolactone (0.7%) group were less likely to develop acute renal failure than those randomized to placebo (5.4%, p=.006). Patients in the placebo group tended to be hospitalized longer than those in the ramipril or spironolactone group (6.8±8.2 days vs. 5.7±3.2 days and 5.8±3.4 days, respectively, p=.08 for the comparison of placebo vs. the active treatment groups using log-rank test). Compared with patients in the placebo group, patients in the spironolactone group were extubated sooner after surgery (576.4±761.5 mins vs. 1091.3±3067.3 mins, p=.04). Neither angiotensin-converting enzyme inhibition nor mineralocorticoid receptor blockade decreased the primary outcome of postoperative atrial fibrillation. Treatment with an angiotensin-converting enzyme inhibitor or mineralocorticoid receptor antagonist was associated with decreased acute renal failure. Spironolactone use was also associated with a shorter duration of mechanical ventilation after surgery.


Analysis of dose intensity for chemotherapy in early (stage II) and advanced breast cancer.
In chemotherapy of advanced breast cancer, the dose intensities of regimens containing cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) and cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) correlate with remission rate. The correlation is even better if dose intensity is calculated from doses actually given instead of from targeted doses. Also, in adjuvant chemotherapy of stage II breast cancer, the dose intensities of CMF-containing regimens correlate with relapse-free survival. The adjuvant trials analyzed included studies containing only 1 or 2 of C, M, or F or with L-phenylalanine mustard (melphalan) instead of C. Three-year relapse-free survival was clearly related to dose intensity whether the analysis was of trials containing all 4 prognostic groups [women less than 50 yr with 1-3 and greater than 3 positive nodes; and those greater than or equal to 50 yr with 1-3 and greater than 3 positive nodes (P less than .00001)] or of trials in which each of these 4 groups were analyzed separately (P less than .005). In multivariate analysis, dose intensity correlated with relapse-free survival (P less than .00001), independent of the number of positive nodes or menopausal status. Randomized trials will be required before we can determine if prospective increases of dose intensity will improve outcome of chemotherapy in breast cancer.


Skin manifestations help identifying different phenotypes of paediatric SAPHO syndrome.
to evaluate whether the heterogeneous skin manifestations might influence the disease presentation and outcome of a cohort of SAPHO children. the clinical, serological, imaging and therapeutic data of 14 SAPHO patients, followed between 2001 and 2022 at the Unit for Autoinflammatory diseases at the Gaslini Hospital, were reviewed. According to their cutaneous manifestations, patients were divided into 2 groups: the acne-hidradenitis suppurativa (HS) and the Palmo-Plantar Pustulosis (PPP) group. Data were retrieved from the Eurofever database. all patients presented bone involvement characterized by Chronic Recurrent multifocal Osteomyelitis (CRMO): 8 patients presented acne-HS while 6 patients had PPP. In the PPP group, all patients were female, characterized by a prepuberal disease onset with osteoarticular manifestations, followed by the appearance of PPP in the following 6 months. This group responded well to the treatments. In the acne-HS group, 7/8 patients were male: the disease onset was characterized by skin manifestations in pubertal age, followed by osteoarticular manifestations in the following year. This group presented a severe refractory skin disease that required in most cases the addition of biological therapies. A literature review confirmed our data highlighting the association males-acne-puberal age and female-PPP-prepuberal age. paediatric SAPHO patients should be mainly stratified according to their skin involvement. In fact, our data suggest that two different skin phenotypes may be identified in SAPHO: the first is constituted by prepuberal females with PPP and a prevalent osteoarticular involvement, while the second by puberal males with a difficult-to-treat acne-HS.


Protein composition of the photosystem II core complex in genetically engineered mutants of the cyanobacterium Synechocystis sp. PCC 6803.
The presence of four photosystem II proteins, CP47, CP43, D1 and D2, was monitored in mutants of Synechocystis sp. PCC 6803 that have modified or inactivated genes for CP47, CP43, or D2. It was observed that: (1) thylakoids from mutants without a functional gene encoding CP47 are also depleted in D1 and D2; (2) inactivation of the gene for CP43 leads to decreased but significant levels of CP47, D1 and D2; (3) deletion of part of both genes encoding D2, together with deletion of part of the CP43-encoding gene causes a complete loss of CP47 and D1; (4) thylakoids from a site-directed mutant in which the His-214 residue of D2 has been replaced by asparagine do not contain detectable photosystem II core proteins. However, in another site-directed mutant, in which His-197 has been replaced by tyrosine, some CP47 as well as breakdown products of CP43, but no D1 and D2, can be detected. These data could indicate a central function of CP47 and D2 in stable assembly of the photosystem II complex. CP43, however, is somewhat less critical for formation of the core complex, although CP43 is required for a physiologically functional photosystem II unit. A possible model for the assembly of the photosystem II core complex is proposed.


Shoulder reflexes.
Dynamic shoulder stability is dependent on muscular coordination and sensory inputs. In the shoulder, mechanoreceptors are found in the coracoacromial ligament, the rotator cuff tendons, the musculotendinous junctions of the rotator cuff and in the capsule. The number of receptors in the capsule is small compared to the number in the other shoulder structures. Proprioceptive information from numerous receptors in muscles and tendons is mediated via fast conducting nervefibers and probably contribute more to kinaestethic sensation than information from capsule and ligaments. Therefore it seems likely that the joint receptors have a more distinct role for the kinaestethic sense than muscle receptors. In cats a direct reflex from the afferents innervating the shoulder to the muscles around the shoulder has been presented. The reflex had an extremely short latency (2.7-3.1 ms). In man, a very long latency (300 ms) excitatory reflex has been found when nerves in the capsule were stimulated electrically during shoulder surgery. In addition, when the anterior-inferior capsule was excited in conscious humans with modest amplitude electrical stimuli during muscle activity, a strong inhibition was found with an average latency of 33 ms. Stimulation of the sensory nerves in the coracoacromial ligament has also been found to modify muscle activity strongly. Even though our understanding of the control of shoulder motion is incomplete, it is clear that sensory inputs can strongly modify muscle activity around the shoulder. This has implications for rehabilitation and shoulder surgery.


In vivo expression of transforming growth factor-beta1 in humans: stimulation by cyclosporine.
Transforming growth factor-beta1 (TGF-beta1) is an immunoregulatory and fibrogenic cytokine. In an earlier in vitro study, we demonstrated that cyclosporine (CsA) increases TGF-beta1 transcription rate in human T lymphocytes. Herein, we explored whether CsA augments the in vivo expression of TGF-beta1 in humans. The inherent difficulty in studying the in vivo effect of CsA in humans was circumvented by investigating stable end-stage renal disease patients who were preconditioned with CsA before their living donor renal transplantation. Sera and peripheral blood mononuclear cells were obtained from CsA-preconditioned patients and quantified for TGF-beta1 expression at the mRNA (by competitive polymerase chain reaction) and protein (sandwich enzyme-linked immunosorbent assay) levels. Our studies demonstrated a significant increase in TGF-beta1 expression after CsA therapy. The stimulatory effect was unique to TGF-beta1, and CsA did not increase interleukin (IL)-10, IL-6, IL-2, or tumor necrosis factor-alpha expression. Our first-time demonstration of a TGF-beta1-selective in vivo stimulatory effect of CsA in humans: (1) advances a TGF-beta1-centered hypothesis for the beneficial (immunosuppression) and detrimental (fibrosis, hypertension) effects of CsA use, and (2) broadens the mechanism of immunosuppressive action of CsA to include heightened expression of an endogenous immunosuppressive cytokine.


Phosphorylation of a novel cytoskeletal protein (RsmP) regulates rod-shaped morphology in Corynebacterium glutamicum.
Corynebacteria grow by wall extension at the cell poles, with DivIVA being an essential protein orchestrating cell elongation and morphogenesis. DivIVA is considered a scaffolding protein able to recruit other proteins and enzymes involved in polar peptidoglycan biosynthesis. Partial depletion of DivIVA induced overexpression of cg3264, a previously uncharacterized gene that encodes a novel coiled coil-rich protein specific for corynebacteria and a few other actinomycetes. By partial depletion and overexpression of Cg3264, we demonstrated that this protein is an essential cytoskeletal element needed for maintenance of the rod-shaped morphology of Corynebacterium glutamicum, and it was therefore renamed RsmP (rod-shaped morphology protein). RsmP forms long polymers in vitro in the absence of any cofactors, thus resembling eukaryotic intermediate filaments. We also investigated whether RsmP could be regulated post-translationally by phosphorylation, like eukaryotic intermediate filaments. RsmP was phosphorylated in vitro by the PknA protein kinase and to a lesser extent by PknL. A mass spectrometric analysis indicated that phosphorylation exclusively occurred on a serine (Ser-6) and two threonine (Thr-168 and Thr-211) residues. We confirmed that mutagenesis to alanine (phosphoablative protein) totally abolished PknA-dependent phosphorylation of RsmP. Interestingly, when the three residues were converted to aspartic acid, the phosphomimetic protein accumulated at the cell poles instead of making filaments along the cell, as observed for the native or phosphoablative RsmP proteins, indicating that phosphorylation of RsmP is necessary for directing cell growth at the cell poles.


A specific complement-fixation test for infection with poliomyelitis virus.
A complement-fixing antigen has been developed, using as source of material CNS tissue from newborn mice infected with the newborn mouse-adapted strain of the Lansing type, MEF1 virus. With this antigen, specific reactions have been obtained with sera from mice, cotton rats, and monkeys immunized with the Lansing-type virus, and from monkeys and chimpanzees convalescent from infection with this virus. Twenty-one of 35 human sera obtained from individuals convalescent from poliomyelitis were positive and 6 of 22 from apparently normal persons having Lansing-neutralizing antibody, while this held true for only 1 of 19 from those having no Lansing-neutralizing antibody. The fact that positive results were found in sera from patients having an infection with poliomyelitis virus of the Brunhilde type and at the same time no Lansing-neutralizing antibody brings up the possibility of the existence of a cross-reaction in complement fixation between the two types.


Comprehensive drug programs: the Dade County example.
The authors present data from a survey of four methadone maintenance programs, five outpatient clinics, six nonresidential facilities, and nine therapeutic communities affiliated with the Dade County Comprehensive Drug Program. The treatment population included more blacks but fewer Latins than the general county population. Primary drugs of abuse were narcotics in methadone clinics and "softer" drugs in outpatient and nonresidential facilities. Most patients were either self- or court referrals. Direct per patient costs, which were lowest in the outpatient clinics, averaged $1,041. The authors suggest that their data may aid other comprehensive drug treatment programs in establishing guidelines.


Esophageal small cell carcinoma with synchronous renal cell carcinoma: a case report with review of the literature.
Synchronous malignancies with an esophageal malignancy are not uncommon. However synchronous esophageal and renal cell carcinoma (RCC) is rare with only 11 cases reported in the world literature, the esophageal malignancies being adenocarcinomas or squamous cell carcinomas. Here, we report the first case of synchronous small cell carcinoma (SCC) of the esophagus with a RCC. SCC of the esophagus is an aggressive malignancy with poor prognosis constituting 0.8-2.4% of all esophageal malignancies, currently treated with induction chemotherapy followed by chemoradiotherapy. Our patient underwent chemoradiotherapy for the SCC of the esophagus followed by radical nephrectomy for the RCC. He developed metastatic disease and died 8 months after diagnosis. Larger case series are required to develop a treatment algorithm for such a rare presentation. The key points of this report are: (1) Synchronous RCC with a primary esophageal carcinoma is a rare presentation. (2) This is the first described case report of a SCC of the esophagus with a synchronous RCC. (3) Overall prognosis in a synchronous presentation is determined by the primary esophageal malignancy. (4) Esophageal carcinomas with synchronous malignancies have a poorer prognosis compared to isolated esophageal carcinoma.


Phosphorylation of DHBV pre-S: identification of the major site of phosphorylation and effects of mutations on the virus life cycle.
Four potential serine/threonine phosphorylation sites [(S/T)-P motif], designated P1-P4, on the pre-S protein of duck hepatitis B virus (DHBV) have been mutated. Mutants include single (P2, P3, P4) and double amino acid substitutions (P1 + P2, P3 + P4) and one with all four sites mutated (4P). Serine at position 118 (P3) was identified as the major site of phosphorylation by Western blotting and radioimmunoprecipitation after in vitro cell labeling with [35S]methionine or [33P]orthophosphate. Mutant virions generated by transfection of LMH cells were infectious both in vitro in duck hepatocyte primary cultures and in vivo in Pekin ducks. Intracellular relaxed circular (RC) and covalently closed circular (ccc) DNA syntheses were not affected by the P3 mutation or even the quadruple mutant. Extracellular virus production was slightly increased when the P3 site was mutated. CsCl gradient centrifugation showed no clear difference between mutant and wild-type virus with respect to the ratios of enveloped virus and nucleocapsid particles in hepatocyte culture supernatants. Trypsin or V8 protease digestion with or without NP-40 indicated that phosphorylation of the pre-S domain is not involved in determining the transmembrane topology of DHBV large protein. This phenotypic analysis indicates that DHBV pre-S phosphorylation has no apparent effect on DHBV replication and formation of mature viral particles in duck hepatocyte primary culture and does not affect infectivity in ducklings.


Contrast-enhanced whole-heart coronary magnetic resonance angiography at 3 T using interleaved echo planar imaging.
The goal of this work was to reduce the scan time of contrast-enhanced whole-heart coronary magnetic resonance angiography (MRA) by using a gradient echo interleaved echo planar imaging (GRE-EPI) sequence at 3 T field strength. A GRE-EPI sequence was optimized to acquire contrast-enhanced whole-heart coronary MRA at 3 T. First-order phase correction was used for alignment of the odd and even echoes in the GRE-EPI echo train. Single and dual reference scan techniques for estimation of the linear phase correction parameters were evaluated using both phantom and volunteer studies. The GRE-EPI readout was combined with parallel imaging for a further reduction in scan time. To avoid image distortions, calibration signals for coil sensitivity estimation were acquired in a separate low resolution GRE scan before the whole-heart GRE-EPI scan. Eight healthy volunteers were scanned with the optimized contrast-enhanced GRE-EPI sequence. GRE-EPI images were acquired during slow infusion (0.3 mL/s) of 0.1 mmol/kg body weight of Gd-BOPTA. For comparison purposes, the same 8 volunteers were scanned again in a separate scan session using a traditional GRE sequence with double the dose (0.2 mmol/kg body weight) of the same contrast agent with the same injection rate. The contrast-enhanced GRE-EPI and contrast-enhanced GRE techniques were compared in terms of relative signal-to-noise ratio (rSNR), relative contrast-to-noise ratio (rCNR), image quality scores, and visualized vessel lengths. Both, phantom and volunteer studies demonstrated that the dual reference scan phase correction technique was a key step for obtaining satisfactory image quality using GRE-EPI at 3 T. Whole-heart coronary MRA with a spatial resolution of 1.0 x 1.0 x 2.0 mm3 was acquired with the GRE-EPI sequence in an average scan time of 2.5 +/- 0.6 minutes, compared with 8.6 +/- 2.7 minutes for the GRE technique. The GRE-EPI technique had lower rCNR compared with the GRE sequence. The image quality and coronary artery visualization with the GRE-EPI technique were adequate, and there was no statistically significant difference in the image quality scores, rSNR, and visualized coronary artery lengths between the GRE-EPI and GRE techniques. Contrast-enhanced whole-heart coronary MRA using the GRE-EPI technique resulted in excellent delineation of all the major coronary arteries and compared with current GRE techniques demonstrated a factor of 2 reduction in contrast agent dose and a factor of 3 reduction in scan time.


Palladium-catalyzed conjugate addition of organosiloxanes to alpha,beta-unsaturated carbonyl compounds and nitroalkenes.
The addition of aryltrialkoxysilanes to alpha,beta-unsaturated carbonyl compounds (ketones, aldehydes) and nitroalkenes in the presence of SbCl(3), TBAF, AcOH, and a catalytic amount of Pd(OAc)(2), in CH(3)CN at 60 degrees C, provides the corresponding conjugate addition products in moderate to good yields. The addition of equimolar amounts of SbCl(3) and TBAF is necessary for this reaction to proceed smoothly. The arylpalladium complex, which is generated by the transmetalation from a putative hypercoordinate silicon compound, is considered to be the catalytically active species.


Antibiotic use and knowledge in the community in Kalamoon, Syrian Arab Republic: a cross-sectional study.
Antibiotic misuse contributes to the growing problem of microbial resistance. To understand the current knowledge and practices regarding antibiotic use among Syrians, we conducted a cross-sectional study of 430 randomly selected adult residents of Kalamoon in the Syrian Arab Republic using a questionnaire. A high proportion (85%) had taken antibiotics in the past 4 weeks and 34% were not aware of the dangers of antibiotics. Of 365 participants, only 43% were prescribed the antibiotic by a physician to treat the condition, while 57% used an old prescription or took someone else's advice. Males, younger individuals, and those with low and medium income and lower educational status showed poorer practice and lower knowledge towards antibiotics. Educational efforts are needed to reduce patient demand for antibiotics.


Overexpression of Gilz Protects Mice Against Lethal Septic Peritonitis.
Sepsis in humans and experimental animals is characterized by an acute inflammatory response. glucocorticoids (GCs) are widely used for the treatment of many inflammatory disorders, yet their effectiveness in sepsis is debatable. One of the major anti-inflammatory proteins induced by GCs is glucocorticoid-induced leucine zipper (GILZ, coded by the TSC22D3 gene). We found that TSC22D3 mRNA expression is downregulated in white blood cells of human sepsis patients. Interestingly, transgenic GILZ-overexpressing mice (GILZ-tg) showed better survival rates in the cecal ligation and puncture (CLP) model of mouse sepsis. To our surprise, GILZ had only mild anti-inflammatory effects in this model, as the systemic proinflammatory response was not significantly reduced in GILZ-tg mice compared with control mice. During CLP, we observed reduced bacterial counts in blood of GILZ-tg mice compared with control mice. We found increased expression of Tsc22d3 mRNA specifically in peritoneal exudate cells in the CLP model, as well as increased capacity for bacterial phagocytosis of CD45 GILZ-tg cells compared with CD45 GILZ-wt cells. Hence, we believe that the protective effects of GILZ in the CLP model can be linked to a more efficient phagocytosis.


Perceptions and experiences of patients attending an opioid substitution clinic in South Africa.
Opioid substitution therapy (OST) is endorsed as the recommended treatment for opioid use disorders. Opioid substitution therapy is not widely used in South Africa, so little is known about its perceived clinical utility in this setting. There is also a paucity of qualitative research that explores the subjective experiences of patients using OST. To explore patients' perceptions and experiences attending a South African OST outpatient clinic (OST-OC). The OST-OC at Stikland Psychiatric Hospital, Cape Town, South Africa. We conducted a qualitative study using semi-structured interviews with eight participants who had been attending the OST-OC for at least 6 months. Transcripts were analysed using Atlas.ti software and thematic content analysis was used to identify themes. Patients stated that OST helped them to regain and maintain a stable lifestyle. Autonomy and agency, the therapeutic relationship and family support were perceived as contributing to successful patient outcomes. The preference for methadone and buprenorphine treatment depended on individual experiences. Patients valued kindness from staff members but reported that improved interactions with some nonclinical staff could better facilitate treatment. Challenges experienced included stigma and cost. This study offers insights about OST that are pertinent to low- and middle-income countries. Reducing the cost of OST, collaborative decision-making between staff and patients, and a non-judgemental attitude by clinical staff were recognised as important factors for optimised service delivery. Understanding patients' experiences of OST in a South African setting will allow for future policy development for the treatment of opioid use disorders in similar settings locally and abroad.


[Angiosarcoma of the breast. Apropos of 8 cases and review of the literature].
The 8 cases of primary breast angiosarcoma which were diagnosed, treated and had their follow-up at the Gustave-Roussy Institute between 1954 and 1995 are reported. The age at presentation ranged from 32 to 68 years. In 4 patients the vascular nature of their mammary lesion was conspicuous by a violaceous discolorations of the overlying skin. No patient had enlarged ipsilateral axillary lymph nodes. One patient had metastases. In 2 out of 5 patients who had a partial surgical or fine-needle biopsy before treatment, the diagnosis was missed, and adequate treatment was unduly delayed. The tumor most often presents as an ill defined area made of dense endothelium-lined papillae. A remarkable picture of "soap bubbles" has been identified in 4 cases. The "meshes" of fatty areas appear to be reinforced as they are infiltrated by tumor cells. This appearance may be specific of mammary angiosarcoma. By the French Cancer Centers' grading system for soft tissue sarcomas in general, grade is III in 3 tumors, II in 2 tumors, I in 3 tumors. Five tumors were treated by total mastectomy only. In 3 cases a total mastectomy was followed by radiation therapy to the chest wall. At diagnosis a chemotherapy was administered only to the patient who had metastases. Median disease-free survival was 9 months. Median overall survival was 13 months. From a review of the literature a simple mastectomy appears to be necessary as well as enough for local treatment. Patients with a grade III angiosarcoma of the breast should be included into a therapeutical trial of adjuvant chemotherapy for soft tissue sarcomas in general.


Microbial Phylogenetic Context Using Phylogenetic Outlines.
Microbial studies typically involve the sequencing and assembly of draft genomes for individual microbes or whole microbiomes. Given a draft genome, one first task is to determine its phylogenetic context, that is, to place it relative to the set of related reference genomes. We provide a new interactive graphical tool that addresses this task using Mash sketches to compare against all bacterial and archaeal representative genomes in the Genome Taxonomy Database taxonomy, all within the framework of SplitsTree5. The phylogenetic context of the query sequences is then displayed as a phylogenetic outline, a new type of phylogenetic network that is more general than a phylogenetic tree, but significantly less complex than other types of phylogenetic networks. We propose to use such networks, rather than trees, to represent phylogenetic context, because they can express uncertainty in the placement of taxa, whereas a tree must always commit to a specific branching pattern. We illustrate the new method using a number of draft genomes of different assembly quality.


Primed monocytes: putative culprits of chronic low-grade inflammation and impaired innate immune responses in patients on hemodialysis.
End-stage renal disease patients are known to be in a state of chronic low-grade inflammation and to have high infection-related morbidity and mortality. However, the precise mechanisms are not understood. The purpose of this study was to determine the mechanisms underlying chronic low-grade inflammation and defects in innate immune responses in hemodialysis (HD) patients. In 33 HD patients, we measured the basal status of toll-like receptor 4 (TLR4) positivity in the CD14-positive monocyte population in the peripheral blood (not strong, i.e., CD14(low)), with plasma levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β, IL-6, IL-8, IL-10, and IL-12p70 compared with 22 healthy controls. After stimulation by lipopolysaccharide (LPS), the plasma cytokine response was also compared. In the basal state, the percentage of peripheral blood TLR4(+)CD14(low) monocytes and plasma cytokines were significantly higher in HD patients (p < 0.05), suggesting that preactivated primed monocytes might be responsible for the chronic inflammatory state in HD patients. However, upon LPS challenge, the fold increase in plasma cytokine response was significantly reduced in HD patients (p < 0.05) compared with controls. More importantly, the fold increase of these cytokines showed a positive correlation with plasma albumin (p < 0.05) and a negative correlation with C-reactive protein (CRP) (p < 0.05), suggesting the presence of a possible link between chronic low-grade inflammation and suboptimal innate immune response. Chronic low-grade inflammation due to preactivated peripheral blood CD14(+) leukocyte subset might be a mechanism for impaired innate immune responses, thus resulting in the high rates of infection-related morbidity and mortality observed in HD patients.


Probing the Anticancer Action of Oridonin with Fluorescent Analogues: Visualizing Subcellular Localization to Mitochondria.
Oridonin (1) is a complex ent-kaurane diterpenoid exhibiting remarkable antitumor activity. However, the detailed mechanism or cellular target that underlies this activity has not yet been identified. Herein, we report an efficient approach for exploring the anticancer mechanism of oridonin through development of the potent fluorescent analogues. A series of novel fluorescent oridonin probes linked with coumarin moieties were designed, synthesized, and characterized. Fluorescence microscopy and confocal imaging studies suggested that fluorescent oridonin probe 17d was rapidly taken up into tumor cells and the mitochondrion was the main site of its accumulation. Moreover, we confirmed that cytochrome c played an important role in oridonin induced mitochondrion-mediated apoptosis and α,β-unsaturated ketone is the active moiety of oridonin, which is crucial to its uptake, localization, and cytotoxicity. Our results provide new insights on the molecular mechanism of oridonin and would be useful for its further development into an antitumor agent.


Vitamin D and food allergies in children: A systematic review and meta-analysis.
Vitamin D insufficiency has been associated with immune dysfunction and linked to the epidemic of atopic diseases in the Western hemisphere, yet there are studies with conflicting results, and the risk has not been quantified uniformly across studies. To perform a systematic review and meta-analysis to evaluate and quantify if vitamin D deficiency is associated with the presence and persistence of food allergy. A systematic review was undertaken to assess for the association between food allergy and vitamin D status in children. A total of 368 citations relevant to this systematic review were identified. In the whole review, 5105 children were included. We did not find a significant association between 25 hydroxy vitamin D (25(OH)D) status and risk of food allergy in children (odds ratio [OR] 1.35 [95% confidence interval {CI}, 0.79-2.29]; p = 0.27, I2 = 58.3%). We conducted subgroup analyses based on different cutoffs of the 25(OH)D status (20 versus 30 ng/mL). Only one study used 30 ng/mL and found that children with <30 ng/mL were more likely to report food allergy than children with a 25(OH)D status of ≥30 ng/mL (OR 2.04 [95% CI, 1.02-4.04]; p = 0.04). Four studies compared children with a 25(OH)D status of <20 ng/mL to children with a 25(OH)D status of ≥20 ng/mL and found no significant differences (OR 1.18 [95% CI, 0.62-2.27]; p = 0.62, I2 = 62.7%). Based on the studies analyzed, this systematic review did not identify a significant association between vitamin D status and food allergy. Interpretation of the included studies was limited by a lack of a standard definition for vitamin D deficiency and insufficient knowledge regarding the optimal vitamin D status needed to impact immune function. Longitudinal studies are warranted to assess if vitamin D might contribute to the development of food allergy.


Botanical medicine and cancer: a review of the safety and efficacy.
It is currently estimated that > 50% of all patients diagnosed with cancer explore complementary and alternative medicine - especially herbal medicine. We conducted a comprehensive review to assess the safety and efficacy of herbal medicines commonly used by patients in an attempt to: prevent cancer; treat cancer; and treat adverse effects associated with conventional cancer treatments. Current evidence suggests that Asian ginseng, garlic, green tea, tomatoes and soy intake as part of the diet may be useful in preventing various cancers; additional research is needed in order to determine the efficacy of essiac, evening primrose oil, mistletoe, reishi, shiitake and turmeric as cancer treatments; and ginger may be effective in treating chemotherapy-induced nausea and vomiting.


Texture analysis of sonographic features of the parotid gland in Sjögren's syndrome.
The purpose of this study was to develop a method for quantitative analysis of the sonographic features of parotid glands as a noninvasive tool for the diagnosis of Sjögren's syndrome. Sonographic texture analyses were performed on the parotid glands of 44 patients with Sjögren's syndrome, 83 healthy volunteers, and 17 patients with chronic parotitis, using a fast Fourier transform program. Texture analysis of sonographic studies of the parotid gland using a Fourier transform showed that the sum of the normalized radial power spectrum in the low-spatial-frequency region (S value) of the parotid gland was significantly higher (p < .0001) in the patients with definite Sjögren's syndrome [6.70 +/- 2.13 (x10(5))] than in the 72 age-matched normal volunteers [3.25 +/- 1.08 (x10(5))]. However, patients with probable Sjögren's syndrome showed S values [3.92 +/- 1.88 (x10(5))] similar to those of the controls. On the other hand, SDs of the echo levels in the parotid gland showed significantly greater (p < .0001) values in patients with definite (4.63 1.07) and probable (4.53 1.47) Sjögren's syndrome than in the normal controls (3.30 0.76). Discriminant analysis showed that a combination of these two distinctive values increased diagnostic accuracy to 96.9%. Furthermore, S values and SDs correlated well with the qualitative grading of sonographic features and with the gradings of sialography. The system we describe for texture analysis of sonographic images is useful in the diagnosis of Sjögren's syndrome.